Datasets:

hazyresearch

/

based-fda

like 2

Follow

HazyResearch 30

idK181324_s6000_e8000

K181324.txt

predicate device name

FilmArray Respiratory Panel 2 plus (RP2plus)

results. Table 3: Interpretation of Controls Field on the FilmArray Pneumonia Panel plus Test Report Control Result Explanation Action Passed The run was successfully completed AND Both pouch controls were successful. None Report the results provided on the test report. Failed The run was completed BUT At least one of the pouch controls (RNA Process Control and/or QSM) failed. Repeat the test using a new pouch. If the error persists, contact Customer Technical Support for further instruction. Invalid The controls are invalid because the run did not complete. (Typically this indicates a software or hardware error). Note any error codes displayed during the run and the Run Status field in the Run Information section of the report. Refer to the appropriate FilmArray Operator’s Manual or contact Customer Technical Support for further instruction. Once the error is resolved, repeat the test or repeat the test using another instrument. Detection Summary The Detection Summary section is displayed on the first page of the report and lists the Detected results under each category (Bacteria, Antimicrobial Resistance Genes, Atypical Bacteria, and Viruses), including the semi-quantitative ‘Bin (copies/mL)’ results for Bacteria. If there are no Detected results in a specific category, the result shown is Detected: None. 13 Result Summary The Results Summary is displayed on the second page of the report and provides a full list of test results for each organism and antimicrobial resistance gene including the ‘Bin (copies/mL)’ result for Bacteria. Possible results for each organism are Detected, Not Detected, Invalid, and N/A. The Table provides an explanation for each interpretation and any follow-up necessary to obtain a final result. Table 4: Reporting of Results and Required Actions Result Explanation Action Detected The run was successfully completed AND The pouch controls were successful (Passed) AND The assay(s) for the organism were POSITIVEa Report results. Not Detected The run was successfully completed AND The pouch controls were successful (Passed) AND The assay(s) for the organism were NEGATIVEb Report results. Invalid The pouch controls were not successful (Failed) OR The run was not successful (Run Status displayed as: Aborted, Incomplete, Instrument Error or Software Error) SeeTable 3 for instruction. N/A (Antimicrobial Resistance Genes only The run was successfully completed AND The pouch controls were successful (Passed) AND The assay(s) for the organism(s) associated with the antimicrobial resistance gene were NEGATIVE so the results of the antimicrobial resistance gene are not applicable to the test results. Report results. a. For bacteria, the organism calculated value must be greater than or equal to 103.5 copies/mL for the assay to be POSITIVE. b. For bacteria, a NEGATIVE assay result may indicate no amplification or amplification with an organism calculated value less than 103.5 copies/mL J. Substantial Equivalence Information: 1. Predicate device name(s): FilmArray Respiratory Panel 2 plus (RP2plus) 2. Predicate 510(k) number(s): DEN170017 14 3. Comparison with predicate: Similarities Item New Device: FilmArray Pneumonia Panel plus (K181324) Predicate: FilmArray Respiratory Panel 2 plus (DEN170017) Indication for Use The FilmArray Pneumonia Panel plus is a multiplexed nucleic acid test intended for use with FilmArray, FilmArray 2.0, or FilmArray Torch systems for the simultaneous detection and identification of multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like specimens (induced or expectorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL or mini-BAL) obtained from individuals meeting MERS-CoV clinical and/or epidemiological criteria. Testing with FilmArray Pneumonia Panel plus should not be performed unless the patient meets clinical and/or epidemiologic criteria for testing suspected MERS-CoV specimens. This includes: clinical signs and symptoms associated with MERS-CoV infection, contact with a probable or confirmed MERS-CoV case, history of travel to geographic locations where MERS-CoV cases were detected, or other epidemiological links for which MERS-CoV testing may be indicated. The following bacteria are reported semi-qualitatively with bins representing approximately 104, 105, 106, or ≥107 genomic copies of bacterial nucleic acid per milliliter (copies/mL) of specimen, to aid in estimating relative abundance of nucleic acid from these common bacteria within a specimen: Bacteria reported with bins of 104, 105, 106, or ≥107 copies/mL: Acinetobacter calcoaceticus- baumannii complex, Enterobacter cloacae complex, Escherichia coli, Haemophilus influenzae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Moraxella catarrhalis, Proteus spp., Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes Atypical Bacteria: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae Antimicrobial Resistance Genes: CTX-M, IMP, KPC, mecA/C + MREJ, NDM, Oxa48-like, VIM Viruses: Adenovirus, Coronavirus, Human Metapneumovirus, Human Rhinovirus/Enterovirus, Influenza A, Influenza B, Middle East Respiratory Syndrome Coronavirus, Parainfluenza virus, The FilmArray Respiratory Panel 2 plus (RP2plus) is a multiplexed nucleic acid test intended for use with FilmArray 2.0 or FilmArray Torch systems for the simultaneous qualitative detection and identification of nucleic acids from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and multiple common viral and bacterial respiratory pathogens in nasopharyngeal swabs (NPS) obtained from individuals meeting MERS- CoV clinical and/or epidemiological criteria. Testing with the FilmArray RP2plus should not be performed unless the patient meets clinical and/or epidemiologic criteria for testing suspected MERS-CoV specimens. This includes: clinical signs and symptoms associated with MERS-CoV infection, contact with a probable or confirmed MERS-CoV case, history of travel to geographic locations where MERS-CoV cases were detected, or other epidemiological links for which MERS-CoV testing may be indicated. The detection and identification of specific viral and bacterial nucleic acids from MERS-CoV and other respiratory pathogens in individuals meeting MERS-CoV clinical and/or epidemiological criteria aids in the differential diagnosis of MERS-CoV infection, if used in conjunction with other clinical and epidemiological information in accordance with the guidelines provided by the appropriate public health authorities. FilmArray RP2plus MERS-CoV positive results are for the presumptive identification of MERS-CoV. The definitive identification of MERS-CoV requires additional testing and confirmation procedures in consultation with the appropriate public health authorities (e.g., local or state public health departments, etc.) for whom reporting is necessary. The diagnosis of MERS- CoV infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of MERS-CoV. FilmArray RP2plus MERS-CoV negative results, even in the context of a FilmArray RP2plus positive result for one or more of the common respiratory pathogens, do not preclude MERS-CoV infection and should not be used as the sole basis for patient management decisions. The levels of MERS-CoV that would be present in NPS specimens from individuals with early infection and from asymptomatic MERS-CoV carriers are not well understood. The FilmArray RP2plus MERS-CoV negative results may also be due to lower respiratory tract 15 Similarities Respiratory Syncytial virus The detection and identification of specific viral and bacterial nucleic acids from MERS-CoV and other respiratory pathogens, as well as the estimation of relative abundance of nucleic acid from common bacterial analytes, within specimens collected from individuals meeting MERS-CoV clinical and/or epidemiological criteria aids in the differential diagnosis of MERS-CoV infection, if used in conjunction with other clinical and epidemiological information in accordance with the guidelines provided by the appropriate public health authorities. FilmArray Pneumonia Panel plus MERS-CoV positive results are for the presumptive identification of MERS- CoV. The definitive identification of MERS-CoV requires additional testing and confirmation procedures in consultation with the appropriate public health authorities (e.g., local or state public health departments, etc.) for whom reporting is necessary. The diagnosis of MERS-CoV infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of MERS-CoV. FilmArray Pneumonia Panel plus MERS-CoV negative results, even in the context of a FilmArray Pneumonia Panel plus positive result for one or more of the common respiratory pathogens, do not preclude Predicate device name:

idK181324_s92000_e94000

K181324.txt

proposed labeling

The labeling is sufficient and satisfies the requirements of 21 CFR parts 801 and 809 as well as the Special Controls for this type of device.

the Tm and checking for potential errors associated with the melt data analysis. As part of the release of the FilmArray Respiratory Panel test, the Melt Detector was optimized on a training data set and validated against the Clinical Evaluation Data. The FilmArray Pouch Module Software was also tested and successfully executed to demonstrate compatibility with the FilmArray software. In addition, because the panel can be used on both the FilmArray v1.5 and v2.0 Systems, the Analysis Software compares the proper .dll files as part of verification testing to ensure that the proper files are used. The FilmArray pouch module software is designed so that pouch modules compatible with the FilmArray 1.5 systems cannot be installed on the FilmArray 2.0 systems and vice versa. Note, the firm states that the FilmArray Torch software is similar to the FilmArray 2.0 system software. The firm also stated that as part of the release of the FilmArray Pneumonia Panel plus, a regression test was successfully executed to show that the release candidate pouch module produced the same results as those submitted for review. Further, as detailed in the cybersecurity review, the firm has implemented measures such as encrypting database passwords to address the potential risk for modification of test data in the database that could impact listed test results. After mitigation, all risk scores were at a Low or Immeasurable level. Architecture Design Chart: A detailed structure of the software used in the FilmArray System was provided. Software Requirements Specification (SRS): SRS documentation was provided describing requirements and specifications for each of the software components of the FilmArray System was described. Traceability Analysis: Documentation of traceability matrix that links all product requirements, functional specifications, and verification and validation testing for the complete FilmArray system was provided. Software Development Environment Description: A description of FilmArray software development environment was provided and was acceptable. 132 Verification and Validation Testing: The sponsor provided adequate documentation of verification and validation (V & V) testing covering all software/instrument components of the FilmArray System. V &V testing of FilmArray System software was successfully completed at the individual component and system integration levels. The normal operation and user interface of all FilmArray software components were also tested and verified. Revision Level History: The firm provided a software revision level history that detailed the updates to the system software corresponding to each version. Unresolved Anomalies: All major residual risks and unresolved anomalies were properly mitigated. Any remaining anomalies did not present major concerns for safety and efficacy for either the user or the patient. EMC Testing: This submission does not include any new hardware and therefore there are no updates requiring EMC testing. 5. Specimen Identification: The Sample ID can be entered manually or scanned in by using the FilmArray barcode scanner. 6. Specimen Sampling and Handling: N/A 7. Calibration: N/A 6. Quality Control: See section M (d) for information on internal and external controls. O. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Not applicable P. Proposed Labeling: The labeling is sufficient and satisfies the requirements of 21 CFR parts 801 and 809 as well as the Special Controls for this type of device. Q. Patient Perspectives 133 This submission did not include specific information on patient perspectives for this device. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. The potential value of “semi quantitative” bin reporting to help determine the clinical significance of the pathogens/resistance markers reported needs to be established by the individual testing site in consideration of current testing practices. Reporting and interpretation can be patient/institution specific and guidelines should be established and local education facilitated by joint decisions between various clinical care groups (Laboratory, Infectious Diseases, Pulmonologists, Intensivists, Infection Control, Pharmacy, antibiotic stewardship committee, etc.) Proposed labeling:

idK190219_s0_e2000

K190219.txt

purpose for submission

Clearance of device to detect and identify Varizella Zoster Virus DNA in cerebrospinal fluid

STANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K190219 B. Purpose for Submission: Clearance of device to detect and identify Varizella Zoster Virus DNA in cerebrospinal fluid C. Measurand: Varizella zoster virus DNA D. Type of Test: Realtime Polymerase Chain Reaction E. Applicant: DiaSorin F. Proprietary and Established Names: Simplexa VZV Direct, Simplexa VZV Positive Control Pack G. Regulatory Information: Table 1: Regulatory Information Regulation Section Classification Product Code(s) Panel 21 CFR 866.3970 - Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Class II PLO MI - Microbiology 21 CFR 862.2570 - Instrumentation for clinical multiplex test systems Class II OOI CH - Clinical Chemistry H. Intended Use: 1. Intended use(s): SimplexaVZV Direct: The DiaSorin Molecular Simplexa VZV Direct assay is intended 2 for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZV infection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack. The Simplexa VZV Positive Control Pack is intended to be used as a control with the Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): Rx - For Prescription Use Only For in vitro diagnostic use 4. Special instrument requirements: The Simplexa VZV Direct assay is for use with the LIAISON MDX instrument (with LIAISON MDX Studio Software) I. Device Description: The Simplexa VZV Direct assay is a real-time polymerase chain reaction (PCR) system that enables the direct amplification and detection of VZV DNA from unprocessed cerebral spinal fluid (CSF) specimens without nucleic acid extraction. The system consists of the Simplexa VZV Direct, the Simplexa VZV Positive Control Pack, and the Direct Amplification Disc. The assay is performed on the LIAISON MDX instrument which is controlled by an external computer equipped with LIAISON MDX Studio Software. The Direct Amplification Disk (DAD) consumable, disposable discs into which the PCR reagents and test samples are manually pipetted in, is compartmentalized into eight separate wedges and up to eight separate specimens or controls may be processed on each disc. The disc may be reused until all wedges have been utilized. Each wedge contains sample and reagent input wells, microfluidic channels and laser activated valves to control the fluid flow, and a reaction chamber. In the Simplexa VZV Direct assay, fluorescent probes are used together with corresponding forward and reverse primers to amplify VZV and internal control targets. A well-conserved region of the VZV DNA polymerase gene is targeted to identify VZV DNA in the specimen. An internal control is used to detect PCR failure and/or inhibition. 3 The LIAISON MDX instrument is a rapid real-time Polymerase Chain Reaction (PCR thermocycler used for the identification of nucleic acid from biological specimens. The LIAISON MDX instrument automates amplification, fluorescence-based detection and result interpretation. The LIAISON MDX system was previously referred to as the 3M Integrated Cycler system which was previously cleared via the premarket notification under K102314. Results are reported as “Detected”, Not Detected”, “invalid” (due to failure of the Internal Control or inadequate sample volume) or with a specific error code and may be printed. J. Substantial Equivalence Information: 1. Predicate device name(s): FilmArray Meningitis/Encephalitis (ME) Panel for use with FilmArray and FilmArray 2.0 systems 2. Predicate 510(k) number(s): K160462 3. Comparison with the predicate: Table 2: General Device Characteristic Similarities Similarities Item Predicate (K160462) New Device (K190219) Intended Use The FilmArray Meningitis/ Encephalitis (ME) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray and FilmArray 2.0 systems. The FilmArray ME Panel is capable of simultaneous detection and identification of multiple bacterial, viral, and yeast nucleic acids directly from cerebrospinal fluid (CSF) specimens obtained via lumbar puncture from individuals with signs and/or symptoms of meningitis and/or encephalitis. The following organisms are identified using the FilmArray ME Panel: Bacteria: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis (encapsulated), Streptococcus agalactiae, Streptococcus pneumoniae Viruses: Cytomegalovirus, Enterovirus, Herpes simplex virus 1, Herpes simplex virus 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus, Yeast: Cryptococcus neoformans/gattii. The FilmArray ME Panel is indicated as an aid in the diagnosis of specific agents The DiaSorin Molecular Simplexa VZV Direct assay is intended for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZVinfection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack: The Simplexa VZV Positive Control Pack is intended to be used as a control with the 4 Similarities Item Predicate (K160462) New Device (K190219) of meningitis and/or encephalitis and results are meant to be used in conjunction with other clinical, epidemiological, and laboratory data. Results from the FilmArray ME Panel are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out co-infection with organisms not included in the FilmArray ME Panel. The agent detected may not be the definite cause of the disease. Negative results do not preclude central nervous system central nervous system (CNS) infection. Not all agents of the central nervous system (CNS) infection are detected by this test and sensitivity in clinical use may differ from that described in the package insert. The FilmArray ME Panel is not intended for testing of specimens collected from indwelling central nervous system medical devices. The FilmArray ME Panel is intended to be used in conjunction with standard of care culture for organism recovery, serotyping, and antimicrobial susceptibility testing. Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. Product Code PLO Same Regulation Number 21 CFR 866.3970 – Device Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Same Organism detected Varicella zoster virus Same Measurand DNA from varicella zoster virus Same General Technology Fluorescence based PCR system Same Sample Type CSF Same Automated System Yes Same 5 Table 3: General Device Characteristic Differences Differences Item Predicate (K160462) New Device (K190219) Number of Analytes Multiplex Singleplex Additional Assay targets Detection and identification from different bacteria, fungi and viruses causing signs and symptoms of meningitis and/or encephalitis None Extraction Yes None Amplification Nested PCR reactions One PCR reaction Detection Melting Curve Analysis based on fluorescent double stranded DNA binding dye Detection of fluorescence from fluorophore labeled probes Instrument FilmArray or FilmArray 2.0 system LIAISON MDX K. Standard/Guidance Document Referenced (if applicable): • FDA Guidance: Format for Traditional and Abbreviated 510(k) - Guidance for Industry and FDA Staff, July 07, 2015 • FDA Guidance: Off-The-Shelf Software Use in Medical Devices: Guidance for Industry, FDA Reviewers, and Compliance, September 9, 1999 • FDA Guidance: Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices: Guidance for Industry and FDA Staff, May 11, 2005 • FDA Guidance: General Principles of Software Validation: Guid Purpose for submission:

idK190219_s0_e2000

K190219.txt

measurand

Varizella zoster virus DNA

STANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K190219 B. Purpose for Submission: Clearance of device to detect and identify Varizella Zoster Virus DNA in cerebrospinal fluid C. Measurand: Varizella zoster virus DNA D. Type of Test: Realtime Polymerase Chain Reaction E. Applicant: DiaSorin F. Proprietary and Established Names: Simplexa VZV Direct, Simplexa VZV Positive Control Pack G. Regulatory Information: Table 1: Regulatory Information Regulation Section Classification Product Code(s) Panel 21 CFR 866.3970 - Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Class II PLO MI - Microbiology 21 CFR 862.2570 - Instrumentation for clinical multiplex test systems Class II OOI CH - Clinical Chemistry H. Intended Use: 1. Intended use(s): SimplexaVZV Direct: The DiaSorin Molecular Simplexa VZV Direct assay is intended 2 for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZV infection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack. The Simplexa VZV Positive Control Pack is intended to be used as a control with the Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): Rx - For Prescription Use Only For in vitro diagnostic use 4. Special instrument requirements: The Simplexa VZV Direct assay is for use with the LIAISON MDX instrument (with LIAISON MDX Studio Software) I. Device Description: The Simplexa VZV Direct assay is a real-time polymerase chain reaction (PCR) system that enables the direct amplification and detection of VZV DNA from unprocessed cerebral spinal fluid (CSF) specimens without nucleic acid extraction. The system consists of the Simplexa VZV Direct, the Simplexa VZV Positive Control Pack, and the Direct Amplification Disc. The assay is performed on the LIAISON MDX instrument which is controlled by an external computer equipped with LIAISON MDX Studio Software. The Direct Amplification Disk (DAD) consumable, disposable discs into which the PCR reagents and test samples are manually pipetted in, is compartmentalized into eight separate wedges and up to eight separate specimens or controls may be processed on each disc. The disc may be reused until all wedges have been utilized. Each wedge contains sample and reagent input wells, microfluidic channels and laser activated valves to control the fluid flow, and a reaction chamber. In the Simplexa VZV Direct assay, fluorescent probes are used together with corresponding forward and reverse primers to amplify VZV and internal control targets. A well-conserved region of the VZV DNA polymerase gene is targeted to identify VZV DNA in the specimen. An internal control is used to detect PCR failure and/or inhibition. 3 The LIAISON MDX instrument is a rapid real-time Polymerase Chain Reaction (PCR thermocycler used for the identification of nucleic acid from biological specimens. The LIAISON MDX instrument automates amplification, fluorescence-based detection and result interpretation. The LIAISON MDX system was previously referred to as the 3M Integrated Cycler system which was previously cleared via the premarket notification under K102314. Results are reported as “Detected”, Not Detected”, “invalid” (due to failure of the Internal Control or inadequate sample volume) or with a specific error code and may be printed. J. Substantial Equivalence Information: 1. Predicate device name(s): FilmArray Meningitis/Encephalitis (ME) Panel for use with FilmArray and FilmArray 2.0 systems 2. Predicate 510(k) number(s): K160462 3. Comparison with the predicate: Table 2: General Device Characteristic Similarities Similarities Item Predicate (K160462) New Device (K190219) Intended Use The FilmArray Meningitis/ Encephalitis (ME) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray and FilmArray 2.0 systems. The FilmArray ME Panel is capable of simultaneous detection and identification of multiple bacterial, viral, and yeast nucleic acids directly from cerebrospinal fluid (CSF) specimens obtained via lumbar puncture from individuals with signs and/or symptoms of meningitis and/or encephalitis. The following organisms are identified using the FilmArray ME Panel: Bacteria: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis (encapsulated), Streptococcus agalactiae, Streptococcus pneumoniae Viruses: Cytomegalovirus, Enterovirus, Herpes simplex virus 1, Herpes simplex virus 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus, Yeast: Cryptococcus neoformans/gattii. The FilmArray ME Panel is indicated as an aid in the diagnosis of specific agents The DiaSorin Molecular Simplexa VZV Direct assay is intended for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZVinfection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack: The Simplexa VZV Positive Control Pack is intended to be used as a control with the 4 Similarities Item Predicate (K160462) New Device (K190219) of meningitis and/or encephalitis and results are meant to be used in conjunction with other clinical, epidemiological, and laboratory data. Results from the FilmArray ME Panel are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out co-infection with organisms not included in the FilmArray ME Panel. The agent detected may not be the definite cause of the disease. Negative results do not preclude central nervous system central nervous system (CNS) infection. Not all agents of the central nervous system (CNS) infection are detected by this test and sensitivity in clinical use may differ from that described in the package insert. The FilmArray ME Panel is not intended for testing of specimens collected from indwelling central nervous system medical devices. The FilmArray ME Panel is intended to be used in conjunction with standard of care culture for organism recovery, serotyping, and antimicrobial susceptibility testing. Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. Product Code PLO Same Regulation Number 21 CFR 866.3970 – Device Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Same Organism detected Varicella zoster virus Same Measurand DNA from varicella zoster virus Same General Technology Fluorescence based PCR system Same Sample Type CSF Same Automated System Yes Same 5 Table 3: General Device Characteristic Differences Differences Item Predicate (K160462) New Device (K190219) Number of Analytes Multiplex Singleplex Additional Assay targets Detection and identification from different bacteria, fungi and viruses causing signs and symptoms of meningitis and/or encephalitis None Extraction Yes None Amplification Nested PCR reactions One PCR reaction Detection Melting Curve Analysis based on fluorescent double stranded DNA binding dye Detection of fluorescence from fluorophore labeled probes Instrument FilmArray or FilmArray 2.0 system LIAISON MDX K. Standard/Guidance Document Referenced (if applicable): • FDA Guidance: Format for Traditional and Abbreviated 510(k) - Guidance for Industry and FDA Staff, July 07, 2015 • FDA Guidance: Off-The-Shelf Software Use in Medical Devices: Guidance for Industry, FDA Reviewers, and Compliance, September 9, 1999 • FDA Guidance: Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices: Guidance for Industry and FDA Staff, May 11, 2005 • FDA Guidance: General Principles of Software Validation: Guid Measurand:

idK190219_s0_e2000

K190219.txt

type of test

Realtime Polymerase Chain Reaction

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K190219 B. Purpose for Submission: Clearance of device to detect and identify Varizella Zoster Virus DNA in cerebrospinal fluid C. Measurand: Varizella zoster virus DNA D. Type of Test: Realtime Polymerase Chain Reaction E. Applicant: DiaSorin F. Proprietary and Established Names: Simplexa VZV Direct, Simplexa VZV Positive Control Pack G. Regulatory Information: Table 1: Regulatory Information Regulation Section Classification Product Code(s) Panel 21 CFR 866.3970 - Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Class II PLO MI - Microbiology 21 CFR 862.2570 - Instrumentation for clinical multiplex test systems Class II OOI CH - Clinical Chemistry H. Intended Use: 1. Intended use(s): SimplexaVZV Direct: The DiaSorin Molecular Simplexa VZV Direct assay is intended 2 for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZV infection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack. The Simplexa VZV Positive Control Pack is intended to be used as a control with the Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): Rx - For Prescription Use Only For in vitro diagnostic use 4. Special instrument requirements: The Simplexa VZV Direct assay is for use with the LIAISON MDX instrument (with LIAISON MDX Studio Software) I. Device Description: The Simplexa VZV Direct assay is a real-time polymerase chain reaction (PCR) system that enables the direct amplification and detection of VZV DNA from unprocessed cerebral spinal fluid (CSF) specimens without nucleic acid extraction. The system consists of the Simplexa VZV Direct, the Simplexa VZV Positive Control Pack, and the Direct Amplification Disc. The assay is performed on the LIAISON MDX instrument which is controlled by an external computer equipped with LIAISON MDX Studio Software. The Direct Amplification Disk (DAD) consumable, disposable discs into which the PCR reagents and test samples are manually pipetted in, is compartmentalized into eight separate wedges and up to eight separate specimens or controls may be processed on each disc. The disc may be reused until all wedges have been utilized. Each wedge contains sample and reagent input wells, microfluidic channels and laser activated valves to control the fluid flow, and a reaction chamber. In the Simplexa VZV Direct assay, fluorescent probes are used together with corresponding forward and reverse primers to amplify VZV and internal control targets. A well-conserved region of the VZV DNA polymerase gene is targeted to identify VZV DNA in the specimen. An internal control is used to detect PCR failure and/or inhibition. 3 The LIAISON MDX instrument is a rapid real-time Polymerase Chain Reaction (PCR thermocycler used for the identification of nucleic acid from biological specimens. The LIAISON MDX instrument automates amplification, fluorescence-based detection and result interpretation. The LIAISON MDX system was previously referred to as the 3M Integrated Cycler system which was previously cleared via the premarket notification under K102314. Results are reported as “Detected”, Not Detected”, “invalid” (due to failure of the Internal Control or inadequate sample volume) or with a specific error code and may be printed. J. Substantial Equivalence Information: 1. Predicate device name(s): FilmArray Meningitis/Encephalitis (ME) Panel for use with FilmArray and FilmArray 2.0 systems 2. Predicate 510(k) number(s): K160462 3. Comparison with the predicate: Table 2: General Device Characteristic Similarities Similarities Item Predicate (K160462) New Device (K190219) Intended Use The FilmArray Meningitis/ Encephalitis (ME) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray and FilmArray 2.0 systems. The FilmArray ME Panel is capable of simultaneous detection and identification of multiple bacterial, viral, and yeast nucleic acids directly from cerebrospinal fluid (CSF) specimens obtained via lumbar puncture from individuals with signs and/or symptoms of meningitis and/or encephalitis. The following organisms are identified using the FilmArray ME Panel: Bacteria: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis (encapsulated), Streptococcus agalactiae, Streptococcus pneumoniae Viruses: Cytomegalovirus, Enterovirus, Herpes simplex virus 1, Herpes simplex virus 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus, Yeast: Cryptococcus neoformans/gattii. The FilmArray ME Panel is indicated as an aid in the diagnosis of specific agents The DiaSorin Molecular Simplexa VZV Direct assay is intended for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZVinfection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack: The Simplexa VZV Positive Control Pack is intended to be used as a control with the 4 Similarities Item Predicate (K160462) New Device (K190219) of meningitis and/or encephalitis and results are meant to be used in conjunction with other clinical, epidemiological, and laboratory data. Results from the FilmArray ME Panel are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out co-infection with organisms not included in the FilmArray ME Panel. The agent detected may not be the definite cause of the disease. Negative results do not preclude central nervous system central nervous system (CNS) infection. Not all agents of the central nervous system (CNS) infection are detected by this test and sensitivity in clinical use may differ from that described in the package insert. The FilmArray ME Panel is not intended for testing of specimens collected from indwelling central nervous system medical devices. The FilmArray ME Panel is intended to be used in conjunction with standard of care culture for organism recovery, serotyping, and antimicrobial susceptibility testing. Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. Product Code PLO Same Regulation Number 21 CFR 866.3970 – Device Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Same Organism detected Varicella zoster virus Same Measurand DNA from varicella zoster virus Same General Technology Fluorescence based PCR system Same Sample Type CSF Same Automated System Yes Same 5 Table 3: General Device Characteristic Differences Differences Item Predicate (K160462) New Device (K190219) Number of Analytes Multiplex Singleplex Additional Assay targets Detection and identification from different bacteria, fungi and viruses causing signs and symptoms of meningitis and/or encephalitis None Extraction Yes None Amplification Nested PCR reactions One PCR reaction Detection Melting Curve Analysis based on fluorescent double stranded DNA binding dye Detection of fluorescence from fluorophore labeled probes Instrument FilmArray or FilmArray 2.0 system LIAISON MDX K. Standard/Guidance Document Referenced (if applicable): • FDA Guidance: Format for Traditional and Abbreviated 510(k) - Guidance for Industry and FDA Staff, July 07, 2015 • FDA Guidance: Off-The-Shelf Software Use in Medical Devices: Guidance for Industry, FDA Reviewers, and Compliance, September 9, 1999 • FDA Guidance: Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices: Guidance for Industry and FDA Staff, May 11, 2005 • FDA Guidance: General Principles of Software Validation: Guid Type of test:

idK190219_s0_e2000

K190219.txt

predicate device name

FilmArray Meningitis/Encephalitis (ME) Panel for use with FilmArray and FilmArray 2.0 systems

STANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K190219 B. Purpose for Submission: Clearance of device to detect and identify Varizella Zoster Virus DNA in cerebrospinal fluid C. Measurand: Varizella zoster virus DNA D. Type of Test: Realtime Polymerase Chain Reaction E. Applicant: DiaSorin F. Proprietary and Established Names: Simplexa VZV Direct, Simplexa VZV Positive Control Pack G. Regulatory Information: Table 1: Regulatory Information Regulation Section Classification Product Code(s) Panel 21 CFR 866.3970 - Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Class II PLO MI - Microbiology 21 CFR 862.2570 - Instrumentation for clinical multiplex test systems Class II OOI CH - Clinical Chemistry H. Intended Use: 1. Intended use(s): SimplexaVZV Direct: The DiaSorin Molecular Simplexa VZV Direct assay is intended 2 for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZV infection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack. The Simplexa VZV Positive Control Pack is intended to be used as a control with the Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): Rx - For Prescription Use Only For in vitro diagnostic use 4. Special instrument requirements: The Simplexa VZV Direct assay is for use with the LIAISON MDX instrument (with LIAISON MDX Studio Software) I. Device Description: The Simplexa VZV Direct assay is a real-time polymerase chain reaction (PCR) system that enables the direct amplification and detection of VZV DNA from unprocessed cerebral spinal fluid (CSF) specimens without nucleic acid extraction. The system consists of the Simplexa VZV Direct, the Simplexa VZV Positive Control Pack, and the Direct Amplification Disc. The assay is performed on the LIAISON MDX instrument which is controlled by an external computer equipped with LIAISON MDX Studio Software. The Direct Amplification Disk (DAD) consumable, disposable discs into which the PCR reagents and test samples are manually pipetted in, is compartmentalized into eight separate wedges and up to eight separate specimens or controls may be processed on each disc. The disc may be reused until all wedges have been utilized. Each wedge contains sample and reagent input wells, microfluidic channels and laser activated valves to control the fluid flow, and a reaction chamber. In the Simplexa VZV Direct assay, fluorescent probes are used together with corresponding forward and reverse primers to amplify VZV and internal control targets. A well-conserved region of the VZV DNA polymerase gene is targeted to identify VZV DNA in the specimen. An internal control is used to detect PCR failure and/or inhibition. 3 The LIAISON MDX instrument is a rapid real-time Polymerase Chain Reaction (PCR thermocycler used for the identification of nucleic acid from biological specimens. The LIAISON MDX instrument automates amplification, fluorescence-based detection and result interpretation. The LIAISON MDX system was previously referred to as the 3M Integrated Cycler system which was previously cleared via the premarket notification under K102314. Results are reported as “Detected”, Not Detected”, “invalid” (due to failure of the Internal Control or inadequate sample volume) or with a specific error code and may be printed. J. Substantial Equivalence Information: 1. Predicate device name(s): FilmArray Meningitis/Encephalitis (ME) Panel for use with FilmArray and FilmArray 2.0 systems 2. Predicate 510(k) number(s): K160462 3. Comparison with the predicate: Table 2: General Device Characteristic Similarities Similarities Item Predicate (K160462) New Device (K190219) Intended Use The FilmArray Meningitis/ Encephalitis (ME) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray and FilmArray 2.0 systems. The FilmArray ME Panel is capable of simultaneous detection and identification of multiple bacterial, viral, and yeast nucleic acids directly from cerebrospinal fluid (CSF) specimens obtained via lumbar puncture from individuals with signs and/or symptoms of meningitis and/or encephalitis. The following organisms are identified using the FilmArray ME Panel: Bacteria: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis (encapsulated), Streptococcus agalactiae, Streptococcus pneumoniae Viruses: Cytomegalovirus, Enterovirus, Herpes simplex virus 1, Herpes simplex virus 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus, Yeast: Cryptococcus neoformans/gattii. The FilmArray ME Panel is indicated as an aid in the diagnosis of specific agents The DiaSorin Molecular Simplexa VZV Direct assay is intended for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZVinfection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack: The Simplexa VZV Positive Control Pack is intended to be used as a control with the 4 Similarities Item Predicate (K160462) New Device (K190219) of meningitis and/or encephalitis and results are meant to be used in conjunction with other clinical, epidemiological, and laboratory data. Results from the FilmArray ME Panel are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out co-infection with organisms not included in the FilmArray ME Panel. The agent detected may not be the definite cause of the disease. Negative results do not preclude central nervous system central nervous system (CNS) infection. Not all agents of the central nervous system (CNS) infection are detected by this test and sensitivity in clinical use may differ from that described in the package insert. The FilmArray ME Panel is not intended for testing of specimens collected from indwelling central nervous system medical devices. The FilmArray ME Panel is intended to be used in conjunction with standard of care culture for organism recovery, serotyping, and antimicrobial susceptibility testing. Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. Product Code PLO Same Regulation Number 21 CFR 866.3970 – Device Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Same Organism detected Varicella zoster virus Same Measurand DNA from varicella zoster virus Same General Technology Fluorescence based PCR system Same Sample Type CSF Same Automated System Yes Same 5 Table 3: General Device Characteristic Differences Differences Item Predicate (K160462) New Device (K190219) Number of Analytes Multiplex Singleplex Additional Assay targets Detection and identification from different bacteria, fungi and viruses causing signs and symptoms of meningitis and/or encephalitis None Extraction Yes None Amplification Nested PCR reactions One PCR reaction Detection Melting Curve Analysis based on fluorescent double stranded DNA binding dye Detection of fluorescence from fluorophore labeled probes Instrument FilmArray or FilmArray 2.0 system LIAISON MDX K. Standard/Guidance Document Referenced (if applicable): • FDA Guidance: Format for Traditional and Abbreviated 510(k) - Guidance for Industry and FDA Staff, July 07, 2015 • FDA Guidance: Off-The-Shelf Software Use in Medical Devices: Guidance for Industry, FDA Reviewers, and Compliance, September 9, 1999 • FDA Guidance: Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices: Guidance for Industry and FDA Staff, May 11, 2005 • FDA Guidance: General Principles of Software Validation: Guid Predicate device name:

idK190219_s0_e2000

K190219.txt

applicant

DiaSorin

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K190219 B. Purpose for Submission: Clearance of device to detect and identify Varizella Zoster Virus DNA in cerebrospinal fluid C. Measurand: Varizella zoster virus DNA D. Type of Test: Realtime Polymerase Chain Reaction E. Applicant: DiaSorin F. Proprietary and Established Names: Simplexa VZV Direct, Simplexa VZV Positive Control Pack G. Regulatory Information: Table 1: Regulatory Information Regulation Section Classification Product Code(s) Panel 21 CFR 866.3970 - Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Class II PLO MI - Microbiology 21 CFR 862.2570 - Instrumentation for clinical multiplex test systems Class II OOI CH - Clinical Chemistry H. Intended Use: 1. Intended use(s): SimplexaVZV Direct: The DiaSorin Molecular Simplexa VZV Direct assay is intended 2 for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZV infection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack. The Simplexa VZV Positive Control Pack is intended to be used as a control with the Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): Rx - For Prescription Use Only For in vitro diagnostic use 4. Special instrument requirements: The Simplexa VZV Direct assay is for use with the LIAISON MDX instrument (with LIAISON MDX Studio Software) I. Device Description: The Simplexa VZV Direct assay is a real-time polymerase chain reaction (PCR) system that enables the direct amplification and detection of VZV DNA from unprocessed cerebral spinal fluid (CSF) specimens without nucleic acid extraction. The system consists of the Simplexa VZV Direct, the Simplexa VZV Positive Control Pack, and the Direct Amplification Disc. The assay is performed on the LIAISON MDX instrument which is controlled by an external computer equipped with LIAISON MDX Studio Software. The Direct Amplification Disk (DAD) consumable, disposable discs into which the PCR reagents and test samples are manually pipetted in, is compartmentalized into eight separate wedges and up to eight separate specimens or controls may be processed on each disc. The disc may be reused until all wedges have been utilized. Each wedge contains sample and reagent input wells, microfluidic channels and laser activated valves to control the fluid flow, and a reaction chamber. In the Simplexa VZV Direct assay, fluorescent probes are used together with corresponding forward and reverse primers to amplify VZV and internal control targets. A well-conserved region of the VZV DNA polymerase gene is targeted to identify VZV DNA in the specimen. An internal control is used to detect PCR failure and/or inhibition. 3 The LIAISON MDX instrument is a rapid real-time Polymerase Chain Reaction (PCR thermocycler used for the identification of nucleic acid from biological specimens. The LIAISON MDX instrument automates amplification, fluorescence-based detection and result interpretation. The LIAISON MDX system was previously referred to as the 3M Integrated Cycler system which was previously cleared via the premarket notification under K102314. Results are reported as “Detected”, Not Detected”, “invalid” (due to failure of the Internal Control or inadequate sample volume) or with a specific error code and may be printed. J. Substantial Equivalence Information: 1. Predicate device name(s): FilmArray Meningitis/Encephalitis (ME) Panel for use with FilmArray and FilmArray 2.0 systems 2. Predicate 510(k) number(s): K160462 3. Comparison with the predicate: Table 2: General Device Characteristic Similarities Similarities Item Predicate (K160462) New Device (K190219) Intended Use The FilmArray Meningitis/ Encephalitis (ME) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray and FilmArray 2.0 systems. The FilmArray ME Panel is capable of simultaneous detection and identification of multiple bacterial, viral, and yeast nucleic acids directly from cerebrospinal fluid (CSF) specimens obtained via lumbar puncture from individuals with signs and/or symptoms of meningitis and/or encephalitis. The following organisms are identified using the FilmArray ME Panel: Bacteria: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis (encapsulated), Streptococcus agalactiae, Streptococcus pneumoniae Viruses: Cytomegalovirus, Enterovirus, Herpes simplex virus 1, Herpes simplex virus 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus, Yeast: Cryptococcus neoformans/gattii. The FilmArray ME Panel is indicated as an aid in the diagnosis of specific agents The DiaSorin Molecular Simplexa VZV Direct assay is intended for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZVinfection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack: The Simplexa VZV Positive Control Pack is intended to be used as a control with the 4 Similarities Item Predicate (K160462) New Device (K190219) of meningitis and/or encephalitis and results are meant to be used in conjunction with other clinical, epidemiological, and laboratory data. Results from the FilmArray ME Panel are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out co-infection with organisms not included in the FilmArray ME Panel. The agent detected may not be the definite cause of the disease. Negative results do not preclude central nervous system central nervous system (CNS) infection. Not all agents of the central nervous system (CNS) infection are detected by this test and sensitivity in clinical use may differ from that described in the package insert. The FilmArray ME Panel is not intended for testing of specimens collected from indwelling central nervous system medical devices. The FilmArray ME Panel is intended to be used in conjunction with standard of care culture for organism recovery, serotyping, and antimicrobial susceptibility testing. Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. Product Code PLO Same Regulation Number 21 CFR 866.3970 – Device Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Same Organism detected Varicella zoster virus Same Measurand DNA from varicella zoster virus Same General Technology Fluorescence based PCR system Same Sample Type CSF Same Automated System Yes Same 5 Table 3: General Device Characteristic Differences Differences Item Predicate (K160462) New Device (K190219) Number of Analytes Multiplex Singleplex Additional Assay targets Detection and identification from different bacteria, fungi and viruses causing signs and symptoms of meningitis and/or encephalitis None Extraction Yes None Amplification Nested PCR reactions One PCR reaction Detection Melting Curve Analysis based on fluorescent double stranded DNA binding dye Detection of fluorescence from fluorophore labeled probes Instrument FilmArray or FilmArray 2.0 system LIAISON MDX K. Standard/Guidance Document Referenced (if applicable): • FDA Guidance: Format for Traditional and Abbreviated 510(k) - Guidance for Industry and FDA Staff, July 07, 2015 • FDA Guidance: Off-The-Shelf Software Use in Medical Devices: Guidance for Industry, FDA Reviewers, and Compliance, September 9, 1999 • FDA Guidance: Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices: Guidance for Industry and FDA Staff, May 11, 2005 • FDA Guidance: General Principles of Software Validation: Guid Applicant:

idK190219_s0_e2000

K190219.txt

proprietary and established names

Simplexa VZV Direct, Simplexa VZV Positive Control Pack

IAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K190219 B. Purpose for Submission: Clearance of device to detect and identify Varizella Zoster Virus DNA in cerebrospinal fluid C. Measurand: Varizella zoster virus DNA D. Type of Test: Realtime Polymerase Chain Reaction E. Applicant: DiaSorin F. Proprietary and Established Names: Simplexa VZV Direct, Simplexa VZV Positive Control Pack G. Regulatory Information: Table 1: Regulatory Information Regulation Section Classification Product Code(s) Panel 21 CFR 866.3970 - Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Class II PLO MI - Microbiology 21 CFR 862.2570 - Instrumentation for clinical multiplex test systems Class II OOI CH - Clinical Chemistry H. Intended Use: 1. Intended use(s): SimplexaVZV Direct: The DiaSorin Molecular Simplexa VZV Direct assay is intended 2 for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZV infection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack. The Simplexa VZV Positive Control Pack is intended to be used as a control with the Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): Rx - For Prescription Use Only For in vitro diagnostic use 4. Special instrument requirements: The Simplexa VZV Direct assay is for use with the LIAISON MDX instrument (with LIAISON MDX Studio Software) I. Device Description: The Simplexa VZV Direct assay is a real-time polymerase chain reaction (PCR) system that enables the direct amplification and detection of VZV DNA from unprocessed cerebral spinal fluid (CSF) specimens without nucleic acid extraction. The system consists of the Simplexa VZV Direct, the Simplexa VZV Positive Control Pack, and the Direct Amplification Disc. The assay is performed on the LIAISON MDX instrument which is controlled by an external computer equipped with LIAISON MDX Studio Software. The Direct Amplification Disk (DAD) consumable, disposable discs into which the PCR reagents and test samples are manually pipetted in, is compartmentalized into eight separate wedges and up to eight separate specimens or controls may be processed on each disc. The disc may be reused until all wedges have been utilized. Each wedge contains sample and reagent input wells, microfluidic channels and laser activated valves to control the fluid flow, and a reaction chamber. In the Simplexa VZV Direct assay, fluorescent probes are used together with corresponding forward and reverse primers to amplify VZV and internal control targets. A well-conserved region of the VZV DNA polymerase gene is targeted to identify VZV DNA in the specimen. An internal control is used to detect PCR failure and/or inhibition. 3 The LIAISON MDX instrument is a rapid real-time Polymerase Chain Reaction (PCR thermocycler used for the identification of nucleic acid from biological specimens. The LIAISON MDX instrument automates amplification, fluorescence-based detection and result interpretation. The LIAISON MDX system was previously referred to as the 3M Integrated Cycler system which was previously cleared via the premarket notification under K102314. Results are reported as “Detected”, Not Detected”, “invalid” (due to failure of the Internal Control or inadequate sample volume) or with a specific error code and may be printed. J. Substantial Equivalence Information: 1. Predicate device name(s): FilmArray Meningitis/Encephalitis (ME) Panel for use with FilmArray and FilmArray 2.0 systems 2. Predicate 510(k) number(s): K160462 3. Comparison with the predicate: Table 2: General Device Characteristic Similarities Similarities Item Predicate (K160462) New Device (K190219) Intended Use The FilmArray Meningitis/ Encephalitis (ME) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray and FilmArray 2.0 systems. The FilmArray ME Panel is capable of simultaneous detection and identification of multiple bacterial, viral, and yeast nucleic acids directly from cerebrospinal fluid (CSF) specimens obtained via lumbar puncture from individuals with signs and/or symptoms of meningitis and/or encephalitis. The following organisms are identified using the FilmArray ME Panel: Bacteria: Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis (encapsulated), Streptococcus agalactiae, Streptococcus pneumoniae Viruses: Cytomegalovirus, Enterovirus, Herpes simplex virus 1, Herpes simplex virus 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus, Yeast: Cryptococcus neoformans/gattii. The FilmArray ME Panel is indicated as an aid in the diagnosis of specific agents The DiaSorin Molecular Simplexa VZV Direct assay is intended for use on the LIAISON MDX instrument for the qualitative detection of varicella-zoster virus (VZV) DNA in cerebrospinal fluid (CSF) from patients with signs and/or symptoms of meningitis and/or encephalitis. This test is intended as an aid in the diagnosis of VZV infections of the central nervous system (CNS). Negative results do not preclude VZVinfection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use as a donor screening test. The assay is for professional use only. Simplexa VZV Positive Control Pack: The Simplexa VZV Positive Control Pack is intended to be used as a control with the 4 Similarities Item Predicate (K160462) New Device (K190219) of meningitis and/or encephalitis and results are meant to be used in conjunction with other clinical, epidemiological, and laboratory data. Results from the FilmArray ME Panel are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out co-infection with organisms not included in the FilmArray ME Panel. The agent detected may not be the definite cause of the disease. Negative results do not preclude central nervous system central nervous system (CNS) infection. Not all agents of the central nervous system (CNS) infection are detected by this test and sensitivity in clinical use may differ from that described in the package insert. The FilmArray ME Panel is not intended for testing of specimens collected from indwelling central nervous system medical devices. The FilmArray ME Panel is intended to be used in conjunction with standard of care culture for organism recovery, serotyping, and antimicrobial susceptibility testing. Simplexa VZV Direct kit. This control is not intended for use with other assays or systems. Product Code PLO Same Regulation Number 21 CFR 866.3970 – Device Device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid Same Organism detected Varicella zoster virus Same Measurand DNA from varicella zoster virus Same General Technology Fluorescence based PCR system Same Sample Type CSF Same Automated System Yes Same 5 Table 3: General Device Characteristic Differences Differences Item Predicate (K160462) New Device (K190219) Number of Analytes Multiplex Singleplex Additional Assay targets Detection and identification from different bacteria, fungi and viruses causing signs and symptoms of meningitis and/or encephalitis None Extraction Yes None Amplification Nested PCR reactions One PCR reaction Detection Melting Curve Analysis based on fluorescent double stranded DNA binding dye Detection of fluorescence from fluorophore labeled probes Instrument FilmArray or FilmArray 2.0 system LIAISON MDX K. Standard/Guidance Document Referenced (if applicable): • FDA Guidance: Format for Traditional and Abbreviated 510(k) - Guidance for Industry and FDA Staff, July 07, 2015 • FDA Guidance: Off-The-Shelf Software Use in Medical Devices: Guidance for Industry, FDA Reviewers, and Compliance, September 9, 1999 • FDA Guidance: Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices: Guidance for Industry and FDA Staff, May 11, 2005 • FDA Guidance: General Principles of Software Validation: Guid Proprietary and established names:

idK190219_s12000_e14000

K190219.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable.

tested at seven clinical sites in a blinded manner and randomized with VZV negative samples. The samples were stored at 2-8 °C for up to 7 days post collection and at <-70 °C thereafter. Simplexa VZV Direct test results for contrived samples were compared to the same Composite Reference Method described for the prospective clinical study above. The contrived sample study demonstrated a positive percent agreement of 100% (120/120) with a 95% Confidence Interval of 96.9-100.0%. The results of the Clinical Study stratified by the age of the subjects is shown in Table 17. Table 17: Simplexa VZV Direct Clinical Study Results Stratified Patient Age and Gender Female Male Total Age N Detected Not Detected N Detected Not Detected N Detected Not Detected Birth to 1 month 5 0.0% (0/5) 100.0% (5/5) 6 0.0% (0/6) 100.0% (6/6) 11 0.0% (0/11) 100.0% (11/11) >1 month to 2 years 6 0.0% (0/6) 100.0% (6/6) 11 0.0% (0/11) 100.0% (11/11) 17 0.0% (0/17) 100.0% (17/17) >2 years to 12 years 8 0.0% (0/8) 100.0% (8/8) 6 0.0% (0/6) 100.0% (6/6) 14 0.0% (0/14) 100.0% (14/14) >12 years to 21 years 21 0.0% (0/21) 100.0% (21/21) 13 7.7% (1/13) 92.3% (12/13) 34 2.9% (1/34) 97.1% (33/34) >21 years to 60 years 191 1.6% (3/191) 98.4% (188/191) 155 3.2% (5/155) 96.8% (150/155) 346 2.3% (8/346) 97.7% (338/346) >60 years 99 2.0% (2/99) 98.0% (97/99) 116 2.6% (3/116) 97.4% (113/116) 215 2.3% (5/215) 97.7% (210/215) Total 330 1.5% (5/330) 98.5% (325/330) 307 2.9% (9/307) 97.1% (298/307) 637 2.2% (14/637) 97.8% (623/637) 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: Not applicable N. Instrument Name: Liason MDX instrument O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, 20 or mobile device? Yes ____x____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ____x____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ___x_____ or No ________ 3. Specimen Identification: Specimens are identified by scanning a bar code label or by typing in an appropriate identifier. 4. Specimen Sampling and Handling: The Simplexa VZV Assay is for the use with CSF. Samples can be stored refrigerated for up to 72 hours, and can be stored freezed for up to 30 days. 5. Calibration: End-user calibration for for the LIASON MDX instrument is not necessary. Calibration of the optical modules (excitation and emission gain settings) is performed during the manufacturing process. And the values are stored in the instrument firmware. 6. Quality Control: The assay does not require calibration. The assay contains an internal control for PCR function. DiaSorin Molecular offers optional external QC materials that are intended for use with the assay. Controls are packaged in single use aliquots and stored frozen, once thawed the controls are stable for 30 minutes at laboratory temperature. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Not applicable. Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable. 21 R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK190219_s12000_e14000

K190219.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

ples were tested at seven clinical sites in a blinded manner and randomized with VZV negative samples. The samples were stored at 2-8 °C for up to 7 days post collection and at <-70 °C thereafter. Simplexa VZV Direct test results for contrived samples were compared to the same Composite Reference Method described for the prospective clinical study above. The contrived sample study demonstrated a positive percent agreement of 100% (120/120) with a 95% Confidence Interval of 96.9-100.0%. The results of the Clinical Study stratified by the age of the subjects is shown in Table 17. Table 17: Simplexa VZV Direct Clinical Study Results Stratified Patient Age and Gender Female Male Total Age N Detected Not Detected N Detected Not Detected N Detected Not Detected Birth to 1 month 5 0.0% (0/5) 100.0% (5/5) 6 0.0% (0/6) 100.0% (6/6) 11 0.0% (0/11) 100.0% (11/11) >1 month to 2 years 6 0.0% (0/6) 100.0% (6/6) 11 0.0% (0/11) 100.0% (11/11) 17 0.0% (0/17) 100.0% (17/17) >2 years to 12 years 8 0.0% (0/8) 100.0% (8/8) 6 0.0% (0/6) 100.0% (6/6) 14 0.0% (0/14) 100.0% (14/14) >12 years to 21 years 21 0.0% (0/21) 100.0% (21/21) 13 7.7% (1/13) 92.3% (12/13) 34 2.9% (1/34) 97.1% (33/34) >21 years to 60 years 191 1.6% (3/191) 98.4% (188/191) 155 3.2% (5/155) 96.8% (150/155) 346 2.3% (8/346) 97.7% (338/346) >60 years 99 2.0% (2/99) 98.0% (97/99) 116 2.6% (3/116) 97.4% (113/116) 215 2.3% (5/215) 97.7% (210/215) Total 330 1.5% (5/330) 98.5% (325/330) 307 2.9% (9/307) 97.1% (298/307) 637 2.2% (14/637) 97.8% (623/637) 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: Not applicable N. Instrument Name: Liason MDX instrument O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, 20 or mobile device? Yes ____x____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ____x____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ___x_____ or No ________ 3. Specimen Identification: Specimens are identified by scanning a bar code label or by typing in an appropriate identifier. 4. Specimen Sampling and Handling: The Simplexa VZV Assay is for the use with CSF. Samples can be stored refrigerated for up to 72 hours, and can be stored freezed for up to 30 days. 5. Calibration: End-user calibration for for the LIASON MDX instrument is not necessary. Calibration of the optical modules (excitation and emission gain settings) is performed during the manufacturing process. And the values are stored in the instrument firmware. 6. Quality Control: The assay does not require calibration. The assay contains an internal control for PCR function. DiaSorin Molecular offers optional external QC materials that are intended for use with the assay. Controls are packaged in single use aliquots and stored frozen, once thawed the controls are stable for 30 minutes at laboratory temperature. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Not applicable. Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable. 21 R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK190219_s12000_e14000

K190219.txt

applicant

DiaSorin

were tested at seven clinical sites in a blinded manner and randomized with VZV negative samples. The samples were stored at 2-8 °C for up to 7 days post collection and at <-70 °C thereafter. Simplexa VZV Direct test results for contrived samples were compared to the same Composite Reference Method described for the prospective clinical study above. The contrived sample study demonstrated a positive percent agreement of 100% (120/120) with a 95% Confidence Interval of 96.9-100.0%. The results of the Clinical Study stratified by the age of the subjects is shown in Table 17. Table 17: Simplexa VZV Direct Clinical Study Results Stratified Patient Age and Gender Female Male Total Age N Detected Not Detected N Detected Not Detected N Detected Not Detected Birth to 1 month 5 0.0% (0/5) 100.0% (5/5) 6 0.0% (0/6) 100.0% (6/6) 11 0.0% (0/11) 100.0% (11/11) >1 month to 2 years 6 0.0% (0/6) 100.0% (6/6) 11 0.0% (0/11) 100.0% (11/11) 17 0.0% (0/17) 100.0% (17/17) >2 years to 12 years 8 0.0% (0/8) 100.0% (8/8) 6 0.0% (0/6) 100.0% (6/6) 14 0.0% (0/14) 100.0% (14/14) >12 years to 21 years 21 0.0% (0/21) 100.0% (21/21) 13 7.7% (1/13) 92.3% (12/13) 34 2.9% (1/34) 97.1% (33/34) >21 years to 60 years 191 1.6% (3/191) 98.4% (188/191) 155 3.2% (5/155) 96.8% (150/155) 346 2.3% (8/346) 97.7% (338/346) >60 years 99 2.0% (2/99) 98.0% (97/99) 116 2.6% (3/116) 97.4% (113/116) 215 2.3% (5/215) 97.7% (210/215) Total 330 1.5% (5/330) 98.5% (325/330) 307 2.9% (9/307) 97.1% (298/307) 637 2.2% (14/637) 97.8% (623/637) 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: Not applicable N. Instrument Name: Liason MDX instrument O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, 20 or mobile device? Yes ____x____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ____x____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ___x_____ or No ________ 3. Specimen Identification: Specimens are identified by scanning a bar code label or by typing in an appropriate identifier. 4. Specimen Sampling and Handling: The Simplexa VZV Assay is for the use with CSF. Samples can be stored refrigerated for up to 72 hours, and can be stored freezed for up to 30 days. 5. Calibration: End-user calibration for for the LIASON MDX instrument is not necessary. Calibration of the optical modules (excitation and emission gain settings) is performed during the manufacturing process. And the values are stored in the instrument firmware. 6. Quality Control: The assay does not require calibration. The assay contains an internal control for PCR function. DiaSorin Molecular offers optional external QC materials that are intended for use with the assay. Controls are packaged in single use aliquots and stored frozen, once thawed the controls are stable for 30 minutes at laboratory temperature. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Not applicable. Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable. 21 R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Applicant:

idK150526_s0_e2000

K150526.txt

purpose for submission

New Device

ANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: k150526 B. Purpose for Submission: New Device C. Measurand: IgG4 subclass Antibody D. Type of Test: Quantitative, turbidimetric E. Applicant: The Binding Site Group, Ltd. F. Proprietary and Established Names: Optilite® IgG4 Kit G. Regulatory Information: 1. Regulation section: 21 CFR §866.5510 - Immunoglobulins A, G, M, D, E Immunological Test System 2. Classification: Class II 3. Product code: CFN - Method, Nephelometric, Immunoglobulins (G, A, M) 4. Panel: Immunology (82) H. Intended Use: 1. Intended use(s): 2 The Optilite IgG4 kit is intended for the quantitative in vitro measurement of IgG4 in serum using the Binding Site Optilite analyser. Measurement of this immunoglobulin is an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test result should be used in conjunction with other laboratory and clinical findings. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Optilite analyzer (k141100) I. Device Description: The device consists of the following: polyclonal monospecific sheep anti-IgG4 antisera coated onto polystyrene latex in liquid form in the presence of preservatives; IgG4 calibrator and Controls (Low, High and Elevated levels) in stabilized liquid form with preservatives; and Reaction Buffer (with 0.099% sodium azide as preservative). J. Substantial Equivalence Information: 1. Predicate device names: Binding Site Human IgG and IgG subclass (IgG1, IgG2, IgG3, IgG4) liquid reagent kits for use on the SPAplus 2. Predicate 510(k) number: k072889 3. Comparison with predicate: 3 Similarities Item Device Predicate Assay type Quantitative Same Detection Method Turbidimetric immunoassay Same Sample matrix Serum Same Antibody Polyclonal monospecific sheep anti-human IgG4 (F(ab)2) fragment bound to latex particles Same Traceability Standardized against ERM- DA470k European Reference Material (previously CRM470) Same Open vial stability 3 months Same On board vial stability 30 days Same Reference Ranges (mg/L) (95% percentile range) Adults: 39.2–864 Same Differences Item Device Predicate Intended Use Quantitative measurement of IgG4 in serum Quantitative measurement of Human IgG and IgG subclasses IgG1, IgG2, IgG3, IgG4 in serum Calibrator One Optilite IgG4 Calibrator One calibrator for each: IgG, IgG1, IgG2, IgG3, IgG4 Controls Low, High and Elevated levels, liquid, ready-to-use Low and high IgG and IgG subclasses: IgG1, IgG2, IgG3, IgG4 Instruments Optilite® Analyzer SPAPLUS™ Analyser Measuring range (mg/L) 2.96–216 (1+1 dilution) 37–2700 (1+24 dilution) 179.1–13068 (1+120 dilution) 888–64800 (1+599 dilution) 3–85 (1:2 dilution) 30–850 (1:10 dilution) 120–3400 (1:40 dilution) K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation CLSI C28-A3: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed, a portion of the light is transmitted and focused onto a photo iodide by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: The within-run, between-run, between-day, between-lot and between-instrument precision were determined by testing ten serum samples over 21 days with two runs per day and two replicates per run on three different reagent lots on four analysers. Results are summarized below. Precision Summary Sample Mean (mg/L) Within run Between run Between day Between lot Between instrument Total SD CV% SD CV% SD CV% SD CV% SD CV% SD CV% 1 23.6 0.9 3.6 0.0 0.0 0.9 3.5 0.2 1.0 0.8 3.3 1.2 5.1 2 31.2 0.5 1.4 0.8 2.5 0.9 2.9 0.7 2.3 0.3 0.9 1.3 4.1 3 48.8 0.5 1.0 1.4 2.8 2.1 4.1 1.0 2.0 0.6 1.2 2.5 5.1 4 53.9 2.9 4.8 2.6 4.4 5.2 8.7 3.8 7.1 0.5 1.0 6.5 10.9 5 124.0 1.9 1.5 2.2 1.7 5.7 4.3 0.7 0.5 3.7 3.0 6.5 4.9 6 611.6 9.1 1.4 12.0 1.9 21.2 3.4 7.3 1.2 11.7 1.9 26.0 4.1 7 1148.3 16.4 1.4 25.8 2.1 42.0 3.5 14.3 1.2 28.7 2.5 51.9 4.3 8 1473.6 20.8 1.3 27.8 1.8 51.7 3.3 11.2 0.8 38.7 2.6 62.2 4.0 5 Precision Summary 9 2152.5 23.0 1.1 77.7 3.6 40.1 1.9 39.5 1.8 22.7 1.1 90.4 4.2 10 4371.3 88.3 1.9 86.7 1.8 206.2 4.4 85.4 2.0 123.3 2.8 240.5 5.1 b. Linearity/assay reportable range: A linearity study was performed following CLSI document Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The linearity of this assay has been confirmed using serially diluted serum samples to cover the range 2.8–240.8 mg/L for Optilite analyzer dilution 1+1; 34.5–3010.4 mg/L for Optilite analyzer dilution 1+24; 169.4–14568.4 mg/L for Optilite analyzer dilution 1+120 and 828.0–72249.6 mg/L for Optilite analyzer dilution 1+ 599 with deviation from linearity ≤ 10%. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: An Internal Reference standard (IR) was assigned by comparison with the European Reference Material ERM-DA470k. Value assignment from total IgG to IgG4 was performed following the protocol outlined in Williams et al. 1. Stability: A real-time stability study of unopened kits was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 3 months and 6.5 months. Data support a shelf life claim of 6 months at 2–8o C. Real time stability study is on-going. Open-vial stability was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 1, 2, and 3 months. Data support the open vial stability claim of 3 months at 2–8o C. On-board stability was performed on three lots of Optilite IgG4 kit with testing time intervals at 0, 8, 15, 21, and 32 days. Data support the on-board stability claim of 30 days at 8–12o C, provided that the power is left switched on as stated in the product insert. All stability results were within the sponsor’s acceptance criteria. d. Detection limit: The analytical Purpose for submission:

idK150526_s0_e2000

K150526.txt

measurand

IgG4 subclass Antibody

ANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: k150526 B. Purpose for Submission: New Device C. Measurand: IgG4 subclass Antibody D. Type of Test: Quantitative, turbidimetric E. Applicant: The Binding Site Group, Ltd. F. Proprietary and Established Names: Optilite® IgG4 Kit G. Regulatory Information: 1. Regulation section: 21 CFR §866.5510 - Immunoglobulins A, G, M, D, E Immunological Test System 2. Classification: Class II 3. Product code: CFN - Method, Nephelometric, Immunoglobulins (G, A, M) 4. Panel: Immunology (82) H. Intended Use: 1. Intended use(s): 2 The Optilite IgG4 kit is intended for the quantitative in vitro measurement of IgG4 in serum using the Binding Site Optilite analyser. Measurement of this immunoglobulin is an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test result should be used in conjunction with other laboratory and clinical findings. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Optilite analyzer (k141100) I. Device Description: The device consists of the following: polyclonal monospecific sheep anti-IgG4 antisera coated onto polystyrene latex in liquid form in the presence of preservatives; IgG4 calibrator and Controls (Low, High and Elevated levels) in stabilized liquid form with preservatives; and Reaction Buffer (with 0.099% sodium azide as preservative). J. Substantial Equivalence Information: 1. Predicate device names: Binding Site Human IgG and IgG subclass (IgG1, IgG2, IgG3, IgG4) liquid reagent kits for use on the SPAplus 2. Predicate 510(k) number: k072889 3. Comparison with predicate: 3 Similarities Item Device Predicate Assay type Quantitative Same Detection Method Turbidimetric immunoassay Same Sample matrix Serum Same Antibody Polyclonal monospecific sheep anti-human IgG4 (F(ab)2) fragment bound to latex particles Same Traceability Standardized against ERM- DA470k European Reference Material (previously CRM470) Same Open vial stability 3 months Same On board vial stability 30 days Same Reference Ranges (mg/L) (95% percentile range) Adults: 39.2–864 Same Differences Item Device Predicate Intended Use Quantitative measurement of IgG4 in serum Quantitative measurement of Human IgG and IgG subclasses IgG1, IgG2, IgG3, IgG4 in serum Calibrator One Optilite IgG4 Calibrator One calibrator for each: IgG, IgG1, IgG2, IgG3, IgG4 Controls Low, High and Elevated levels, liquid, ready-to-use Low and high IgG and IgG subclasses: IgG1, IgG2, IgG3, IgG4 Instruments Optilite® Analyzer SPAPLUS™ Analyser Measuring range (mg/L) 2.96–216 (1+1 dilution) 37–2700 (1+24 dilution) 179.1–13068 (1+120 dilution) 888–64800 (1+599 dilution) 3–85 (1:2 dilution) 30–850 (1:10 dilution) 120–3400 (1:40 dilution) K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation CLSI C28-A3: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed, a portion of the light is transmitted and focused onto a photo iodide by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: The within-run, between-run, between-day, between-lot and between-instrument precision were determined by testing ten serum samples over 21 days with two runs per day and two replicates per run on three different reagent lots on four analysers. Results are summarized below. Precision Summary Sample Mean (mg/L) Within run Between run Between day Between lot Between instrument Total SD CV% SD CV% SD CV% SD CV% SD CV% SD CV% 1 23.6 0.9 3.6 0.0 0.0 0.9 3.5 0.2 1.0 0.8 3.3 1.2 5.1 2 31.2 0.5 1.4 0.8 2.5 0.9 2.9 0.7 2.3 0.3 0.9 1.3 4.1 3 48.8 0.5 1.0 1.4 2.8 2.1 4.1 1.0 2.0 0.6 1.2 2.5 5.1 4 53.9 2.9 4.8 2.6 4.4 5.2 8.7 3.8 7.1 0.5 1.0 6.5 10.9 5 124.0 1.9 1.5 2.2 1.7 5.7 4.3 0.7 0.5 3.7 3.0 6.5 4.9 6 611.6 9.1 1.4 12.0 1.9 21.2 3.4 7.3 1.2 11.7 1.9 26.0 4.1 7 1148.3 16.4 1.4 25.8 2.1 42.0 3.5 14.3 1.2 28.7 2.5 51.9 4.3 8 1473.6 20.8 1.3 27.8 1.8 51.7 3.3 11.2 0.8 38.7 2.6 62.2 4.0 5 Precision Summary 9 2152.5 23.0 1.1 77.7 3.6 40.1 1.9 39.5 1.8 22.7 1.1 90.4 4.2 10 4371.3 88.3 1.9 86.7 1.8 206.2 4.4 85.4 2.0 123.3 2.8 240.5 5.1 b. Linearity/assay reportable range: A linearity study was performed following CLSI document Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The linearity of this assay has been confirmed using serially diluted serum samples to cover the range 2.8–240.8 mg/L for Optilite analyzer dilution 1+1; 34.5–3010.4 mg/L for Optilite analyzer dilution 1+24; 169.4–14568.4 mg/L for Optilite analyzer dilution 1+120 and 828.0–72249.6 mg/L for Optilite analyzer dilution 1+ 599 with deviation from linearity ≤ 10%. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: An Internal Reference standard (IR) was assigned by comparison with the European Reference Material ERM-DA470k. Value assignment from total IgG to IgG4 was performed following the protocol outlined in Williams et al. 1. Stability: A real-time stability study of unopened kits was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 3 months and 6.5 months. Data support a shelf life claim of 6 months at 2–8o C. Real time stability study is on-going. Open-vial stability was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 1, 2, and 3 months. Data support the open vial stability claim of 3 months at 2–8o C. On-board stability was performed on three lots of Optilite IgG4 kit with testing time intervals at 0, 8, 15, 21, and 32 days. Data support the on-board stability claim of 30 days at 8–12o C, provided that the power is left switched on as stated in the product insert. All stability results were within the sponsor’s acceptance criteria. d. Detection limit: The analytical Measurand:

idK150526_s0_e2000

K150526.txt

type of test

Quantitative, turbidimetric

STANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: k150526 B. Purpose for Submission: New Device C. Measurand: IgG4 subclass Antibody D. Type of Test: Quantitative, turbidimetric E. Applicant: The Binding Site Group, Ltd. F. Proprietary and Established Names: Optilite® IgG4 Kit G. Regulatory Information: 1. Regulation section: 21 CFR §866.5510 - Immunoglobulins A, G, M, D, E Immunological Test System 2. Classification: Class II 3. Product code: CFN - Method, Nephelometric, Immunoglobulins (G, A, M) 4. Panel: Immunology (82) H. Intended Use: 1. Intended use(s): 2 The Optilite IgG4 kit is intended for the quantitative in vitro measurement of IgG4 in serum using the Binding Site Optilite analyser. Measurement of this immunoglobulin is an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test result should be used in conjunction with other laboratory and clinical findings. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Optilite analyzer (k141100) I. Device Description: The device consists of the following: polyclonal monospecific sheep anti-IgG4 antisera coated onto polystyrene latex in liquid form in the presence of preservatives; IgG4 calibrator and Controls (Low, High and Elevated levels) in stabilized liquid form with preservatives; and Reaction Buffer (with 0.099% sodium azide as preservative). J. Substantial Equivalence Information: 1. Predicate device names: Binding Site Human IgG and IgG subclass (IgG1, IgG2, IgG3, IgG4) liquid reagent kits for use on the SPAplus 2. Predicate 510(k) number: k072889 3. Comparison with predicate: 3 Similarities Item Device Predicate Assay type Quantitative Same Detection Method Turbidimetric immunoassay Same Sample matrix Serum Same Antibody Polyclonal monospecific sheep anti-human IgG4 (F(ab)2) fragment bound to latex particles Same Traceability Standardized against ERM- DA470k European Reference Material (previously CRM470) Same Open vial stability 3 months Same On board vial stability 30 days Same Reference Ranges (mg/L) (95% percentile range) Adults: 39.2–864 Same Differences Item Device Predicate Intended Use Quantitative measurement of IgG4 in serum Quantitative measurement of Human IgG and IgG subclasses IgG1, IgG2, IgG3, IgG4 in serum Calibrator One Optilite IgG4 Calibrator One calibrator for each: IgG, IgG1, IgG2, IgG3, IgG4 Controls Low, High and Elevated levels, liquid, ready-to-use Low and high IgG and IgG subclasses: IgG1, IgG2, IgG3, IgG4 Instruments Optilite® Analyzer SPAPLUS™ Analyser Measuring range (mg/L) 2.96–216 (1+1 dilution) 37–2700 (1+24 dilution) 179.1–13068 (1+120 dilution) 888–64800 (1+599 dilution) 3–85 (1:2 dilution) 30–850 (1:10 dilution) 120–3400 (1:40 dilution) K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation CLSI C28-A3: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed, a portion of the light is transmitted and focused onto a photo iodide by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: The within-run, between-run, between-day, between-lot and between-instrument precision were determined by testing ten serum samples over 21 days with two runs per day and two replicates per run on three different reagent lots on four analysers. Results are summarized below. Precision Summary Sample Mean (mg/L) Within run Between run Between day Between lot Between instrument Total SD CV% SD CV% SD CV% SD CV% SD CV% SD CV% 1 23.6 0.9 3.6 0.0 0.0 0.9 3.5 0.2 1.0 0.8 3.3 1.2 5.1 2 31.2 0.5 1.4 0.8 2.5 0.9 2.9 0.7 2.3 0.3 0.9 1.3 4.1 3 48.8 0.5 1.0 1.4 2.8 2.1 4.1 1.0 2.0 0.6 1.2 2.5 5.1 4 53.9 2.9 4.8 2.6 4.4 5.2 8.7 3.8 7.1 0.5 1.0 6.5 10.9 5 124.0 1.9 1.5 2.2 1.7 5.7 4.3 0.7 0.5 3.7 3.0 6.5 4.9 6 611.6 9.1 1.4 12.0 1.9 21.2 3.4 7.3 1.2 11.7 1.9 26.0 4.1 7 1148.3 16.4 1.4 25.8 2.1 42.0 3.5 14.3 1.2 28.7 2.5 51.9 4.3 8 1473.6 20.8 1.3 27.8 1.8 51.7 3.3 11.2 0.8 38.7 2.6 62.2 4.0 5 Precision Summary 9 2152.5 23.0 1.1 77.7 3.6 40.1 1.9 39.5 1.8 22.7 1.1 90.4 4.2 10 4371.3 88.3 1.9 86.7 1.8 206.2 4.4 85.4 2.0 123.3 2.8 240.5 5.1 b. Linearity/assay reportable range: A linearity study was performed following CLSI document Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The linearity of this assay has been confirmed using serially diluted serum samples to cover the range 2.8–240.8 mg/L for Optilite analyzer dilution 1+1; 34.5–3010.4 mg/L for Optilite analyzer dilution 1+24; 169.4–14568.4 mg/L for Optilite analyzer dilution 1+120 and 828.0–72249.6 mg/L for Optilite analyzer dilution 1+ 599 with deviation from linearity ≤ 10%. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: An Internal Reference standard (IR) was assigned by comparison with the European Reference Material ERM-DA470k. Value assignment from total IgG to IgG4 was performed following the protocol outlined in Williams et al. 1. Stability: A real-time stability study of unopened kits was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 3 months and 6.5 months. Data support a shelf life claim of 6 months at 2–8o C. Real time stability study is on-going. Open-vial stability was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 1, 2, and 3 months. Data support the open vial stability claim of 3 months at 2–8o C. On-board stability was performed on three lots of Optilite IgG4 kit with testing time intervals at 0, 8, 15, 21, and 32 days. Data support the on-board stability claim of 30 days at 8–12o C, provided that the power is left switched on as stated in the product insert. All stability results were within the sponsor’s acceptance criteria. d. Detection limit: The analytical Type of test:

idK150526_s0_e2000

K150526.txt

classification

Class II

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: k150526 B. Purpose for Submission: New Device C. Measurand: IgG4 subclass Antibody D. Type of Test: Quantitative, turbidimetric E. Applicant: The Binding Site Group, Ltd. F. Proprietary and Established Names: Optilite® IgG4 Kit G. Regulatory Information: 1. Regulation section: 21 CFR §866.5510 - Immunoglobulins A, G, M, D, E Immunological Test System 2. Classification: Class II 3. Product code: CFN - Method, Nephelometric, Immunoglobulins (G, A, M) 4. Panel: Immunology (82) H. Intended Use: 1. Intended use(s): 2 The Optilite IgG4 kit is intended for the quantitative in vitro measurement of IgG4 in serum using the Binding Site Optilite analyser. Measurement of this immunoglobulin is an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test result should be used in conjunction with other laboratory and clinical findings. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Optilite analyzer (k141100) I. Device Description: The device consists of the following: polyclonal monospecific sheep anti-IgG4 antisera coated onto polystyrene latex in liquid form in the presence of preservatives; IgG4 calibrator and Controls (Low, High and Elevated levels) in stabilized liquid form with preservatives; and Reaction Buffer (with 0.099% sodium azide as preservative). J. Substantial Equivalence Information: 1. Predicate device names: Binding Site Human IgG and IgG subclass (IgG1, IgG2, IgG3, IgG4) liquid reagent kits for use on the SPAplus 2. Predicate 510(k) number: k072889 3. Comparison with predicate: 3 Similarities Item Device Predicate Assay type Quantitative Same Detection Method Turbidimetric immunoassay Same Sample matrix Serum Same Antibody Polyclonal monospecific sheep anti-human IgG4 (F(ab)2) fragment bound to latex particles Same Traceability Standardized against ERM- DA470k European Reference Material (previously CRM470) Same Open vial stability 3 months Same On board vial stability 30 days Same Reference Ranges (mg/L) (95% percentile range) Adults: 39.2–864 Same Differences Item Device Predicate Intended Use Quantitative measurement of IgG4 in serum Quantitative measurement of Human IgG and IgG subclasses IgG1, IgG2, IgG3, IgG4 in serum Calibrator One Optilite IgG4 Calibrator One calibrator for each: IgG, IgG1, IgG2, IgG3, IgG4 Controls Low, High and Elevated levels, liquid, ready-to-use Low and high IgG and IgG subclasses: IgG1, IgG2, IgG3, IgG4 Instruments Optilite® Analyzer SPAPLUS™ Analyser Measuring range (mg/L) 2.96–216 (1+1 dilution) 37–2700 (1+24 dilution) 179.1–13068 (1+120 dilution) 888–64800 (1+599 dilution) 3–85 (1:2 dilution) 30–850 (1:10 dilution) 120–3400 (1:40 dilution) K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation CLSI C28-A3: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed, a portion of the light is transmitted and focused onto a photo iodide by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: The within-run, between-run, between-day, between-lot and between-instrument precision were determined by testing ten serum samples over 21 days with two runs per day and two replicates per run on three different reagent lots on four analysers. Results are summarized below. Precision Summary Sample Mean (mg/L) Within run Between run Between day Between lot Between instrument Total SD CV% SD CV% SD CV% SD CV% SD CV% SD CV% 1 23.6 0.9 3.6 0.0 0.0 0.9 3.5 0.2 1.0 0.8 3.3 1.2 5.1 2 31.2 0.5 1.4 0.8 2.5 0.9 2.9 0.7 2.3 0.3 0.9 1.3 4.1 3 48.8 0.5 1.0 1.4 2.8 2.1 4.1 1.0 2.0 0.6 1.2 2.5 5.1 4 53.9 2.9 4.8 2.6 4.4 5.2 8.7 3.8 7.1 0.5 1.0 6.5 10.9 5 124.0 1.9 1.5 2.2 1.7 5.7 4.3 0.7 0.5 3.7 3.0 6.5 4.9 6 611.6 9.1 1.4 12.0 1.9 21.2 3.4 7.3 1.2 11.7 1.9 26.0 4.1 7 1148.3 16.4 1.4 25.8 2.1 42.0 3.5 14.3 1.2 28.7 2.5 51.9 4.3 8 1473.6 20.8 1.3 27.8 1.8 51.7 3.3 11.2 0.8 38.7 2.6 62.2 4.0 5 Precision Summary 9 2152.5 23.0 1.1 77.7 3.6 40.1 1.9 39.5 1.8 22.7 1.1 90.4 4.2 10 4371.3 88.3 1.9 86.7 1.8 206.2 4.4 85.4 2.0 123.3 2.8 240.5 5.1 b. Linearity/assay reportable range: A linearity study was performed following CLSI document Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The linearity of this assay has been confirmed using serially diluted serum samples to cover the range 2.8–240.8 mg/L for Optilite analyzer dilution 1+1; 34.5–3010.4 mg/L for Optilite analyzer dilution 1+24; 169.4–14568.4 mg/L for Optilite analyzer dilution 1+120 and 828.0–72249.6 mg/L for Optilite analyzer dilution 1+ 599 with deviation from linearity ≤ 10%. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: An Internal Reference standard (IR) was assigned by comparison with the European Reference Material ERM-DA470k. Value assignment from total IgG to IgG4 was performed following the protocol outlined in Williams et al. 1. Stability: A real-time stability study of unopened kits was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 3 months and 6.5 months. Data support a shelf life claim of 6 months at 2–8o C. Real time stability study is on-going. Open-vial stability was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 1, 2, and 3 months. Data support the open vial stability claim of 3 months at 2–8o C. On-board stability was performed on three lots of Optilite IgG4 kit with testing time intervals at 0, 8, 15, 21, and 32 days. Data support the on-board stability claim of 30 days at 8–12o C, provided that the power is left switched on as stated in the product insert. All stability results were within the sponsor’s acceptance criteria. d. Detection limit: The analytical Classification:

idK150526_s0_e2000

K150526.txt

product code

CFN - Method, Nephelometric, Immunoglobulins (G, A, M)

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: k150526 B. Purpose for Submission: New Device C. Measurand: IgG4 subclass Antibody D. Type of Test: Quantitative, turbidimetric E. Applicant: The Binding Site Group, Ltd. F. Proprietary and Established Names: Optilite® IgG4 Kit G. Regulatory Information: 1. Regulation section: 21 CFR §866.5510 - Immunoglobulins A, G, M, D, E Immunological Test System 2. Classification: Class II 3. Product code: CFN - Method, Nephelometric, Immunoglobulins (G, A, M) 4. Panel: Immunology (82) H. Intended Use: 1. Intended use(s): 2 The Optilite IgG4 kit is intended for the quantitative in vitro measurement of IgG4 in serum using the Binding Site Optilite analyser. Measurement of this immunoglobulin is an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test result should be used in conjunction with other laboratory and clinical findings. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Optilite analyzer (k141100) I. Device Description: The device consists of the following: polyclonal monospecific sheep anti-IgG4 antisera coated onto polystyrene latex in liquid form in the presence of preservatives; IgG4 calibrator and Controls (Low, High and Elevated levels) in stabilized liquid form with preservatives; and Reaction Buffer (with 0.099% sodium azide as preservative). J. Substantial Equivalence Information: 1. Predicate device names: Binding Site Human IgG and IgG subclass (IgG1, IgG2, IgG3, IgG4) liquid reagent kits for use on the SPAplus 2. Predicate 510(k) number: k072889 3. Comparison with predicate: 3 Similarities Item Device Predicate Assay type Quantitative Same Detection Method Turbidimetric immunoassay Same Sample matrix Serum Same Antibody Polyclonal monospecific sheep anti-human IgG4 (F(ab)2) fragment bound to latex particles Same Traceability Standardized against ERM- DA470k European Reference Material (previously CRM470) Same Open vial stability 3 months Same On board vial stability 30 days Same Reference Ranges (mg/L) (95% percentile range) Adults: 39.2–864 Same Differences Item Device Predicate Intended Use Quantitative measurement of IgG4 in serum Quantitative measurement of Human IgG and IgG subclasses IgG1, IgG2, IgG3, IgG4 in serum Calibrator One Optilite IgG4 Calibrator One calibrator for each: IgG, IgG1, IgG2, IgG3, IgG4 Controls Low, High and Elevated levels, liquid, ready-to-use Low and high IgG and IgG subclasses: IgG1, IgG2, IgG3, IgG4 Instruments Optilite® Analyzer SPAPLUS™ Analyser Measuring range (mg/L) 2.96–216 (1+1 dilution) 37–2700 (1+24 dilution) 179.1–13068 (1+120 dilution) 888–64800 (1+599 dilution) 3–85 (1:2 dilution) 30–850 (1:10 dilution) 120–3400 (1:40 dilution) K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation CLSI C28-A3: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed, a portion of the light is transmitted and focused onto a photo iodide by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: The within-run, between-run, between-day, between-lot and between-instrument precision were determined by testing ten serum samples over 21 days with two runs per day and two replicates per run on three different reagent lots on four analysers. Results are summarized below. Precision Summary Sample Mean (mg/L) Within run Between run Between day Between lot Between instrument Total SD CV% SD CV% SD CV% SD CV% SD CV% SD CV% 1 23.6 0.9 3.6 0.0 0.0 0.9 3.5 0.2 1.0 0.8 3.3 1.2 5.1 2 31.2 0.5 1.4 0.8 2.5 0.9 2.9 0.7 2.3 0.3 0.9 1.3 4.1 3 48.8 0.5 1.0 1.4 2.8 2.1 4.1 1.0 2.0 0.6 1.2 2.5 5.1 4 53.9 2.9 4.8 2.6 4.4 5.2 8.7 3.8 7.1 0.5 1.0 6.5 10.9 5 124.0 1.9 1.5 2.2 1.7 5.7 4.3 0.7 0.5 3.7 3.0 6.5 4.9 6 611.6 9.1 1.4 12.0 1.9 21.2 3.4 7.3 1.2 11.7 1.9 26.0 4.1 7 1148.3 16.4 1.4 25.8 2.1 42.0 3.5 14.3 1.2 28.7 2.5 51.9 4.3 8 1473.6 20.8 1.3 27.8 1.8 51.7 3.3 11.2 0.8 38.7 2.6 62.2 4.0 5 Precision Summary 9 2152.5 23.0 1.1 77.7 3.6 40.1 1.9 39.5 1.8 22.7 1.1 90.4 4.2 10 4371.3 88.3 1.9 86.7 1.8 206.2 4.4 85.4 2.0 123.3 2.8 240.5 5.1 b. Linearity/assay reportable range: A linearity study was performed following CLSI document Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The linearity of this assay has been confirmed using serially diluted serum samples to cover the range 2.8–240.8 mg/L for Optilite analyzer dilution 1+1; 34.5–3010.4 mg/L for Optilite analyzer dilution 1+24; 169.4–14568.4 mg/L for Optilite analyzer dilution 1+120 and 828.0–72249.6 mg/L for Optilite analyzer dilution 1+ 599 with deviation from linearity ≤ 10%. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: An Internal Reference standard (IR) was assigned by comparison with the European Reference Material ERM-DA470k. Value assignment from total IgG to IgG4 was performed following the protocol outlined in Williams et al. 1. Stability: A real-time stability study of unopened kits was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 3 months and 6.5 months. Data support a shelf life claim of 6 months at 2–8o C. Real time stability study is on-going. Open-vial stability was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 1, 2, and 3 months. Data support the open vial stability claim of 3 months at 2–8o C. On-board stability was performed on three lots of Optilite IgG4 kit with testing time intervals at 0, 8, 15, 21, and 32 days. Data support the on-board stability claim of 30 days at 8–12o C, provided that the power is left switched on as stated in the product insert. All stability results were within the sponsor’s acceptance criteria. d. Detection limit: The analytical Product code:

idK150526_s0_e2000

K150526.txt

panel

Immunology (82)

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: k150526 B. Purpose for Submission: New Device C. Measurand: IgG4 subclass Antibody D. Type of Test: Quantitative, turbidimetric E. Applicant: The Binding Site Group, Ltd. F. Proprietary and Established Names: Optilite® IgG4 Kit G. Regulatory Information: 1. Regulation section: 21 CFR §866.5510 - Immunoglobulins A, G, M, D, E Immunological Test System 2. Classification: Class II 3. Product code: CFN - Method, Nephelometric, Immunoglobulins (G, A, M) 4. Panel: Immunology (82) H. Intended Use: 1. Intended use(s): 2 The Optilite IgG4 kit is intended for the quantitative in vitro measurement of IgG4 in serum using the Binding Site Optilite analyser. Measurement of this immunoglobulin is an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test result should be used in conjunction with other laboratory and clinical findings. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Optilite analyzer (k141100) I. Device Description: The device consists of the following: polyclonal monospecific sheep anti-IgG4 antisera coated onto polystyrene latex in liquid form in the presence of preservatives; IgG4 calibrator and Controls (Low, High and Elevated levels) in stabilized liquid form with preservatives; and Reaction Buffer (with 0.099% sodium azide as preservative). J. Substantial Equivalence Information: 1. Predicate device names: Binding Site Human IgG and IgG subclass (IgG1, IgG2, IgG3, IgG4) liquid reagent kits for use on the SPAplus 2. Predicate 510(k) number: k072889 3. Comparison with predicate: 3 Similarities Item Device Predicate Assay type Quantitative Same Detection Method Turbidimetric immunoassay Same Sample matrix Serum Same Antibody Polyclonal monospecific sheep anti-human IgG4 (F(ab)2) fragment bound to latex particles Same Traceability Standardized against ERM- DA470k European Reference Material (previously CRM470) Same Open vial stability 3 months Same On board vial stability 30 days Same Reference Ranges (mg/L) (95% percentile range) Adults: 39.2–864 Same Differences Item Device Predicate Intended Use Quantitative measurement of IgG4 in serum Quantitative measurement of Human IgG and IgG subclasses IgG1, IgG2, IgG3, IgG4 in serum Calibrator One Optilite IgG4 Calibrator One calibrator for each: IgG, IgG1, IgG2, IgG3, IgG4 Controls Low, High and Elevated levels, liquid, ready-to-use Low and high IgG and IgG subclasses: IgG1, IgG2, IgG3, IgG4 Instruments Optilite® Analyzer SPAPLUS™ Analyser Measuring range (mg/L) 2.96–216 (1+1 dilution) 37–2700 (1+24 dilution) 179.1–13068 (1+120 dilution) 888–64800 (1+599 dilution) 3–85 (1:2 dilution) 30–850 (1:10 dilution) 120–3400 (1:40 dilution) K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation CLSI C28-A3: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed, a portion of the light is transmitted and focused onto a photo iodide by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: The within-run, between-run, between-day, between-lot and between-instrument precision were determined by testing ten serum samples over 21 days with two runs per day and two replicates per run on three different reagent lots on four analysers. Results are summarized below. Precision Summary Sample Mean (mg/L) Within run Between run Between day Between lot Between instrument Total SD CV% SD CV% SD CV% SD CV% SD CV% SD CV% 1 23.6 0.9 3.6 0.0 0.0 0.9 3.5 0.2 1.0 0.8 3.3 1.2 5.1 2 31.2 0.5 1.4 0.8 2.5 0.9 2.9 0.7 2.3 0.3 0.9 1.3 4.1 3 48.8 0.5 1.0 1.4 2.8 2.1 4.1 1.0 2.0 0.6 1.2 2.5 5.1 4 53.9 2.9 4.8 2.6 4.4 5.2 8.7 3.8 7.1 0.5 1.0 6.5 10.9 5 124.0 1.9 1.5 2.2 1.7 5.7 4.3 0.7 0.5 3.7 3.0 6.5 4.9 6 611.6 9.1 1.4 12.0 1.9 21.2 3.4 7.3 1.2 11.7 1.9 26.0 4.1 7 1148.3 16.4 1.4 25.8 2.1 42.0 3.5 14.3 1.2 28.7 2.5 51.9 4.3 8 1473.6 20.8 1.3 27.8 1.8 51.7 3.3 11.2 0.8 38.7 2.6 62.2 4.0 5 Precision Summary 9 2152.5 23.0 1.1 77.7 3.6 40.1 1.9 39.5 1.8 22.7 1.1 90.4 4.2 10 4371.3 88.3 1.9 86.7 1.8 206.2 4.4 85.4 2.0 123.3 2.8 240.5 5.1 b. Linearity/assay reportable range: A linearity study was performed following CLSI document Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The linearity of this assay has been confirmed using serially diluted serum samples to cover the range 2.8–240.8 mg/L for Optilite analyzer dilution 1+1; 34.5–3010.4 mg/L for Optilite analyzer dilution 1+24; 169.4–14568.4 mg/L for Optilite analyzer dilution 1+120 and 828.0–72249.6 mg/L for Optilite analyzer dilution 1+ 599 with deviation from linearity ≤ 10%. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: An Internal Reference standard (IR) was assigned by comparison with the European Reference Material ERM-DA470k. Value assignment from total IgG to IgG4 was performed following the protocol outlined in Williams et al. 1. Stability: A real-time stability study of unopened kits was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 3 months and 6.5 months. Data support a shelf life claim of 6 months at 2–8o C. Real time stability study is on-going. Open-vial stability was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 1, 2, and 3 months. Data support the open vial stability claim of 3 months at 2–8o C. On-board stability was performed on three lots of Optilite IgG4 kit with testing time intervals at 0, 8, 15, 21, and 32 days. Data support the on-board stability claim of 30 days at 8–12o C, provided that the power is left switched on as stated in the product insert. All stability results were within the sponsor’s acceptance criteria. d. Detection limit: The analytical Panel:

idK150526_s0_e2000

K150526.txt

predicate device name

Binding Site Human IgG and IgG subclass (IgG1, IgG2, IgG3, IgG4) liquid reagent kits for use on the SPAplus

ANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: k150526 B. Purpose for Submission: New Device C. Measurand: IgG4 subclass Antibody D. Type of Test: Quantitative, turbidimetric E. Applicant: The Binding Site Group, Ltd. F. Proprietary and Established Names: Optilite® IgG4 Kit G. Regulatory Information: 1. Regulation section: 21 CFR §866.5510 - Immunoglobulins A, G, M, D, E Immunological Test System 2. Classification: Class II 3. Product code: CFN - Method, Nephelometric, Immunoglobulins (G, A, M) 4. Panel: Immunology (82) H. Intended Use: 1. Intended use(s): 2 The Optilite IgG4 kit is intended for the quantitative in vitro measurement of IgG4 in serum using the Binding Site Optilite analyser. Measurement of this immunoglobulin is an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test result should be used in conjunction with other laboratory and clinical findings. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Optilite analyzer (k141100) I. Device Description: The device consists of the following: polyclonal monospecific sheep anti-IgG4 antisera coated onto polystyrene latex in liquid form in the presence of preservatives; IgG4 calibrator and Controls (Low, High and Elevated levels) in stabilized liquid form with preservatives; and Reaction Buffer (with 0.099% sodium azide as preservative). J. Substantial Equivalence Information: 1. Predicate device names: Binding Site Human IgG and IgG subclass (IgG1, IgG2, IgG3, IgG4) liquid reagent kits for use on the SPAplus 2. Predicate 510(k) number: k072889 3. Comparison with predicate: 3 Similarities Item Device Predicate Assay type Quantitative Same Detection Method Turbidimetric immunoassay Same Sample matrix Serum Same Antibody Polyclonal monospecific sheep anti-human IgG4 (F(ab)2) fragment bound to latex particles Same Traceability Standardized against ERM- DA470k European Reference Material (previously CRM470) Same Open vial stability 3 months Same On board vial stability 30 days Same Reference Ranges (mg/L) (95% percentile range) Adults: 39.2–864 Same Differences Item Device Predicate Intended Use Quantitative measurement of IgG4 in serum Quantitative measurement of Human IgG and IgG subclasses IgG1, IgG2, IgG3, IgG4 in serum Calibrator One Optilite IgG4 Calibrator One calibrator for each: IgG, IgG1, IgG2, IgG3, IgG4 Controls Low, High and Elevated levels, liquid, ready-to-use Low and high IgG and IgG subclasses: IgG1, IgG2, IgG3, IgG4 Instruments Optilite® Analyzer SPAPLUS™ Analyser Measuring range (mg/L) 2.96–216 (1+1 dilution) 37–2700 (1+24 dilution) 179.1–13068 (1+120 dilution) 888–64800 (1+599 dilution) 3–85 (1:2 dilution) 30–850 (1:10 dilution) 120–3400 (1:40 dilution) K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation CLSI C28-A3: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed, a portion of the light is transmitted and focused onto a photo iodide by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: The within-run, between-run, between-day, between-lot and between-instrument precision were determined by testing ten serum samples over 21 days with two runs per day and two replicates per run on three different reagent lots on four analysers. Results are summarized below. Precision Summary Sample Mean (mg/L) Within run Between run Between day Between lot Between instrument Total SD CV% SD CV% SD CV% SD CV% SD CV% SD CV% 1 23.6 0.9 3.6 0.0 0.0 0.9 3.5 0.2 1.0 0.8 3.3 1.2 5.1 2 31.2 0.5 1.4 0.8 2.5 0.9 2.9 0.7 2.3 0.3 0.9 1.3 4.1 3 48.8 0.5 1.0 1.4 2.8 2.1 4.1 1.0 2.0 0.6 1.2 2.5 5.1 4 53.9 2.9 4.8 2.6 4.4 5.2 8.7 3.8 7.1 0.5 1.0 6.5 10.9 5 124.0 1.9 1.5 2.2 1.7 5.7 4.3 0.7 0.5 3.7 3.0 6.5 4.9 6 611.6 9.1 1.4 12.0 1.9 21.2 3.4 7.3 1.2 11.7 1.9 26.0 4.1 7 1148.3 16.4 1.4 25.8 2.1 42.0 3.5 14.3 1.2 28.7 2.5 51.9 4.3 8 1473.6 20.8 1.3 27.8 1.8 51.7 3.3 11.2 0.8 38.7 2.6 62.2 4.0 5 Precision Summary 9 2152.5 23.0 1.1 77.7 3.6 40.1 1.9 39.5 1.8 22.7 1.1 90.4 4.2 10 4371.3 88.3 1.9 86.7 1.8 206.2 4.4 85.4 2.0 123.3 2.8 240.5 5.1 b. Linearity/assay reportable range: A linearity study was performed following CLSI document Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The linearity of this assay has been confirmed using serially diluted serum samples to cover the range 2.8–240.8 mg/L for Optilite analyzer dilution 1+1; 34.5–3010.4 mg/L for Optilite analyzer dilution 1+24; 169.4–14568.4 mg/L for Optilite analyzer dilution 1+120 and 828.0–72249.6 mg/L for Optilite analyzer dilution 1+ 599 with deviation from linearity ≤ 10%. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: An Internal Reference standard (IR) was assigned by comparison with the European Reference Material ERM-DA470k. Value assignment from total IgG to IgG4 was performed following the protocol outlined in Williams et al. 1. Stability: A real-time stability study of unopened kits was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 3 months and 6.5 months. Data support a shelf life claim of 6 months at 2–8o C. Real time stability study is on-going. Open-vial stability was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 1, 2, and 3 months. Data support the open vial stability claim of 3 months at 2–8o C. On-board stability was performed on three lots of Optilite IgG4 kit with testing time intervals at 0, 8, 15, 21, and 32 days. Data support the on-board stability claim of 30 days at 8–12o C, provided that the power is left switched on as stated in the product insert. All stability results were within the sponsor’s acceptance criteria. d. Detection limit: The analytical Predicate device name:

idK150526_s0_e2000

K150526.txt

applicant

The Binding Site Group, Ltd.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: k150526 B. Purpose for Submission: New Device C. Measurand: IgG4 subclass Antibody D. Type of Test: Quantitative, turbidimetric E. Applicant: The Binding Site Group, Ltd. F. Proprietary and Established Names: Optilite® IgG4 Kit G. Regulatory Information: 1. Regulation section: 21 CFR §866.5510 - Immunoglobulins A, G, M, D, E Immunological Test System 2. Classification: Class II 3. Product code: CFN - Method, Nephelometric, Immunoglobulins (G, A, M) 4. Panel: Immunology (82) H. Intended Use: 1. Intended use(s): 2 The Optilite IgG4 kit is intended for the quantitative in vitro measurement of IgG4 in serum using the Binding Site Optilite analyser. Measurement of this immunoglobulin is an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test result should be used in conjunction with other laboratory and clinical findings. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Optilite analyzer (k141100) I. Device Description: The device consists of the following: polyclonal monospecific sheep anti-IgG4 antisera coated onto polystyrene latex in liquid form in the presence of preservatives; IgG4 calibrator and Controls (Low, High and Elevated levels) in stabilized liquid form with preservatives; and Reaction Buffer (with 0.099% sodium azide as preservative). J. Substantial Equivalence Information: 1. Predicate device names: Binding Site Human IgG and IgG subclass (IgG1, IgG2, IgG3, IgG4) liquid reagent kits for use on the SPAplus 2. Predicate 510(k) number: k072889 3. Comparison with predicate: 3 Similarities Item Device Predicate Assay type Quantitative Same Detection Method Turbidimetric immunoassay Same Sample matrix Serum Same Antibody Polyclonal monospecific sheep anti-human IgG4 (F(ab)2) fragment bound to latex particles Same Traceability Standardized against ERM- DA470k European Reference Material (previously CRM470) Same Open vial stability 3 months Same On board vial stability 30 days Same Reference Ranges (mg/L) (95% percentile range) Adults: 39.2–864 Same Differences Item Device Predicate Intended Use Quantitative measurement of IgG4 in serum Quantitative measurement of Human IgG and IgG subclasses IgG1, IgG2, IgG3, IgG4 in serum Calibrator One Optilite IgG4 Calibrator One calibrator for each: IgG, IgG1, IgG2, IgG3, IgG4 Controls Low, High and Elevated levels, liquid, ready-to-use Low and high IgG and IgG subclasses: IgG1, IgG2, IgG3, IgG4 Instruments Optilite® Analyzer SPAPLUS™ Analyser Measuring range (mg/L) 2.96–216 (1+1 dilution) 37–2700 (1+24 dilution) 179.1–13068 (1+120 dilution) 888–64800 (1+599 dilution) 3–85 (1:2 dilution) 30–850 (1:10 dilution) 120–3400 (1:40 dilution) K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation CLSI C28-A3: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed, a portion of the light is transmitted and focused onto a photo iodide by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: The within-run, between-run, between-day, between-lot and between-instrument precision were determined by testing ten serum samples over 21 days with two runs per day and two replicates per run on three different reagent lots on four analysers. Results are summarized below. Precision Summary Sample Mean (mg/L) Within run Between run Between day Between lot Between instrument Total SD CV% SD CV% SD CV% SD CV% SD CV% SD CV% 1 23.6 0.9 3.6 0.0 0.0 0.9 3.5 0.2 1.0 0.8 3.3 1.2 5.1 2 31.2 0.5 1.4 0.8 2.5 0.9 2.9 0.7 2.3 0.3 0.9 1.3 4.1 3 48.8 0.5 1.0 1.4 2.8 2.1 4.1 1.0 2.0 0.6 1.2 2.5 5.1 4 53.9 2.9 4.8 2.6 4.4 5.2 8.7 3.8 7.1 0.5 1.0 6.5 10.9 5 124.0 1.9 1.5 2.2 1.7 5.7 4.3 0.7 0.5 3.7 3.0 6.5 4.9 6 611.6 9.1 1.4 12.0 1.9 21.2 3.4 7.3 1.2 11.7 1.9 26.0 4.1 7 1148.3 16.4 1.4 25.8 2.1 42.0 3.5 14.3 1.2 28.7 2.5 51.9 4.3 8 1473.6 20.8 1.3 27.8 1.8 51.7 3.3 11.2 0.8 38.7 2.6 62.2 4.0 5 Precision Summary 9 2152.5 23.0 1.1 77.7 3.6 40.1 1.9 39.5 1.8 22.7 1.1 90.4 4.2 10 4371.3 88.3 1.9 86.7 1.8 206.2 4.4 85.4 2.0 123.3 2.8 240.5 5.1 b. Linearity/assay reportable range: A linearity study was performed following CLSI document Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The linearity of this assay has been confirmed using serially diluted serum samples to cover the range 2.8–240.8 mg/L for Optilite analyzer dilution 1+1; 34.5–3010.4 mg/L for Optilite analyzer dilution 1+24; 169.4–14568.4 mg/L for Optilite analyzer dilution 1+120 and 828.0–72249.6 mg/L for Optilite analyzer dilution 1+ 599 with deviation from linearity ≤ 10%. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: An Internal Reference standard (IR) was assigned by comparison with the European Reference Material ERM-DA470k. Value assignment from total IgG to IgG4 was performed following the protocol outlined in Williams et al. 1. Stability: A real-time stability study of unopened kits was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 3 months and 6.5 months. Data support a shelf life claim of 6 months at 2–8o C. Real time stability study is on-going. Open-vial stability was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 1, 2, and 3 months. Data support the open vial stability claim of 3 months at 2–8o C. On-board stability was performed on three lots of Optilite IgG4 kit with testing time intervals at 0, 8, 15, 21, and 32 days. Data support the on-board stability claim of 30 days at 8–12o C, provided that the power is left switched on as stated in the product insert. All stability results were within the sponsor’s acceptance criteria. d. Detection limit: The analytical Applicant:

idK150526_s0_e2000

K150526.txt

proprietary and established names

Optilite® IgG4 Kit

EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: k150526 B. Purpose for Submission: New Device C. Measurand: IgG4 subclass Antibody D. Type of Test: Quantitative, turbidimetric E. Applicant: The Binding Site Group, Ltd. F. Proprietary and Established Names: Optilite® IgG4 Kit G. Regulatory Information: 1. Regulation section: 21 CFR §866.5510 - Immunoglobulins A, G, M, D, E Immunological Test System 2. Classification: Class II 3. Product code: CFN - Method, Nephelometric, Immunoglobulins (G, A, M) 4. Panel: Immunology (82) H. Intended Use: 1. Intended use(s): 2 The Optilite IgG4 kit is intended for the quantitative in vitro measurement of IgG4 in serum using the Binding Site Optilite analyser. Measurement of this immunoglobulin is an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test result should be used in conjunction with other laboratory and clinical findings. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Optilite analyzer (k141100) I. Device Description: The device consists of the following: polyclonal monospecific sheep anti-IgG4 antisera coated onto polystyrene latex in liquid form in the presence of preservatives; IgG4 calibrator and Controls (Low, High and Elevated levels) in stabilized liquid form with preservatives; and Reaction Buffer (with 0.099% sodium azide as preservative). J. Substantial Equivalence Information: 1. Predicate device names: Binding Site Human IgG and IgG subclass (IgG1, IgG2, IgG3, IgG4) liquid reagent kits for use on the SPAplus 2. Predicate 510(k) number: k072889 3. Comparison with predicate: 3 Similarities Item Device Predicate Assay type Quantitative Same Detection Method Turbidimetric immunoassay Same Sample matrix Serum Same Antibody Polyclonal monospecific sheep anti-human IgG4 (F(ab)2) fragment bound to latex particles Same Traceability Standardized against ERM- DA470k European Reference Material (previously CRM470) Same Open vial stability 3 months Same On board vial stability 30 days Same Reference Ranges (mg/L) (95% percentile range) Adults: 39.2–864 Same Differences Item Device Predicate Intended Use Quantitative measurement of IgG4 in serum Quantitative measurement of Human IgG and IgG subclasses IgG1, IgG2, IgG3, IgG4 in serum Calibrator One Optilite IgG4 Calibrator One calibrator for each: IgG, IgG1, IgG2, IgG3, IgG4 Controls Low, High and Elevated levels, liquid, ready-to-use Low and high IgG and IgG subclasses: IgG1, IgG2, IgG3, IgG4 Instruments Optilite® Analyzer SPAPLUS™ Analyser Measuring range (mg/L) 2.96–216 (1+1 dilution) 37–2700 (1+24 dilution) 179.1–13068 (1+120 dilution) 888–64800 (1+599 dilution) 3–85 (1:2 dilution) 30–850 (1:10 dilution) 120–3400 (1:40 dilution) K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation CLSI C28-A3: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed, a portion of the light is transmitted and focused onto a photo iodide by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: The within-run, between-run, between-day, between-lot and between-instrument precision were determined by testing ten serum samples over 21 days with two runs per day and two replicates per run on three different reagent lots on four analysers. Results are summarized below. Precision Summary Sample Mean (mg/L) Within run Between run Between day Between lot Between instrument Total SD CV% SD CV% SD CV% SD CV% SD CV% SD CV% 1 23.6 0.9 3.6 0.0 0.0 0.9 3.5 0.2 1.0 0.8 3.3 1.2 5.1 2 31.2 0.5 1.4 0.8 2.5 0.9 2.9 0.7 2.3 0.3 0.9 1.3 4.1 3 48.8 0.5 1.0 1.4 2.8 2.1 4.1 1.0 2.0 0.6 1.2 2.5 5.1 4 53.9 2.9 4.8 2.6 4.4 5.2 8.7 3.8 7.1 0.5 1.0 6.5 10.9 5 124.0 1.9 1.5 2.2 1.7 5.7 4.3 0.7 0.5 3.7 3.0 6.5 4.9 6 611.6 9.1 1.4 12.0 1.9 21.2 3.4 7.3 1.2 11.7 1.9 26.0 4.1 7 1148.3 16.4 1.4 25.8 2.1 42.0 3.5 14.3 1.2 28.7 2.5 51.9 4.3 8 1473.6 20.8 1.3 27.8 1.8 51.7 3.3 11.2 0.8 38.7 2.6 62.2 4.0 5 Precision Summary 9 2152.5 23.0 1.1 77.7 3.6 40.1 1.9 39.5 1.8 22.7 1.1 90.4 4.2 10 4371.3 88.3 1.9 86.7 1.8 206.2 4.4 85.4 2.0 123.3 2.8 240.5 5.1 b. Linearity/assay reportable range: A linearity study was performed following CLSI document Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The linearity of this assay has been confirmed using serially diluted serum samples to cover the range 2.8–240.8 mg/L for Optilite analyzer dilution 1+1; 34.5–3010.4 mg/L for Optilite analyzer dilution 1+24; 169.4–14568.4 mg/L for Optilite analyzer dilution 1+120 and 828.0–72249.6 mg/L for Optilite analyzer dilution 1+ 599 with deviation from linearity ≤ 10%. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: An Internal Reference standard (IR) was assigned by comparison with the European Reference Material ERM-DA470k. Value assignment from total IgG to IgG4 was performed following the protocol outlined in Williams et al. 1. Stability: A real-time stability study of unopened kits was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 3 months and 6.5 months. Data support a shelf life claim of 6 months at 2–8o C. Real time stability study is on-going. Open-vial stability was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 1, 2, and 3 months. Data support the open vial stability claim of 3 months at 2–8o C. On-board stability was performed on three lots of Optilite IgG4 kit with testing time intervals at 0, 8, 15, 21, and 32 days. Data support the on-board stability claim of 30 days at 8–12o C, provided that the power is left switched on as stated in the product insert. All stability results were within the sponsor’s acceptance criteria. d. Detection limit: The analytical Proprietary and established names:

idK150526_s0_e2000

K150526.txt

regulation section

21 CFR §866.5510 - Immunoglobulins A, G, M, D, E Immunological Test System

STANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM 1 A. 510(k) Number: k150526 B. Purpose for Submission: New Device C. Measurand: IgG4 subclass Antibody D. Type of Test: Quantitative, turbidimetric E. Applicant: The Binding Site Group, Ltd. F. Proprietary and Established Names: Optilite® IgG4 Kit G. Regulatory Information: 1. Regulation section: 21 CFR §866.5510 - Immunoglobulins A, G, M, D, E Immunological Test System 2. Classification: Class II 3. Product code: CFN - Method, Nephelometric, Immunoglobulins (G, A, M) 4. Panel: Immunology (82) H. Intended Use: 1. Intended use(s): 2 The Optilite IgG4 kit is intended for the quantitative in vitro measurement of IgG4 in serum using the Binding Site Optilite analyser. Measurement of this immunoglobulin is an aid in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. The test result should be used in conjunction with other laboratory and clinical findings. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Optilite analyzer (k141100) I. Device Description: The device consists of the following: polyclonal monospecific sheep anti-IgG4 antisera coated onto polystyrene latex in liquid form in the presence of preservatives; IgG4 calibrator and Controls (Low, High and Elevated levels) in stabilized liquid form with preservatives; and Reaction Buffer (with 0.099% sodium azide as preservative). J. Substantial Equivalence Information: 1. Predicate device names: Binding Site Human IgG and IgG subclass (IgG1, IgG2, IgG3, IgG4) liquid reagent kits for use on the SPAplus 2. Predicate 510(k) number: k072889 3. Comparison with predicate: 3 Similarities Item Device Predicate Assay type Quantitative Same Detection Method Turbidimetric immunoassay Same Sample matrix Serum Same Antibody Polyclonal monospecific sheep anti-human IgG4 (F(ab)2) fragment bound to latex particles Same Traceability Standardized against ERM- DA470k European Reference Material (previously CRM470) Same Open vial stability 3 months Same On board vial stability 30 days Same Reference Ranges (mg/L) (95% percentile range) Adults: 39.2–864 Same Differences Item Device Predicate Intended Use Quantitative measurement of IgG4 in serum Quantitative measurement of Human IgG and IgG subclasses IgG1, IgG2, IgG3, IgG4 in serum Calibrator One Optilite IgG4 Calibrator One calibrator for each: IgG, IgG1, IgG2, IgG3, IgG4 Controls Low, High and Elevated levels, liquid, ready-to-use Low and high IgG and IgG subclasses: IgG1, IgG2, IgG3, IgG4 Instruments Optilite® Analyzer SPAPLUS™ Analyser Measuring range (mg/L) 2.96–216 (1+1 dilution) 37–2700 (1+24 dilution) 179.1–13068 (1+120 dilution) 888–64800 (1+599 dilution) 3–85 (1:2 dilution) 30–850 (1:10 dilution) 120–3400 (1:40 dilution) K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Second Edition CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach CLSI EP07-A2: Interference Testing in Clinical Chemistry CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation CLSI C28-A3: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory L. Test Principle: The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed, a portion of the light is transmitted and focused onto a photo iodide by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test sample. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: The within-run, between-run, between-day, between-lot and between-instrument precision were determined by testing ten serum samples over 21 days with two runs per day and two replicates per run on three different reagent lots on four analysers. Results are summarized below. Precision Summary Sample Mean (mg/L) Within run Between run Between day Between lot Between instrument Total SD CV% SD CV% SD CV% SD CV% SD CV% SD CV% 1 23.6 0.9 3.6 0.0 0.0 0.9 3.5 0.2 1.0 0.8 3.3 1.2 5.1 2 31.2 0.5 1.4 0.8 2.5 0.9 2.9 0.7 2.3 0.3 0.9 1.3 4.1 3 48.8 0.5 1.0 1.4 2.8 2.1 4.1 1.0 2.0 0.6 1.2 2.5 5.1 4 53.9 2.9 4.8 2.6 4.4 5.2 8.7 3.8 7.1 0.5 1.0 6.5 10.9 5 124.0 1.9 1.5 2.2 1.7 5.7 4.3 0.7 0.5 3.7 3.0 6.5 4.9 6 611.6 9.1 1.4 12.0 1.9 21.2 3.4 7.3 1.2 11.7 1.9 26.0 4.1 7 1148.3 16.4 1.4 25.8 2.1 42.0 3.5 14.3 1.2 28.7 2.5 51.9 4.3 8 1473.6 20.8 1.3 27.8 1.8 51.7 3.3 11.2 0.8 38.7 2.6 62.2 4.0 5 Precision Summary 9 2152.5 23.0 1.1 77.7 3.6 40.1 1.9 39.5 1.8 22.7 1.1 90.4 4.2 10 4371.3 88.3 1.9 86.7 1.8 206.2 4.4 85.4 2.0 123.3 2.8 240.5 5.1 b. Linearity/assay reportable range: A linearity study was performed following CLSI document Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. The linearity of this assay has been confirmed using serially diluted serum samples to cover the range 2.8–240.8 mg/L for Optilite analyzer dilution 1+1; 34.5–3010.4 mg/L for Optilite analyzer dilution 1+24; 169.4–14568.4 mg/L for Optilite analyzer dilution 1+120 and 828.0–72249.6 mg/L for Optilite analyzer dilution 1+ 599 with deviation from linearity ≤ 10%. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: An Internal Reference standard (IR) was assigned by comparison with the European Reference Material ERM-DA470k. Value assignment from total IgG to IgG4 was performed following the protocol outlined in Williams et al. 1. Stability: A real-time stability study of unopened kits was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 3 months and 6.5 months. Data support a shelf life claim of 6 months at 2–8o C. Real time stability study is on-going. Open-vial stability was performed on three lots of Optilite IgG4 kit with testing time intervals at day 0, 1, 2, and 3 months. Data support the open vial stability claim of 3 months at 2–8o C. On-board stability was performed on three lots of Optilite IgG4 kit with testing time intervals at 0, 8, 15, 21, and 32 days. Data support the on-board stability claim of 30 days at 8–12o C, provided that the power is left switched on as stated in the product insert. All stability results were within the sponsor’s acceptance criteria. d. Detection limit: The analytical Regulation section:

idK150526_s2000_e4000

K150526.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

with CLSI EP17-A. The Limit of Blank (LoB) was based on 60 determinations of a blank sample and was 1 Williams, D. R, Wilson, C. I. and Carr-Smith, H.D. Assignment of IgG Subclass Values to the Protein Reference Preparation DA470k. Clin Chem 2009;55(6) Supplement:A132 6 estimated at 95% percentile of the distribution. The Limit of Detection (LoD) was calculated according to the equation: the LoB + 1.645(SDs) where SDs, the standard deviation, was based on 12 determinations of 5 samples with analyte level near the lower limit of the reportable range. The LoQ was calculated and the total error (0.367 mg/L) was within the maximum allowable total error. The tabulated summary is shown below: LoB LoD LoQ 0.000mg/L 0.299mg/L 2.960mg/ L e. Analytical specificity: Interference: Interferences were assessed according to CLSI EP7-A2 by testing five serum samples with different IgG4 concentration ranges: (1) an IgG4 deficient sample, target level 20 mg/L; (2) a sample close to the close to the medical decision point (MDP) at the lower limit of the reference range, target 37 mg/L, (3) a sample with a normal level of IgG4, target level 135 mg/L; (4) a sample close to the upper limit of the reference range, target 845; and (5) a sample with an elevated IgG4 level, target value > 4000 mg/L. Each sample was spiked with interfering substances and tested in triplicate. The manufacturer’s acceptance criteria were that the mean results from the spiked samples must be within ±10% of the mean of the control samples. No significant assay interference effects were observed when the five samples were tested with bilirubin at 200mg/L, hemoglobin at 5g/L, or triglyceride at 1000mg/dL. Intralipid at 250 mg/dL showed signs of interference and lipemic samples are known to interfere in this assay. A warning is included in the product insert that this assay is not suitable for use with lipemic samples. Drug Interference results: The data demonstrated that the assay was not affected by the 14 commonly used drugs tested at the concentrations given below when tested in the5 samples described above. Drug Concentration tested Acetaminophen 1324 μmol/L Acetylsalicylic Acid 3.63 mmol/L Amoxicillin 206 µmol/L Ascorbic Acid 342 μmol/L Caffeine 308 μmol/L Cefotaxime 673 µmol/L Cefuroxime 1416 µmol/L Chloramphenicol 155 µmol/L Cimetidine 79.2 μmol/L Digoxin 7.8 nmol/L Fluconazole 245 µmol/L 7 Drug Concentration tested Ibuprofen 2425 μmol/L Penicillin 75 mg/L Phenytoin 198 μmol/L Antigen Excess Detection The Optilite’s ability to detect antigen excess was evaluated with a sample of 2857 mg/L run neat on three different lots of reagents. This is equivalent to running a sample with a concentration of 71,425 mg/L at the standard measuring dilution of 1:26 (e.g., approximately 26 times the top of the calibration curve). Antigen excess was correctly detected and flagged by the analyser in all cases. The product insert states that: “Antigen excess check warning protection (‘antigen limit low’ flags) may be seen against IgG4 results” and “Potential occurrences of antigen excess cannot be completely excluded; in rare cases samples with monoclonal IgG4 present may give falsely low results due to antigen excess. Where this is possible or suspected it is recommended that the sample is re-assayed at a higher dilution to confirm the result.” f. Assay cut-off: Not applicable. 2. Comparison studies: a. Method comparison with predicate device: A method comparison study between the Optilite IgG4 Kit and the predicate device was performed by analyzing 567 serum samples (26 normal donors and 541 clinical samples, of which 322 were pediatric samples). Of the 567 total samples, 541 were clinical samples which included 199 samples with diagnosis and 342 samples with unavailable clinical information. The 199 samples with diagnoses includes: 45 confirmed hypogammaglobulinaemia; 23 hypergammaglobulinaemia; 1 suspected hypogammaglobulinaemia; 9 suspected hypergammaglobulinaemia; 1 anaphylaxis; 14 endocrine and autoimmune conditions were tested including 1 SLE (pediatric); 3 thyroid related disease (all pediatric); 2 diabetes (all pediatric); 8 obesity (all pediatric); 38 AIP; 5 benign conditions (all pediatric); 2 malignant conditions; 13 developmental conditions (all pediatric); 35 other clinical conditions (e.g. hyperkalemia, implanted device management, fracture, etc). Passing-Bablok regression analysis generated the following result: y = 0.91x + 8.09 (mg/L) with correlation coefficient r = 0.999. The package insert states that “Levels of IgG4 in normal adults may be undetectable; therefore, low IgG4 alone is insufficient evidence of an antibody deficiency disorder requiring Immunoglobulin replacement. Clinical history and other laboratory findings must be taken into account in the diagnosis of antibody deficiency disorder”. b. Matrix comparison: Not applicable 3. Clinical studies: 8 a. Clinical Sensitivity and specificity: Not applicable b. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference Interval: The product insert states the following: The ranges provided have been obtained from a limited number of samples and are intended for guidance purposes only. Expected values may vary with age, sex, sample type, diet and geographical location. Each laboratory should verify the transferability of the expected values to its own population and, if necessary, determine its own reference interval. Adult serum range This range was obtained by measuring the subclass content of sera provided by the Birmingham Blood Transfusion Service taken from healthy UK adult donors and generated using Binding Site’s BN™II subclass kits and verified using 50 US normal samples on the Optilite IgG4 Kit. Forty-eight of the 50 samples tested were within the 95 percentile range accepted criteria. Number (n) Mean (mg/L) Median (mg/L) 95 Percentile Range (mg/L) IgG4 30 280 215.3 39.2–864 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. 9 Proposed labeling:

idK150526_s2000_e4000

K150526.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

in accordance with CLSI EP17-A. The Limit of Blank (LoB) was based on 60 determinations of a blank sample and was 1 Williams, D. R, Wilson, C. I. and Carr-Smith, H.D. Assignment of IgG Subclass Values to the Protein Reference Preparation DA470k. Clin Chem 2009;55(6) Supplement:A132 6 estimated at 95% percentile of the distribution. The Limit of Detection (LoD) was calculated according to the equation: the LoB + 1.645(SDs) where SDs, the standard deviation, was based on 12 determinations of 5 samples with analyte level near the lower limit of the reportable range. The LoQ was calculated and the total error (0.367 mg/L) was within the maximum allowable total error. The tabulated summary is shown below: LoB LoD LoQ 0.000mg/L 0.299mg/L 2.960mg/ L e. Analytical specificity: Interference: Interferences were assessed according to CLSI EP7-A2 by testing five serum samples with different IgG4 concentration ranges: (1) an IgG4 deficient sample, target level 20 mg/L; (2) a sample close to the close to the medical decision point (MDP) at the lower limit of the reference range, target 37 mg/L, (3) a sample with a normal level of IgG4, target level 135 mg/L; (4) a sample close to the upper limit of the reference range, target 845; and (5) a sample with an elevated IgG4 level, target value > 4000 mg/L. Each sample was spiked with interfering substances and tested in triplicate. The manufacturer’s acceptance criteria were that the mean results from the spiked samples must be within ±10% of the mean of the control samples. No significant assay interference effects were observed when the five samples were tested with bilirubin at 200mg/L, hemoglobin at 5g/L, or triglyceride at 1000mg/dL. Intralipid at 250 mg/dL showed signs of interference and lipemic samples are known to interfere in this assay. A warning is included in the product insert that this assay is not suitable for use with lipemic samples. Drug Interference results: The data demonstrated that the assay was not affected by the 14 commonly used drugs tested at the concentrations given below when tested in the5 samples described above. Drug Concentration tested Acetaminophen 1324 μmol/L Acetylsalicylic Acid 3.63 mmol/L Amoxicillin 206 µmol/L Ascorbic Acid 342 μmol/L Caffeine 308 μmol/L Cefotaxime 673 µmol/L Cefuroxime 1416 µmol/L Chloramphenicol 155 µmol/L Cimetidine 79.2 μmol/L Digoxin 7.8 nmol/L Fluconazole 245 µmol/L 7 Drug Concentration tested Ibuprofen 2425 μmol/L Penicillin 75 mg/L Phenytoin 198 μmol/L Antigen Excess Detection The Optilite’s ability to detect antigen excess was evaluated with a sample of 2857 mg/L run neat on three different lots of reagents. This is equivalent to running a sample with a concentration of 71,425 mg/L at the standard measuring dilution of 1:26 (e.g., approximately 26 times the top of the calibration curve). Antigen excess was correctly detected and flagged by the analyser in all cases. The product insert states that: “Antigen excess check warning protection (‘antigen limit low’ flags) may be seen against IgG4 results” and “Potential occurrences of antigen excess cannot be completely excluded; in rare cases samples with monoclonal IgG4 present may give falsely low results due to antigen excess. Where this is possible or suspected it is recommended that the sample is re-assayed at a higher dilution to confirm the result.” f. Assay cut-off: Not applicable. 2. Comparison studies: a. Method comparison with predicate device: A method comparison study between the Optilite IgG4 Kit and the predicate device was performed by analyzing 567 serum samples (26 normal donors and 541 clinical samples, of which 322 were pediatric samples). Of the 567 total samples, 541 were clinical samples which included 199 samples with diagnosis and 342 samples with unavailable clinical information. The 199 samples with diagnoses includes: 45 confirmed hypogammaglobulinaemia; 23 hypergammaglobulinaemia; 1 suspected hypogammaglobulinaemia; 9 suspected hypergammaglobulinaemia; 1 anaphylaxis; 14 endocrine and autoimmune conditions were tested including 1 SLE (pediatric); 3 thyroid related disease (all pediatric); 2 diabetes (all pediatric); 8 obesity (all pediatric); 38 AIP; 5 benign conditions (all pediatric); 2 malignant conditions; 13 developmental conditions (all pediatric); 35 other clinical conditions (e.g. hyperkalemia, implanted device management, fracture, etc). Passing-Bablok regression analysis generated the following result: y = 0.91x + 8.09 (mg/L) with correlation coefficient r = 0.999. The package insert states that “Levels of IgG4 in normal adults may be undetectable; therefore, low IgG4 alone is insufficient evidence of an antibody deficiency disorder requiring Immunoglobulin replacement. Clinical history and other laboratory findings must be taken into account in the diagnosis of antibody deficiency disorder”. b. Matrix comparison: Not applicable 3. Clinical studies: 8 a. Clinical Sensitivity and specificity: Not applicable b. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference Interval: The product insert states the following: The ranges provided have been obtained from a limited number of samples and are intended for guidance purposes only. Expected values may vary with age, sex, sample type, diet and geographical location. Each laboratory should verify the transferability of the expected values to its own population and, if necessary, determine its own reference interval. Adult serum range This range was obtained by measuring the subclass content of sera provided by the Birmingham Blood Transfusion Service taken from healthy UK adult donors and generated using Binding Site’s BN™II subclass kits and verified using 50 US normal samples on the Optilite IgG4 Kit. Forty-eight of the 50 samples tested were within the 95 percentile range accepted criteria. Number (n) Mean (mg/L) Median (mg/L) 95 Percentile Range (mg/L) IgG4 30 280 215.3 39.2–864 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. 9 Conclusion:

idK161217_s0_e2000

K161217.txt

purpose for submission

To obtain a substantial equivalence determination for Ceftriaxone for testing of gram negative bacilli on the VITEK®2 and VITEK®2 Compact Antimicrobial Susceptibility Test (AST) Systems.

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K161217 B. Purpose for Submission: To obtain a substantial equivalence determination for Ceftriaxone for testing of gram negative bacilli on the VITEK®2 and VITEK®2 Compact Antimicrobial Susceptibility Test (AST) Systems. C. Measurand: The VITEK 2 AST-Gram Negative card contains the following concentrations of Ceftriaxone: 0.12, 0.25, 1, 4 and 16μg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result reporting range for the card is ≤ 0.25 - ≥64 µg/mL. D. Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test for Ceftriaxone E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: VITEK®2 Gram Negative Ceftriaxone (≤ 0.25 - ≥64 µg/mL) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System 2. Classification: Class II 2 3. Product code: LON - Fully automated short-term incubation cycle antimicrobial susceptibility system LTW – Susceptibility Test Cards, Antimicrobial LTT – Panels, Test, Susceptibility, Antimicrobial 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 2. Indication(s) for use: VITEK®2 Gram Negative Ceftriaxone is designed for antimicrobial susceptibility testing of Gram negative bacilli. VITEK®2 Gram Negative Ceftriaxone is a quantitative test intended for use with the VITEK®2 and VITEK®2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Ceftriaxone has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella oxytoca Proteus mirabilis Serratia marcescens In vitro data available but clinical significance is unknown: Citrobacter freundii Citrobacter koseri (formerly Citrobacter diversus) Shigella species Providencia species (including Providencia rettgeri) Salmonella species (including Salmonella typhi) The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of 3 isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 3. Special conditions for use statement(s): Prescription use only The following limitations are included in the device labeling: · Perform an alternate method of testing prior to reporting results for the following antibiotic/organism combination Ceftriaxone/Proteus vulgaris · The ability of the AST card to detect resistance with the following combination(s) is unknown because resistant strains were not available at the time of comparable testing. Ceftriaxone: Shigella species, Providencia rettgeri, and Salmonella species. 4. Special instrument requirements: VITEK® 2 and VITEK®2 Compact Systems I. Device Description: The VITEK® 2 AST card is a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 test card contains 64 microwells. A control well containing only culture medium is included on all cards, with the remaining wells containing premeasured amounts of a specific antimicrobial agent in a culture medium base. A suspension of organisms from a pure culture is prepared in a tube containing 0.45-0.5% sterile saline and standardized to a McFarland 0.5 using the DensiCHEK Plus™. The VITEK 2 System automatically fills seals and places the card into the incubator/reader; manual methods can also be used for the inoculation of test cards for use in the VITEK 2 System. The VITEK 2 Compact has a manual filling and sealing operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card. VITEK®2 AST-Gram Negative Ceftriaxone has the following concentrations in the card: 0.12, 0.25, 1, 4 and 16µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 card is ≤ 0.25 - ≥64 µg/mL. J. Substantial Equivalence Information: 1. Predicate device name(s): VITEK®2 AST-GN Doxycycline 4 2. Predicate 510(k) number(s): K121546 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device VITEK®2 AST-GN Ceftriaxone Predicate VITEK®2 AST-GN Doxycyline (K121546) Intended Use The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast. Same Test Method Automated quantitative antimicrobial susceptibility test for use with the VITEK®2 and VITEK®2 Compact Systems to determine the in vitro susceptibility of Gram negative bacilli Same Inoculum Saline suspension of organisms Same Differences Item Device Predicate Antimicrobial Ceftriaxone Doxycycline Antimicrobial Concentration 0.12, 0.25, 1, 4 and 16 1, 4, and 16 Reading Algorithm Growth pattern analysis- Unique to Ceftriaxone Discriminate Analysis - Unique to Doxycycline K. Standard/Guidance Document Referenced (if applicable): CLSI M100-S25 Performance Standards for Antimicrobial Susceptibility Testing CLSI M07-A10: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically 5 Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems L. Test Principle: The VITEK 2 and VITEK 2 Compact Systems utilize automated growth-based detection using attenuation of light measured by an optical scanner. The optics used in the systems use visible light to directly measure organism growth. Transmittance optics are based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. The VITEK 2 System monitors the growth of each well in the card over a defined period of time. An interpretive call is made between 4 and 16 hours for a “rapid” read but may be extended to 18 hours in some instances. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic on the card. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three sites using ten isolates of gram negative bacilli that were consistent with the intended use. Isolates were tested in triplicate over three days for a total of 270 data points. The isolates tested in the reproducibility study included Enterobacter aerogenes (one isolate), E. coli (two isolates), Klebsiella pneumoniae (four isolates), Serratia marcescens (two isolates) and Citrobacter freundii (one isolate). Inocula were prepared both manually and using automatic dilution for testing in the VITEK 2. Inocula were prepared manually for testing in the VITEK 2 Compact. The modal MIC value was determined and the reproducibility was calculated based on MIC values falling within ± 1 dilution of the mode MIC value. Using VITEK 2 automatic and manual dilution options, the best and worst case results were 100%. All results were on scale. Using VITEK 2 Compact and manual dilution, best and worst case reproducibility was 98 Purpose for submission:

idK161217_s0_e2000

K161217.txt

type of test

Automated quantitative or qualitative antimicrobial susceptibility test for Ceftriaxone

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K161217 B. Purpose for Submission: To obtain a substantial equivalence determination for Ceftriaxone for testing of gram negative bacilli on the VITEK®2 and VITEK®2 Compact Antimicrobial Susceptibility Test (AST) Systems. C. Measurand: The VITEK 2 AST-Gram Negative card contains the following concentrations of Ceftriaxone: 0.12, 0.25, 1, 4 and 16μg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result reporting range for the card is ≤ 0.25 - ≥64 µg/mL. D. Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test for Ceftriaxone E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: VITEK®2 Gram Negative Ceftriaxone (≤ 0.25 - ≥64 µg/mL) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System 2. Classification: Class II 2 3. Product code: LON - Fully automated short-term incubation cycle antimicrobial susceptibility system LTW – Susceptibility Test Cards, Antimicrobial LTT – Panels, Test, Susceptibility, Antimicrobial 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 2. Indication(s) for use: VITEK®2 Gram Negative Ceftriaxone is designed for antimicrobial susceptibility testing of Gram negative bacilli. VITEK®2 Gram Negative Ceftriaxone is a quantitative test intended for use with the VITEK®2 and VITEK®2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Ceftriaxone has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella oxytoca Proteus mirabilis Serratia marcescens In vitro data available but clinical significance is unknown: Citrobacter freundii Citrobacter koseri (formerly Citrobacter diversus) Shigella species Providencia species (including Providencia rettgeri) Salmonella species (including Salmonella typhi) The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of 3 isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 3. Special conditions for use statement(s): Prescription use only The following limitations are included in the device labeling: · Perform an alternate method of testing prior to reporting results for the following antibiotic/organism combination Ceftriaxone/Proteus vulgaris · The ability of the AST card to detect resistance with the following combination(s) is unknown because resistant strains were not available at the time of comparable testing. Ceftriaxone: Shigella species, Providencia rettgeri, and Salmonella species. 4. Special instrument requirements: VITEK® 2 and VITEK®2 Compact Systems I. Device Description: The VITEK® 2 AST card is a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 test card contains 64 microwells. A control well containing only culture medium is included on all cards, with the remaining wells containing premeasured amounts of a specific antimicrobial agent in a culture medium base. A suspension of organisms from a pure culture is prepared in a tube containing 0.45-0.5% sterile saline and standardized to a McFarland 0.5 using the DensiCHEK Plus™. The VITEK 2 System automatically fills seals and places the card into the incubator/reader; manual methods can also be used for the inoculation of test cards for use in the VITEK 2 System. The VITEK 2 Compact has a manual filling and sealing operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card. VITEK®2 AST-Gram Negative Ceftriaxone has the following concentrations in the card: 0.12, 0.25, 1, 4 and 16µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 card is ≤ 0.25 - ≥64 µg/mL. J. Substantial Equivalence Information: 1. Predicate device name(s): VITEK®2 AST-GN Doxycycline 4 2. Predicate 510(k) number(s): K121546 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device VITEK®2 AST-GN Ceftriaxone Predicate VITEK®2 AST-GN Doxycyline (K121546) Intended Use The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast. Same Test Method Automated quantitative antimicrobial susceptibility test for use with the VITEK®2 and VITEK®2 Compact Systems to determine the in vitro susceptibility of Gram negative bacilli Same Inoculum Saline suspension of organisms Same Differences Item Device Predicate Antimicrobial Ceftriaxone Doxycycline Antimicrobial Concentration 0.12, 0.25, 1, 4 and 16 1, 4, and 16 Reading Algorithm Growth pattern analysis- Unique to Ceftriaxone Discriminate Analysis - Unique to Doxycycline K. Standard/Guidance Document Referenced (if applicable): CLSI M100-S25 Performance Standards for Antimicrobial Susceptibility Testing CLSI M07-A10: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically 5 Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems L. Test Principle: The VITEK 2 and VITEK 2 Compact Systems utilize automated growth-based detection using attenuation of light measured by an optical scanner. The optics used in the systems use visible light to directly measure organism growth. Transmittance optics are based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. The VITEK 2 System monitors the growth of each well in the card over a defined period of time. An interpretive call is made between 4 and 16 hours for a “rapid” read but may be extended to 18 hours in some instances. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic on the card. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three sites using ten isolates of gram negative bacilli that were consistent with the intended use. Isolates were tested in triplicate over three days for a total of 270 data points. The isolates tested in the reproducibility study included Enterobacter aerogenes (one isolate), E. coli (two isolates), Klebsiella pneumoniae (four isolates), Serratia marcescens (two isolates) and Citrobacter freundii (one isolate). Inocula were prepared both manually and using automatic dilution for testing in the VITEK 2. Inocula were prepared manually for testing in the VITEK 2 Compact. The modal MIC value was determined and the reproducibility was calculated based on MIC values falling within ± 1 dilution of the mode MIC value. Using VITEK 2 automatic and manual dilution options, the best and worst case results were 100%. All results were on scale. Using VITEK 2 Compact and manual dilution, best and worst case reproducibility was 98 Type of test:

idK161217_s0_e2000

K161217.txt

classification

Class II

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K161217 B. Purpose for Submission: To obtain a substantial equivalence determination for Ceftriaxone for testing of gram negative bacilli on the VITEK®2 and VITEK®2 Compact Antimicrobial Susceptibility Test (AST) Systems. C. Measurand: The VITEK 2 AST-Gram Negative card contains the following concentrations of Ceftriaxone: 0.12, 0.25, 1, 4 and 16μg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result reporting range for the card is ≤ 0.25 - ≥64 µg/mL. D. Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test for Ceftriaxone E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: VITEK®2 Gram Negative Ceftriaxone (≤ 0.25 - ≥64 µg/mL) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System 2. Classification: Class II 2 3. Product code: LON - Fully automated short-term incubation cycle antimicrobial susceptibility system LTW – Susceptibility Test Cards, Antimicrobial LTT – Panels, Test, Susceptibility, Antimicrobial 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 2. Indication(s) for use: VITEK®2 Gram Negative Ceftriaxone is designed for antimicrobial susceptibility testing of Gram negative bacilli. VITEK®2 Gram Negative Ceftriaxone is a quantitative test intended for use with the VITEK®2 and VITEK®2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Ceftriaxone has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella oxytoca Proteus mirabilis Serratia marcescens In vitro data available but clinical significance is unknown: Citrobacter freundii Citrobacter koseri (formerly Citrobacter diversus) Shigella species Providencia species (including Providencia rettgeri) Salmonella species (including Salmonella typhi) The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of 3 isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 3. Special conditions for use statement(s): Prescription use only The following limitations are included in the device labeling: · Perform an alternate method of testing prior to reporting results for the following antibiotic/organism combination Ceftriaxone/Proteus vulgaris · The ability of the AST card to detect resistance with the following combination(s) is unknown because resistant strains were not available at the time of comparable testing. Ceftriaxone: Shigella species, Providencia rettgeri, and Salmonella species. 4. Special instrument requirements: VITEK® 2 and VITEK®2 Compact Systems I. Device Description: The VITEK® 2 AST card is a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 test card contains 64 microwells. A control well containing only culture medium is included on all cards, with the remaining wells containing premeasured amounts of a specific antimicrobial agent in a culture medium base. A suspension of organisms from a pure culture is prepared in a tube containing 0.45-0.5% sterile saline and standardized to a McFarland 0.5 using the DensiCHEK Plus™. The VITEK 2 System automatically fills seals and places the card into the incubator/reader; manual methods can also be used for the inoculation of test cards for use in the VITEK 2 System. The VITEK 2 Compact has a manual filling and sealing operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card. VITEK®2 AST-Gram Negative Ceftriaxone has the following concentrations in the card: 0.12, 0.25, 1, 4 and 16µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 card is ≤ 0.25 - ≥64 µg/mL. J. Substantial Equivalence Information: 1. Predicate device name(s): VITEK®2 AST-GN Doxycycline 4 2. Predicate 510(k) number(s): K121546 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device VITEK®2 AST-GN Ceftriaxone Predicate VITEK®2 AST-GN Doxycyline (K121546) Intended Use The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast. Same Test Method Automated quantitative antimicrobial susceptibility test for use with the VITEK®2 and VITEK®2 Compact Systems to determine the in vitro susceptibility of Gram negative bacilli Same Inoculum Saline suspension of organisms Same Differences Item Device Predicate Antimicrobial Ceftriaxone Doxycycline Antimicrobial Concentration 0.12, 0.25, 1, 4 and 16 1, 4, and 16 Reading Algorithm Growth pattern analysis- Unique to Ceftriaxone Discriminate Analysis - Unique to Doxycycline K. Standard/Guidance Document Referenced (if applicable): CLSI M100-S25 Performance Standards for Antimicrobial Susceptibility Testing CLSI M07-A10: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically 5 Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems L. Test Principle: The VITEK 2 and VITEK 2 Compact Systems utilize automated growth-based detection using attenuation of light measured by an optical scanner. The optics used in the systems use visible light to directly measure organism growth. Transmittance optics are based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. The VITEK 2 System monitors the growth of each well in the card over a defined period of time. An interpretive call is made between 4 and 16 hours for a “rapid” read but may be extended to 18 hours in some instances. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic on the card. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three sites using ten isolates of gram negative bacilli that were consistent with the intended use. Isolates were tested in triplicate over three days for a total of 270 data points. The isolates tested in the reproducibility study included Enterobacter aerogenes (one isolate), E. coli (two isolates), Klebsiella pneumoniae (four isolates), Serratia marcescens (two isolates) and Citrobacter freundii (one isolate). Inocula were prepared both manually and using automatic dilution for testing in the VITEK 2. Inocula were prepared manually for testing in the VITEK 2 Compact. The modal MIC value was determined and the reproducibility was calculated based on MIC values falling within ± 1 dilution of the mode MIC value. Using VITEK 2 automatic and manual dilution options, the best and worst case results were 100%. All results were on scale. Using VITEK 2 Compact and manual dilution, best and worst case reproducibility was 98 Classification:

idK161217_s0_e2000

K161217.txt

panel

83 Microbiology

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K161217 B. Purpose for Submission: To obtain a substantial equivalence determination for Ceftriaxone for testing of gram negative bacilli on the VITEK®2 and VITEK®2 Compact Antimicrobial Susceptibility Test (AST) Systems. C. Measurand: The VITEK 2 AST-Gram Negative card contains the following concentrations of Ceftriaxone: 0.12, 0.25, 1, 4 and 16μg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result reporting range for the card is ≤ 0.25 - ≥64 µg/mL. D. Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test for Ceftriaxone E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: VITEK®2 Gram Negative Ceftriaxone (≤ 0.25 - ≥64 µg/mL) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System 2. Classification: Class II 2 3. Product code: LON - Fully automated short-term incubation cycle antimicrobial susceptibility system LTW – Susceptibility Test Cards, Antimicrobial LTT – Panels, Test, Susceptibility, Antimicrobial 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 2. Indication(s) for use: VITEK®2 Gram Negative Ceftriaxone is designed for antimicrobial susceptibility testing of Gram negative bacilli. VITEK®2 Gram Negative Ceftriaxone is a quantitative test intended for use with the VITEK®2 and VITEK®2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Ceftriaxone has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella oxytoca Proteus mirabilis Serratia marcescens In vitro data available but clinical significance is unknown: Citrobacter freundii Citrobacter koseri (formerly Citrobacter diversus) Shigella species Providencia species (including Providencia rettgeri) Salmonella species (including Salmonella typhi) The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of 3 isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 3. Special conditions for use statement(s): Prescription use only The following limitations are included in the device labeling: · Perform an alternate method of testing prior to reporting results for the following antibiotic/organism combination Ceftriaxone/Proteus vulgaris · The ability of the AST card to detect resistance with the following combination(s) is unknown because resistant strains were not available at the time of comparable testing. Ceftriaxone: Shigella species, Providencia rettgeri, and Salmonella species. 4. Special instrument requirements: VITEK® 2 and VITEK®2 Compact Systems I. Device Description: The VITEK® 2 AST card is a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 test card contains 64 microwells. A control well containing only culture medium is included on all cards, with the remaining wells containing premeasured amounts of a specific antimicrobial agent in a culture medium base. A suspension of organisms from a pure culture is prepared in a tube containing 0.45-0.5% sterile saline and standardized to a McFarland 0.5 using the DensiCHEK Plus™. The VITEK 2 System automatically fills seals and places the card into the incubator/reader; manual methods can also be used for the inoculation of test cards for use in the VITEK 2 System. The VITEK 2 Compact has a manual filling and sealing operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card. VITEK®2 AST-Gram Negative Ceftriaxone has the following concentrations in the card: 0.12, 0.25, 1, 4 and 16µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 card is ≤ 0.25 - ≥64 µg/mL. J. Substantial Equivalence Information: 1. Predicate device name(s): VITEK®2 AST-GN Doxycycline 4 2. Predicate 510(k) number(s): K121546 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device VITEK®2 AST-GN Ceftriaxone Predicate VITEK®2 AST-GN Doxycyline (K121546) Intended Use The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast. Same Test Method Automated quantitative antimicrobial susceptibility test for use with the VITEK®2 and VITEK®2 Compact Systems to determine the in vitro susceptibility of Gram negative bacilli Same Inoculum Saline suspension of organisms Same Differences Item Device Predicate Antimicrobial Ceftriaxone Doxycycline Antimicrobial Concentration 0.12, 0.25, 1, 4 and 16 1, 4, and 16 Reading Algorithm Growth pattern analysis- Unique to Ceftriaxone Discriminate Analysis - Unique to Doxycycline K. Standard/Guidance Document Referenced (if applicable): CLSI M100-S25 Performance Standards for Antimicrobial Susceptibility Testing CLSI M07-A10: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically 5 Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems L. Test Principle: The VITEK 2 and VITEK 2 Compact Systems utilize automated growth-based detection using attenuation of light measured by an optical scanner. The optics used in the systems use visible light to directly measure organism growth. Transmittance optics are based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. The VITEK 2 System monitors the growth of each well in the card over a defined period of time. An interpretive call is made between 4 and 16 hours for a “rapid” read but may be extended to 18 hours in some instances. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic on the card. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three sites using ten isolates of gram negative bacilli that were consistent with the intended use. Isolates were tested in triplicate over three days for a total of 270 data points. The isolates tested in the reproducibility study included Enterobacter aerogenes (one isolate), E. coli (two isolates), Klebsiella pneumoniae (four isolates), Serratia marcescens (two isolates) and Citrobacter freundii (one isolate). Inocula were prepared both manually and using automatic dilution for testing in the VITEK 2. Inocula were prepared manually for testing in the VITEK 2 Compact. The modal MIC value was determined and the reproducibility was calculated based on MIC values falling within ± 1 dilution of the mode MIC value. Using VITEK 2 automatic and manual dilution options, the best and worst case results were 100%. All results were on scale. Using VITEK 2 Compact and manual dilution, best and worst case reproducibility was 98 Panel:

idK161217_s0_e2000

K161217.txt

intended use

The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K161217 B. Purpose for Submission: To obtain a substantial equivalence determination for Ceftriaxone for testing of gram negative bacilli on the VITEK®2 and VITEK®2 Compact Antimicrobial Susceptibility Test (AST) Systems. C. Measurand: The VITEK 2 AST-Gram Negative card contains the following concentrations of Ceftriaxone: 0.12, 0.25, 1, 4 and 16μg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result reporting range for the card is ≤ 0.25 - ≥64 µg/mL. D. Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test for Ceftriaxone E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: VITEK®2 Gram Negative Ceftriaxone (≤ 0.25 - ≥64 µg/mL) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System 2. Classification: Class II 2 3. Product code: LON - Fully automated short-term incubation cycle antimicrobial susceptibility system LTW – Susceptibility Test Cards, Antimicrobial LTT – Panels, Test, Susceptibility, Antimicrobial 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 2. Indication(s) for use: VITEK®2 Gram Negative Ceftriaxone is designed for antimicrobial susceptibility testing of Gram negative bacilli. VITEK®2 Gram Negative Ceftriaxone is a quantitative test intended for use with the VITEK®2 and VITEK®2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Ceftriaxone has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella oxytoca Proteus mirabilis Serratia marcescens In vitro data available but clinical significance is unknown: Citrobacter freundii Citrobacter koseri (formerly Citrobacter diversus) Shigella species Providencia species (including Providencia rettgeri) Salmonella species (including Salmonella typhi) The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of 3 isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 3. Special conditions for use statement(s): Prescription use only The following limitations are included in the device labeling: · Perform an alternate method of testing prior to reporting results for the following antibiotic/organism combination Ceftriaxone/Proteus vulgaris · The ability of the AST card to detect resistance with the following combination(s) is unknown because resistant strains were not available at the time of comparable testing. Ceftriaxone: Shigella species, Providencia rettgeri, and Salmonella species. 4. Special instrument requirements: VITEK® 2 and VITEK®2 Compact Systems I. Device Description: The VITEK® 2 AST card is a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 test card contains 64 microwells. A control well containing only culture medium is included on all cards, with the remaining wells containing premeasured amounts of a specific antimicrobial agent in a culture medium base. A suspension of organisms from a pure culture is prepared in a tube containing 0.45-0.5% sterile saline and standardized to a McFarland 0.5 using the DensiCHEK Plus™. The VITEK 2 System automatically fills seals and places the card into the incubator/reader; manual methods can also be used for the inoculation of test cards for use in the VITEK 2 System. The VITEK 2 Compact has a manual filling and sealing operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card. VITEK®2 AST-Gram Negative Ceftriaxone has the following concentrations in the card: 0.12, 0.25, 1, 4 and 16µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 card is ≤ 0.25 - ≥64 µg/mL. J. Substantial Equivalence Information: 1. Predicate device name(s): VITEK®2 AST-GN Doxycycline 4 2. Predicate 510(k) number(s): K121546 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device VITEK®2 AST-GN Ceftriaxone Predicate VITEK®2 AST-GN Doxycyline (K121546) Intended Use The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast. Same Test Method Automated quantitative antimicrobial susceptibility test for use with the VITEK®2 and VITEK®2 Compact Systems to determine the in vitro susceptibility of Gram negative bacilli Same Inoculum Saline suspension of organisms Same Differences Item Device Predicate Antimicrobial Ceftriaxone Doxycycline Antimicrobial Concentration 0.12, 0.25, 1, 4 and 16 1, 4, and 16 Reading Algorithm Growth pattern analysis- Unique to Ceftriaxone Discriminate Analysis - Unique to Doxycycline K. Standard/Guidance Document Referenced (if applicable): CLSI M100-S25 Performance Standards for Antimicrobial Susceptibility Testing CLSI M07-A10: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically 5 Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems L. Test Principle: The VITEK 2 and VITEK 2 Compact Systems utilize automated growth-based detection using attenuation of light measured by an optical scanner. The optics used in the systems use visible light to directly measure organism growth. Transmittance optics are based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. The VITEK 2 System monitors the growth of each well in the card over a defined period of time. An interpretive call is made between 4 and 16 hours for a “rapid” read but may be extended to 18 hours in some instances. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic on the card. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three sites using ten isolates of gram negative bacilli that were consistent with the intended use. Isolates were tested in triplicate over three days for a total of 270 data points. The isolates tested in the reproducibility study included Enterobacter aerogenes (one isolate), E. coli (two isolates), Klebsiella pneumoniae (four isolates), Serratia marcescens (two isolates) and Citrobacter freundii (one isolate). Inocula were prepared both manually and using automatic dilution for testing in the VITEK 2. Inocula were prepared manually for testing in the VITEK 2 Compact. The modal MIC value was determined and the reproducibility was calculated based on MIC values falling within ± 1 dilution of the mode MIC value. Using VITEK 2 automatic and manual dilution options, the best and worst case results were 100%. All results were on scale. Using VITEK 2 Compact and manual dilution, best and worst case reproducibility was 98 Intended use:

idK161217_s0_e2000

K161217.txt

predicate device name

VITEK®2 AST-GN Doxycycline

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K161217 B. Purpose for Submission: To obtain a substantial equivalence determination for Ceftriaxone for testing of gram negative bacilli on the VITEK®2 and VITEK®2 Compact Antimicrobial Susceptibility Test (AST) Systems. C. Measurand: The VITEK 2 AST-Gram Negative card contains the following concentrations of Ceftriaxone: 0.12, 0.25, 1, 4 and 16μg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result reporting range for the card is ≤ 0.25 - ≥64 µg/mL. D. Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test for Ceftriaxone E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: VITEK®2 Gram Negative Ceftriaxone (≤ 0.25 - ≥64 µg/mL) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System 2. Classification: Class II 2 3. Product code: LON - Fully automated short-term incubation cycle antimicrobial susceptibility system LTW – Susceptibility Test Cards, Antimicrobial LTT – Panels, Test, Susceptibility, Antimicrobial 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 2. Indication(s) for use: VITEK®2 Gram Negative Ceftriaxone is designed for antimicrobial susceptibility testing of Gram negative bacilli. VITEK®2 Gram Negative Ceftriaxone is a quantitative test intended for use with the VITEK®2 and VITEK®2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Ceftriaxone has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella oxytoca Proteus mirabilis Serratia marcescens In vitro data available but clinical significance is unknown: Citrobacter freundii Citrobacter koseri (formerly Citrobacter diversus) Shigella species Providencia species (including Providencia rettgeri) Salmonella species (including Salmonella typhi) The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of 3 isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 3. Special conditions for use statement(s): Prescription use only The following limitations are included in the device labeling: · Perform an alternate method of testing prior to reporting results for the following antibiotic/organism combination Ceftriaxone/Proteus vulgaris · The ability of the AST card to detect resistance with the following combination(s) is unknown because resistant strains were not available at the time of comparable testing. Ceftriaxone: Shigella species, Providencia rettgeri, and Salmonella species. 4. Special instrument requirements: VITEK® 2 and VITEK®2 Compact Systems I. Device Description: The VITEK® 2 AST card is a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 test card contains 64 microwells. A control well containing only culture medium is included on all cards, with the remaining wells containing premeasured amounts of a specific antimicrobial agent in a culture medium base. A suspension of organisms from a pure culture is prepared in a tube containing 0.45-0.5% sterile saline and standardized to a McFarland 0.5 using the DensiCHEK Plus™. The VITEK 2 System automatically fills seals and places the card into the incubator/reader; manual methods can also be used for the inoculation of test cards for use in the VITEK 2 System. The VITEK 2 Compact has a manual filling and sealing operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card. VITEK®2 AST-Gram Negative Ceftriaxone has the following concentrations in the card: 0.12, 0.25, 1, 4 and 16µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 card is ≤ 0.25 - ≥64 µg/mL. J. Substantial Equivalence Information: 1. Predicate device name(s): VITEK®2 AST-GN Doxycycline 4 2. Predicate 510(k) number(s): K121546 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device VITEK®2 AST-GN Ceftriaxone Predicate VITEK®2 AST-GN Doxycyline (K121546) Intended Use The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast. Same Test Method Automated quantitative antimicrobial susceptibility test for use with the VITEK®2 and VITEK®2 Compact Systems to determine the in vitro susceptibility of Gram negative bacilli Same Inoculum Saline suspension of organisms Same Differences Item Device Predicate Antimicrobial Ceftriaxone Doxycycline Antimicrobial Concentration 0.12, 0.25, 1, 4 and 16 1, 4, and 16 Reading Algorithm Growth pattern analysis- Unique to Ceftriaxone Discriminate Analysis - Unique to Doxycycline K. Standard/Guidance Document Referenced (if applicable): CLSI M100-S25 Performance Standards for Antimicrobial Susceptibility Testing CLSI M07-A10: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically 5 Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems L. Test Principle: The VITEK 2 and VITEK 2 Compact Systems utilize automated growth-based detection using attenuation of light measured by an optical scanner. The optics used in the systems use visible light to directly measure organism growth. Transmittance optics are based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. The VITEK 2 System monitors the growth of each well in the card over a defined period of time. An interpretive call is made between 4 and 16 hours for a “rapid” read but may be extended to 18 hours in some instances. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic on the card. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three sites using ten isolates of gram negative bacilli that were consistent with the intended use. Isolates were tested in triplicate over three days for a total of 270 data points. The isolates tested in the reproducibility study included Enterobacter aerogenes (one isolate), E. coli (two isolates), Klebsiella pneumoniae (four isolates), Serratia marcescens (two isolates) and Citrobacter freundii (one isolate). Inocula were prepared both manually and using automatic dilution for testing in the VITEK 2. Inocula were prepared manually for testing in the VITEK 2 Compact. The modal MIC value was determined and the reproducibility was calculated based on MIC values falling within ± 1 dilution of the mode MIC value. Using VITEK 2 automatic and manual dilution options, the best and worst case results were 100%. All results were on scale. Using VITEK 2 Compact and manual dilution, best and worst case reproducibility was 98 Predicate device name:

idK161217_s0_e2000

K161217.txt

applicant

bioMérieux, Inc.

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K161217 B. Purpose for Submission: To obtain a substantial equivalence determination for Ceftriaxone for testing of gram negative bacilli on the VITEK®2 and VITEK®2 Compact Antimicrobial Susceptibility Test (AST) Systems. C. Measurand: The VITEK 2 AST-Gram Negative card contains the following concentrations of Ceftriaxone: 0.12, 0.25, 1, 4 and 16μg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result reporting range for the card is ≤ 0.25 - ≥64 µg/mL. D. Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test for Ceftriaxone E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: VITEK®2 Gram Negative Ceftriaxone (≤ 0.25 - ≥64 µg/mL) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System 2. Classification: Class II 2 3. Product code: LON - Fully automated short-term incubation cycle antimicrobial susceptibility system LTW – Susceptibility Test Cards, Antimicrobial LTT – Panels, Test, Susceptibility, Antimicrobial 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 2. Indication(s) for use: VITEK®2 Gram Negative Ceftriaxone is designed for antimicrobial susceptibility testing of Gram negative bacilli. VITEK®2 Gram Negative Ceftriaxone is a quantitative test intended for use with the VITEK®2 and VITEK®2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Ceftriaxone has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella oxytoca Proteus mirabilis Serratia marcescens In vitro data available but clinical significance is unknown: Citrobacter freundii Citrobacter koseri (formerly Citrobacter diversus) Shigella species Providencia species (including Providencia rettgeri) Salmonella species (including Salmonella typhi) The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of 3 isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 3. Special conditions for use statement(s): Prescription use only The following limitations are included in the device labeling: · Perform an alternate method of testing prior to reporting results for the following antibiotic/organism combination Ceftriaxone/Proteus vulgaris · The ability of the AST card to detect resistance with the following combination(s) is unknown because resistant strains were not available at the time of comparable testing. Ceftriaxone: Shigella species, Providencia rettgeri, and Salmonella species. 4. Special instrument requirements: VITEK® 2 and VITEK®2 Compact Systems I. Device Description: The VITEK® 2 AST card is a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 test card contains 64 microwells. A control well containing only culture medium is included on all cards, with the remaining wells containing premeasured amounts of a specific antimicrobial agent in a culture medium base. A suspension of organisms from a pure culture is prepared in a tube containing 0.45-0.5% sterile saline and standardized to a McFarland 0.5 using the DensiCHEK Plus™. The VITEK 2 System automatically fills seals and places the card into the incubator/reader; manual methods can also be used for the inoculation of test cards for use in the VITEK 2 System. The VITEK 2 Compact has a manual filling and sealing operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card. VITEK®2 AST-Gram Negative Ceftriaxone has the following concentrations in the card: 0.12, 0.25, 1, 4 and 16µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 card is ≤ 0.25 - ≥64 µg/mL. J. Substantial Equivalence Information: 1. Predicate device name(s): VITEK®2 AST-GN Doxycycline 4 2. Predicate 510(k) number(s): K121546 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device VITEK®2 AST-GN Ceftriaxone Predicate VITEK®2 AST-GN Doxycyline (K121546) Intended Use The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast. Same Test Method Automated quantitative antimicrobial susceptibility test for use with the VITEK®2 and VITEK®2 Compact Systems to determine the in vitro susceptibility of Gram negative bacilli Same Inoculum Saline suspension of organisms Same Differences Item Device Predicate Antimicrobial Ceftriaxone Doxycycline Antimicrobial Concentration 0.12, 0.25, 1, 4 and 16 1, 4, and 16 Reading Algorithm Growth pattern analysis- Unique to Ceftriaxone Discriminate Analysis - Unique to Doxycycline K. Standard/Guidance Document Referenced (if applicable): CLSI M100-S25 Performance Standards for Antimicrobial Susceptibility Testing CLSI M07-A10: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically 5 Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems L. Test Principle: The VITEK 2 and VITEK 2 Compact Systems utilize automated growth-based detection using attenuation of light measured by an optical scanner. The optics used in the systems use visible light to directly measure organism growth. Transmittance optics are based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. The VITEK 2 System monitors the growth of each well in the card over a defined period of time. An interpretive call is made between 4 and 16 hours for a “rapid” read but may be extended to 18 hours in some instances. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic on the card. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three sites using ten isolates of gram negative bacilli that were consistent with the intended use. Isolates were tested in triplicate over three days for a total of 270 data points. The isolates tested in the reproducibility study included Enterobacter aerogenes (one isolate), E. coli (two isolates), Klebsiella pneumoniae (four isolates), Serratia marcescens (two isolates) and Citrobacter freundii (one isolate). Inocula were prepared both manually and using automatic dilution for testing in the VITEK 2. Inocula were prepared manually for testing in the VITEK 2 Compact. The modal MIC value was determined and the reproducibility was calculated based on MIC values falling within ± 1 dilution of the mode MIC value. Using VITEK 2 automatic and manual dilution options, the best and worst case results were 100%. All results were on scale. Using VITEK 2 Compact and manual dilution, best and worst case reproducibility was 98 Applicant:

idK161217_s0_e2000

K161217.txt

proprietary and established names

VITEK®2 Gram Negative Ceftriaxone (≤ 0.25 - ≥64 µg/mL)

IAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K161217 B. Purpose for Submission: To obtain a substantial equivalence determination for Ceftriaxone for testing of gram negative bacilli on the VITEK®2 and VITEK®2 Compact Antimicrobial Susceptibility Test (AST) Systems. C. Measurand: The VITEK 2 AST-Gram Negative card contains the following concentrations of Ceftriaxone: 0.12, 0.25, 1, 4 and 16μg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result reporting range for the card is ≤ 0.25 - ≥64 µg/mL. D. Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test for Ceftriaxone E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: VITEK®2 Gram Negative Ceftriaxone (≤ 0.25 - ≥64 µg/mL) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System 2. Classification: Class II 2 3. Product code: LON - Fully automated short-term incubation cycle antimicrobial susceptibility system LTW – Susceptibility Test Cards, Antimicrobial LTT – Panels, Test, Susceptibility, Antimicrobial 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 2. Indication(s) for use: VITEK®2 Gram Negative Ceftriaxone is designed for antimicrobial susceptibility testing of Gram negative bacilli. VITEK®2 Gram Negative Ceftriaxone is a quantitative test intended for use with the VITEK®2 and VITEK®2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Ceftriaxone has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella oxytoca Proteus mirabilis Serratia marcescens In vitro data available but clinical significance is unknown: Citrobacter freundii Citrobacter koseri (formerly Citrobacter diversus) Shigella species Providencia species (including Providencia rettgeri) Salmonella species (including Salmonella typhi) The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of 3 isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 3. Special conditions for use statement(s): Prescription use only The following limitations are included in the device labeling: · Perform an alternate method of testing prior to reporting results for the following antibiotic/organism combination Ceftriaxone/Proteus vulgaris · The ability of the AST card to detect resistance with the following combination(s) is unknown because resistant strains were not available at the time of comparable testing. Ceftriaxone: Shigella species, Providencia rettgeri, and Salmonella species. 4. Special instrument requirements: VITEK® 2 and VITEK®2 Compact Systems I. Device Description: The VITEK® 2 AST card is a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 test card contains 64 microwells. A control well containing only culture medium is included on all cards, with the remaining wells containing premeasured amounts of a specific antimicrobial agent in a culture medium base. A suspension of organisms from a pure culture is prepared in a tube containing 0.45-0.5% sterile saline and standardized to a McFarland 0.5 using the DensiCHEK Plus™. The VITEK 2 System automatically fills seals and places the card into the incubator/reader; manual methods can also be used for the inoculation of test cards for use in the VITEK 2 System. The VITEK 2 Compact has a manual filling and sealing operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card. VITEK®2 AST-Gram Negative Ceftriaxone has the following concentrations in the card: 0.12, 0.25, 1, 4 and 16µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 card is ≤ 0.25 - ≥64 µg/mL. J. Substantial Equivalence Information: 1. Predicate device name(s): VITEK®2 AST-GN Doxycycline 4 2. Predicate 510(k) number(s): K121546 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device VITEK®2 AST-GN Ceftriaxone Predicate VITEK®2 AST-GN Doxycyline (K121546) Intended Use The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast. Same Test Method Automated quantitative antimicrobial susceptibility test for use with the VITEK®2 and VITEK®2 Compact Systems to determine the in vitro susceptibility of Gram negative bacilli Same Inoculum Saline suspension of organisms Same Differences Item Device Predicate Antimicrobial Ceftriaxone Doxycycline Antimicrobial Concentration 0.12, 0.25, 1, 4 and 16 1, 4, and 16 Reading Algorithm Growth pattern analysis- Unique to Ceftriaxone Discriminate Analysis - Unique to Doxycycline K. Standard/Guidance Document Referenced (if applicable): CLSI M100-S25 Performance Standards for Antimicrobial Susceptibility Testing CLSI M07-A10: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically 5 Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems L. Test Principle: The VITEK 2 and VITEK 2 Compact Systems utilize automated growth-based detection using attenuation of light measured by an optical scanner. The optics used in the systems use visible light to directly measure organism growth. Transmittance optics are based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. The VITEK 2 System monitors the growth of each well in the card over a defined period of time. An interpretive call is made between 4 and 16 hours for a “rapid” read but may be extended to 18 hours in some instances. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic on the card. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three sites using ten isolates of gram negative bacilli that were consistent with the intended use. Isolates were tested in triplicate over three days for a total of 270 data points. The isolates tested in the reproducibility study included Enterobacter aerogenes (one isolate), E. coli (two isolates), Klebsiella pneumoniae (four isolates), Serratia marcescens (two isolates) and Citrobacter freundii (one isolate). Inocula were prepared both manually and using automatic dilution for testing in the VITEK 2. Inocula were prepared manually for testing in the VITEK 2 Compact. The modal MIC value was determined and the reproducibility was calculated based on MIC values falling within ± 1 dilution of the mode MIC value. Using VITEK 2 automatic and manual dilution options, the best and worst case results were 100%. All results were on scale. Using VITEK 2 Compact and manual dilution, best and worst case reproducibility was 98 Proprietary and established names:

idK161217_s0_e2000

K161217.txt

regulation section

21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K161217 B. Purpose for Submission: To obtain a substantial equivalence determination for Ceftriaxone for testing of gram negative bacilli on the VITEK®2 and VITEK®2 Compact Antimicrobial Susceptibility Test (AST) Systems. C. Measurand: The VITEK 2 AST-Gram Negative card contains the following concentrations of Ceftriaxone: 0.12, 0.25, 1, 4 and 16μg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result reporting range for the card is ≤ 0.25 - ≥64 µg/mL. D. Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test for Ceftriaxone E. Applicant: bioMérieux, Inc. F. Proprietary and Established Names: VITEK®2 Gram Negative Ceftriaxone (≤ 0.25 - ≥64 µg/mL) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System 2. Classification: Class II 2 3. Product code: LON - Fully automated short-term incubation cycle antimicrobial susceptibility system LTW – Susceptibility Test Cards, Antimicrobial LTT – Panels, Test, Susceptibility, Antimicrobial 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 2. Indication(s) for use: VITEK®2 Gram Negative Ceftriaxone is designed for antimicrobial susceptibility testing of Gram negative bacilli. VITEK®2 Gram Negative Ceftriaxone is a quantitative test intended for use with the VITEK®2 and VITEK®2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. Ceftriaxone has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: Enterobacter aerogenes Escherichia coli Klebsiella pneumoniae Klebsiella oxytoca Proteus mirabilis Serratia marcescens In vitro data available but clinical significance is unknown: Citrobacter freundii Citrobacter koseri (formerly Citrobacter diversus) Shigella species Providencia species (including Providencia rettgeri) Salmonella species (including Salmonella typhi) The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of 3 isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., S. pneumoniae and clinically significant yeast. 3. Special conditions for use statement(s): Prescription use only The following limitations are included in the device labeling: · Perform an alternate method of testing prior to reporting results for the following antibiotic/organism combination Ceftriaxone/Proteus vulgaris · The ability of the AST card to detect resistance with the following combination(s) is unknown because resistant strains were not available at the time of comparable testing. Ceftriaxone: Shigella species, Providencia rettgeri, and Salmonella species. 4. Special instrument requirements: VITEK® 2 and VITEK®2 Compact Systems I. Device Description: The VITEK® 2 AST card is a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK® 2 test card contains 64 microwells. A control well containing only culture medium is included on all cards, with the remaining wells containing premeasured amounts of a specific antimicrobial agent in a culture medium base. A suspension of organisms from a pure culture is prepared in a tube containing 0.45-0.5% sterile saline and standardized to a McFarland 0.5 using the DensiCHEK Plus™. The VITEK 2 System automatically fills seals and places the card into the incubator/reader; manual methods can also be used for the inoculation of test cards for use in the VITEK 2 System. The VITEK 2 Compact has a manual filling and sealing operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card. VITEK®2 AST-Gram Negative Ceftriaxone has the following concentrations in the card: 0.12, 0.25, 1, 4 and 16µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 card is ≤ 0.25 - ≥64 µg/mL. J. Substantial Equivalence Information: 1. Predicate device name(s): VITEK®2 AST-GN Doxycycline 4 2. Predicate 510(k) number(s): K121546 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device VITEK®2 AST-GN Ceftriaxone Predicate VITEK®2 AST-GN Doxycyline (K121546) Intended Use The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast. Same Test Method Automated quantitative antimicrobial susceptibility test for use with the VITEK®2 and VITEK®2 Compact Systems to determine the in vitro susceptibility of Gram negative bacilli Same Inoculum Saline suspension of organisms Same Differences Item Device Predicate Antimicrobial Ceftriaxone Doxycycline Antimicrobial Concentration 0.12, 0.25, 1, 4 and 16 1, 4, and 16 Reading Algorithm Growth pattern analysis- Unique to Ceftriaxone Discriminate Analysis - Unique to Doxycycline K. Standard/Guidance Document Referenced (if applicable): CLSI M100-S25 Performance Standards for Antimicrobial Susceptibility Testing CLSI M07-A10: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically 5 Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems L. Test Principle: The VITEK 2 and VITEK 2 Compact Systems utilize automated growth-based detection using attenuation of light measured by an optical scanner. The optics used in the systems use visible light to directly measure organism growth. Transmittance optics are based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. The VITEK 2 System monitors the growth of each well in the card over a defined period of time. An interpretive call is made between 4 and 16 hours for a “rapid” read but may be extended to 18 hours in some instances. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic on the card. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was conducted at three sites using ten isolates of gram negative bacilli that were consistent with the intended use. Isolates were tested in triplicate over three days for a total of 270 data points. The isolates tested in the reproducibility study included Enterobacter aerogenes (one isolate), E. coli (two isolates), Klebsiella pneumoniae (four isolates), Serratia marcescens (two isolates) and Citrobacter freundii (one isolate). Inocula were prepared both manually and using automatic dilution for testing in the VITEK 2. Inocula were prepared manually for testing in the VITEK 2 Compact. The modal MIC value was determined and the reproducibility was calculated based on MIC values falling within ± 1 dilution of the mode MIC value. Using VITEK 2 automatic and manual dilution options, the best and worst case results were 100%. All results were on scale. Using VITEK 2 Compact and manual dilution, best and worst case reproducibility was 98 Regulation section:

idK161217_s4000_e6000

K161217.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

unknown because resistant strains were not available at the time of comparative testing. Ceftriaxone: Shigella species, Providencia rettgeri, Salmonella species, and Shigella species.” Challenge Data-Manual Dilution: The challenge set of 102 isolates evaluated using the VITEK 2 and inoculated using the manual dilution method demonstrated an EA and CA of 96.1 % (Table 4). A total of 24 isolates were determined to have evaluable results. Of these isolates, 20 were within essential agreement (EA) for a percent EA of evaluable isolates of 83.3%.The results were acceptable. 10 Table 4: Performance of Challenge Isolates, VITEK 2 Manual Dilution Method VITEK 2 COMPACT: The challenge set of 102 isolates was also evaluated using the VITEK 2 Compact and inoculated using the manual dilution method demonstrated an EA of 96.1% and CA of 97.1% (Table 5). A total of 23 isolates were determined to have evaluable results. Of these isolates, 19 were within essential agreement (EA) for a percent EA of evaluable isolates of 82.6%. Table 5: Performance of Challenge Isolates, VITEK 2 Compact, Manual Dilution Method Even though the EA of evaluable was low, the overall performance of the VITEK 2 Compact (manual dilution) was considered acceptable based on the acceptable performance in overall EA, the reproducibility study, and QC (Table 2) b. Matrix comparison: Not Applicable 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: Not Applicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable EA Tot No. EA EA % Eval Tot No. Eval EA Eval EA % No. CA CA % No. R min maj vmj Challenge 102 98 96.1 24 20 83.3 98 96.1 13 3 1 0 EA Tot No. EA EA % Eval Tot No. Eval EA Eval EA % No. CA CA % No. R min maj vmj Challenge 102 98 96.1 23 19 82.6 99 97.1 13 2 1 0 11 4. Clinical cut-off: Not Applicable 5. Expected values/Reference range: Table 6: Interpretive Criteria for Ceftriaxone (FDA Drug Label) Organism FDA Interpretive Criteria for Ceftriaxone MIC (µg/mL) S I R Enterobacteriaceae ≤1 2 ≥4 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK161217_s4000_e6000

K161217.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

) is unknown because resistant strains were not available at the time of comparative testing. Ceftriaxone: Shigella species, Providencia rettgeri, Salmonella species, and Shigella species.” Challenge Data-Manual Dilution: The challenge set of 102 isolates evaluated using the VITEK 2 and inoculated using the manual dilution method demonstrated an EA and CA of 96.1 % (Table 4). A total of 24 isolates were determined to have evaluable results. Of these isolates, 20 were within essential agreement (EA) for a percent EA of evaluable isolates of 83.3%.The results were acceptable. 10 Table 4: Performance of Challenge Isolates, VITEK 2 Manual Dilution Method VITEK 2 COMPACT: The challenge set of 102 isolates was also evaluated using the VITEK 2 Compact and inoculated using the manual dilution method demonstrated an EA of 96.1% and CA of 97.1% (Table 5). A total of 23 isolates were determined to have evaluable results. Of these isolates, 19 were within essential agreement (EA) for a percent EA of evaluable isolates of 82.6%. Table 5: Performance of Challenge Isolates, VITEK 2 Compact, Manual Dilution Method Even though the EA of evaluable was low, the overall performance of the VITEK 2 Compact (manual dilution) was considered acceptable based on the acceptable performance in overall EA, the reproducibility study, and QC (Table 2) b. Matrix comparison: Not Applicable 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: Not Applicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable EA Tot No. EA EA % Eval Tot No. Eval EA Eval EA % No. CA CA % No. R min maj vmj Challenge 102 98 96.1 24 20 83.3 98 96.1 13 3 1 0 EA Tot No. EA EA % Eval Tot No. Eval EA Eval EA % No. CA CA % No. R min maj vmj Challenge 102 98 96.1 23 19 82.6 99 97.1 13 2 1 0 11 4. Clinical cut-off: Not Applicable 5. Expected values/Reference range: Table 6: Interpretive Criteria for Ceftriaxone (FDA Drug Label) Organism FDA Interpretive Criteria for Ceftriaxone MIC (µg/mL) S I R Enterobacteriaceae ≤1 2 ≥4 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK163517_s0_e2000

K163517.txt

purpose for submission

To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only).

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K163517 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only). C. Measurand: Telavancin 0.016 – 256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem® s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL G. Regulatory Information: 1. Regulation section: 1 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 2 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. 2. Indication(s) for use: The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Telavancin MTS at concentrations of 0.016- 256 μg/mL should be interpreted at 16- 20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Telavancin according to the FDA label: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: Manual reading only I. Device Description: The Telavancin MIC Test Strip (MTS) is made of special high quality paper impregnated with a predefined concentration of gradient Telavancin, across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Telavancin code (TLV) and the MIC reading scale in µg/ml. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly form the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Predicate K153687 Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton Agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual: the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (μg/mL) Same Differences Item Device Predicate Antibiotic Telavancin Vancomycin Incubation 35 ± 2°C for 16-20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Documents Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: Reproducibility testing was performed using three methicillin-sensitive Staphylococcus aureus isolates (MSSA), two methicillin-resistant Staphylococcus aureus isolate (MRSA), one vancomycin-resistant Staphylococcus aureus isolate (VRSA), one vancomycin-intermediate Staphylococcus aureus isolate (VISA), and three Enterococcus faecalis (vancomycin-sensitive) isolates. These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2 below. Table 2: Quality Control Test Results for Telavancin 5 Organism Expected Result Concentratio n (μg/mL) Reference MTS S. aureus ATCC 29213 0.03 – 0.12 μg/mL 0.016 0.03 22 2 0.06 32 52 0.12 7 7 0.25 E. faecalis ATCC 29212 0.03 – 0.12 μg/mL 0.016 0.03 11 0.06 40 46 0.12 21 4 0.25 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1 x 108 CFU/mL. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 441 organisms were tested and all organisms grew in the study. There were 304 ( Purpose for submission:

idK163517_s0_e2000

K163517.txt

measurand

Telavancin 0.016 – 256 µg/mL

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K163517 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only). C. Measurand: Telavancin 0.016 – 256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem® s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL G. Regulatory Information: 1. Regulation section: 1 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 2 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. 2. Indication(s) for use: The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Telavancin MTS at concentrations of 0.016- 256 μg/mL should be interpreted at 16- 20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Telavancin according to the FDA label: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: Manual reading only I. Device Description: The Telavancin MIC Test Strip (MTS) is made of special high quality paper impregnated with a predefined concentration of gradient Telavancin, across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Telavancin code (TLV) and the MIC reading scale in µg/ml. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly form the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Predicate K153687 Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton Agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual: the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (μg/mL) Same Differences Item Device Predicate Antibiotic Telavancin Vancomycin Incubation 35 ± 2°C for 16-20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Documents Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: Reproducibility testing was performed using three methicillin-sensitive Staphylococcus aureus isolates (MSSA), two methicillin-resistant Staphylococcus aureus isolate (MRSA), one vancomycin-resistant Staphylococcus aureus isolate (VRSA), one vancomycin-intermediate Staphylococcus aureus isolate (VISA), and three Enterococcus faecalis (vancomycin-sensitive) isolates. These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2 below. Table 2: Quality Control Test Results for Telavancin 5 Organism Expected Result Concentratio n (μg/mL) Reference MTS S. aureus ATCC 29213 0.03 – 0.12 μg/mL 0.016 0.03 22 2 0.06 32 52 0.12 7 7 0.25 E. faecalis ATCC 29212 0.03 – 0.12 μg/mL 0.016 0.03 11 0.06 40 46 0.12 21 4 0.25 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1 x 108 CFU/mL. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 441 organisms were tested and all organisms grew in the study. There were 304 ( Measurand:

idK163517_s0_e2000

K163517.txt

type of test

Quantitative AST growth based detection

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K163517 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only). C. Measurand: Telavancin 0.016 – 256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem® s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL G. Regulatory Information: 1. Regulation section: 1 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 2 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. 2. Indication(s) for use: The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Telavancin MTS at concentrations of 0.016- 256 μg/mL should be interpreted at 16- 20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Telavancin according to the FDA label: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: Manual reading only I. Device Description: The Telavancin MIC Test Strip (MTS) is made of special high quality paper impregnated with a predefined concentration of gradient Telavancin, across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Telavancin code (TLV) and the MIC reading scale in µg/ml. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly form the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Predicate K153687 Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton Agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual: the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (μg/mL) Same Differences Item Device Predicate Antibiotic Telavancin Vancomycin Incubation 35 ± 2°C for 16-20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Documents Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: Reproducibility testing was performed using three methicillin-sensitive Staphylococcus aureus isolates (MSSA), two methicillin-resistant Staphylococcus aureus isolate (MRSA), one vancomycin-resistant Staphylococcus aureus isolate (VRSA), one vancomycin-intermediate Staphylococcus aureus isolate (VISA), and three Enterococcus faecalis (vancomycin-sensitive) isolates. These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2 below. Table 2: Quality Control Test Results for Telavancin 5 Organism Expected Result Concentratio n (μg/mL) Reference MTS S. aureus ATCC 29213 0.03 – 0.12 μg/mL 0.016 0.03 22 2 0.06 32 52 0.12 7 7 0.25 E. faecalis ATCC 29212 0.03 – 0.12 μg/mL 0.016 0.03 11 0.06 40 46 0.12 21 4 0.25 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1 x 108 CFU/mL. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 441 organisms were tested and all organisms grew in the study. There were 304 ( Type of test:

idK163517_s0_e2000

K163517.txt

classification

Class II

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K163517 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only). C. Measurand: Telavancin 0.016 – 256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem® s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL G. Regulatory Information: 1. Regulation section: 1 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 2 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. 2. Indication(s) for use: The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Telavancin MTS at concentrations of 0.016- 256 μg/mL should be interpreted at 16- 20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Telavancin according to the FDA label: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: Manual reading only I. Device Description: The Telavancin MIC Test Strip (MTS) is made of special high quality paper impregnated with a predefined concentration of gradient Telavancin, across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Telavancin code (TLV) and the MIC reading scale in µg/ml. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly form the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Predicate K153687 Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton Agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual: the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (μg/mL) Same Differences Item Device Predicate Antibiotic Telavancin Vancomycin Incubation 35 ± 2°C for 16-20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Documents Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: Reproducibility testing was performed using three methicillin-sensitive Staphylococcus aureus isolates (MSSA), two methicillin-resistant Staphylococcus aureus isolate (MRSA), one vancomycin-resistant Staphylococcus aureus isolate (VRSA), one vancomycin-intermediate Staphylococcus aureus isolate (VISA), and three Enterococcus faecalis (vancomycin-sensitive) isolates. These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2 below. Table 2: Quality Control Test Results for Telavancin 5 Organism Expected Result Concentratio n (μg/mL) Reference MTS S. aureus ATCC 29213 0.03 – 0.12 μg/mL 0.016 0.03 22 2 0.06 32 52 0.12 7 7 0.25 E. faecalis ATCC 29212 0.03 – 0.12 μg/mL 0.016 0.03 11 0.06 40 46 0.12 21 4 0.25 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1 x 108 CFU/mL. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 441 organisms were tested and all organisms grew in the study. There were 304 ( Classification:

idK163517_s0_e2000

K163517.txt

product code

JWY – Manual Antimicrobial Test Systems

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K163517 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only). C. Measurand: Telavancin 0.016 – 256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem® s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL G. Regulatory Information: 1. Regulation section: 1 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 2 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. 2. Indication(s) for use: The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Telavancin MTS at concentrations of 0.016- 256 μg/mL should be interpreted at 16- 20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Telavancin according to the FDA label: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: Manual reading only I. Device Description: The Telavancin MIC Test Strip (MTS) is made of special high quality paper impregnated with a predefined concentration of gradient Telavancin, across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Telavancin code (TLV) and the MIC reading scale in µg/ml. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly form the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Predicate K153687 Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton Agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual: the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (μg/mL) Same Differences Item Device Predicate Antibiotic Telavancin Vancomycin Incubation 35 ± 2°C for 16-20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Documents Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: Reproducibility testing was performed using three methicillin-sensitive Staphylococcus aureus isolates (MSSA), two methicillin-resistant Staphylococcus aureus isolate (MRSA), one vancomycin-resistant Staphylococcus aureus isolate (VRSA), one vancomycin-intermediate Staphylococcus aureus isolate (VISA), and three Enterococcus faecalis (vancomycin-sensitive) isolates. These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2 below. Table 2: Quality Control Test Results for Telavancin 5 Organism Expected Result Concentratio n (μg/mL) Reference MTS S. aureus ATCC 29213 0.03 – 0.12 μg/mL 0.016 0.03 22 2 0.06 32 52 0.12 7 7 0.25 E. faecalis ATCC 29212 0.03 – 0.12 μg/mL 0.016 0.03 11 0.06 40 46 0.12 21 4 0.25 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1 x 108 CFU/mL. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 441 organisms were tested and all organisms grew in the study. There were 304 ( Product code:

idK163517_s0_e2000

K163517.txt

panel

83 – Microbiology

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K163517 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only). C. Measurand: Telavancin 0.016 – 256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem® s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL G. Regulatory Information: 1. Regulation section: 1 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 2 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. 2. Indication(s) for use: The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Telavancin MTS at concentrations of 0.016- 256 μg/mL should be interpreted at 16- 20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Telavancin according to the FDA label: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: Manual reading only I. Device Description: The Telavancin MIC Test Strip (MTS) is made of special high quality paper impregnated with a predefined concentration of gradient Telavancin, across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Telavancin code (TLV) and the MIC reading scale in µg/ml. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly form the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Predicate K153687 Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton Agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual: the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (μg/mL) Same Differences Item Device Predicate Antibiotic Telavancin Vancomycin Incubation 35 ± 2°C for 16-20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Documents Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: Reproducibility testing was performed using three methicillin-sensitive Staphylococcus aureus isolates (MSSA), two methicillin-resistant Staphylococcus aureus isolate (MRSA), one vancomycin-resistant Staphylococcus aureus isolate (VRSA), one vancomycin-intermediate Staphylococcus aureus isolate (VISA), and three Enterococcus faecalis (vancomycin-sensitive) isolates. These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2 below. Table 2: Quality Control Test Results for Telavancin 5 Organism Expected Result Concentratio n (μg/mL) Reference MTS S. aureus ATCC 29213 0.03 – 0.12 μg/mL 0.016 0.03 22 2 0.06 32 52 0.12 7 7 0.25 E. faecalis ATCC 29212 0.03 – 0.12 μg/mL 0.016 0.03 11 0.06 40 46 0.12 21 4 0.25 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1 x 108 CFU/mL. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 441 organisms were tested and all organisms grew in the study. There were 304 ( Panel:

idK163517_s0_e2000

K163517.txt

intended use

The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures.

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K163517 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only). C. Measurand: Telavancin 0.016 – 256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem® s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL G. Regulatory Information: 1. Regulation section: 1 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 2 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. 2. Indication(s) for use: The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Telavancin MTS at concentrations of 0.016- 256 μg/mL should be interpreted at 16- 20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Telavancin according to the FDA label: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: Manual reading only I. Device Description: The Telavancin MIC Test Strip (MTS) is made of special high quality paper impregnated with a predefined concentration of gradient Telavancin, across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Telavancin code (TLV) and the MIC reading scale in µg/ml. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly form the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Predicate K153687 Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton Agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual: the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (μg/mL) Same Differences Item Device Predicate Antibiotic Telavancin Vancomycin Incubation 35 ± 2°C for 16-20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Documents Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: Reproducibility testing was performed using three methicillin-sensitive Staphylococcus aureus isolates (MSSA), two methicillin-resistant Staphylococcus aureus isolate (MRSA), one vancomycin-resistant Staphylococcus aureus isolate (VRSA), one vancomycin-intermediate Staphylococcus aureus isolate (VISA), and three Enterococcus faecalis (vancomycin-sensitive) isolates. These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2 below. Table 2: Quality Control Test Results for Telavancin 5 Organism Expected Result Concentratio n (μg/mL) Reference MTS S. aureus ATCC 29213 0.03 – 0.12 μg/mL 0.016 0.03 22 2 0.06 32 52 0.12 7 7 0.25 E. faecalis ATCC 29212 0.03 – 0.12 μg/mL 0.016 0.03 11 0.06 40 46 0.12 21 4 0.25 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1 x 108 CFU/mL. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 441 organisms were tested and all organisms grew in the study. There were 304 ( Intended use:

idK163517_s0_e2000

K163517.txt

predicate device name

Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K163517 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only). C. Measurand: Telavancin 0.016 – 256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem® s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL G. Regulatory Information: 1. Regulation section: 1 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 2 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. 2. Indication(s) for use: The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Telavancin MTS at concentrations of 0.016- 256 μg/mL should be interpreted at 16- 20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Telavancin according to the FDA label: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: Manual reading only I. Device Description: The Telavancin MIC Test Strip (MTS) is made of special high quality paper impregnated with a predefined concentration of gradient Telavancin, across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Telavancin code (TLV) and the MIC reading scale in µg/ml. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly form the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Predicate K153687 Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton Agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual: the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (μg/mL) Same Differences Item Device Predicate Antibiotic Telavancin Vancomycin Incubation 35 ± 2°C for 16-20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Documents Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: Reproducibility testing was performed using three methicillin-sensitive Staphylococcus aureus isolates (MSSA), two methicillin-resistant Staphylococcus aureus isolate (MRSA), one vancomycin-resistant Staphylococcus aureus isolate (VRSA), one vancomycin-intermediate Staphylococcus aureus isolate (VISA), and three Enterococcus faecalis (vancomycin-sensitive) isolates. These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2 below. Table 2: Quality Control Test Results for Telavancin 5 Organism Expected Result Concentratio n (μg/mL) Reference MTS S. aureus ATCC 29213 0.03 – 0.12 μg/mL 0.016 0.03 22 2 0.06 32 52 0.12 7 7 0.25 E. faecalis ATCC 29212 0.03 – 0.12 μg/mL 0.016 0.03 11 0.06 40 46 0.12 21 4 0.25 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1 x 108 CFU/mL. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 441 organisms were tested and all organisms grew in the study. There were 304 ( Predicate device name:

idK163517_s0_e2000

K163517.txt

applicant

Liofilchem® s.r.l.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K163517 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only). C. Measurand: Telavancin 0.016 – 256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem® s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL G. Regulatory Information: 1. Regulation section: 1 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 2 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. 2. Indication(s) for use: The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Telavancin MTS at concentrations of 0.016- 256 μg/mL should be interpreted at 16- 20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Telavancin according to the FDA label: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: Manual reading only I. Device Description: The Telavancin MIC Test Strip (MTS) is made of special high quality paper impregnated with a predefined concentration of gradient Telavancin, across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Telavancin code (TLV) and the MIC reading scale in µg/ml. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly form the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Predicate K153687 Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton Agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual: the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (μg/mL) Same Differences Item Device Predicate Antibiotic Telavancin Vancomycin Incubation 35 ± 2°C for 16-20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Documents Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: Reproducibility testing was performed using three methicillin-sensitive Staphylococcus aureus isolates (MSSA), two methicillin-resistant Staphylococcus aureus isolate (MRSA), one vancomycin-resistant Staphylococcus aureus isolate (VRSA), one vancomycin-intermediate Staphylococcus aureus isolate (VISA), and three Enterococcus faecalis (vancomycin-sensitive) isolates. These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2 below. Table 2: Quality Control Test Results for Telavancin 5 Organism Expected Result Concentratio n (μg/mL) Reference MTS S. aureus ATCC 29213 0.03 – 0.12 μg/mL 0.016 0.03 22 2 0.06 32 52 0.12 7 7 0.25 E. faecalis ATCC 29212 0.03 – 0.12 μg/mL 0.016 0.03 11 0.06 40 46 0.12 21 4 0.25 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1 x 108 CFU/mL. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 441 organisms were tested and all organisms grew in the study. There were 304 ( Applicant:

idK163517_s0_e2000

K163517.txt

proprietary and established names

Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL

EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K163517 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only). C. Measurand: Telavancin 0.016 – 256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem® s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL G. Regulatory Information: 1. Regulation section: 1 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 2 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. 2. Indication(s) for use: The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Telavancin MTS at concentrations of 0.016- 256 μg/mL should be interpreted at 16- 20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Telavancin according to the FDA label: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: Manual reading only I. Device Description: The Telavancin MIC Test Strip (MTS) is made of special high quality paper impregnated with a predefined concentration of gradient Telavancin, across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Telavancin code (TLV) and the MIC reading scale in µg/ml. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly form the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Predicate K153687 Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton Agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual: the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (μg/mL) Same Differences Item Device Predicate Antibiotic Telavancin Vancomycin Incubation 35 ± 2°C for 16-20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Documents Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: Reproducibility testing was performed using three methicillin-sensitive Staphylococcus aureus isolates (MSSA), two methicillin-resistant Staphylococcus aureus isolate (MRSA), one vancomycin-resistant Staphylococcus aureus isolate (VRSA), one vancomycin-intermediate Staphylococcus aureus isolate (VISA), and three Enterococcus faecalis (vancomycin-sensitive) isolates. These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2 below. Table 2: Quality Control Test Results for Telavancin 5 Organism Expected Result Concentratio n (μg/mL) Reference MTS S. aureus ATCC 29213 0.03 – 0.12 μg/mL 0.016 0.03 22 2 0.06 32 52 0.12 7 7 0.25 E. faecalis ATCC 29212 0.03 – 0.12 μg/mL 0.016 0.03 11 0.06 40 46 0.12 21 4 0.25 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1 x 108 CFU/mL. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 441 organisms were tested and all organisms grew in the study. There were 304 ( Proprietary and established names:

idK163517_s0_e2000

K163517.txt

regulation section

866.1640 Antimicrobial Susceptibility Test Powder

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K163517 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Telavancin in concentrations of 0.016 – 256 µg/mL for susceptibility testing of Staphylococcus aureus (including methicillin-resistant isolates) and Enterococcus faecalis (vancomycin-susceptible isolates only). C. Measurand: Telavancin 0.016 – 256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem® s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Telavancin 0.016 – 256 μg/mL G. Regulatory Information: 1. Regulation section: 1 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY – Manual Antimicrobial Test Systems 4. Panel: 2 83 – Microbiology H. Intended Use: 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. 2. Indication(s) for use: The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Telavancin MTS at concentrations of 0.016- 256 μg/mL should be interpreted at 16- 20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Telavancin according to the FDA label: Staphylococcus aureus (including methicillin-resistant isolates) Enterococcus faecalis (vancomycin-susceptible isolates only) 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: Manual reading only I. Device Description: The Telavancin MIC Test Strip (MTS) is made of special high quality paper impregnated with a predefined concentration of gradient Telavancin, across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the Telavancin code (TLV) and the MIC reading scale in µg/ml. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent diffuses into the agar for over an hour. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly form the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Liofilchem MIC Test Strip (MTS) – Vancomycin 0.016 – 256 μg/mL 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Predicate K153687 Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton Agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual: the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (μg/mL) Same Differences Item Device Predicate Antibiotic Telavancin Vancomycin Incubation 35 ± 2°C for 16-20 hours 35 ± 2°C for 24 hours K. Standard/Guidance Documents Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015” CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty- Fifth Informational Supplement, January 2016” L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: Reproducibility testing was performed using three methicillin-sensitive Staphylococcus aureus isolates (MSSA), two methicillin-resistant Staphylococcus aureus isolate (MRSA), one vancomycin-resistant Staphylococcus aureus isolate (VRSA), one vancomycin-intermediate Staphylococcus aureus isolate (VISA), and three Enterococcus faecalis (vancomycin-sensitive) isolates. These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2 below. Table 2: Quality Control Test Results for Telavancin 5 Organism Expected Result Concentratio n (μg/mL) Reference MTS S. aureus ATCC 29213 0.03 – 0.12 μg/mL 0.016 0.03 22 2 0.06 32 52 0.12 7 7 0.25 E. faecalis ATCC 29212 0.03 – 0.12 μg/mL 0.016 0.03 11 0.06 40 46 0.12 21 4 0.25 The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately 1 x 108 CFU/mL. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 441 organisms were tested and all organisms grew in the study. There were 304 ( Regulation section:

idK163517_s2000_e4000

K163517.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

ates that were tested within seven days of collection and 137 (31.1%) isolates that were tested within one year of collection. The study included 351 S. aureus (201 MSSA and 150 MRSA) and 90 E. faecalis isolates. In addition to clinical isolates, 63 S. aureus and 8 E. faecalis challenge isolates were tested for a combined total of 414 S. aureus and 98 E. faecalis isolates tested. Results obtained with Liofilchem MIC Test Strip (MTS) with Telavancin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. The performance is listed in Table 3 below: Table 3: Performance of S. aureus (201 MSSA and 150 MRSA clinical isolates) and 90 E. faecalis clinical isolates 6 EA Tot* EA N EA% Eval. EA N Eval. EA% CA N CA% #NS min maj vmj S. aureus ≤0.12 (Susceptible), -- (Intermediate), -- (Resistant) S. aureus (combined MSSA and MRSA) 414 404 97.6 404 97.6 411 99.3 45** N/A 3 0 E. faecalis ≤0.25 (Susceptible), -- (Intermediate), -- (Resistant) E. faecalis (vancomycin sensitive) 98 94 95.9 93 95.9 98 100 8 N/A 0 0 *EA – Essential Agreement maj – major discrepancies CA – Category Agreement vmj – very major discrepancies NS – Non-susceptible isolates min – minor discrepancies **The labeled breakpoint for Telavancin was altered from ≤ 1 to ≤ 0.12 for S. aureus on February 7, 2014. The majority of these isolates (44/45) were drawn the challenge group of MRSA isolates, and 43 of these isolates would have been identified as susceptible prior to this change in breakpoint. The MIC results for these isolates remained the same, and the change in the MIC interpretive criteria did not affect the performance calculations. Essential agreement (EA) is when the Liofilchem MIC Test Strip (MTS) results agree with the reference test panel results exactly or within one doubling dilution of the reference method. Category agreement (CA) is when the Liofilchem MIC Test Strip (MTS) result interpretation agrees exactly with the reference panel result interpretation. For clinical and challenge isolates tested with the Liofilchem MTS for Telavancin, the overall %EA and %CA met the acceptance criteria of greater than or equal to 90% (Table 3). There were 3 major errors when testing S. aureus 0.7%, no major errors with E. faecalis and no very major errors for either isolate which met the acceptance criteria. MIC Trends: 7 Using the data provided by the sponsor in the diagonal table format recommended in the AST Guidance, an analysis was conducted to check for trending in MIC values. This trending calculation takes into account MIC values that are determined to be ≤1 and ≥1 doubling dilutions compared to the reference method irrespective of whether the device MIC values are on-scale or not. A higher MIC reading trend was observed in the overall performance for S. aureus isolates and a lower MIC reading trend was observed in the overall performance for E. faecalis compared to the CLSI broth micro-dilution reference method, as summarized in Table 4. Table 4: Trending – All Clinical and Challenge Isolates Organism ≥ -3 ≥ -2 ≥ -1 Exact ≥ +1 ≥ +2 ≥ +3 Eval. Non-eval. S. aureus 0 5 42 203 159 4 1 414 0 0 1.2% 10.1% 49% 38.4% (39.6% all dilutions higher)a 1.0% 0.2% E. faecalis 1 3 18 68 7 0 0 97 1 1.0% 3.1% 18.6% (22.7% all dilutions lower)b 70% 7.2% 0 0 a. Difference: 95% CI (-33.76% to -22.53%) b. Difference: 95% CI (5.47% to 25.45%) The trending towards higher MIC values and the potential for occurrence of major errors for Telavancin when testing S. aureus (both MSSA and MRSA) isolates was addressed in the labeling by adding the following footnote: “The Liofilchem MIC Test Strip (MTS) telavancin values tended to be in exact agreement or at least one doubling dilution higher when testing S. aureus compared to the CLSI reference broth microdilution.” In addition, the trending towards lower MIC values and the potential for occurrence of very major error(s) when testing E. faecalis isolates was addressed in the labeling by adding the following footnote: “The Liofilchem MIC Test Strip (MTS) telavancin values tended to be in exact agreement or at least one doubling dilution lower when testing E. faecalis compared to the CLSI reference broth microdilution.” 3. Clinical studies: 8 a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: Table 5. Interpretive Criteria for Telavancin (FDA Drug Label) Organism FDA Interpretive Criteria for Telavancin MIC (µg/mL) S I R S. aureus (including MRSA) ≤ 0.12 -- -- E. faecalis (vancomycin- susceptible isolates only) ≤ 0.25 -- -- N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK163517_s2000_e4000

K163517.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

%) isolates that were tested within seven days of collection and 137 (31.1%) isolates that were tested within one year of collection. The study included 351 S. aureus (201 MSSA and 150 MRSA) and 90 E. faecalis isolates. In addition to clinical isolates, 63 S. aureus and 8 E. faecalis challenge isolates were tested for a combined total of 414 S. aureus and 98 E. faecalis isolates tested. Results obtained with Liofilchem MIC Test Strip (MTS) with Telavancin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately 108 CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at 35°C ±2 for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the reference method. The performance is listed in Table 3 below: Table 3: Performance of S. aureus (201 MSSA and 150 MRSA clinical isolates) and 90 E. faecalis clinical isolates 6 EA Tot* EA N EA% Eval. EA N Eval. EA% CA N CA% #NS min maj vmj S. aureus ≤0.12 (Susceptible), -- (Intermediate), -- (Resistant) S. aureus (combined MSSA and MRSA) 414 404 97.6 404 97.6 411 99.3 45** N/A 3 0 E. faecalis ≤0.25 (Susceptible), -- (Intermediate), -- (Resistant) E. faecalis (vancomycin sensitive) 98 94 95.9 93 95.9 98 100 8 N/A 0 0 *EA – Essential Agreement maj – major discrepancies CA – Category Agreement vmj – very major discrepancies NS – Non-susceptible isolates min – minor discrepancies **The labeled breakpoint for Telavancin was altered from ≤ 1 to ≤ 0.12 for S. aureus on February 7, 2014. The majority of these isolates (44/45) were drawn the challenge group of MRSA isolates, and 43 of these isolates would have been identified as susceptible prior to this change in breakpoint. The MIC results for these isolates remained the same, and the change in the MIC interpretive criteria did not affect the performance calculations. Essential agreement (EA) is when the Liofilchem MIC Test Strip (MTS) results agree with the reference test panel results exactly or within one doubling dilution of the reference method. Category agreement (CA) is when the Liofilchem MIC Test Strip (MTS) result interpretation agrees exactly with the reference panel result interpretation. For clinical and challenge isolates tested with the Liofilchem MTS for Telavancin, the overall %EA and %CA met the acceptance criteria of greater than or equal to 90% (Table 3). There were 3 major errors when testing S. aureus 0.7%, no major errors with E. faecalis and no very major errors for either isolate which met the acceptance criteria. MIC Trends: 7 Using the data provided by the sponsor in the diagonal table format recommended in the AST Guidance, an analysis was conducted to check for trending in MIC values. This trending calculation takes into account MIC values that are determined to be ≤1 and ≥1 doubling dilutions compared to the reference method irrespective of whether the device MIC values are on-scale or not. A higher MIC reading trend was observed in the overall performance for S. aureus isolates and a lower MIC reading trend was observed in the overall performance for E. faecalis compared to the CLSI broth micro-dilution reference method, as summarized in Table 4. Table 4: Trending – All Clinical and Challenge Isolates Organism ≥ -3 ≥ -2 ≥ -1 Exact ≥ +1 ≥ +2 ≥ +3 Eval. Non-eval. S. aureus 0 5 42 203 159 4 1 414 0 0 1.2% 10.1% 49% 38.4% (39.6% all dilutions higher)a 1.0% 0.2% E. faecalis 1 3 18 68 7 0 0 97 1 1.0% 3.1% 18.6% (22.7% all dilutions lower)b 70% 7.2% 0 0 a. Difference: 95% CI (-33.76% to -22.53%) b. Difference: 95% CI (5.47% to 25.45%) The trending towards higher MIC values and the potential for occurrence of major errors for Telavancin when testing S. aureus (both MSSA and MRSA) isolates was addressed in the labeling by adding the following footnote: “The Liofilchem MIC Test Strip (MTS) telavancin values tended to be in exact agreement or at least one doubling dilution higher when testing S. aureus compared to the CLSI reference broth microdilution.” In addition, the trending towards lower MIC values and the potential for occurrence of very major error(s) when testing E. faecalis isolates was addressed in the labeling by adding the following footnote: “The Liofilchem MIC Test Strip (MTS) telavancin values tended to be in exact agreement or at least one doubling dilution lower when testing E. faecalis compared to the CLSI reference broth microdilution.” 3. Clinical studies: 8 a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: Table 5. Interpretive Criteria for Telavancin (FDA Drug Label) Organism FDA Interpretive Criteria for Telavancin MIC (µg/mL) S I R S. aureus (including MRSA) ≤ 0.12 -- -- E. faecalis (vancomycin- susceptible isolates only) ≤ 0.25 -- -- N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK182922_s0_e2000

K182922.txt

purpose for submission

To obtain a substantial equivalence determination for Omadacycline (OMC) at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram-negative and non-fastidious Gram-positive organisms

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K182922 B. Purpose for Submission: To obtain a substantial equivalence determination for Omadacycline (OMC) at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram-negative and non-fastidious Gram-positive organisms C. Measurand: Omadacycline 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth-based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: MTS Omadacycline 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem MTS (MIC Test Strip) Omadacycline 0.002-32 μg/mL is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The MTS Omadacycline at concentrations of 0.002-32 μg/mL should be interpreted at 16-20 hours of incubation. MTS Omadacycline can be used to determine the MIC of omadacycline against the following bacteria. Omadacycline has been shown to be active both clinically and in vitro against these bacterial species according to the FDA drug approved label: Gram-Positive bacteria Staphylococcus aureus Staphylococcus lugdunensis Enterococcus faecalis Gram-Negative bacteria Enterobacter cloacae Klebsiella pneumoniae Omadacycline has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug approved label: Gram-Positive bacteria Enterococcus faecium (vancomycin-susceptible and -resistant isolates) Gram-Negative bacteria Escherichia coli Citrobacter freundii Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): 3 · For prescription use · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] · The ability of the MTS to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Omadacycline: Citrobacter koseri · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. · The safety and efficacy of omadacycline in treating Community-Acquired Bacterial Pneumonia (CABP) infections due to Gram-negative organisms other than K. pneumoniae and Gram-positive organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · Omadacycline is not active in vitro against Morganella spp., Proteus The safety and efficacy of omadacycline in treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) infections due to Gram-negative organisms other than K. pneumoniae and E. cloacae and Gram-positive organisms other than S. aureus (MRSA and MSSA), S. lugdunensis, and E. faecalis may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · 4. Special instrument requirements: spp., and Providencia spp. Manual reading only I. Device Description: The Omadacycline MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of omadacycline across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Omadacycline code (OMC) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of 4 antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two- fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Result MIC Same Differences Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents against Gram-negative and Gram- positive organisms Quantitative susceptibility to antimicrobial agents to Gram- positive organisms Antibiotic Omadacycline code (OMC) Vancomycin code (VA) Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC as 80% inhibition when trailing is seen Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC at 100% inhibition Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours 5 K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. Given that omadacycline is a bacteriostatic drug, the ellipse should be interpreted at 80% inhibition when trailing is observed. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reprodu Purpose for submission:

idK182922_s0_e2000

K182922.txt

measurand

Omadacycline 0.002-32 μg/mL

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K182922 B. Purpose for Submission: To obtain a substantial equivalence determination for Omadacycline (OMC) at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram-negative and non-fastidious Gram-positive organisms C. Measurand: Omadacycline 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth-based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: MTS Omadacycline 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem MTS (MIC Test Strip) Omadacycline 0.002-32 μg/mL is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The MTS Omadacycline at concentrations of 0.002-32 μg/mL should be interpreted at 16-20 hours of incubation. MTS Omadacycline can be used to determine the MIC of omadacycline against the following bacteria. Omadacycline has been shown to be active both clinically and in vitro against these bacterial species according to the FDA drug approved label: Gram-Positive bacteria Staphylococcus aureus Staphylococcus lugdunensis Enterococcus faecalis Gram-Negative bacteria Enterobacter cloacae Klebsiella pneumoniae Omadacycline has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug approved label: Gram-Positive bacteria Enterococcus faecium (vancomycin-susceptible and -resistant isolates) Gram-Negative bacteria Escherichia coli Citrobacter freundii Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): 3 · For prescription use · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] · The ability of the MTS to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Omadacycline: Citrobacter koseri · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. · The safety and efficacy of omadacycline in treating Community-Acquired Bacterial Pneumonia (CABP) infections due to Gram-negative organisms other than K. pneumoniae and Gram-positive organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · Omadacycline is not active in vitro against Morganella spp., Proteus The safety and efficacy of omadacycline in treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) infections due to Gram-negative organisms other than K. pneumoniae and E. cloacae and Gram-positive organisms other than S. aureus (MRSA and MSSA), S. lugdunensis, and E. faecalis may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · 4. Special instrument requirements: spp., and Providencia spp. Manual reading only I. Device Description: The Omadacycline MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of omadacycline across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Omadacycline code (OMC) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of 4 antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two- fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Result MIC Same Differences Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents against Gram-negative and Gram- positive organisms Quantitative susceptibility to antimicrobial agents to Gram- positive organisms Antibiotic Omadacycline code (OMC) Vancomycin code (VA) Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC as 80% inhibition when trailing is seen Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC at 100% inhibition Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours 5 K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. Given that omadacycline is a bacteriostatic drug, the ellipse should be interpreted at 80% inhibition when trailing is observed. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reprodu Measurand:

idK182922_s0_e2000

K182922.txt

type of test

Quantitative Antimicrobial Susceptibility Test growth-based detection

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K182922 B. Purpose for Submission: To obtain a substantial equivalence determination for Omadacycline (OMC) at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram-negative and non-fastidious Gram-positive organisms C. Measurand: Omadacycline 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth-based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: MTS Omadacycline 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem MTS (MIC Test Strip) Omadacycline 0.002-32 μg/mL is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The MTS Omadacycline at concentrations of 0.002-32 μg/mL should be interpreted at 16-20 hours of incubation. MTS Omadacycline can be used to determine the MIC of omadacycline against the following bacteria. Omadacycline has been shown to be active both clinically and in vitro against these bacterial species according to the FDA drug approved label: Gram-Positive bacteria Staphylococcus aureus Staphylococcus lugdunensis Enterococcus faecalis Gram-Negative bacteria Enterobacter cloacae Klebsiella pneumoniae Omadacycline has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug approved label: Gram-Positive bacteria Enterococcus faecium (vancomycin-susceptible and -resistant isolates) Gram-Negative bacteria Escherichia coli Citrobacter freundii Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): 3 · For prescription use · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] · The ability of the MTS to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Omadacycline: Citrobacter koseri · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. · The safety and efficacy of omadacycline in treating Community-Acquired Bacterial Pneumonia (CABP) infections due to Gram-negative organisms other than K. pneumoniae and Gram-positive organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · Omadacycline is not active in vitro against Morganella spp., Proteus The safety and efficacy of omadacycline in treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) infections due to Gram-negative organisms other than K. pneumoniae and E. cloacae and Gram-positive organisms other than S. aureus (MRSA and MSSA), S. lugdunensis, and E. faecalis may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · 4. Special instrument requirements: spp., and Providencia spp. Manual reading only I. Device Description: The Omadacycline MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of omadacycline across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Omadacycline code (OMC) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of 4 antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two- fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Result MIC Same Differences Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents against Gram-negative and Gram- positive organisms Quantitative susceptibility to antimicrobial agents to Gram- positive organisms Antibiotic Omadacycline code (OMC) Vancomycin code (VA) Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC as 80% inhibition when trailing is seen Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC at 100% inhibition Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours 5 K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. Given that omadacycline is a bacteriostatic drug, the ellipse should be interpreted at 80% inhibition when trailing is observed. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reprodu Type of test:

idK182922_s0_e2000

K182922.txt

classification

Class II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K182922 B. Purpose for Submission: To obtain a substantial equivalence determination for Omadacycline (OMC) at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram-negative and non-fastidious Gram-positive organisms C. Measurand: Omadacycline 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth-based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: MTS Omadacycline 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem MTS (MIC Test Strip) Omadacycline 0.002-32 μg/mL is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The MTS Omadacycline at concentrations of 0.002-32 μg/mL should be interpreted at 16-20 hours of incubation. MTS Omadacycline can be used to determine the MIC of omadacycline against the following bacteria. Omadacycline has been shown to be active both clinically and in vitro against these bacterial species according to the FDA drug approved label: Gram-Positive bacteria Staphylococcus aureus Staphylococcus lugdunensis Enterococcus faecalis Gram-Negative bacteria Enterobacter cloacae Klebsiella pneumoniae Omadacycline has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug approved label: Gram-Positive bacteria Enterococcus faecium (vancomycin-susceptible and -resistant isolates) Gram-Negative bacteria Escherichia coli Citrobacter freundii Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): 3 · For prescription use · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] · The ability of the MTS to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Omadacycline: Citrobacter koseri · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. · The safety and efficacy of omadacycline in treating Community-Acquired Bacterial Pneumonia (CABP) infections due to Gram-negative organisms other than K. pneumoniae and Gram-positive organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · Omadacycline is not active in vitro against Morganella spp., Proteus The safety and efficacy of omadacycline in treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) infections due to Gram-negative organisms other than K. pneumoniae and E. cloacae and Gram-positive organisms other than S. aureus (MRSA and MSSA), S. lugdunensis, and E. faecalis may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · 4. Special instrument requirements: spp., and Providencia spp. Manual reading only I. Device Description: The Omadacycline MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of omadacycline across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Omadacycline code (OMC) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of 4 antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two- fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Result MIC Same Differences Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents against Gram-negative and Gram- positive organisms Quantitative susceptibility to antimicrobial agents to Gram- positive organisms Antibiotic Omadacycline code (OMC) Vancomycin code (VA) Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC as 80% inhibition when trailing is seen Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC at 100% inhibition Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours 5 K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. Given that omadacycline is a bacteriostatic drug, the ellipse should be interpreted at 80% inhibition when trailing is observed. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reprodu Classification:

idK182922_s0_e2000

K182922.txt

product code

JWY - Manual Antimicrobial Susceptibility Test Systems

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K182922 B. Purpose for Submission: To obtain a substantial equivalence determination for Omadacycline (OMC) at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram-negative and non-fastidious Gram-positive organisms C. Measurand: Omadacycline 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth-based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: MTS Omadacycline 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem MTS (MIC Test Strip) Omadacycline 0.002-32 μg/mL is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The MTS Omadacycline at concentrations of 0.002-32 μg/mL should be interpreted at 16-20 hours of incubation. MTS Omadacycline can be used to determine the MIC of omadacycline against the following bacteria. Omadacycline has been shown to be active both clinically and in vitro against these bacterial species according to the FDA drug approved label: Gram-Positive bacteria Staphylococcus aureus Staphylococcus lugdunensis Enterococcus faecalis Gram-Negative bacteria Enterobacter cloacae Klebsiella pneumoniae Omadacycline has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug approved label: Gram-Positive bacteria Enterococcus faecium (vancomycin-susceptible and -resistant isolates) Gram-Negative bacteria Escherichia coli Citrobacter freundii Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): 3 · For prescription use · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] · The ability of the MTS to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Omadacycline: Citrobacter koseri · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. · The safety and efficacy of omadacycline in treating Community-Acquired Bacterial Pneumonia (CABP) infections due to Gram-negative organisms other than K. pneumoniae and Gram-positive organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · Omadacycline is not active in vitro against Morganella spp., Proteus The safety and efficacy of omadacycline in treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) infections due to Gram-negative organisms other than K. pneumoniae and E. cloacae and Gram-positive organisms other than S. aureus (MRSA and MSSA), S. lugdunensis, and E. faecalis may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · 4. Special instrument requirements: spp., and Providencia spp. Manual reading only I. Device Description: The Omadacycline MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of omadacycline across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Omadacycline code (OMC) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of 4 antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two- fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Result MIC Same Differences Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents against Gram-negative and Gram- positive organisms Quantitative susceptibility to antimicrobial agents to Gram- positive organisms Antibiotic Omadacycline code (OMC) Vancomycin code (VA) Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC as 80% inhibition when trailing is seen Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC at 100% inhibition Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours 5 K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. Given that omadacycline is a bacteriostatic drug, the ellipse should be interpreted at 80% inhibition when trailing is observed. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reprodu Product code:

idK182922_s0_e2000

K182922.txt

panel

83 – Microbiology

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K182922 B. Purpose for Submission: To obtain a substantial equivalence determination for Omadacycline (OMC) at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram-negative and non-fastidious Gram-positive organisms C. Measurand: Omadacycline 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth-based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: MTS Omadacycline 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem MTS (MIC Test Strip) Omadacycline 0.002-32 μg/mL is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The MTS Omadacycline at concentrations of 0.002-32 μg/mL should be interpreted at 16-20 hours of incubation. MTS Omadacycline can be used to determine the MIC of omadacycline against the following bacteria. Omadacycline has been shown to be active both clinically and in vitro against these bacterial species according to the FDA drug approved label: Gram-Positive bacteria Staphylococcus aureus Staphylococcus lugdunensis Enterococcus faecalis Gram-Negative bacteria Enterobacter cloacae Klebsiella pneumoniae Omadacycline has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug approved label: Gram-Positive bacteria Enterococcus faecium (vancomycin-susceptible and -resistant isolates) Gram-Negative bacteria Escherichia coli Citrobacter freundii Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): 3 · For prescription use · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] · The ability of the MTS to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Omadacycline: Citrobacter koseri · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. · The safety and efficacy of omadacycline in treating Community-Acquired Bacterial Pneumonia (CABP) infections due to Gram-negative organisms other than K. pneumoniae and Gram-positive organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · Omadacycline is not active in vitro against Morganella spp., Proteus The safety and efficacy of omadacycline in treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) infections due to Gram-negative organisms other than K. pneumoniae and E. cloacae and Gram-positive organisms other than S. aureus (MRSA and MSSA), S. lugdunensis, and E. faecalis may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · 4. Special instrument requirements: spp., and Providencia spp. Manual reading only I. Device Description: The Omadacycline MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of omadacycline across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Omadacycline code (OMC) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of 4 antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two- fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Result MIC Same Differences Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents against Gram-negative and Gram- positive organisms Quantitative susceptibility to antimicrobial agents to Gram- positive organisms Antibiotic Omadacycline code (OMC) Vancomycin code (VA) Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC as 80% inhibition when trailing is seen Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC at 100% inhibition Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours 5 K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. Given that omadacycline is a bacteriostatic drug, the ellipse should be interpreted at 80% inhibition when trailing is observed. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reprodu Panel:

idK182922_s0_e2000

K182922.txt

predicate device name

Liofilchem MTS, vancomycin

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K182922 B. Purpose for Submission: To obtain a substantial equivalence determination for Omadacycline (OMC) at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram-negative and non-fastidious Gram-positive organisms C. Measurand: Omadacycline 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth-based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: MTS Omadacycline 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem MTS (MIC Test Strip) Omadacycline 0.002-32 μg/mL is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The MTS Omadacycline at concentrations of 0.002-32 μg/mL should be interpreted at 16-20 hours of incubation. MTS Omadacycline can be used to determine the MIC of omadacycline against the following bacteria. Omadacycline has been shown to be active both clinically and in vitro against these bacterial species according to the FDA drug approved label: Gram-Positive bacteria Staphylococcus aureus Staphylococcus lugdunensis Enterococcus faecalis Gram-Negative bacteria Enterobacter cloacae Klebsiella pneumoniae Omadacycline has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug approved label: Gram-Positive bacteria Enterococcus faecium (vancomycin-susceptible and -resistant isolates) Gram-Negative bacteria Escherichia coli Citrobacter freundii Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): 3 · For prescription use · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] · The ability of the MTS to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Omadacycline: Citrobacter koseri · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. · The safety and efficacy of omadacycline in treating Community-Acquired Bacterial Pneumonia (CABP) infections due to Gram-negative organisms other than K. pneumoniae and Gram-positive organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · Omadacycline is not active in vitro against Morganella spp., Proteus The safety and efficacy of omadacycline in treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) infections due to Gram-negative organisms other than K. pneumoniae and E. cloacae and Gram-positive organisms other than S. aureus (MRSA and MSSA), S. lugdunensis, and E. faecalis may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · 4. Special instrument requirements: spp., and Providencia spp. Manual reading only I. Device Description: The Omadacycline MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of omadacycline across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Omadacycline code (OMC) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of 4 antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two- fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Result MIC Same Differences Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents against Gram-negative and Gram- positive organisms Quantitative susceptibility to antimicrobial agents to Gram- positive organisms Antibiotic Omadacycline code (OMC) Vancomycin code (VA) Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC as 80% inhibition when trailing is seen Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC at 100% inhibition Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours 5 K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. Given that omadacycline is a bacteriostatic drug, the ellipse should be interpreted at 80% inhibition when trailing is observed. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reprodu Predicate device name:

idK182922_s0_e2000

K182922.txt

applicant

Liofilchem s.r.l.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K182922 B. Purpose for Submission: To obtain a substantial equivalence determination for Omadacycline (OMC) at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram-negative and non-fastidious Gram-positive organisms C. Measurand: Omadacycline 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth-based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: MTS Omadacycline 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem MTS (MIC Test Strip) Omadacycline 0.002-32 μg/mL is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The MTS Omadacycline at concentrations of 0.002-32 μg/mL should be interpreted at 16-20 hours of incubation. MTS Omadacycline can be used to determine the MIC of omadacycline against the following bacteria. Omadacycline has been shown to be active both clinically and in vitro against these bacterial species according to the FDA drug approved label: Gram-Positive bacteria Staphylococcus aureus Staphylococcus lugdunensis Enterococcus faecalis Gram-Negative bacteria Enterobacter cloacae Klebsiella pneumoniae Omadacycline has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug approved label: Gram-Positive bacteria Enterococcus faecium (vancomycin-susceptible and -resistant isolates) Gram-Negative bacteria Escherichia coli Citrobacter freundii Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): 3 · For prescription use · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] · The ability of the MTS to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Omadacycline: Citrobacter koseri · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. · The safety and efficacy of omadacycline in treating Community-Acquired Bacterial Pneumonia (CABP) infections due to Gram-negative organisms other than K. pneumoniae and Gram-positive organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · Omadacycline is not active in vitro against Morganella spp., Proteus The safety and efficacy of omadacycline in treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) infections due to Gram-negative organisms other than K. pneumoniae and E. cloacae and Gram-positive organisms other than S. aureus (MRSA and MSSA), S. lugdunensis, and E. faecalis may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · 4. Special instrument requirements: spp., and Providencia spp. Manual reading only I. Device Description: The Omadacycline MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of omadacycline across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Omadacycline code (OMC) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of 4 antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two- fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Result MIC Same Differences Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents against Gram-negative and Gram- positive organisms Quantitative susceptibility to antimicrobial agents to Gram- positive organisms Antibiotic Omadacycline code (OMC) Vancomycin code (VA) Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC as 80% inhibition when trailing is seen Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC at 100% inhibition Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours 5 K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. Given that omadacycline is a bacteriostatic drug, the ellipse should be interpreted at 80% inhibition when trailing is observed. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reprodu Applicant:

idK182922_s0_e2000

K182922.txt

proprietary and established names

MTS Omadacycline 0.002-32 μg/mL

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K182922 B. Purpose for Submission: To obtain a substantial equivalence determination for Omadacycline (OMC) at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram-negative and non-fastidious Gram-positive organisms C. Measurand: Omadacycline 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth-based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: MTS Omadacycline 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem MTS (MIC Test Strip) Omadacycline 0.002-32 μg/mL is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The MTS Omadacycline at concentrations of 0.002-32 μg/mL should be interpreted at 16-20 hours of incubation. MTS Omadacycline can be used to determine the MIC of omadacycline against the following bacteria. Omadacycline has been shown to be active both clinically and in vitro against these bacterial species according to the FDA drug approved label: Gram-Positive bacteria Staphylococcus aureus Staphylococcus lugdunensis Enterococcus faecalis Gram-Negative bacteria Enterobacter cloacae Klebsiella pneumoniae Omadacycline has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug approved label: Gram-Positive bacteria Enterococcus faecium (vancomycin-susceptible and -resistant isolates) Gram-Negative bacteria Escherichia coli Citrobacter freundii Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): 3 · For prescription use · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] · The ability of the MTS to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Omadacycline: Citrobacter koseri · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. · The safety and efficacy of omadacycline in treating Community-Acquired Bacterial Pneumonia (CABP) infections due to Gram-negative organisms other than K. pneumoniae and Gram-positive organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · Omadacycline is not active in vitro against Morganella spp., Proteus The safety and efficacy of omadacycline in treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) infections due to Gram-negative organisms other than K. pneumoniae and E. cloacae and Gram-positive organisms other than S. aureus (MRSA and MSSA), S. lugdunensis, and E. faecalis may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · 4. Special instrument requirements: spp., and Providencia spp. Manual reading only I. Device Description: The Omadacycline MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of omadacycline across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Omadacycline code (OMC) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of 4 antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two- fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Result MIC Same Differences Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents against Gram-negative and Gram- positive organisms Quantitative susceptibility to antimicrobial agents to Gram- positive organisms Antibiotic Omadacycline code (OMC) Vancomycin code (VA) Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC as 80% inhibition when trailing is seen Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC at 100% inhibition Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours 5 K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. Given that omadacycline is a bacteriostatic drug, the ellipse should be interpreted at 80% inhibition when trailing is observed. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reprodu Proprietary and established names:

idK182922_s0_e2000

K182922.txt

regulation section

866.1640 Antimicrobial Susceptibility Test Powder

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K182922 B. Purpose for Submission: To obtain a substantial equivalence determination for Omadacycline (OMC) at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram-negative and non-fastidious Gram-positive organisms C. Measurand: Omadacycline 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth-based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: MTS Omadacycline 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem MTS (MIC Test Strip) Omadacycline 0.002-32 μg/mL is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in µg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The MTS Omadacycline at concentrations of 0.002-32 μg/mL should be interpreted at 16-20 hours of incubation. MTS Omadacycline can be used to determine the MIC of omadacycline against the following bacteria. Omadacycline has been shown to be active both clinically and in vitro against these bacterial species according to the FDA drug approved label: Gram-Positive bacteria Staphylococcus aureus Staphylococcus lugdunensis Enterococcus faecalis Gram-Negative bacteria Enterobacter cloacae Klebsiella pneumoniae Omadacycline has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug approved label: Gram-Positive bacteria Enterococcus faecium (vancomycin-susceptible and -resistant isolates) Gram-Negative bacteria Escherichia coli Citrobacter freundii Citrobacter koseri Klebsiella aerogenes Klebsiella oxytoca 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): 3 · For prescription use · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] · The ability of the MTS to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Omadacycline: Citrobacter koseri · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. · The safety and efficacy of omadacycline in treating Community-Acquired Bacterial Pneumonia (CABP) infections due to Gram-negative organisms other than K. pneumoniae and Gram-positive organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · Omadacycline is not active in vitro against Morganella spp., Proteus The safety and efficacy of omadacycline in treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) infections due to Gram-negative organisms other than K. pneumoniae and E. cloacae and Gram-positive organisms other than S. aureus (MRSA and MSSA), S. lugdunensis, and E. faecalis may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. · 4. Special instrument requirements: spp., and Providencia spp. Manual reading only I. Device Description: The Omadacycline MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of omadacycline across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Omadacycline code (OMC) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of 4 antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two- fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Result MIC Same Differences Item Device Liofilchem MTS, Omadacycline (K182922) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents against Gram-negative and Gram- positive organisms Quantitative susceptibility to antimicrobial agents to Gram- positive organisms Antibiotic Omadacycline code (OMC) Vancomycin code (VA) Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC as 80% inhibition when trailing is seen Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip; interpret the MIC at 100% inhibition Incubation 35 ± 2°C for 16 – 20 hours 35 ± 2°C for 24 hours 5 K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 μg/mL is considered to be the same as 0.12 μg/mL for reporting purposes. Given that omadacycline is a bacteriostatic drug, the ellipse should be interpreted at 80% inhibition when trailing is observed. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reprodu Regulation section:

idK182922_s4000_e6000

K182922.txt

proposed labeling

The labeling supports the finding of substantial equivalence for this device.

obacteriaceae (all) Clinical 496 494 99.6 488 486 99.6 478 96.4 16 18 0 0 Challenge 82 82 100 41 41 100 71 86.6 49 11 0 0 Combined 578 576 99.7 529 527 99.6 549 95.0 65 29 0 0 10 EA – Essential agreement maj – Major errors CA – Category agreement vmj – Very major errors EVAL – Evaluable isolates min – Minor errors R – Resistant isolates Essential Agreement (EA) is when the Liofilchem MIC Test Strip (MST) results agree exactly or within one doubling dilution of the reference broth microdilution results. Category Agreement (CA) is when the Liofilchem MIC Test Strip (MST) result interpretation agrees exactly with the reference broth microdilution result interpretation. The overall performance of S. aureus (both MRSA and MSSA) isolates when evaluated with ABSSSI breakpoints is acceptable with 98.9% EA and 96.0% CA. The overall performance of S. aureus (MSSA only) isolates when assessed with CAPB breakpoints is acceptable with 98.5% EA and 96.9% CA. According to the drug label for Omadacycline, only MSSA isolates are indicated for CAPB; however, MRSA were included in the study to further assess the performance of the Omadacycline MTS. The inclusion of MRSA isolates in the study demonstrated equivalent performance (i.e., 98.9% EA and 96.6% CA). There were no major or very major errors. The evaluation of S. lugdunensis isolates yielded a performance of 100% EA and 87.1% CA (12.9% minor error rate). Given that all results were within EA and that there were no major or very major errors, the overall performance was deemed acceptable. The evaluation of E. faecalis (VSE and VRE) isolates yielded a performance of 98.3% EA and 84.3% CA (15.7% minor error rate). Given that all results were within EA and that there were no major or very major errors, the overall performance was deemed acceptable. In addition, there was no significant difference noted in the performance between vancomycin-susceptible E. faecalis and vancomycin-resistant E. faecalis isolates. The overall performance of E. faecium (VSE and VRE) isolates is acceptable with 100% EA and 98.0% CA. There were no major or very major errors and no difference noted in the performance between vancomycin-susceptible E. faecium and vancomycin-resistant E. faecium isolates. The overall performance of all Enterobacteriaceae isolates is acceptable with 99.7% EA and 95.0% CA. In addition, the performance for each Gram-negative organism was evaluated separately and results for each demonstrated >90% EA and >90% CA with no major or very major errors and was, therefore, deemed acceptable. Resistance Mechanisms: Molecular characterization of challenge isolates was provided with respect to tetracycline-specific resistance mechanisms for both MTS and reference method to include tet(A), tet(D), tet(G) for Gram-negative organisms and tet(K) and tet(M) for Gram-positive organisms. Specifically, six K. pneumoniae and three E. cloacae encoding tet(A) were evaluated in which all isolates were found to be resistant to omadacycline by 11 both methods. In addition, one E. cloacae isolate encoding tet(G) was found to be resistant to omadacycline. Furthermore, one E. cloacae isolate encoding tet(D) was found to be intermediate by both methods. Regarding Gram-positive isolates, one E. faecalis and two S. aureus isolates encoding tet(M) were tested. The E. faecalis isolate and one of the two S. aureus isolates were found to be resistant while the other was found to be susceptible by both methods. In addition, two S. aureus isolate encoding tet(k) were evaluated and found to be resistant. Given that some claimed organisms with their associated resistance mechanisms were not available [e.g., tet(B), tet(L)] during the time of testing, the following limitation was included in the labeling: · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] Trending: Trending was assessed separately for Gram-positive and Gram-negative groups using data for challenge and clinical isolates (Tables 5 and 6). No significant trending (i.e., ≥30% difference) was observed for Gram-negative, S. aureus, or E. faecalis isolates; however, trending was observed for S. lugdunensis which tended to be in exact agreement or higher when compared to the reference method. The difference between higher and lower dilutions for this organism was >30%. Given the observed trending, the following was included in the labeling: · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. Table 5. Trending for Gram-positive Organisms by Species Total ≥1 dil. lower Exact ≤1 dil. higher S. aureus (MSSA+MRSA)a 175 45 118 12 (25.71%) (67.43%) (6.86%) E. faecalis (VSE+VRE)b 121 10 74 37 (8.26%) (61.16%) (30.58%) E. faecium (VSE+VRE)c 100 10 79 11 (10.00%) (79.00%) (11.00%) S. lugdunensisd 70 2 37 31 (2.86%) (52.86%) (44.29%) aDifference between the higher and lower dilutions for S. aureus is: -18.86%; 95% C.I. (-26.38% to - 11.28%) 12 bDifference between the higher and lower dilutions for E. faecalis is: 22.31%; 95% C.I. (12.53% to 31.78%) cDifference between the higher and lower dilutions for E. faecium is: 1.00%; 95% C.I. (-7.82% to 9.85%) dDifference between the higher and lower dilutions for S. lugdunensis is: 41.43%; 95% C.I. (28.37% to 53.24%) Table 6. Trending for Enterobacteriaceae by Species Total ≥1 dil. lower Exact ≤1 dil. higher All Enterobacteriaceaea 546 115 367 64 (21.06%) (67.22%) (11.72%) aDifference between the higher and lower dilutions for all Enterobacteriaceae is: -9.34%; 95% C.I. (- 13.70% to -4.97%) b. Matrix comparison: Not Applicable 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: Not Applicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable 4. Clinical cut-off: Not Applicable 13 5. Expected values/Reference range: The FDA susceptibility interpretive criteria for Omadacycline are as listed in Table 7. Table 7: FDA Interpretive Criteria for Omadacycline (µg/mL) Organisms S I R ABSSSI Enterobacteriaceae ≤4 8 ≥16 S. aureus (MSSA + MRSA) ≤0.5 1 ≥2 S. lugdunensis ≤0.12 0.25 ≥0.5 E. faecalis ≤0.25 0.5 ≥1 CABP Enterobacteriaceae ≤4 8 ≥16 S. aureus (MSSA only) ≤0.25 0.5 ≥1 N. Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK182922_s4000_e6000

K182922.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

points Enterobacteriaceae (all) Clinical 496 494 99.6 488 486 99.6 478 96.4 16 18 0 0 Challenge 82 82 100 41 41 100 71 86.6 49 11 0 0 Combined 578 576 99.7 529 527 99.6 549 95.0 65 29 0 0 10 EA – Essential agreement maj – Major errors CA – Category agreement vmj – Very major errors EVAL – Evaluable isolates min – Minor errors R – Resistant isolates Essential Agreement (EA) is when the Liofilchem MIC Test Strip (MST) results agree exactly or within one doubling dilution of the reference broth microdilution results. Category Agreement (CA) is when the Liofilchem MIC Test Strip (MST) result interpretation agrees exactly with the reference broth microdilution result interpretation. The overall performance of S. aureus (both MRSA and MSSA) isolates when evaluated with ABSSSI breakpoints is acceptable with 98.9% EA and 96.0% CA. The overall performance of S. aureus (MSSA only) isolates when assessed with CAPB breakpoints is acceptable with 98.5% EA and 96.9% CA. According to the drug label for Omadacycline, only MSSA isolates are indicated for CAPB; however, MRSA were included in the study to further assess the performance of the Omadacycline MTS. The inclusion of MRSA isolates in the study demonstrated equivalent performance (i.e., 98.9% EA and 96.6% CA). There were no major or very major errors. The evaluation of S. lugdunensis isolates yielded a performance of 100% EA and 87.1% CA (12.9% minor error rate). Given that all results were within EA and that there were no major or very major errors, the overall performance was deemed acceptable. The evaluation of E. faecalis (VSE and VRE) isolates yielded a performance of 98.3% EA and 84.3% CA (15.7% minor error rate). Given that all results were within EA and that there were no major or very major errors, the overall performance was deemed acceptable. In addition, there was no significant difference noted in the performance between vancomycin-susceptible E. faecalis and vancomycin-resistant E. faecalis isolates. The overall performance of E. faecium (VSE and VRE) isolates is acceptable with 100% EA and 98.0% CA. There were no major or very major errors and no difference noted in the performance between vancomycin-susceptible E. faecium and vancomycin-resistant E. faecium isolates. The overall performance of all Enterobacteriaceae isolates is acceptable with 99.7% EA and 95.0% CA. In addition, the performance for each Gram-negative organism was evaluated separately and results for each demonstrated >90% EA and >90% CA with no major or very major errors and was, therefore, deemed acceptable. Resistance Mechanisms: Molecular characterization of challenge isolates was provided with respect to tetracycline-specific resistance mechanisms for both MTS and reference method to include tet(A), tet(D), tet(G) for Gram-negative organisms and tet(K) and tet(M) for Gram-positive organisms. Specifically, six K. pneumoniae and three E. cloacae encoding tet(A) were evaluated in which all isolates were found to be resistant to omadacycline by 11 both methods. In addition, one E. cloacae isolate encoding tet(G) was found to be resistant to omadacycline. Furthermore, one E. cloacae isolate encoding tet(D) was found to be intermediate by both methods. Regarding Gram-positive isolates, one E. faecalis and two S. aureus isolates encoding tet(M) were tested. The E. faecalis isolate and one of the two S. aureus isolates were found to be resistant while the other was found to be susceptible by both methods. In addition, two S. aureus isolate encoding tet(k) were evaluated and found to be resistant. Given that some claimed organisms with their associated resistance mechanisms were not available [e.g., tet(B), tet(L)] during the time of testing, the following limitation was included in the labeling: · Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the MTS Omadacycline for non-fastidious gram-negative bacilli and gram-positive cocci is unknown for the following: Enterobacteriaceae [tet(B)]; Enterococcus species [tet(K), tet(L)]; S. aureus [tet(L)] Trending: Trending was assessed separately for Gram-positive and Gram-negative groups using data for challenge and clinical isolates (Tables 5 and 6). No significant trending (i.e., ≥30% difference) was observed for Gram-negative, S. aureus, or E. faecalis isolates; however, trending was observed for S. lugdunensis which tended to be in exact agreement or higher when compared to the reference method. The difference between higher and lower dilutions for this organism was >30%. Given the observed trending, the following was included in the labeling: · Liofilchem MIC Test Strip (MTS) Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing S. lugdunensis compared to the CLSI reference broth microdilution. Table 5. Trending for Gram-positive Organisms by Species Total ≥1 dil. lower Exact ≤1 dil. higher S. aureus (MSSA+MRSA)a 175 45 118 12 (25.71%) (67.43%) (6.86%) E. faecalis (VSE+VRE)b 121 10 74 37 (8.26%) (61.16%) (30.58%) E. faecium (VSE+VRE)c 100 10 79 11 (10.00%) (79.00%) (11.00%) S. lugdunensisd 70 2 37 31 (2.86%) (52.86%) (44.29%) aDifference between the higher and lower dilutions for S. aureus is: -18.86%; 95% C.I. (-26.38% to - 11.28%) 12 bDifference between the higher and lower dilutions for E. faecalis is: 22.31%; 95% C.I. (12.53% to 31.78%) cDifference between the higher and lower dilutions for E. faecium is: 1.00%; 95% C.I. (-7.82% to 9.85%) dDifference between the higher and lower dilutions for S. lugdunensis is: 41.43%; 95% C.I. (28.37% to 53.24%) Table 6. Trending for Enterobacteriaceae by Species Total ≥1 dil. lower Exact ≤1 dil. higher All Enterobacteriaceaea 546 115 367 64 (21.06%) (67.22%) (11.72%) aDifference between the higher and lower dilutions for all Enterobacteriaceae is: -9.34%; 95% C.I. (- 13.70% to -4.97%) b. Matrix comparison: Not Applicable 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: Not Applicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable 4. Clinical cut-off: Not Applicable 13 5. Expected values/Reference range: The FDA susceptibility interpretive criteria for Omadacycline are as listed in Table 7. Table 7: FDA Interpretive Criteria for Omadacycline (µg/mL) Organisms S I R ABSSSI Enterobacteriaceae ≤4 8 ≥16 S. aureus (MSSA + MRSA) ≤0.5 1 ≥2 S. lugdunensis ≤0.12 0.25 ≥0.5 E. faecalis ≤0.25 0.5 ≥1 CABP Enterobacteriaceae ≤4 8 ≥16 S. aureus (MSSA only) ≤0.25 0.5 ≥1 N. Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK163260_s0_e2000

K163260.txt

purpose for submission

To obtain a substantial equivalence determination for the SeptiCyte LAB

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT Purpose for submission:

idK163260_s0_e2000

K163260.txt

measurand

LAMP1, CEACAM4, PLA2G7, PLAC8

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT Measurand:

idK163260_s0_e2000

K163260.txt

type of test

Reverse transcription + quantitative PCR (RT-qPCR)

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT Type of test:

idK163260_s0_e2000

K163260.txt

classification

Class II

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT Classification:

idK163260_s0_e2000

K163260.txt

product code

PRE

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT Product code:

idK163260_s0_e2000

K163260.txt

panel

83: Microbiology

30 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT Panel:

idK163260_s0_e2000

K163260.txt

indications for use

Same as Intended Use.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT Indications for use:

idK163260_s0_e2000

K163260.txt

predicate device name

B·R·A·H·M·S PCT Sensitive KRYPTOR

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT Predicate device name:

idK163260_s0_e2000

K163260.txt

510k number

K163260

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT 510k number:

idK163260_s0_e2000

K163260.txt

applicant

Immunexpress, Inc.

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT Applicant:

idK163260_s0_e2000

K163260.txt

proprietary and established names

SeptiCyte LAB

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT Proprietary and established names:

idK163260_s0_e2000

K163260.txt

regulation section

21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION A. 510(k) Number: K163260 B. Purpose for Submission: To obtain a substantial equivalence determination for the SeptiCyte LAB C. Measurand: Four mRNA transcript immune biomarkers: LAMP1, CEACAM4, PLA2G7, PLAC8 D. Type of Test: Reverse transcription + quantitative PCR (RT-qPCR) E. Applicant: Immunexpress, Inc. F. Proprietary and Established Names: SeptiCyte LAB G. Regulatory Information: 1. Regulation section: 21 CFR 866.3215; Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis 2. Classification: Class II (Special Controls) 3. Product code: PRE 4. Panel: 83: Microbiology Page 2 of 30 H. Intended Use: 1. Intended use(s): The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. 2. Indication(s) for use: Same as Intended Use. 3. Special conditions for use statement(s): Blood must be collected in PAXgene Blood RNA Tube (K042613) 4. Special instrument requirements: Applied Biosystems7500 FastDx Real-Time PCR Instrument QIAcube (optional, for automated RNA extraction) Spectrophotometer (e.g., Nanodrop) I. Device Description: The SeptiCyte LAB is an in vitro diagnostic test for simultaneous amplification and detection of four RNA transcripts (LAMP1, CEACAM4, PLA2G7, PLAC8) using total RNA extracted from human blood. The test has been designed, manufactured, and validated for use on the ABI 7500 Fast Dx real-time thermal cycler. Each SeptiCyte LAB kit includes, in two boxes, the reagents sufficient for up to 12 patient samples. The specimen used for the SeptiCyte LAB is a 2.5 mL sample of whole blood collected by venipuncture using the PAXgene collection tubes within the PAXgene Blood RNA System (Qiagen, kit catalogue # 762164; Becton Dickinson, Collection Tubes catalogue number 762165; FDA 510k number K042613). A white blood count (WBC) of 2.7 X 105 WBC/mL or greater must be verified prior to testing patients. Total RNA isolation is performed using the procedures specified in the PAXgene Blood RNA kit (a component of the PAXgene Blood RNA System). The purified total RNA must be evaluated for concentration (A260 indicating a concentration of ≥2 ng/µL) and purity (as estimated by A260/A280 ratio ≥ 1.6). RNA specimens may need to be adjusted in concentration to facilitate a constant input volume of 10 µL. If purified total RNA is <2 ng/ Page 3 of 30 µL then the sample is too dilute to use. If purified total RNA concentration is >50 ng/µL and ≤ 500 ng/ μL , the specimen must be diluted 10-fold with SeptiCyte LAB Diluent (1 μL RNA into 9μL Diluent) to ≤ 50 ng/µL to prevent exceeding 500 ng total input into the RT reaction. If total RNA concentration is >500 ng/µL, the specimen must be diluted 50-fold with SeptiCyte LAB Diluent (1 μL RNA into 49μL Diluent). Patient RNA samples are normalized to concentrations between 2 ng/µL to 50 ng/µL using SeptiCyte LAB Diluent to result in a 20 ng to 500 ng of RNA input per RT reaction for the SeptiCyte LAB . Purified total RNA should be tested immediately after extraction or stored frozen in single-use portions at or below -70°C until ready for testing. The SeptiCyte LAB uses quantitative, real-time determination of the amount of each transcript in the sample based on the detection of fluorescence by the qPCR instrument (Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562). The SeptiCyte LAB includes an RT step which converts the Extracted RNA to cDNA. The cDNA is immediately run in the qPCR portion of the test. Transcripts CEACAM4, LAMP1, and PLAC8 are amplified, detected, and quantified in a multiplex reaction. There is a separate reaction (singleplex) well for PLA2G7. The reported score is calculated based on the difference between two pairwise combinations of the four markers, using SeptiCyte Analysis software which accompanies the SeptiCyte LAB . The software is designed to analyze .sds run files from the ABI 7500 Fast Dx instrument, compute the likelihood of sepsis for each patient sample, and generate a separate Patient Report for each sample. The SeptiCyte LAB quantifies the gene expression levels of four host immune Response mRNA targets, to produce a quantitative score (the SeptiScore) ranging from 0 – 10. The SeptiScore is interpreted by means of four Interpretation Bands, which directly correlate with an increased likelihood of sepsis. The SeptiCyte LAB is a quantitative blood test that combines the results of four RNA transcripts (CEACAM4, LAMP1, PLA2G7, and PLAC8) as a single numerical result. PAXgene Blood RNA tube extraction utilizes manual extraction with the IVD version of the QIAGEN PAXgene Blood RNA Kit. Both standard or accelerated RNA extraction can be performed. The standard PAXgene Blood RNA tube processing , which is performed according to manufacturer instructions, includes the 2 hour room temperature incubation prior to extraction while the accelerated processing does not include the 2 hour room temperature incubation prior to extraction. The median turnaround time for the SeptiCyte LAB including all steps from the start of the blood draw to the report generation, but excluding the standard 2 hour pre-incubation step was 4 h 23 min. If the 2 hour pre- incubation in included, the turnaround time results are about 6.5 hours. Semi-automated extraction PAXgene Blood RNA Tube, using the QIAGEN QIAcube System can also be utilized. J. Substantial Equivalence Information: 1. Predicate device name(s): Page 4 of 30 B·R·A·H·M·S PCT Sensitive KRYPTOR 2. Predicate 510(k) number(s): DEN150009 3. Comparison with predicate: Predicate Comparison Item Device Predicate SeptiCyte LAB (K163260) B·R·A·H·M·S PCT Sensitive KRYPTOR (DEN150009) Intended Use/ Indications for Use The SeptiCyte LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene Blood RNA Tube. The SeptiCyte LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The SeptiCyte LAB generates a score (SeptiSCORE ) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. The SeptiCyte LAB is intended for in-vitro diagnostic use. The B·R·A·H·M·S PCT sensitive KRYPTOR is an immunofluorescent assay using Time-Resolved Amplified Cryptate Emission (TRACE) technology to determine the concentration of PCT (procalcitonin) in human serum and EDTA or heparin plasma. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended to be performed on the B·R·A·H·M·S KRYPTOR analyzer family. The B·R·A·H·M·S PCT sensitive KRYPTOR is intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock. The B·R·A·H·M·S PCT sensitive KRYPT Regulation section:

idK163260_s16000_e18000

K163260.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

20.1 62.5 16.7 0.7 4. Clinical cut-off: SeptiSCORE cut-off values were established prior to the clinical trial. The following SeptiSCORE Interpretation tables are the results from non-interventional observational clinical trials, the VENUS trial (Clinicaltrials.gov identifier: NCT02127502) and (MARS) clinical trial (NCT01905033) using either the Forced Diagnosis (Table 16) or Page 28 of 30 the Consensus Diagnosis (Table 17). The SeptiSCORE values for African Americans included in the clinical study and apparently healthy African Americans (not part of the clinical study) showed there may be a small positive bias (higher SeptiSCORE) when compared to other racial and ethnic groups. Table 16: Recommendations for interpretation of SeptiSCORE values using the Forced Diagnosis SeptiSCORE Interpretation Band Interpretation Prevalence Sepsis Likelihood Ratio SIRS Sepsis Band 4 (6-10) Sepsis is > 82% likely 18% 82% 5.61 Band 3 (4.5-5.9) Sepsis is > 49% likely 51% 49% 1.15 Band 2 (3.1-4.4) Sepsis is > 22% likely 78% 22% 0.35 Band 1 (0-3.0) Sepsis is < 16% likely 84% 16% 0.23 Table 17: Recommendations for interpretation of SeptiSCORE values using the Consensus Diagnosis SeptiSCORE Interpretation Band Interpretation Prevalence Sepsis Likelihood Ratio SIRS Sepsis Band 4 (6-10) Sepsis is > 84% likely 16% 84% 6.71 Band 3 (4.5-5.9) Sepsis is > 48% likely 52% 48% 1.17 Band 2 (3.1-4.4) Sepsis is > 20% likely 80% 20% 0.31 Band 1 (0-3.0) Sepsis is < 11% likely 89% 11% 0.16 5. Expected values/Reference range: See Clinical cut-off. Predictive values depend on the likelihood ratios and the prevalence of disease. Laboratories and other users should establish their own reference intervals for their patient populations using the SeptiCyte LAB to reflect potential sources of variability, such as patient gender, race, age, and preparation techniques. N. Instrument Name: The SeptiCyte LAB uses the Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562. SeptiCyte Analysis software. O. System Descriptions: 1. Modes of Operation: See Device Description (Section I) above Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ____X____ or No ________ Page 29 of 30 Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ___X_____ or No ____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X____ or No ________ Note: The software V1.3 is intended to be run only using Windows 7 (not Windows 8.1) and was validated to run only using Windows 7. 3. Specimen Identification: The Sample IDs (for 1, 2 or 3 samples) for a run are entered into the ABI-7500 Fast Dx setup screen, by the laboratory operator when setting up the run. The laboratory operator types in the sample IDs through the keyboard attached to the ABI-7500 Fast Dx console. The SeptiCyte LAB does not provide any provision for data entry other than by the keyboard. This does not preclude the use of a bar code reader if the laboratory has a reader that can be attached to the ABI-7500 Fast Dx and used as a data input device. This, however, would be part of the laboratory operations, and would occur outside of the instructions provided with the SeptiCyte LAB. The sample IDs are automatically embedded in the SDS file, along with the associated real-time RT-qPCR data, as created by the ABI-7500 Fast Dx during the run. SDS file is exported by the ABI-7500 Fast Dx and manually transferred to the computer running SeptiCyte Analysis software. SDS file is read by the SeptiCyte Analysis Software. The SeptiCyte Analysis Software parses the contents of the SDS file, and uses each embedded Sample ID to search in the local HL7 directory for the first instance of an HL7 file that contains the corresponding Sample ID tag within the appropriate HL7 file element. Once the SeptiCyte Analysis software locates the corresponding HL7 file, it reads the contents of this file, and then populates the relevant fields on the patient report with the following patient demographic information: Patient Name, Medical Report , Blood Collection Date, Sample ID. Alternatively, if no corresponding HL7 file is available in the local HL7 directory, then the SeptiCyte Analysis software generates a report with only the Sample ID field populated taking information from the ABI-7500 Fast Dx SDS file. In such a case, the Sample ID would need to be manually linked to the patient demographic information after the report was generated. The SeptiCyte LAB Analysis Software imports patient demographic information from the LIMS system via file system transfer. Further the software exports patient and report information to the LIMS system. 4. Specimen Sampling and Handling: See Section I- Device description 5. Calibration: No calibrators are run as part of the SeptiCyte LAB protocol. Page 30 of 30 6. Quality Control: See Section 1C - Traceability, Stability, Expected values (controls, calibrators, or methods): P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: N/A Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: 1. The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK163260_s16000_e18000

K163260.txt

conclusion

1. The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

1 % 20.1 62.5 16.7 0.7 4. Clinical cut-off: SeptiSCORE cut-off values were established prior to the clinical trial. The following SeptiSCORE Interpretation tables are the results from non-interventional observational clinical trials, the VENUS trial (Clinicaltrials.gov identifier: NCT02127502) and (MARS) clinical trial (NCT01905033) using either the Forced Diagnosis (Table 16) or Page 28 of 30 the Consensus Diagnosis (Table 17). The SeptiSCORE values for African Americans included in the clinical study and apparently healthy African Americans (not part of the clinical study) showed there may be a small positive bias (higher SeptiSCORE) when compared to other racial and ethnic groups. Table 16: Recommendations for interpretation of SeptiSCORE values using the Forced Diagnosis SeptiSCORE Interpretation Band Interpretation Prevalence Sepsis Likelihood Ratio SIRS Sepsis Band 4 (6-10) Sepsis is > 82% likely 18% 82% 5.61 Band 3 (4.5-5.9) Sepsis is > 49% likely 51% 49% 1.15 Band 2 (3.1-4.4) Sepsis is > 22% likely 78% 22% 0.35 Band 1 (0-3.0) Sepsis is < 16% likely 84% 16% 0.23 Table 17: Recommendations for interpretation of SeptiSCORE values using the Consensus Diagnosis SeptiSCORE Interpretation Band Interpretation Prevalence Sepsis Likelihood Ratio SIRS Sepsis Band 4 (6-10) Sepsis is > 84% likely 16% 84% 6.71 Band 3 (4.5-5.9) Sepsis is > 48% likely 52% 48% 1.17 Band 2 (3.1-4.4) Sepsis is > 20% likely 80% 20% 0.31 Band 1 (0-3.0) Sepsis is < 11% likely 89% 11% 0.16 5. Expected values/Reference range: See Clinical cut-off. Predictive values depend on the likelihood ratios and the prevalence of disease. Laboratories and other users should establish their own reference intervals for their patient populations using the SeptiCyte LAB to reflect potential sources of variability, such as patient gender, race, age, and preparation techniques. N. Instrument Name: The SeptiCyte LAB uses the Applied Biosystems 7500 Fast Dx Real-Time PCR Instrument, Applied Biosystems, Foster City, CA, catalogue number 4406985; FDA 510k number K082562. SeptiCyte Analysis software. O. System Descriptions: 1. Modes of Operation: See Device Description (Section I) above Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ____X____ or No ________ Page 29 of 30 Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ___X_____ or No ____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ____X____ or No ________ Note: The software V1.3 is intended to be run only using Windows 7 (not Windows 8.1) and was validated to run only using Windows 7. 3. Specimen Identification: The Sample IDs (for 1, 2 or 3 samples) for a run are entered into the ABI-7500 Fast Dx setup screen, by the laboratory operator when setting up the run. The laboratory operator types in the sample IDs through the keyboard attached to the ABI-7500 Fast Dx console. The SeptiCyte LAB does not provide any provision for data entry other than by the keyboard. This does not preclude the use of a bar code reader if the laboratory has a reader that can be attached to the ABI-7500 Fast Dx and used as a data input device. This, however, would be part of the laboratory operations, and would occur outside of the instructions provided with the SeptiCyte LAB. The sample IDs are automatically embedded in the SDS file, along with the associated real-time RT-qPCR data, as created by the ABI-7500 Fast Dx during the run. SDS file is exported by the ABI-7500 Fast Dx and manually transferred to the computer running SeptiCyte Analysis software. SDS file is read by the SeptiCyte Analysis Software. The SeptiCyte Analysis Software parses the contents of the SDS file, and uses each embedded Sample ID to search in the local HL7 directory for the first instance of an HL7 file that contains the corresponding Sample ID tag within the appropriate HL7 file element. Once the SeptiCyte Analysis software locates the corresponding HL7 file, it reads the contents of this file, and then populates the relevant fields on the patient report with the following patient demographic information: Patient Name, Medical Report , Blood Collection Date, Sample ID. Alternatively, if no corresponding HL7 file is available in the local HL7 directory, then the SeptiCyte Analysis software generates a report with only the Sample ID field populated taking information from the ABI-7500 Fast Dx SDS file. In such a case, the Sample ID would need to be manually linked to the patient demographic information after the report was generated. The SeptiCyte LAB Analysis Software imports patient demographic information from the LIMS system via file system transfer. Further the software exports patient and report information to the LIMS system. 4. Specimen Sampling and Handling: See Section I- Device description 5. Calibration: No calibrators are run as part of the SeptiCyte LAB protocol. Page 30 of 30 6. Quality Control: See Section 1C - Traceability, Stability, Expected values (controls, calibrators, or methods): P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: N/A Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: 1. The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK173817_s0_e2000

K173817.txt

purpose for submission

To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K173817 B. Purpose for Submission: To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli C. Measurand: Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL G. Regulatory Information: 1. Regulation section: 21 CFR 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code(s): JWY – Manual Antimicrobial Test Systems Page 2 of 11 4. Panel: Microbiology (83) H. Intended Use/Indications for Use: 1. Intended Use (s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Ceftazidime-avibactam MTS at concentrations of 0.016/4-256/4 μg/mL should be interpreted at 16-20 hours of incubation. Ceftazidime-avibactam has been shown to be active both clinically and in vitro against the non-fastidious bacteria listed below: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa The following in vitro data are available but their clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Providencia stuartii 2. Indications for Use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use Only Limitations: · Enzyme group characterization was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Page 3 of 11 Ceftazidime/avibactam MTS for non-fastidious gram negative bacilli is unknown for the following: Enterobacteriaceae (TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). · Due to the lack of an intermediate interpretive category for ceftazidime/avibactam, testing of P. aeruginosa with this drug has resulted in major discrepancies for isolates that are otherwise within essential agreement of the reference method. Testing should be confirmed using an alternative testing/reference method prior to reporting results for P. aeruginosa when the MTS MIC is 16 µg/mL. 4. Special instrument requirements: Manual reading only I. Device Description: The Ceftazidime/avibactam MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Ceftazidime/avibactam across 15 two-fold dilutions like those dilutions of a conventional MIC method. One side of the strip is labelled with the Ceftazidime/avibactam code (CZA) and the MIC reading scale is in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip is single use only. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, Vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Page 4 of 11 Similarities Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, Vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculum Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied to agar with swab manually or with rotation plate Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (µg/mL) Same Differences Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, vancomycin (K153687) Antimicrobial Agent Ceftazidime/avibactam Vancomycin Incubation 35°C ± 2°C for 16-20 hours 35°C ± 2°C for 24 hours K. Standard/Guidance Document Referenced (if applicable) · FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) · CLSI M07-10, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition” (January 2015) · CLSI M100-S27, “Performance Standards for Antimicrobial Susceptibility Testing”; Twenty-Seventh Informational Supplement (January 2017) L. Test Principle: MIC Test Strips (MTS) are made of special high quality paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MTS is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MTS. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects Page 5 of 11 below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 µg/mL is considered to be the same as 0.12 µg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three clinical sites using ten isolates of Gram-negative bacilli consistent with the Intended Use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested in the reproducibility study included E. coli (two isolates), K. pneumoniae (one isolate), E. cloacae (one isolate), and P. aeruginosa (six isolates). The mode MIC value was determined and the reproducibility was calculated based on MIC values that fell within +/- one doubling dilution from the mode MIC value. Both intra-site and inter-site reproducibility for Ceftazidime/avibactam MTS was calculated. There were no off-scale MIC results. The combined reproducibility results for all three sites were acceptable and demonstrated ≥95% reproducibility. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing FDA/CLSI recommended QC organisms were tested throughout the comparative testing at three study sites. The organisms tested were P. aeruginosa ATCC 27853, K. pneumoniae ATCC 700603, and E. coli ATCC 25922. These recommended QC organisms were tested a minimum of 20 times/site by both the Liofilchem Ceftaz Purpose for submission:

idK173817_s0_e2000

K173817.txt

measurand

Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K173817 B. Purpose for Submission: To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli C. Measurand: Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL G. Regulatory Information: 1. Regulation section: 21 CFR 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code(s): JWY – Manual Antimicrobial Test Systems Page 2 of 11 4. Panel: Microbiology (83) H. Intended Use/Indications for Use: 1. Intended Use (s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Ceftazidime-avibactam MTS at concentrations of 0.016/4-256/4 μg/mL should be interpreted at 16-20 hours of incubation. Ceftazidime-avibactam has been shown to be active both clinically and in vitro against the non-fastidious bacteria listed below: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa The following in vitro data are available but their clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Providencia stuartii 2. Indications for Use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use Only Limitations: · Enzyme group characterization was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Page 3 of 11 Ceftazidime/avibactam MTS for non-fastidious gram negative bacilli is unknown for the following: Enterobacteriaceae (TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). · Due to the lack of an intermediate interpretive category for ceftazidime/avibactam, testing of P. aeruginosa with this drug has resulted in major discrepancies for isolates that are otherwise within essential agreement of the reference method. Testing should be confirmed using an alternative testing/reference method prior to reporting results for P. aeruginosa when the MTS MIC is 16 µg/mL. 4. Special instrument requirements: Manual reading only I. Device Description: The Ceftazidime/avibactam MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Ceftazidime/avibactam across 15 two-fold dilutions like those dilutions of a conventional MIC method. One side of the strip is labelled with the Ceftazidime/avibactam code (CZA) and the MIC reading scale is in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip is single use only. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, Vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Page 4 of 11 Similarities Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, Vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculum Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied to agar with swab manually or with rotation plate Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (µg/mL) Same Differences Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, vancomycin (K153687) Antimicrobial Agent Ceftazidime/avibactam Vancomycin Incubation 35°C ± 2°C for 16-20 hours 35°C ± 2°C for 24 hours K. Standard/Guidance Document Referenced (if applicable) · FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) · CLSI M07-10, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition” (January 2015) · CLSI M100-S27, “Performance Standards for Antimicrobial Susceptibility Testing”; Twenty-Seventh Informational Supplement (January 2017) L. Test Principle: MIC Test Strips (MTS) are made of special high quality paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MTS is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MTS. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects Page 5 of 11 below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 µg/mL is considered to be the same as 0.12 µg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three clinical sites using ten isolates of Gram-negative bacilli consistent with the Intended Use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested in the reproducibility study included E. coli (two isolates), K. pneumoniae (one isolate), E. cloacae (one isolate), and P. aeruginosa (six isolates). The mode MIC value was determined and the reproducibility was calculated based on MIC values that fell within +/- one doubling dilution from the mode MIC value. Both intra-site and inter-site reproducibility for Ceftazidime/avibactam MTS was calculated. There were no off-scale MIC results. The combined reproducibility results for all three sites were acceptable and demonstrated ≥95% reproducibility. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing FDA/CLSI recommended QC organisms were tested throughout the comparative testing at three study sites. The organisms tested were P. aeruginosa ATCC 27853, K. pneumoniae ATCC 700603, and E. coli ATCC 25922. These recommended QC organisms were tested a minimum of 20 times/site by both the Liofilchem Ceftaz Measurand:

idK173817_s0_e2000

K173817.txt

type of test

Quantitative Antimicrobial Susceptibility Test growth based detection

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K173817 B. Purpose for Submission: To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli C. Measurand: Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL G. Regulatory Information: 1. Regulation section: 21 CFR 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code(s): JWY – Manual Antimicrobial Test Systems Page 2 of 11 4. Panel: Microbiology (83) H. Intended Use/Indications for Use: 1. Intended Use (s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Ceftazidime-avibactam MTS at concentrations of 0.016/4-256/4 μg/mL should be interpreted at 16-20 hours of incubation. Ceftazidime-avibactam has been shown to be active both clinically and in vitro against the non-fastidious bacteria listed below: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa The following in vitro data are available but their clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Providencia stuartii 2. Indications for Use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use Only Limitations: · Enzyme group characterization was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Page 3 of 11 Ceftazidime/avibactam MTS for non-fastidious gram negative bacilli is unknown for the following: Enterobacteriaceae (TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). · Due to the lack of an intermediate interpretive category for ceftazidime/avibactam, testing of P. aeruginosa with this drug has resulted in major discrepancies for isolates that are otherwise within essential agreement of the reference method. Testing should be confirmed using an alternative testing/reference method prior to reporting results for P. aeruginosa when the MTS MIC is 16 µg/mL. 4. Special instrument requirements: Manual reading only I. Device Description: The Ceftazidime/avibactam MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Ceftazidime/avibactam across 15 two-fold dilutions like those dilutions of a conventional MIC method. One side of the strip is labelled with the Ceftazidime/avibactam code (CZA) and the MIC reading scale is in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip is single use only. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, Vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Page 4 of 11 Similarities Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, Vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculum Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied to agar with swab manually or with rotation plate Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (µg/mL) Same Differences Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, vancomycin (K153687) Antimicrobial Agent Ceftazidime/avibactam Vancomycin Incubation 35°C ± 2°C for 16-20 hours 35°C ± 2°C for 24 hours K. Standard/Guidance Document Referenced (if applicable) · FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) · CLSI M07-10, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition” (January 2015) · CLSI M100-S27, “Performance Standards for Antimicrobial Susceptibility Testing”; Twenty-Seventh Informational Supplement (January 2017) L. Test Principle: MIC Test Strips (MTS) are made of special high quality paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MTS is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MTS. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects Page 5 of 11 below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 µg/mL is considered to be the same as 0.12 µg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three clinical sites using ten isolates of Gram-negative bacilli consistent with the Intended Use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested in the reproducibility study included E. coli (two isolates), K. pneumoniae (one isolate), E. cloacae (one isolate), and P. aeruginosa (six isolates). The mode MIC value was determined and the reproducibility was calculated based on MIC values that fell within +/- one doubling dilution from the mode MIC value. Both intra-site and inter-site reproducibility for Ceftazidime/avibactam MTS was calculated. There were no off-scale MIC results. The combined reproducibility results for all three sites were acceptable and demonstrated ≥95% reproducibility. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing FDA/CLSI recommended QC organisms were tested throughout the comparative testing at three study sites. The organisms tested were P. aeruginosa ATCC 27853, K. pneumoniae ATCC 700603, and E. coli ATCC 25922. These recommended QC organisms were tested a minimum of 20 times/site by both the Liofilchem Ceftaz Type of test:

idK173817_s0_e2000

K173817.txt

classification

Class II

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K173817 B. Purpose for Submission: To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli C. Measurand: Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL G. Regulatory Information: 1. Regulation section: 21 CFR 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code(s): JWY – Manual Antimicrobial Test Systems Page 2 of 11 4. Panel: Microbiology (83) H. Intended Use/Indications for Use: 1. Intended Use (s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Ceftazidime-avibactam MTS at concentrations of 0.016/4-256/4 μg/mL should be interpreted at 16-20 hours of incubation. Ceftazidime-avibactam has been shown to be active both clinically and in vitro against the non-fastidious bacteria listed below: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa The following in vitro data are available but their clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Providencia stuartii 2. Indications for Use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use Only Limitations: · Enzyme group characterization was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Page 3 of 11 Ceftazidime/avibactam MTS for non-fastidious gram negative bacilli is unknown for the following: Enterobacteriaceae (TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). · Due to the lack of an intermediate interpretive category for ceftazidime/avibactam, testing of P. aeruginosa with this drug has resulted in major discrepancies for isolates that are otherwise within essential agreement of the reference method. Testing should be confirmed using an alternative testing/reference method prior to reporting results for P. aeruginosa when the MTS MIC is 16 µg/mL. 4. Special instrument requirements: Manual reading only I. Device Description: The Ceftazidime/avibactam MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Ceftazidime/avibactam across 15 two-fold dilutions like those dilutions of a conventional MIC method. One side of the strip is labelled with the Ceftazidime/avibactam code (CZA) and the MIC reading scale is in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip is single use only. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, Vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Page 4 of 11 Similarities Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, Vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculum Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied to agar with swab manually or with rotation plate Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (µg/mL) Same Differences Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, vancomycin (K153687) Antimicrobial Agent Ceftazidime/avibactam Vancomycin Incubation 35°C ± 2°C for 16-20 hours 35°C ± 2°C for 24 hours K. Standard/Guidance Document Referenced (if applicable) · FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) · CLSI M07-10, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition” (January 2015) · CLSI M100-S27, “Performance Standards for Antimicrobial Susceptibility Testing”; Twenty-Seventh Informational Supplement (January 2017) L. Test Principle: MIC Test Strips (MTS) are made of special high quality paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MTS is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MTS. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects Page 5 of 11 below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 µg/mL is considered to be the same as 0.12 µg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three clinical sites using ten isolates of Gram-negative bacilli consistent with the Intended Use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested in the reproducibility study included E. coli (two isolates), K. pneumoniae (one isolate), E. cloacae (one isolate), and P. aeruginosa (six isolates). The mode MIC value was determined and the reproducibility was calculated based on MIC values that fell within +/- one doubling dilution from the mode MIC value. Both intra-site and inter-site reproducibility for Ceftazidime/avibactam MTS was calculated. There were no off-scale MIC results. The combined reproducibility results for all three sites were acceptable and demonstrated ≥95% reproducibility. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing FDA/CLSI recommended QC organisms were tested throughout the comparative testing at three study sites. The organisms tested were P. aeruginosa ATCC 27853, K. pneumoniae ATCC 700603, and E. coli ATCC 25922. These recommended QC organisms were tested a minimum of 20 times/site by both the Liofilchem Ceftaz Classification:

idK173817_s0_e2000

K173817.txt

product code

JWY – Manual Antimicrobial Test Systems

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K173817 B. Purpose for Submission: To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli C. Measurand: Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL G. Regulatory Information: 1. Regulation section: 21 CFR 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code(s): JWY – Manual Antimicrobial Test Systems Page 2 of 11 4. Panel: Microbiology (83) H. Intended Use/Indications for Use: 1. Intended Use (s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Ceftazidime-avibactam MTS at concentrations of 0.016/4-256/4 μg/mL should be interpreted at 16-20 hours of incubation. Ceftazidime-avibactam has been shown to be active both clinically and in vitro against the non-fastidious bacteria listed below: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa The following in vitro data are available but their clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Providencia stuartii 2. Indications for Use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use Only Limitations: · Enzyme group characterization was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Page 3 of 11 Ceftazidime/avibactam MTS for non-fastidious gram negative bacilli is unknown for the following: Enterobacteriaceae (TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). · Due to the lack of an intermediate interpretive category for ceftazidime/avibactam, testing of P. aeruginosa with this drug has resulted in major discrepancies for isolates that are otherwise within essential agreement of the reference method. Testing should be confirmed using an alternative testing/reference method prior to reporting results for P. aeruginosa when the MTS MIC is 16 µg/mL. 4. Special instrument requirements: Manual reading only I. Device Description: The Ceftazidime/avibactam MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Ceftazidime/avibactam across 15 two-fold dilutions like those dilutions of a conventional MIC method. One side of the strip is labelled with the Ceftazidime/avibactam code (CZA) and the MIC reading scale is in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip is single use only. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, Vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Page 4 of 11 Similarities Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, Vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculum Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied to agar with swab manually or with rotation plate Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (µg/mL) Same Differences Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, vancomycin (K153687) Antimicrobial Agent Ceftazidime/avibactam Vancomycin Incubation 35°C ± 2°C for 16-20 hours 35°C ± 2°C for 24 hours K. Standard/Guidance Document Referenced (if applicable) · FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) · CLSI M07-10, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition” (January 2015) · CLSI M100-S27, “Performance Standards for Antimicrobial Susceptibility Testing”; Twenty-Seventh Informational Supplement (January 2017) L. Test Principle: MIC Test Strips (MTS) are made of special high quality paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MTS is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MTS. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects Page 5 of 11 below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 µg/mL is considered to be the same as 0.12 µg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three clinical sites using ten isolates of Gram-negative bacilli consistent with the Intended Use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested in the reproducibility study included E. coli (two isolates), K. pneumoniae (one isolate), E. cloacae (one isolate), and P. aeruginosa (six isolates). The mode MIC value was determined and the reproducibility was calculated based on MIC values that fell within +/- one doubling dilution from the mode MIC value. Both intra-site and inter-site reproducibility for Ceftazidime/avibactam MTS was calculated. There were no off-scale MIC results. The combined reproducibility results for all three sites were acceptable and demonstrated ≥95% reproducibility. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing FDA/CLSI recommended QC organisms were tested throughout the comparative testing at three study sites. The organisms tested were P. aeruginosa ATCC 27853, K. pneumoniae ATCC 700603, and E. coli ATCC 25922. These recommended QC organisms were tested a minimum of 20 times/site by both the Liofilchem Ceftaz Product code:

idK173817_s0_e2000

K173817.txt

panel

Microbiology (83)

11 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K173817 B. Purpose for Submission: To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli C. Measurand: Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL G. Regulatory Information: 1. Regulation section: 21 CFR 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code(s): JWY – Manual Antimicrobial Test Systems Page 2 of 11 4. Panel: Microbiology (83) H. Intended Use/Indications for Use: 1. Intended Use (s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Ceftazidime-avibactam MTS at concentrations of 0.016/4-256/4 μg/mL should be interpreted at 16-20 hours of incubation. Ceftazidime-avibactam has been shown to be active both clinically and in vitro against the non-fastidious bacteria listed below: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa The following in vitro data are available but their clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Providencia stuartii 2. Indications for Use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use Only Limitations: · Enzyme group characterization was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Page 3 of 11 Ceftazidime/avibactam MTS for non-fastidious gram negative bacilli is unknown for the following: Enterobacteriaceae (TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). · Due to the lack of an intermediate interpretive category for ceftazidime/avibactam, testing of P. aeruginosa with this drug has resulted in major discrepancies for isolates that are otherwise within essential agreement of the reference method. Testing should be confirmed using an alternative testing/reference method prior to reporting results for P. aeruginosa when the MTS MIC is 16 µg/mL. 4. Special instrument requirements: Manual reading only I. Device Description: The Ceftazidime/avibactam MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Ceftazidime/avibactam across 15 two-fold dilutions like those dilutions of a conventional MIC method. One side of the strip is labelled with the Ceftazidime/avibactam code (CZA) and the MIC reading scale is in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip is single use only. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, Vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Page 4 of 11 Similarities Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, Vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculum Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied to agar with swab manually or with rotation plate Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (µg/mL) Same Differences Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, vancomycin (K153687) Antimicrobial Agent Ceftazidime/avibactam Vancomycin Incubation 35°C ± 2°C for 16-20 hours 35°C ± 2°C for 24 hours K. Standard/Guidance Document Referenced (if applicable) · FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) · CLSI M07-10, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition” (January 2015) · CLSI M100-S27, “Performance Standards for Antimicrobial Susceptibility Testing”; Twenty-Seventh Informational Supplement (January 2017) L. Test Principle: MIC Test Strips (MTS) are made of special high quality paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MTS is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MTS. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects Page 5 of 11 below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 µg/mL is considered to be the same as 0.12 µg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three clinical sites using ten isolates of Gram-negative bacilli consistent with the Intended Use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested in the reproducibility study included E. coli (two isolates), K. pneumoniae (one isolate), E. cloacae (one isolate), and P. aeruginosa (six isolates). The mode MIC value was determined and the reproducibility was calculated based on MIC values that fell within +/- one doubling dilution from the mode MIC value. Both intra-site and inter-site reproducibility for Ceftazidime/avibactam MTS was calculated. There were no off-scale MIC results. The combined reproducibility results for all three sites were acceptable and demonstrated ≥95% reproducibility. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing FDA/CLSI recommended QC organisms were tested throughout the comparative testing at three study sites. The organisms tested were P. aeruginosa ATCC 27853, K. pneumoniae ATCC 700603, and E. coli ATCC 25922. These recommended QC organisms were tested a minimum of 20 times/site by both the Liofilchem Ceftaz Panel:

idK173817_s0_e2000

K173817.txt

indications for use

Same as Intended Use

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K173817 B. Purpose for Submission: To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli C. Measurand: Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL G. Regulatory Information: 1. Regulation section: 21 CFR 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code(s): JWY – Manual Antimicrobial Test Systems Page 2 of 11 4. Panel: Microbiology (83) H. Intended Use/Indications for Use: 1. Intended Use (s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Ceftazidime-avibactam MTS at concentrations of 0.016/4-256/4 μg/mL should be interpreted at 16-20 hours of incubation. Ceftazidime-avibactam has been shown to be active both clinically and in vitro against the non-fastidious bacteria listed below: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa The following in vitro data are available but their clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Providencia stuartii 2. Indications for Use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use Only Limitations: · Enzyme group characterization was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Page 3 of 11 Ceftazidime/avibactam MTS for non-fastidious gram negative bacilli is unknown for the following: Enterobacteriaceae (TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). · Due to the lack of an intermediate interpretive category for ceftazidime/avibactam, testing of P. aeruginosa with this drug has resulted in major discrepancies for isolates that are otherwise within essential agreement of the reference method. Testing should be confirmed using an alternative testing/reference method prior to reporting results for P. aeruginosa when the MTS MIC is 16 µg/mL. 4. Special instrument requirements: Manual reading only I. Device Description: The Ceftazidime/avibactam MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Ceftazidime/avibactam across 15 two-fold dilutions like those dilutions of a conventional MIC method. One side of the strip is labelled with the Ceftazidime/avibactam code (CZA) and the MIC reading scale is in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip is single use only. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, Vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Page 4 of 11 Similarities Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, Vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculum Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied to agar with swab manually or with rotation plate Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (µg/mL) Same Differences Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, vancomycin (K153687) Antimicrobial Agent Ceftazidime/avibactam Vancomycin Incubation 35°C ± 2°C for 16-20 hours 35°C ± 2°C for 24 hours K. Standard/Guidance Document Referenced (if applicable) · FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) · CLSI M07-10, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition” (January 2015) · CLSI M100-S27, “Performance Standards for Antimicrobial Susceptibility Testing”; Twenty-Seventh Informational Supplement (January 2017) L. Test Principle: MIC Test Strips (MTS) are made of special high quality paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MTS is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MTS. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects Page 5 of 11 below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 µg/mL is considered to be the same as 0.12 µg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three clinical sites using ten isolates of Gram-negative bacilli consistent with the Intended Use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested in the reproducibility study included E. coli (two isolates), K. pneumoniae (one isolate), E. cloacae (one isolate), and P. aeruginosa (six isolates). The mode MIC value was determined and the reproducibility was calculated based on MIC values that fell within +/- one doubling dilution from the mode MIC value. Both intra-site and inter-site reproducibility for Ceftazidime/avibactam MTS was calculated. There were no off-scale MIC results. The combined reproducibility results for all three sites were acceptable and demonstrated ≥95% reproducibility. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing FDA/CLSI recommended QC organisms were tested throughout the comparative testing at three study sites. The organisms tested were P. aeruginosa ATCC 27853, K. pneumoniae ATCC 700603, and E. coli ATCC 25922. These recommended QC organisms were tested a minimum of 20 times/site by both the Liofilchem Ceftaz Indications for use:

idK173817_s0_e2000

K173817.txt

predicate device name

Liofilchem MTS, Vancomycin

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K173817 B. Purpose for Submission: To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli C. Measurand: Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL G. Regulatory Information: 1. Regulation section: 21 CFR 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code(s): JWY – Manual Antimicrobial Test Systems Page 2 of 11 4. Panel: Microbiology (83) H. Intended Use/Indications for Use: 1. Intended Use (s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Ceftazidime-avibactam MTS at concentrations of 0.016/4-256/4 μg/mL should be interpreted at 16-20 hours of incubation. Ceftazidime-avibactam has been shown to be active both clinically and in vitro against the non-fastidious bacteria listed below: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa The following in vitro data are available but their clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Providencia stuartii 2. Indications for Use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use Only Limitations: · Enzyme group characterization was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Page 3 of 11 Ceftazidime/avibactam MTS for non-fastidious gram negative bacilli is unknown for the following: Enterobacteriaceae (TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). · Due to the lack of an intermediate interpretive category for ceftazidime/avibactam, testing of P. aeruginosa with this drug has resulted in major discrepancies for isolates that are otherwise within essential agreement of the reference method. Testing should be confirmed using an alternative testing/reference method prior to reporting results for P. aeruginosa when the MTS MIC is 16 µg/mL. 4. Special instrument requirements: Manual reading only I. Device Description: The Ceftazidime/avibactam MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Ceftazidime/avibactam across 15 two-fold dilutions like those dilutions of a conventional MIC method. One side of the strip is labelled with the Ceftazidime/avibactam code (CZA) and the MIC reading scale is in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip is single use only. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, Vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Page 4 of 11 Similarities Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, Vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculum Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied to agar with swab manually or with rotation plate Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (µg/mL) Same Differences Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, vancomycin (K153687) Antimicrobial Agent Ceftazidime/avibactam Vancomycin Incubation 35°C ± 2°C for 16-20 hours 35°C ± 2°C for 24 hours K. Standard/Guidance Document Referenced (if applicable) · FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) · CLSI M07-10, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition” (January 2015) · CLSI M100-S27, “Performance Standards for Antimicrobial Susceptibility Testing”; Twenty-Seventh Informational Supplement (January 2017) L. Test Principle: MIC Test Strips (MTS) are made of special high quality paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MTS is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MTS. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects Page 5 of 11 below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 µg/mL is considered to be the same as 0.12 µg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three clinical sites using ten isolates of Gram-negative bacilli consistent with the Intended Use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested in the reproducibility study included E. coli (two isolates), K. pneumoniae (one isolate), E. cloacae (one isolate), and P. aeruginosa (six isolates). The mode MIC value was determined and the reproducibility was calculated based on MIC values that fell within +/- one doubling dilution from the mode MIC value. Both intra-site and inter-site reproducibility for Ceftazidime/avibactam MTS was calculated. There were no off-scale MIC results. The combined reproducibility results for all three sites were acceptable and demonstrated ≥95% reproducibility. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing FDA/CLSI recommended QC organisms were tested throughout the comparative testing at three study sites. The organisms tested were P. aeruginosa ATCC 27853, K. pneumoniae ATCC 700603, and E. coli ATCC 25922. These recommended QC organisms were tested a minimum of 20 times/site by both the Liofilchem Ceftaz Predicate device name:

idK173817_s0_e2000

K173817.txt

applicant

Liofilchem s.r.l.

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K173817 B. Purpose for Submission: To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli C. Measurand: Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL G. Regulatory Information: 1. Regulation section: 21 CFR 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code(s): JWY – Manual Antimicrobial Test Systems Page 2 of 11 4. Panel: Microbiology (83) H. Intended Use/Indications for Use: 1. Intended Use (s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Ceftazidime-avibactam MTS at concentrations of 0.016/4-256/4 μg/mL should be interpreted at 16-20 hours of incubation. Ceftazidime-avibactam has been shown to be active both clinically and in vitro against the non-fastidious bacteria listed below: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa The following in vitro data are available but their clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Providencia stuartii 2. Indications for Use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use Only Limitations: · Enzyme group characterization was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Page 3 of 11 Ceftazidime/avibactam MTS for non-fastidious gram negative bacilli is unknown for the following: Enterobacteriaceae (TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). · Due to the lack of an intermediate interpretive category for ceftazidime/avibactam, testing of P. aeruginosa with this drug has resulted in major discrepancies for isolates that are otherwise within essential agreement of the reference method. Testing should be confirmed using an alternative testing/reference method prior to reporting results for P. aeruginosa when the MTS MIC is 16 µg/mL. 4. Special instrument requirements: Manual reading only I. Device Description: The Ceftazidime/avibactam MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Ceftazidime/avibactam across 15 two-fold dilutions like those dilutions of a conventional MIC method. One side of the strip is labelled with the Ceftazidime/avibactam code (CZA) and the MIC reading scale is in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip is single use only. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, Vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Page 4 of 11 Similarities Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, Vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculum Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied to agar with swab manually or with rotation plate Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (µg/mL) Same Differences Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, vancomycin (K153687) Antimicrobial Agent Ceftazidime/avibactam Vancomycin Incubation 35°C ± 2°C for 16-20 hours 35°C ± 2°C for 24 hours K. Standard/Guidance Document Referenced (if applicable) · FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) · CLSI M07-10, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition” (January 2015) · CLSI M100-S27, “Performance Standards for Antimicrobial Susceptibility Testing”; Twenty-Seventh Informational Supplement (January 2017) L. Test Principle: MIC Test Strips (MTS) are made of special high quality paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MTS is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MTS. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects Page 5 of 11 below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 µg/mL is considered to be the same as 0.12 µg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three clinical sites using ten isolates of Gram-negative bacilli consistent with the Intended Use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested in the reproducibility study included E. coli (two isolates), K. pneumoniae (one isolate), E. cloacae (one isolate), and P. aeruginosa (six isolates). The mode MIC value was determined and the reproducibility was calculated based on MIC values that fell within +/- one doubling dilution from the mode MIC value. Both intra-site and inter-site reproducibility for Ceftazidime/avibactam MTS was calculated. There were no off-scale MIC results. The combined reproducibility results for all three sites were acceptable and demonstrated ≥95% reproducibility. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing FDA/CLSI recommended QC organisms were tested throughout the comparative testing at three study sites. The organisms tested were P. aeruginosa ATCC 27853, K. pneumoniae ATCC 700603, and E. coli ATCC 25922. These recommended QC organisms were tested a minimum of 20 times/site by both the Liofilchem Ceftaz Applicant:

idK173817_s0_e2000

K173817.txt

proprietary and established names

Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K173817 B. Purpose for Submission: To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli C. Measurand: Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL G. Regulatory Information: 1. Regulation section: 21 CFR 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code(s): JWY – Manual Antimicrobial Test Systems Page 2 of 11 4. Panel: Microbiology (83) H. Intended Use/Indications for Use: 1. Intended Use (s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Ceftazidime-avibactam MTS at concentrations of 0.016/4-256/4 μg/mL should be interpreted at 16-20 hours of incubation. Ceftazidime-avibactam has been shown to be active both clinically and in vitro against the non-fastidious bacteria listed below: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa The following in vitro data are available but their clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Providencia stuartii 2. Indications for Use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use Only Limitations: · Enzyme group characterization was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Page 3 of 11 Ceftazidime/avibactam MTS for non-fastidious gram negative bacilli is unknown for the following: Enterobacteriaceae (TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). · Due to the lack of an intermediate interpretive category for ceftazidime/avibactam, testing of P. aeruginosa with this drug has resulted in major discrepancies for isolates that are otherwise within essential agreement of the reference method. Testing should be confirmed using an alternative testing/reference method prior to reporting results for P. aeruginosa when the MTS MIC is 16 µg/mL. 4. Special instrument requirements: Manual reading only I. Device Description: The Ceftazidime/avibactam MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Ceftazidime/avibactam across 15 two-fold dilutions like those dilutions of a conventional MIC method. One side of the strip is labelled with the Ceftazidime/avibactam code (CZA) and the MIC reading scale is in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip is single use only. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, Vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Page 4 of 11 Similarities Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, Vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculum Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied to agar with swab manually or with rotation plate Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (µg/mL) Same Differences Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, vancomycin (K153687) Antimicrobial Agent Ceftazidime/avibactam Vancomycin Incubation 35°C ± 2°C for 16-20 hours 35°C ± 2°C for 24 hours K. Standard/Guidance Document Referenced (if applicable) · FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) · CLSI M07-10, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition” (January 2015) · CLSI M100-S27, “Performance Standards for Antimicrobial Susceptibility Testing”; Twenty-Seventh Informational Supplement (January 2017) L. Test Principle: MIC Test Strips (MTS) are made of special high quality paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MTS is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MTS. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects Page 5 of 11 below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 µg/mL is considered to be the same as 0.12 µg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three clinical sites using ten isolates of Gram-negative bacilli consistent with the Intended Use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested in the reproducibility study included E. coli (two isolates), K. pneumoniae (one isolate), E. cloacae (one isolate), and P. aeruginosa (six isolates). The mode MIC value was determined and the reproducibility was calculated based on MIC values that fell within +/- one doubling dilution from the mode MIC value. Both intra-site and inter-site reproducibility for Ceftazidime/avibactam MTS was calculated. There were no off-scale MIC results. The combined reproducibility results for all three sites were acceptable and demonstrated ≥95% reproducibility. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing FDA/CLSI recommended QC organisms were tested throughout the comparative testing at three study sites. The organisms tested were P. aeruginosa ATCC 27853, K. pneumoniae ATCC 700603, and E. coli ATCC 25922. These recommended QC organisms were tested a minimum of 20 times/site by both the Liofilchem Ceftaz Proprietary and established names:

idK173817_s0_e2000

K173817.txt

regulation section

21 CFR 866.1640 Antimicrobial Susceptibility Test Powder

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K173817 B. Purpose for Submission: To obtain a substantial equivalence determination of the Liofilchem MIC Test Strip (MTS) containing Ceftazidime/avibactam at concentrations of 0.016/4 – 256/4 µg/mL for susceptibility testing of select Gram-negative bacilli C. Measurand: Ceftazidime/avibactam 0.016/4 – 256/4 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Ceftazidime-avibactam 0.016/4 – 256/4 µg/mL G. Regulatory Information: 1. Regulation section: 21 CFR 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code(s): JWY – Manual Antimicrobial Test Systems Page 2 of 11 4. Panel: Microbiology (83) H. Intended Use/Indications for Use: 1. Intended Use (s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Ceftazidime-avibactam MTS at concentrations of 0.016/4-256/4 μg/mL should be interpreted at 16-20 hours of incubation. Ceftazidime-avibactam has been shown to be active both clinically and in vitro against the non-fastidious bacteria listed below: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa The following in vitro data are available but their clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Providencia stuartii 2. Indications for Use: Same as Intended Use 3. Special conditions for use statement(s): For Prescription Use Only Limitations: · Enzyme group characterization was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Page 3 of 11 Ceftazidime/avibactam MTS for non-fastidious gram negative bacilli is unknown for the following: Enterobacteriaceae (TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). · Due to the lack of an intermediate interpretive category for ceftazidime/avibactam, testing of P. aeruginosa with this drug has resulted in major discrepancies for isolates that are otherwise within essential agreement of the reference method. Testing should be confirmed using an alternative testing/reference method prior to reporting results for P. aeruginosa when the MTS MIC is 16 µg/mL. 4. Special instrument requirements: Manual reading only I. Device Description: The Ceftazidime/avibactam MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Ceftazidime/avibactam across 15 two-fold dilutions like those dilutions of a conventional MIC method. One side of the strip is labelled with the Ceftazidime/avibactam code (CZA) and the MIC reading scale is in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. The MIC Test Strip is single use only. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, Vancomycin 2. Predicate 510(k) number(s): K153687 3. Comparison with predicate: Page 4 of 11 Similarities Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, Vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculum Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied to agar with swab manually or with rotation plate Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC (µg/mL) Same Differences Item Device: Liofilchem MTS, Ceftazidime/avibactam (K173817) Predicate Device: Liofilchem MTS, vancomycin (K153687) Antimicrobial Agent Ceftazidime/avibactam Vancomycin Incubation 35°C ± 2°C for 16-20 hours 35°C ± 2°C for 24 hours K. Standard/Guidance Document Referenced (if applicable) · FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) · CLSI M07-10, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition” (January 2015) · CLSI M100-S27, “Performance Standards for Antimicrobial Susceptibility Testing”; Twenty-Seventh Informational Supplement (January 2017) L. Test Principle: MIC Test Strips (MTS) are made of special high quality paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MTS is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of μg/mL at the point where the edge of the inhibition ellipse intersects the MTS. Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects Page 5 of 11 below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125 µg/mL is considered to be the same as 0.12 µg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three clinical sites using ten isolates of Gram-negative bacilli consistent with the Intended Use. Testing was performed on three separate days and in triplicate for a total of 270 data points among the sites. The isolates tested in the reproducibility study included E. coli (two isolates), K. pneumoniae (one isolate), E. cloacae (one isolate), and P. aeruginosa (six isolates). The mode MIC value was determined and the reproducibility was calculated based on MIC values that fell within +/- one doubling dilution from the mode MIC value. Both intra-site and inter-site reproducibility for Ceftazidime/avibactam MTS was calculated. There were no off-scale MIC results. The combined reproducibility results for all three sites were acceptable and demonstrated ≥95% reproducibility. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing FDA/CLSI recommended QC organisms were tested throughout the comparative testing at three study sites. The organisms tested were P. aeruginosa ATCC 27853, K. pneumoniae ATCC 700603, and E. coli ATCC 25922. These recommended QC organisms were tested a minimum of 20 times/site by both the Liofilchem Ceftaz Regulation section:

idK173817_s4000_e6000

K173817.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

EM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). In addition, given that Ceftazidime/avibactam is not active against bacteria that produce metallo-beta lactamases and may not have activity against Gram-negative bacteria that overexpress efflux pumps or have porin mutations, the following was included in the labeling: Ceftazidime/avibactam is not active against bacteria that produce metallo-beta lactamases and may not have activity against gram-negative bacteria that overexpress efflux pumps or have porin mutations. MIC Trends: Using the combined clinical and challenge data for Enterobacteriaceae and P. aeruginosa, an analysis of trending was conducted. This trending calculation considers MIC values that are determined to be one or more doubling dilution lower or higher compared to the reference method irrespective whether the device MIC values are on-scale or not. The evaluable data for trend analysis is presented in Table 4 for all organisms. Table 4. Trending Analysis of Evaluable Clinical and Challenge Results for Enterobacteriaceae Ceftazidime/ avibactam 0.016/8 – 256/8 µg/mL Total Isolat es Difference in MIC as Compared to the CLSI Reference Method ≥ 2 dilution lower 1 dilution lower Exact 1 dilution higher ≥ 2 dilution higher C. freundiia 12 0 1 5 (41.67%) 6 0 1 (8.33%) 6 (50.0%) C. koserib 9 0 2 6 (66.67%) 1 0 2 (22.22%) 1 (11.11%) E. aerogenesc 8 0 2 3 (37.5%) 2 1 2 (25.0%) 3 (37.5%) E. cloacaed 39 0 8 24 (61.54%) 7 0 8 (20.51%) (17.95%) E. colie 96 2 14 65 (67.71%) 14 1 16 (16.67%) 62 (15.63%) K. oxytocaf 32 1 5 21 (65.63%) 5 0 6 (18.75_ 5 (15.63%) Page 10 of 11 K. pneumoniaeg 64 0 7 47 (73.44%) 9 1 7 (10.94%) 10 (15.63%) Proteus spp.h 42 0 6 12 (28.57%) 24 0 6 (14.29%) 24 (57.14%) P. stuartiii 10 0 1 5 (50.0%) 4 0 1 (10.0%) 4 (40.0%) All Enterobacteriaceaej 312 3 46 188 (60.26%) 72 3 49 (15.73%) 75 (24.04) P. aeruginosa.k 175 1 24 91 (52.0%) 44 15 25 (14.29%) 59 (33.71%) a Difference: 41.67%: 95% CI (5.08% to 67.22%) b Difference: -11.11%: 95% CI (-44.89% to 24.97%) c Difference: 12.5%: 95% CI (-29.07% to 49.08%) d Difference: -2.56%: 95% CI (-20.06% to 15.08%) e Difference: -1.04%: 95% CI (-11.57% to 9.5%) f Difference: -3.13%: 95% CI (-21.86% to 15.78%) g Difference: 4.69%: 95% CI (-7.44% to 16.83%) h Difference: 42.86%: 95% CI (22.69% to 58.54%) I Difference: 30.0%; 95% CI (-8.24% to 59.88%) j Difference: 8.33%; 95% CI (2.07% to 14.54%) k Difference: 19.43%; 95% CI (10.55% to 27.95%) Note: A positive percent difference value indicates higher MIC when compared to the reference method. A negative percent difference value indicates lower MIC when compared to the reference method. Despite the small number of available isolates with evaluable data, a higher MIC reading trend was observed in the overall performance of C. freundii, Proteus spp., and P. stuartii compared to CLSI broth microdilution. This observation raises concerns for potential major errors with these groups of organisms. This trending appears to be consistent with the observed high major error rate. To address the potential occurrence of major error(s) when using the Ceftazidime/avibactam MTS, the following statement was added as a footnote in the Performance Characteristics section of the labeling, “Drug Specific Supplement for MIC Test Strip (MTS), Ceftazidime-avibactam (CZA)”: Liofilchem MIC Test Strip (MTS) Ceftazidime-avibactam MIC values tended to be in exact agreement or at least one doubling dilution higher when testing C. freundii, Proteus species, and P. stuartii compared to the CLSI reference broth microdilution. b. Matrix comparison: Not applicable Page 11 of 11 3. Clinical studies: a. Clinical sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: The interpretive criteria for Ceftazidime/avibactam are shown in Table 5. Table 5. Interpretive Criteria for Ceftazidime/avibactam (FDA Drug Label) Organism FDA Interpretive Criteria for Ceftazidime/avibactam (µg/mL) S I R Enterobacteriaceae and P. aeruginosa ≤8/4 NA ≥16/4 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK173817_s4000_e6000

K173817.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

(TEM, SHV, CTX-M, KPC, AmpC, and OXA); Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD). In addition, given that Ceftazidime/avibactam is not active against bacteria that produce metallo-beta lactamases and may not have activity against Gram-negative bacteria that overexpress efflux pumps or have porin mutations, the following was included in the labeling: Ceftazidime/avibactam is not active against bacteria that produce metallo-beta lactamases and may not have activity against gram-negative bacteria that overexpress efflux pumps or have porin mutations. MIC Trends: Using the combined clinical and challenge data for Enterobacteriaceae and P. aeruginosa, an analysis of trending was conducted. This trending calculation considers MIC values that are determined to be one or more doubling dilution lower or higher compared to the reference method irrespective whether the device MIC values are on-scale or not. The evaluable data for trend analysis is presented in Table 4 for all organisms. Table 4. Trending Analysis of Evaluable Clinical and Challenge Results for Enterobacteriaceae Ceftazidime/ avibactam 0.016/8 – 256/8 µg/mL Total Isolat es Difference in MIC as Compared to the CLSI Reference Method ≥ 2 dilution lower 1 dilution lower Exact 1 dilution higher ≥ 2 dilution higher C. freundiia 12 0 1 5 (41.67%) 6 0 1 (8.33%) 6 (50.0%) C. koserib 9 0 2 6 (66.67%) 1 0 2 (22.22%) 1 (11.11%) E. aerogenesc 8 0 2 3 (37.5%) 2 1 2 (25.0%) 3 (37.5%) E. cloacaed 39 0 8 24 (61.54%) 7 0 8 (20.51%) (17.95%) E. colie 96 2 14 65 (67.71%) 14 1 16 (16.67%) 62 (15.63%) K. oxytocaf 32 1 5 21 (65.63%) 5 0 6 (18.75_ 5 (15.63%) Page 10 of 11 K. pneumoniaeg 64 0 7 47 (73.44%) 9 1 7 (10.94%) 10 (15.63%) Proteus spp.h 42 0 6 12 (28.57%) 24 0 6 (14.29%) 24 (57.14%) P. stuartiii 10 0 1 5 (50.0%) 4 0 1 (10.0%) 4 (40.0%) All Enterobacteriaceaej 312 3 46 188 (60.26%) 72 3 49 (15.73%) 75 (24.04) P. aeruginosa.k 175 1 24 91 (52.0%) 44 15 25 (14.29%) 59 (33.71%) a Difference: 41.67%: 95% CI (5.08% to 67.22%) b Difference: -11.11%: 95% CI (-44.89% to 24.97%) c Difference: 12.5%: 95% CI (-29.07% to 49.08%) d Difference: -2.56%: 95% CI (-20.06% to 15.08%) e Difference: -1.04%: 95% CI (-11.57% to 9.5%) f Difference: -3.13%: 95% CI (-21.86% to 15.78%) g Difference: 4.69%: 95% CI (-7.44% to 16.83%) h Difference: 42.86%: 95% CI (22.69% to 58.54%) I Difference: 30.0%; 95% CI (-8.24% to 59.88%) j Difference: 8.33%; 95% CI (2.07% to 14.54%) k Difference: 19.43%; 95% CI (10.55% to 27.95%) Note: A positive percent difference value indicates higher MIC when compared to the reference method. A negative percent difference value indicates lower MIC when compared to the reference method. Despite the small number of available isolates with evaluable data, a higher MIC reading trend was observed in the overall performance of C. freundii, Proteus spp., and P. stuartii compared to CLSI broth microdilution. This observation raises concerns for potential major errors with these groups of organisms. This trending appears to be consistent with the observed high major error rate. To address the potential occurrence of major error(s) when using the Ceftazidime/avibactam MTS, the following statement was added as a footnote in the Performance Characteristics section of the labeling, “Drug Specific Supplement for MIC Test Strip (MTS), Ceftazidime-avibactam (CZA)”: Liofilchem MIC Test Strip (MTS) Ceftazidime-avibactam MIC values tended to be in exact agreement or at least one doubling dilution higher when testing C. freundii, Proteus species, and P. stuartii compared to the CLSI reference broth microdilution. b. Matrix comparison: Not applicable Page 11 of 11 3. Clinical studies: a. Clinical sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: The interpretive criteria for Ceftazidime/avibactam are shown in Table 5. Table 5. Interpretive Criteria for Ceftazidime/avibactam (FDA Drug Label) Organism FDA Interpretive Criteria for Ceftazidime/avibactam (µg/mL) S I R Enterobacteriaceae and P. aeruginosa ≤8/4 NA ≥16/4 N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK172745_s0_e2000

K172745.txt

purpose for submission

New device

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172745 B. Purpose for Submission: New device C. Measurand: IgG Anti-Nuclear Antibodies (ANA) D. Type of Test: Qualitative or semi-quantitative, indirect immunofluorescence E.Applicant: IMMCO Diagnostics, Inc. F.Proprietary and Established Names: ImmuGlo HEp-2 Elite IFA G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100 ‒ Antinuclear antibody immunological test system 2. Classification: Class II 3. Product code: DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control 4. Panel: Immunology (82) 2 H. Intended Use: 1. Intended use: The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. 2. Indication for use: Same as Intended Use 3. Special conditions for use statement: For Prescription Use Only 4. Special instrument requirements: Fluorescence microscope for manual operation 200× or higher magnification, 490 nm excitation filter, 510 nm barrier filter I. Device Description: The kit is an indirect immunofluorescence assay (IFA) to detect IgG anti-nuclear antibodies (ANA) against proteins presented in HEp-2 cell lines. The standard test kit contains: · Substrate slides: barcoded glass slides with standard and engineered DFS70-knock-out HEp-2 cells attached in a monolayer in the slide wells · ANA homogeneous pattern positive control · ANA DFS70 pattern positive control · Negative Control · Conjugate: anti-human IgG FITC conjugate containing Evan's blue counterstain. Binds fluorescein to reactive antibodies reacting against HEp-2 antigens · Buffered diluent provided for specimen dilutions · Wash buffer: phosphate buffered saline (PBS) diluent removes reagents and unbound antibodies after incubation steps · Mounting medium provided for coverslipping of slides to view under fluorescence microscope · Coverslips Optional components: The standard kit format supplies the Conjugate and Evan’s blue counterstain as one pre- formulated reagent, however, they may also be supplied separately to accommodate laboratory workflow. The formulation is intended to be separate but functionally identical. 3 J. Substantial Equivalence Information: 1. Predicate device name: ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS 2. Predicate 510(k) number: K883883 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi- quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. Indirect immunofluorescence (IF) antibody test for the detection and quantitation of anti- nuclear antibodies (ANA) in human serum Methodology Indirect immunofluorescence Same Matrix Serum Same Detection of antibodies Anti-nuclear antibodies Same Component Set Includes positive control, negative control, conjugate, diluent, wash buffer, mounting medium, substrate slides, coverslips Same Conjugate FITC IgG Same Screening dilution 1:40 Same Reading Fluorescence microscope Same Storage 2–8° C Same Differences Item Device Predicate Substrate Standard HEp-2 cells mixed with engineered HEp-2 with the PSIP1 gene knocked out in 1:9 ratio Standard HEp-2 cells Positive control ANA homogenous, DFS70 Ab ANA homogenous 4 K. Standard/Guidance Document Referenced (if applicable): Org Standard ID Version Date Title CLSI EP05 A3 Sep 2014 Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP06 A Apr 2003 Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07 A2 Dec 2002 Interference Testing in Clinical Chemistry CLSI EP12 A2 Jan 2014 User Protocol for Evaluation of Qualitative Test Performance L. Test Principle: In the indirect IFA method used in this kit, patient sera are incubated on HEp-2 cell substrates to allow binding of antibodies. Any antibodies not bound are removed by washing with buffer. Bound antibodies of the IgG class are detected by incubation of the substrate with fluorescein-labeled anti-human IgG conjugate. Reactions are observed under a fluorescence microscope equipped with appropriate filters. The presence of nuclear and cytoplasmic patterns AC-1 to AC-28 as described by ICAP1 is demonstrated by green fluorescence of specific structures in the cells. A majority (~90%) of the cells present on the substrate are devoid of a functional PSIP1 gene which eliminates the relevant antigenic target of the DFS70 pattern. This may aid in discrimination of ANA homogeneous and speckled patterns from the DFS pattern. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. The titers are determined by testing serial dilutions of patient samples and reported as the highest reciprocal dilution with a positive reaction. M. Performance Characteristics: 1. Analytical performance: All results presented below met the manufacturer’s pre-determined acceptance criteria. Interpretation of Results: Results should be reported as negative, positive, or, if end-point titer has been determined, positive with titer. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. Users should only read only fields that contain specific staining of the HEp-2 substrates. 1. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PL, Fritzler MJ, Garcia- De La Torre I, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. “Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015” Front Immunol, 2015; 6:412. doi: 10.3389/fimmu.2015.00412. PMID: 2634773 5 The International Consensus on Antinuclear Antibody Patterns report recommends a standardized nomenclature and reporting format for IFA patterns.1. Major nuclear patterns that are recommended to be reported include Homogeneous (AC-1), Speckled (AC-2, AC-4, AC-5), Centromere (AC-3), Discrete Nuclear Dots (AC-6, AC-7) and Nucleolar (AC-8, AC-9, AC-10). Major cytoplasmic patterns include Fibrillar (AC-15, AC-16, AC-17), Speckled (AC-18, AC-19, AC-20), Reticular/AMA (AC-21), Polar Golgi-like (AC-22) and Rods and rings (AC-23). Including the most commonly and mandated to be reported patterns described above, a total of 28 patterns are described in the ICAP reference.1 Interpretation of DFS70 pattern on HEp-2 ELITE IFA substrate: In the ~10% baseline HEp-2 cells in each well, a dense fine speckled pattern will be observed on interphase nuclei. Chromatin-associated staining is seen on mitotic nuclei. The remaining ~90% of HEp-2 cells have the PSIP1 gene encoding the LEDGF antigen knocked out and therefore will not produce a similar pattern. If 10% of the HEp-2 cells have brighter fluorescence corresponding to DFS70 pattern and rest of the cells present additional patterns or fine speckled signal above cut-off, it indicates the presence of mixed patterns. Closer analysis of such patterns is essential to confirm if other antibody specificity is present in addition to the DFS70 pattern associated with LEDGF/PSIP1. Due to the high prevalence of AC-2 patterns in an ANA screening population and relatively low association with autoimmune rheumatic diseases, the ICAP committee recommends all clinical labs report the DFS70 pattern. a. Precision/Reproducibility: The sponsor modeled precision studies based on CLSI guideline EP05 Purpose for submission:

idK172745_s0_e2000

K172745.txt

measurand

IgG Anti-Nuclear Antibodies (ANA)

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172745 B. Purpose for Submission: New device C. Measurand: IgG Anti-Nuclear Antibodies (ANA) D. Type of Test: Qualitative or semi-quantitative, indirect immunofluorescence E.Applicant: IMMCO Diagnostics, Inc. F.Proprietary and Established Names: ImmuGlo HEp-2 Elite IFA G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100 ‒ Antinuclear antibody immunological test system 2. Classification: Class II 3. Product code: DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control 4. Panel: Immunology (82) 2 H. Intended Use: 1. Intended use: The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. 2. Indication for use: Same as Intended Use 3. Special conditions for use statement: For Prescription Use Only 4. Special instrument requirements: Fluorescence microscope for manual operation 200× or higher magnification, 490 nm excitation filter, 510 nm barrier filter I. Device Description: The kit is an indirect immunofluorescence assay (IFA) to detect IgG anti-nuclear antibodies (ANA) against proteins presented in HEp-2 cell lines. The standard test kit contains: · Substrate slides: barcoded glass slides with standard and engineered DFS70-knock-out HEp-2 cells attached in a monolayer in the slide wells · ANA homogeneous pattern positive control · ANA DFS70 pattern positive control · Negative Control · Conjugate: anti-human IgG FITC conjugate containing Evan's blue counterstain. Binds fluorescein to reactive antibodies reacting against HEp-2 antigens · Buffered diluent provided for specimen dilutions · Wash buffer: phosphate buffered saline (PBS) diluent removes reagents and unbound antibodies after incubation steps · Mounting medium provided for coverslipping of slides to view under fluorescence microscope · Coverslips Optional components: The standard kit format supplies the Conjugate and Evan’s blue counterstain as one pre- formulated reagent, however, they may also be supplied separately to accommodate laboratory workflow. The formulation is intended to be separate but functionally identical. 3 J. Substantial Equivalence Information: 1. Predicate device name: ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS 2. Predicate 510(k) number: K883883 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi- quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. Indirect immunofluorescence (IF) antibody test for the detection and quantitation of anti- nuclear antibodies (ANA) in human serum Methodology Indirect immunofluorescence Same Matrix Serum Same Detection of antibodies Anti-nuclear antibodies Same Component Set Includes positive control, negative control, conjugate, diluent, wash buffer, mounting medium, substrate slides, coverslips Same Conjugate FITC IgG Same Screening dilution 1:40 Same Reading Fluorescence microscope Same Storage 2–8° C Same Differences Item Device Predicate Substrate Standard HEp-2 cells mixed with engineered HEp-2 with the PSIP1 gene knocked out in 1:9 ratio Standard HEp-2 cells Positive control ANA homogenous, DFS70 Ab ANA homogenous 4 K. Standard/Guidance Document Referenced (if applicable): Org Standard ID Version Date Title CLSI EP05 A3 Sep 2014 Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP06 A Apr 2003 Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07 A2 Dec 2002 Interference Testing in Clinical Chemistry CLSI EP12 A2 Jan 2014 User Protocol for Evaluation of Qualitative Test Performance L. Test Principle: In the indirect IFA method used in this kit, patient sera are incubated on HEp-2 cell substrates to allow binding of antibodies. Any antibodies not bound are removed by washing with buffer. Bound antibodies of the IgG class are detected by incubation of the substrate with fluorescein-labeled anti-human IgG conjugate. Reactions are observed under a fluorescence microscope equipped with appropriate filters. The presence of nuclear and cytoplasmic patterns AC-1 to AC-28 as described by ICAP1 is demonstrated by green fluorescence of specific structures in the cells. A majority (~90%) of the cells present on the substrate are devoid of a functional PSIP1 gene which eliminates the relevant antigenic target of the DFS70 pattern. This may aid in discrimination of ANA homogeneous and speckled patterns from the DFS pattern. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. The titers are determined by testing serial dilutions of patient samples and reported as the highest reciprocal dilution with a positive reaction. M. Performance Characteristics: 1. Analytical performance: All results presented below met the manufacturer’s pre-determined acceptance criteria. Interpretation of Results: Results should be reported as negative, positive, or, if end-point titer has been determined, positive with titer. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. Users should only read only fields that contain specific staining of the HEp-2 substrates. 1. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PL, Fritzler MJ, Garcia- De La Torre I, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. “Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015” Front Immunol, 2015; 6:412. doi: 10.3389/fimmu.2015.00412. PMID: 2634773 5 The International Consensus on Antinuclear Antibody Patterns report recommends a standardized nomenclature and reporting format for IFA patterns.1. Major nuclear patterns that are recommended to be reported include Homogeneous (AC-1), Speckled (AC-2, AC-4, AC-5), Centromere (AC-3), Discrete Nuclear Dots (AC-6, AC-7) and Nucleolar (AC-8, AC-9, AC-10). Major cytoplasmic patterns include Fibrillar (AC-15, AC-16, AC-17), Speckled (AC-18, AC-19, AC-20), Reticular/AMA (AC-21), Polar Golgi-like (AC-22) and Rods and rings (AC-23). Including the most commonly and mandated to be reported patterns described above, a total of 28 patterns are described in the ICAP reference.1 Interpretation of DFS70 pattern on HEp-2 ELITE IFA substrate: In the ~10% baseline HEp-2 cells in each well, a dense fine speckled pattern will be observed on interphase nuclei. Chromatin-associated staining is seen on mitotic nuclei. The remaining ~90% of HEp-2 cells have the PSIP1 gene encoding the LEDGF antigen knocked out and therefore will not produce a similar pattern. If 10% of the HEp-2 cells have brighter fluorescence corresponding to DFS70 pattern and rest of the cells present additional patterns or fine speckled signal above cut-off, it indicates the presence of mixed patterns. Closer analysis of such patterns is essential to confirm if other antibody specificity is present in addition to the DFS70 pattern associated with LEDGF/PSIP1. Due to the high prevalence of AC-2 patterns in an ANA screening population and relatively low association with autoimmune rheumatic diseases, the ICAP committee recommends all clinical labs report the DFS70 pattern. a. Precision/Reproducibility: The sponsor modeled precision studies based on CLSI guideline EP05 Measurand:

idK172745_s0_e2000

K172745.txt

type of test

Qualitative or semi-quantitative, indirect immunofluorescence

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172745 B. Purpose for Submission: New device C. Measurand: IgG Anti-Nuclear Antibodies (ANA) D. Type of Test: Qualitative or semi-quantitative, indirect immunofluorescence E.Applicant: IMMCO Diagnostics, Inc. F.Proprietary and Established Names: ImmuGlo HEp-2 Elite IFA G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100 ‒ Antinuclear antibody immunological test system 2. Classification: Class II 3. Product code: DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control 4. Panel: Immunology (82) 2 H. Intended Use: 1. Intended use: The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. 2. Indication for use: Same as Intended Use 3. Special conditions for use statement: For Prescription Use Only 4. Special instrument requirements: Fluorescence microscope for manual operation 200× or higher magnification, 490 nm excitation filter, 510 nm barrier filter I. Device Description: The kit is an indirect immunofluorescence assay (IFA) to detect IgG anti-nuclear antibodies (ANA) against proteins presented in HEp-2 cell lines. The standard test kit contains: · Substrate slides: barcoded glass slides with standard and engineered DFS70-knock-out HEp-2 cells attached in a monolayer in the slide wells · ANA homogeneous pattern positive control · ANA DFS70 pattern positive control · Negative Control · Conjugate: anti-human IgG FITC conjugate containing Evan's blue counterstain. Binds fluorescein to reactive antibodies reacting against HEp-2 antigens · Buffered diluent provided for specimen dilutions · Wash buffer: phosphate buffered saline (PBS) diluent removes reagents and unbound antibodies after incubation steps · Mounting medium provided for coverslipping of slides to view under fluorescence microscope · Coverslips Optional components: The standard kit format supplies the Conjugate and Evan’s blue counterstain as one pre- formulated reagent, however, they may also be supplied separately to accommodate laboratory workflow. The formulation is intended to be separate but functionally identical. 3 J. Substantial Equivalence Information: 1. Predicate device name: ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS 2. Predicate 510(k) number: K883883 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi- quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. Indirect immunofluorescence (IF) antibody test for the detection and quantitation of anti- nuclear antibodies (ANA) in human serum Methodology Indirect immunofluorescence Same Matrix Serum Same Detection of antibodies Anti-nuclear antibodies Same Component Set Includes positive control, negative control, conjugate, diluent, wash buffer, mounting medium, substrate slides, coverslips Same Conjugate FITC IgG Same Screening dilution 1:40 Same Reading Fluorescence microscope Same Storage 2–8° C Same Differences Item Device Predicate Substrate Standard HEp-2 cells mixed with engineered HEp-2 with the PSIP1 gene knocked out in 1:9 ratio Standard HEp-2 cells Positive control ANA homogenous, DFS70 Ab ANA homogenous 4 K. Standard/Guidance Document Referenced (if applicable): Org Standard ID Version Date Title CLSI EP05 A3 Sep 2014 Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP06 A Apr 2003 Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07 A2 Dec 2002 Interference Testing in Clinical Chemistry CLSI EP12 A2 Jan 2014 User Protocol for Evaluation of Qualitative Test Performance L. Test Principle: In the indirect IFA method used in this kit, patient sera are incubated on HEp-2 cell substrates to allow binding of antibodies. Any antibodies not bound are removed by washing with buffer. Bound antibodies of the IgG class are detected by incubation of the substrate with fluorescein-labeled anti-human IgG conjugate. Reactions are observed under a fluorescence microscope equipped with appropriate filters. The presence of nuclear and cytoplasmic patterns AC-1 to AC-28 as described by ICAP1 is demonstrated by green fluorescence of specific structures in the cells. A majority (~90%) of the cells present on the substrate are devoid of a functional PSIP1 gene which eliminates the relevant antigenic target of the DFS70 pattern. This may aid in discrimination of ANA homogeneous and speckled patterns from the DFS pattern. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. The titers are determined by testing serial dilutions of patient samples and reported as the highest reciprocal dilution with a positive reaction. M. Performance Characteristics: 1. Analytical performance: All results presented below met the manufacturer’s pre-determined acceptance criteria. Interpretation of Results: Results should be reported as negative, positive, or, if end-point titer has been determined, positive with titer. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. Users should only read only fields that contain specific staining of the HEp-2 substrates. 1. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PL, Fritzler MJ, Garcia- De La Torre I, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. “Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015” Front Immunol, 2015; 6:412. doi: 10.3389/fimmu.2015.00412. PMID: 2634773 5 The International Consensus on Antinuclear Antibody Patterns report recommends a standardized nomenclature and reporting format for IFA patterns.1. Major nuclear patterns that are recommended to be reported include Homogeneous (AC-1), Speckled (AC-2, AC-4, AC-5), Centromere (AC-3), Discrete Nuclear Dots (AC-6, AC-7) and Nucleolar (AC-8, AC-9, AC-10). Major cytoplasmic patterns include Fibrillar (AC-15, AC-16, AC-17), Speckled (AC-18, AC-19, AC-20), Reticular/AMA (AC-21), Polar Golgi-like (AC-22) and Rods and rings (AC-23). Including the most commonly and mandated to be reported patterns described above, a total of 28 patterns are described in the ICAP reference.1 Interpretation of DFS70 pattern on HEp-2 ELITE IFA substrate: In the ~10% baseline HEp-2 cells in each well, a dense fine speckled pattern will be observed on interphase nuclei. Chromatin-associated staining is seen on mitotic nuclei. The remaining ~90% of HEp-2 cells have the PSIP1 gene encoding the LEDGF antigen knocked out and therefore will not produce a similar pattern. If 10% of the HEp-2 cells have brighter fluorescence corresponding to DFS70 pattern and rest of the cells present additional patterns or fine speckled signal above cut-off, it indicates the presence of mixed patterns. Closer analysis of such patterns is essential to confirm if other antibody specificity is present in addition to the DFS70 pattern associated with LEDGF/PSIP1. Due to the high prevalence of AC-2 patterns in an ANA screening population and relatively low association with autoimmune rheumatic diseases, the ICAP committee recommends all clinical labs report the DFS70 pattern. a. Precision/Reproducibility: The sponsor modeled precision studies based on CLSI guideline EP05 Type of test:

idK172745_s0_e2000

K172745.txt

classification

Class II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172745 B. Purpose for Submission: New device C. Measurand: IgG Anti-Nuclear Antibodies (ANA) D. Type of Test: Qualitative or semi-quantitative, indirect immunofluorescence E.Applicant: IMMCO Diagnostics, Inc. F.Proprietary and Established Names: ImmuGlo HEp-2 Elite IFA G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100 ‒ Antinuclear antibody immunological test system 2. Classification: Class II 3. Product code: DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control 4. Panel: Immunology (82) 2 H. Intended Use: 1. Intended use: The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. 2. Indication for use: Same as Intended Use 3. Special conditions for use statement: For Prescription Use Only 4. Special instrument requirements: Fluorescence microscope for manual operation 200× or higher magnification, 490 nm excitation filter, 510 nm barrier filter I. Device Description: The kit is an indirect immunofluorescence assay (IFA) to detect IgG anti-nuclear antibodies (ANA) against proteins presented in HEp-2 cell lines. The standard test kit contains: · Substrate slides: barcoded glass slides with standard and engineered DFS70-knock-out HEp-2 cells attached in a monolayer in the slide wells · ANA homogeneous pattern positive control · ANA DFS70 pattern positive control · Negative Control · Conjugate: anti-human IgG FITC conjugate containing Evan's blue counterstain. Binds fluorescein to reactive antibodies reacting against HEp-2 antigens · Buffered diluent provided for specimen dilutions · Wash buffer: phosphate buffered saline (PBS) diluent removes reagents and unbound antibodies after incubation steps · Mounting medium provided for coverslipping of slides to view under fluorescence microscope · Coverslips Optional components: The standard kit format supplies the Conjugate and Evan’s blue counterstain as one pre- formulated reagent, however, they may also be supplied separately to accommodate laboratory workflow. The formulation is intended to be separate but functionally identical. 3 J. Substantial Equivalence Information: 1. Predicate device name: ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS 2. Predicate 510(k) number: K883883 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi- quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. Indirect immunofluorescence (IF) antibody test for the detection and quantitation of anti- nuclear antibodies (ANA) in human serum Methodology Indirect immunofluorescence Same Matrix Serum Same Detection of antibodies Anti-nuclear antibodies Same Component Set Includes positive control, negative control, conjugate, diluent, wash buffer, mounting medium, substrate slides, coverslips Same Conjugate FITC IgG Same Screening dilution 1:40 Same Reading Fluorescence microscope Same Storage 2–8° C Same Differences Item Device Predicate Substrate Standard HEp-2 cells mixed with engineered HEp-2 with the PSIP1 gene knocked out in 1:9 ratio Standard HEp-2 cells Positive control ANA homogenous, DFS70 Ab ANA homogenous 4 K. Standard/Guidance Document Referenced (if applicable): Org Standard ID Version Date Title CLSI EP05 A3 Sep 2014 Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP06 A Apr 2003 Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07 A2 Dec 2002 Interference Testing in Clinical Chemistry CLSI EP12 A2 Jan 2014 User Protocol for Evaluation of Qualitative Test Performance L. Test Principle: In the indirect IFA method used in this kit, patient sera are incubated on HEp-2 cell substrates to allow binding of antibodies. Any antibodies not bound are removed by washing with buffer. Bound antibodies of the IgG class are detected by incubation of the substrate with fluorescein-labeled anti-human IgG conjugate. Reactions are observed under a fluorescence microscope equipped with appropriate filters. The presence of nuclear and cytoplasmic patterns AC-1 to AC-28 as described by ICAP1 is demonstrated by green fluorescence of specific structures in the cells. A majority (~90%) of the cells present on the substrate are devoid of a functional PSIP1 gene which eliminates the relevant antigenic target of the DFS70 pattern. This may aid in discrimination of ANA homogeneous and speckled patterns from the DFS pattern. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. The titers are determined by testing serial dilutions of patient samples and reported as the highest reciprocal dilution with a positive reaction. M. Performance Characteristics: 1. Analytical performance: All results presented below met the manufacturer’s pre-determined acceptance criteria. Interpretation of Results: Results should be reported as negative, positive, or, if end-point titer has been determined, positive with titer. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. Users should only read only fields that contain specific staining of the HEp-2 substrates. 1. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PL, Fritzler MJ, Garcia- De La Torre I, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. “Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015” Front Immunol, 2015; 6:412. doi: 10.3389/fimmu.2015.00412. PMID: 2634773 5 The International Consensus on Antinuclear Antibody Patterns report recommends a standardized nomenclature and reporting format for IFA patterns.1. Major nuclear patterns that are recommended to be reported include Homogeneous (AC-1), Speckled (AC-2, AC-4, AC-5), Centromere (AC-3), Discrete Nuclear Dots (AC-6, AC-7) and Nucleolar (AC-8, AC-9, AC-10). Major cytoplasmic patterns include Fibrillar (AC-15, AC-16, AC-17), Speckled (AC-18, AC-19, AC-20), Reticular/AMA (AC-21), Polar Golgi-like (AC-22) and Rods and rings (AC-23). Including the most commonly and mandated to be reported patterns described above, a total of 28 patterns are described in the ICAP reference.1 Interpretation of DFS70 pattern on HEp-2 ELITE IFA substrate: In the ~10% baseline HEp-2 cells in each well, a dense fine speckled pattern will be observed on interphase nuclei. Chromatin-associated staining is seen on mitotic nuclei. The remaining ~90% of HEp-2 cells have the PSIP1 gene encoding the LEDGF antigen knocked out and therefore will not produce a similar pattern. If 10% of the HEp-2 cells have brighter fluorescence corresponding to DFS70 pattern and rest of the cells present additional patterns or fine speckled signal above cut-off, it indicates the presence of mixed patterns. Closer analysis of such patterns is essential to confirm if other antibody specificity is present in addition to the DFS70 pattern associated with LEDGF/PSIP1. Due to the high prevalence of AC-2 patterns in an ANA screening population and relatively low association with autoimmune rheumatic diseases, the ICAP committee recommends all clinical labs report the DFS70 pattern. a. Precision/Reproducibility: The sponsor modeled precision studies based on CLSI guideline EP05 Classification:

idK172745_s0_e2000

K172745.txt

product code

DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172745 B. Purpose for Submission: New device C. Measurand: IgG Anti-Nuclear Antibodies (ANA) D. Type of Test: Qualitative or semi-quantitative, indirect immunofluorescence E.Applicant: IMMCO Diagnostics, Inc. F.Proprietary and Established Names: ImmuGlo HEp-2 Elite IFA G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100 ‒ Antinuclear antibody immunological test system 2. Classification: Class II 3. Product code: DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control 4. Panel: Immunology (82) 2 H. Intended Use: 1. Intended use: The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. 2. Indication for use: Same as Intended Use 3. Special conditions for use statement: For Prescription Use Only 4. Special instrument requirements: Fluorescence microscope for manual operation 200× or higher magnification, 490 nm excitation filter, 510 nm barrier filter I. Device Description: The kit is an indirect immunofluorescence assay (IFA) to detect IgG anti-nuclear antibodies (ANA) against proteins presented in HEp-2 cell lines. The standard test kit contains: · Substrate slides: barcoded glass slides with standard and engineered DFS70-knock-out HEp-2 cells attached in a monolayer in the slide wells · ANA homogeneous pattern positive control · ANA DFS70 pattern positive control · Negative Control · Conjugate: anti-human IgG FITC conjugate containing Evan's blue counterstain. Binds fluorescein to reactive antibodies reacting against HEp-2 antigens · Buffered diluent provided for specimen dilutions · Wash buffer: phosphate buffered saline (PBS) diluent removes reagents and unbound antibodies after incubation steps · Mounting medium provided for coverslipping of slides to view under fluorescence microscope · Coverslips Optional components: The standard kit format supplies the Conjugate and Evan’s blue counterstain as one pre- formulated reagent, however, they may also be supplied separately to accommodate laboratory workflow. The formulation is intended to be separate but functionally identical. 3 J. Substantial Equivalence Information: 1. Predicate device name: ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS 2. Predicate 510(k) number: K883883 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi- quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. Indirect immunofluorescence (IF) antibody test for the detection and quantitation of anti- nuclear antibodies (ANA) in human serum Methodology Indirect immunofluorescence Same Matrix Serum Same Detection of antibodies Anti-nuclear antibodies Same Component Set Includes positive control, negative control, conjugate, diluent, wash buffer, mounting medium, substrate slides, coverslips Same Conjugate FITC IgG Same Screening dilution 1:40 Same Reading Fluorescence microscope Same Storage 2–8° C Same Differences Item Device Predicate Substrate Standard HEp-2 cells mixed with engineered HEp-2 with the PSIP1 gene knocked out in 1:9 ratio Standard HEp-2 cells Positive control ANA homogenous, DFS70 Ab ANA homogenous 4 K. Standard/Guidance Document Referenced (if applicable): Org Standard ID Version Date Title CLSI EP05 A3 Sep 2014 Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP06 A Apr 2003 Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07 A2 Dec 2002 Interference Testing in Clinical Chemistry CLSI EP12 A2 Jan 2014 User Protocol for Evaluation of Qualitative Test Performance L. Test Principle: In the indirect IFA method used in this kit, patient sera are incubated on HEp-2 cell substrates to allow binding of antibodies. Any antibodies not bound are removed by washing with buffer. Bound antibodies of the IgG class are detected by incubation of the substrate with fluorescein-labeled anti-human IgG conjugate. Reactions are observed under a fluorescence microscope equipped with appropriate filters. The presence of nuclear and cytoplasmic patterns AC-1 to AC-28 as described by ICAP1 is demonstrated by green fluorescence of specific structures in the cells. A majority (~90%) of the cells present on the substrate are devoid of a functional PSIP1 gene which eliminates the relevant antigenic target of the DFS70 pattern. This may aid in discrimination of ANA homogeneous and speckled patterns from the DFS pattern. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. The titers are determined by testing serial dilutions of patient samples and reported as the highest reciprocal dilution with a positive reaction. M. Performance Characteristics: 1. Analytical performance: All results presented below met the manufacturer’s pre-determined acceptance criteria. Interpretation of Results: Results should be reported as negative, positive, or, if end-point titer has been determined, positive with titer. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. Users should only read only fields that contain specific staining of the HEp-2 substrates. 1. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PL, Fritzler MJ, Garcia- De La Torre I, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. “Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015” Front Immunol, 2015; 6:412. doi: 10.3389/fimmu.2015.00412. PMID: 2634773 5 The International Consensus on Antinuclear Antibody Patterns report recommends a standardized nomenclature and reporting format for IFA patterns.1. Major nuclear patterns that are recommended to be reported include Homogeneous (AC-1), Speckled (AC-2, AC-4, AC-5), Centromere (AC-3), Discrete Nuclear Dots (AC-6, AC-7) and Nucleolar (AC-8, AC-9, AC-10). Major cytoplasmic patterns include Fibrillar (AC-15, AC-16, AC-17), Speckled (AC-18, AC-19, AC-20), Reticular/AMA (AC-21), Polar Golgi-like (AC-22) and Rods and rings (AC-23). Including the most commonly and mandated to be reported patterns described above, a total of 28 patterns are described in the ICAP reference.1 Interpretation of DFS70 pattern on HEp-2 ELITE IFA substrate: In the ~10% baseline HEp-2 cells in each well, a dense fine speckled pattern will be observed on interphase nuclei. Chromatin-associated staining is seen on mitotic nuclei. The remaining ~90% of HEp-2 cells have the PSIP1 gene encoding the LEDGF antigen knocked out and therefore will not produce a similar pattern. If 10% of the HEp-2 cells have brighter fluorescence corresponding to DFS70 pattern and rest of the cells present additional patterns or fine speckled signal above cut-off, it indicates the presence of mixed patterns. Closer analysis of such patterns is essential to confirm if other antibody specificity is present in addition to the DFS70 pattern associated with LEDGF/PSIP1. Due to the high prevalence of AC-2 patterns in an ANA screening population and relatively low association with autoimmune rheumatic diseases, the ICAP committee recommends all clinical labs report the DFS70 pattern. a. Precision/Reproducibility: The sponsor modeled precision studies based on CLSI guideline EP05 Product code:

idK172745_s0_e2000

K172745.txt

panel

Immunology (82)

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172745 B. Purpose for Submission: New device C. Measurand: IgG Anti-Nuclear Antibodies (ANA) D. Type of Test: Qualitative or semi-quantitative, indirect immunofluorescence E.Applicant: IMMCO Diagnostics, Inc. F.Proprietary and Established Names: ImmuGlo HEp-2 Elite IFA G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100 ‒ Antinuclear antibody immunological test system 2. Classification: Class II 3. Product code: DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control 4. Panel: Immunology (82) 2 H. Intended Use: 1. Intended use: The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. 2. Indication for use: Same as Intended Use 3. Special conditions for use statement: For Prescription Use Only 4. Special instrument requirements: Fluorescence microscope for manual operation 200× or higher magnification, 490 nm excitation filter, 510 nm barrier filter I. Device Description: The kit is an indirect immunofluorescence assay (IFA) to detect IgG anti-nuclear antibodies (ANA) against proteins presented in HEp-2 cell lines. The standard test kit contains: · Substrate slides: barcoded glass slides with standard and engineered DFS70-knock-out HEp-2 cells attached in a monolayer in the slide wells · ANA homogeneous pattern positive control · ANA DFS70 pattern positive control · Negative Control · Conjugate: anti-human IgG FITC conjugate containing Evan's blue counterstain. Binds fluorescein to reactive antibodies reacting against HEp-2 antigens · Buffered diluent provided for specimen dilutions · Wash buffer: phosphate buffered saline (PBS) diluent removes reagents and unbound antibodies after incubation steps · Mounting medium provided for coverslipping of slides to view under fluorescence microscope · Coverslips Optional components: The standard kit format supplies the Conjugate and Evan’s blue counterstain as one pre- formulated reagent, however, they may also be supplied separately to accommodate laboratory workflow. The formulation is intended to be separate but functionally identical. 3 J. Substantial Equivalence Information: 1. Predicate device name: ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS 2. Predicate 510(k) number: K883883 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi- quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. Indirect immunofluorescence (IF) antibody test for the detection and quantitation of anti- nuclear antibodies (ANA) in human serum Methodology Indirect immunofluorescence Same Matrix Serum Same Detection of antibodies Anti-nuclear antibodies Same Component Set Includes positive control, negative control, conjugate, diluent, wash buffer, mounting medium, substrate slides, coverslips Same Conjugate FITC IgG Same Screening dilution 1:40 Same Reading Fluorescence microscope Same Storage 2–8° C Same Differences Item Device Predicate Substrate Standard HEp-2 cells mixed with engineered HEp-2 with the PSIP1 gene knocked out in 1:9 ratio Standard HEp-2 cells Positive control ANA homogenous, DFS70 Ab ANA homogenous 4 K. Standard/Guidance Document Referenced (if applicable): Org Standard ID Version Date Title CLSI EP05 A3 Sep 2014 Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP06 A Apr 2003 Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07 A2 Dec 2002 Interference Testing in Clinical Chemistry CLSI EP12 A2 Jan 2014 User Protocol for Evaluation of Qualitative Test Performance L. Test Principle: In the indirect IFA method used in this kit, patient sera are incubated on HEp-2 cell substrates to allow binding of antibodies. Any antibodies not bound are removed by washing with buffer. Bound antibodies of the IgG class are detected by incubation of the substrate with fluorescein-labeled anti-human IgG conjugate. Reactions are observed under a fluorescence microscope equipped with appropriate filters. The presence of nuclear and cytoplasmic patterns AC-1 to AC-28 as described by ICAP1 is demonstrated by green fluorescence of specific structures in the cells. A majority (~90%) of the cells present on the substrate are devoid of a functional PSIP1 gene which eliminates the relevant antigenic target of the DFS70 pattern. This may aid in discrimination of ANA homogeneous and speckled patterns from the DFS pattern. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. The titers are determined by testing serial dilutions of patient samples and reported as the highest reciprocal dilution with a positive reaction. M. Performance Characteristics: 1. Analytical performance: All results presented below met the manufacturer’s pre-determined acceptance criteria. Interpretation of Results: Results should be reported as negative, positive, or, if end-point titer has been determined, positive with titer. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. Users should only read only fields that contain specific staining of the HEp-2 substrates. 1. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PL, Fritzler MJ, Garcia- De La Torre I, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. “Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015” Front Immunol, 2015; 6:412. doi: 10.3389/fimmu.2015.00412. PMID: 2634773 5 The International Consensus on Antinuclear Antibody Patterns report recommends a standardized nomenclature and reporting format for IFA patterns.1. Major nuclear patterns that are recommended to be reported include Homogeneous (AC-1), Speckled (AC-2, AC-4, AC-5), Centromere (AC-3), Discrete Nuclear Dots (AC-6, AC-7) and Nucleolar (AC-8, AC-9, AC-10). Major cytoplasmic patterns include Fibrillar (AC-15, AC-16, AC-17), Speckled (AC-18, AC-19, AC-20), Reticular/AMA (AC-21), Polar Golgi-like (AC-22) and Rods and rings (AC-23). Including the most commonly and mandated to be reported patterns described above, a total of 28 patterns are described in the ICAP reference.1 Interpretation of DFS70 pattern on HEp-2 ELITE IFA substrate: In the ~10% baseline HEp-2 cells in each well, a dense fine speckled pattern will be observed on interphase nuclei. Chromatin-associated staining is seen on mitotic nuclei. The remaining ~90% of HEp-2 cells have the PSIP1 gene encoding the LEDGF antigen knocked out and therefore will not produce a similar pattern. If 10% of the HEp-2 cells have brighter fluorescence corresponding to DFS70 pattern and rest of the cells present additional patterns or fine speckled signal above cut-off, it indicates the presence of mixed patterns. Closer analysis of such patterns is essential to confirm if other antibody specificity is present in addition to the DFS70 pattern associated with LEDGF/PSIP1. Due to the high prevalence of AC-2 patterns in an ANA screening population and relatively low association with autoimmune rheumatic diseases, the ICAP committee recommends all clinical labs report the DFS70 pattern. a. Precision/Reproducibility: The sponsor modeled precision studies based on CLSI guideline EP05 Panel:

idK172745_s0_e2000

K172745.txt

intended use

The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings.

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172745 B. Purpose for Submission: New device C. Measurand: IgG Anti-Nuclear Antibodies (ANA) D. Type of Test: Qualitative or semi-quantitative, indirect immunofluorescence E.Applicant: IMMCO Diagnostics, Inc. F.Proprietary and Established Names: ImmuGlo HEp-2 Elite IFA G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100 ‒ Antinuclear antibody immunological test system 2. Classification: Class II 3. Product code: DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control 4. Panel: Immunology (82) 2 H. Intended Use: 1. Intended use: The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. 2. Indication for use: Same as Intended Use 3. Special conditions for use statement: For Prescription Use Only 4. Special instrument requirements: Fluorescence microscope for manual operation 200× or higher magnification, 490 nm excitation filter, 510 nm barrier filter I. Device Description: The kit is an indirect immunofluorescence assay (IFA) to detect IgG anti-nuclear antibodies (ANA) against proteins presented in HEp-2 cell lines. The standard test kit contains: · Substrate slides: barcoded glass slides with standard and engineered DFS70-knock-out HEp-2 cells attached in a monolayer in the slide wells · ANA homogeneous pattern positive control · ANA DFS70 pattern positive control · Negative Control · Conjugate: anti-human IgG FITC conjugate containing Evan's blue counterstain. Binds fluorescein to reactive antibodies reacting against HEp-2 antigens · Buffered diluent provided for specimen dilutions · Wash buffer: phosphate buffered saline (PBS) diluent removes reagents and unbound antibodies after incubation steps · Mounting medium provided for coverslipping of slides to view under fluorescence microscope · Coverslips Optional components: The standard kit format supplies the Conjugate and Evan’s blue counterstain as one pre- formulated reagent, however, they may also be supplied separately to accommodate laboratory workflow. The formulation is intended to be separate but functionally identical. 3 J. Substantial Equivalence Information: 1. Predicate device name: ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS 2. Predicate 510(k) number: K883883 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi- quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. Indirect immunofluorescence (IF) antibody test for the detection and quantitation of anti- nuclear antibodies (ANA) in human serum Methodology Indirect immunofluorescence Same Matrix Serum Same Detection of antibodies Anti-nuclear antibodies Same Component Set Includes positive control, negative control, conjugate, diluent, wash buffer, mounting medium, substrate slides, coverslips Same Conjugate FITC IgG Same Screening dilution 1:40 Same Reading Fluorescence microscope Same Storage 2–8° C Same Differences Item Device Predicate Substrate Standard HEp-2 cells mixed with engineered HEp-2 with the PSIP1 gene knocked out in 1:9 ratio Standard HEp-2 cells Positive control ANA homogenous, DFS70 Ab ANA homogenous 4 K. Standard/Guidance Document Referenced (if applicable): Org Standard ID Version Date Title CLSI EP05 A3 Sep 2014 Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP06 A Apr 2003 Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07 A2 Dec 2002 Interference Testing in Clinical Chemistry CLSI EP12 A2 Jan 2014 User Protocol for Evaluation of Qualitative Test Performance L. Test Principle: In the indirect IFA method used in this kit, patient sera are incubated on HEp-2 cell substrates to allow binding of antibodies. Any antibodies not bound are removed by washing with buffer. Bound antibodies of the IgG class are detected by incubation of the substrate with fluorescein-labeled anti-human IgG conjugate. Reactions are observed under a fluorescence microscope equipped with appropriate filters. The presence of nuclear and cytoplasmic patterns AC-1 to AC-28 as described by ICAP1 is demonstrated by green fluorescence of specific structures in the cells. A majority (~90%) of the cells present on the substrate are devoid of a functional PSIP1 gene which eliminates the relevant antigenic target of the DFS70 pattern. This may aid in discrimination of ANA homogeneous and speckled patterns from the DFS pattern. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. The titers are determined by testing serial dilutions of patient samples and reported as the highest reciprocal dilution with a positive reaction. M. Performance Characteristics: 1. Analytical performance: All results presented below met the manufacturer’s pre-determined acceptance criteria. Interpretation of Results: Results should be reported as negative, positive, or, if end-point titer has been determined, positive with titer. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. Users should only read only fields that contain specific staining of the HEp-2 substrates. 1. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PL, Fritzler MJ, Garcia- De La Torre I, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. “Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015” Front Immunol, 2015; 6:412. doi: 10.3389/fimmu.2015.00412. PMID: 2634773 5 The International Consensus on Antinuclear Antibody Patterns report recommends a standardized nomenclature and reporting format for IFA patterns.1. Major nuclear patterns that are recommended to be reported include Homogeneous (AC-1), Speckled (AC-2, AC-4, AC-5), Centromere (AC-3), Discrete Nuclear Dots (AC-6, AC-7) and Nucleolar (AC-8, AC-9, AC-10). Major cytoplasmic patterns include Fibrillar (AC-15, AC-16, AC-17), Speckled (AC-18, AC-19, AC-20), Reticular/AMA (AC-21), Polar Golgi-like (AC-22) and Rods and rings (AC-23). Including the most commonly and mandated to be reported patterns described above, a total of 28 patterns are described in the ICAP reference.1 Interpretation of DFS70 pattern on HEp-2 ELITE IFA substrate: In the ~10% baseline HEp-2 cells in each well, a dense fine speckled pattern will be observed on interphase nuclei. Chromatin-associated staining is seen on mitotic nuclei. The remaining ~90% of HEp-2 cells have the PSIP1 gene encoding the LEDGF antigen knocked out and therefore will not produce a similar pattern. If 10% of the HEp-2 cells have brighter fluorescence corresponding to DFS70 pattern and rest of the cells present additional patterns or fine speckled signal above cut-off, it indicates the presence of mixed patterns. Closer analysis of such patterns is essential to confirm if other antibody specificity is present in addition to the DFS70 pattern associated with LEDGF/PSIP1. Due to the high prevalence of AC-2 patterns in an ANA screening population and relatively low association with autoimmune rheumatic diseases, the ICAP committee recommends all clinical labs report the DFS70 pattern. a. Precision/Reproducibility: The sponsor modeled precision studies based on CLSI guideline EP05 Intended use:

idK172745_s0_e2000

K172745.txt

predicate device name

ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172745 B. Purpose for Submission: New device C. Measurand: IgG Anti-Nuclear Antibodies (ANA) D. Type of Test: Qualitative or semi-quantitative, indirect immunofluorescence E.Applicant: IMMCO Diagnostics, Inc. F.Proprietary and Established Names: ImmuGlo HEp-2 Elite IFA G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100 ‒ Antinuclear antibody immunological test system 2. Classification: Class II 3. Product code: DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control 4. Panel: Immunology (82) 2 H. Intended Use: 1. Intended use: The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. 2. Indication for use: Same as Intended Use 3. Special conditions for use statement: For Prescription Use Only 4. Special instrument requirements: Fluorescence microscope for manual operation 200× or higher magnification, 490 nm excitation filter, 510 nm barrier filter I. Device Description: The kit is an indirect immunofluorescence assay (IFA) to detect IgG anti-nuclear antibodies (ANA) against proteins presented in HEp-2 cell lines. The standard test kit contains: · Substrate slides: barcoded glass slides with standard and engineered DFS70-knock-out HEp-2 cells attached in a monolayer in the slide wells · ANA homogeneous pattern positive control · ANA DFS70 pattern positive control · Negative Control · Conjugate: anti-human IgG FITC conjugate containing Evan's blue counterstain. Binds fluorescein to reactive antibodies reacting against HEp-2 antigens · Buffered diluent provided for specimen dilutions · Wash buffer: phosphate buffered saline (PBS) diluent removes reagents and unbound antibodies after incubation steps · Mounting medium provided for coverslipping of slides to view under fluorescence microscope · Coverslips Optional components: The standard kit format supplies the Conjugate and Evan’s blue counterstain as one pre- formulated reagent, however, they may also be supplied separately to accommodate laboratory workflow. The formulation is intended to be separate but functionally identical. 3 J. Substantial Equivalence Information: 1. Predicate device name: ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS 2. Predicate 510(k) number: K883883 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi- quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. Indirect immunofluorescence (IF) antibody test for the detection and quantitation of anti- nuclear antibodies (ANA) in human serum Methodology Indirect immunofluorescence Same Matrix Serum Same Detection of antibodies Anti-nuclear antibodies Same Component Set Includes positive control, negative control, conjugate, diluent, wash buffer, mounting medium, substrate slides, coverslips Same Conjugate FITC IgG Same Screening dilution 1:40 Same Reading Fluorescence microscope Same Storage 2–8° C Same Differences Item Device Predicate Substrate Standard HEp-2 cells mixed with engineered HEp-2 with the PSIP1 gene knocked out in 1:9 ratio Standard HEp-2 cells Positive control ANA homogenous, DFS70 Ab ANA homogenous 4 K. Standard/Guidance Document Referenced (if applicable): Org Standard ID Version Date Title CLSI EP05 A3 Sep 2014 Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP06 A Apr 2003 Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07 A2 Dec 2002 Interference Testing in Clinical Chemistry CLSI EP12 A2 Jan 2014 User Protocol for Evaluation of Qualitative Test Performance L. Test Principle: In the indirect IFA method used in this kit, patient sera are incubated on HEp-2 cell substrates to allow binding of antibodies. Any antibodies not bound are removed by washing with buffer. Bound antibodies of the IgG class are detected by incubation of the substrate with fluorescein-labeled anti-human IgG conjugate. Reactions are observed under a fluorescence microscope equipped with appropriate filters. The presence of nuclear and cytoplasmic patterns AC-1 to AC-28 as described by ICAP1 is demonstrated by green fluorescence of specific structures in the cells. A majority (~90%) of the cells present on the substrate are devoid of a functional PSIP1 gene which eliminates the relevant antigenic target of the DFS70 pattern. This may aid in discrimination of ANA homogeneous and speckled patterns from the DFS pattern. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. The titers are determined by testing serial dilutions of patient samples and reported as the highest reciprocal dilution with a positive reaction. M. Performance Characteristics: 1. Analytical performance: All results presented below met the manufacturer’s pre-determined acceptance criteria. Interpretation of Results: Results should be reported as negative, positive, or, if end-point titer has been determined, positive with titer. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. Users should only read only fields that contain specific staining of the HEp-2 substrates. 1. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PL, Fritzler MJ, Garcia- De La Torre I, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. “Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015” Front Immunol, 2015; 6:412. doi: 10.3389/fimmu.2015.00412. PMID: 2634773 5 The International Consensus on Antinuclear Antibody Patterns report recommends a standardized nomenclature and reporting format for IFA patterns.1. Major nuclear patterns that are recommended to be reported include Homogeneous (AC-1), Speckled (AC-2, AC-4, AC-5), Centromere (AC-3), Discrete Nuclear Dots (AC-6, AC-7) and Nucleolar (AC-8, AC-9, AC-10). Major cytoplasmic patterns include Fibrillar (AC-15, AC-16, AC-17), Speckled (AC-18, AC-19, AC-20), Reticular/AMA (AC-21), Polar Golgi-like (AC-22) and Rods and rings (AC-23). Including the most commonly and mandated to be reported patterns described above, a total of 28 patterns are described in the ICAP reference.1 Interpretation of DFS70 pattern on HEp-2 ELITE IFA substrate: In the ~10% baseline HEp-2 cells in each well, a dense fine speckled pattern will be observed on interphase nuclei. Chromatin-associated staining is seen on mitotic nuclei. The remaining ~90% of HEp-2 cells have the PSIP1 gene encoding the LEDGF antigen knocked out and therefore will not produce a similar pattern. If 10% of the HEp-2 cells have brighter fluorescence corresponding to DFS70 pattern and rest of the cells present additional patterns or fine speckled signal above cut-off, it indicates the presence of mixed patterns. Closer analysis of such patterns is essential to confirm if other antibody specificity is present in addition to the DFS70 pattern associated with LEDGF/PSIP1. Due to the high prevalence of AC-2 patterns in an ANA screening population and relatively low association with autoimmune rheumatic diseases, the ICAP committee recommends all clinical labs report the DFS70 pattern. a. Precision/Reproducibility: The sponsor modeled precision studies based on CLSI guideline EP05 Predicate device name:

idK172745_s0_e2000

K172745.txt

applicant

IMMCO Diagnostics, Inc.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172745 B. Purpose for Submission: New device C. Measurand: IgG Anti-Nuclear Antibodies (ANA) D. Type of Test: Qualitative or semi-quantitative, indirect immunofluorescence E.Applicant: IMMCO Diagnostics, Inc. F.Proprietary and Established Names: ImmuGlo HEp-2 Elite IFA G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100 ‒ Antinuclear antibody immunological test system 2. Classification: Class II 3. Product code: DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control 4. Panel: Immunology (82) 2 H. Intended Use: 1. Intended use: The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. 2. Indication for use: Same as Intended Use 3. Special conditions for use statement: For Prescription Use Only 4. Special instrument requirements: Fluorescence microscope for manual operation 200× or higher magnification, 490 nm excitation filter, 510 nm barrier filter I. Device Description: The kit is an indirect immunofluorescence assay (IFA) to detect IgG anti-nuclear antibodies (ANA) against proteins presented in HEp-2 cell lines. The standard test kit contains: · Substrate slides: barcoded glass slides with standard and engineered DFS70-knock-out HEp-2 cells attached in a monolayer in the slide wells · ANA homogeneous pattern positive control · ANA DFS70 pattern positive control · Negative Control · Conjugate: anti-human IgG FITC conjugate containing Evan's blue counterstain. Binds fluorescein to reactive antibodies reacting against HEp-2 antigens · Buffered diluent provided for specimen dilutions · Wash buffer: phosphate buffered saline (PBS) diluent removes reagents and unbound antibodies after incubation steps · Mounting medium provided for coverslipping of slides to view under fluorescence microscope · Coverslips Optional components: The standard kit format supplies the Conjugate and Evan’s blue counterstain as one pre- formulated reagent, however, they may also be supplied separately to accommodate laboratory workflow. The formulation is intended to be separate but functionally identical. 3 J. Substantial Equivalence Information: 1. Predicate device name: ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS 2. Predicate 510(k) number: K883883 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi- quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. Indirect immunofluorescence (IF) antibody test for the detection and quantitation of anti- nuclear antibodies (ANA) in human serum Methodology Indirect immunofluorescence Same Matrix Serum Same Detection of antibodies Anti-nuclear antibodies Same Component Set Includes positive control, negative control, conjugate, diluent, wash buffer, mounting medium, substrate slides, coverslips Same Conjugate FITC IgG Same Screening dilution 1:40 Same Reading Fluorescence microscope Same Storage 2–8° C Same Differences Item Device Predicate Substrate Standard HEp-2 cells mixed with engineered HEp-2 with the PSIP1 gene knocked out in 1:9 ratio Standard HEp-2 cells Positive control ANA homogenous, DFS70 Ab ANA homogenous 4 K. Standard/Guidance Document Referenced (if applicable): Org Standard ID Version Date Title CLSI EP05 A3 Sep 2014 Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP06 A Apr 2003 Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07 A2 Dec 2002 Interference Testing in Clinical Chemistry CLSI EP12 A2 Jan 2014 User Protocol for Evaluation of Qualitative Test Performance L. Test Principle: In the indirect IFA method used in this kit, patient sera are incubated on HEp-2 cell substrates to allow binding of antibodies. Any antibodies not bound are removed by washing with buffer. Bound antibodies of the IgG class are detected by incubation of the substrate with fluorescein-labeled anti-human IgG conjugate. Reactions are observed under a fluorescence microscope equipped with appropriate filters. The presence of nuclear and cytoplasmic patterns AC-1 to AC-28 as described by ICAP1 is demonstrated by green fluorescence of specific structures in the cells. A majority (~90%) of the cells present on the substrate are devoid of a functional PSIP1 gene which eliminates the relevant antigenic target of the DFS70 pattern. This may aid in discrimination of ANA homogeneous and speckled patterns from the DFS pattern. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. The titers are determined by testing serial dilutions of patient samples and reported as the highest reciprocal dilution with a positive reaction. M. Performance Characteristics: 1. Analytical performance: All results presented below met the manufacturer’s pre-determined acceptance criteria. Interpretation of Results: Results should be reported as negative, positive, or, if end-point titer has been determined, positive with titer. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. Users should only read only fields that contain specific staining of the HEp-2 substrates. 1. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PL, Fritzler MJ, Garcia- De La Torre I, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. “Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015” Front Immunol, 2015; 6:412. doi: 10.3389/fimmu.2015.00412. PMID: 2634773 5 The International Consensus on Antinuclear Antibody Patterns report recommends a standardized nomenclature and reporting format for IFA patterns.1. Major nuclear patterns that are recommended to be reported include Homogeneous (AC-1), Speckled (AC-2, AC-4, AC-5), Centromere (AC-3), Discrete Nuclear Dots (AC-6, AC-7) and Nucleolar (AC-8, AC-9, AC-10). Major cytoplasmic patterns include Fibrillar (AC-15, AC-16, AC-17), Speckled (AC-18, AC-19, AC-20), Reticular/AMA (AC-21), Polar Golgi-like (AC-22) and Rods and rings (AC-23). Including the most commonly and mandated to be reported patterns described above, a total of 28 patterns are described in the ICAP reference.1 Interpretation of DFS70 pattern on HEp-2 ELITE IFA substrate: In the ~10% baseline HEp-2 cells in each well, a dense fine speckled pattern will be observed on interphase nuclei. Chromatin-associated staining is seen on mitotic nuclei. The remaining ~90% of HEp-2 cells have the PSIP1 gene encoding the LEDGF antigen knocked out and therefore will not produce a similar pattern. If 10% of the HEp-2 cells have brighter fluorescence corresponding to DFS70 pattern and rest of the cells present additional patterns or fine speckled signal above cut-off, it indicates the presence of mixed patterns. Closer analysis of such patterns is essential to confirm if other antibody specificity is present in addition to the DFS70 pattern associated with LEDGF/PSIP1. Due to the high prevalence of AC-2 patterns in an ANA screening population and relatively low association with autoimmune rheumatic diseases, the ICAP committee recommends all clinical labs report the DFS70 pattern. a. Precision/Reproducibility: The sponsor modeled precision studies based on CLSI guideline EP05 Applicant:

idK172745_s0_e2000

K172745.txt

proprietary and established names

ImmuGlo HEp-2 Elite IFA

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172745 B. Purpose for Submission: New device C. Measurand: IgG Anti-Nuclear Antibodies (ANA) D. Type of Test: Qualitative or semi-quantitative, indirect immunofluorescence E.Applicant: IMMCO Diagnostics, Inc. F.Proprietary and Established Names: ImmuGlo HEp-2 Elite IFA G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100 ‒ Antinuclear antibody immunological test system 2. Classification: Class II 3. Product code: DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control 4. Panel: Immunology (82) 2 H. Intended Use: 1. Intended use: The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. 2. Indication for use: Same as Intended Use 3. Special conditions for use statement: For Prescription Use Only 4. Special instrument requirements: Fluorescence microscope for manual operation 200× or higher magnification, 490 nm excitation filter, 510 nm barrier filter I. Device Description: The kit is an indirect immunofluorescence assay (IFA) to detect IgG anti-nuclear antibodies (ANA) against proteins presented in HEp-2 cell lines. The standard test kit contains: · Substrate slides: barcoded glass slides with standard and engineered DFS70-knock-out HEp-2 cells attached in a monolayer in the slide wells · ANA homogeneous pattern positive control · ANA DFS70 pattern positive control · Negative Control · Conjugate: anti-human IgG FITC conjugate containing Evan's blue counterstain. Binds fluorescein to reactive antibodies reacting against HEp-2 antigens · Buffered diluent provided for specimen dilutions · Wash buffer: phosphate buffered saline (PBS) diluent removes reagents and unbound antibodies after incubation steps · Mounting medium provided for coverslipping of slides to view under fluorescence microscope · Coverslips Optional components: The standard kit format supplies the Conjugate and Evan’s blue counterstain as one pre- formulated reagent, however, they may also be supplied separately to accommodate laboratory workflow. The formulation is intended to be separate but functionally identical. 3 J. Substantial Equivalence Information: 1. Predicate device name: ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS 2. Predicate 510(k) number: K883883 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi- quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. Indirect immunofluorescence (IF) antibody test for the detection and quantitation of anti- nuclear antibodies (ANA) in human serum Methodology Indirect immunofluorescence Same Matrix Serum Same Detection of antibodies Anti-nuclear antibodies Same Component Set Includes positive control, negative control, conjugate, diluent, wash buffer, mounting medium, substrate slides, coverslips Same Conjugate FITC IgG Same Screening dilution 1:40 Same Reading Fluorescence microscope Same Storage 2–8° C Same Differences Item Device Predicate Substrate Standard HEp-2 cells mixed with engineered HEp-2 with the PSIP1 gene knocked out in 1:9 ratio Standard HEp-2 cells Positive control ANA homogenous, DFS70 Ab ANA homogenous 4 K. Standard/Guidance Document Referenced (if applicable): Org Standard ID Version Date Title CLSI EP05 A3 Sep 2014 Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP06 A Apr 2003 Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07 A2 Dec 2002 Interference Testing in Clinical Chemistry CLSI EP12 A2 Jan 2014 User Protocol for Evaluation of Qualitative Test Performance L. Test Principle: In the indirect IFA method used in this kit, patient sera are incubated on HEp-2 cell substrates to allow binding of antibodies. Any antibodies not bound are removed by washing with buffer. Bound antibodies of the IgG class are detected by incubation of the substrate with fluorescein-labeled anti-human IgG conjugate. Reactions are observed under a fluorescence microscope equipped with appropriate filters. The presence of nuclear and cytoplasmic patterns AC-1 to AC-28 as described by ICAP1 is demonstrated by green fluorescence of specific structures in the cells. A majority (~90%) of the cells present on the substrate are devoid of a functional PSIP1 gene which eliminates the relevant antigenic target of the DFS70 pattern. This may aid in discrimination of ANA homogeneous and speckled patterns from the DFS pattern. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. The titers are determined by testing serial dilutions of patient samples and reported as the highest reciprocal dilution with a positive reaction. M. Performance Characteristics: 1. Analytical performance: All results presented below met the manufacturer’s pre-determined acceptance criteria. Interpretation of Results: Results should be reported as negative, positive, or, if end-point titer has been determined, positive with titer. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. Users should only read only fields that contain specific staining of the HEp-2 substrates. 1. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PL, Fritzler MJ, Garcia- De La Torre I, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. “Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015” Front Immunol, 2015; 6:412. doi: 10.3389/fimmu.2015.00412. PMID: 2634773 5 The International Consensus on Antinuclear Antibody Patterns report recommends a standardized nomenclature and reporting format for IFA patterns.1. Major nuclear patterns that are recommended to be reported include Homogeneous (AC-1), Speckled (AC-2, AC-4, AC-5), Centromere (AC-3), Discrete Nuclear Dots (AC-6, AC-7) and Nucleolar (AC-8, AC-9, AC-10). Major cytoplasmic patterns include Fibrillar (AC-15, AC-16, AC-17), Speckled (AC-18, AC-19, AC-20), Reticular/AMA (AC-21), Polar Golgi-like (AC-22) and Rods and rings (AC-23). Including the most commonly and mandated to be reported patterns described above, a total of 28 patterns are described in the ICAP reference.1 Interpretation of DFS70 pattern on HEp-2 ELITE IFA substrate: In the ~10% baseline HEp-2 cells in each well, a dense fine speckled pattern will be observed on interphase nuclei. Chromatin-associated staining is seen on mitotic nuclei. The remaining ~90% of HEp-2 cells have the PSIP1 gene encoding the LEDGF antigen knocked out and therefore will not produce a similar pattern. If 10% of the HEp-2 cells have brighter fluorescence corresponding to DFS70 pattern and rest of the cells present additional patterns or fine speckled signal above cut-off, it indicates the presence of mixed patterns. Closer analysis of such patterns is essential to confirm if other antibody specificity is present in addition to the DFS70 pattern associated with LEDGF/PSIP1. Due to the high prevalence of AC-2 patterns in an ANA screening population and relatively low association with autoimmune rheumatic diseases, the ICAP committee recommends all clinical labs report the DFS70 pattern. a. Precision/Reproducibility: The sponsor modeled precision studies based on CLSI guideline EP05 Proprietary and established names:

idK172745_s0_e2000

K172745.txt

regulation section

21 CFR §866.5100 ‒ Antinuclear antibody immunological test system

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K172745 B. Purpose for Submission: New device C. Measurand: IgG Anti-Nuclear Antibodies (ANA) D. Type of Test: Qualitative or semi-quantitative, indirect immunofluorescence E.Applicant: IMMCO Diagnostics, Inc. F.Proprietary and Established Names: ImmuGlo HEp-2 Elite IFA G. Regulatory Information: 1. Regulation section: 21 CFR §866.5100 ‒ Antinuclear antibody immunological test system 2. Classification: Class II 3. Product code: DHN ‒ Antinuclear Antibody, Indirect Immunofluorescent, Antigen, Control 4. Panel: Immunology (82) 2 H. Intended Use: 1. Intended use: The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi-quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. 2. Indication for use: Same as Intended Use 3. Special conditions for use statement: For Prescription Use Only 4. Special instrument requirements: Fluorescence microscope for manual operation 200× or higher magnification, 490 nm excitation filter, 510 nm barrier filter I. Device Description: The kit is an indirect immunofluorescence assay (IFA) to detect IgG anti-nuclear antibodies (ANA) against proteins presented in HEp-2 cell lines. The standard test kit contains: · Substrate slides: barcoded glass slides with standard and engineered DFS70-knock-out HEp-2 cells attached in a monolayer in the slide wells · ANA homogeneous pattern positive control · ANA DFS70 pattern positive control · Negative Control · Conjugate: anti-human IgG FITC conjugate containing Evan's blue counterstain. Binds fluorescein to reactive antibodies reacting against HEp-2 antigens · Buffered diluent provided for specimen dilutions · Wash buffer: phosphate buffered saline (PBS) diluent removes reagents and unbound antibodies after incubation steps · Mounting medium provided for coverslipping of slides to view under fluorescence microscope · Coverslips Optional components: The standard kit format supplies the Conjugate and Evan’s blue counterstain as one pre- formulated reagent, however, they may also be supplied separately to accommodate laboratory workflow. The formulation is intended to be separate but functionally identical. 3 J. Substantial Equivalence Information: 1. Predicate device name: ImmuGlo ANTINUCLEAR ANTIBODY (ANA) TEST (HEP-2) CELLS 2. Predicate 510(k) number: K883883 3. Comparison with predicate: Similarities Item Device Predicate Intended Use The ImmuGlo HEp-2 Elite IFA is an indirect immunofluorescence antibody test for the qualitative or semi- quantitative detection of anti-nuclear antibodies (ANA) of the IgG isotype in human serum utilizing standard HEp-2 cells and engineered HEp-2 cells as a substrate. The ImmuGlo HEp-2 Elite IFA is intended for use as an aid in the diagnosis of systemic rheumatic diseases in conjunction with other clinical and laboratory findings. Indirect immunofluorescence (IF) antibody test for the detection and quantitation of anti- nuclear antibodies (ANA) in human serum Methodology Indirect immunofluorescence Same Matrix Serum Same Detection of antibodies Anti-nuclear antibodies Same Component Set Includes positive control, negative control, conjugate, diluent, wash buffer, mounting medium, substrate slides, coverslips Same Conjugate FITC IgG Same Screening dilution 1:40 Same Reading Fluorescence microscope Same Storage 2–8° C Same Differences Item Device Predicate Substrate Standard HEp-2 cells mixed with engineered HEp-2 with the PSIP1 gene knocked out in 1:9 ratio Standard HEp-2 cells Positive control ANA homogenous, DFS70 Ab ANA homogenous 4 K. Standard/Guidance Document Referenced (if applicable): Org Standard ID Version Date Title CLSI EP05 A3 Sep 2014 Evaluation of Precision Performance of Quantitative Measurement Methods CLSI EP06 A Apr 2003 Evaluation of the Linearity of Quantitative Measurement Procedures CLSI EP07 A2 Dec 2002 Interference Testing in Clinical Chemistry CLSI EP12 A2 Jan 2014 User Protocol for Evaluation of Qualitative Test Performance L. Test Principle: In the indirect IFA method used in this kit, patient sera are incubated on HEp-2 cell substrates to allow binding of antibodies. Any antibodies not bound are removed by washing with buffer. Bound antibodies of the IgG class are detected by incubation of the substrate with fluorescein-labeled anti-human IgG conjugate. Reactions are observed under a fluorescence microscope equipped with appropriate filters. The presence of nuclear and cytoplasmic patterns AC-1 to AC-28 as described by ICAP1 is demonstrated by green fluorescence of specific structures in the cells. A majority (~90%) of the cells present on the substrate are devoid of a functional PSIP1 gene which eliminates the relevant antigenic target of the DFS70 pattern. This may aid in discrimination of ANA homogeneous and speckled patterns from the DFS pattern. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. The titers are determined by testing serial dilutions of patient samples and reported as the highest reciprocal dilution with a positive reaction. M. Performance Characteristics: 1. Analytical performance: All results presented below met the manufacturer’s pre-determined acceptance criteria. Interpretation of Results: Results should be reported as negative, positive, or, if end-point titer has been determined, positive with titer. It is recommended that patient samples demonstrating specific fluorescence reactions at a dilution of 1:40 be reported as positive. Each laboratory must determine its own normal values to account for differences in microscopy systems, personnel, and training. Users should only read only fields that contain specific staining of the HEp-2 substrates. 1. Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PL, Fritzler MJ, Garcia- De La Torre I, Herold M, Mimori T, Satoh M, von Mühlen CA, Andrade LE. “Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015” Front Immunol, 2015; 6:412. doi: 10.3389/fimmu.2015.00412. PMID: 2634773 5 The International Consensus on Antinuclear Antibody Patterns report recommends a standardized nomenclature and reporting format for IFA patterns.1. Major nuclear patterns that are recommended to be reported include Homogeneous (AC-1), Speckled (AC-2, AC-4, AC-5), Centromere (AC-3), Discrete Nuclear Dots (AC-6, AC-7) and Nucleolar (AC-8, AC-9, AC-10). Major cytoplasmic patterns include Fibrillar (AC-15, AC-16, AC-17), Speckled (AC-18, AC-19, AC-20), Reticular/AMA (AC-21), Polar Golgi-like (AC-22) and Rods and rings (AC-23). Including the most commonly and mandated to be reported patterns described above, a total of 28 patterns are described in the ICAP reference.1 Interpretation of DFS70 pattern on HEp-2 ELITE IFA substrate: In the ~10% baseline HEp-2 cells in each well, a dense fine speckled pattern will be observed on interphase nuclei. Chromatin-associated staining is seen on mitotic nuclei. The remaining ~90% of HEp-2 cells have the PSIP1 gene encoding the LEDGF antigen knocked out and therefore will not produce a similar pattern. If 10% of the HEp-2 cells have brighter fluorescence corresponding to DFS70 pattern and rest of the cells present additional patterns or fine speckled signal above cut-off, it indicates the presence of mixed patterns. Closer analysis of such patterns is essential to confirm if other antibody specificity is present in addition to the DFS70 pattern associated with LEDGF/PSIP1. Due to the high prevalence of AC-2 patterns in an ANA screening population and relatively low association with autoimmune rheumatic diseases, the ICAP committee recommends all clinical labs report the DFS70 pattern. a. Precision/Reproducibility: The sponsor modeled precision studies based on CLSI guideline EP05 Regulation section:

idK172745_s8000_e10000

K172745.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable.

Assay cut-off, above 5. Expected values/Reference range: A cohort of 128 normal human serum samples was tested on the HEp-2 Elite IFA at the 1:40 initial dilution. Qualitative results demonstrating ANA prevalence in reference populations for this study are below: Reported ANA-positive n, and percent positive on HEp-2 Elite IFA on normal human samples Patient Status Total n Positive n % normal human sera 128 7 5.5% Of the seven ANA-positive samples, three were DFS(+), two were AMA(+), and two were centromere(+). N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable. 16 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK172745_s8000_e10000

K172745.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

off See Assay cut-off, above 5. Expected values/Reference range: A cohort of 128 normal human serum samples was tested on the HEp-2 Elite IFA at the 1:40 initial dilution. Qualitative results demonstrating ANA prevalence in reference populations for this study are below: Reported ANA-positive n, and percent positive on HEp-2 Elite IFA on normal human samples Patient Status Total n Positive n % normal human sera 128 7 5.5% Of the seven ANA-positive samples, three were DFS(+), two were AMA(+), and two were centromere(+). N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable. 16 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK160082_s0_e2000

K160082.txt

purpose for submission

To make a substantial equivalence determination for the Puritan® Opti-Tranz™ Cary-Blair Collection and Transport System for the collection, transport and storage of fecal specimens for laboratory culture of bacteria and yeast.

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K160082 B. Purpose for Submission: To make a substantial equivalence determination for the Puritan® Opti-Tranz™ Cary-Blair Collection and Transport System for the collection, transport and storage of fecal specimens for laboratory culture of bacteria and yeast. C. Measurand: Not applicable. D. Type of Test: Collection and transport culture medium device E. Applicant: Puritan Medical Products, LLC F. Proprietary and Established Names: Puritan® Opti-Tranz™ Cary-Blair Collection and Transport System G. Regulatory Information: 1. Regulation section: 866.2390; Transport Culture Medium 2. Classification: Class I 3. Product code: JSM; Culture Media, Non-Propagating Transport LIO: Device, Specimen Collection 2 JTW: System, Transport, Aerobic 4. Panel: 83- Microbiology H. Intended Use: 1. Intended use(s): The Puritan Opti-Tranz Cary-Blair Collection and Transport System is intended for use in the collection and transport of clinical fecal and rectal swab specimens to preserve the viability of enteric bacteria during transport from the collection site to the testing laboratory for bacteriological examination and culture. 2. Indication(s) for use: Same as intended use. 3. Special conditions for use statement(s): For prescription use only. 4. Special instrument requirements: None. I. Device Description: Puritan® Opti-Tranz™ Cary-Blair Collection and Transport System is comprised of a peel pouch containing a rayon tipped swab applicator for collecting specimens and a polypropylene, round-bottomed, capped tube containing 5 ml of a semi-solid Cary-Blair medium. Cary-Blair medium is a non-nutritive balanced salt solution containing disodium phosphate to provide buffering capability, sodium chloride and calcium chloride to provide essential ions that help maintain osmotic balance. Agar is a solidifying agent and gives a semisolid texture to the medium. Sodium thioglycollate helps maintained an oxygen-reduced environment to help maintain the viability of enteric bacteria during the transport to the laboratory. The semi-solid Cary Blair medium is composed of the following components: · Sodium chloride 5.0 g/L · Disodium Phosphate, 1.1 g/L 3 · Sodium thioglycollate 1.5 g/L · Calcium chloride, 0.09 g/L · Bacteriological agar, 5.6 g/L · Deionized water 1 L J. Substantial Equivalence Information: 1. Predicate device name(s): Copan Venturi Transystem Cary-Blair Medium product (132C) 2. Predicate 510(k) number(s): k946286 3. Comparison with predicate: Similarities Item Device Predicate Puritan® Opti-Tranz™ Cary- Blair Collection and Transport System (k160082) Copan Venturi Transystem Cary-Blair Medium product (132C) (k946286) Intended Use The Puritan Opti-Tranz Cary- Blair Collection and Transport System is intended for use in the collection and transport of clinical fecal and rectal swab specimens to preserve the viability of enteric bacteria during transport from the collection site to the testing laboratory for bacteriological examination and culture. Copan Venturi Transystem Cary-Blair Medium product (132C) is a sterile ready-to-use system intended for the safe collection, transport, and preservation of clinical specimens for bacteriological examination. Product 132C is supplied with a plastic applicator swab. The Venturi Transystem with Cary-Blair Transport Medium is recommended for the collection and transport of fecal and rectal swab samples for the investigation of enteric pathogenic bacteria. 4 Similarities Item Device Predicate Puritan® Opti-Tranz™ Cary- Blair Collection and Transport System (k160082) Copan Venturi Transystem Cary-Blair Medium product (132C) (k946286) Specimen Storage Up to 48 h at 20 – 25 oC and up to 72 h at refrigerated conditions 2 – 8 oC Same Tube Polypropylene, round bottom Same Medium Volume 5 mL Same Single Use Device Yes Same Packaging Peel pouch Same Swab Rayon Same Medium Formulation Sodium chloride 5.0 g/L Disodium Phosphate, 1.1 g/L Sodium thioglycollate 1.5 g/L Calcium chloride, 0.09 g/L Bacteriological agar, 5.6 g/L Deionized water 1 L Same Differences Item Device Predicate Organisms Tested Campylobacter jejuni Enterococcus faecalis Escherichia coli Salmonella typhimurium Shigella sonnei Vibrio parahaemolyticus Yersinia enterocolitica Campylobacter jejuni Escherichia coli Shigella flexneri Yersinia enterocolitica pH 6.9 – 7.5 8.4 ± 0.2 Shelf life 20 months 24 months K. Standard/Guidance Document Referenced (if applicable): Quality Control of Microbiological Transport Systems; Approved Standard – Second Edition, M40-A2, Clinical and Laboratory Standards Institute (CLSI), Wayne, PA, 2014. L. Test Principle: Not applicable. M. Performance Characteristics (if/when applicable): 5 1. Analytical performance: Analytical studies were conducted to determine the ability of the Puritan® Opti-Tranz™ Cary-Blair Collection and Transport System to maintain the viability of enteric microorganisms. The performance of the Puritan® Opti-Tranz™ Cary-Blair Collection and Transport System was determined using quantitative colony enumeration techniques outlined in the Clinical and Laboratory Standards Institute (CLSI) M40-A2 document. Bacterial viability studies were performed. The swabs from each transport system were inoculated with 100 µL of select bacterial concentrations prepared in a fecal matrix and/or 0.85% phosphate buffered saline (PBS). To facilitate testing, a homogeneous fecal matrix was prepared by diluting pre-screened negative fresh clinical fecal material in 0.85% PBS to a 30% concentration by volume. Once inoculated, the swabs were then placed in their respective transport tubes and held at various time intervals; at the designated time intervals the swabs were removed and processed. To test the viability at various time intervals the inoculated swabs were held at room temperature for 0, 24, and 48 hours and refrigerated for 0, 24, 48, and 72 hours. The eight ATCC strains listed in Table 1 below were used to evaluate the performance of the Puritan Opti-Tranz Cary-Blair Collection and Transport System. This device was tested using the swabs included with the transport kit. Viability studies were conducted in duplicate at 0, 24, and 48 at room temperature (20-25°C) and at 0, 24, 48, and 72 hours at refrigerated temperatures (2-8°C) using the Roll-Plate and Swab Elution Methods. * ‘NO’ indicates that strain was not tested in the column heading matrix; ‘YES’ indicates that the strain was tested in the column heading matrix. Roll-Plate Method: Bacterial suspensions were prepared from fresh18-24 hour cultures of each microorganism in a separate vial containing 10 mL of fecal matrix or 0.85% sterile saline to obtain 1.5 x 108 CFU/mL suspensions. One log10 serial dilutions were made and 100 µL aliquots of dilutions were absorbed into the swabs and immediately placed into the Table 1: Enteric bacteria evaluated for stability in Puritan Opti-Tranz Cary- Blair Collection and Transport System Microorganism ATCC # Fecal Matrix* 0.85% Saline* Campylobacter jejuni ATCC 33291 NO YES Escherichia coli ATCC 25922 NO YES Escherichia coli 0157:H7 ATCC 700728 YES YES Salmonella typhimurium ATCC 14028 YES YES Shigella sonnei ATCC 12022 NO YES Vibrio parahaemolyticus ATCC 17802 YES YES Vancomycin-resistant Enterococcus faecalis (VRE) ATCC 51299 NO YES Yersinia enterocolitica ATCC 9610 NO YES 6 Puritan Opti-Tranz Cary-Blair medium. For fecal specimens, the final dilution prior to swab inoculation was done with fecal matrix to maximize the amount of fecal material on the swab. After incubation at each time point, the swabs were removed from the transport tubes and used to inoculate the entire surface of the appropriate agar plate. The plates were incubated in appropriate culture conditions for 24-48 hours or until countable colonies were visible. Manual colony counts were conducted for each time interval for each swab- organism combination. The dilution yielding colony counts nearest to zero (not to exceed 250 CFU) was reported. Log10 increases or decreases in survival are based on a comparison between time-zero and the last time point collected for each Purpose for submission: