VITEK® 2 AST-Gram Positive Fosfomycin is designed for antimicrobial susceptibility testing of Gram positive microorganisms and is 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. VITEK® 2 AST-Gram Positive Fosfomycin is a quantitative test. Fosfomycin 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:
Enterococcus faecalis

The VITEK® 2 Gram-Positive Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant aerobic Gram-positive microorganisms to antimicrobial agents when used as instructed.

Device Description

The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh(1) and Gerlach(0). The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique(3).

Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. 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 contained on the card.

VITEK® 2 AST-GP Fosfomycin (<8 - ≥256 µg/mL) has the following concentrations in the card: 8, 16, 32 and 128 ug/mL (equivalent standard method concentration by efficacy in ug/mL).

AI/ML Overview

The medical device is the VITEK® 2 AST-Gram Positive Fosfomycin (≤8 - ≥256 µg/mL).

Here's the detailed information regarding its acceptance criteria and the study proving it meets those criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for antimicrobial susceptibility test (AST) systems are typically defined by the FDA Class II Special Controls Guidance Document. For the VITEK® 2 AST-GP Fosfomycin, the key performance metrics are Essential Agreement (EA) and Category Agreement (CA), along with the rates of Very Major Errors (VME), Major Errors (ME), and Minor Errors (mE).

Performance Metric	Acceptance Criteria (Implicit from FDA Guidance)	Reported Device Performance
Overall Essential Agreement (%EA)	Generally ≥ 90%	97.2% (388/399)
Very Major Errors (VME)	As low as possible, typically < 1.5%	0.0% (0/1)
Major Errors (ME)	As low as possible, typically < 3.0%	0.0% (0/385)
Minor Errors (mE)	As low as possible, typically < 10%	3.3% (13/399)
Overall Category Agreement (%CA)	Generally ≥ 90%	96.7% (386/399)

Note: The document explicitly states "VITEK® 2 AST-GP Fosfomycin demonstrated substantially equivalent performance when compared with the CLSI agar dilution reference method, as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)." While specific numerical acceptance thresholds are not explicitly listed in this document, the reported performance clearly meets the general expectations for substantial equivalence based on FDA guidance for AST systems.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Test Set: 399 isolates.
Data Provenance: The study involved an "external evaluation" conducted with "fresh and stock clinical isolates, as well as a set of challenge strains." This suggests a combination of prospective clinical samples (fresh isolates) and retrospective/archived samples (stock clinical isolates and challenge strains). The country of origin is not specified but is implicitly within the scope of where such FDA-regulated clinical trials are conducted.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of study (Antimicrobial Susceptibility Testing) does not typically involve human experts establishing a "ground truth" in the way, for example, a radiology AI study would. The ground truth is established by a reference laboratory method. In this case, the CLSI agar dilution reference method was used. This is a standardized laboratory procedure, not reliant on expert subjective interpretation.

4. Adjudication Method for the Test Set

Not applicable. As noted above, the ground truth is established by a standardized laboratory reference method (CLSI agar dilution), not by human expert consensus or adjudication. Discrepancies would be resolved through re-testing or investigation of methods, rather than expert adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

Not applicable. This is an antimicrobial susceptibility test system, not an AI-assisted diagnostic imaging system that involves human readers. The VITEK® 2 system is essentially an automated laboratory test.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, this study represents a standalone (algorithm only) performance evaluation. The VITEK® 2 system performs the antimicrobial susceptibility testing automatically. Its results are compared directly against the CLSI agar dilution reference method.

7. The Type of Ground Truth Used

The ground truth used was the CLSI agar dilution reference method. This is a well-established, standardized laboratory method for determining the minimum inhibitory concentration (MIC) of an antimicrobial agent against a microorganism, which then translates into interpretive categories (susceptible, intermediate, resistant).

8. The Sample Size for the Training Set

The document does not explicitly state the sample size for the training set. It describes the performance evaluation conducted with "fresh and stock clinical isolates, as well as a set of challenge strains" which refers to the test set. For an AST system like VITEK® 2, the "training" (development and calibration) would involve a substantial, diverse collection of bacterial strains with known resistance profiles, but the specific number used to initially develop the "growth pattern analysis" algorithm is not provided in this summary.

9. How the Ground Truth for the Training Set Was Established

The ground truth for the development/training of microbial AST systems, including the VITEK® 2, is typically established using established reference laboratory methods, primarily agar dilution or broth microdilution, in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. These methods define the true minimum inhibitory concentration (MIC) for various microorganisms against specific antimicrobial agents. This extensive dataset of MICs across a wide range of strains would be used to develop and fine-tune the "Growth Pattern Analysis" algorithm of the VITEK® 2 system to accurately determine MICs and interpretive categories.

Summary

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September 14, 2021

bioMérieux, Inc. Debra Broyles Sr. Regulatory Affairs Specialist 595 Anglum Road Hazelwood, Missouri 63042

Re: K202396

Trade/Device Name: VITEK 2 AST-Gram Positive Fosfomycin (≤8 - ≥256 µg/mL) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System Regulatory Class: Class II Product Code: LON, LTW, LTT Dated: August 20, 2020 Received: August 21, 2020

Dear Debra Broyles:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Ribhi Shawar, Ph.D. (ABMM) Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

Device Name

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
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Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) SUMMARY

VITEK® 2 AST-Gram Positive Fosfomycin (≤8 - ≥256 µg/mL)

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Debra BroylesSenior Regulatory Affairs Specialist
Phone Number:	314 -731-8805
Fax Number:	314-731-8689
Date of Preparation:	August 5, 2020
Device Name:
Formal/Trade Name:	VITEK® 2 AST-Gram Positive Fosfomycin (≤8 - ≥256µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code: LON
Common Name:	VITEK® 2 AST-GP Fosfomycin (≤8 - ≥256 µg/mL)
Predicate Device:	VITEK® 2 AST-GP Dalbavancin (≤0.015 – ≥1 µg/mL)(K190616)

D. Device Description:

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VITEK® 2 AST-GP Fosfomycin (<8 - ≥256 µg/mL) has the following concentrations in the card: 8, 16, 32 and 128 ug/mL (equivalent standard method concentration by efficacy in ug/mL).

E. Substantial Equivalence Information:

The similarities and differences of the VITEK® 2 AST-Gram Positive Fosfomycin (≤8 - ≥256 ug/mL) when compared to the predicate device, VITEK® 2 AST-Gram Positive Dalbavancin (<0.015 ->1 ug/mL). are described in the Table 1 below.

Item	Device:VITEK® 2 AST-GPFosfomycin(≤8 - ≥256 µg/mL)	Predicate:VITEK® 2 AST-GPDalbavancin(≤ 0.015 – ≥ 1 µg/mL)(K190616)
Similarities
Intended Use	VITEK® 2 AST-Gram PositiveFosfomycin is designed forantimicrobial susceptibilitytesting of Gram positivemicroorganisms and is intendedfor use with the VITEK® 2 andVITEK® 2 Compact Systems asa laboratory aid in thedetermination of in vitrosusceptibility to antimicrobialagents. VITEK® 2 AST-GramPositive Fosfomycin is aquantitative test. Fosfomycin	VITEK® 2 AST-Gram PositiveDalbavancin is designed forantimicrobial susceptibilitytesting of Gram positive bacilliand is intended for use with theVITEK® 2 and VITEK® 2Compact Systems as alaboratory aid in thedetermination of in vitrosusceptibility to antimicrobialagents. VITEK® 2 AST-GramPositive Dalbavancin is aquantitative test. Dalbavancin
Item	Device:VITEK® 2 AST-GPFosfomycin(≤8 - ≥256 µg/mL)	Predicate:VITEK® 2 AST-GPDalbavancin( ≤ 0.015 – ≥ 1 µg/mL)(K190616)
	Similarities
	has been shown to be activeagainst most strains of themicroorganisms listed below,according to the FDA label forthis antimicrobial.Active in vitro and in clinicalinfections:	has been shown to be activeagainst most strains of themicroorganisms listed below,according to the FDA label forthis antimicrobial.Active both in vitro and inclinical infections
	Enterococcus faecalis	Staphylococcus aureus(including methicillin-resistantisolates)
	The VITEK® 2 Gram-PositiveSusceptibility Card is intendedfor use with the VITEK® 2Systems in clinical laboratoriesas an in vitro test to determinethe susceptibility of clinicallysignificant aerobic Grampositive microorganisms toantimicrobial agents when usedas instructed.	Enterococcus faecalis(vancomycin-susceptibleisolates only)Streptococcus agalactiaeThe VITEK® 2 Gram-PositiveSusceptibility Card is intendedfor use with the VITEK® 2Systems in clinical laboratoriesas an in vitro test to determinethe susceptibility ofStaphylococcus spp.,Enterococcus spp., and S.agalactiae to antimicrobialagents when used as instructed.
Test Methodology	Automated quantitativeantimicrobial susceptibility testfor use with the VITEK® 2 andVITEK® 2 Compact Systems todetermine the in vitrosusceptibility of	Same
Item	Device:VITEK® 2 AST-GPFosfomycin( $ \leq 8 - \geq 256 $ µg/mL)	Predicate:VITEK® 2 AST-GPDalbavancin( $ \leq 0.015 - \geq 1 $ µg/mL)(K190616)
Similarities
Inoculum	Saline suspension of organism	Same
Test Card	Gram Positive (AST-GP)Susceptibility Card	Same
Instrument	VITEK® 2 and VITEK® 2Compact Systems	Same
Analysis Algorithm	Growth Pattern Analysis	Same
Differences
AntimicrobialAgent	Fosfomycin	Dalbavancin
Concentrations	8, 16, 32, 128	0.0625, 0.125, 0.25, 0.5
Indicatedorganisms	Enterococcus faecalis	Staphylococcus aureus(including methicillin-resistantisolates)Enterococcus faecalis(vancomycin-susceptibleisolates only)Streptococcus agalactiae

Table 1・ Substantial Equivalence

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F. Intended Use:

Active in vitro and in clinical infections:

Enterococcus faecalis

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G. Performance Overview and Conclusion:

VITEK® 2 AST-GP Fosfomycin demonstrated substantially equivalent performance when compared with the CLSI agar dilution reference method, as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009).

The Premarket Notification (510[k]) presents data in support of VITEK® 2 AST-GP Fosfomycin. An external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains. The external evaluations were designed to confirm the acceptability of VITEK® 2 AST-GP Fosfomycin by comparing its performance with the CLSI agar dilution reference method incubated at 16-20 hrs. The data is representative of performance on both the VITEK® 2 Compact instrument platforms.

The VITEK® 2 AST-GP Fosfomycin demonstrated acceptable performance as presented in Table 2 below:

OverallPerformance(with thereferencemethod)	%EA	VME	ME	mE	%CA	VME	ME	mE
	(388/399)97.2	N/A	N/A	N/A	(386/399)96.7	(0/1)0.0	(0/385)0.0	(13/399)3.3

Table 2: VITEK® 2 AST-GP Fosfomycin Performance

Reproducibility and Quality Control demonstrated acceptable results.

H. References:

1. MacLowry, J.D. and Marsh, H.H., Semi-automatic Microtechnique for Serial Dilution Antibiotic Sensitivity Testing in the Clinical laboratory, Journal of Laboratory Clinical Medicine, 72:685-687, 1968.
1. Gerlach, E.H., Microdilution 1: A Comparative Study, p. 63-76. Current Techniques for Antibiotic Susceptibility Testing. A. Balows (ed.), Charles C. Thomas, Springfield, IL, 1974.

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1. Barry, A.L., The Antimicrobic Susceptibility Test, Principles and Practices, Lea and Febiger, Philadelphia, PA, 1976.

Regulation Number and Section

§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.

(a)
Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”