VITEK® 2 AST-Gram Positive Linezolid 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 Linezolid is a quantitative test. Linezolid 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 faecium (vancomycin-resistant isolates only) Staphylococcus aureus (including methicillin-resistant isolates) Streptococcus agalactiae

In vitro data are available, but clinical significance is unknown: Enterococcus faecalis (including vancomycin-resistant isolates) Enterococcus faecium (vancomycin-susceptible isolates) Staphylococcus epidermidis (including methicillin-resistant isolates) Staphylococcus haemolyticus

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 Staphylococcus spp., Enterococcus spp., and S. agalactiae 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 (2). 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 Linezolid has the following concentrations in the card: 0.5, 1, and 2 ug/mL (equivalent standard method concentration by efficacy in us/mL).

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and the study that proves the device meets those criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for antimicrobial susceptibility test (AST) systems are generally defined by guidance documents such as the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems." While explicit numerical acceptance criteria (e.g., "EA must be > 90%") are not directly stated in the provided text as a separate table, it can be inferred from the "Performance Overview and Conclusion" section and the structure of the performance data presented.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance (Linezolid)
Essential Agreement (EA)	High percentage, typically >90% for AST systems. Specific thresholds not explicitly stated but implied by "acceptable performance."	Enterococcus spp.: 99.8% (402/403) Staphylococcus spp.: 97.2% (379/390) Streptococcus agalactiae: 100% (64/64)
Category Agreement (CA)	High percentage, typically >90% for AST systems. Specific thresholds not explicitly stated but implied by "acceptable performance."	Enterococcus spp.: 98.0% (395/403) Staphylococcus spp.: 99.7% (389/390) Streptococcus agalactiae: 100% (64/64)
Very Major Errors (VME)	Low percentage, typically <1.5% - <3% for AST systems. Specific thresholds not explicitly stated but implied by "acceptable performance."	Enterococcus spp.: 0.0% (0/8) Staphylococcus spp.: 0.0% (0/11) Streptococcus agalactiae: 0.0% (0/0)
Major Errors (ME)	Low percentage, typically <1.5% - <3% for AST systems. Specific thresholds not explicitly stated but implied by "acceptable performance."	Enterococcus spp.: 0.0% (0/389) Staphylococcus spp.: 0.3% (1/379) Streptococcus agalactiae: 0.0% (0/64)
Minor Errors (mE)	Low percentage, typically <3% - <7% for AST systems. Specific thresholds not explicitly stated but implied by "acceptable performance."	Enterococcus spp.: 2.0% (8/403) Staphylococcus spp.: 0.0% (0/390) Streptococcus agalactiae: 0.0% (0/64)
Reproducibility	High percentage, typically >= 95%	Staphylococcus spp.: 100% (Only explicitly stated for Staphylococcus spp. in the table)

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

Sample Size:
- Enterococcus spp.: 403 isolates (for EA and CA analysis).
- Staphylococcus spp.: 390 isolates (for EA and CA analysis).
- Streptococcus agalactiae: 64 isolates (for EA and CA analysis).
- Total isolates for Linezolid across all species shown in the main table: 403 + 390 + 64 = 857 isolates.
- Staphylococcus haemolyticus (specific note): 35 isolates were used when evaluating performance for this specific species.
Data Provenance: The study used "fresh and stock clinical isolates, as well as a set of challenge strains." This indicates a mix of retrospective (stock isolates) and potentially prospective (fresh clinical isolates) data. The geographic origin of the data (e.g., country of origin) is not specified in the provided text.

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

This information is not specified in the provided text. The ground truth was established by the "CLSI agar dilution reference method," which is a laboratory standard rather than a consensus by human experts in the typical sense for imaging or clinical diagnosis. Clinical and Laboratory Standards Institute (CLSI) methods are highly standardized.

4. Adjudication Method for the Test Set

This type of information (e.g., 2+1, 3+1 expert adjudication) is typically relevant to diagnostic devices where human interpretation might be subjective. For an automated antimicrobial susceptibility test system comparing its results to a standardized reference laboratory method (CLSI agar dilution), an adjudication method as commonly understood in medical imaging studies is not applicable or described. The comparison is objective against the reference method.

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

An MRMC study is not applicable here. This device (VITEK 2 AST-GP Linezolid) is an automated system for antimicrobial susceptibility testing, not an AI-assisted diagnostic tool for human readers. There is no human-in-the-loop component described for its core function that would necessitate such a study.

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

Yes, a standalone performance evaluation was done. The VITEK® 2 AST-GP Linezolid system, which is described as an "Automated quantitative antimicrobial susceptibility test," was directly compared to the "CLSI agar dilution reference method." The results presented in Table 2 are the direct output of the VITEK® 2 system. This is a standalone performance evaluation of the device.

7. The Type of Ground Truth Used

The ground truth used was the CLSI agar dilution reference method. This is a validated, standardized laboratory method considered the gold standard for determining minimum inhibitory concentrations (MICs) of antimicrobials.

8. The Sample Size for the Training Set

The provided text describes a "Special 510(k) Submission" for a device that is essentially an updated version of a previously cleared device (K032766) with a change in breakpoints for Staphylococcus species. The study described focuses on validating the performance of this updated device against a reference method.

There is no explicit mention of a separate "training set" size in the context of machine learning or algorithm development. The VITEK® 2 system itself uses "Discriminant Analysis" algorithms, suggesting a historical development and training process, but the current document focuses on the validation of the updated breakpoints rather than the de novo development of the algorithm. If "training set" refers to the data used historically to develop the "Discriminant Analysis" algorithm, that information is not provided.

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

Given that no explicit "training set" is described for this specific submission's validation study, the method for establishing ground truth for a training set (if one was used for the initial development of the VITEK® 2's "Discriminant Analysis" algorithm) is not detailed in the provided text. The current document focuses on comparing the device's output to the CLSI agar dilution reference method for validation.

Summary

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February 4, 2022

bioMérieux, Inc Esther Hernandez Regulatory Affairs Specialist 595 Anglum Rd. Hazelwood, Missouri 63042

Re: K212849

Trade/Device Name: VITEK 2 AST-Gram Positive Linezolid (<0.5 ->8 ug/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 Dated: September 8, 2021 Received: September 9, 2021

Dear Esther Hernandez:

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

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) 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., D(ABMM), F(AAM) Branch Chief 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)
-------------------------------------------------	--

Prescription Use (Part 21 CFR 801 Subpart D)

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

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Image /page/3/Picture/0 description: The image shows the logo for bioMérieux, a French multinational biotechnology company. The logo consists of a blue circle on top and a yellow-green gradient circle on the bottom. The word "BIOMÉRIEUX" is written in white letters inside the blue circle.

VITEK® 2 AST-GP Linezolid Special 510(k) Submission

510(k) SUMMARY

VITEK® 2 AST-GP Linezolid

A. 510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Esther HernandezRegulatory Affairs Specialist
Phone Number:	314-731-8841
Fax Number:	314-731-8689
Date of Preparation:	September 03, 2021
Device Name:
Formal/Trade Name:	VITEK® 2 AST- Gram Positive Linezolid (≤ 0.5 -> 8 µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code LON
Common Name:	VITEK® 2 AST-GP Linezolid
Predicate Device:	VITEK® 2 AST-GP Linezolid (K032766)

D. Device Description:

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

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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 Linezolid has the following concentrations in the card: 0.5, 1, and 2 ug/mL (equivalent standard method concentration by efficacy in us/mL).

E. Substantial Equivalence Information

The similarities and differences of the VITEK 2 AST-GP Linezolid when compared to the predicate device. VITEK 2 AST-GP Linezolid (K032766), are described in the following table. The only difference between both devices is the change in breakpoints for Staphylococcus species.

Device and PredicateDevice(s):	Device: K212849	Predicate Device: K032766
Device Trade Name	VITEK 2 AST-GP Linezolid	VITEK 2 AST-GP Linezolid
General Device Characteristic Similarities
Intended Use/Indicationsfor Use	VITEK® 2 AST-Gram PositiveLinezolid is designed for antimicrobialsusceptibility testing of Gram positivemicroorganisms and is intended for usewith the VITEK® 2 and VITEK® 2Compact Systems as a laboratory aid inthe determination of in vitrosusceptibility to antimicrobial agents.VITEK® 2 AST-Gram PositiveLinezolid is a quantitative test.Linezolid has been shown to be activeagainst most strains of themicroorganisms listed below,according to the FDA label for thisantimicrobial.	Intended use(s):The VITEK 2 AntimicrobialSusceptibility Test (AST) is intended tobe used with the VITEK 2 System forthe automated quantitative or qualitativesusceptibility testing of isolated coloniesfor most clinically significant aerobicgram-negative bacilli, Staphylococcusspp. , Enterococcus spp. , Streptococcusagalactiae , and S. pneumoniae .The VITEK 2 Gram PositiveSusceptibility Card is intended for usewith theVITEK 2 System in clinical laboratoriesas an in vitro test to determine thesusceptibility of Staphylococcus spp. ,Enterococcus spp. , and S. agalactiae toantimicrobial agents when used as
	Active in vitro and in clinicalinfections:Enterococcus faecium (vancomycin-resistant isolates only)Staphylococcus aureus (includingmethicillin-resistant isolates)Streptococcus agalactiae	instructed in the Online ProductInformation.Indication(s) for use:The indication will include the testing oflinezolid at concentrations of 0.5, 1, and2 for a calling range of < 0.5 -> 8µg/ml on the VITEK 2 Gram PositiveSusceptibility Card.
	In vitro data are available, but clinicalsignificance is unknown:Enterococcus faecalis (includingvancomycin-resistant isolates)Enterococcus faecium (vancomycin-susceptible isolates)Staphylococcus epidermidis (includingmethicillin-resistant isolates)Staphylococcus haemolyticus
	The VITEK® 2 Gram-positiveSusceptibility Card is intended for usewith the VITEK® 2 Systems in clinicallaboratories as an in vitro test todetermine the susceptibility ofStaphylococcus spp., Enterococcusspp., and S. agalactiae to antimicrobialagents when used as instructed.
Test Methodology	Automated quantitative antimicrobialsusceptibility test for use with theVITEK® 2 and VITEK® 2 CompactSystems to determine the in vitrosusceptibility of microorganisms	Same
Antimicrobial Agent	Linezolid	Same
Inoculum	Saline suspension of organism	Same
Test Card	Gram-positive (AST-GP) SusceptibilityCard	Same
Analysis Algorithms	Discriminant Analysis	Same
Instrument	VITEK® 2 and VITEK® 2 CompactSystems	Same
Concentrations	0.5, 1, 2	Same
General Device Characteristic Differences
Staphylococcus spp.	S ≤ 4, I -, R >8 µg/mL	Susceptible-only category

Table1: Substantial Equivalence

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Image /page/5/Picture/0 description: The image shows the logo for bioMérieux, a French multinational biotechnology company. The logo consists of a blue semi-circle at the top with the company name "BIOMÉRIEUX" in white text. Below the blue semi-circle is a semi-circle that transitions from yellow to green.

VITEK® 2 AST-GP Linezolid Special 510(k) Submission

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VITEK® 2 AST-GP Linezolid Special 510(k) Submission

Breakpoints	S < 4 ug/mL

F. Intended Use:

Active in vitro and in clinical infections:

Enterococcus faecium (vancomycin-resistant isolates only) Staphylococcus aureus (including methicillin-resistant isolates) Streptococcus agalactiae

G. Performance Overview and Conclusion:

VITEK® 2 AST-GP Linezolid demonstrated substantially equivalent performance when compared with the 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).

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The Premarket Notification (Special 510[k]) presents data in support of VITEK® 2 AST- GP Linezolid. 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 Linezolid by comparing its performance with the CLSI agar dilution reference method incubated at 16-20 hours (20-24 hours for Streptococcus agalactiae). The data is representative of performance on both the VITEK® 2 and VITEK® 2 Compact instrument platforms.

VITEK® 2 AST-GP Linezolid (≤0.5 ->8 µg/mL) demonstrated acceptable performance as presented in Table 2 below:

Antimicrobial	Comment	Essential Agreement				Category Agreement				%Reproducibility
		%Error				% Error
		%EA	VME	ME	mE	%CA	VME	ME	mE
Linezolid	#, EEnterococcusspp.	(402/403)99.8%	N/A	N/A	N/A	(395/403)98.0%	(0/8)0.0%	(0/389)0.0%	(8/403)2.0%
	#, EStaphylococcusspp.	(379/390)97.2%	N/A	N/A	N/A	(389/390)99.7%	(0/11)0.0%	(1/379)0.3%	(0/390)0.0%	100%
	#, EStreptococcusagalactiae	(64/64)100%	N/A	N/A	N/A	(64/64)100%	(0/0)0.0%	(0/64)0.0%	(0/64)0.0%
VITEK 2 AST-Gram Positive Linezolid MIC values tended to be in exact agreement or at least one doubling dilution higher whentesting Staphylococcus haemolyticus compared to the CLSI reference agar dilution method.When evaluating performance of the clinical and challenge isolates, testing with Staphylococcus haemolyticus isolates yielded an EAof 82.9% (29/35) and an CA of 97.1% (34/35). There was one major error (2.9%%, 1/35).

Table 2: VITEK® 2 AST-GP Linezolid Performance

Key

= US Food and Drug Administration 510(k) cleared

E = External performance data

Quality Control demonstrated acceptable results.

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

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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.”