The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 and VITEK® 2 Compact Systems for the automated quantitative or qualitative susceptibility testing of most clinically significant aerobic gram-positive cocci such as Staphylococcus spp., Enterococcus spp., Streptococcus agalactiae, and S. pneumoniae. VITEK® 2 Gram Positive Meropenem is designed for antimicrobial susceptibility testing of Staphylococcus aureus and Staphylococcus epidermidis. VITEK 2 Gram Positive Meropenem is a qualitative tool. It 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.

Device Description

The VITEK 2 AST Cards are essentially miniaturized versions of the doubling dilution technique for determining the minimum inhibitory concentration (MIC) microdilution methodology. The bacterial isolate to be tested is diluted to a standardized concentration in 0.45% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK 2 automatically fills, seals and places the card into the incubator/reader. 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 along with the interpretive category result for each antibiotic contained on the card.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the VITEK® 2 Gram Positive Meropenem as described in the provided 510(k) summary:

Acceptance Criteria and Device Performance Study

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance
Overall Category Agreement	Substantial equivalence to the NCCLS (now CLSI) reference agar dilution method. Specifically, high percentage agreement.	100% Overall Category Agreement when compared to the agar dilution reference method.
Reproducibility	Acceptable results.	Demonstrated acceptable results.
Quality Control	Acceptable results.	Demonstrated acceptable results.

Explanation of Acceptance Criteria: The primary acceptance criterion for this device, a Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility Device, is "substantial equivalence" to a predicate device and a recognized reference method. For AST devices, this typically translates to high percentage agreement with the reference method across several categories: Essential Agreement (EA), Category Agreement (CA), and often minor, major, and very major error rates. While specific numeric acceptance thresholds for these error rates are not explicitly stated as "acceptance criteria" here, the 100% overall Category Agreement indicates that these thresholds were met implicitly, given the FDA clearance.

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

Sample Size for Test Set: Not explicitly stated as a single number. The study was conducted with "fresh and stock clinical isolates and stock challenge strains." The text notes that "external evaluations were designed to confirm the [performance] of VITEK 2 Gram Positive Meropenem by comparing its performance with the CLSI (NCCLS) agar dilution reference method." This implies a sufficiently large and diverse set of isolates was used to achieve the reported 100% agreement.
Data Provenance: The study was an "external evaluation," which suggests controlled laboratory settings, likely in the US given the FDA submission. The terms "fresh and stock clinical isolates" indicate a mix of recently isolated clinical samples and established strains from laboratory collections. "Stock challenge strains" are typically well-characterized strains used for robust validation. The text does not explicitly state the country of origin of the clinical data but "external evaluation" for an FDA submission generally implies US-based data gathered specifically for regulatory purposes. It is a prospective study in the sense that the device's performance was evaluated against a reference method on these isolates for the purpose of this submission.

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

Number of Experts: Not specified.
Qualifications of Experts: Not specified. However, for a reference method like NCCLS/CLSI agar dilution, the ground truth would be established by trained microbiologists following standardized laboratory protocols. The method itself is the "gold standard" here, and the "experts" would be the personnel carrying out the reference testing accurately.

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable in the traditional sense of human consensus for image interpretation. The ground truth (reference method result) is established objectively by the agar dilution method, which produces a Minimum Inhibitory Concentration (MIC) value. The VITEK 2 result (MIC and interpretive category) is then compared directly to this reference MIC and category. Discrepancies would be resolved by retesting according to established microbiology laboratory procedures, not typically by an adjudication panel comparing interpretations.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

MRMC Study Done: No. This device is an automated antimicrobial susceptibility testing system, not an imaging device requiring human-in-the-loop interpretation. Therefore, a multi-reader multi-case comparative effectiveness study comparing human readers with and without AI assistance is not relevant to this type of device.

6. Standalone Performance Study

Standalone Study Done: Yes. The entire study described is a standalone performance evaluation. The VITEK 2 Gram Positive Meropenem's performance (its ability to determine antimicrobial susceptibility) was directly compared to the NCCLS reference agar dilution method. This is a direct measure of the algorithm/device's accuracy without human intervention influencing the result generation. The device automatically performs the test and generates the interpretive category.

7. Type of Ground Truth Used

Type of Ground Truth: The ground truth was established using the NCCLS (now CLSI) reference agar dilution method. This is considered the "gold standard" for determining Minimum Inhibitory Concentrations (MICs) and interpretive categories (Susceptible, Intermediate, Resistant) for antimicrobial agents.

8. Sample Size for the Training Set

Sample Size for Training Set: Not explicitly stated. The document describes a performance evaluation (test set) but does not detail the size or nature of a separate training set. For an AST device like VITEK 2, development often involves extensive internal testing and optimization (which could be considered a form of "training" or development data) using a large library of characterized strains, before formal external validation is performed. The 510(k) summary focuses on the validation study demonstrating performance.

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

Ground Truth for Training Set: Not explicitly detailed. Similar to the test set, the ground truth for any development or "training" data for an AST device would typically be established using the CLSI/NCCLS reference methods (such as agar dilution or broth microdilution) to determine the true MICs and interpretive categories of the bacterial isolates used in development. This is a standard and robust method for establishing ground truth in microbiology.

Summary

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K050816

Image /page/0/Picture/1 description: The image shows the date "MAY 12 2005" in bold, sans-serif font at the top left. Below the date is the word "BIOMÉRIEUX" in a stylized font. To the right of the word is a circular seal with a line extending below it.

510(k) SUMMARY

VITEK® 2 Gram Positive Meropenem

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Jolyn TenlladoRegulatory Affairs Specialist
Phone Number:	314-731-8386
Fax Number:	314-731-8689
Date of Preparation:	March 30, 2005
B. Device Name:
Formal/Trade Name:	VITEK® 2 Gram Positive Meropenem (<0.5 - ≥16ug/ml)
Classification Name:	Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility Device,21 CFR 866.1645
Common Name:	VITEK 2 AST-GP Meropenem
C. Predicate Device:	VITEK 2 Gram Positive AST for Sparfloxacin(N50510/S141)

D. 510(k) Summary:

VITEK® 2 Gram Positive Meropenem is designed for antimicrobial susceptibility testing of Staphylococcus aureus and Staphylococcus epidermidis. It 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. The antimicrobial presented in VITEK 2 AST Cards is in concentrations equivalent by efficacy to standard method concentrations in mcg/ml. The VITEK 2 AST Cards are essentially miniaturized versions of the doubling dilution technique for determining the minimum inhibitory concentration (MIC) microdilution methodology.

The bacterial isolate to be tested is diluted to a standardized concentration in 0.45% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK 2 automatically fills, seals and places the card into the incubator/reader. 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

bioMérieux, Inc.

595 Anglum Road, Hazelwood, Missouri 63042-2320, USA Phone: 314/731-8500 800/638-4835 Fax: 314/731-8700

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to 18 hours). At the completion of the incubation cycle, a report is generated that to 10 hours). 7 k the becalong with the interpretive category result for each antibiotic contained on the card.

VITEK 2 Gram Positive Meropenem demonstrated substantially equivalent performance when compared with the NCCLS reference agar dilution method, as defined in the FDA when comparis with and Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, Issued Feb. 5, 2003.

The Premarket Notification (510[k]) presents data in support of VITEK 2 Gram Positive Meropenem. An external evaluation was conducted with fresh and stock clinical isolates and stock challenge strains. The external evaluations were designed to confirm the and stock challerige of VITEK 2 Gram Positive Meropenem by comparing its performance with the CLSI (NCCLS) agar dilution reference method. The data is representative of performance on both the VITEK 2 and VITEK 2 Compact instrument platforms, as performance the AST Equivalency Study presented in the VITEK 2 Compact premarket notification, K050002. VITEK 2 Gram Positive Meropenem demonstrated acceptable performance of 100% overall Category Agreement when compared to the agar dilution perference method. Reproducibility and Quality Control demonstrated acceptable results.

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes entwined around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" arranged in a circular fashion around the symbol. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 1 2 2005

Ms. Jolyn Tenllado Regulatory Affairs Specialist BioMérieux, Inc. 595 Anglum Road Hazelwood, MO 63042-2320

K050816 Re:

R050010
Trade/Device Name: VITEK® 2 Gram Positive Meropenem (≤0.5 - ≥16 µg/ml) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility Devices Regulatory Class: Class II

Product Code: LON Dated: March 30, 2005 Received: March 31, 2005

Dear Ms. Tenllado:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your becamined the device is substantially equivalent (for the indications ferenced above and nave uses and legally marketed predicate devices marketed in interstate for use stated in the encrosure) to regard ment date of the Medical Device Amendments, or to comments prior to May 20, 1978, the occordance with the provisions of the Federal Food, Drug, devices that have been recensement in quire approval of a premarket approval application (PMA). and Cosmetic Ac. (Therefore, market the general controls provisions of the Act. The You may, therefore, market the do rees, courements for annual registration, listing of general controls provisions of the rice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), If your device is classified (360 a00 vo) into s. Existing major regulations affecting your device in the contributions of it may be subject to such additional controllar containt of the same of to 895. In addition, FDA can be found in Thio 21, South on a soncerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean Please be advised that FDA s issuation of a buice complies with other requirements of the Act that IDA has made a determination administered by other Federal agencies. You must of ally receral statutes and regulations and limited to: registration and listing (21 comply with an the Ace S requirements, and 809); and good manufacturing practice CFN I all 8077, labeling (21 CF regulation (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) I ms letter will anow you to oogin mailing of substantial equivalence of your device to a legally premarket notification: " " results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In of quostions on the promebialion and Safety at (240)276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Tou may of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

Sally a Forg

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): 40508): حالا

Device Name: VITEK® 2 Gram Positive Meropenem (≤0.5 – ≥16 µg/ml)

Indications For Use:

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the The VITER 2 And VITEK® 2 Compact Systems for the automated quantitative or qualitative VITER 2 and VTTER 2 Oompact Oyeans for the most clinically significant aerobic gramsusceptibility testing of listiated spp., Entercoccus spp., Streptococcus agalactiae, and S. pneumoniae.

S. prieumoniae.
VITEK® 2 Gram Positive Meropenem is designed for antimicrobial Corpora Regitive of Staphylococcus aureus and Staphylococcus epidemidis. VITEK 2 Gram Positive of Staphylococus adretis and Claphylooded for use with the VITEK 2 and VITEK 2 Meropenent is a qualifulive tool. It in the determination of in vitro susceptibility to antimicrobial agents.

X Prescription Use (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Freddie L. Lape

Division Sign-Off

Page 1 of 1

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K050816

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.”