VITEK® 2 AST-GP Cefoxitin Screen is designed to predict mecA-mediated oxacillin resistance in Staphylococcus spp. 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 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 Streptococcus agalactiae to antimicrobial agents when used as instructed.

Device Description

VITEK® 2 AST-GP Cefoxitin Screen is designed to predict mecA-mediated oxacillin resistance in Staphylococcus spp. The cefoxitin screen and oxacillin work in combination to determine the final interpretation reported for oxacillin. The VITEK® 2 AST-GP Cefoxitin Screen is a qualitative test based on the CLSI, "Disk Diffusion Test for Prediction of mecAmediated resistance in Staphylococci." The VITEK® 2 AST-GP Cefoxitin Screen test 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 VITEK® 2 card is inoculated with a standardized organism suspension, and growth inside the card is optically monitored throughout the incubation cycle. Results are automatically calculated once a predetermined growth threshold is reached and a report is generated that contains the MIC result and the interpretive category result.

The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh('') 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. For the VITEK 2 Cefoxitin Screen, the report will list either a positive or negative result. The VITEK 2 Cefoxitin Screen and oxacillin work in combination to determine the final oxacillin interpretation based on the CLSI recommendations.

NOTE: Final determination of the oxacillin interpretation is based on forcing rules as managed by the VITEK 2 Systems software. Both the VITEK 2 AST-GP Cefoxitin Screen test and Oxacillin test must finalize before any forcing rules are applied.

VITEK® 2 AST-GP Cefoxitin Screen has the following concentrations in the card: 4 and 5 ug/mL (equivalent standard method concentration by efficacy in ug/mL).

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The device is a qualitative test designed to predict mecA-mediated oxacillin resistance in Staphylococcus spp. The performance is measured by Category Agreement (CA) and various error rates (Very Major Error - VME, Major Error - ME, Minor Error - mE).

Antimicrobial + Cefoxitin Screen	Performance Metric	Acceptance Criteria (Implied by reported performance)	Reported Device Performance
S. aureus & S. lugdunensis	% Category Agreement (CA)	> 95% (common benchmark for AST devices)	98.7% (525 / 532)
	% Very Major Error (VME)	As low as possible, typically < 1.5%	0.6% (1 / 177)
	% Major Error (ME)	As low as possible, typically < 3%	1.7% (6 / 355)
	% Minor Error (mE)	N/A (Not Applicable as a primary criterion for qualitative)	N/A
Other Staphylococcus species (excluding S. pseudintermedius & S. schleiferi)	% Category Agreement (CA)	> 95% (common benchmark for AST devices)	97.8% (261 / 267)
	% Very Major Error (VME)	As low as possible, typically < 1.5%	0.0% (0 / 125)
	% Major Error (ME)	As low as possible, typically < 3%	4.2% (6 / 142)
	% Minor Error (mE)	N/A (Not Applicable as a primary criterion for qualitative)	N/A

Note: The document implicitly defines acceptance by presenting the achieved performance as "acceptable performance." Common regulatory expectations for AST devices have been used to infer typical acceptance targets.

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

Sample Size for Test Set:
- S. aureus & S. lugdunensis: 532 isolates tested (Denominator for Category Agreement)
- Other Staphylococcus species: 267 isolates tested (Denominator for Category Agreement)
Data Provenance: The study involved an "external evaluation" conducted with "fresh and stock clinical isolates, as well as a set of challenge strains." This indicates a mix of clinical samples and potentially curated reference strains. The document does not specify the country of origin of the data. It is a retrospective study since it uses existing clinical isolates and challenge strains.

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

The document does not explicitly state the number of experts or their qualifications. However, it indicates that the device performance was compared against the CLSI disk diffusion method ("Performance Standards for Antimicrobial Disk Susceptibility Tests", Approved Standard -13th Edition (January 2018)). This implies that the ground truth was established by adherence to a standardized, expert-approved reference method, rather than through individual expert consensus on specific cases.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method beyond the direct comparison to the CLSI disk diffusion reference method. There is no mention of a human-in-the-loop process requiring adjudication for conflicting interpretations.

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

No, an MRMC comparative effectiveness study was not done. This device is an automated antimicrobial susceptibility testing system, not an AI-assisted diagnostic tool that would typically involve human readers.

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

Yes, a standalone performance assessment was done. The VITEK® 2 AST-GP Cefoxitin Screen is an automated system that generates results directly, which are then compared to the CLSI disk diffusion reference method. There is no human interpretation step in the device's output itself for this performance evaluation. The "report will list either a positive or negative result."

7. The Type of Ground Truth Used

The ground truth used was based on the CLSI disk diffusion method ("Performance Standards for Antimicrobial Disk Susceptibility Tests", Approved Standard -13th Edition (January 2018)), which is a recognized reference standard for antimicrobial susceptibility testing.

8. The Sample Size for the Training Set

The document does not specify the sample size for the training set. It only describes the external evaluation using clinical isolates and challenge strains. Since the device uses a "Discriminant Analysis" algorithm, it implies a training phase, but the details are not provided in this summary.

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

The document does not explicitly describe how the ground truth for the training set was established. However, given that the final performance is benchmarked against the CLSI disk diffusion method, it is highly probable that the training set's ground truth was also established using this or a similar accepted reference method.

Summary

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October 13, 2022

bioMérieux, Inc Nathan Hardesty Associate Director, Regulatory Affairs Clinical Microbiology 595 Anglum Rd. Hazelwood, Missouri 63042

Re: K220805

Trade/Device Name: VITEK 2 AST-Gram Positive Cefoxitin Screen 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: March 17, 2022 Received: March 18, 2022

Dear Nathan Hardesty:

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

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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 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 (OS) 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,

For: Uwe Scherf, Ph.D. Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics 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 Cefoxitin Screen

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Nathan HardestyAssociate Director Regulatory Affairs, Microbiology
Phone Number:	314-731-8666
Fax Number:	314-731-8689
Date of Preparation:	January 31, 2022
B. Device Name:
Formal/Trade Name:	VITEK® 2 AST-Gram Positive Cefoxitin Screen
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code: LON, LTW, LTT
Common Name:	VITEK® 2 AST-GP Cefoxitin Screen
C. Predicate Device:	VITEK® 2 Gram Positive Cefoxitin Screen (K053097)

D. Device Description:

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VITEK® 2 AST-GP Cefoxitin Screen has the following concentrations in the card: 4 and 5 ug/mL (equivalent standard method concentration by efficacy in ug/mL).

E. Substantial Equivalence Information:

The similarities and differences of the VITEK® 2 AST-GP Cefoxitin Screen when compared to the predicate device, VITEK® 2 Cefoxitin Screen (K053097), are described in the Table 1 below.

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Table 1: Substantial Equivalence
Item	Device:VITEK® 2 AST-Gram PositiveCefoxitin Screen	Predicate:VITEK® 2 AST-Gram PositiveCefoxitin Screen (K053097)
Similarities
Intended Use	VITEK® 2 AST-Gram PositiveCefoxitin Screen test is designed topredict mecA-mediated oxacillinresistance in Staphylococcus spp. It isintended for use with the VITEK® 2and VITEK® 2 Compact Systems as alaboratory aid in the determination of invitro susceptibility to antimicrobialagents.The VITEK® 2 AST 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 Streptococcus agalactiae toantimicrobial agents when used asinstructed.	VITEK® 2 Gram Positive CefoxitinScreen test is designed to predictmecA-mediated resistance inStaphylococci. It is intended for usewith the VITEK® 2 and VITEK® 2Compact Systems as a laboratory aidin the determination of in vitrosusceptibility to antimicrobial agents.The VITEK® 2 AST Gram-PositiveSusceptibility Card is intended for usewith the VITEK® 2 Systems inclinical laboratories as an in vitro testto determine the susceptibility ofStaphylococcus spp., Enterococcusspp., and Streptococcus agalactiae toantimicrobial agents when used asinstructed.
Test Methodology	Automated qualitative antimicrobialsusceptibility test for use with theVITEK® 2 and VITEK® 2 CompactSystems to determine the in vitrosusceptibility of microorganisms	Same
Inoculum	Saline suspension of organism	Same
Test Card	Gram Positive (AST-GP) SusceptibilityCard	Same
Instrument	VITEK® 2 and VITEK® 2 CompactSystems	Same
AnalysisAlgorithm	Discriminant Analysis	Same
Differences
Concentrations	4, 5	6

F. Intended Use:

VITEK® 2 AST-GP Cefoxitin Screen is designed to predict mecA-mediated oxacillin resistance in Staphylococcus spp. It is intended for use with the VITEK® 2 and VITEK® 2

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Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents.

G. Performance Overview and Conclusion:

VITEK® 2 AST-GP Cefoxitin Screen demonstrated substantially equivalent performance when compared with the CLSI disk diffusion method, as defined "Performance Standards for Antimicrobial Disk Susceptibility Tests", Approved Standard -13th Edition (January 2018).

The Premarket Notification (510[k]) presents data in support of VITEK® 2 AST-GP Cefoxitin Screen. 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 Cefoxitin Screen by comparing its performance with the CLSI test for detecting methicillin (oxacillin) resistance with cefoxitin disk diffusion incubated at 33-35°C for 16-18 hrs with S. aureus and S. lugdunensis, and 24 hours for other Staphylococcus (excluding S. pseudintermedius & S. schleiferi). The data is representative of performance on both the VITEK® 2 and VITEK® 2 Compact instrument platforms.

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

Antimicrobial	Comment2	Essential Agreement				Category Agreement
		% Error				% Error
		% EA	VME	ME	mE	% CA	VME	ME	mE
Oxacillin +Cefoxitin Screen	S. aureus & S. lugdunensis#, E, Ref. =CLSI DiskDiffusion	-	-	-	-	98.7%(525 / 532)	0.6%(1 / 177)	1.7%(6 / 355)	N/A

Table 2

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OtherStaphylococcusspecies (notincluding S.Pseudinterme-dius or S.Schleiferi )#, E, Ref. =CLSI DiskDiffussion	-	-	-	97.8%(261 / 267)	0.0 %(0 / 125)	4.2%(6 / 142)	N/A
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Reproducibility and Quality Control demonstrated acceptable results.

In conclusion the performance data presented in this submission supports a substantial equivalence decision. VITEK® 2 AST Gram Positive Cefoxitin Screen test in this 510(k) is substantially equivalent to the predicate VITEK® 2 AST Gram Positive Cefoxitin Screen Test (K053097).

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.
Barry, A.L., The Antimicrobic Susceptibility Test, Principles and Practices, Lea and 3. Febiger, Philadelphia, PA, 1976.
CLSI M02, "Performance Standards for Antimicrobial Disk Susceptibility Tests", Approved 4. Standard -13th Edition (January 2018)
1. CLSI M100, "Performance Standards for Antimicrobial Susceptibility Testing; 31th Edition", (March 2021)

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.”