VITEK 2 AST-Yeast Voriconazole is designed for antifungal susceptibility testing of Candida species 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 antifungal agents. VITEK 2 AST-Yeast Voriconazole is a quantitative test. Voriconazole has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antifungal.

Active in vitro and in clinical infections: Candida krusei Candida parapsilosis Candida tropicalis

The VITEK 2 Fungal 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 yeasts to antifungal 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. The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique. 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-YS Voriconazole has the following concentrations in the card: 0.03125, 0.125, 0.25, 1, and 2 (equivalent standard method concentration by efficacy in ug/mL).

AI/ML Overview

The provided FDA 510(k) summary describes the VITEK® 2 AST-Yeast Voriconazole device, which is an antimicrobial susceptibility test system.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance:

The acceptance criteria are implicitly derived from the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems and are presented through "Essential Agreement" (EA) and "Category Agreement" (CA) performance metrics, along with error rates. The table below summarizes the reported performance for each microorganism. The specific acceptance thresholds for EA and CA are not explicitly stated as numerical percentages (e.g., >90% EA, >90% CA) with the exception of the individual error types (VME, ME, mE) having specified maximum allowable percentages. However, it is implied that the presented results were deemed acceptable by the FDA.

Antimicrobial	Microorganism	Essential Agreement %	VME (%)	ME (%)	mE (%)	Category Agreement %	VME (%) (Cat Ag)	ME (%) (Cat Ag)	mE (%) (Cat Ag)	% Reproducibility
Voriconazole	C. albicans	88.7 (228/257)	N/A	N/A	N/A	86.0 (221/257)	33.3 (4/12)	1.3 (3/237)	11.3 (29/257)	100
Voriconazole	C. krusei	100.0 (76/76)	N/A	N/A	N/A	98.7 (75/76)	0.0 (0/0)	0.0 (0/74)	1.3 (1/76)	Not Specified
Voriconazole	C. parapsilosis	94.6 (70/74)	N/A	N/A	N/A	94.6 (70/74)	0.0 (0/1)	1.5 (1/68)	4.1 (3/74)	Not Specified
Voriconazole	C. tropicalis	97.7 (85/87)	N/A	N/A	N/A	90.8 (79/87)	0.0 (0/2)	2.6 (2/77)	6.9 (6/87)	Not Specified

Key Definitions:

Essential Agreement (EA): Agreement between the MIC results of the test device and the reference method within plus or minus one doubling dilution.
Category Agreement (CA): Agreement between the interpretive categories (Susceptible, Intermediate, Resistant) of the test device and the reference method.
Very Major Error (VME): The test device reports susceptible, but the reference method reports resistant.
Major Error (ME): The test device reports resistant, but the reference method reports susceptible.
Minor Error (mE): Any other disagreement in interpretive category (e.g., susceptible vs. intermediate, resistant vs. intermediate).

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

The sample sizes for the test set (external evaluation) are provided for each microorganism:

C. albicans: 257 isolates
C. krusei: 76 isolates
C. parapsilosis: 74 isolates
C. tropicalis: 87 isolates

Data Provenance: The study conducted an "external evaluation" with "fresh and stock clinical isolates, as well as a set of challenge strains." The document does not specify the country of origin of the data nor explicitly state if it was retrospective or prospective. However, "fresh clinical isolates" typically implies a prospective collection, while "stock clinical isolates" could be either.

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

The ground truth was established by the "CLSI broth microdilution reference method." This is a standardized laboratory method, not reliant on human expert adjudication in the same way an imaging study would be. Therefore, the concept of "experts" and their qualifications as typically applied to visual diagnostic tasks (e.g., radiologists) is not directly applicable here. The ground truth method itself (CLSI broth microdilution) is the expert-defined standard.

4. Adjudication Method for the Test Set:

Not applicable in the human expert sense. The "adjudication method" for determining the ground truth in this context is the CLSI broth microdilution reference method, which serves as the gold standard for antimicrobial susceptibility testing. The device's results are compared directly against this established reference.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices where human readers interpret results, often in conjunction with AI. The VITEK® 2 AST-Yeast Voriconazole is an automated in vitro diagnostic device for antimicrobial susceptibility testing; its performance is evaluated by comparing its automated output to a gold standard laboratory method, not by how it assists human readers.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:

Yes, a standalone performance evaluation was done. The VITEK® 2 AST-Yeast Voriconazole system is an automated device designed to determine antimicrobial susceptibility without human interpretation of the primary data once the sample is loaded. The performance metrics (Essential Agreement, Category Agreement, error rates) directly reflect the device's standalone capability compared to the reference method.

7. The Type of Ground Truth Used:

The ground truth used was the CLSI broth microdilution reference method, incubated for 24 hours (up to 48 hours for slowly growing isolates). This is a well-established and scientifically accepted standard in microbiology for determining minimum inhibitory concentrations (MICs) of antifungal agents.

8. The Sample Size for the Training Set:

The document does not explicitly state the sample size for the training set. The descriptions focus on the "external evaluation" (test set). For IVD devices like this, the 'training set' often corresponds to historical data, internal studies, and method development efforts that lead to the final algorithm and concentration ranges. Without further information, the exact size of the training set used to develop the VITEK® 2 AST-Yeast Voriconazole algorithm is not provided in this 510(k) summary.

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

Similar to the answer for point 8, the document does not explicitly describe how the ground truth for any potential training set was established. However, given that the final performance is benchmarked against the CLSI broth microdilution reference method, it is highly probable that any internal development or training data would also have used this or a similar established reference method to determine the true susceptibility of isolates.

Summary

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June 12, 2024

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

Re: K232967

Trade/Device Name: VITEK 2 AST-Yeast Voriconazole (< 0.03125 -> 4 us/mL) Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: Class II Product Code: NGZ, LON, LRG, LTT, LTW Dated: May 7, 2024 Received: May 7, 2024

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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,

Natasha Griffin -S

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

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Indications for Use

510(k) Number (if known) K232967

Device Name VITEK 2 AST-Yeast Voriconazole (< 0.03125 - > 4 ug/mL)

Indications for Use (Describe)

Active in vitro and in clinical infections: Candida krusei Candida parapsilosis Candida tropicalis

The VITEK 2 Fungal Susceptibility Card is intended for use with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinicant yeasts to antifungal agents when used as instructed.

Type of Use (Select one or both, as applicable)
-------------------------------------------------	--

X 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-YS Voriconazole

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:	May 07, 2024
B. Device Name:
Formal/Trade Name:	VITEK® 2 AST-Yeast Voriconazole (≤ 0.03125-≥4µg/mL)
Classification Name:	21 CFR 866.1640Antimicrobial Susceptibility test powderProduct Code NGZ, LRG, LTT, LTW, LON
Common Name:	VITEK® 2 AST-YS Voriconazole
C. Predicate Device:	VITEK® 2 AST-Yeast Fluconazole (K213241)

D. 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() 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

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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-YS Voriconazole has the following concentrations in the card: 0.03125, 0.125, 0.25, 1, and 2 (equivalent standard method concentration by efficacy in ug/mL).

E. Substantial Equivalence Information

The similarities and differences of the VITEK 2 AST-YS Voriconazole when compared to the predicate device, VITEK 2 AST-YS Fluconazole (K213241), are described in the following table. The only difference between both devices are the Indications for Use and the breakpoints used to analyze the data performance. The below table provides the similarities and differences:

Item	Device:VITEK® 2 AST-YS Voriconazole(K232967)	Predicate:VITEK® 2 AST-YS Fluconazole(K213241)
Similarities
IntendedUse	VITEK 2 AST-Yeast Voriconazole isdesigned for antifungal susceptibilitytesting of Candida species and isintended for use with the VITEK 2and VITEK 2 Compact Systems as alaboratory aid in the determination ofin vitro susceptibility to antifungalagents. VITEK 2 AST-YeastVoriconazole is a quantitative test.Voriconazole has been shown to beactive against most strains of themicroorganisms listed below,according to the FDA label for thisantifungal.The VITEK 2 Fungal SusceptibilityCard is intended for use with theVITEK 2 Systems in clinicallaboratories as an in vitro test todetermine the susceptibility ofclinically significant yeasts toantifungal agents when used asinstructed.	VITEK 2 AST-Yeast Fluconazole isdesigned for antifungal susceptibilitytesting of Candida species and isintended for use with the VITEK 2and VITEK 2 Compact Systems as alaboratory aid in the determination ofin vitro susceptibility to antifungalagents. VITEK 2 AST-YeastFluconazole is a quantitative test.Fluconazole has been shown to beactive against most strains of themicroorganisms listed below,according to the FDA label for thisantifungal.The VITEK 2 Fungal SusceptibilityCard is intended for use with theVITEK 2 Systems in clinicallaboratories as an in vitro test todetermine the susceptibility ofclinically significant yeasts toantifungal agents when used asinstructed.
Test	Automated quantitative antimicrobial	Automated quantitative antimicrobial

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Methodo-logy	susceptibility test for use with theVITEK 2 and VITEK 2 CompactSystems to determine the in vitrosusceptibility of yeast.	susceptibility test for use with theVITEK 2 and VITEK 2 CompactSystems to determine the invitro susceptibility of yeast
Inoculum	Saline suspension of organism	Saline suspension of organism
Test Card	VITEK 2 Yeast Susceptibility TestCard	VITEK 2 Yeast Susceptibility Test Card
Instrument	VITEK 2 and VITEK 2 CompactSystems	VITEK 2 and VITEK 2 CompactSystems
AnalysisAlgorithms	Discriminant Analysis	Discriminant Analysis
Differences
AntifungalAgent	Voriconazole	Fluconazole
Anti-microbialConcentra-tions	0.03125, 0.125, 0.25, 1, 2	2, 4, 8, 16, 32, 64
Indicationsfor Use	Active in vitro and in clinicalinfections:Candida kruseiCandida parapsilosisCandida tropicalis	Active in vitro and in clinicalinfections:Candida albicansCandida parapsilosisCandida tropicalis

F. Intended Use:

Active in vitro and in clinical infections: Candida krusei Candida parapsilosis

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Candida tropicalis

G. Performance Overview:

VITEK® 2 AST-YS Voriconazole demonstrated substantially equivalent performance when compared with the CLSI broth microdilution 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 (Traditional 510[k]) presents data in support of VITEK® 2 AST-YS Voriconazole. 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- YS Voriconazole by comparing its performance with the CLSI broth microdilution reference method incubated for 24 hours (up to 48 hours that are not growing well). The data is representative of performance on both the VITEK® 2 and VITEK® 2 Compact instrument platforms.

VITEK® 2 AST-YS Voriconazole demonstrated acceptable performance as presented in the table below.

Antimicrobial	AntimicrobialCode	AntibioticVersion	Bp1	Comment	Essential Agreement% Error				Category Agreement% Error				%Repro- duc-ibilityy
					% EA	VME	ME	mE	% CA	VME	ME	mE
Voriconazole	VRC	vrc02n	CLSI(FDA)	#, EC.albicans *	(228/257)88.7	N/A	N/A	N/A	(221/257)86.0	(4/12)33.3	(3/237)1.3	(29/257)11.3	100
				#, EC.krusei	(76/76)100.0	N/A	N/A	N/A	(75/76)98.7	(0/0)0.0	(0/74)0.0	(1/76)1.3

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#, EC. parapsilosis	(70/74)94.6	N/A	N/A	N/A	(70/74)94.6	(0/1)0.0	(1/68)1.5	(3/74)4.1
#, EC. tropicalis	(85/87)97.7	N/A	N/A	N/A	(79/87)90.8	(0/2)0.0	(2/77)2.6	(6/87)6.9
VITEK® 2 Voriconazole MIC values for C. parapsilosistended to be in exact agreement or at least one doublingdilution higher than the reference MIC values. VoriconazoleMIC values for C. krusei tended to be in exact agreement orat least one doubling dilution lower than the reference MICvalues.*C. albicans is not an FDA Indicated for Use species. Analternative testing method should be performed prior to reportingresults.

1 Abbreviations - Bp = breakpoint committee; EA = essential agreement; CA = category agreement; VME=Very Major Error (susceptible result with resistant reference result); ME Major Error (resistant result with susceptible reference result); mE = minor Error (susceptible or resistant result with an intermediate reference result, or an intermediate result with a susceptible or resistant reference result).

= US Food and Drug Administration 510(k) cleared

CLSI = Clinical and Laboratory Standards Institute

E = External performance data

N/A = Not applicable

Reproducibility and Quality Control demonstrated acceptable results.

H. Conclusion:

The performance data presented in this submission support a substantial equivalence decision. VITEK® 2 AST-YS Voriconazole (≤ 0.03215 - ≥4 µg/mL) is substantially equivalent to VITEK® 2 AST-YS Fluconazole (K213241).

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.

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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.

Regulation Number and Section

§ 866.1640 Antimicrobial susceptibility test powder.

(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).