VITEK® 2 AST-Yeast Fluconazole 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 Fluconazole is a quantitative test. Fluconazole 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 albicans 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 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-YS Fluconazole has the following concentrations in the card: 2, 4, 8, 16, 32, and 64 (equivalent standard method concentration by efficacy in us/mL).

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the VITEK® 2 AST-Yeast Fluconazole device, based on the provided document:

Acceptance Criteria and Device Performance

Criteria Type	Acceptance Criteria	Reported Device Performance
Overall Essential Agreement (EA)	Not explicitly stated as a numerical threshold in the provided text, but the study was designed to confirm "acceptability" by comparison to the CLSI broth microdilution reference method. Commonly, 90% or higher is expected for FDA clearance of AST systems.	96.2% overall Essential Agreement with the CLSI broth microdilution reference method when testing C. albicans, C. parapsilosis, and C. tropicalis. Specifically, for Candida parapsilosis, an overall essential agreement rate of 99.1% was observed.
Overall Category Agreement (CA)	Not explicitly stated as a numerical threshold in the provided text, but the study was designed to confirm "acceptability" by comparison to the CLSI broth microdilution reference method. Commonly, 90% or higher is expected for FDA clearance of AST systems.	93.7% overall Category Agreement with the CLSI broth microdilution reference method when testing C. albicans, C. parapsilosis, and C. tropicalis. Specifically, for Candida parapsilosis, an overall category agreement rate of 94.5% was observed.
Very Major Errors (VME)	Not explicitly stated as a numerical threshold, but VME are generally expected to be very low, typically < 1.5% or 3%.	7.7% (2/26) for Fluconazole overall. For Candida parapsilosis, two VME were observed out of 14 results, with one of these

| Major Errors (ME) | Not explicitly stated as a numerical threshold, but ME are generally expected to be low, typically < 3%. | 3.0% (12/398) for Fluconazole overall. |
| Minor Errors (mE) | Not explicitly stated as a numerical threshold, but mE are generally expected to be low, typically < 10%. | 3.2% (14/442) for Fluconazole overall. |
| Reproducibility | "Acceptable results" | 100% Reproducibility reported for Fluconazole. (The table shows "%Reproducibility" column with "100" for Fluconazole, though the full context of this 100% isn't detailed in what "reproducibility" exactly refers to within this specific table line item). The text also states "Reproducibility and Quality Control demonstrated acceptable results." |

Note on Acceptance Criteria: While explicit numerical thresholds for EA, CA, VME, ME, and mE are not directly listed as "acceptance criteria" in the provided text, these metrics are standard for evaluating AST systems. The statement "VITEK® 2 AST-YS Fluconazole demonstrated acceptable performance" in conjunction with the reported percentages implies that these percentages met the required performance standards for substantial equivalence. The document references the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)," which would contain the specific performance criteria.

Study Details

Sample Size Used for the Test Set and Data Provenance:
- Sample Size: The device performance table indicates a total of 442 isolates tested (denominator for EA and CA percentages). For VME analysis, 26 susceptible reference results (total) and for ME analysis, 398 instances (total, meaning the total population excluding those susceptible) were used. The number of Candida parapsilosis specific results cited are 14.
- Data Provenance: The external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains. The document does not specify the country of origin but implies clinical relevance. The study appears to be prospective or designed to simulate prospective use for evaluation, as it uses clinical and challenge strains. It is an "external evaluation," which typically means the testing was done at multiple sites.
Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- Not Applicable. This is an in vitro diagnostic device for antimicrobial susceptibility testing. The ground truth is established by a reference laboratory method (CLSI broth microdilution), not by human experts. The "experts" in this context would be laboratory personnel meticulously performing the reference method.
Adjudication Method for the Test Set:
- Not Applicable. As the ground truth is established by a quantitative laboratory method (CLSI broth microdilution), there is no human adjudication process involved for ambiguous interpretations. The comparison is directly between the MIC values and categorical interpretations (S, I, R) from the device and the reference method. Errors (VME, ME, mE) are calculated based on discrepancies from the reference method.
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No. This is an in vitro diagnostic device, not an imaging or interpretive device that relies on human readers. Therefore, an MRMC study is not relevant or performed for this type of product. The "readers" are the automated VITEK® 2 systems themselves.
Standalone (Algorithm-Only) Performance:
- Yes. The study evaluates the performance of the VITEK® 2 AST-YS Fluconazole device in conjunction with the VITEK® 2 and VITEK® 2 Compact Systems. This is a standalone evaluation of the integrated system (test card + instrument + embedded analysis algorithms) against the CLSI reference method, without a human in the loop for interpretation of the raw data generated by the system. The system automatically generates the MIC value and interpretive category.
Type of Ground Truth Used:
- CLSI broth microdilution reference method. This is a universally accepted, gold standard laboratory method for determining minimum inhibitory concentrations (MICs) of antifungal agents. The reference method was incubated at 24 hours (or up to 48 hours for isolates with slow growth).
Sample Size for the Training Set:
- Not explicitly stated in the provided document. The document details the "Premarket Notification (Special 510[k]) presents data in support of VITEK® 2 AST-YS Fluconazole." This implies that the data presented here is for the validation or test set, used to demonstrate substantial equivalence. The VITEK® 2 system's "Discriminant Analysis" algorithms would have been developed and refined (trained) on prior datasets, but the size and nature of those training sets are not part of this 510(k) summary. These types of devices often use extensive historical isolate collections for algorithm development.
How the Ground Truth for the Training Set Was Established:
- Not explicitly stated in the provided document for the training set. However, given the nature of the device and the reference method used for the test set, it is highly probable that the ground truth for any training sets used for the "Discriminant Analysis" algorithms would also have been established via the CLSI broth microdilution reference method or similar established laboratory methods.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is a symbol representing the Department of Health & Human Services - USA. To the right of this symbol, there is the FDA logo in blue, with the words "U.S. FOOD & DRUG" above the word "ADMINISTRATION".

February 25, 2022

BioMerieux, Inc. Esther Hernandez Regulatory Affairs Specialist 595 Anglum Road Hazelwood, Missouri 63042

Re: K213241

Trade/Device Name: VITEK 2 AST-Yeast Fluconazole (<=0.5->=64 ug/mL), VITEK 2 AST-YS Fluconazole (<= 0.5->=64 ug/mL), VITEK 2 AST-YS Fluconazole 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 29, 2021 Received: September 30, 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

{1}------------------------------------------------

requirements, including, but not limited to: registration and listing (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,

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 Ouality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known)

K213241

Device Name

VITEK® 2 AST-Yeast Fluconazole (≤0.5 - ≥64 ug/mL)

Indications for Use (Describe)

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

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995,

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

510(k) SUMMARY

VITEK® 2 AST-YS Fluconazole

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 29, 2021
B. Device Name:
Formal/Trade Name:	VITEK® 2 AST-Yeast Fluconazole (≤ 0.5 – ≥64 µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code LON
Common Name:	VITEK® 2 AST-YS Fluconazole
C. Predicate Device:	VITEK® 2 AST-Yeast Fluconazole (K133817)

D. Device Description:

{4}------------------------------------------------

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 Fluconazole has the following concentrations in the card: 2, 4, 8, 16, 32, and 64 (equivalent standard method concentration by efficacy in us/mL).

E. Substantial Equivalence Information

The similarities and differences of the VITEK 2 AST-YS Fluconazole when compared to the predicate device, VITEK 2 AST-YS Fluconazole (K133817), 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 Fluconazole	Predicate:VITEK® 2 AST-GN Fluconazole(K133817)
Intended Use	VITEK® 2 AST-Yeast Fluconazoleis designed for antifungalsusceptibility testing of Candidaspecies and is intended for use withthe VITEK® 2 and VITEK® 2Compact Systems as a laboratory aidin the determination of in vitrosusceptibility to antifungal agents.VITEK® 2 AST-Yeast Fluconazoleis a quantitative test. Fluconazolehas been shown to be active againstmost strains of the microorganismslisted below, according to the FDAlabel for this antifungal.Active in vitro and in clinicalinfections:Candida albicansCandida parapsilosisCandida tropicalisThe VITEK® 2 Fungal SusceptibilityCard is intended for use with theVITEK® 2 Systems in clinicallaboratories as an in vitro test todetermine the susceptibility of	VITEK® 2 AST-Yeast Fluconazole isdesigned for antifungal susceptibilitytesting of Candida species and is aquantitative test intended for use withthe VITEK® 2 and VITEK® 2Compact Systems as a laboratory aidin the determination of in vitrosusceptibility to antifungal agents.VITEK® 2 AST-Yeast Fluconazolehas been shown to be active againstmost strains of the microorganismslisted below, according to the FDAlabel for this antifungal.Active in vitro and in clinicalinfections:Candida albicansCandida parapsilosisCandida tropicalisThe following in vitro data areavailable, but their clinicalsignificance is unknown:Candida dubliniensisCandida guilliermondiiCandida lusitaniae

{5}------------------------------------------------

	clinically significant yeasts toantifungal agents when used asinstructed.	The VITEK® 2 AntimicrobialSusceptibility Test (AST) is intended tofor use with the VITEK 2 Systems forthe automated quantitative or qualitativesusceptibility testing of isolated coloniesfor most clinically significant aerobicGram-negative bacilli, Staphylococcusspp., Enterococcus spp., Streptococcusspp. and clinical significant yeast.
Test Methodology	Automated quantitative antimicrobialsusceptibility test for use with theVITEK® 2 and VITEK® 2 CompactSystems to determine the in vitrosusceptibility of yeast.	Same
Antimicrobial Agent	Fluconazole	Same
Inoculum	Saline suspension of organism	Same
Test Card	VITEK® 2 Yeast (AST) SusceptibilityTest Card	Same
Analysis Algorithms	Discriminant Analysis	Same
Instrument	VITEK® 2 and VITEK® 2 CompactSystems	Same
Concentrations	2, 4, 8, 16, 32, 64	Same
	Differences
Indications for Use	Candida albicansCandida parapsilosisCandida tropicalis	Candida albicansCandida parapsilosisCandida tropicalisCandida dubliniensisCandida guilliermondiiCandida lusitaniae
Breakpoints for Candidaspp.	Candida albicans: ≤2 (S), 4 (I), ≥8 (R)Candida parapsilosis: ≤2 (S), 4 (I),≥8 (R)Candida tropicalis: ≤2 (S), 4 (I), ≥8(R)	Candida spp.: ≤8 (S), 16-32 (I), ≥64(R)

F. Intended Use:

VITEK® 2 AST-Yeast Fluconazole 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 antifiungal agents. VITEK® 2 AST-Yeast Fluconazole is a quantitative test. Fluconazole 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:

{6}------------------------------------------------

Image /page/6/Picture/0 description: The image shows the logo for bioMerieux. The logo consists of a stylized circular graphic with vertical lines on the left half and a curved line extending from the right side. Below the graphic, the word "BIOMERIEUX" is written in a sans-serif font, with the letters evenly spaced.

Candida albicans 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 veasts to antifungal agents when used as instructed.

G. Performance Overview:

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

VITEK® 2 AST-YS Fluconazole demonstrated acceptable performance of 96.2% overall Essential Agreement and 93.7% overall Category Agreement with the reference method when testing C. albicans. C. parapsilosis, and C. tropicalis.

Antimicrobial	Anti-microbialCode	AntibioticVersion	Bp1	Comment	Essential Agreement				Category Agreement				%Repro-ducibility
					% EA	VME	ME	mE	% CA	VME	ME	mE
Fluconazole	FLU	flu02n	CLSI(FDA)	#, E,	(425/442)96.2	N/A	N/A	N/A	(414/442)93.7	(2/26)7.7	(12/398)3.0	(14/442)3.2	100
An overall essential agreement rate of 99.1% and an overall categoryagreement rate of 94.5% were observed for Candida parapsilosis whentested with VITEK 2 Fluconazole. Compared to the reference brothmicrodilution, two of 14 results for Candida parapsilosis (one of whichwas in essential agreement) resulted in very major errors.VITEK 2 Fluconazole MIC values tended to be in exact agreement or atleast one doubling dilution higher when testing C. albicans, Cparapsilosis, and C. tropicalis compared to the broth microdilutionreference method.

{7}------------------------------------------------

Abbreviations - Bo = breakpoint committee; EA = essential agreement; VME = Very Major Error(susceptbleresult withesistantreferenceresult; ME Major Enror (resistant with succeptible reference result); mE = minor (susceptible or resistant result, or an intermediate result, or an internediate result, or an internedia 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-Yeast Fluconazole (≤ 0.5 –>64 µg/mL) is substantially equivalent to VITEK® 2 AST-Yeast Fluconazole (K133817).

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.

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.”