VITEK 2 AST-Yeast Anidulafungin 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 Anidulafungin is a quantitative test. Anidulafungin 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 glabrata Candida parapsilosis Candida tropicalis

In vitro data are available, but clinical significance is unknown: Candida guillermondii Candida krusei

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 Anidulafungin has the following concentrations in the card: 0.0625, 0.125, 0.5, 2, and 8 (equivalent standard method concentration by efficacy in ug/mL).

AI/ML Overview

Here's an analysis of the acceptance criteria and the study proving the device meets those criteria, based on the provided text.

Device: VITEK 2 AST-Yeast Anidulafungin

Indications for Use: Antifungal susceptibility testing of Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. guilliermondii, C. krusei) as a laboratory aid in determining in vitro susceptibility to antifungal agents.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly state the acceptance criteria in a separate table directly defining thresholds for Essential Agreement (EA), Category Agreement (CA), or error rates (VME, ME, mE) that the device must meet for approval. Instead, it presents the results of the performance study and implies that these results were deemed "acceptable" by the FDA. The performance is compared to 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)". This guidance document would contain the specific acceptance criteria.

However, based on the presented "Performance Overview" (Page 7) and the overall context of AST device approvals, typical acceptance criteria for Essential Agreement and Category Agreement are usually in the range of 90-95% or higher, with Very Major Error (VME) and Major Error (ME) rates usually being low (e.g., <3% or <1.5%).

Here's the reported device performance:

Antimicrobial	Species	Essential Agreement (% EA)	Category Agreement (% CA)	VME (%)	ME (%)	mE (%)	Reproducibility (%)
Anidulafungin	C. albicans	100% (206/206)	100% (206/206)	0.0% (0/0)	0.0% (0/206)	0.0% (0/206)	98.15%
	C. glabrata	97.4% (113/116)	98.3% (114/116)	0.0% (0/4)	0.9% (1/111)	0.9% (1/116)
	C. guilliermondii	90.5% (19/21)	90.5% (19/21)	0.0% (0/0)	0.0% (0/20)	9.5% (2/21)
	C. krusei	98.6% (68/69)	100% (69/69)	0.0% (0/0)	0.0% (0/69)	0.0% (0/69)
	C. parapsilosis	100% (72/72)	86.1% (62/72)	0.0% (0/0)	1.6% (1/62)	12.5% (9/72)
	C. tropicalis	97.5% (79/81)	96.3% (78/81)	33.3% (1/3)	0.0% (0/77)	2.5% (2/81)

Note on C. tropicalis VME: The document specifically highlights: "When evaluating VITEK 2 AST-YS Anidulafungin, there was a single very major error (VMJ) that resulted in an unacceptable VMJ rate of 33.3% (1/3) with C. tropicalis." Despite this, the overall conclusion states "VITEK® 2 AST-YS Anidulafungin demonstrated acceptable performance." This suggests that either the unacceptably high VME for C. tropicalis was mitigated by other factors (e.g., small sample size for VME calculation, or specific post-market surveillance requirements), or it points to a known limitation that the FDA found acceptable for clearance under the stated conditions.

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

Sample Size for Test Set:
- C. albicans: 206 isolates
- C. glabrata: 116 isolates
- C. guilliermondii: 21 isolates
- C. krusei: 69 isolates
- C. parapsilosis: 72 isolates
- C. tropicalis: 81 isolates
- Total Isolates: 565 isolates across the specified Candida species.
Data Provenance: The study involved an "external evaluation" conducted 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 or whether it was retrospective or prospective. Typically, "clinical isolates" imply prospective collection from real patient samples, and "stock isolates" could be reference strains or previously collected clinical isolates. "External evaluation" implies data was collected from multiple sites, which is standard for clinical trials of this nature.

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

This information is not provided in the document. For antimicrobial susceptibility testing (AST) devices, the ground truth is established by a reference method (here, the CLSI broth microdilution reference method), not by human expert interpretation of images or data in a consensus setting.

4. Adjudication Method for the Test Set

Not applicable. The ground truth for AST devices is established by a standardized laboratory reference method (CLSI broth microdilution), not through expert adjudication of ambiguous cases like in imaging studies.

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

No, an MRMC comparative effectiveness study was not performed. This type of study (comparing human readers with and without AI assistance on diagnostic tasks) is not relevant for an automated antimicrobial susceptibility testing device like the VITEK 2 AST-Yeast Anidulafungin. This device provides quantitative MIC values and interpretive categories, not an interpretation of a medical image or clinical data that would involve human readers.

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

Yes, the performance study effectively evaluates the standalone performance of the VITEK 2 AST-Yeast Anidulafungin system. The device automatically reads and interprets the growth patterns in the microdilution wells to generate MIC values and interpretive categories (Susceptible, Intermediate, Resistant). This automated result is then compared directly to the established ground truth (CLSI broth microdilution reference method). While human operators physically load the cards, the core performance being evaluated is the device's automated analysis.

7. The Type of Ground Truth Used

The type of ground truth used was the CLSI broth microdilution reference method (Clinical and Laboratory Standards Institute). This is a well-established, standardized, and validated laboratory method for determining the minimum inhibitory concentration (MIC) of an antimicrobial agent against a microorganism. The reference method results serve as the "gold standard" for accuracy in AST device performance studies.

8. The Sample Size for the Training Set

The document does not provide specific details about the training set size. The device uses "Discriminant Analysis" algorithms. Typically, for a device like this, the algorithms would be developed and refined using a large dataset of isolates with known reference MICs to optimize the mapping between the device's optical measurements and the true MICs. However, the exact size of this internal development/training set is not disclosed in this summary. The provided performance data (the "test set") is for validation purposes, distinct from the training set.

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

While not explicitly stated for a "training set" in this document, it is highly probable that the ground truth for any isolates used during the development and training of the VITEK 2 system's algorithms would also have been established using the CLSI broth microdilution reference method or similar highly standardized and validated laboratory methods, consistent with industry best practices for AST device development. This ensures that the algorithm learns from accurate data.

Summary

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June 7, 2024

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

Re: K232963

Trade/Device Name: VITEK 2 AST-Yeast Anidulafungin (< 0.015 -> 8 us/mL) Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: Class II Product Code: NGZ, LTT, LTW, LRG, LON Dated: September 21, 2023 Received: September 21, 2023

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/cdrb/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 QS 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 (QS) 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,

Ribhi Shawar -S

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) K232963

Device Name VITEK 2 AST-Yeast Anidulafungin (< 0.015 - > 8 ug/mL)

Indications for Use (Describe)

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

In vitro data are available, but clinical significance is unknown: Candida guillermondii Candida krusei

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)
区 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 Anidulafungin

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:	02 May, 2024
B. Device Name:	Formal/Trade Name:	VITEK® 2 AST-Yeast Anidulafungin (≤ 0.015 – ≥8 $ \mu $ g/mL)
	Classification Name:	21 CFR 866.1640Antimicrobial susceptibility test powderProduct Code NGZ, LRG, LTT, LTW, LON
	Common Name:	VITEK® 2 AST-YS Anidulafungin
C. Predicate Device:	VITEK® 2 AST-Yeast Caspofungin (K213899)

D. Device Description:

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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 Anidulafungin has the following concentrations in the card: 0.0625, 0.125, 0.5, 2, and 8 (equivalent standard method concentration by efficacy in ug/mL).

E. Substantial Equivalence Information

The similarities and differences of the VITEK 2 AST-YS Anidulafungin when compared to the predicate device, VITEK 2 AST-YS Caspofungin (K213899), 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 Anidulafungin(K232963)	Predicate:VITEK® 2 AST-YS Caspofungin(K213899)
Similarities
IntendedUse	VITEK 2 AST-Yeast Anidulafunginis designed for antifungalsusceptibility testing of Candidaspecies and is intended for use withthe VITEK 2 and VITEK 2 CompactSystems as a laboratory aid in thedetermination of in vitrosusceptibility to antifungal agents.VITEK 2 AST-Yeast Anidulafunginis a quantitative test. Anidulafunginhas been shown to be active againstmost strains of the microorganismslisted below, according to the FDAlabel for this antifungal.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 Caspofungin isdesigned for antifungal susceptibilitytesting of Candida species and isintended for use with the VITEK 2 andVITEK 2 Compact Systems as alaboratory aid in the determination of invitro susceptibility to antifungal agents.VITEK 2 AST-Yeast Caspofungin is aquantitative test. Caspofungin has beenshown to be active against most strainsof the microorganisms listed below,according to the FDA label for thisantifungal.The VITEK 2 Fungal SusceptibilityCard is intended for use with the VITEK2 Systems in clinical laboratories as anin vitro test to determine thesusceptibility of clinically significantyeasts to antifungal agents when used asinstructed.

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TestMethodology	Automated quantitative antimicrobialsusceptibility test for use with theVITEK 2 and VITEK 2 CompactSystems to determine the in vitrosusceptibility of yeast.	Automated quantitative antimicrobialsusceptibility test for use with the VITEK2 and VITEK 2 Compact Systems todetermine the in vitro susceptibility ofyeast.
Inoculum	Saline suspension of organism	Saline suspension of organism
Test Card	VITEK 2 Yeast Susceptibility Test Card	VITEK 2 Yeast Susceptibility Test Card
Instrument	VITEK 2 and VITEK 2 CompactSystems	VITEK 2 and VITEK 2 Compact Systems
AnalysisAlgorithms	Discriminant Analysis	Discriminant Analysis
Differences
AntifungalAgent	Anidulafungin	Caspofungin
AntimicrobialConcentrations	0.0625, 0.125, 0.5, 2, 8	0.125, 0.5, 2, 8
ClaimedSpecies	Active in vitro and in clinicalinfections:Candida albicansCandida glabrataCandida parapsilosisCandida tropicalisIn vitro data are available, but clinicalsignificance is unknown:Candida guilliermondiiCandida krusei	Active in vitro and in clinical infections:Candida albicansCandida guilliermondiiCandida kruseiCandida parapsilosisCandida tropicalis

F. Intended Use:

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VITEK® 2 AST-Yeast Anidulafungin is designed for antifungal susceptibility testing of Candida species and is intended for use with the VITEK® 2 Systems as a laboratory aid in the determination of in vitro susceptibility to antifungal agents. VITEK 2 AST-Yeast Anidulafungin is a quantitative test. Anidulafungin 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 glabrata Candida parapsilosis Candida tropicalis

In vitro data are available, but clinical significance is unknown: Candida guilliermondii Candida krusei

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.

G. Performance Overview:

VITEK® 2 AST-YS Anidulafungin 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 Anidulafungin. 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 Anidulafungin by comparing its performance with the CLSI broth microdilution reference method incubated for 24 hours for isolates 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 Anidulafungin demonstrated acceptable performance as presented in the table below.

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Antimicrobial	Antimicrobial Code	Antibiotic Version	Bp1	Comment	Essential Agreement			Category Agreement				% Reproducibility
					% EA	VME	ME	mE	% CA	VME	ME	mE
Anidulafungin	ANI	ani01n	CLSI (FDA)	#, EC. albicans	(206/206)100	N/A	N/A	N/A	(206/206)100	(0/0)0.0	(0/206)0.0	(0/206)0.0	98.15
				#, EC. glabrata	(113/116)97.4	N/A	N/A	N/A	(114/116)98.3	(0/4)0.0	(1/111)0.9	(1/116)0.9
				#, EC. guilliermondii	(19/21)90.5	N/A	N/A	N/A	(19/21)90.5	(0/0)0.0	(0/20)0.0	(2/21)9.5
				#, EC. krusei	(68/69)98.6	N/A	N/A	N/A	(69/69)100	(0/0)0.0	(0/69)0.0	(0/69)0.0
				#, EC. parapsilosis	(72/72)100	N/A	N/A	N/A	(62/72)86.1	(0/0)0.0	(1/62)1.6	(9/72)12.5
				#, EC. tropicalis	(79/81)97.5	N/A	N/A	N/A	(78/81)96.3	(1/3)33.3*	(0/77)0.0	(2/81)2.5
VITEK® 2 Anidulafungin MIC values for C. albicans tended to be inexact agreement or at least one doubling dilution lower than thereference MIC values. Anidulafungin MIC values for C. glabrata andC. krusei tended to be in exact agreement or at least one doublingdilution higher than the reference MIC values.*When evaluating VITEK 2 AST-YS Anidulafungin, there was asingle very major error (VMJ) that resulted in an unacceptable VMJrate of 33.3% (1/3) with C. tropicalis .

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

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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 Anidulafungin (≤0.015 –>8 µg/mL) is substantially equivalent to VITEK® 2 AST-YS Caspofungin (K213899).

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

§ 866.1640 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).