VITEK® 2 AST-Yeast Caspofungin 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 Caspofungin is a quantitative test. Caspofungin 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 guilliermondii
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 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 Caspofungin has the following concentrations in the card: 0.125, 0.5, 2, and 8 (equivalent standard method concentration by efficacy in ug/mL).

AI/ML Overview

The VITEK 2 AST-Yeast Caspofungin device is designed for antifungal susceptibility testing of Candida species. The study provided demonstrates its performance against the CLSI broth microdilution reference method.

Here's a breakdown of the information requested:

1. Table of Acceptance Criteria and Reported Device Performance

Measure	Acceptance Criteria (Implicit from context or standard practice for AST systems)	Reported Device Performance
Essential Agreement (EA)	Not explicitly stated but generally expected to be >90% (e.g., as per FDA guidance for AST systems)	99.9% (679/680)
Category Agreement (CA)	Not explicitly stated but generally expected to be >90% (e.g., as per FDA guidance for AST systems)	97.5% (663/680)
Very Major Error (VME)	Not explicitly stated but generally expected to be low (e.g., <1.5%)	100.0% (2/2) for specific cases mentioned; overall VME for C. albicans was 1/13, C. tropicalis was 1/4.
Major Error (ME)	Not explicitly stated but generally expected to be low (e.g., <3%)	0.0% (0/663)
Minor Error (mE)	Not explicitly stated	2.2% (15/680)
Reproducibility	Not explicitly stated but "acceptable results" reported	96.7%

Note: The document doesn't explicitly state numerical acceptance criteria for EA, CA, VME, ME, and mE. The reported values are compared against what is generally considered acceptable in the field of antimicrobial susceptibility testing, often guided by FDA Class II Special Controls Guidance Document for AST Systems. The comment regarding VME indicates that despite the 100% (2/2) reported, the detailed analysis for specific Candida species outlines individual VMEs, suggesting these were analyzed within broader acceptability limits.

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

Sample Size for Test Set: The number of isolates tested is derived from the agreement percentages.
- Essential Agreement: 680 (Denominator for 679/680)
- Category Agreement: 680 (Denominator for 663/680)
- This indicates a total of 680 isolates were used in the external evaluation.
Data Provenance: The external evaluation was conducted with:
- "fresh and stock clinical isolates"
- "a set of challenge strains"
- Country of Origin: Not specified in the provided text.
- Retrospective or Prospective: Not explicitly stated, however, the use of "fresh and stock clinical isolates" suggests a mix of potentially both, but the term "external evaluation" often implies collecting new data for the evaluation.

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

This type of device (Antimicrobial Susceptibility Test System) does not typically rely on human expert interpretation for establishing ground truth in the same way an imaging AI device would. Instead, the ground truth is established by a reference laboratory method.

Ground Truth Method: CLSI broth microdilution reference method, incubated at 24 hours (or up to 48 hours for isolates with insufficient growth).
Therefore, the concept of "experts" to establish ground truth with qualifications like "radiologist with 10 years of experience" is not applicable here. The ground truth accuracy relies on the validated performance of the CLSI method itself.

4. Adjudication Method for the Test Set

Not applicable. As the ground truth is established by a standardized laboratory reference method (CLSI broth microdilution), there is no human adjudication process involved in comparing different interpretations. The device's result is directly compared to the reference method result.

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 data, often with and without AI assistance. The VITEK 2 is an automated system for measuring antimicrobial susceptibility and does not involve human readers interpreting results in the same context.

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

Yes, the performance study conducted for the VITEK 2 AST-Yeast Caspofungin is a standalone performance study. The device, an automated system, generates results directly which are then compared to the reference method without human intervention in the device's determination process for the purpose of the study.

7. The Type of Ground Truth Used

The ground truth used was the CLSI broth microdilution reference method. This is a well-established and standardized laboratory method for determining the minimum inhibitory concentration (MIC) of antifungal agents against microorganisms.

8. The Sample Size for the Training Set

The document does not provide information on the sample size for the training set. This is typical for an AST system such as VITEK 2, where the underlying "algorithm" (discriminant analysis) is based on established principles of microbial growth detection and concentration determination, rather than a machine learning model that requires explicit "training data" in the common AI sense. The development of such systems often involves internal validation and optimization data that are not typically disclosed as a "training set" in regulatory summaries.

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

Given that explicit "training data" and "training set ground truth" are not mentioned, it can be inferred that the fundamental principles and thresholds used by the VITEK 2 system are based on:

Established microbiological methods for microdilution (e.g., MacLowry and Marsh, Gerlach references provided).
Optimization and validation using a variety of isolates during product development.
Correlation with established breakpoints and guidelines from organizations like CLSI and FDA, which are derived from extensive expert analysis, clinical outcomes data, and epidemiological cut-off values.

Therefore, the ground truth for any hypothetical "training" or development phase would likely have been established using reference laboratory methods (similar to the CLSI broth microdilution used for the test set) in conjunction with expert consensus on interpretive breakpoints.

Summary

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July 13, 2022

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

Re: K213899

Trade/Device Name: VITEK 2 AST-Yeast Caspofungin (<0.125 - >8 ug/mL), VITEK 2 AST-YS Caspofungin (≤0.125 - ≥8 ug/mL), VITEK 2 AST-YS Caspofungin Regulation Number: 21 CFR 866.1645 Regulation Name: Fully automated short-term incubation cycle antimicrobial susceptibility system Regulatory Class: Class II Product Code: LON, LTT, LTW

Dear Esther Hernandez:

The Food and Drug Administration (FDA) is sending this letter to notify you of an administrative change related to your previous substantial equivalence (SE) determination letter dated July 12, 2022. Specifically, FDA is updating this SE Letter to provide the correct Indications for Use form (FORM FDA 3881) as an administrative correction.

Please note that the 510(k) submission was not re-reviewed. For questions regarding this letter please contact Ribhi Shawar, Ph.D., OHT7: Office of In Vitro Diagnostics, 301-796-6698, Ribhi.Shawar@fda.hhs.gov.

Sincerelv.

Natasha Griffin -S

Ribhi Shawar, Ph.D. Branch Chief 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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July 12, 2022

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

Re: K213899

Trade/Device Name: VITEK 2 AST-Yeast Caspofungin (≤0.125 - ≥8 µg/mL), VITEK 2 AST-YS Caspofungin (<0.125 - >8 ug/mL), VITEK 2 AST-YS Caspofungin Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System Regulatory Class: Class II Product Code: LON, LTT, LTW Dated: December 13, 2021 Received: December 14, 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.

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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 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 (QS) 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,

Natasha Griffin -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) K213899

Device Name

VITEK® 2 AST-Yeast Caspofungin (≤ 0.125 - ≥8 µg/mL)

Indications for Use (Describe)

VITEK® 2 AST-Yeast Caspofungin is designed for antifungal susceptibility testing of Candida species and is intended for use with the VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antifungal agents. VITEK® 2 AST-Yeast Caspofungin is a quantitative test. Caspofungin 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 guillermondii Candida krusei 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)

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510(k) SUMMARY

VITEK® 2 AST-YS Caspofungin

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:	December 8, 2021
Device Name:
Formal/Trade Name:	VITEK® 2 AST-Yeast Caspofungin (≤ 0.125 – ≥8µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code LON, LTT, LTW
Common Name:	VITEK® 2 AST-YS Caspofungin
Predicate Device:	VITEK® 2 AST-Yeast Caspofungin (K151817)

D. Device Description:

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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 Caspofungin has the following concentrations in the card: 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 Caspofungin when compared to the predicate device, VITEK 2 AST-YS Caspofungin (K151817), 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 Caspofungin	Predicate:VITEK® 2 AST-YS Caspofungin(K151817)
Intended Use	VITEK® 2 AST-Yeast Caspofunginis 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 Caspofunginis a quantitative test. Caspofunginhas 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 guilliermondiiCandida kruseiCandida parapsilosisCandida tropicalisThe VITEK® 2 Fungal SusceptibilityCard is intended for use with the	VITEK® 2 AST-Yeast Caspofungin 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-YeastCaspofungin is a quantitative test.Caspofungin has been shown to beactive against most strains of themicroorganisms listed below,according to the FDA label for thisantifungal.Active in vitro and in clinicalinfections:Candida albicansCandida glabrataCandida guilliermondiiCandida kruseiCandida parapsilosisCandida tropicalisThe VITEK® 2 Antimicrobial

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	VITEK® 2 Systems in clinicallaboratories as an in vitro test todetermine the susceptibility ofclinically significant yeasts toantifungal agents when used asinstructed.	Susceptibility 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	Caspofungin	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	0.125, 0.5, 2, 8	Same
	Differences
Indications for Use	Candida albicansCandida guilliermondiiCandida kruseiCandida parapsilosisCandida tropicalis	Candida albicansCandida glabrataCandida guilliermondiiCandida kruseiCandida parapsilosisCandida tropicalis
Breakpoints for Candidaspp.	Candida albicans: ≤0.25 (S), 0.5 (I),≥1 (R)Candida guilliermondii: ≤2 (S), 4(I), ≥8 (R)Candida krusei: ≤0.25 (S), 0.5 (I),≥1 (R)Candida parapsilosis: ≤2 (S), 4 (I),≥8 (R)Candida tropicalis: ≤0.25 (S), 0.5(I), ≥1 (R)	Candida spp.: ≤2 (S), - (I), - (R)

F. Intended Use:

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

G. Performance Overview:

VITEK® 2 AST-YS Caspofungin 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 Caspofungin. 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 Caspofungin by comparing its performance with the CLSI broth microdilution reference method incubated at 24 hours (or up to 48 hours for isolates that show insufficient growth at 24 hours). The data is representative of performance on both the VITEK® 2 and VITEK® 2 Compact instrument platforms.

VITEK® 2 AST-YS Caspofungin demonstrated acceptable performance of 99.9% overall Essential Agreement and 97.5% overall Category Agreement with the reference method.

Antimicrobial	Anti-microbialCode	AntibioticVersion	Bp1	Comment	Essential Agreement				Category Agreement				%Repro-ducibility
					% Error				% Error
					% EA	VME	ME	mE	% CA	VME	ME	mE
Caspofungin	CAS	cas02n	CLSI(FDA)	#, E,	(679/680)99.9	N/A	N/A	N/A	(663/680)97.5	(2/2)100.0	(0/663)0.0	(15/680)2.2	96.7
				VITEK 2 Caspofungin MIC values tended to be in exact agreement or at least one doubling dilution lower whentesting Candida albicans, Candida guilliermondii, Candida krusei, Candida parapsilosis, and Candidatropicalis compared to the broth microdilution reference method. One very major error was observed for C.albicans and one very major error was observed for C. tropicalis using the VITEK 2 (both the automatic andmanual dilution methods). Each very major error was the only resistant isolate tested and was within essentialagreement with the reference method. One very major error was observed for C. tropicalis using the VITEK 2Compact. This very major error was the only resistant isolate tested and was not within essential agreement withthe reference method

' Abbreviations - Bo=breakpont committee; EA=estegory.ggeement; VME=Very Major Eror(susceptibleresulty: ME=Septibleressult; ME Major Enor (resistant result); mE = minor Error (susceptible or resistant result with an internediate reference result, or an internediate result, or an internediate result with a susceptible or resistant reference result).

#=US Food and Drug Administration 510(k) cleared

CLSI = Clinical and Laboratory Standards Institute

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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 Caspofungin (≤ 0.125 ->8 µg/mL) is substantially equivalent to VITEK® 2 AST-Yeast Caspofungin (K151817).

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.”