VITEK® 2 AST- Gram Positive Clindamycin Resistance is designed for antimicrobial susceptibility testing of Staphylococcus aureus, Staphylococcus lugdunensis, and Coagulase Negative Staphylococcus spp. VITEK® 2 AST- Gram Positive Inducible Clindamycin Resistance is a qualitative test. It is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents.

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic Gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and yeast.

Device Description

The VITEK® 2 AST Cards are essentially miniaturized versions of the doubling dilution technique for determining the minimum inhibitory concentration (MIC) microdilution methodology. The isolate to be tested is diluted to a standardized concentration in 0.45 - 0.50% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling and sealing operation. The VITEK® 2 monitors the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card.

AI/ML Overview

The provided text describes the acceptance criteria and the study that proves the device meets the acceptance criteria for the VITEK® 2 AST-Gram Positive Inducible Clindamycin Resistance system.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for antimicrobial susceptibility test (AST) systems are typically defined by specific percentages for Essential Agreement (%EA), Category Agreement (%CA), Very Major Errors (VME), Major Errors (ME), and Minor Errors (mE). While the table in the document only explicitly lists values for %CA, VME, ME, and mE under "Overall Performance" (implying these are the performance metrics assessed against the reference method), it also mentions adhering to 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 numerical acceptance criteria.

Based on the provided text, here's the reported performance:

Performance Metric	Reported Device Performance	Acceptance Criteria (Implied by FDA Guidance and Acceptable Performance)
%CA (Category Agreement)	97.7%	Acceptance Criteria for AST Systems (Typically per FDA Guidance):
VME (Very Major Error)	1.5%	Generally < 1.5% for VME (Often 1.5% or 2.0%)
ME (Major Error)	2.4%	Generally < 3.0% for ME (Often 3.0%)
mE (Minor Error)	N/A (Not explicitly given a value, but implied to be acceptable)	Generally < 10.0% for mE (Often 10.0%)
%EA (Essential Agreement)	N/A (Not explicitly given a value in the table)	Generally > 90% (Often 90% or 95%)

Note: The table in the document is missing a reported value for 'mE' under the "Overall Performance" heading and the %EA column has "N/A" for reported performance. However, the text clearly states, "The VITEK® 2 AST-GP Inducible Clindamycin Resistance demonstrated acceptable performance as presented in Table 1 below." This implies that the metrics presented or implied within the table (even if not explicitly filled in) met the established acceptance criteria. For a comprehensive understanding of the numerical acceptance criteria, the specific FDA guidance document cited would need to be consulted.

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

Test Set Sample Size: Not explicitly stated as a numerical count of isolates in the provided text. The text mentions "an external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This suggests a diverse collection but no specific number.
Data Provenance:
- Country of Origin: Not specified in the provided text.
- Retrospective or Prospective: Not explicitly stated. However, "fresh and stock clinical isolates" indicates a mix of prospectively collected (fresh) and retrospectively collected (stock) isolates. "Challenge strains" are typically laboratory-maintained strains and are neither purely retrospective nor prospective in the clinical sense.

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

Number of Experts: Not applicable. The ground truth for this device is not established by human experts in a subjective reading task like image interpretation. Instead, it is established by a reference laboratory method.
Qualifications of Experts: Not applicable, as the ground truth is derived from a standardized laboratory method.

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable. The ground truth is established by a defined laboratory methodology (CLSI broth microdilution reference method), not by expert consensus requiring adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

MRMC Study: No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging AI algorithms where the AI assists human readers. This device is an automated antimicrobial susceptibility testing system, and its performance is compared against a gold standard laboratory method, not typically against human interpretation of the AST results.
Effect Size: Not applicable.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)

Standalone Performance: Yes, the study evaluated the standalone performance of the VITEK® 2 AST-GP Inducible Clindamycin Resistance system. The comparison "with the CLSI broth microdilution reference method" directly assesses the ability of the VITEK® 2 system to accurately determine susceptibility, independent of human interpretation or assistance beyond the initial sample preparation and loading.

7. Type of Ground Truth Used

Type of Ground Truth: The ground truth used was the CLSI broth microdilution reference method, incubated at 16-20 hours. This is a recognized laboratory standard for determining antimicrobial susceptibility.

8. Sample Size for the Training Set

Training Set Sample Size: Not explicitly stated. The document describes the external evaluation (test set) but does not provide details on the training set used for the development or initial validation of the VITEK® 2 system's internal algorithms. For a commercially available AST system, the "training" (or more accurately, the development and internal validation) would involve a large, diverse set of isolates representative of the target organisms and resistance patterns.

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

Ground Truth for Training Set: While not explicitly detailed for a specific training set, it can be inferred that any isolates used during the development and internal validation of the VITEK® 2 system's algorithms would have had their ground truth established using standard reference methods, similar to the test set (e.g., CLSI broth microdilution or agar dilution methods). The principle is consistent: compare the device's output against an accepted, accurate laboratory method.

Summary

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December 10, 2018

bioMerieux, Inc Cherece Jones Staff Regulatory Affairs Specialist 595 Anglum Rd. Hazelwood, Missouri 63042

Re: K181766

Trade/Device Name: VITEK 2 AST-Gram Positive Inducible Clindamycin Resistance Regulation Number: 21 CFR 866.1645 Regulation Name: Fully automated short-term incubation cycle antimicrobial susceptibility system Regulatory Class: Class II Product Code: LON, LTW, LTT Dated: December 5, 2018 Received: December 6, 2018

Dear Cherece Jones:

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 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

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for devices or postmarketing safety reporting (21 CFR 4. Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Steven R. Gitterman -S for

Uwe Scherf, M. Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K181766

Device Name

VITEK® 2 AST- Gram Positive Inducible Clindamycin Resistance

Indications for Use (Describe)

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-GP Inducible Clindamycin Resistance

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Cherece L. JonesStaff Regulatory Affairs Specialist
Phone Number:	314-731-8684
Fax Number:	314-731-8689
Date of Preparation:	November 16, 2018
1. Device Name:
Formal/Trade Name:	VITEK® 2 AST-Gram Positive Inducible ClindamycinResistance
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code: LON
Common Name:	VITEK® 2 AST-GP Inducible Clindamycin Resistance
2. Predicate Device:	VITEK® 2 AST-ST Inducible Clindamycin Resistance(K111909)

D. 510(k) Summary:

VITEK® 2 Gram Positive Inducible Clindamycin Resistance is designed for antimicrobial susceptibility testing of Staphylococcus aureus, and Staphylococcus lugdunensis, and Coagulase Negative Staphylococcus spp. VITEK® 2 Gram Positive Inducible Clindamycin Resistance is a qualitative test. It is intended for use with the VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents.

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies

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for the most clinically significant aerobic Gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and yeast.

The antimicrobial presented in VITEK® 2 AST-GP Cards is in concentrations equivalent by efficacy to standard method concentrations in mcg/ml. The VITEK® 2 AST Cards are essentially miniaturized versions of the doubling dilution technique for determining the minimum inhibitory concentration (MIC) microdilution methodology.

The isolate to be tested is diluted to a standardized concentration in 0.45 - 0.50% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling and sealing operation. The VITEK® 2 monitors the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cvcle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card.

VITEK® 2 AST-GP Inducible Clindamycin Resistance 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 (510[k]) presents data in support of VITEK® 2 AST-GP Inducible Clindamycin Resistance. An external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains. The external evaluations were designed to confirm the acceptability of VITEK® 2 AST-GP Inducible Clindamycin Resistance by comparing its performance with the CLSI broth microdilution reference method incubated at 16-20 hrs. The data is representative of performance on both the VITEK®2 and VITEK®2 Compact instrument platforms.

The VITEK® 2 AST-GP Inducible Clindamycin Resistance demonstrated acceptable performance as presented in Table 1 below:

Overall Performance(with the referencemethod)	%EA	VME	ME	mE	%CA	VME	ME	mE
N/A	N/A	N/A	N/A	97.7	1.5	2.4	N/A

Table 1: VITEK® 2 AST-GP Inducible Clindamycin Resistance Performance

Reproducibility and Quality Control demonstrated acceptable results.

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.”