VITEK® 2 Gram Negative Doxycycline is designed for antimicrobial susceptibility testing of Gramnegative bacilli. VITEK 2 Gram Negative Doxycycline is a quantitative test 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. Doxycycline has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections
Acinetobacter species
Enterobacter aerogenes
Escherichia coli
Klebsiella species
Shigella species

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 System 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., S. pneumoniae, and clinically significant 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

Here's an analysis of the acceptance criteria and study detailed in the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance
Overall Essential Agreement (EA)	Not explicitly stated, but generally >90% for AST systems	97.6%
Overall Category Agreement (CA)	Not explicitly stated, but generally >90% for AST systems	95.1%

Note: The document states "VITEK® 2 GN Doxycycline 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." This guidance document would contain the specific acceptance criteria for EA and CA, which are generally high for such devices (e.g., >90% or >95%). Since the device met the criteria, we can infer that the reported values satisfy regulatory thresholds.

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

Sample Size: Not explicitly stated as a single number. The study used "fresh and stock clinical isolates, as well as a set of challenge strains." The exact number of isolates for the external evaluation is not provided.
Data Provenance: The document mentions "An external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This indicates a mix of retrospective (stock clinical isolates) and potentially prospective (fresh clinical isolates) data. The country of origin is not specified, but bioMérieux, Inc. is located in Hazelwood, MO, USA, and the submission is to the FDA, suggesting the data is likely from the US or a region adhering to similar clinical standards.

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

This information is not provided in the document. The ground truth (reference method) used was the CLSI broth microdilution reference method. While this method involves expert execution and interpretation, the document does not detail the number or qualifications of individuals performing or verifying the reference method results.

4. Adjudication Method for the Test Set

This information is not provided in the document. For antimicrobial susceptibility testing, discrepancies would typically be resolved by repeat testing or referral to a third, expert laboratory, but the specific adjudication method is not mentioned.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, an MRMC comparative effectiveness study was not done. This device is an automated antimicrobial susceptibility testing (AST) system. It directly produces interpretive results (susceptible, intermediate, resistant) based on Minimum Inhibitory Concentration (MIC) values. It is not designed to assist human readers in interpreting images or clinical cases, but rather to automate a laboratory test. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply here.

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

Yes, a standalone performance evaluation was conducted. The VITEK® 2 system is a fully automated system. The evaluation compared the device's automated results (MIC values and interpretive categories) directly against the CLSI broth microdilution reference method, which is the gold standard for AST. This is a standalone assessment of the device's performance.

7. The Type of Ground Truth Used

Expert Consensus / Reference Method: The ground truth was established using the CLSI (Clinical and Laboratory Standards Institute) broth microdilution reference method, which is the gold standard for determining antimicrobial susceptibility. This method is internationally recognized and relies on standardized protocols and expert interpretation.

8. The Sample Size for the Training Set

This information is not provided in the document. The document focuses on the external evaluation (test set) for validation. VITEK® 2 systems are pre-calibrated and validated; specific "training sets" in the machine learning sense are not typically reported in 510(k) summaries for these types of devices, as they often rely on established biochemical and growth kinetics algorithms rather than deep learning models requiring explicit training data.

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

This information is not provided in the document, as no specific "training set" in the context of a machine learning model is described for this device. The underlying algorithms and interpretations for VITEK® 2 systems are developed based on extensive microbiology principles and correlation with reference methods over many years of research and development. The ground truth for the development and internal validation of such systems would also involve the CLSI broth microdilution reference method.

Summary

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K12/546

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NOV 2 0 2012 1

510(k) SUMMARY

VITEK® 2 Gram Negative Doxycycline

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Jennifer Chia-Hsuan Lin

Regulatory Affairs Specialist

Phone Number:

Fax Number:

314-731-8689

314 -731-8639

May 24, 2012

B. Device Name:

Formal/Trade Name:

Date of Preparation:

Classification Name:

21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial

Common Name:

VITEK® 2 AST-GN Doxycycline

Susceptibility System Product Code LON

VITEK® 2 Gram Negative Doxycycline

C. Predicate Device:

VITEK® 2 Gram Negative Imipenem (K103752)

D. 510(k) Summary:

VITEK® 2 Gram Negative Doxycycline is designed for antimicrobial susceptibility testing of Gramnegative bacilli. VITEK 2 GN Doxycycline is a quantitative test 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. Doxycycline has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections Acinetobacter species Enterobacter aerogenes Escherichia coli Klebsiella species Shigella species

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

bioMérieux, Inc.

Phone: 314/731-8500 800/638-4835 595 Anglum Road, Hazelwood, Missouri 63042-2320, USA Fax: 314/731-8700 http://www.biomerieux-usa.com

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

VITEK® 2 GN Doxycycline 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 GN Doxycycline. 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 GN Doxycycline by comparing its performance with the CLSI broth microditution reference method incubated at 24 hrs. The data is representative of performance on both the VITEK® 2 and VITEK® 2 Compact instrument platforms. VITEK® 2 GN Doxycycline demonstrated acceptable performance of 97.6% overall Essential Agreement and 95.1% overall Category Agreement with the reference method. Reproducibility and Quality Control demonstrated acceptable results using both the VITEK 2 and VITEK 2 Compact instrument systems.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol featuring three curved shapes that resemble a human figure.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

bioMerieux. Inc. C/O Jennifer Chia-Hsuan Lin. Regulatory Affairs Specialist 595 Anglum Road Hazelwood MO 63042

NOV 2 0 2012

Re: K121546

VITEK®2 Gram Negative Doxycycline 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: October 19, 2012 Received: October 22, 2012

Dear Ms. Lin:

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. 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.

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Sally A. Hojvat

Sally A. Hojvat, 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):_ K12 1846 / S00 1

Device Name: VITEK® 2 Gram Negative Doxycycline (<0.5 ->16 ug/mL)

Indications For Use:

VITEK® 2 Gram Negative Doxycline is designed for antimicrobial susceptibility testing of Gramnegative bacilli. VITEK 2 Gram Negative Doxycycline is a quantitative test 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. Doxycycline has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections

Acinetobacter species Enterobacter aerogenes Escherichia coli Klebsiella species Shigella species

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Jayart
Division Sign-Off

Division Sign-C

Office of In Vitro Diagnostic Device Evaluation and Safety

510(K) KIZ 1 244

Page 1 of 1

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.”