VITEK® 2 Gram Negative Ceftolozane Tazobactam is designed for antimicrobial susceptibility testing of Gram negative bacilli 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 antimicrobial agents. VITEK® 2 Gram Negative Ceftolozane/Tazobactam is a quantitative test. Ceftolozane Tazobactam 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 Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa

In vitro data available but clinical significance is unknown Citrobacter freundii Citrobacter koseri Enterobacter aerogenes Enterobacter cloacae Proteus vulgaris Providencia stuartii Serratia liquefacians

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, Staphylococus spp., Enterococcus spp. 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 provided text regarding the acceptance criteria and study for the VITEK® 2 AST-GN Ceftolozane/Tazobactam device.

It's important to note that this document is a 510(k) summary, which provides an overview. More detailed information about the study design, particularly regarding the training set and specific expert qualifications, might be found in the full 510(k) submission, which is not provided here.

Acceptance Criteria and Device Performance

1. Table of Acceptance Criteria and Reported Device Performance

Performance Measure	Acceptance Criteria (Target)	Reported Device Performance (VITEK® 2 AST-GN Ceftolozane/Tazobactam)
Essential Agreement (EA)	Not explicitly stated in the summary, but implied to be high. The FDA Class II Special Controls Guidance Document for AST Systems typically requires high agreement.	94.8% (Overall)
Category Agreement (CA)	Not explicitly stated in the summary, but implied to be high. The FDA Class II Special Controls Guidance Document for AST Systems typically requires high agreement.	98.4% (Overall)
Reproducibility	Acceptable (implied as part of standard AST system validation)	Acceptable results
Quality Control	Acceptable (implied as part of standard AST system validation)	Acceptable results

Explanation of Agreement Measures:

Essential Agreement (EA): Compares the MIC (Minimum Inhibitory Concentration) results from the device to the reference method within one doubling dilution.
Category Agreement (CA): Compares the interpretive category (Susceptible, Intermediate, Resistant) from the device to the reference method.

Note: The specific numerical acceptance criteria (e.g., "EA > 90%") for AST systems are often detailed in the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems," which is referenced in the document but not fully quoted here. However, the reported performance values of 94.8% EA and 98.4% CA are generally considered excellent for AST systems.

Study Details

2. Sample size used for the test set and the data provenance

Sample Size for Test Set: The document states an "external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains." It does not provide an exact number of isolates for the test set.
Data Provenance:
- Country of Origin: Not specified in the provided text.
- Retrospective or Prospective: Both "fresh" clinical isolates (suggesting prospective collection or recent isolates) and "stock" clinical isolates (suggesting retrospective/archived) were used. Additionally, "challenge strains" were included, which are typically well-characterized strains used for validation.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided in the text. Establishing ground truth for AST systems doesn't typically involve multiple human "experts" in the same way an imaging study would. Instead, the ground truth is established by a reference method, performed in a laboratory setting.

4. Adjudication method for the test set

The concept of "adjudication" in the sense of multiple human readers resolving discrepancies is not applicable here. The test set's ground truth is determined by the CLSI broth microdilution reference method. Discrepancies between the device and the reference method would be analyzed in terms of "major errors," "minor errors," and "very major errors" as defined in AST guidance documents, rather than human adjudication.

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 (VITEK® 2 AST-GN) is an automated system for determining antimicrobial susceptibility, not an AI-assisted diagnostic tool that human readers would interpret. Its function is to provide a result (MIC and interpretive category) from a sample, not to assist humans in interpreting complex images or clinical data.

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

Yes, this was a standalone performance study. The VITEK® 2 system is an automated instrument that processes samples and provides results without human intervention for interpretation once the test is initiated. The "performance" described (Essential Agreement, Category Agreement) directly refers to the algorithm/system's output compared to the reference method.

7. The type of ground truth used

The ground truth used was the CLSI broth microdilution reference method, incubated at 16-20 hours. This is the gold standard method for determining antimicrobial susceptibility in microbiology laboratories.

8. The sample size for the training set

This information is not provided in the text. For a microbiology AST system like VITEK® 2, the "training set" would likely refer to the isolates used during the development and calibration of the instrument's algorithms (e.g., growth curve analysis, MIC determination). The summary focuses on the external evaluation data, which serves as the independent test set.

9. How the ground truth for the training set was established

This information is not provided in the text. By inference, it would have been established by the same means as the test set: the CLSI broth microdilution reference method.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

February 13, 2017

BIOMÉRIEUX, INC CHERECE JONES STAFF REGULATORY AFFAIRS SPECIALIST 595 ANGLUM RD. HAZELWOOD MO 63042

Re: K161510

Trade/Device Name: VITEK 2 AST-GN Ceftolozane/Tazobactam (≤0.25 - ≥ 32 µg/ml) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System Regulatory Class: II Product Code: LON, LTW, LTT Dated: January 12, 2017 Received: January 13, 2017

Dear Ms. 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. 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 Parts 801 and 809); 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 regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Ribhi Shawar -A

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) K161510

Device Name

VITEK® 2 AST-GN Ceftolozane/Tazobactam (≤0.25 ->32 µg/mL)

Indications for Use (Describe)

Active in vitro and in clinical infections Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa

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.

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510(k) SUMMARY

VITEK® 2 AST-GN Ceftolozane/Tazobactam

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:	May 31, 2016
Device Name:
Formal/Trade Name:	VITEK® 2 AST-GN Ceftolozane/Tazobactam (≤ 0.25 -> 32 µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code LON
Common Name:	VITEK® 2 AST-GN Ceftolozane/Tazobactam
Predicate Device:	VITEK® 2 GN Doxycycline (K121546)

D. 510(k) Summary:

VITEK® 2 Gram Negative Ceftolozane/Tazobactam is designed for antimicrobial susceptibility testing of Gram negative bacilli 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 antimicrobial agents. VITEK®2 Gram Negative Ceftolozane/Tazobactam is a quantitative test. Ceftolozane/Tazobactam 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 Enterobacter cloacae

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Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa

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 clinically significant yeast

The antimicrobial presented in VITEK® 2 AST-GN 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.

VITEK® 2 AST-GN Ceftolozane/Tazobactam 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-GN Ceftolozane/Tazobactam. 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-GN Ceftolozane/Tazobactam by comparing its performance with the CLSI broth microdilution reference method incubated at 16-20 hrs. The data is

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representative of performance on both the VITEK® 2 and VITEK® 2 Compact instrument platforms. VITEK® 2 AST-GN Ceftolozane/Tazobactam demonstrated acceptable performance of 94.8% overall Essential Agreement and 98.4% overall Category Agreement with the reference method. 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.”