The BD Phoenix™ Automated Microbiology System is intended for in vitro quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most Gram-negative aerobic and facultative anaerobic bacteria isolates from pure culture for Enterobacteriaceae and Non-Enteriaceae and most Gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus, Enterococcus and Streptococcus.

Ceftolozane/tazobactam has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobial agent.

Active In Vitro and in Clinical Infections Against: Gram-negative bacteria Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa

Active In Vitro but clinical significance is unknown: Gram-negative bacteria Citrobacter koseri Morganella morganii Proteus vulgaris Providencia stuartii Serratia liquefaciens Serratia marcescens

Device Description

The BD Phoenix™ Automated Microbiology System (Phoenix System) is an automated system for the rapid identification (ID) and antimicrobial susceptibility testing (AST) of clinically relevant bacterial isolates. The system includes the following components:

. BD Phoenix instrument and software.
. BD Phoenix panels containing biochemicals for organism ID testing and antimicrobial agents for AST determinations.
. BD Phoenix ID Broth used for performing ID tests and preparing AST Broth inoculum.
. BD Phoenix AST Broth used for performing AST tests only.
. BD Phoenix AST Indicator solution added to the AST Broth to aid in bacterial growth determination.

The Phoenix panel is a sealed and self-inoculating molded polystyrene tray with 136 micro-wells containing dried reagents. Organisms for susceptibility testing must be a pure culture and preliminarily identified as a Gram-negative or Gram-positive isolate. Phoenix panels are inoculated with a specified organism density and placed into the instrument. Inoculum for use with the Phoenix system may be prepared either manually or may be automated using the BD PhoenixTM AP System.

The Phoenix AST method is a broth based microdilution test. The Phoenix System utilizes a redox indicator for the detection of organism growth in the presence of an antimicrobial agent. Measurements of changes to the indicator as well as bacterial turbidity are used in the determination of bacterial growth. Each AST panel configuration contains several antimicrobial agents with a wide range of two-fold doubling dilution concentrations.

The instrument houses the panels where they are continuously incubated at a nominal temperature of 35 ℃ ± 1 °C. The instrument takes readings of the panels every 20 minutes. The readings are interpreted to give an identification of the isolate, minimum inhibitory concentration (MIC) values and category interpretations, S, I, R or N (susceptible, intermediate, resistant or not susceptible).

AI/ML Overview

Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (from FDA guidance)	Reported Device Performance (BD Phoenix™ Automated Microbiology System - GN Ceftolozane/Tazobactam)
Essential Agreement (EA)	> 90%	96.5% (all organisms)
Category Agreement (CA)	> 90%	97.0% (all organisms)
Very Major Error Rate (vmj)	Not explicitly stated in provided text for acceptance, but errors are recognized.	18.2% (2/11) observed with E. coli initially; additional study with 66 resistant E. coli showed no vmj errors.
Major Error Rate (maj)	Not explicitly stated in provided text for acceptance.	Not specified in the provided text, but implied as satisfactory since overall CA is >90%.
Minor Error Rate (min)	Not explicitly stated in provided text for acceptance.	Not specified in the provided text, but implied as satisfactory since overall CA is >90%.
Reproducibility	> 95% (± 1 dilution agreement)	> 95% (± 1 dilution agreement) across test sites

Note on Vmj Error: While a significant initial Vmj error rate was noted for E. coli, the submission indicates that additional testing and replicate analysis demonstrated no Vmj errors, suggesting the device ultimately met an acceptable standard for this metric.

Sample Size and Data Provenance (Test Set)

Sample Size:
- Clinical and Challenge Isolates: 1179 isolates in total ("All Organisms" in the performance table).
  - Specifically, 1034 Enterobacteriaceae isolates.
  - Specifically, 145 Pseudomonas aeruginosa isolates.
  - An "additional comparative study" included 66 resistant E. coli isolates to further investigate very major errors.
- Reproducibility Test: A "panel of Gram-negative isolates" was used, tested in triplicate on three different days. The exact number of isolates is not specified.
Data Provenance: The isolates were tested "across multiple geographically diverse sites across the United States." Whether the data was purely retrospective or involved prospective collection is not explicitly stated, but "clinical, stock and challenge isolates" suggests a mix, possibly including isolates collected for the purpose of the study (prospective) and pre-existing isolates (retrospective/stock).

Number of Experts and Qualifications (Ground Truth for Test Set)

The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the test set.

Adjudication Method (Test Set)

The document does not explicitly describe an adjudication method for the test set. The "ground truth" was established by comparing the device's results to the CLSI reference broth microdilution method or to "expected results" for challenge isolates. This implies a direct comparison rather than a human expert adjudication process for the final MIC values.

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

No. The study described is a standalone performance evaluation of an automated antimicrobial susceptibility testing (AST) system compared to a reference method, not a comparative effectiveness study involving human readers with and without AI assistance. Therefore, there is no effect size reported for human readers' improvement with AI.

Standalone Performance Study

Yes. The study described is a standalone performance study. The "BD Phoenix™ Automated Microbiology System" (the algorithm/device) was directly compared to the CLSI reference broth microdilution method, which served as the gold standard for establishing ground truth for antimicrobial susceptibility.

Type of Ground Truth Used (Test Set)

The primary type of ground truth used was:

Reference Method Comparison: For clinical isolates, the BD Phoenix System results were compared to the results obtained from the CLSI reference broth microdilution method (AST panels prepared according to CLSI M07). This is a recognized laboratory standard.
Expected Results: For challenge isolates, the BD Phoenix System results were compared to "expected results." These expected results are typically derived from extensive prior characterization of these specific isolates, often using reference methods or phenotypic/genotypic analysis.

Sample Size for the Training Set

The document does not provide information on the sample size for a training set. This is typical for an AST device evaluation, where the "training" (if it occurs) is usually part of the initial development and validation of the instrument's growth detection and MIC interpretation algorithms, and not explicitly detailed in a 510(k) submission focused on the performance of a new antimicrobial agent on an existing system. The collected data represents the test set for evaluating the performance of the system with the new drug.

How the Ground Truth for the Training Set Was Established

As no training set is explicitly mentioned or detailed, the method for establishing its ground truth is not provided. The entire submission focuses on the performance of the device against a defined test set where the CLSI reference method served as the ground truth.

Summary

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January 5, 2018

Becton, Dickinson, and Company Laura Stewart Regulatory Affairs Specialist 7 Loveton Circle Mc 694 Sparks, Maryland 21152

Re: K173252

Trade/Device Name: BD Phoenix Automated Microbiology System - GN Ceftolozane/tazobactam (0.25/4-32/4 µg/mL) 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 6, 2017 Received: October 10, 2017

Dear Laura Stewart:

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR

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Part 820); 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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,

Ribhi Shawar -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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2020 See PRA Statement below.

510(k) Number (if known) K173252

Device Name

BD Phoenix™ Automated Microbiology System - GN Ceftolozane/Tazobactam (0.25/4-32/4ug/mL)

Indications for Use (Describe)

Ceftolozane/tazobactam has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobial agent.

Active In Vitro and in Clinical Infections Against: Gram-negative bacteria Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa

Active In Vitro but clinical significance is unknown: Gram-negative bacteria Citrobacter koseri Morganella morganii Proteus vulgaris Providencia stuartii Serratia liquefaciens Serratia marcescens

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

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Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) PRAStaff@fda.hhs.gov " An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

FORM FDA 3881 (7/17)

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510(k) Summary:

BD Phoenix™ Automated Microbiology System - GN Ceftolozane/Tazobactam (0.25/4-32/4 μg/mL)

Summary Preparation Date:

10/6/2017

Submitted by:

BD Diagnostic Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, Maryland 21152

Contact:

Laura Stewart Regulatory Affairs Specialist Tel: 410-316-4435 Fax: 410-316-4188 Email: laura.stewart@bd.com

Proprietary Names:

BD Phoenix™ Automated Microbiology System – GN Ceftolozane/Tazobactam (0.25/4-32/4 μg/mL)

Common Names: Antimicrobial susceptibility test system-short incubation

Regulatory Information

Regulation section: 21 CFR 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.

Classification: Class II

Review Panel: Microbiology

Product Code: LON

Predicate Device

BD Phoenix™ Automated Microbiology System - GN Tigecycline (0.25-16 µg/mL) [510(k) K132909]

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Device Establishment

Becton, Dickinson and Company 7 Loveton Circle Sparks. Marvland 21152 Registration Number: 1119779

Performance Standards

Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems. August 28. 2009.

CLSI M100 27th Edition, Performance Standards For Antimicrobial Susceptibility Testing, (InVitro Diagnostics). Recognition Number 7-271.

CLSI M07-A10, Methods For Dilution Antimicrobial Susceptibility Tests For Bacteria That Grow Aerobically; Approved Standard - Tenth Edition. (InVitro Diagnostics). Recognition Number 7-254.

Intended Use

The BD Phoenix™ Automated Microbiology System is intended for the in virro rapid identification (ID) and quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most Gram negative aerobic and facultative anaerobic bacteria belonging to the family Enterobacteriaceae and non-Enterobacteriaceae.

Special Conditions for Use Statement: For prescription use.

Special Instrument Requirements: BD Phoenix™ Automated Microbiology System

Device Description

. BD Phoenix instrument and software.
. BD Phoenix panels containing biochemicals for organism ID testing and antimicrobial agents for AST determinations.
. BD Phoenix ID Broth used for performing ID tests and preparing AST Broth inoculum.
. BD Phoenix AST Broth used for performing AST tests only.
. BD Phoenix AST Indicator solution added to the AST Broth to aid in bacterial growth determination.

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the indicator as well as bacterial turbidity are used in the determination of bacterial growth. Each AST panel configuration contains several antimicrobial agents with a wide range of two-fold doubling dilution concentrations.

Device Comparison

The BD Phoenix™ Automated Microbiology System demonstrated substantially equivalent performance for inoculum prepared manually and inoculum prepared with the BD Phoenix™ AP instrument when compared with the CLSI reference broth microdilution method. This premarket notification provides data supporting the use of the BD Phoenix™ Automated Microbiology System Gram negative ID/AST or AST only Phoenix panels with this antimicrobial agent.

Summary of Substantial Equivalence= Testing

The BD Phoenix™ Automated Microbiology System has demonstrated substantially equivalent performance when compared to the CLSI reference broth microdilution method (AST panels prepared according to CLSI M07). The system has been evaluated as defined in the FDA guidance document, "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", August 28, 2009. Shelf life (stability data) for the drug is being collected and will be maintained on file at BD as indicated in the guidance document.

Analytical Performance

Reproducibility

Intra- and inter-site reproducibility of this antimicrobial agent in the BD Phoenix System was evaluated at three sites using a panel of Gram-negative isolates. Each site tested the isolates in triplicate on three different days using one lot of Gram Negative Phoenix panels containing this antimicrobial agent and associated reagents.

The results of the study demonstrate that for this antimicrobial agent and the Gram-negative organisms tested there was an overall reproducibility across test sites of greater than 95% (± 1 dilution) agreement when compared to the test mode.

Clinical Performance Studies

Clinical, stock and challenge isolates were tested across multiple geographically diverse sites across the United States to demonstrate the performance of the Phoenix antimicrobial susceptibility test with a Gram

The term "substantial equivalence" as used in this 510(k) notification is limited to the definition of substantial equivalence as found in the Federal Food, Drug and Cosmetic Act, as amended and as applied under 21 CFR 807, Subpart E under which a device can be marketed without pre-market approval or reclassification of substantial equivalency under this notification is not intended to have any bearing whatsoever on the resolution of patent infringement suits or any other patent matters. No statements related to, or in support of substantial equivalence herein shall be construed as an admission against interest under the US Patent Laws or their application by the courts.

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Negative Phoenix Panel containing this antimicrobial agent. Phoenix System results for Challenge set isolates were compared to the expected results. Phoenix System results for clinical isolates were compared to the results obtained from the CLSI reference broth microdilution method.

The performance of the Phoenix System was assessed by calculating Essential Agreement (EA) and Category Agreement (CA) to expected/reference results for all isolates tested. Essential Agreement (EA) occurs when the BD Phoenix™ Automated Microbiology System agrees exactly or within ± one two-fold dilution to the reference result. Category Agreement (CA) occurs when the BD PhoenixTM Automated Microbiology System agrees with the reference method with respect to the FDA categorical interpretive criteria (susceptible, intermediate, resistant or not susceptible).

The following table summarizes the performance for Clinical and Challenge isolates tested in this study.

Antimicrobial	Concentration	EA (n)	EA (%)	CA (n)	CA (%)
Ceftolozane/tazobactam#, **	0.25/4-32/4 μg/mL	Enterobacteriaceae
		1034	96.5	1034	96.8*
		Pseudomonas aeruginosa
		145	96.6	145	98.6
		All Organisms
		1179	96.5	1179	97.0*

Performance of BD Phoenix System for Ceftolozane/tazobactam with GN Organisms

*A very major (vmj) error rate of 18.2% (2/11) was observed with E. coli. EA and CA for E. coli were > 98.5%. Reference method testing performed in replicates on the two vmj error E. coli isolates showed no vmj errors. An additional comparative study that included 66 resistant E. coli isolates also showed no vmj errors.

BD Phoenix Ceftolozane/Tazobactam MIC values tended to be in exact agreement or at least one doubling dilution higher when testing Enterobacteriaceae or P. aeruginosa compared to the reference broth micro-dilution. ** Enzyme group characterization was not available at the time of comparative testing, and therefore the performance of the BD Phoenix Ceftolozane/Tazobactam is unknown for the following: Pseudomonas aeruginosa (chromosomal AmpC, loss of OprD, and up-regulation MexXY, MexAB); Enterobacteriaceae (metallo-beta-lactamases).

Conclusions Drawn from Substantial Equivalence Studies

The data collected from the substantial equivalence studies demonstrate that testing on the BD Phoenix™ Automated Microbiology System with this antimicrobial agent is substantially equivalent as outlined in the FDA draft guidance document, "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", August 28, 2009. Technological characteristics of this system are substantially equivalent to those used in the BD Phoenix™ Automated Microbiology System - GN Tigecycline (0.25-16 ug/mL), which received approval by the FDA under 510(k) number K132909, February 14, 2014.

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.”