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 and facultative anaerobic bacteria isolates from pure culture for Enterobacteriaceae and most Gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus, Enterococcus and Streptococcus.

Ceftazidime/avibactam 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 Citrobacter freundii complex Citrobacter koseri Escherichia coli Enterobacter aerogenes Enterobacter cloacae Klebsiella pneumoniae Klebsiella oxytoca Proteus spp. Pseudomonas aeruginosa

Active In Vitro but clinical significance is unknown Morganella morganii Providencia stuartii 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 Phoenix™ 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

Here's an analysis of the provided text regarding the acceptance criteria and the study proving the device meets them:

1. A table of acceptance criteria and the reported device performance

The document references the FDA guidance document, "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", August 28, 2009 for the acceptance criteria. While the specific numerical thresholds for Essential Agreement (EA) and Category Agreement (CA) from this guidance aren't explicitly stated in the provided text, the reported performance is presented. Typically, for AST devices, acceptance criteria are set for these metrics.

Acceptance Criterion	Reported Device Performance (Ceftazidime/avibactam with GN Organisms)
Essential Agreement (EA)	97.8%
Category Agreement (CA)	99.3%
Site Reproducibility	>95% (+/- 1 dilution) agreement

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

Sample Size for Test Set: 1348 isolates (This is the 'n' value reported for EA and CA).
Data Provenance:
- Clinical Studies: The study used "Clinical, stock and challenge isolates".
- Geographic Origin: Tested "across multiple geographically diverse sites across the United States."
- Retrospective or Prospective: Not explicitly stated, but the nature of a clinical study comparing to a reference method often involves prospective collection and testing or retrospective testing of collected isolates from clinical settings. The term "Clinical isolates were compared to the results obtained from the CLSI reference broth microdilution method" suggests these were real-world samples. "Challenge isolates" often refers to a pre-defined set of strains used to test specific performance aspects.

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

This information is not explicitly provided in the text. The ground truth for clinical isolates was established by the "CLSI reference broth microdilution method." While this is a standardized laboratory method, the number and qualifications of individuals performing these reference tests (who could be considered experts in applying the reference method) are not detailed.

4. Adjudication method for the test set

This information is not explicitly provided. The comparison is between the BD Phoenix System results and the CLSI reference broth microdilution method results. It's implied that discrepancies were evaluated to determine EA and CA, but a formal adjudication process (e.g., 2+1, 3+1 expert review in case of disagreement between tests) is not described.

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

This is not an MRMC study. The device is an automated antimicrobial susceptibility testing (AST) system. It performs the test and provides results (MIC values and categorical interpretations) directly, without requiring human "readers" in the same way an imaging or diagnostic AI system would. Therefore, the concept of "human readers improving with AI vs without AI assistance" does not apply here. This is an automated system being compared to a reference standard.

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

Yes, this is essentially a standalone (algorithm only) performance study. The BD Phoenix Automated Microbiology System is an automated device designed to determine antimicrobial susceptibility without continuous human intervention in the result interpretation once the samples are loaded. The study assesses the performance of this automated system directly against a reference method.

7. The type of ground truth used

Clinical Isolates: The ground truth for clinical isolates was established by the CLSI reference broth microdilution method. This is a laboratory-based, standardized, and widely accepted "gold standard" method for antimicrobial susceptibility testing.
Challenge Isolates: The ground truth for challenge isolates was compared to "expected results." This implies a pre-defined, known susceptibility profile for these specific strains, likely determined by the CLSI reference method or other validated methods.

8. The sample size for the training set

The document does not explicitly state the sample size for a training set. The descriptions focus on the validation (test) set. Automated microbiology systems like the BD Phoenix are generally developed and validated extensively over time, but the specific "training set" used for this particular antimicrobial agent's incorporation is not detailed in this regulatory summary. The system itself is "predicated" on an earlier cleared device (VITEK®2), suggesting that the base technology has been "trained" over many years/studies.

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

As the document does not explicitly identify a "training set" for this specific clearance, it also does not describe how its ground truth was established. For the system as a whole, the ground truth would have been established through extensive comparisons to reference methods (like CLSI broth microdilution) during its initial development and subsequent updates.

Summary

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

March 21, 2017

BECTON, DICKINSON & COMPANY MONICA GIGUERE REGULATORY AFFAIRS PROJECT MANAGER 7 LOVETON CIRCLE MC 694 SPARKS MD 21152

Re: K163637 Trade/Device Name: BD Phoenix Automated Microbiology System - GN Ceftazidime/avibactam (0.25/4- 32/4ug/mL) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System Regulatory Class: II Product Code: LON Dated: December 21, 2016 Received: December 23, 2016

Dear Ms. Giguere:

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 of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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/Resourcesfor You/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) K163637

Device Name

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

Indications for Use (Describe)

Ceftazidime/avibactam 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 but clinical significance is unknown Morganella morganii Providencia stuartii Serratia marcescens

Type of Use (Select one or both, as applicable)

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

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510(k) SUMMARY

SUBMITTED BY:	Becton, Dickinson and Company7 Loveton CircleSparks, MD 21152Phone: 410-316-4827Fax: 410-316-4499
CONTACT NAME:	Monica Giguere, RACRegulatory Affairs Project Manager
DATE PREPARED:	December 21, 2016
DEVICE TRADE NAME:	BD Phoenix™ Automated Microbiology System - GNCeftazidime/avibactam (0.25/4-32/4 ug/mL)
DEVICE COMMON NAME:	Antimicrobial susceptibility test system-short incubation
DEVICE CLASSIFICATION:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility System.(Product Code LON)
PREDICATE DEVICES:	VITEK®2 Gram Negative Doxycycline (K121546,November 20, 2012)
INTENDED USE:	The BD Phoenix Automated Microbiology System is intendedfor the in vitro rapid identification (ID) and quantitativedetermination of antimicrobial susceptibility by minimalinhibitory concentration (MIC) of Gram Negative aerobic andfacultative anaerobic bacteria belonging to the familyEnterobacteriaceae and non-Enterobacteriaceae.

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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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 M7). 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.

Site 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.

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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 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 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 Phoenix™ 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 (%)
Ceftazidime/avibactam	0.25/4-32/4 µg/mL	1348	97.8	1348	99.3

Performance of BD Phoenix System for Ceftazidime/avibactam with GN Organisms

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 VITEK®2 Gram Negative Doxycycline, which received clearance by the FDA under K121546, November 20, 2012.

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.”