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

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

This premarket notification is for the addition of the antimicrobial agent Tigecycline at concentrations of 0.25 - 16pg/mL to Gram-negative ID/AST or AST only Phoenix panels. Tigecycline 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.

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 or 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 aqents 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 Study for BD Phoenix™ Automated Microbiology System - Tigecycline

1. Table of Acceptance Criteria and Reported Device Performance

Parameter	Acceptance Criteria	Reported Device Performance
Site Reproducibility	> 95% agreement (+/- 1 dilution) across test sites compared to the "test mode" for the antimicrobial agent and Gram-negative organisms.	> 95% overall reproducibility across test sites (+/- 1 dilution) agreement compared to the test mode.
Essential Agreement (EA)	Not explicitly stated as a numerical criterion in the provided text, but the study aims to demonstrate "substantially equivalent performance" to the CLSI reference method. For AST systems, typical FDA guidance expects high EA.	97.5% EA for Tigecycline (n=884 isolates).
Category Agreement (CA)	Not explicitly stated as a numerical criterion in the provided text, but the study aims to demonstrate "substantially equivalent performance" to the CLSI reference method. For AST systems, typical FDA guidance expects high CA.	97.4% CA for Tigecycline (n=884 isolates).
Substantial Equivalence	The device demonstrates substantially equivalent performance when compared to the CLSI reference broth microdilution method and the VITEK® System, as outlined in the FDA guidance document "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA," August 28, 2009.	The study concludes that the data demonstrate substantial equivalence to the CLSI reference method and the VITEK® system.

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

Test Set Sample Size:
- Clinical Studies (Primary Performance Evaluation): 884 isolates for Tigecycline (as indicated by the 'n' in the EA and CA percentages). This number includes clinical, stock, and challenge isolates.
- Site Reproducibility: A "panel of Gram-negative isolates" was tested, with each isolate tested in triplicate on three different days. The exact number of unique isolates in this panel is not specified.
Data Provenance: Multiple geographically diverse sites across the United States. The study included both clinical isolates and stock/challenge isolates.

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

The document does not explicitly state the number of experts used or their detailed qualifications (e.g., radiologist with 10 years of experience). However, the ground truth for the clinical isolates was established by the CLSI reference broth microdilution method, which is a standardized laboratory procedure, not typically an expert consensus per se. For challenge isolates, ground truth was "expected results," implying pre-defined or historically validated results often derived from expert validation of strains or widely accepted reference methods.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method in the context of expert review for establishing ground truth, as the ground truth was primarily based on the CLSI reference method or "expected results" for challenge isolates. The comparison was statistical (Essential Agreement, Category Agreement) against these established reference values.

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

No, an MRMC comparative effectiveness study involving human readers improving with or without AI assistance was not conducted or described. This study is an evaluation of an automated microbiology system's performance against a reference method, not an assessment of human reader performance.

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

Yes, a standalone study was performed. The BD Phoenix™ Automated Microbiology System operates without human intervention once the inoculated panel is placed in the instrument. The results (ID, MIC values, and category interpretations S, I, R, or N) are generated solely by the system's internal algorithms and sensors. The performance assessed (EA and CA) directly reflects the algorithm's standalone accuracy against the reference method.

7. Type of Ground Truth Used

Clinical Isolates: The CLSI reference broth microdilution method was used to establish the ground truth for clinical isolates. This is a widely accepted laboratory standard for antimicrobial susceptibility testing.
Challenge Isolates: "Expected results" were used. This typically refers to results for well-characterized strains where the true susceptibility is known or has been extensively validated.

8. Sample Size for the Training Set

The document does not provide any information regarding the sample size used for the training set of the BD Phoenix™ system's algorithms. The summary focuses solely on the validation/test studies for the new antimicrobial agent Tigecycline.

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

The document does not provide any information on how the ground truth for the training set was established. This information would typically be part of the initial development and validation of the BD Phoenix™ system itself, rather than a submission for adding a new antimicrobial agent.

Summary

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$\Upsilon 132909$

510(k) SUMMARY

FEB 1 4 2014

SUBMITTED BY: Becton, Dickinson and Company 7 Loveton Circle Sparks. MD 21152 Phone: 410-316-4975 Fax: 410-316-4188
CONTACT NAME: Katie Covle Requlatory Affairs Specialist

DATE PREPARED: February 5, 2014

DEVICE TRADE NAME: BD Phoenix™ Automated Microbiology System -Tigecycline (0.25 - 16ug/mL)

DEVICE COMMON NAME: Automated microbiology system

DEVICE CLASSIFICATION: 21 CFR 866.1645, Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility Device, Product Code (LON)

PREDICATE DEVICES: VITEK® System (PMA No. N50510)

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

DEVICE DESCRIPTION:

. BD Phoenix instrument and software.
. BD Phoenix panels containing biochemicals for organism ID testing and antimicrobial agents or 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 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 ongoing and will be maintained on file at BD. There have been no previous submissions for this formulation of drug for which FDA has provided feedback related to data or information needed to support substantial equivalence.

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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.

The results of the study demonstrate that for this antimicrobial agent and the Gramnegative 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 the isolates tested in this study.

Antimicrobial	Concentration	EA (n)	EA (%)	CA (n)	CA (%)
Tigecycline	0.25 - 16µg/mL	884	97.5	884	97.4

Performance of BD Phoenix System for Gram-Negative Organisms by Drug

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® system, which received approval by the FDA under PMA number N50510.

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Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which features three wavy lines that form a stylized human figure. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the symbol.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

BECTON, DICKINSON AND COMPANY KATIE COYLE 7 LOVETON CIRCLE MC 614 SPARKS MD 21152

February 14. 2014

Re: K132909

Trade/Device Name: BD Phoenix Automated Microbiology System Tigecycline (0.25-16 ug/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 19, 2013 Received: December 20, 2013

Dear Ms. Coyle:

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 (QS) regulation (21 CFR Part 820); and if applicable, the

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Page 2-Ms. Coyle

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 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/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Uwe Scherf -S for

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): K132909

Device Name: BD Phoenix™ Automated Microbiology System for use with the antimicrobial agent Tigecycline (0.25 - 16ug/mL) - Gram-negative ID/AST or AST only Phoenix Panels.

Indications for Use:

Active In Vitro and in Clinical Infections Against:

Citrobacter freundii Enterobacter cloacae Escherichia coli

Klebsiella oxvtoca Klebsiella pneumoniae

Active In Vitro

Serratia marcescens Citrobacter koseri Enterobacter aerogenes

Prescription Use × (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of Center for Devices and Radiological Health (CDRH)

Image /page/5/Picture/16 description: The image shows the words "Ribhi Shawar" and the letters "FDA" in a stylized font. Below this is the date and time "2014.02.13 11:48:21 -05'00'". The letters "FDA" are in a larger font and are partially obscured by the date and time.

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.”