(87 days)
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, and Streptococcus.
Meropenem-vaborbactam 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 Enterobacter cloacae species complex Escherichia coli Klebsiella pneumoniae
Active In Vitro but clinical significance is unknown Citrobacter freundii Citrobacter koseri Enterobacter aerogenes Klebsiella oxytoca Morganella morganii Proteus mirabilis Providencia spp. Serratia marcescens
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).
1. Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (FDA Guidance) | Reported Device Performance (Meropenem-vaborbactam - GN) |
|---|---|---|
| Essential Agreement (EA) | FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (August 28, 2009) | 98.9% (n=1141) |
| Category Agreement (CA) | FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (August 28, 2009) | 99.7% (n=1141) |
| Site Reproducibility | >95% (+/- 1 dilution) agreement across test sites | >95% (+/- 1 dilution) agreement |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size for Clinical and Challenge Isolates: 1141 isolates.
- Data Provenance: The study used a combination of clinical, stock, and challenge isolates. These were tested across multiple geographically diverse sites across the United States. This indicates a prospective and multi-site approach for clinical data collection, supplemented with controlled "stock" and "challenge" isolates. Specific details on the breakdown of clinical vs. stock/challenge isolates are not provided, nor is the exact number of contributing sites.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number of experts used or their qualifications for establishing ground truth. However, the ground truth for clinical isolates was established by the CLSI reference broth microdilution method. This is a standardized laboratory method, and its execution would typically involve trained laboratory personnel rather than a subjective expert consensus in the way a radiologist reads an image. For "expected results" for challenge isolates, this typically refers to pre-determined, known susceptibility profiles.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method in the traditional sense of multiple expert readers. The comparison is made against the CLSI reference broth microdilution method for clinical isolates and "expected results" for challenge isolates. These are objective, laboratory-based methods, removing the need for a subjective adjudication process by human experts.
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, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not done. The device is an automated microbiology system that performs antimicrobial susceptibility testing (AST) and does not involve human readers in the interpretation of results in the way an AI for image analysis would. Therefore, the concept of human readers improving with or without AI assistance is not applicable to this device.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done
Yes, a standalone performance study was done. The BD Phoenix Automated Microbiology System is an automated system providing quantitative determination of antimicrobial susceptibility. Its performance (Essential Agreement and Category Agreement) was directly compared to the CLSI reference broth microdilution method, which represents its standalone performance without human interpretation of the primary data generated by the system.
7. The Type of Ground Truth Used
- Clinical Isolates: The ground truth was established using the CLSI reference broth microdilution method (AST panels prepared according to CLSI M7). This is a gold standard laboratory method for antimicrobial susceptibility testing.
- Challenge Isolates: The ground truth was based on "expected results," implying pre-defined or known susceptibility profiles for these controlled isolates.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" or its sample size. This type of device is an automated laboratory instrument, and its performance is typically evaluated against reference methods rather than through a machine learning training paradigm with separate training and test sets as seen in AI imaging devices. The "training" in this context would likely refer to the initial development and calibration of the system by the manufacturer using internal data, which is not detailed in this regulatory summary.
9. How the Ground Truth for the Training Set Was Established
Since a "training set" is not explicitly discussed as per the typical AI/ML development cycle, there is no information on how its ground truth was established within this document. The focus of the 510(k) submission is on the comparison of the device's performance against established reference methods (CLSI broth microdilution) for the purpose of demonstrating substantial equivalence.
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February 9, 2018
Becton, Dickinson and Company Monica Giguere Regulatory Affairs Project Manager 7 Loveton Circle Sparks, Maryland 21152
Re: K173523
Trade/Device Name: BD Phoenix Automated Microbiology System - GN Meropenem-vaborbactam (0.125/8-32/8 ug/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: November 10, 2017 Received: November 14, 2017
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 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 mediation-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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Indications for Use
510(k) Number (if known) K173523
Device Name
BD Phoenix™ Automated Microbiology System - GN Meropenem-vaborbactam (0.125/8-32/8μg/mL)
Indications for Use (Describe)
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, and Streptococcus.
Meropenem-vaborbactam 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 Enterobacter cloacae species complex Escherichia coli Klebsiella pneumoniae
Active In Vitro but clinical significance is unknown Citrobacter freundii Citrobacter koseri Enterobacter aerogenes Klebsiella oxytoca Morganella morganii Proteus mirabilis Providencia spp. Serratia marcescens
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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510(k) SUMMARY
| SUBMITTED BY: | Becton, Dickinson and Company7 Loveton Circle MC 694Sparks, MD 21152Phone: 410-316-4827Fax: 410-316-4499 |
|---|---|
| CONTACT NAME: | Monica Giguere, RACRegulatory Affairs Project Manager |
| DATE PREPARED: | November 10, 2017 |
| DEVICE TRADE NAME: | BD Phoenix™ Automated Microbiology System – GNMeropenem-vaborbactam (0.125/8-32/8 µg/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: | BD Phoenix™ Automated Microbiology System - GNTigecycline (0.25-16 µg/mL) |
| 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:
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.
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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).
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. 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.
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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 (%) |
|---|---|---|---|---|---|
| Meropenem-vaborbactam | 0.125/8-32/8 $\mu$ g/mL | 1141 | 98.9 | 1141 | 99.7 |
Performance of BD Phoenix System for Meropenem-vaborbactam - GN
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.
§ 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.”