(25 days)
The BD PhoenixTM Automated Microbiology System is intended for the rapid identification and in vitro antimicrobial susceptibility testing of isolates from pure culture of most aerobic and facultative anaerobic Gram-negative and Gram-positive bacteria of human origin.
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-Enteropacteriaceae and most Gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus and Enterococcus.
This premarket notification is for the addition of the antimicrobial agent nalidixic acid at concentrations of 2-32 µg/mL to Gram-negative ID/AST or AST only Phoenix panels. nalidixic acid 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 species Escherichia coli
Morganella morganii Proteus mirabilis
Proteus vulgaris Providencia rettgeri
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. For each isolate, an inoculation equivalent to a 0.5 McFarland standard is prepared in Phoenix ID Broth.
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°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, or R (sensitive, intermediate, or resistant).
Acceptance Criteria and Study Findings for BD Phoenix™ Automated Microbiology System - Nalidixic Acid
The BD Phoenix™ Automated Microbiology System, featuring Nalidixic Acid (2-32 µg/mL), demonstrated substantially equivalent performance compared to the NCCLS reference broth microdilution method for antimicrobial susceptibility testing. This was evaluated according to the FDA Draft guidance document, "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices", March 8, 2000.
1. Acceptance Criteria and Reported Device Performance
| Metric | Acceptance Criteria | Reported Device Performance (Nalidixic Acid) |
|---|---|---|
| Essential Agreement (EA) | Not explicitly stated (implied to be high given successful equivalence claim) | 96.1% (n=2062) |
| Category Agreement (CA) | Not explicitly stated (implied to be high given successful equivalence claim) | 98.5% (n=2062) |
| Intra-site Reproducibility | >90% | >90% |
| Inter-site Reproducibility | >95% | >95% |
2. Sample Size and Data Provenance
- Test Set Sample Size: 2062 isolates for Essential Agreement (EA) and Category Agreement (CA) evaluation for Nalidixic Acid.
- Data Provenance: The clinical studies were conducted across "multiple geographically diverse sites across the United States." The data includes "clinical, stock and challenge isolates." This indicates a mix of retrospective (stock/challenge isolates) and prospective (clinical isolates) data, all originating from the United States.
3. Number and Qualifications of Experts for Ground Truth
The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the test set. However, the ground truth was established by comparison to the NCCLS reference broth microdilution method, which is a standardized and widely accepted laboratory procedure. The execution and interpretation of this method would rely on trained laboratory personnel, rather than "experts" in the context of clinical interpretation like radiologists.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method for the test set in the traditional sense (e.g., 2+1, 3+1 for discordant reads). Instead, the Phoenix System's results (MIC values and category interpretations) were directly compared to the results obtained from the NCCLS reference broth microdilution method. Discordant results were likely assessed for agreement within specific parameters (e.g., ± one two-fold dilution for EA).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was performed or described. This study focuses on the standalone performance of the automated system against a reference method, not on human reader performance with or without AI assistance.
6. Standalone (Algorithm Only) Performance
Yes, a standalone study was performed. The entire evaluation focuses on the performance of the BD Phoenix™ Automated Microbiology System (an algorithm-based automated system) in determining antimicrobial susceptibility without explicit human-in-the-loop intervention for the interpretation of the primary readings. The system itself reads panels and interprets results.
7. Type of Ground Truth Used
The ground truth used was established by the NCCLS reference broth microdilution method. This is a laboratory-based, gold-standard method for determining Minimum Inhibitory Concentrations (MICs) and categorical interpretations (S, I, R) of antimicrobial agents against bacterial isolates.
8. Sample Size for the Training Set
The document does not explicitly state the sample size for a "training set." This type of premarket notification for an antimicrobial susceptibility device typically doesn't detail a machine learning training phase in the same way as AI/ML software as a medical device (SaMD). The system's underlying algorithms and interpretations are likely based on established microbiological principles and validated against large datasets during its development. The clinical studies described here serve as a validation against a reference method rather than directly contributing to an iterative training process for a novel AI model.
9. How Ground Truth for the Training Set was Established
As noted above, a distinct "training set" with ground truth establishment in the context of modern AI/ML is not explicitly described. However, the system's foundational development and internal validation would have relied on NCCLS reference broth microdilution methods or equivalent established microbiological techniques to define the ground truth for calibrating its detection and interpretation algorithms. The Phoenix System utilizes a redox indicator and bacterial turbidity measurements to determine growth, and the algorithms would have been developed and refined to correlate these measurements with known MICs from reference methods.
§ 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.”