(90 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 aerobic and facultative anaerobic bacteria isolates from pure culture for Enterobacterales and Non-Enterobacterales and most Gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus, Enterococcus, and Streptococcus.
This premarket notification is for the BD Phoenix Automated Microbiology System with Imipenem-relebactam at a concentration of 0.0625/4-16/4 µg/mL. Testing is indicated for Acinetobacter calcoaceticus-baumannii complex, Enterobacterales, and Pseudomonas aeruginosa, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC).
The BD Phoenix Automated Microbiology System - GN Imipenem-relebactam (0.0625/4 - 16/4 µg/mL) has demonstrated acceptable performance with the following organisms:
- Acinetobacter calcoaceticus-baumannii complex
- Enterobacterales (Citrobacter amalonaticus, Citrobacter braakii, Citrobacter farmeri, Citrobacter freundii, Citrobacter koseri, Citrobacter youngae, Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, and Serratia marcescens)
- Pseudomonas aeruginosa
The Phoenix AST method is a broth-based microdilution test. The Phoenix panel is a sealed and self-inoculating molded polystyrene tray with 136 micro-wells containing dried reagents. The ID/AST combination panel includes an ID side (51 wells) with dried substrates for bacterial identification and an AST side (85 wells). The AST panel contains a wide range of two-fold doubling dilution concentrations of antimicrobial agents and growth and fluorescent controls at appropriate well locations. The AST panel does not include wells for isolate identification.
The Phoenix System utilizes a redox indicator for the detection of organism growth in the presence of an antimicrobial agent. The organism to be tested must be a pure culture and be preliminarily identified as Gram-positive or Gram-negative. Colonies are then suspended in ID broth and equated to a 0.5 McFarland suspension using a nephelometer device. A further dilution is made into AST broth (a cation-adjusted formulation of Mueller-Hinton broth containing 0.010% Tween 80), to which the redox-buffered oxidation-reduction AST indicator solution is added producing a blue color in the wells. The concentration of organisms in the final AST broth suspension is approximately 5 X 10^5 CFU/mL.
The Phoenix AST Broth is poured into the inoculation port of the AST panel and the inoculum flows into the panel, filling panel wells. Polyethylene caps are applied to seal the inoculation ports. An air admittance port is located in the panel lid to ensure adequate oxygen tension in the panel for the duration of the test. Inoculated panels are barcode scanned and loaded into the BD Phoenix Automated Microbiology System instrument where panels are continuously incubated at 35 °C ± 1 °C.
Continuous measurements of changes to the indicator as well as bacterial turbidity are used in the determination of bacterial growth. The instrument takes readings every 20 minutes. Organisms growing in the presence of a given antimicrobial agent reduce the indicator (changing it to a pink color). This signals organism growth and resistance to that antimicrobial agent. Organisms killed or inhibited by the antimicrobial agent do not cause reduction of the indicator and therefore do not produce a color change. The Phoenix instrument reads and records the results of the antimicrobial tests contained in the panel and interprets the reactions (based on the organism identification) to give a minimal inhibitory concentration (MIC) value and category interpretations (susceptible, intermediate, resistant, or not susceptible). AST results are available within 16 hours. This is an auto read result; no manual readings are possible with this system.
Additional comments concerning specific organism/antimicrobial combinations are provided from the software-driven expert system (BDXpert), using rules derived from CLSI documentation and/or the FDA-approved drug labeling.
The provided FDA 510(k) clearance letter describes the acceptance criteria and the study that proves the BD Phoenix™ Automated Microbiology System - GN Imipenem-relebactam (0.0625/4 - 16/4 µg/mL) device meets those criteria for Antimicrobial Susceptibility Testing (AST).
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The core acceptance criteria for AST devices are related to Essential Agreement (EA) and Category Agreement (CA) with a reference method. The study aims to demonstrate that the device's performance is substantially equivalent to the established reference method.
| Performance Metric | Acceptance Criteria (from AST Special Controls Guidance document) | Reported Device Performance (Combined Clinical & Challenge Data) |
|---|---|---|
| Essential Agreement (EA) Rate | Overall EA and CA rates greater than 90% | Acinetobacter baumannii/calcoaceticus complex: 96.7% |
| Enterobacterales: 93.0% | ||
| Pseudomonas aeruginosa: 99.0% | ||
| Category Agreement (CA) Rate | Overall EA and CA rates greater than 90% | Acinetobacter baumannii/calcoaceticus complex: 97.8% |
| Enterobacterales: 98.6% | ||
| Pseudomonas aeruginosa: 97.9% | ||
| Major Discrepancies (Maj) | Should be minimized (no specific percentage stated for general acceptance, but ideally very low or 0%) | 0 (for combined clinical and challenge data) |
| Very Major Discrepancies (Vmj) | Should be minimized (no specific percentage stated for general acceptance, but ideally very low or 0%) | 0 (for combined clinical and challenge data) |
| Minor Discrepancies (Min) | Should be minimized (no specific percentage stated for general acceptance) | 19 (for combined clinical and challenge data across all organisms) |
| Reproducibility | Greater than 95% (± 1 dilution) agreement when compared to the test mode | 100% (Manual PhoenixSpec Nephelometer) |
| 100% (Phoenix AP Instrument) | ||
| Growth Failure Rate | Not explicitly stated an acceptance criterion, but 0% reported is excellent. | 0% |
| Quality Control Testing (QC Organisms) | Results acceptable for greater than 95% of tests. | Met acceptance criteria (explicitly stated for QC results in document). |
Note: The document mentions "The performance of the BD Phoenix Imipenem-relebactam met the combined acceptance criteria for all tested organisms, with overall EA and CA rates greater than 90%." This implicitly sets the 90% for EA and CA as the acceptance threshold.
2. Sample Size Used for the Test Set and Data Provenance
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Clinical Isolates (Test Set):
- Total: 1,111 isolates (862 fresh, 249 stock)
- Organisms:
- Acinetobacter baumannii/calcoaceticus complex (83 isolates)
- Citrobacter freundii (21 isolates)
- Citrobacter species (9 isolates)
- Citrobacter koseri (26 isolates)
- Enterobacter cloacae (60 isolates)
- Escherichia coli (359 isolates)
- Klebsiella aerogenes (58 isolates)
- Klebsiella oxytoca (47 isolates)
- Klebsiella pneumoniae (198 isolates)
- Pseudomonas aeruginosa (176 isolates)
- Serratia marcescens (74 isolates)
- Provenance: Conducted at three U.S. clinical sites. Data consists of fresh and stock isolates, implying a mix of retrospective (stock) and prospective (fresh) collection.
-
Challenge Isolates (Test Set):
- Total: 85 isolates (these are specific strains with known resistance mechanisms)
- Organisms:
- Acinetobacter baumannii (7 isolates)
- Citrobacter freundii (2 isolates)
- Citrobacter koseri (2 isolates)
- Enterobacter cloacae (12 isolates)
- Escherichia coli (19 isolates)
- Klebsiella aerogenes (4 isolates)
- Klebsiella pneumoniae (24 isolates)
- Pseudomonas aeruginosa (15 isolates)
- Provenance: Tested at "each study site" (implying the same three U.S. clinical sites as for clinical isolates). These are typically retrospective isolates chosen to challenge the system.
-
Reproducibility Isolates:
- Total: 15 on-scale isolates (tested in triplicate over three days at three sites, for 405 data points).
- Organisms: Enterobacter cloacae (2), Escherichia coli (5), Klebsiella aerogenes (1), Klebsiella pneumoniae (3) and Pseudomonas aeruginosa (4).
- Provenance: Conducted at three clinical sites (for manual method) and three internal BD sites (for Phoenix AP instrument).
3. Number of Experts Used to Establish Ground Truth and Qualifications
This type of medical device (automated microbiology system for AST) does not typically involve human experts to establish "ground truth" in the same way an imaging AI might.
- Ground Truth Establishment: The ground truth for antimicrobial susceptibility testing is established by a reference method, specifically the CLSI frozen broth microdilution reference panel, prepared according to CLSI M07 guidelines. This is a standardized, laboratory-based method, not dependent on expert visual interpretation.
- No "experts" in the human-reader sense are described as establishing ground truth for the test set. The expertise lies in adherence to CLSI standards and methodologies.
4. Adjudication Method for the Test Set
- No human adjudication method (e.g., 2+1, 3+1) is mentioned or applicable for this type of device.
- The comparison is directly between the result from the BD Phoenix system and the CLSI frozen broth microdilution reference panel. Discrepancies are categorized as minor, major, or very major based on established AST definitions (Essential Agreement and Category Agreement).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC study was NOT done. This type of study is relevant for diagnostic imaging interpretation devices where human reader performance is a key metric. For an automated microbiology system, the comparison is to a "gold standard" laboratory method (CLSI microdilution), not to human interpretation or human improvement with AI assistance.
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 system is an automated device that reads and interprets the results without human subjective input in the interpretative step. The "human-in-the-loop" aspects are limited to initial inoculum preparation (though automated options are also available and validated) and loading the panel, not interpreting the results. The comparison is the device's output (MIC and category) against the reference method.
7. The Type of Ground Truth Used
- The ground truth used is the CLSI frozen broth microdilution reference panel, which serves as the gold standard reference method for antimicrobial susceptibility testing.
8. The Sample Size for the Training Set
- The document does not explicitly state a separate "training set" sample size. For this type of automated system, which uses a growth-based detection principle rather than a machine learning model trained on large datasets of examples, the concept of a distinct "training set" in the modern AI sense is typically not applicable.
- The system's "training" or development would involve extensive internal R&D, algorithm refinement, and validation using proprietary data over time, which precedes a 510(k) submission. The data provided in the 510(k) is for the validation/test set to demonstrate performance.
9. How the Ground Truth for the Training Set Was Established
- As a conventional, growth-based automated system rather than a machine learning device, there isn't a "training set" with ground truth established in the sense of human labeling or annotation.
- The system operates based on predefined biochemical reactions and growth kinetics, and its algorithms are built upon established microbiological principles and CLSI guidelines. Any internal development and testing would likewise use CLSI reference methods to establish expected outcomes for algorithm development and calibration.
§ 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.”