(88 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, This premarket notification is for the BD Phoenix™ Automated Microbiology System with Ciprofloxacin at a concentration of 0.0156-4 ug/mL. Ciprofloxacin 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.
This submission is for a range extension of a single antimicrobial cleared for use on BD Phoenix ID/AST or AST only panels. The ID portion of the ID/AST combination panel was not subject to review in this submission.
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 105 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 ℃ ± 1 ℃.
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 BD Phoenix Automated Microbiology System - GN Ciprofloxacin (0.0156-4 ug/mL) is an antimicrobial susceptibility testing system. The provided text describes the performance characteristics of this device, particularly for Salmonella species, and the study conducted to demonstrate its performance against acceptance criteria.
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (General for AST devices based on FDA guidance) | Reported Device Performance (Salmonella Species) |
|---|---|---|
| Essential Agreement (EA) | Overall EA > 90% (when compared to reference method within ±1 serial two-fold dilution) | Combined Clinical and Challenge: 98.4% (127/129) |
| Category Agreement (CA) | Overall CA > 90% (when reference method agrees exactly with device interpretation) | Combined Clinical and Challenge: 94.6% (122/129) |
| Minor Discrepancies (Min) | Acceptable level generally specified in guidance; often tied to reaching target EA/CA | 7 (Combined Clinical and Challenge) |
| Major Discrepancies (Maj) | 0% or very low percentage (often 95% agreement (±1 dilution) | Manual Inoculation: 100% (378/378) |
| Phoenix AP Inoculation: 99.7% (377/378) |
(Note: The document states "The BD Phoenix Ciprofloxacin performance met the acceptance criteria for Salmonella with overall EA and CA greater than 90%." The specific numerical acceptance criteria for Min, Maj, Vmj are usually found in the referenced guidance documents but are not explicitly detailed as numerical percentages in the provided text for the device itself, other than the observed performance.)
2. Sample Size Used for the Test Set and Data Provenance:
- Clinical Isolates: 47 (fresh: 7 (14.9%), stock: 40 (85.1%))
- Organisms: Salmonella species (43 isolates), Salmonella enterica ssp. enterica serovar Typhi (4).
- Provenance: "Clinical testing was conducted at three U.S. sites." (Suggests prospective and retrospective clinical data from U.S. sources).
- Challenge Isolates: 82 stock isolates
- Organisms: Salmonella species (79), Salmonella enterica ssp. enterica serovar Typhi (3).
- Provenance: "Additional stock challenge isolates were tested at each study site." (Implying laboratory-controlled challenge strains, likely geographically diverse or from culture collections, but no specific country of origin is mentioned beyond "U.S. sites" for the clinical part which also conducted challenge testing).
- Reproducibility Study Isolates: 14 isolates of non-fastidious Gram-negative organisms (including Pseudomonas aeruginosa (1), Salmonella enterica ssp. enterica serovar Paratyphi A (1), and Salmonella species (11)).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
The ground truth was established using the CLSI frozen broth microdilution reference panel, prepared according to CLSI M07 guidelines. This is a standardized laboratory reference method, implicitly implying experts in microbiology and antimicrobial susceptibility testing were involved in its execution and interpretation, rather than individual "experts" reviewing each case for a ground truth panel. The document does not specify the number or qualifications of "experts" as individuals but relies on the standardized, recognized reference method.
4. Adjudication Method for the Test Set:
Not applicable in the typical sense of expert adjudication for diagnostic imaging or similar devices. The ground truth is determined by a universally accepted reference laboratory method (CLSI frozen broth microdilution). The comparison involves measuring agreement between the device and this reference method.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
A multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. The 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 performance study was conducted. The "BD Phoenix Automated Microbiology System" is an automated device, and its performance was evaluated against a reference method (CLSI frozen broth microdilution) without human intervention in the MIC determination or category interpretation on the device side. The reported Essential Agreement (EA) and Category Agreement (CA) metrics represent this standalone algorithmic performance.
7. Type of Ground Truth Used:
The ground truth used was expert consensus methodology/reference standard, specifically the CLSI frozen broth microdilution reference panel prepared according to CLSI M07 guidelines. This is the gold standard for antimicrobial susceptibility testing.
8. Sample Size for the Training Set:
The document does not explicitly state the sample size for a training set. This type of device (AST system) is typically developed and validated against extensive datasets during its initial creation and subsequent range extensions. However, the provided text describes the validation/test set used for this specific premarket notification (47 clinical isolates and 82 challenge isolates for Salmonella). This suggests a re-evaluation of performance based on updated breakpoints rather than a new algorithm development requiring a separate training set description in this 510(k) summary.
9. How the Ground Truth for the Training Set Was Established:
As no explicit training set sample size is provided, the method for establishing its ground truth is also not detailed. However, if a training phase was involved in the initial development of the BD Phoenix system, it would have traditionally relied on similar reference methodologies like CLSI broth microdilution to establish accurate MIC values and corresponding susceptibility categories.
§ 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.”