(51 days)
The BD Phoenix™ 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-Enterobacteriaceae and most Gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus and Enterococcus.
This premarket notification is for the antimicrobial agent nitrofurantoin at concentrations of 16-512 µg/mL to Gram Positive ID/AST or AST only Phoenix panels. Nitrofurantoin has been shown to be active in viro 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:
Staphylococcus aureus
Enterococcus faecalis
Active In Vitro Against:
Staphylococcus species
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. 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).
Here's a breakdown of the acceptance criteria and study information based on the provided text for the BD Phoenix™ Automated Microbiology System – Nitrofurantoin 16-512 µg/mL:
Acceptance Criteria and Device Performance Study
The study aimed to demonstrate substantial equivalence of the BD Phoenix™ Automated Microbiology System's performance with Nitrofurantoin to the NCCLS reference broth microdilution method.
1. Table of Acceptance Criteria and Reported Device Performance
| Measure | Acceptance Criteria (Implicit) | Reported Device Performance (Table 1: Performance of BD Phoenix System for Gram-Positive Organisms by Drug) |
|---|---|---|
| Essential Agreement (EA) | Not explicitly stated but implied to be high, generally ≥ 90% in similar premarket notifications for AST devices. | Not explicitly detailed in the provided "Table 1" for Nitrofurantoin. The table lacks clear performance metrics despite its heading. |
| Category Agreement (CA) | Not explicitly stated but implied to be high, generally ≥ 90% for clinical isolates in similar premarket notifications for AST devices, comparing to reference. | Not explicitly detailed in the provided "Table 1" for Nitrofurantoin. The table lacks clear performance metrics despite its heading. |
| Intra-site Reproducibility | Greater than 90% (explicitly stated) | Greater than 90% |
| Inter-site Reproducibility | Greater than 95% (explicitly stated) | Greater than 95% |
Note: The provided "Table 1: Performance of BD Phoenix System for Gram-Positive Organisms by Drug" for Nitrofurantoin is incomplete and unreadable in the given text (e.g., "CA ( m (0/p 0 4 4 3 1 1 (0)01" and "Fre 00 € 1 5 C F 00 2"). Therefore, the specific EA and CA values for Nitrofurantoin cannot be extracted from this table. However, the text states "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." and "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, 'Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices', March 8, 2000." This strongly implies that the system met the FDA's expected performance criteria for EA and CA, even if the numbers are redacted/unreadable.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Description: Clinical, stock, and challenge isolates.
- Sample Size: Not explicitly stated for each category of isolates. The study mentions "all isolates tested" when discussing EA and CA, but the total number is not provided.
- Data Provenance: Multiple geographically diverse sites across the United States. The text indicates that these were both clinical (patient-derived) and stock/challenge (laboratory culture) isolates.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Number of Experts: Not applicable in the typical sense for this device.
- Qualifications of Experts: The ground truth for antimicrobial susceptibility testing (AST) is established by the NCCLS reference broth microdilution method. This is a standardized laboratory procedure, not an interpretation by individual human experts. The accuracy of this reference method is maintained through strict protocols and quality control.
4. Adjudication Method for the Test Set
- Adjudication Method: Not applicable. The comparison is made directly between the BD Phoenix System's results and the results obtained from the objective NCCLS reference broth microdilution method. There is no human adjudication process described for reconciling differences in interpretations, as the reference method is considered the gold standard.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
- MRMC Study Done: No, an MRMC comparative effectiveness study was not performed.
- The study design is focused on the performance of the automated system compared to a reference standard, not on how human readers' performance might change with or without AI assistance. The device is a standalone AST system.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- Standalone Study Done: Yes, this entire study is a standalone performance evaluation. The BD Phoenix Automated Microbiology System is an automated device designed to rapidly identify and perform antimicrobial susceptibility testing. Its performance is assessed directly against the NCCLS reference method without human interpretation as part of the primary outcome measure (EA and CA). The system "takes readings of the panels every 20 minutes" and "The readings are interpreted to give... MIC values and category interpretations, S. I, or R."
7. Type of Ground Truth Used
- Type of Ground Truth: The ground truth used for performance comparison was the NCCLS reference broth microdilution method. For challenge isolates, "expected results" (presumably pre-determined by the reference method or established concentrations) were used.
8. Sample Size for the Training Set
- Sample Size for Training Set: The document does not explicitly mention a separate "training set" or its size. This type of device's "training" for new antimicrobial agents typically involves extensive characterization and validation of the reagent formulations, the optical detection system's algorithms, and the interpretive criteria (breakpoints) based on established microbiological principles and a large body of data. The "challenge" and "stock" isolates, along with clinical isolates, might contribute to the refinement or validation of the system's interpretive algorithms for a new drug, but a distinct "training set" in the machine learning sense is not detailed.
9. How the Ground Truth for the Training Set Was Established
- How Ground Truth for Training Set Was Established: As above, if "training" refers to the development and internal validation of the system's algorithms and interpretive logic for a new antimicrobial agent, the ground truth would be established through:
- NCCLS reference broth microdilution method: Providing the gold standard for MIC values and category interpretations.
- Extensive microbiological data: Including known strains with characterized susceptibility profiles, and possibly retrospective or prospective data used during the internal development phase.
- FDA guidance and clinical breakpoints: The system's interpretations (S, I, R) are based on FDA categorical interpretive criteria and established clinical breakpoints, which are derived from comprehensive clinical and pharmacological data for the antimicrobial agent against various organisms.
§ 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.”