BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM-IMIPENEM 1-16 UG/ML GRAM-NEGATIVE ID/AST OR AST ONLY PHOENIX PANELS

K032275 · Becton, Dickinson & CO · LON · Sep 29, 2003 · Microbiology

Device Facts

• Record ID: K032275
• Device Name: BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM-IMIPENEM 1-16 UG/ML GRAM-NEGATIVE ID/AST OR AST ONLY PHOENIX PANELS
• Applicant: Becton, Dickinson & CO
• Product Code: LON · Microbiology
• Decision Date: Sep 29, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1645
• Device Class: Class 2

Indications for Use

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.

Device Story

System performs automated antimicrobial susceptibility testing (AST) for gram-negative bacteria. Input: pure culture bacterial isolates suspended in broth, equated to 0.5 McFarland standard, inoculated into 136-well polystyrene trays containing dried reagents and redox indicator. Operation: instrument continuously incubates panels at 35°C; optical system monitors color change (blue to pink/colorless) every 20 minutes to detect growth via redox reduction. Output: MIC values and categorical interpretations (SIR). Used in clinical microbiology laboratories; operated by laboratory technicians. Software-driven 'EXPERT' system interprets results based on NCCLS rules. Benefits: rapid, automated determination of antibiotic susceptibility to guide clinical treatment decisions.

Clinical Evidence

Performance evaluated via multi-site clinical study (6 sites) and challenge testing using fresh clinical and stock isolates. Combined dataset (n=2680) showed 97.2% Essential Agreement and 96.8% Category Agreement compared to NCCLS reference method. Very major discrepancy rate was 0.04% (1/2680), major discrepancy rate 1.04% (28/2680), and minor discrepancy rate 2.13% (57/2680). Reproducibility >95%.

Technological Characteristics

System uses colorimetric oxidation-reduction redox indicator in cation-adjusted Mueller-Hinton broth with 0.01% Tween 80. Hardware includes automated incubator and optical reader for 136-well polystyrene trays. Connectivity: automated data recording and expert system interpretation. Sterilization: not specified. Software: rule-based expert system using NCCLS-derived criteria.

Indications for Use

Indicated for in vitro rapid identification and quantitative antimicrobial susceptibility testing (MIC) of gram-negative aerobic and facultative anaerobic bacteria (Enterobacteriaceae and non-Enterobacteriaceae). Excludes Proteus mirabilis and Proteus vulgaris/penneri.

Regulatory Classification

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.

Special Controls

*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.”

Predicate Devices

• VITEK® System (PMA No. N50510)
• BD Phoenix™ Automated Microbiology System with Gatifloxacin (K020321)
• BD Phoenix™ Automated Microbiology System with Ofloxacin (K020323)
• BD Phoenix™ Automated Microbiology System with Levofloxacin (K020322)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
k032275

B. Analyte:
Imipenem 1 – 16 µg/mL Gram-Negative AST

C. Type of Test:
Antimicrobial Susceptibility Test (Quantitative) colorimetric oxidation-reduction, growth-based

D. Applicant:
Becton, Dickinson & Company

E. Proprietary and Established Names:
BD Phoenix™ Automated Microbiology System – Imipenem Gram-Negative

F. Regulatory Information:
1. Regulation section:
21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle
Antimicrobial
2. Classification:
Class II
3. Product Code:
LON
4. Panel:
83

G. Intended Use:
1. Intended use(s):
BD Phoenix™ Automated Microbiology System:
The BD Phoenix™ Automated Microbiology System is intended for
in vitro quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration of gram-negative aerobic and facultative anaerobic bacteria belonging to the family Enterobacteriaceae and
non-Enterobacteriaceae and gram-positive bacteria belonging to the genera Staphylococcus and Enterococcus.

The BD Phoenix™ GN Panel:
The BD Phoenix™ Automated Microbiology System is intended for the in vitro rapid identification (ID) and quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of gram-negative aerobic and facultative anaerobic bacteria belonging to the family Enterobacteriaceae and non-Enterobacteriaceae.

2. Indication(s) for use:

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This submission is for the addition of the antibiotic imipenem at concentrations of 1 - 16 µg/mL to the gram negative susceptibility panel.

3. **Special condition for use statement(s):**
Results for *Proteus mirabilis* and *Proteus vulgaris/penneri* have been excluded in the BD Phoenix™ therefore no results will be reported. An alternate method should be performed when this combination is identified.

4. **Special instrument Requirements:**
Not applicable

**H. Device Description:**

The BD Phoenix™ Automated Microbiology System includes instrumentation and software, sealed and self-inoculating molded polystyrene trays with 136 micro-wells containing dried reagents, and specific inoculum broth formulations for ID and AST Indicator. 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 broth, and equated to a 0.5 McFarland with the recommendation to use the BD CrystalSpec™ Nephelometer. A further dilution is made into an AST broth, which contains an AST indicator, prior to inoculating the panel. The AST broth is a cation-adjusted formulation of Mueller-Hinton broth containing 0.01% Tween 80. After adding the indicator solution to the AST inoculum the color is blue and after inoculation and incubation goes to pink to colorless as reduction in the panel well proceeds. Inoculated panels are barcode scanned and loaded into the BD Phoenix™ Automated Microbiology System instrument where the panels are continuously incubated at 35°C. The AST has a final inoculum of 5 × 10⁵ CFU/ml. The instrument incubates, reads and records the results of the biochemical substrates and antimicrobial agents and interprets the reactions to give an ID of the isolate and MIC value and category interpretation of the antimicrobial agents. Organisms growing in the presence of a given antimicrobic agent reduce the indicator, signaling organism growth and resistance to the antimicrobic agent. Organisms killed or inhibited by a given antimicrobic do not cause reduction of the indicator and therefore do not produce a color change. Additional interpretation is done using software driven "EXPERT" System using rules derived from the NCCLS documentation.

Readings are taken every 20 minutes with an ID result available between 2-12 hours and an AST result available between 4-16 hours. This is only an autoread result; there are no manual readings possible.

**I. Substantial Equivalence Information:**

1. **Predicate device name(s):**
VITEK® System

2. **Predicate K number(s):**
N50510

3. **Comparison with predicate:**

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| 1. | Isolated colonies from culture used | Isolated colonies from culture used |
| 2. | Inoculum density equated to 0.5 McFarland standard | Inoculum density equated to 0.5 McFarland standard |
| 3. | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) |
| 4. | <16 hours | <16 hours |
| Differences | | |
| Item | Device | Predicate |
| 1. | Results are determined from serial twofold dilutions of antimicrobial agents | Results are determined from extrapolation of doubling dilutions |
| 2. | Automated growth based enhanced by use of a redox indicator (colorimetric oxidation-reduction) to detect organism growth. | Automated growth based with detection using an attenuation of light measured by an optical scanner. |

J. Standard/Guidance Document Referenced (if applicable):
“Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA”; NCCLS M7 (M100-S13)
“Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard.”

K. Test Principle:
The system employs conventional, colorimetric, fluorogenic and chromogenic substrates to identify the genus and species of the isolate. The AST portion of the BD Phoenix™ Automated Microbiology System is a broth based microdilution method that utilizes a redox indicator (colorimetric oxidation-reduction) to enhance detection of organism growth. The MIC is determined by comparing growth in wells containing serial two-fold dilutions of an antibiotic to the growth in “growth control wells” which contain no antibiotic.

L. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Reproducibility between sites was performed at three sites for three days in triplicate for &gt;95% reproducibility on eight isolates. One QC isolate was included in the reproducibility study to provide more on-scale results.
b. Linearity/assay reportable range:

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Not applicable

c. Traceability (controls, calibrators, or method):

The recommended QC isolate was tested a sufficient number of times with acceptable results with the reference method. The Phoenix results demonstrated that the system can produce QC results in the recommended range.

| ORGANISM | conc. | Reference | | Phoenix | |
| --- | --- | --- | --- | --- | --- |
| | | | | | |
| E. coli
ATCC 25922
Expected Range:
≤1 μg/mL | ≤1 | | 372 | | 378 |
| | 2 | | 1 | | 2 |
| | 4 | | 1 | | |
| | 8 | | | | 1 |
| | 16 | | | | 1 |
| | >16 | | | | 2 |
| | | | | | |
| P. aeruginosa
ATCC 25922
Expected Range:
≤1 - 4 μg/mL | ≤1 | | 6 | | 3 |
| | 2 | | 344 | | 320 |
| | 4 | | 24 | | 43 |
| | 8 | | | | |
| | 16 | | | | |
| | >16 | | | | 8 |
| | | | | | |
| | | | | | |

Inoculum density control: The organism suspension density of the ID broth was equivalent to a 0.5 McFarland standard using the BBL™ CrystalSpec™ Nephelometer which was verified each day of testing. Internal data was used to demonstrate that the use of the BBL™ CrystalSpec™ Nephelometer would produce reproducible results. Five different instruments were used.

d. Detection limit:
Not applicable

e. Analytical specificity:
Not applicable

f. Assay cut-off:
Not applicable

2. Comparison studies:

a. Method comparison with predicate device:
The NCCLS recommended broth dilution reference panel was prepared according to the NCCLS recommendation. Clinical testing was performed at six sites. The testing included both fresh clinical isolates and stock isolates along

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with a challenge set with known results. The test device had a growth rate of &gt;99%. A comparison was provided to the reference method with the following agreement.

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 2589 | 2519 | 97.3 | 278 | 243 | 87.4 | 2507 | 96.8 | 114 | 53 | 28 | 1 |
| Challenge | 91 | 87 | 95.6 | 10 | 6 | 60.0 | 87 | 95.6 | 5 | 4 | 0 | 0 |
| Combined | 2680 | 2606 | 97.2 | 288 | 249 | 86.5 | 2594 | 96.8 | 119 | 57 | 28 | 1 |

EA-Essential Agreement
CA-Category Agreement
R-resistant isolates

maj-major discrepancies
vmj-very major discrepancies
min- minor discrepancies

Essential agreement (EA) is when the BD Phoenix™ panels agree with the reference test panel results exactly or within one doubling dilution of the reference method. Category agreement (CA) is when the BD Phoenix™ panel result interpretation agrees exactly with the reference panel result interpretation.

b. Matrix comparison:
Not applicable

3. Clinical studies:
a. Clinical sensitivity:
Not applicable
b. Clinical specificity:
Not applicable
c. Other clinical supportive data (when a and b are not applicable):
Not applicable

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
≤4(S), 8(I), ≥16(R)
The expected value range, interpretative criteria and QC are the same as recommended in NCCLS. All values will be included in the package insert.

M. Conclusion:
This demonstrates acceptable performance as described in the FDA guidance document, "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA" and therefore the testing of imipenem on the BD Phoenix™ Automated Microbiology System is substantially equivalent to other commercial devices such as bioMerieux VITEK® AST panels.