BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM-CEFOXITIN-GRAM NEGATIVE

K032567 · Becton, Dickinson & CO · LON · Sep 17, 2003 · Microbiology

Device Facts

• Record ID: K032567
• Device Name: BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM-CEFOXITIN-GRAM NEGATIVE
• Applicant: Becton, Dickinson & CO
• Product Code: LON · Microbiology
• Decision Date: Sep 17, 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) and identification (ID) of bacterial isolates; utilizes sealed, self-inoculating polystyrene trays with 136 micro-wells containing dried reagents; requires pure culture inoculum equated to 0.5 McFarland standard. Instrument incubates panels at 35°C; monitors growth via colorimetric oxidation-reduction indicator (blue to pink/colorless); reads results every 20 minutes. Software-driven 'EXPERT' system interprets biochemical reactions and MIC values based on NCCLS rules. Provides quantitative MIC and qualitative category interpretations (S, I, R). Used in clinical microbiology laboratories; operated by trained laboratory personnel. Benefits include rapid, automated determination of antibiotic susceptibility to guide clinical treatment decisions.

Clinical Evidence

Performance evaluated via method comparison study at four sites using 1,124 clinical and challenge isolates. Combined results showed 96.4% Essential Agreement (EA) and 92.4% Category Agreement (CA) compared to NCCLS broth microdilution reference method. Reproducibility testing on 23 isolates across three sites demonstrated >95% reproducibility. Quality control testing met NCCLS recommended ranges >95% of the time.

Technological Characteristics

Automated microbiology system; polystyrene trays with 136 micro-wells; colorimetric oxidation-reduction sensing principle; 35°C incubation; software-driven expert system for rule-based interpretation; automated barcode scanning; no manual readings possible.

Indications for Use

Indicated for testing Enterobacteriaceae using cefoxitin at concentrations of 0.5-64 ug/ml in gram negative ID/AST or AST BD Phoenix™ panels.

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 (N50510)

Submission Summary (Full Text)

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

A. 510(k) Number:
k032567

B. Analyte:
Cefoxitin at 0.5-64 ug/ml

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

D. Applicant:
Becton, Dickinson and Company

E. Proprietary and Established Names:
BD Phoenix™ Automated Microbiology System – cefoxitin – 0.5-64 ug/ml

F. Regulatory Information:
1. Regulation section:
CFR 866.1645 Short Term Antimicrobial Susceptibility Test System
2. Classification:
Class II
3. Product Code:
LON Automated short incubation AST system
4. Panel:
83 Microbiology

G. Intended Use:
1. Intended use(s):
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:
This submission is for the addition of cefoxitin at concentrations of 0.5-64 ug/ml to gram negative ID/AST or AST BD Phoenix™ panels for testing Enterobacteriaceae.

3. Special condition for use statement(s):

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Not applicable

# 4. Special instrument Requirements:

Not applicable

# H. Device Description:

The BD Phoenix™ 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 $0.5\mathrm{McFarland}$ 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 $35^{\circ}\mathrm{C}$ . The AST has a final inoculum of $5\times 10^{5}$ 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 a 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:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Specimen | Isolated colonies from culture used | Isolated colonies from culture used |
| Inoculum | Inoculum density to 0.5 McFarland standard | Inoculum density to 0.5 McFarland standard |
| Incubation | <16 hours | < 16 hours |
| Panels | Dried antibiotics at different concentrations | Dried antibiotics at different concentrations |

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| Results | MIC and SIR results available | MIC and SIR results available |
| --- | --- | --- |
| Differences | | |
| Item | Device | Predicate |
| Results | Results based on readings from serial dilutions of antibiotics | Results based on extrapolation of several concentrations of an antibiotic |
| Technology | 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 Phoenix™ 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:
Inter-site and intra-site reproducibility was performed on 23 on-scale isolates tested 3 times at each of the three sites with &gt;95% reproducibility.
b. Linearity/assay reportable range:
Not applicable
c. Traceability (controls, calibrators, or method):
The NCCLS recommended Quality Control strain was tested with expected results &gt;95% of the time. The Phoenix results demonstrate that the system can produce QC results in the recommended range.

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| Organism | Concentration ug/ml | Reference results | Phoenix™ results |
| --- | --- | --- | --- |
| E. coli ATCC 25922 (range 2-8 ug/ml ) | ≤ 0.5 | | |
| | 1 | | |
| | 2 | 69 | 17 |
| | 4 | 99 | 171 |
| | 8 | 13 | |
| | 16 | | 1 |
| | >16 | 3 | 1 |

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.

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 reference panel prepared according to the NCCLS recommendation was used to compare the Phoenix™ results. Clinical testing was performed at four sites. The testing included both fresh clinical isolates and stock isolates along with a challenge set with known results. There was a 0.3% no growth rate in the study. A comparison was provided to the reference method with the following agreement.

| | total | EA | % EA | Total evalu-able | EA of evalu-able | % EA | CA | % CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 1064 | 1025 | 96.3 | 975 | 943 | 96.7 | 984 | 92.5 | 148 | 75 | 3 | 2 |
| Challenge | 60 | 59 | 98.3 | 58 | 57 | 98.3 | 55 | 91.7 | 6 | 4 | 1 | 0 |
| Combined | 1124 | 1084 | 96.4 | 1033 | 1000 | 96.8 | 1039 | 92.4 | 154 | 79 | 3 | 2 |

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

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

Evaluable(EA) results are those that fall within the test range of the reference method and could also be on-scale with the new device if within the plus/minus one well variability. EA is when there is agreement between the reference method and the Phoenix™ within plus or minus one

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serial two-fold dilution of antibiotic. CA is when the interpretation of the reference method agrees exactly with the interpretation of the Phoenix™ result. The %EA, CA and reproducibility are all acceptable with acceptable discrepancy rates when compared to the reference method as described in the FDA guidance document, “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA”.

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:
≤ 8 (S), 16 (I), ≥ 32 (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:
Data analysis when analyzed as recommended in the “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” demonstrates that the Phoenix™ System is substantially equivalent to the predicate.