BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM-CEFTRIAXONE 0.5-64 UG/ML

K032655 · Becton, Dickinson & CO · LON · Oct 6, 2003 · Microbiology

Device Facts

• Record ID: K032655
• Device Name: BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM-CEFTRIAXONE 0.5-64 UG/ML
• Applicant: Becton, Dickinson & CO
• Product Code: LON · Microbiology
• Decision Date: Oct 6, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1645
• Device Class: Class 2

Intended 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

BD Phoenix System performs rapid identification and antimicrobial susceptibility testing (AST) on bacterial isolates. Input: pure culture bacterial isolates inoculated into sealed, 136-well polystyrene panels containing biochemicals and antimicrobial agents. Process: panels incubated at 35°C; instrument performs automated optical readings every 20 minutes measuring redox indicator changes and turbidity to detect growth. Output: identification of isolate, MIC values, and category interpretations (S, I, or R). Used in clinical microbiology laboratories by trained technicians. Healthcare providers use output to guide antibiotic therapy selection. Benefits: rapid, standardized susceptibility testing to inform clinical decision-making for bacterial infections.

Clinical Evidence

Performance evaluated using clinical, stock, and challenge isolates across multiple US sites. Compared against NCCLS reference broth microdilution method. For Ceftriaxone (0.5-64 µg/mL), study of 1791 Gram-negative isolates showed 95.8% Essential Agreement (EA) and 91.0% Category Agreement (CA). Reproducibility study (intra-site >90%, inter-site >95%) confirmed system consistency.

Technological Characteristics

System: Automated microbiology analyzer. Materials: Molded polystyrene trays, cation-adjusted Mueller-Hinton broth with 0.01% Tween 80. Sensing: Colorimetric oxidation-reduction (redox indicator). Energy: Electrical (35°C incubation). Connectivity: Automated barcode scanning, software-driven interpretation. Software: Rule-based 'EXPERT' system derived from NCCLS documentation.

Indications for Use

Indicated for in vitro quantitative determination of antimicrobial susceptibility by MIC of Gram-negative aerobic/facultative anaerobic bacteria (Enterobacteriaceae, Non-Enterobacteriaceae) and Gram-positive bacteria (Staphylococcus, Enterococcus) from pure culture. Includes addition of Ceftriaxone (0.5-64 µg/mL).

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:
k032655

B. Analyte:
Ceftriaxone at 0.5-64 ug/mL -AST

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 – Ceftriaxone 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 (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.

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.

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2. Indication(s) for use:
This submission is for the addition of ceftriaxone at concentrations of 0.5-64 ug/mL to gram negative ID/AST or AST BD Phoenix™ panels for testing Enterobacteriaceae, Pseudomonas aeruginosa and other non-Enterobacteriaceae.

3. Special condition for use statement(s):
Results for 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™ 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 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:

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| 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 | Dried antibiotics |
| Differences | | |
| Item | Device | Predicate |
| Results | Results based on readings from serial dilutions of antibiotics | Results based on extrapolation of a 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 12 on-scale isolates, tested 3 times at each of the three sites. The reproducibility was &gt;95%.
b. Linearity/assay reportable range:
Not applicable
c. Traceability (controls, calibrators, or method):

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NCCLS recommended Quality Control strains were tested (see table below). The Phoenix results demonstrate that the system can produce QC results in the recommended range.

| Organism | Concentration | Reference results | PhoenixTM results |
| --- | --- | --- | --- |
| | | | |
| E. coliATCC 25922(range ≤ 0.5ug/ml) | ≤ 0.5 | 182 | 190 |
| | 1 | | |
| | 2 | | |
| | 4 | | |
| | | | |
| P aeruginosaATCC 27853(range NCCLS8-64 ug/mLFDA 8-32ug/mL) | 2 | | |
| | 4 | 6 | |
| | 8 | 126 | 91 |
| | 16 | 36 | 95 |
| | 32 | 7 | |
| | 64 | 3 | |
| | | | |
| P. aeruginosaATCC 35032(range ref 4-32ug/mLPhoenixTM 4-16 ug/mL | 4 | | |
| | 8 | 112 | 24 |
| | 16 | 66 | 161 |
| | 32 | 5 | 4 |
| | 64 | | |
| | >64 | | |

The ATTCC 27853 Pseudomonas aeruginosa presented a slightly more resistant trend than the reference method result and an even more of a resistant trend with the ATCC 35032 Pseudomonas aeruginosa. This trend was also apparent in the clinical data.

Inoculum density control: The organism suspension density of the ID broth was equivalent to a 0.5 McFarland standard using the $\mathrm{BBL}^{\mathrm{TM}}$ CrystalSpec™ Nephelometer which was verified each day of testing. Internal data was used to demonstrate that the use of the $\mathrm{BBL}^{\mathrm{TM}}$ CrystalSpec™ Nephelometer would produce reproducible results.

The growth rate was $&gt;90\%$

d. Detection limit: Not applicable
e. Analytical specificity: Not applicable
f. Assay cut-off: Not applicable

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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 &lt;1% 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 | 1696 | 1625 | 95.8 | 443 | 383 | 86.5 | 1542 | 90.9 | 291 | 148 | 4 | 2 |
| Challenge | 95 | 91 | 95.8 | 23 | 19 | 82.6 | 87 | 91.6 | 25 | 7 | 0 | 1 |
| Combined | 1791 | 1716 | 95.8 | 466 | 402 | 86.3 | 1629 | 91 | 316 | 155 | 4 | 3 |

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 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), 16-32 (I), ≥ 64 (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.

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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 Vitek® System.