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

K060257 · Becton, Dickinson & CO · LON · Apr 14, 2006 · Microbiology

Device Facts

• Record ID: K060257
• Device Name: BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM - CEFOXITIN - 0.5-64 UG/ML
• Applicant: Becton, Dickinson & CO
• Product Code: LON · Microbiology
• Decision Date: Apr 14, 2006
• 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

The BD Phoenix System is an automated microbiology platform for rapid identification and antimicrobial susceptibility testing (AST) of bacterial isolates. It utilizes sealed, self-inoculating polystyrene panels containing 136 micro-wells with dried reagents. Input consists of pure bacterial cultures prepared in Phoenix ID or AST broth to a 0.5 McFarland standard. The system performs broth microdilution testing, using a redox indicator and turbidity measurements to detect bacterial growth in the presence of antimicrobial agents. Panels are incubated at 35°C within the instrument, which performs automated readings every 20 minutes. The system software interprets these readings to provide MIC values and categorical interpretations (S, I, or R). Used in clinical laboratory settings by trained personnel, the system aids clinicians in selecting appropriate antibiotic therapy by identifying bacterial susceptibility profiles, potentially improving patient outcomes through targeted treatment.

Clinical Evidence

Performance evaluated by comparing Phoenix System results for clinical and challenge isolates against the CLSI reference broth microdilution method. Metrics included Essential Agreement (EA) and Category Agreement (CA). Reproducibility was assessed at three sites, demonstrating >90% intra-site and >95% inter-site reproducibility. Data supports the addition of cefoxitin to the system's AST panel configurations.

Technological Characteristics

Broth microdilution system using redox indicator (colorimetric oxidation-reduction). Materials: molded polystyrene trays with 136 micro-wells. Energy: 35°C incubation. Connectivity: barcode scanning, automated instrument reading. Software: rule-based 'EXPERT' system using CLSI M7/M100-S16 standards. Inoculum: 0.5 McFarland standard via nephelometer.

Indications for Use

Indicated for in vitro quantitative determination of antimicrobial susceptibility by MIC of Gram-negative aerobic/facultative anaerobic bacteria (Enterobacteriaceae and Non-Enterobacteriaceae) and Gram-positive bacteria (Staphylococcus, Enterococcus, and Streptococcus) from pure culture. Includes addition of cefoxitin (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 (PMA No. N50510)
• BD Phoenix™ Automated Microbiology System with Gatifloxacin (K020321)
• BD Phoenix™ Automated Microbiology System with Cefoxitin - 0.5-64 µg/ml (K032567)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number: K060257/S1

B. Purpose for Submission: Submission of the antibiotic cefoxitin at concentrations of 0.5 - 64 µg/mL for additional organisms groups to the Gram Negative ID/AST or AST only Phoenix™ panel.

C. Measurand: Cefoxitin at 0.5 - 64 µg/mL

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

E. Applicant: Becton, Dickinson & Company

F. Proprietary and Established Names: BD Phoenix™ Automated Microbiology System – Cefoxitin 0.5 - 64 µg/mL Gram Negative (GN) panel

G. 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 Microbiology

H. Intended Use:

1. Intended use(s): Cefoxitin at concentrations of 0.5 - 64 µg/mL on the Phoenix™ Gram Negative ID/AST and AST only panel is intended for use with the Phoenix™ system in clinical laboratories as an in vitro test to determine the susceptibility of most Gram-negative aerobic and facultative anaerobic bacteria isolates

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from pure culture for Enterobacteriaceae and non-Enterobacteriaceae to antimicrobial agents when used as instructed in the Phoenix™ system user's manual.

The BD Phoenix™ Automated Microbiology System is intended for the in vitro quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most gram-negative aerobic and facultative anaerobic bacteria belonging to the family Enterobacteriaceae and non-Enterobacteriaceae and gram-positive bacteria belonging to the genera Staphylococcus, Streptococcus and Enterococcus.

2. Indication(s) for use:
This submission is for the addition of the antibiotic cefoxitin at concentrations of 0.5 - 64 µg/mL for additional organism groups to the Gram Negative ID/AST or AST only Phoenix™ panel.

3. Special condition for use statement(s):
Prescription Use Only

4. Special instrument Requirements:
Not Applicable

I. Device Description:

This submission is for the AST Panel only. The ID system was not reviewed. 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 the 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 broth containing Tween 80. After adding the indicator solution to the AST inoculum, the color is blue, and after inoculation and incubation, it changes to pink then 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 resulting AST has a final inoculum of 5 × 10⁵ CFU/ml. The instrument incubates, reads and records the results of the antimicrobial agents and interprets the reactions to give an 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 Clinical and Laboratory Standards Institute (CLSI). Readings are taken every 20 minutes an AST

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result available between 4-16 hours. This is only an autoread result; there are no manual readings possible.

## J. Substantial Equivalence Information:

1. Predicate device name(s): VITEK® System
2. Predicate K number(s): N50510
3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended use | Intended for the in vitro rapid quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most bacteria. | same |
| Isolates | Isolated colonies from culture used | Isolated colonies from culture used |
| Results | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) |
| Incubation conditions | <16 hours | <16 hours |
| Type of Test | Automated | Automated |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Reading algorithm | Results are determined from serial twofold dilutions of antimicrobial agents | Results are determined from extrapolation of doubling dilutions |
| 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. |
| | | |

## K. Standard/Guidance Document Referenced (if applicable):

"Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA"; CLSI M7 (M100-S16)"Methods

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for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard."

# L. Test Principle:

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.

# M. Performance Characteristics (if/when applicable):

# 1. Analytical performance:

# a. Precision/Reproducibility

Intersite and Intrasite testing demonstrated $&gt;95\%$ reproducibility. The ten isolate study described in the guidance document was used (10 organisms tested 3 times on 3 days at 3 sites).

# b. Linearity/assay reportable range:

Not applicable

# c. Traceability, Stability, Expected values (controls, calibrators, or method)

| Organism | Concentration μg/ml | Reference Results | PhoenixTM Results |
| --- | --- | --- | --- |
| | | | |
| E. coliATCC 25922ExpectedRange<=0.5 μg/mL | <=0.5 | 182 | 190 |
| | 1 | | |
| | 2 | | |
| | 4 | | |
| | 8 | | |
| | 16 | | |
| | 32 | | |
| | 64 | | |

PhoenixTM produced acceptable QC results as compared to the reference method results $&gt;95\%$ of the time.

Inoculum density control: The organisms suspension density of the ID broth was equivalent to a 0.5McFarland 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

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e. Analytical specificity:
Not applicable

f. Assay cut-off:
Not applicable

2. Comparison studies:

a. Method comparison with predicate device:
The broth dilution reference panel was prepared according to the CLSI recommendation and used to compare with 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. Performance charts below include all data, original and the additional organisms for fresh and challenge organisms.

Cefoxitin (FOX) - GN Clinical and Challenge Data Additional Organism Groups

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA Tot | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Combined | 1397 | 1353 | 96.9 | 1096 | 1059 | 96.6 | 1397 | 1303 | 93.3 | 384 | 87 | 5 | 2 |

EA-Essential Agreement
maj-major discrepancies
CA-Category Agreement
vmj-very major discrepancies
R-resistant isolates
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. Evaluable (Eval) are results that are within the test range and on scale.

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

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5. Expected values/Reference range:

Interpretive criteria = ≤ 8 (S), 16 (I), ≥ 32 (R) for Enterobacteriaceae

N. Proposed Labeling

The expected value range, interpretive criteria and QC for gram negative panels are included in the package insert. The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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