BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM - MOXIFLOXACIN-0.125-8 AND CIPROFLOXACIN-0.25 - 4 UG/ML

K060217 · Becton, Dickinson & CO · LON · Apr 12, 2006 · Microbiology

Device Facts

• Record ID: K060217
• Device Name: BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM - MOXIFLOXACIN-0.125-8 AND CIPROFLOXACIN-0.25 - 4 UG/ML
• Applicant: Becton, Dickinson & CO
• Product Code: LON · Microbiology
• Decision Date: Apr 12, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1645
• Device Class: Class 2

Indications for Use

The BD PhoenixTM 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™ Automated Microbiology System performs antimicrobial susceptibility testing (AST) on bacterial isolates. Input: pure culture colonies suspended in broth, equated to 0.5 McFarland standard using BD CrystalSpec™ Nephelometer, and inoculated into 136-well polystyrene trays containing dried reagents and AST indicator. Instrument incubates panels at 35°C; continuously monitors colorimetric oxidation-reduction (blue to pink/colorless) to detect growth. Readings taken every 20 minutes; results available in 4-16 hours. Software interprets biochemical/antimicrobial reactions to provide MIC values and categorical interpretations (SIR). System uses 'EXPERT' software rules derived from CLSI documentation to assist clinical decision-making. Benefits include automated, rapid determination of antibiotic susceptibility to guide targeted antimicrobial therapy.

Clinical Evidence

Performance evaluated using clinical, stock, and challenge isolates across multiple US sites. Results compared to CLSI reference broth microdilution method. Metrics include Essential Agreement (EA) and Category Agreement (CA). Intra-site reproducibility >90%; inter-site reproducibility >95%.

Technological Characteristics

Automated microbiology system; 136-well molded polystyrene panels; redox indicator-based growth detection; continuous incubation at 35°C; optical turbidity/redox measurement every 20 minutes; standalone instrument with integrated software.

Indications for Use

Indicated for in vitro quantitative determination of antimicrobial susceptibility (MIC) of Gram-negative aerobic/facultative anaerobic bacteria (Enterobacteriaceae and Non-Enterobacteriaceae) and Gram-positive bacteria (Staphylococcus, Enterococcus, and Streptococcus) from pure culture. Contraindicated for non-pure cultures.

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 PhoenixTM Automated Microbiology System with Gatifloxacin (K020321)
• Moxifloxacin (K031306)
• Ciprofloxacin (K052269)

Submission Summary (Full Text)

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3510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE

A. 510(k) Number:
k060217

B. Purpose for Submission:
To add additional organism groups to the antibiotics moxifloxacin on the BD
Phoenix™ gram-positive ID/AST or AST panel only, and ciprofloxacin on the BD
Phoenix™ gram-negative ID/AST or AST panel only

C. Measurand:
Moxifloxacin 0.125 – 8 µg/mL
Ciprofloxacin 0.25 – 4 µg/mL

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

E. Applicant:
Becton, Dickinson & Company

F. Proprietary and Established Names:
BD Phoenix™ Automated Microbiology System – Moxifloxacin (GP) 0.125 – 8
µg/mL, and Ciprofloxacin (GN) 0.25 – 4 µg/mL

G. Regulatory Information:

1. Regulation section:
21 CFR 866.1645 Fully Automated Short-Term Incubation Cycle Antimicrobial
Susceptibility System

2. Classification:
II

3. Product code:
LON System, Test, Automated, Antimicrobial Susceptibility, Short Incubation

4. Panel:
83 Microbiology

H. Intended Use:

1. Intended use(s):
Moxifloxacin at 0.125 – 8 µg/mL on the Phoenix™ Gram Positive ID/AST or

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AST only panel, Ciprofloxacin at 0.25 – 4 µg/mL on the Phoenix™ Gram Negative ID/AST or AST only panel is intended for use with the BD Phoenix Automated Microbiology System for the 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.

2. Indication(s) for use:
This submission is for the addition of the antibiotics Moxifloxacin at 0.125 – 8 µg/mL on the Phoenix™ Gram Positive ID/AST or AST only panel, and Ciprofloxacin at 0.25 – 4 µg/mL on the Phoenix™ Gram Negative ID/AST or AST only panel.

3. Special conditions for use statement(s):
For prescription use only
Results for S. maltophilia with ciprofloxacin 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

I. 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

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"EXPERT" System using rules derived from the CLSI documentation.

Readings are taken every 20 minutes with an AST 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 510(k) number(s): N50510
3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| 1. Intended Use | Intended for the in vitro quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most bacteria. | Same |
| 2. Isolates | Isolated colonies from culture used | Isolated colonies from culture used |
| 3. Result Reported | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) |
| 4. Incubation Time | <16 hours | <16 hours |
| 5. Type of Test | Automated | Automated |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| 1. Results achieved | Results are determined from serial twofold dilutions of antimicrobial agents | Results are determined from extrapolation of doubling dilutions |
| 2. Sample Preparation | Inoculum density equated to 0.5 McFarland standard | Inoculum density equated to 1.0 McFarland standard |
| 3. Technology | Automated growth based enhanced by use of a | Automated growth based with detection using an |

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| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | redox indicator (colorimetric oxidation-reduction) to detect organism growth. | attenuation of light measured by an optical scanner. |

K. Standard/Guidance Document Referenced (if applicable):
“Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test Systems; Guidance for Industry and FDA”; CLSI M7 (M100-S16) “Methods 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 contains 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 methods):
Quality Control was performed on every test occasion with the following results. BD Phoenix™ produced acceptable QC results as compared to the reference method results &gt;95% of the time.

Moxifloxacin – Gram Positive Quality Control Table

| ORGANISM | conc. (μg/mL) | Reference | | BD Phoenix™ | |
| --- | --- | --- | --- | --- | --- |
| | | | | | |
| E. faecalis
ATCC 10741
Expected Range:
0.25 - 2 μg/mL | ≤0.125 | | | 5 | |
| | 0.25 | | 89 | 15 | |
| | 0.5 | | 151 | 105 | |
| | 1 | | 4 | 111 | |
| | 2 | | | 11 | |

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| | | | | | |
| --- | --- | --- | --- | --- | --- |
| E. faecalis
ATCC 29212
Expected Range :
≤0.5 μg/mL | ≤0.125 | | 61 | | 32 |
| | 0.25 | | 234 | | 112 |
| | 0.5 | | 7 | | 91 |
| | 1 | | | | 11 |
| | | | | | |
| S. aureus
ATCC 29213
Expected Range :
≤0.125 μg/mL | ≤0.125 | | 241 | | 247 |
| | 0.25 | | 2 | | 1 |
| | 0.5 | | 1 | | |
| | | | | | |
| | | | | | |

## Ciprofloxacin – Gram Negative Quality Control Table

| ORGANISM | conc. (μg/mL) | Reference | | BD Phoenix™ | |
| --- | --- | --- | --- | --- | --- |
| | | | | | |
| E. coli | ≤0.25 | | 369 | | 385 |
| ATCC 25922 | 0.5 | | | | 1 |
| Expected Range: | | | | | |
| ≤0.25 μg/mL | | | | | |
| | | | | | |
| P. aeruginosa
ATCC 27853
Expected Range :
≤1 μg/mL | ≤0.25 | | 299 | | 3 |
| | 0.5 | | 68 | | 361 |
| | 1 | | 1 | | 19 |
| | | | | | |
| | | | | | |

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 broth dilution reference panel was prepared according to the CLSI recommendation and used to compare with the BD Phoenix™ results. Clinical testing was performed at several sites. The testing included both fresh clinical isolates and stock isolates along with a challenge set with known

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results. Performance charts below include all data, original and the additional organisms for fresh and challenge organisms.

## Gram Positive (GP) Accuracy Summary Clinical and Challenge Cleared
### Performance Claims with Additional Organisms

| Moxifloxacin | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Combined (Original Data and Additional Org) | 1777 | 1706 | 96 | 650 | 618 | 95.1 | 1601 | 90.1 | 307 | 163 | 9 | 4 |

The gram positive table above includes *Staphylococcus* spp., *E. faecalis* and Other *Enterococcus* organisms.

## Gram Negative (GN) Accuracy Summary Clinical and Challenge Cleared
### Performance Claims with Additional Organisms

| Ciprofloxacin | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Combined (Original Data and Additional Org) | 2836 | 2802 | 98.8 | 358 | 344 | 96.1 | 2700 | 95.2 | 650 | 125 | 7 | 4 |

The gram negative table above includes *Enterobacteriaceae*, *P. aeruginosa* and other Non- *Enterobacteriaceae*.

- 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 EA is when the MIC result is on scale for both the BD Phoenix™ and the reference and have on-scale EA.

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

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4. Clinical cut-off:
Not Applicable

5. Expected values/Reference range:
Moxifloxacin
Enterobacteriaceae ≤2(S), 4 (I), ≥8 (R)
Staphylococcus species ≤2(S), 4 (I), ≥8 (R)
Enterococcus species ≤1(S), 2 (I), ≥4 (R)
Ciprofloxacin ≤1(S), 2 (I), ≥4 (R)

N. Proposed Labeling:
The interpretive criteria and QC will be included in the package insert.

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