BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM - DAPTOMYCIN 0.125 - 32 UG/ML

K051689 · Becton, Dickinson & CO · LON · Aug 5, 2005 · Microbiology

Device Facts

• Record ID: K051689
• Device Name: BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM - DAPTOMYCIN 0.125 - 32 UG/ML
• Applicant: Becton, Dickinson & CO
• Product Code: LON · Microbiology
• Decision Date: Aug 5, 2005
• 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

The BD Phoenix System is an automated microbiology platform for rapid identification and antimicrobial susceptibility testing (AST) of bacterial isolates. The system utilizes sealed, self-inoculating polystyrene panels containing biochemicals and antimicrobial agents. Input consists of bacterial isolates prepared in Phoenix ID or AST broth. The system continuously incubates panels and performs optical readings every 20 minutes using a redox indicator to detect organism growth and turbidity changes in the presence of antimicrobial agents. The system software processes these readings to determine minimum inhibitory concentration (MIC) values and categorical interpretations (S, I, R, or N). Used in clinical microbiology laboratories by trained personnel, the system provides automated results that assist clinicians in selecting appropriate antibiotic therapy for patients with bacterial infections.

Clinical Evidence

Clinical performance was evaluated by comparing the BD Phoenix System results for clinical, stock, and challenge isolates against the CLSI reference broth microdilution method. Testing included Gram-positive isolates. Results demonstrated 97.7% Essential Agreement (EA) and 98.8% Category Agreement (CA) for Daptomycin. Intra- and inter-site reproducibility exceeded 95%.

Technological Characteristics

Automated microbiology system using sealed, 136-well molded polystyrene panels with dried reagents. Employs broth microdilution method with redox indicator for growth detection. Continuous incubation at nominal temperature with optical readings every 20 minutes. System includes instrument, software, ID/AST broth, and AST indicator solution.

Indications for Use

Indicated for the addition of daptomycin (0.125 – 32 µg/mL) to the gram-positive susceptibility panel for Staphylococcus and Enterococcus species. For prescription use only.

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
ASSAY ONLY TEMPLATE

A. 510(k) Number:
k051689

B. Purpose for Submission:
Addition of daptomycin to the BD Phoenix™ Automated Microbiology System

C. Measurand:
Daptomycin 0.125 - 32 µg/ml

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

E. Applicant:
Becton, Dickinson & Company

F. Proprietary and Established Names:
BD Phoenix™ Automated Microbiology System – Daptomycin Gram Positive Panel

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):
The BD Phoenix™ Automated Microbiology System is intended for in vitro
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 and
most gram-positive bacteria isolates from pure culture belonging to the genera
Staphylococcus and Enterococcus.

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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-positive aerobic and facultative anaerobic bacteria belonging to the genera Staphylococcus and Enterococcus.

2. Indication(s) for use:
This submission is for the addition of the antibiotic daptomycin at concentrations of 0.125 – 32 µg/mL to the gram positive susceptibility panel.

3. Special conditions for use statement(s):
For prescription use only

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 "EXPERT" System using rules derived from the Clinical and Laboratory Standards Institute (CLSI).

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.

J. Substantial Equivalence Information:

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1. Predicate device name(s): VITEK® System
2. Predicate 510(k) number(s): N50510
3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| 1. | Isolated colonies from culture used | Isolated colonies from culture used |
| 2. | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) |
| 3. | <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. | Inoculum density equated to 0.5 McFarland standard | Inoculum density equated to 1.0 McFarland standard |
| 3. | 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 Systems; Guidance for Industry and FDA"; CLSI M7 (M100-S15) "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard."

L. 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

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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:
Forty gram-positive on-scale organisms were evaluated for site to site and inter site reproducibility demonstrating &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):
The FDA and CLSI recommended QC isolates, *E. faecalis* ATCC 29212 and *S. aureus* ATCC 29213 were tested on every test occasion with the reference method and the BD Phoenix™. The reference method QC results were in range for every day tested. The Phoenix™ was tested a sufficient number of times to demonstrate that the system can produce QC results in the CLSI recommended ranges most of the time. Two additional QC organisms were also tested, *S. aureus* ATCC 25923 and *S. sciuri* ATCC 29062 with results included in the QC table below. All QC organisms had the same mode with the reference and the BD Phoenix™ however, only the FDA and CLSI recommended QC isolates will be included in the package insert.

Quality Control Table

| ORGANISM | conc. | Reference | | Phoenix | |
| --- | --- | --- | --- | --- | --- |
| | | | | | |
| E. faecalis | 0.5 | 1 | | | |
| ATCC 29212 | 1 | 9 | | 4 | |
| Expected Range : | 2 | 120 | | 150 | |
| 1 – 4 μg/mL | 4 | 34 | | 7 | |
| | | | | | |
| S. aureus | ≤0.125 | 4 | | | |
| ATCC 25923 | 0.25 | 15 | | | |
| Expected Range : | 0.5 | 144 | | 162 | |
| 0.25 - 1μg/mL | 1 | 1 | | 1 | |
| | | | | | |
| S. aureus | 0.25 | 31 | | | |
| ATCC 29213 | 0.5 | 131 | | 162 | |
| Expected Range: | 1 | 2 | | | |
| 0.25 - 1 μg/mL | | | | | |

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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 CLSI recommended broth dilution reference panel was prepared according to the CLSI recommendation. Clinical testing was performed at four sites. The concentration of calcium on the Mueller Hinton Broth was adjusted to 50 ug/mL as recommended by the CLSI and FDA. The testing included both fresh clinical isolates and stock isolates along with a challenge set with known results. The test device had a growth rate of &gt;95%. A comparison was provided to the reference method with the following agreement.

Summary Table

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #NS |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 1521 | 1482 | 97.4 | 1476 | 1449 | 98.2 | 1502 | 98.8 | 10 |
| Challenge | 47 | 45 | 95.7 | 43 | 41 | 95.3 | 47 | 100 | 3 |
| Combined | 1568 | 1527 | 97.4 | 1519 | 1490 | 98.1 | 1549 | 98.8 | 13 |

EA-Essential Agreement
NS-not susceptible

CA-Category Agreement

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

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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.

There appears to be a trend where the test device is slightly more resistant than the test device as reflected in the Accuracy studies however results are still within essential agreement.

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: Staphylococcus spp. ≤1 (S) Enterococcus spp. ≤4 (S)

The current absence of data on resistant strains precludes defining any results other than "Susceptible". Strains yielding MIC results suggestive of a "non-susceptible" category should be submitted to a reference laboratory for further testing.

N. Proposed Labeling:

The Interpretative criteria, QC isolates and the expected ranges are the same as recommended by FDA and CLSI. All values will be included in the package insert.

O. Conclusion:

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