BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM-NITROFURANTOIN (GP) 4-128 UG/ML

K082852 · Becton, Dickinson & CO · LON · Jan 29, 2009 · Microbiology

Device Facts

• Record ID: K082852
• Device Name: BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM-NITROFURANTOIN (GP) 4-128 UG/ML
• Applicant: Becton, Dickinson & CO
• Product Code: LON · Microbiology
• Decision Date: Jan 29, 2009
• 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 in vitro rapid identification (ID) of gram positive bacteria from pure culture belonging to the genera Staphylococcus, Enterococcus, other gram positive cocci and gram positive bacilli. The BD Phoenix™ Automated Microbiology System is also intended for the quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most gram positive bacterial isolates from pure culture belonging to the genera Staphylococcus and Enterococcus.

Device Story

BD Phoenix System is an automated microbiology platform for rapid identification and antimicrobial susceptibility testing (AST) of bacterial isolates. System components include instrument, software, molded polystyrene panels with 136 micro-wells, ID broth, AST broth, and AST indicator solution. Process: pure culture isolates are inoculated into panels; panels are placed in the instrument for continuous incubation at 35°C. Instrument performs automated readings every 20 minutes using redox indicator changes and bacterial turbidity to detect growth in the presence of antimicrobial agents. Output: MIC values and categorical interpretations (S, I, R, or N). Used in clinical microbiology laboratories by trained technicians. Results assist clinicians in selecting appropriate antibiotic therapy for patients with bacterial infections.

Clinical Evidence

Performance evaluated via multi-site clinical study comparing BD Phoenix results to CLSI reference broth microdilution method. Study included clinical, stock, and challenge isolates. Results for Nitrofurantoin (4–128 µg/mL) showed 98.5% Essential Agreement (n=979) and 100.0% Category Agreement (n=979). Reproducibility testing at three sites demonstrated >90% intra-site and >95% inter-site reproducibility for Gram-positive isolates.

Technological Characteristics

System utilizes broth microdilution in a 136-well molded polystyrene panel. Sensing principle: redox indicator and turbidity measurement via automated optical reading every 20 minutes. Incubation: 35°C. Connectivity: integrated instrument and software. Software-based interpretation of MIC and categorical results.

Indications for Use

Indicated for in vitro quantitative MIC determination of antimicrobial susceptibility for Gram-positive bacteria (Staphylococcus, Enterococcus, Streptococcus) from pure culture. Specifically active against S. aureus, Enterococci (e.g., E. faecalis), and coagulase-negative staphylococci (e.g., S. epidermidis, S. saprophyticus).

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 ASSAY ONLY TEMPLATE

A. 510(k) Number:
k082852

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

C. Measurand:
Nitrofurantoin 4 – 128 µg/mL

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

E. Applicant:
Becton, Dickinson & Company

F. Proprietary and Established Names:
BD Phoenix™ Automated Microbiology System – Nitrofurantoin (4 – 128 µg/mL)

G. Regulatory Information:

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

2. Classification:
Class II

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

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4. Panel:

Microbiology

H. Intended Use:

1. Intended use(s):

The BD Phoenix™ Automated Microbiology System is intended for the in vitro rapid identification (ID) of gram positive bacteria from pure culture belonging to the genera Staphylococcus, Enterococcus, other gram positive cocci and gram positive bacilli. The BD Phoenix™ Automated Microbiology System is also intended for the quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most gram positive bacterial isolates from pure culture belonging to the genera Staphylococcus and Enterococcus.

2. Indication(s) for use:

This premarket notification is indicated for the addition of the antimicrobial agent nitrofurantoin at concentrations of 4 – 128μg/mL to Gram-positive ID/AST or AST only Phoenix panels for testing S. aureus, Enterococci (e.g. E. faecalis) with activity against Coagulase-negative staphylococci (including S. epidermidis and S. saprophyticus).

3. Special conditions for use statement(s):

Prescription use

Results of E. faecium with nitrofurantoin 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

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of Mueller-Hinton broth containing 0.01% Tween 80. After adding the indicator solution to the AST inoculum the color turns to blue. After inoculation and incubation, the color changes to pink then 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 x 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 CLSI documentation.

Readings are taken every 20 minutes with an AST result available between 4-16 hours. This is only an autoread result; no manual readings are possible with this system.

## 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 rapid identification (ID) 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. | Intended for the determination of in vitro susceptibility to antimicrobial agents for rapidly growing, aerobic and/or facultative anaerobic Gram-negative and Gram-positive bacteria. |
| Inoculum | Isolated colonies from culture | Isolated colonies from culture |
| Incubation Time | < 16 hours | <16 hours |
| Result Reported | Report results as | Report results as |

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | minimum inhibitory concentration (MIC) and categorical interpretation (SIR) | minimum inhibitory concentration (MIC) and categorical interpretation (SIR) |
| Technology | Automated | Automated |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Results Achieved | Serial twofold dilutions of antimicrobic | Extrapolation of doubling dilutions |

## 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-S18) “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard.”

## L. Test Principle:

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:

Ten gram positive isolates 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 Quality Control (QC) isolates, S.

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aureus ATCC 25922 and E. faecalis ATCC 29212 were tested on every test occasion with the reference method and the BD Phoenix™. There appears to be no difference between the modes of the BD Phoenix™ and the reference method. The reference method QC results were in range for every day tested. The BD Phoenix™ was tested a sufficient number of times to demonstrate that the system can produce QC results in the recommended ranges.

Quality Control Table

| ORGANISM | Conc (ug/mL) | Reference | BD Phoenix™ |
| --- | --- | --- | --- |
| | | | |
| E. faecalis ATCC 29212
Expected Range: 4 – 16 μg/mL | <=4 | 3 | |
| | 8 | 80 | 60 |
| | 16 | | 25 |
| | | | |
| S. aureus ATCC 29213
Expected Range: 8 – 32 μg/mL | 8 | 13 | 3 |
| | 16 | 71 | 83 |
| | | | |

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. The test device had a growth rate of &gt;90%. A comparison was provided to the reference method with the following agreement.

Gram Positive (GP) Accuracy Summary Clinical and Challenge

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 848 | 837 | 98.7 | 804 | 802 | 99.8 | 848 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 131 | 127 | 96.9 | 131 | 127 | 96.9 | 131 | 100 | 0 | 0 | 0 | 0 |
| Combined | 979 | 964 | 98.5 | 935 | 929 | 99.4 | 979 | 100 | 0 | 0 | 0 | 0 |

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

maj-major discrepancies
vmj-very major discrepancies
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

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
Staphylococcus species ≤32(S), 64 (I), ≥128 (R)
Enterococcus species ≤32(S), 64 (I), ≥128 (R)

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N. Proposed Labeling:

The labeling is sufficient and satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

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

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