BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM - CEFAZOLIN (GN) 0.5-32UG/ML

K063811 · Becton, Dickinson & CO · LON · Feb 9, 2007 · Microbiology

Device Facts

• Record ID: K063811
• Device Name: BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM - CEFAZOLIN (GN) 0.5-32UG/ML
• Applicant: Becton, Dickinson & CO
• Product Code: LON · Microbiology
• Decision Date: Feb 9, 2007
• 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. The system utilizes sealed, self-inoculating polystyrene panels containing biochemicals and antimicrobial agents in two-fold dilution concentrations. Input consists of pure culture bacterial isolates inoculated into broth. The instrument continuously incubates panels at 35°C, taking optical readings every 20 minutes to monitor bacterial turbidity and redox indicator changes. The system software processes these measurements to determine organism identification and minimum inhibitory concentration (MIC) values, providing category interpretations (S, I, or R). Used in clinical laboratory settings by trained personnel, the output assists clinicians in selecting appropriate antibiotic therapy for patients with bacterial infections.

Clinical Evidence

Performance evaluated via clinical, stock, and challenge isolates across multiple U.S. sites. Results compared to CLSI reference broth microdilution method. Metrics included Essential Agreement (EA) and Category Agreement (CA). Intra-site reproducibility >90%; inter-site reproducibility >95% for Gram-negative isolates.

Technological Characteristics

Materials: molded polystyrene trays. Sensing: colorimetric oxidation-reduction (redox indicator). Energy: thermal (35°C incubation). Form factor: multi-well panels. Connectivity: automated instrument-based. Software: rule-based 'EXPERT' system using CLSI guidelines. Sterilization: not specified.

Indications for Use

Indicated for the quantitative determination of antimicrobial susceptibility (MIC) of gram-negative aerobic and facultative anaerobic bacteria (Enterobacteriaceae and non-Enterobacteriaceae) and gram-positive bacteria (Staphylococcus, Streptococcus, and Enterococcus) to cefazolin. This submission specifically addresses the removal of limitations for Klebsiella oxytoca and Proteus mirabilis.

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)

{0}

Page 1 of 6

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

A. 510(k) Number: K063811

B. Purpose for Submission: Removal of the limitations for Klebsiella oxytoca and Proteus mirabilis with the antimicrobial agent cefazolin at concentrations of 0.5 - 32 µg/mL, for the Gram Negative ID/AST or AST only Phoenix™ panel.

C. Measurands: Cefazolin at 0.5 - 32 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 – Cefazolin at 0.5 - 32 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): Cefazolin at 0.5 - 32 µg/mL on the Phoenix™ Gram Negative ID/AST and AST only panels are intended for use with the BD Phoenix™ Automated Microbiology System for the in vitro quantitative determination of antimicrobial

{1}

Page 2 of 6

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:
Removal of the limitations for Klebsiella oxytoca and Proteus mirabilis with the antimicrobial agent cefazolin at concentrations of 0.5 - 32 µg/mL for the Gram Negative ID/AST or AST only
Phoenix™ panel, using a new cefazolin formulation.

3. Special condition for use statement
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 biochemical substrates and antimicrobial agents and interprets the reactions to give a 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 AST result available between 4-16 hours. This is only an autoread result; there are no manual readings possible.

J. Substantial Equivalence Information:

{2}

Page 3 of 6

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. |
| Sample Preparation | Inoculum density equated to 0.5 McFarland standard | Inoculum density equated to 1.0 McFarland standard |

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

{3}

Page 4 of 6

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

Fourteen isolates were evaluated. The overall inter-site demonstrated &gt;95% reproducibility and an overall intra-site of &gt;95%. 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)

The FDA recommended Quality Control isolate *E. coli* ATCC 25922 was performed during the testing of all isolates on each day of testing with the following results. The table below includes the concentrations tested around the expected range with the frequency of the reference and the Phoenix™ results at each concentration. The Phoenix™ was tested a sufficient number of times to demonstrate that the system can produce QC results in the recommended ranges most of the time.

| Organism | Concentration μg/ml | Reference Results | Phoenix™ Results |
| --- | --- | --- | --- |
| Cefazolin | | | |
| E. coli ATCC 25922 | <=0.5 | | |
| Expected Range | 1 | 1 | |
| 1-4 μg/mL | 2 | 79 | 94 |
| | 4 | 4 | |
| | 8 | | 1 |
| | NC | 1 | |

Phoenix produced acceptable QC results as compared to the expected results &gt;95% of the time. The mode for the Phoenix™ is the same as the mode generated by the reference method.

No trending has been observed.

{4}

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. 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 Phoenix™ results. Clinical testing was performed at four sites on 874 clinical isolates and compared with the reference method results performed at the same time. An additional 182 challenge isolates were tested and compared to an expected result, determined by repeated reference testing. The test device had a growth rate of $&gt;95\%$ . A comparison was provided to the reference method with the following agreement.

CZ GN Accuracy Summary Clinical and Challenge

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA Tot | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 874 | 841 | 96.2 | 609 | 577 | 94.7 | 874 | 838 | 95.9 | 286 | 28 | 5 | 3 |
| Challenge | 182 | 178 | 97.8 | 81 | 78 | 96.3 | 182 | 175 | 96.2 | 105 | 3 | 2 | 2 |
| Combined | 1056 | 1019 | 96.5 | 690 | 655 | 94.9 | 1056 | 1013 | 95.9 | 391 | 31 | 7 | 5 |

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 (Eval) are results that are within the test range and on scale.

The EA and CA were within acceptable limits. The overall vmj rate was $1.3\%$ (5/391), maj rate was $1.1\%$ (7/627) and the min rate was $2.9\%$ (31/1056). Of the 31 min, 22 were within essential agreement.

# b. Matrix comparison:

Not applicable

{5}

Page 6 of 6

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: Enterobacteriacae ≤8 (S), 16(I), ≥32(R)

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

N. Conclusion:

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