BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM-AMOXICILLIN-CLAVULANATE (GN) 0.5/0.25-32/16 UG/ML, AMPICILLIN-SULBACTAM (GN) 0.

K061327 · Becton, Dickinson & CO · LON · Jul 3, 2006 · Microbiology

Device Facts

• Record ID: K061327
• Device Name: BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM-AMOXICILLIN-CLAVULANATE (GN) 0.5/0.25-32/16 UG/ML, AMPICILLIN-SULBACTAM (GN) 0.
• Applicant: Becton, Dickinson & CO
• Product Code: LON · Microbiology
• Decision Date: Jul 3, 2006
• 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

System performs rapid identification and antimicrobial susceptibility testing (AST) of bacterial isolates. Input: pure culture bacterial isolates inoculated into sealed, 136-well molded polystyrene panels containing biochemicals and antimicrobial agents. Operation: panels incubated at 35°C; instrument performs automated optical readings every 20 minutes using redox indicators and turbidity measurements to detect growth. Output: identification of isolate, MIC values, and categorical interpretations (S, I, or R). Used in clinical microbiology laboratories by trained technicians. Results assist clinicians in selecting appropriate antibiotic therapy for patients with bacterial infections.

Clinical Evidence

Bench testing only. Performance evaluated using clinical and challenge isolates compared to CLSI broth microdilution reference method. Results: Amoxicillin-clavulanate (EA 96.7%, CA 90.9%), Ampicillin-sulbactam (EA 97.2%, CA 87.5%), Ticarcillin (EA 94.7%, CA 92.7%). Reproducibility >95%. Quality control results met acceptance criteria.

Technological Characteristics

Automated growth-based system using colorimetric oxidation-reduction (redox) indicator. Materials: molded polystyrene trays with 136 micro-wells. Energy: 35°C incubation. Connectivity: barcode scanning, automated instrument reading. Software: expert rule-based interpretation. Sterilization: not specified.

Indications for Use

Indicated for quantitative determination of antimicrobial susceptibility (MIC) of gram-negative aerobic and facultative anaerobic bacteria (Enterobacteriaceae and non-Enterobacteriaceae) to amoxicillin-clavulanate, ampicillin-sulbactam, and ticarcillin. Prescription use only. Excludes Acinetobacter/Proteus species for ampicillin-sulbactam and Proteus vulgaris/penneri for ticarcillin.

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 Amoxicillin-clavulanate (K031912)
• BD Phoenix™ Automated Microbiology System with Ampicillin-sulbactam (K043389)
• BD Phoenix™ Automated Microbiology System with Ticarcillin (K031984)

Submission Summary (Full Text)

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

A. 510(k) Number:
k061327

B. Purpose for Submission:
To add additional organism groups to the antibiotics amoxicillin-clavulanate, ampicillin-sulbactam, and ticarcillin on the BD Phoenix™ gram-negative ID/AST or AST panel only

C. Measurand:
Amoxicillin-clavulanate 0.5/0.25 – 32/16 µg/mL
Ampicillin-sulbactam 0.5/0.25 – 32/16 µg/mL
Ticarcillin 1 – 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 – Amoxicillin-clavulanate (0.5/0.25 – 32/16 µg/mL), Ampicillin-sulbactam (0.5/0.25 – 32/16 µg/mL), Ticarcillin (1 – 128 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:

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1. Intended use(s):

Amoxicillin-clavulanate at 0.5/0.25 – 32/16 µg/mL, Ampicillin-sulbactam at 0.5/0.25 – 32/16 µg/mL, Ticarcillin at 1 – 128 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.

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 isolates from pure culture for Enterobacteriaceae and non – Enterobacteriaceae and most Gram-positive bacteria isolates from pure culture belonging to the genera Staphylococcus and Enterococcus.

2. Indication(s) for use:

This device is indicated for additional organism groups and amoxicillin-clavulanate at 0.5/0.25 – 32/16 µg/mL, ampicillin-sulbactam at 0.5/0.25 – 32/16 µg/mL, ticarcillin at 1 – 128 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 Acinetobacter species and Proteus species with ampicillin-sulbactam has been excluded in the BD Phoenix™ therefore no results will be reported. An alternate method should be performed when this combination is identified.

Results for Proteus vulgaris/penneri with ticarcillin has 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

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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 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 × 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 NCCLS documentation.

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:

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 rapid identification (ID) and 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 |

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| 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 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-S16) "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 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 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:

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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.

Amoxicillin-Clavulanate Gram Negative Quality Control Table

| ORGANISM | conc. (μg/mL) | Reference | | BD Phoenix™ | |
| --- | --- | --- | --- | --- | --- |
| | | | | | |
| E. coli ATCC 25922
Expected Range: 2/1 – 8/4 μg/mL | 2 | | 2 | | |
| | 4 | | 239 | | 7 |
| | 8 | | 143 | | 375 |
| | 16 | | | | 2 |
| | >32 | | 1 | | 3 |
| | | | | | |
| E. coli ATCC 35218
Expected Range: 4/2 – 16/8 μg/mL | 4 | | 1 | | |
| | 8 | | 375 | | 380 |
| | 16 | | 6 | | 2 |
| | 32 | | | | 1 |
| | >32 | | 5 | | 9 |

Ampicillin-Sulbactam Gram Negative Quality Control Table

| ORGANISM | conc. (μg/mL) | Reference | | BD Phoenix™ | |
| --- | --- | --- | --- | --- | --- |
| | | | | | |
| E. coli ATCC 25922
Expected Range: 2/1 – 8/4 μg/mL | 2 | | 32 | | 7 |
| | 4 | | 165 | | 189 |
| | 8 | | 2 | | 2 |
| | 16 | | 1 | | 5 |
| | >32 | | | | 2 |
| | | | | | |
| E. coli ATCC 35218
Expected Range: 8/4 – 32/16 μg/mL | 8 | | | | 8 |
| | 16 | | 149 | | 188 |
| | 32 | | 50 | | 4 |
| | >32 | | | | 2 |
| | | | | | |

Ticarcillin Gram Negative Quality Control Table

| ORGANISM | conc. (μg/mL) | Reference | | BD Phoenix™ | |
| --- | --- | --- | --- | --- | --- |
| | | | | | |
| E. coli ATCC 25922
Expected Range: 4 – 16 μg/mL | 4 | | 63 | | |
| | 8 | | 181 | | 375 |
| | 16 | | 139 | | 6 |
| | 32 | | 2 | | 4 |
| | 64 | | | | 1 |
| | >128 | | | | 1 |

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| | | | | | |
| --- | --- | --- | --- | --- | --- |
| P. aeruginosa
ATCC 27853
Expected Range:
8 – 32 μg/mL | 8 | | 1 | | 1 |
| | 16 | | 313 | | 151 |
| | 32 | | 61 | | 221 |
| | 64 | | 9 | | 2 |
| | 128 | | | | 2 |
| | >128 | | | | 8 |
| | | | | | |

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

Gram Negative (GN) Accuracy Summary Clinical and Challenge with Additional Organisms Included

| Amoxicillin-Clavulanate | EA Tot | EA % | EA % | Eval EA Tot | Eval EA % | Eval EA % | CA % | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Combined (Original Data and Additional Org) | 2249 | 2174 | 96.7 | 1439 | 1382 | 96.0 | 2044 | 90.9 | 991 | 162 | 26 | 17 |

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Gram Negative (GN) Accuracy Summary Clinical and Challenge with Additional Organisms Included

| Ampicillin-Sulbactam | EA Tot | EA % | EA % | Eval EA Tot | Eval EA % | Eval EA % | CA % | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Combined (Original Data and Additional Org) | 1305 | 1269 | 97.2 | 850 | 827 | 97.3 | 1142 | 87.5 | 649 | 155 | 6 | 2 |

Gram Negative (GN) Accuracy Summary Clinical and Challenge with Additional Organisms Included

| Ticarcillin | EA Tot | EA % | EA % | Eval EA Tot | Eval EA % | Eval EA % | CA % | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Combined (Original Data and Additional Org) | 2882 | 2728 | 94.7 | 1270 | 1156 | 91.0 | 2673 | 92.7 | 1424 | 139 | 53 | 17 |

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 (SIR) 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:

Amoxicillin - clavulanate
Enterobacteriaceae ≤8/4(S), 16/8 (I), ≥32/16

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Ampicillin – sulbactam

Enterobacteriaceae ≤8/4(S), 16/8 (I), ≥32/16 (R)

Ticarcillin

Enterobacteriaceae ≤16 (S), 32 – 64 (I), ≥128(R)

Pseudomonas aeruginosa ≤64 (S), ≥128(R)

Non – Enterobacteriaceae ≤16 (S), 32 – 64 (I), ≥128(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.

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