BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM - CEFUROXIME (STREP) 0.125 - 4UG/ML

K052270 · Becton, Dickinson & CO · LON · Oct 5, 2005 · Microbiology

Device Facts

• Record ID: K052270
• Device Name: BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM - CEFUROXIME (STREP) 0.125 - 4UG/ML
• Applicant: Becton, Dickinson & CO
• Product Code: LON · Microbiology
• Decision Date: Oct 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 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, Enterococcus, and Streptococcus. This premarket notification is for the addition of the antimicrobial agent cefuroxime at concentrations of 0.125-4 µg/mL to Streptococcus ID/AST or AST only Phoenix panels. Cefuroxime has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobial agent. Active In Vitro and in Clinical Infections Against: Streptococcus pneumoniae Streptococcus pyogenes (and other streptococci)

Device Story

System uses sealed, self-inoculating polystyrene trays with 136 micro-wells containing dried reagents; organism suspension (0.5 McFarland) prepared in AST-S broth with redox indicator. Instrument continuously incubates panels at 35°C; performs automated colorimetric oxidation-reduction readings every 20 minutes to detect growth. System interprets biochemical/antimicrobial reactions to provide ID and MIC values. Software-driven 'EXPERT' system applies CLSI-derived rules for final interpretation. Used in clinical microbiology laboratories; operated by trained laboratory personnel. Output provides MIC values and categorical interpretations (SIR) to assist clinicians in selecting appropriate antibiotic therapy for bacterial infections.

Clinical Evidence

Clinical performance evaluated by comparing BD Phoenix results to CLSI reference broth microdilution method across multiple US sites. Metrics included Essential Agreement (EA) and Category Agreement (CA). Intra-site reproducibility >90%, inter-site reproducibility >95% for streptococcal isolates.

Technological Characteristics

System consists of automated instrument, software, and molded polystyrene panels (136 wells). Uses broth microdilution method with redox indicator for growth detection. Incubation at 35°C with automated optical reading every 20 minutes. Connectivity: Automated system.

Indications for Use

Indicated for in vitro rapid identification and antimicrobial susceptibility testing of Streptococcus species from pure culture. 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: K052270

B. Purpose for Submission: Addition of the antibiotic Cefuroxime at 0.125 – 4 µg/mL to the Phoenix™ SMIC/ID and SMIC Panels

C. Measurand: Cefuroxime at 0.125 – 4 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 – Cefuroxime (Strep) at 0.125 – 4 µg/mL

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): BD Phoenix™ Automated Microbiology System: 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 belonging to the family Enterobacteriaceae and non -

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Enterobacteriaceae and gram-positive bacteria belonging to the genera Staphylococcus, Enterococcus and Streptococcus.

The BD Phoenix™ SMIC/ID and SMIC Panel is intended for the in vitro rapid identification (ID) of bacteria from pure culture belonging to the genera Streptococcus. The BD Phoenix™ SMIC/ID and SMIC panels are also intended for the quantitative determination of antimicrobial susceptibility by minimal inhibitory concentration (MIC) of most bacteria isolates from pure culture belonging to the genera Streptococcus when used with the BD Phoenix™ Automated Microbiology System.

2. Indication(s) for use:
This submission is for the addition of the antibiotic cefuroxime at concentrations of 0.125 – 4 µg/mL to the Phoenix™ SMIC/ID and SMIC Streptococcus Panels.

3. Special condition for use statement(s):
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-S 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-S broth, which contains an AST-S indicator, prior to inoculating the panel. The AST-S broth is a non-blood, cation-adjusted broth containing purified water, Tween 80, pancreatic digest of casein, peptones and other additional supplements for optimization of streptococcal growth. After adding the indicator solution to the AST-S 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 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).

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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 K number(s): N50510
3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| 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 |
| 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 |
| Inoculum preparation | Inoculum density equated to 0.5 McFarland standard | Inoculum density equated to 1.0 McFarland standard |
| 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. |

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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-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 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:
13 isolates were evaluated for site to site and intra-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 method):
CLSI recommended Quality Control strain was tested at the concentrations listed (see table below). The Phoenix™ results demonstrated that the system can produce QC results in the recommended range. The modes for the reference method and the Phoenix™ were the same.

| Organism | Concentration μg/mL | Reference results | Phoenix™ results |
| --- | --- | --- | --- |
| | | | |
| S. pneumoniae ATCC 49619
Expected range 0.25 – 1 μg/mL | <=0.125 | | 1 |
| | 0.25 | 70 | 67 |
| | 0.5 | 54 | 54 |
| | 1 | | |
| | 2 | | |
| | 4 | | |
| | >4 | | |

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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 $\mathrm{BBL}^{\mathrm{TM}}$ 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. Additional testing on 5 streptococcal strains was performed to demonstrate acceptable performance for streptococcal species.

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 with $2.5 - 5\%$ lysed horse blood was prepared according to the CLSI recommendation and used to compare with the PhoenixTM results. Clinical testing was performed at four sites using both fresh clinical isolates and stock isolates, along with a challenge set with known results. A total of 1938 bacterial strains, of which 735 were fresh isolates $(38\%)$ , 798 were stock isolates $(41.2\%)$ , and 494 $(25.5\%)$ were recent isolates, were tested with the following performance (see table below). Of that total, 915 were S. pneumoniae isolates, which were appropriate for Category Agreement performance evaluation.

The CLSI provides breakpoints for cefuroxime only for S. pneumoniae. With the exception of S. pneumoniae, SIR interpretation results for all other streptococci against cefuroxime will be automatically suppressed from reporting by the Phoenix BDXpert Triggered Rules software; only MIC results will be reported.

Therefore, the table below contains performance data for all Streptococcus species for EA and Eval EA, and S. pneumoniae only for CA and the error rates.

Clinical and Challenge Data for Streptococcus species

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA Tot | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 1812 | 1759 | 97.1 | 309 | 287 | 92.9 | 820 | 796 | 97.1 | 214 | 22 | 1 | 1 |
| Challenge | 126 | 125 | 99.2 | 30 | 30 | 100.0 | 95 | 94 | 98.9 | 56 | 1 | 0 | 0 |
| Combined | 1938 | 1884 | 97.2 | 339 | 317 | 93.5 | 915 | 890 | 97.3 | 270 | 23 | 1 | 1 |

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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.

Because of the limited number of on-scale results, no real trending was observed.

The test device had a growth rate of &gt;95%.

**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**
Interpretive criteria
S. pneumoniae = ≤ 0.5 (S), 1 (I), ≥ 2 (R)

**N. Proposed Labeling:**

The expected value range, interpretive criteria and QC are the same as recommended by 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.