BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM - TETRACYCLINE (STREP) 0.0625 - 16 UG/ML

K050881 · Becton, Dickinson & CO · LON · May 12, 2005 · Microbiology

Device Facts

• Record ID: K050881
• Device Name: BD PHOENIX AUTOMATED MICROBIOLOGY SYSTEM - TETRACYCLINE (STREP) 0.0625 - 16 UG/ML
• Applicant: Becton, Dickinson & CO
• Product Code: LON · Microbiology
• Decision Date: May 12, 2005
• 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

System performs automated identification and antimicrobial susceptibility testing (AST) for Streptococcus species. Input: pure culture bacterial isolates suspended in broth, equated to 0.5 McFarland standard. Process: Inoculated polystyrene trays with 136 micro-wells containing dried reagents and redox indicator are loaded into instrument; continuous incubation at 35°C; instrument performs colorimetric oxidation-reduction measurements every 20 minutes. Growth in presence of antibiotic prevents indicator reduction (color change); lack of growth indicates inhibition. Output: MIC values and categorical interpretations (SIR) generated via software-driven 'EXPERT' system using CLSI rules. Used in clinical microbiology laboratories; operated by laboratory technicians. Benefits: rapid, automated determination of antibiotic susceptibility to guide clinical treatment decisions.

Clinical Evidence

Performance evaluated via method comparison against CLSI broth dilution reference panels. Study included 1568 isolates (clinical and challenge sets). Results: 95.2% Essential Agreement (EA), 97.8% Category Agreement (CA). Discrepancy analysis: 20 minor, 9 major, 5 very major discrepancies. Reproducibility: >95% across 3 sites using 10 isolates tested 3 times over 3 days. QC testing with S. pneumoniae ATCC 49619 confirmed results within expected ranges.

Technological Characteristics

Automated microbiology system; molded polystyrene panels (136 micro-wells); redox indicator-based growth detection; turbidity measurement; continuous incubation at 35°C; 20-minute reading interval; software-based interpretation of MIC and categorical results; connectivity to laboratory information systems.

Indications for Use

Indicated for in vitro rapid identification and antimicrobial susceptibility testing (MIC) of Streptococcus species from pure culture isolates. 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)

{0}

Page 1 of 7

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

A. 510(k) Number:
K050881

B. Purpose for Submission:
Addition of the antibiotic tetracycline to the Phoenix™ SMIC/ID and SMIC Panels

C. Measurand:
Tetracycline 0.0625 – 16µg/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 – Tetracycline (strep) 0.0625 – 16µg/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

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

{1}

Page 2 of 7

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 tetracycline at concentrations of $0.0625 - 16\ \mu\mathrm{g/mL}$ 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 $0.5\ \mathrm{McFarland}$ 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 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 $35^{\circ}\mathrm{C}$. The resulting AST has a final inoculum of $5\times 10^{5}\ \mathrm{CFU/ml}$. 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).

{2}

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. |

## 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

{3}

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:

Fifteen on-scale 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 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 | PhoenixTM results |
| --- | --- | --- | --- |
| | | | |
| S. pneumoniae ATCC 49619 Expected range 0.125 –0.5 μg/mL | <= 0.0625 | | |
| | 0.125 | 24 | 1 |
| | 0.25 | 98 | 121 |
| | 0.5 | 3 | 1 |
| | 1 | | |
| | 2 | | |
| | 4 | | |
| | 8 | | |
| | 16 | | |
| | >16 | | |

{4}

Inoculum density control: The organism suspension density of the ID broth was equivalent to a $0.5\mathrm{McFarland}$ 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 $2 - 5\%$ 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. The testing included both fresh clinical isolates and stock isolates along with a challenge set with known results. The study included 1568 isolates with the following performance.

| | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA N | CA % | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 1452 | 1381 | 95.1 | 932 | 882 | 94.6 | 1419 | 97.7 | 525 | 20 | 9 | 4 |
| Challenge | 116 | 111 | 95.7 | 66 | 62 | 93.9 | 115 | 99.1 | 53 | 0 | 0 | 1 |
| Combined | 1568 | 1492 | 95.2 | 998 | 944 | 94.6 | 1534 | 97.8 | 578 | 20 | 9 | 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 test device had a growth rate of $&gt;95\%$ .

# b. Matrix comparison:

Not applicable

{5}

Page 6 of 7

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:
S. pneumoniae and other Streptococcus spp.
Interpretive criteria = ≤ 2 (S), 4 (I), ≥ 8 (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.

{6}

Page 7 of 7