VITEK 2 AST GP CEFTAROLINE

K141149 · bioMerieux, Inc. · LON · Jun 20, 2014 · Microbiology

Device Facts

• Record ID: K141149
• Device Name: VITEK 2 AST GP CEFTAROLINE
• Applicant: bioMerieux, Inc.
• Product Code: LON · Microbiology
• Decision Date: Jun 20, 2014
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1645
• Device Class: Class 2

Intended Use

VITEK® 2 Gram Positive Ceftaroline is designed for antimicrobial susceptibility testing of Gram positive microorganisms and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 Gram Positive Ceftaroline is a quantitative test. Ceftaroline has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections Staphylococcus aureus (including methicillin-susceptible and -resistant isolates) The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., and clinically significant yeast.

Device Story

VITEK® 2 AST-GP Ceftaroline test card; 64 micro-wells containing premeasured antibiotic concentrations and culture media. Input: isolated bacterial colonies diluted in 0.45-0.5% saline. Operation: VITEK® 2 system automatically fills, seals, and incubates cards; VITEK® 2 Compact uses manual filling/sealing. System monitors growth via optical light detection over incubation period. Output: quantitative MIC value and interpretive category (S, I, R). Used in clinical microbiology laboratories by technicians/microbiologists. Results assist clinicians in selecting appropriate antimicrobial therapy for Gram-positive infections.

Clinical Evidence

Bench testing only. Performance evaluated using fresh and stock clinical isolates and challenge strains. Compared against CLSI broth microdilution reference method (16-20 hours incubation). Results: 97.9% overall essential agreement and 99.2% overall category agreement. Reproducibility and quality control testing demonstrated acceptable results.

Technological Characteristics

Miniaturized broth microdilution card; automated incubation and optical growth monitoring; quantitative MIC determination; compatible with VITEK® 2 and VITEK® 2 Compact systems; standalone laboratory instrument platform.

Indications for Use

Indicated for antimicrobial susceptibility testing of isolated colonies of Staphylococcus aureus (including methicillin-susceptible and -resistant isolates) to determine in vitro susceptibility to Ceftaroline. For use by laboratory professionals in clinical settings.

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® 2 AST-GP Clindamycin (k122547)

Submission Summary (Full Text)

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

A. 510(k) Number:
k141149

B. Purpose for Submission:
To obtain clearance for the addition of Ceftaroline to the VITEK® 2 and VITEK® 2 Compact Antimicrobial Susceptibility Test (AST) Systems

C. Measurand:
VITEK® 2 AST-GP Ceftaroline concentrations of 0.25, 0.5, 1, 2μg/mL; the MIC result range for the card is ≤ 0.06 - ≥ 4μg/mL

D. Type of Test:
Quantitative growth based detection algorithm using optics light detection

E. Applicant:
bioMérieux, Inc.

F. Proprietary and Established Names:
VITEK® 2 AST-GP Ceftaroline

G. Regulatory Information:
1. Regulation section:
866.1645 Short-Term Antimicrobial Susceptibility Test System
2. Classification:
Class II
3. Product code:
LON System, Test, Automated, Antimicrobial Susceptibility, Short Incubation

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4. Panel:

83, Microbiology

H. Intended Use:

1. Intended use(s):

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast.

2. Indication(s) for use:

VITEK® 2 Gram Positive Ceftaroline is designed for antimicrobial susceptibility testing of Gram positive microorganisms and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 Gram Positive Ceftaroline is a quantitative test. Ceftaroline has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections

Staphylococcus aureus (including methicillin-susceptible and -resistant isolates) The

VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant yeast.

3. Special conditions for use statement(s):

For prescription use only

4. Special instrument requirements:

VITEK® 2 and the VITEK® 2 Compact Systems

VITEK® 2 Systems 7.01 (PC version) software

I. Device Description:

Each VITEK® 2 test card contains 64 micro-wells. A control well containing only microbiological culture media is resident on all cards. The remaining wells contain

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premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with $0.45 - 0.5\%$ saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

The VITEK® 2 AST-GP Ceftaroline has the following concentrations in the card: 0.25, 0.5, 1, and $2\mu \mathrm{g / mL}$ (equivalent standard method concentration by efficacy in $\mu \mathrm{g / mL}$ ). The MIC result range for the VITEK® 2 card is $\leq 0.06 - \geq 4\mu \mathrm{g / mL}$ .

The MIC ranges, interpretative criteria and equivalent concentrations are as follows:

| VITEK® 2 GP | Equivalent Standard Method Concentration by Efficacy in μg/mL | MIC Ranges and FDA/CLSI Categories, MIC in μg/mL | | |
| --- | --- | --- | --- | --- |
| | | S. aureus | | |
| | | S | I | R |
| Ceftaroline | 0.25, 0.5, 1, 2 | ≤1 | 2 | ≥4 |

# J. Substantial Equivalence Information:

1. Predicate device name(s):

VITEK® 2 AST-GP Clindamycin

2. Predicate 510(k) number(s):

k122547

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | Determine antimicrobial susceptibility to antimicrobial agents | Same |
| Inoculation and test organism | Isolated colonies | Same |
| Test Card | VITEK® 2 card format with base broth | Same |
| Instrument | VITEK® 2 and VITEK®2 Compact Systems | Same |
| Differences | | |
| Item | Device | Predicate |

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Antibiotic | Ceftaroline- specific concentrations | Clindamycin- specific concentrations |
| Reading algorithm | Unique for Ceftaroline | Unique for Clindamycin |

## K. Standard/Guidance Document Referenced (if applicable):

Class II Special Controls Guidance Document: “Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA”, August 28, 2009

CLSI M7-A8 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard”, January 2009

CLSI M100-S20* and S23 “Performance Standards for Antimicrobial Susceptibility; Twenty-First Information Supplement”, January, 2010, and 2013

*Ceftaroline QC parameters

## L. Test Principle:

Each VITEK® 2 test card contains 64 micro-wells. A control well containing only microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 – 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals, and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

The VITEK® 2 AST-GP Ceftaroline has the following concentrations in the card: 0.25, 0.5, 1, and 2 µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK® 2 card is ≤0.06- ≥4 µg/mL

## M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Reproducibility was demonstrated using ten S. aureus isolates at three sites on three separate days in triplicates. The study included the Auto-dilution and the Manual dilution with the VITEK®2, and the Manual dilution with the VITEK®2 Compact. All results were >95% reproducible.

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b. Linearity/assay reportable range:

Not Applicable

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The recommended QC isolates were tested on every test occasion with the reference method and the VITEK®2. The reference method QC results were in range for every day tested. The VITEK®2 was tested a sufficient number of times to demonstrate that the system can produce QC results in the recommended range. The ceftaroline test results demonstrate that the VITEK®2 can produce QC results within the expected range.

Quality Control was performed during the studies using both the auto-dilution and the manual method of diluting the organisms. Results demonstrated that methods were comparable with the same mode.

Quality Control Summary (VITEK®2, Auto and Manual dilution)

| Organism | Ceftaroline (μg/ml) | Auto-dilution | | Manual dilution | |
| --- | --- | --- | --- | --- | --- |
| | | Ref. | Test | Ref. | Test |
| S. aureus
ATCC 29213 | ≤0.03 | | | | |
| Expected Range
0.12- 0.5 μg/mL | 0.06 | | | | 1 |
| | 0.12 | 66 | 4 | 61 | 4 |
| | 0.25 | 168 | 230 | 165 | 221 |
| | 0.5 | | | | |

An additional QC study was performed with the VITEK®2 Compact, the secondary option, at three sites. VITEK®2 Compact does not have a functionality to support auto dilution to inoculate the card. Results were as follows:

Quality Control Summary (VITEK®2 Compact, Manual dilution)

| Organism | Ceftaroline (μg/ml) | Manual-dilution | |
| --- | --- | --- | --- |
| | | Ref. | Test |
| S. aureus
ATCC 29213 | ≤0.03 | | |
| Expected Range
0.12- 0.5 μg/mL | 0.06 | | 1 |
| | 0.12 | 61 | 8 |
| | 0.25 | 153 | 205 |
| | 0.5 | | |

Inoculum density control was monitored using the DensiCHEK™ Plus instrument. This was standardized weekly with all results recorded and in the expected range. Verification was performed during internal testing.

d. Detection limit: Not Applicable

e. Analytical specificity: Not Applicable

f. Assay cut-off: Not Applicable

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2. Comparison studies:

The reference method follows the CLSI approved broth microdilution testing conditions for ceftaroline:

- Medium: Mueller-Hinton broth with the appropriate dilutions of antimicrobial solution added.
- Inoculum: Direct colony suspension
- Incubation: 35°C, ambient air, 16 - 20 hours

It is noted in the FDA approved pharmaceutical labeling for ceftaroline that broth dilution MICs need to be read within 18 hours due to degradation of ceftaroline activity by 24 hours. The sponsor conducted a study with 52 S. aureus isolates to evaluate the 18hrs vs. 20hrs read for the reference method result. The 20hrs read and the 18hrs read were in agreement.

a. Method comparison with predicate device:

Clinical comparative study was performed at three external sites using the VITEK®2 AST-GP Ceftaroline card and the reference broth microdilution containing Ceftaroline. A total of 302 clinical isolates were tested by auto inoculation and 106 of the 302 isolates were stock isolates (35.1%, 106/302). All Staphylococcus aureus isolates grew in the study.

The clinical isolates were comprised of 48.8% of oxacillin resistant S. aureus (MRSA) and 51.2% of oxacillin susceptible S. aureus (MSSA); all 78 challenge isolates were MRSA and were tested at one external site. The VITEK®2 performance was presented in the table below:

Performance Summary Table (VITEK®2, Auto Dilution)

| | Total | EA | %EA | Eval EA Total | Eval EA | Eval %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | | | | | | | | | | | | |
| MRSA | 148 | 148 | 100 | 148 | 148 | 100 | 148 | 100 | 0 | 0 | 0 | 0 |
| Challenge (MRSA) | 78 | 77 | 98.7 | 78 | 77 | 98.7 | 76 | 97.4 | 0 | 2 | 0 | 0 |
| MSSA | 154 | 147 | 95.5 | 145 | 138 | 95.2 | 153 | 99.4 | 0 | 1 | 0 | 0 |
| Combined | 380 | 372 | 97.9 | 371 | 363 | 97.8 | 377 | 99.2 | 0 | 3 | 0 | 0 |

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

maj-major discrepancies
vmj-very major discrepancies
min- minor discrepancies

MRSA (clinical+ challenge)

The majority of MIC values were at 0.5μg/mL; there were 14 isolates at the breakpoint of 1μg/mL, with one minor error, but within EA. The other minor error was two dilutions higher [reference: 0.5 (S), VITEK®2: 2 (I)].

MSSA

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The MIC result ranges were 0.125- 0.25μg/mL, with 116 MSSA at 0.25μg/mL. There was one minor error [reference: 2 (I), VITEK®2: 0.25(S)].

The comparative study did not include any ceftaroline resistant S. aureus and a limitation is in place for the ceftaroline/S. aureus combination in the labeling.

Manual Dilution:

The challenge set of 78 S. aureus isolates were tested at one external site by manual inoculation method for VITEK®2 and VITEK®2 Compact with the following performance.

Comparison Challenge Data - VITEK®2, and VITEK®2 Compact (Manual dilution)

| | Total | EA | %EA | Eval EA Total | Eval EA | Eval %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| VITEK2 | 78 | 77 | 98.7 | 78 | 77 | 98.7 | 78 | 100 | 0 | 0 | 0 | 0 |
| VITEK2 Compact | 78 | 78 | 100 | 78 | 78 | 100 | 78 | 100 | 0 | 0 | 0 | 0 |

The performance of the optional VITEK®2 Compact was evaluated in the QC, challenge, and reproducibility studies.

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): None

4. Clinical cut-off: Not applicable

5. Expected values/Reference range:

The interpretative criteria and QC ranges are as recommended in the approved drug label.

S. aureus (including MRSA): ≤1(S), 2(I), ≥4(R)

N. Proposed Labeling:

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

O. Conclusion:

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

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