← Product Code [JWY](/productcode/JWY) · K093604

# ETEST MOXIFLOXACIN 0.002-32 UG/ML (K093604)

_Ab Biomerieux · JWY · Aug 25, 2010 · Microbiology · SESE_

**Canonical URL:** https://fda-staging.innolitics.com/device/K093604

## Device Facts

- **Applicant:** Ab Biomerieux
- **Product Code:** [JWY](/productcode/JWY.md)
- **Decision Date:** Aug 25, 2010
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1640
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

This submission is for Etest® Moxifloxacin for MIC determinations across 0.002-32 µg/mL with B. fragilis, B. thetaiotaomirron, C. perfringens and Peptostreptoroccus spp. Etest® is a quantitative technique for determination of antimicrobial susceptibility of both non-fastidious Gram negative and Gram positive aerobic bacteria such as Enterobaterianas, Staphylocourus and Entervacus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, Streptowers and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC) in ug/mL of different antimicrobial agents against microorganisms as tested on agar using overnight incubation.

## Device Story

Etest® is a manual, quantitative antimicrobial susceptibility test (AST) system. It consists of a 5mm x 60mm inert, non-porous plastic strip containing a predefined exponential gradient of dried, stabilized moxifloxacin. The strip is applied to an inoculated agar plate; the antibiotic diffuses into the agar, creating a concentration gradient. Following overnight incubation, a symmetrical inhibition ellipse forms around the strip. The Minimum Inhibitory Concentration (MIC) is determined by reading the value where the ellipse edge intersects the strip. Used in clinical laboratories by trained personnel to guide antibiotic therapy by identifying susceptibility (S), intermediate (I), or resistance (R) of anaerobic bacteria to moxifloxacin. Results assist clinicians in selecting appropriate antimicrobial treatments based on achievable systemic concentrations.

## Clinical Evidence

Performance evaluated using 471 total isolates (418 clinical/stock, 53 challenge) including B. fragilis, B. thetaiotaomicron, C. perfringens, and Peptostreptococcus spp. Compared against CLSI agar dilution reference method. Combined results showed 96.2% Essential Agreement (EA) and 92.2% Category Agreement (CA). No major or very major errors were observed. Reproducibility study at three sites using 27 organisms demonstrated 100% reproducibility.

## Technological Characteristics

Quantitative antimicrobial susceptibility test strip. Features a predefined antibiotic gradient of Moxifloxacin (0.002-32 µg/mL). Operates via diffusion on agar media. Manual interpretation of growth inhibition ellipse. No software or electronic components.

## Regulatory Identification

An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.

## Predicate Devices

- Etest® (k000298)

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k093604

B. Purpose for Submission:
To obtain a substantial equivalence determination for Etest® strip for determining susceptibility of anaerobic organisms to moxifloxacin

C. Measurand:
Moxifloxacin concentrations of 0.002 – 32 µg/mL

D. Type of Test:
Etest® is a quantitative Antimicrobial Susceptibility Test (AST) growth based detection method. The Etest strip contains a predefined exponential gradient of antibiotic and has the MIC reading scale in µg/mL. The gradient covers a continuous concentration range across 15 two-fold dilutions of a conventional MIC method.

E. Applicant:
AB BioMerieux

F. Proprietary and Established Names:
Etest® Moxifloxacin for Antimicrobial Susceptibility Testing

G. Regulatory Information:
1. Regulation section:
866.1640 Antimicrobial Susceptibility Test (AST) Powder
2. Classification:
II
3. Product code:
JWY - Manual Antimicrobial Susceptibility Test Systems

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4. Panel:

83 Microbiology

H. Intended Use:

1. Intended use(s):

Etest® is a quantitative technique for determination of antimicrobial susceptibility of both non-fastidious Gram-negative and Gram positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC) in $\mu \mathrm{g} / \mathrm{mL}$ of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation.

2. Indication(s) for use:

Etest® is a quantitative technique for determination of antimicrobial susceptibility of both non-fastidious Gram-negative and Gram positive aerobic bacteria such as Enterobacteriaceae, Pseudomonas, Staphylococcus and Enterococcus species and fastidious bacteria, such as anaerobes, N. gonorrhoeae, S. pneumoniae, Streptococcus and Haemophilus species. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC) in $\mu \mathrm{g} / \mathrm{mL}$ of different antimicrobial agents against microorganisms as tested on agar media using overnight incubation.

This $510(\mathrm{k})$ submission is for the addition of the antibiotic moxifloxacin at concentrations of $0.002 - 32\mu \mathrm{g / mL}$ to the Etest® strip for testing of Bacteroides fragilis, Bacteroides thetaiotaomicron, Clostridium perfringens, and Peptostreptococcus spp.

3. Special conditions for use statement(s):

For prescription use

4. Special instrument requirements:

Manual readings only

I. Device Description:

Etest® consists of a thin, inert and non-porous plastic strip, 5mm wide and 60 mm

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long. One side of the strip carries a two-letter code designating the identity of the antibiotic and is calibrated with MIC values in terms of  $\mu \mathrm{g} / \mathrm{mL}$ . A predefined exponential gradient of the dried and stabilized antibiotic covers a continuous concentration range across 15 two-fold dilutions of a conventional MIC method.

For anaerobic bacteria, the MIC interpretive criteria for moxifloxacin are as follows:

MIC  $(\mu \mathrm{g} / \mathrm{mL})$  Interpretation\*

$\leq 2$  Susceptible (S)

4 Intermediate (I)

$\geq 8$  Resistant (R)

$^{*}\mathrm{S} =$  Susceptible: Attainable levels in blood or tissue on usual usage, including oral administration when applicable.

$\mathrm{I} =$  Intermediate: The intermediate category implies clinical efficacy in body sites where the drugs are physiologically concentrated (e.g. quinolones and B-lactams in urine), or when a higher than normal dosage of drug can be used (e.g. B-lactams). The "intermediate" category also includes a "buffer zone" which should prevent small, uncontrolled, technical factors from causing major discrepancies in interpretations, especially for drugs with narrow pharmacotoxicity margins.

$\mathrm{R} =$  Resistant to usually achievable systemic concentrations.

# J. Substantial Equivalence Information:

1. Predicate device name(s):

Etest®

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

k000298

3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Intended Use | Quantitative susceptibility to antimicrobial agents | Same  |
|  Incubation Temperature | 35° | Same  |
|  Inoculation | Isolated colonies from culture used | Same  |
|  Result | MIC | MIC  |
|  Differences  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Antibiotic | Moxifloxacin | Other antibiotics  |

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|  Differences  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Incubation Atmosphere | Anaerobic | Aerobic and microaerophilic  |

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

1. Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm071462.pdf

2. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria, Approved Standard - 7th Edition, Document M11-A7

L. Test Principle:

The Etest® gradient technology is based on a combination of the concepts of dilution and diffusion test methods for susceptibility testing. Etest® directly quantifies antimicrobial susceptibility in terms of discrete MIC values. When the Etest® strip is applied to an inoculated agar plate, the antibiotic is immediately released from the plastic surface into the agar. A predefined, continuous gradient of antibiotic concentrations is created and maintained directly underneath the strip. After incubation whereby bacterial growth becomes visible, a symmetrical inhibition ellipse centered along the strip will be seen. The MIC value in ug/mL is read where the ellipse edge intersects the strip. Since Etest® generates MIC values which fall between two-fold dilutions for interpretation; the MIC value read must be recorded to the next two-fold dilution.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

A reproducibility study was conducted at three study sites. Twenty seven anaerobic organisms (11 B. fragilis, 10 B. thetaiotaomicrons, 3 C. perfringens, and 3 Peptostreptococcus species) were tested at each site. Reference method plates were read visually in accordance with CLSI standard. Reproducibility was calculated as the percent of results for the combined sites which were within +/- one doubling dilution of the mode MIC value for all sites.

For the sake of reproducibility calculations, off-scale values are handled in two ways; "best case" and "worst case" scenarios. Best case calculation for reproducibility assumes the off-scale result is within one well from the mode

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MIC value. Worst case calculation for reproducibility assuming the off-scale result is greater than one well from the mode MIC value. There were no off-scale results in this study. So, only one value for overall reproducibility is reported.

The overall reproducibility was 100% for 27 organisms with on-scale results tested by Etest at 3 sites.

b. Linearity/assay reportable range: Not applicable

c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolates were tested a sufficient number of times with acceptable results with the reference method. The Etest® results demonstrate that the system can produce QC results in the recommended range.

Moxifloxacin quality control data for anaerobic bacteria from combined sites is shown below. At least 20 test results per organism at each site were available.

|  QC Organism | MIC range (μg/mL) | MIC value (μg/mL) | Reference Frequency | Etest Frequency  |
| --- | --- | --- | --- | --- |
|  B. fragilis
ATCC 25285
Acceptable MIC range: 0.12 - 0.5 μg/mL | 0.12 - 0.5 | 0.06 | 0 | 0  |
|   |   |  0.125 | 47 | 9  |
|   |   |  0.25 | 21 | 59  |
|   |   |  0.5 | 0 | 0  |
|   |   |  1 | 0 | 0  |
|  |   |   |   |   |
|  B. thetaiotaomicron
ATCC 29741
Acceptable MIC range: 1 - 4 μg/mL | 1 - 4 | 0.5 | 0 | 0  |
|   |   |  1 | 35 | 30  |
|   |   |  2 | 33 | 35  |
|   |   |  4 | 0 | 2  |
|   |   |  8 | 0 | 0  |
|  |   |   |   |   |
|  E. lentum ATCC 43055
Acceptable MIC range: 0.12 - 0.5 μg/mL | 0.12 - 0.5 | 0.06 | 0 | 0  |
|   |   |  0.125 | 32 | 40  |
|   |   |  0.25 | 34 | 26  |
|   |   |  0.5 | 2 |   |
|   |   |  1 | 0 | 0  |
|  |   |   |   |   |
|  C. difficile
ATCC 700057
Acceptable MIC | 1 - 4 | 0.5 | 0 | 0  |
|   |   |  1 | 20 | 43  |
|   |   |  2 | 46 | 22  |

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|  range: | 4 | 0 | 0  |
| --- | --- | --- | --- |
|  1-4 μg/mL | 8 | 0 | 0  |

All QC values were in the expected range. Etest results with *B. fragilis* tended towards a one doubling dilution higher than the reference standard.

A 0.5 McFarland was used to prepare inoculum for reference agar dilution method. A 1.0 McFarland standard was prepared for the Etest inoculum. Colony count was performed periodically at each site to verify that the inoculum density was in the expected CFU/mL.

Inoculum density control for QC organisms ranged between 0.7X10⁸ CFU/mL and 2.7 X 10⁸ CFU/mL for direct inoculum E-test and between 0.7X10⁸ CFU/mL and 1.6 X10⁸ CFU/mL for the reference agar dilution method. The growth rate was 100% for all organisms tested.

*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 agar dilution was used as the reference method to determine susceptibility. Clinical testing was performed at three sites. Etest and reference agar dilution were set up on *Brucella* blood agar (*Brucella* agar with 5% blood and 1% hemin and vitamin k).

Clinical testing was performed on 418 anaerobic stock and fresh clinical isolates (207 *B. fragilis*, 116 *B. thetaiotaomicrons*, 61 *C. perfringens*, and 34 *Peptostreptococcus* species). In total, 213 isolates were freshly collected clinical isolates representing 51% of the total.

In addition, a set of 53 challenge isolates was tested (25 *B. fragilis*, 21 *B. thetaiotaomicron*, 4 *C. perfringens*, and 3 *Peptostreptococcus* species).

Performance was compared to the CLSI agar dilution reference method. The performance evaluations are shown in the tables below.

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Summary of essential and category agreement results for Challenge and Clinical strains (UPDATED)

B. fragilis

|   | Total Tested | #EA | %EA Total | Total Evaluable | #EA of Evaluable | %EA Evaluable | #CA | %CA | #R | #vmj | #maj | #min  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Clinical | 207 | 200 | 96.6 | 196 | 189 | 96.4 | 179 | 91.3 | 10 | 0 | 0 | 17  |
|  Challenge | 25 | 24 | 96.0 | 25 | 24 | 96.0 | 23 | 92.0 | 3 | 0 | 0 | 2  |
|  Both | 232 | 224 | 96.6 | 221 | 213 | 96.4 | 202 | 91.4 | 13 | 0 | 0 | 19  |

B. thetaiotaomicron

|   | Total Tested | #EA | %EA Total | Total Evaluable | #EA of Evaluable | %EA Evaluable | #CA | %CA | #R | #vmj | #maj | #min  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Clinical | 116 | 115 | 99.1 | 108 | 107 | 99.1 | 99 | 91.7 | 8 | 0 | 1 | 8  |
|  Challenge | 21 | 19 | 90.5 | 20 | 18 | 90.0 | 17 | 85.0 | 2 | 0 | 0 | 3  |
|  Both | 137 | 134 | 97.8 | 128 | 125 | 97.7 | 116 | 90.6 | 10 | 0 | 1 | 11  |

C. perfringens

|   | Total Tested | #EA | %EA Total | Total Evaluable | #EA of Evaluable | %EA Evaluable | #CA | %CA | #R | #vmj | #maj | #min  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Clinical | 61 | 60 | 98.4 | 61 | 60 | 98.4 | 59 | 96.7 | 0 | 0 | 0 | 2  |
|  Challenge | 4 | 4 | 100 | 4 | 4 | 100 | 4 | 100 | 0 | 0 | 0 | 0  |
|  Both | 65 | 64 | 98.5 | 65 | 64 | 98.5 | 63 | 96.9 | 0 | 0 | 0 | 2  |

Peptostreptococcus spp.

|   | Total Tested | #EA | %EA Total | Total Evaluable | #EA of Evaluable | %EA Evaluable | #CA | %CA | #R | #vmj | #maj | #min  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Clinical | 34 | 30 | 88.2 | 33 | 29 | 87.9 | 32 | 97.0 | 2 | 0 | 0 | 1  |
|  Challenge | 3 | 2 | 66.7 | 3 | 2 | 66.7 | 2 | 66.7 | 1 | 0 | 0 | 1  |
|  Both | 37 | 32 | 86.5 | 36 | 31 | 86.1 | 34 | 94.4 | 3 | 0 | 0 | 2  |

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ALL ISOLATES

|   | Total Tested | #EA | %EA Total | Total Evaluable | #EA of Evaluable | %EA Evaluable | #CA | %CA | #R | #vmj | #maj | #min  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Clinical | 418 | 405 | 96.9 | 398 | 385 | 96.7 | 369 | 92.7 | 20 | 0 | 1 | 28  |
|  Challenge | 53 | 49 | 92.5 | 52 | 48 | 92.3 | 46 | 88.5 | 6 | 0 | 0 | 6  |
|  Both | 471 | 454 | 96.4 | 450 | 433 | 96.2 | 415 | 92.2 | 26 | 0 | 1 | 34  |

EA-Essential Agreement

CA-Category Agreement

R-Resistant isolates.

Essential agreement (EA) is when the Etest® agree with the reference test panel results exactly or within one doubling dilution of the reference method. Category agreement (CA) is when the Etest® result interpretation agrees exactly with the reference panel result interpretation based on interpretive criteria.

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# Summary of essential and category agreement results for Challenge and Clinical strains (Updated)

Clinical data

|  Organism group | Total Tested | #EA | %EA Total | Total Evaluable | #EA of Evaluable | %EA Evaluable | #CA | %CA | #R | #vmj | #maj | #min  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  B. fragilis | 207 | 200 | 96.6 | 196 | 189 | 96.4 | 179 | 91.3 | 10 | 0 | 0 | 17  |
|  B. thetaiotaomicron | 116 | 115 | 99.1 | 108 | 107 | 99.1 | 99 | 91.7 | 8 | 0 | 1 | 8  |
|  C. perfringens | 61 | 60 | 98.4 | 61 | 60 | 98.4 | 59 | 96.7 | 0 | 0 | 0 | 2  |
|  Peptostreptococcus spp. | 34 | 30 | 88.2 | 33 | 29 | 87.9 | 32 | 97.0 | 2 | 0 | 0 | 1  |
|  TOTAL | 418 | 405 | 96.9 | 398 | 385 | 96.7 | 369 | 92.7 | 20 | 0 | 1 | 28  |

Challenge

|  B. fragilis | 25 | 24 | 96.0 | 25 | 24 | 96.0 | 23 | 92.0 | 3 | 0 | 0 | 2  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  B. thetaiotaomicron | 21 | 19 | 90.5 | 20 | 18 | 90.0 | 17 | 85.0 | 2 | 0 | 0 | 3  |
|  C. perfringens | 4 | 4 | 100 | 4 | 4 | 100 | 4 | 100 | 0 | 0 | 0 | 0  |
|  Peptostreptococcus spp. | 3 | 2 | 66.7 | 3 | 2 | 66.7 | 2 | 66.7 | 1 | 0 | 0 | 1  |
|  TOTAL | 53 | 49 | 92.5 | 52 | 48 | 92.3 | 46 | 88.5 | 6 | 0 | 0 | 6  |

Clinical and Challenge Combined

|  All organisms | 471 | 454 | 96.4 | 450 | 433 | 96.2 | 415 | 92.2 | 26 | 0 | 1 | 34  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |

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For 418 fresh clinical/stock isolates, the EA/CA for Etest were 96.7%, and 92.7%, respectively.

For 53 challenge organisms, the EA /CA for Etest were 92.5%, and 88.7%, respectively. The CA of 88.7% is acceptable in light of a very good EA and the occurrence of only minor discrepancies (i.e. no maj or vmj discrepancies).

For 471 clinical and challenge organisms combined, the EA /CA for Etest were 96.2%, and 92.2%, respectively.

A total of 26 organisms were classified as resistant to moxifloxacin and there were no maj or vmj errors seen.

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:

According to the FDA drug label, Moxifloxacin has been shown to be active against most strains of the following anaerobic microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section of the label.

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Bacteroides fragilis
Bacteroides thetaiotaomicron
Clostridium perfringens
Peptostreptococcus species

For the above anaerobic bacteria, the MIC (μg/mL) interpretive criteria for moxifloxacin are as follows:

≤ 2 Susceptible (S); 4 Intermediate (I); ≥ 8 Resistant (R)

The Interpretative criteria, QC isolates and the expected ranges are the same as recommended by the CLSI and the FDA. However, the FDA drug label does not provide QC ranges or interpretive criteria for Clostridium difficile.

## N. Proposed Labeling:

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

## O. Conclusion:

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

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**Source:** [https://fda-staging.innolitics.com/device/K093604](https://fda-staging.innolitics.com/device/K093604)

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