← Product Code [JWY](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY) · K162854

# Liofilchem MIC Test Strip (MTS) Meropenem 0.002-32.0 ug/ml (K162854)

_Liofilchem s.r.l. · JWY · Dec 19, 2016 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K162854

## Device Facts

- **Applicant:** Liofilchem s.r.l.
- **Product Code:** [JWY](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY.md)
- **Decision Date:** Dec 19, 2016
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1640
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

The Liofilchem® MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorthoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in ug/mL of antimicrobial agents against . teria as tested on agar media using overnight incubation and manual reading procedures. The indications for use of this 510(k) is specifically for the Meropenen MTS at concentrations of 0.002-32 ug/mL. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against meropenem according to the FDA label are: Escherichia coli Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa

## Device Story

Liofilchem MIC Test Strip (MTS) is a quantitative antimicrobial susceptibility test (AST) device. It consists of a specialized paper strip impregnated with a predefined concentration gradient of the antibiotic Meropenem (0.002-32 ug/mL). The strip is placed on inoculated agar media and incubated overnight. The device functions by creating a stable concentration gradient of the antibiotic in the agar; the minimum inhibitory concentration (MIC) is determined by observing the point of intersection between the bacterial growth inhibition ellipse and the strip. The test is performed in clinical microbiology laboratories by trained technicians. The output is a visual MIC value (ug/mL), which healthcare providers use to guide antibiotic therapy selection and dosing for patients with bacterial infections. The device provides a standardized, manual method for determining susceptibility, aiding in the management of bacterial infections.

## Clinical Evidence

No clinical data provided. Performance is established via bench testing comparing the MTS method to reference broth microdilution methods for determining MIC values for specified bacterial species.

## Technological Characteristics

Specialized paper strip impregnated with predefined antimicrobial concentration gradient (15 two-fold dilutions). Manual reading of inhibition ellipse. Media: Mueller Hinton agar. Incubation: 35 ± 2°C for 16-20 hours. Standalone, non-electronic, manual test system.

## 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.

## Submission Summary (Full Text)

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>
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
K162854

B. Purpose for Submission:
To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing Meropenem at concentrations of 0.002-32 µg/mL for susceptibility testing of, E. coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa

C. Measurand:
Meropenem 0.002-32 µg/mL

D. Type of Test:
Quantitative AST growth based detection

E. Applicant:
Liofilchem s.r.l.

F. Proprietary and Established Names:
Liofilchem MIC Test Strip (MTS)-Meropenem 0.002-32 µg/mL

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

{1}

4. Panel:

83 – Microbiology

H. Intended Use:

1. Intended use(s):

The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in $\mu \mathrm{g} / \mathrm{mL}$ of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures.

2. Indication(s) for use:

The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of non-fastidious Gram negative and Gram positive aerobic bacteria (for example, Enterobacteriaceae, Pseudomonas, Enterococcus and Staphylococcus species) and fastidious bacteria (for example, anaerobes, Haemophilus and Streptococcus species and N. gonorrhoeae). MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in $\mu \mathrm{g} / \mathrm{mL}$ of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures.

The indications for use of this $510(\mathrm{k})$ is specifically for the Meropenem MTS at concentrations of $0.002 - 32~\mu \mathrm{g / mL}$.

The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Meropenem according to the FDA label are:

Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa

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3. Special conditions for use statement(s):

For prescription use

The following limitation is included in the Liofilchem Meropenem MIC Test Strip (MTS) package insert supplement:

The ability of the Liofilchem MIC Test Strip (MTS) to detect resistance is unknown for the following antibiotic/organism combination, because an insufficient number of resistant isolates were available during the comparative testing: Meropenem-Proteus mirabilis

4. Special instrument requirements:

Manual reading only

I. Device Description:

The meropenem MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of meropenem across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the meropenem code (MRP) and the MIC reading scale in $\mu \mathrm{g} / \mathrm{mL}$. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of $\mu \mathrm{g} / \mathrm{mL}$ at the point where the edge of the inhibition ellipse intersects the MIC Test Strip.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Liofilchem MTS, Vancomycin

2. Predicate $510(\mathbf{k})$ number(s):

K153687

3. Comparison with predicate:

{3}

4
Table 1: Comparison with the Predicate Device

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate K153687  |
|  Intended Use | Quantitative susceptibility to antimicrobial agents against specified gram negative organisms | Same  |
|  Media | Mueller Hinton agar | Same  |
|  Inoculation | Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied applied to agar with swab manually | Same  |
|  Reading | Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip | Same  |
|  Result | MIC | Same  |
|  Differences  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Antibiotic | Meropenem | Vancomycin  |
|  Incubation | 35 ± 2°C for 16-20hrs | 35 ± 2°C for 24hrs  |

K. Standard/Guidance Document Referenced:

"Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA"

CLSI M07-A10 "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015"

CLSI M100-S26 "Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016"

L. Test Principle:

MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of $\mu \mathrm{g} / \mathrm{mL}$ at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip.

Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to $(\geq)$ the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than $(<)$ the lowest value. An MIC of $0.125\mu \mathrm{g} / \mathrm{mL}$ is considered to be the same as $0.12\mu \mathrm{g} / \mathrm{mL}$ for reporting purposes.

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An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two fold value before categorization.

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

### a. Precision/Reproducibility:

Reproducibility testing was performed using five *Pseudomonas aeruginosa* isolates and five *Enterobacteriaceae* isolates (three *E. coli*, one *K. pneumoniae*, and one *Enterobacter cloacae*). These ten organisms were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within +/- one doubling dilution of the mode. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable.

### b. Linearity/assay reportable range:

Not applicable

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

The recommended Quality Control (QC) isolates were tested a sufficient number of times at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than 95% of the time. The results are summarized in Table 2.

Table 2: Meropenem MTS QC results

|  Organism | Concentration (μg/mL) | Reference | MTS  |
| --- | --- | --- | --- |
|  E. coli
ATCC 25922
Expected Results
0.008-0.06 μg/mL | ≤0.002 |  |   |
|   |  0.004 |  |   |
|   |  0.008 |  |   |
|   |  0.015 | 12 | 15  |
|   |  0.03 | 45 | 45  |
|   |  0.06 | 3 |   |
|   |  0.12 |  |   |
|  |   |   |   |
|  P. aeruginosa
ATCC 27853
Expected Results
0.25 – 1 μg/mL | 0.015 |  |   |
|   |  0.03 |  |   |
|   |  0.06 |  |   |
|   |  0.12 |  |   |
|   |  0.25 | 33 | 31  |
|   |  0.5 | 19 | 27  |
|   |  1 | 8 | 2  |
|   |  2 |  |   |

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The QC results were acceptable.

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:

Clinical testing was conducted at three sites (two U.S. sites and one outside the U.S.). A total of 327 organisms were tested and all organisms grew in the studies. All isolates tested were fresh. The clinical testing included 278 (85%) fresh (isolated no longer than seven days prior to testing) and 49 (15%) recent clinical isolates (isolated no longer than one year prior to testing). The study included 192 Enterobacteriaceae and 135 Pseudomonas aeruginosa clinical isolates. The Enterobacteriaceae tested were Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis.

A total of 75 challenge isolates were also evaluated (31 Enterobacteriaceae and 44 P. aeruginosa. The performance is shown in Table 3.

Table 3: Performance of Enterobacteriaceae and Pseudomonas aeruginosa isolates

|  Meropenem | EA Tot | EA N | EA % | Eval. EA Tot | Eval. EA N | Eval. EA % | CA N | CA % | #R | min | maj | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Enterobacteriaceae  |   |   |   |   |   |   |   |   |   |   |   |   |
|  E. coli  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 103 | 102 | 99 | 99 | 98 | 99 | 102 | 99 | 13 | 1 | 0 | 0  |
|  Challenge | 15 | 15 | 100 | 15 | 15 | 100 | 14 | 93.3 | 2 | 1 | 0 | 0  |
|  Combined | 118 | 117 | 99.2 | 114 | 113 | 99.1 | 116 | 98.3 | 15 | 2 | 0 | 0  |
|  K. pneumoniae  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 58 | 58 | 100 | 54 | 54 | 100 | 58 | 100 | 9 | 0 | 0 | 0  |
|  Challenge | 14 | 13 | 92.9 | 13 | 12 | 92.3 | 11 | 78.6 | 9 | 3 | 0 | 0  |
|  Combined | 72 | 71 | 98.6 | 67 | 66 | 98.5 | 69 | 95.8 | 18 | 3 | 0 | 0  |
|  P. mirabilis  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 31 | 30 | 96.8 | 31 | 30 | 96.8 | 31 | 100 | 0 | 0 | 0 | 0  |
|  Challenge | 2 | 2 | 100 | 2 | 2 | 100 | 2 | 100 | 1 | 0 | 0 | 0  |
|  Combined | 33 | 32 | 97.0 | 33 | 32 | 97 | 33 | 100 | 1 | 0 | 0 | 0  |
|  Enterobacteriaceae | 223 | 220 | 98.7 | 214 | 211 | 98.6 | 218 | 97.8 | 34 | 5 | 0 | 0  |

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|  Meropenem | EA Tot | EA N | EA % | Eval. EA Tot | Eval. EA N | Eval. EA % | CA N | CA % | #R | min | maj | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Pseudomonas aeruginosa  |   |   |   |   |   |   |   |   |   |   |   |   |
|  Clinical | 135 | 123 | 91.1 | 105 | 93 | 88.6 | 129 | 95.6 | 43 | 6 | 0 | 0  |
|  Challenge | 44 | 42 | 95.5 | 17 | 15 | 88.2 | 44 | 100 | 40 | 0 | 0 | 0  |
|  All P. aeruginosa | 179 | 165 | 92.2 | 122 | 108 | 88.5 | 173 | 96.6 | 83 | 6 | 0 | 0  |
|  All organisms | 402 | 385 | 95.8 | 336 | 319 | 94.9 | 391 | 97.3 | 117 | 11 | 0 | 0  |

EA - Essential Agreement maj - major discrepancies
CA - Category Agreement vmj- very major discrepancies
R- resistant isolates min- minor discrepancies

Essential Agreement (EA) is when the Liofilchem MIC Test Strip (MST) results agree exactly or within one doubling dilution of the reference broth microdilution results. Category Agreement (CA) is when the Liofilchem MIC Test Strip (MST) result interpretation agrees exactly with the reference broth microdilution result interpretation.

In the challenge study, low CA was observed for  $K$  pneumoniae (78.6%, 11/14); however, this was mainly due to three minor errors. The % Evaluable EA was 92.3%.

Enterobacteriaceae: The overall performance for Enterobacteriaceae was acceptable, with an EA of  $98.7\%$ , a CA of  $97.8\%$ , and a minor discrepancy rate of  $2.24\%$  (5/223).

Pseudomonas aeruginosa: The overall performance for  $P$  aeruginosa was acceptable, with an EA of  $92.2\%$ , a CA of  $96.6\%$ , and a minor discrepancy rate of  $3.35\%$  (6/179).

# Resistant Organisms:

A total of 117 resistant isolates were identified out of 402 organisms tested  $(29.1\%)$  in the combined challenge and clinical study for the Liofilchem MIC Test Strip (MST). However,  $P.$  mirabilis had an insufficient number of resistant isolates tested during the comparative study. This was addressed by adding the following limitation in the Liofilchem Meropenem MIC Test Strip (MTS) package insert supplement:

The ability of the Liofilchem MIC Test Strip (MTS) to detect resistance is unknown for the following antibiotic/organism combination, because an insufficient number of resistant isolates were available during the comparative testing: Meropenem-Proteus mirabilis

# MIC Trends:

Using the combined clinical and challenge data for Pseudomonas aeruginosa an analysis of the trending was conducted using 122 evaluable results plus an additional 13 results where an assignment for trend analysis was made through other considerations. The combined data of 135 results constitute the number of evaluable data for trend analysis. The analysis is presented in Table 4.

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Table 4: Trending Summary of Clinical and Challenge Isolates Results of P. aeruginosa*

|   | Total No Isolates | ≤-1 | Exact | ≥+1  |
| --- | --- | --- | --- | --- |
|  Clinical | 105 | 20 | 48 | 37  |
|  Challenge | 30 | 0 | 6 | 24  |
|  Combined | 135 | 20 (14.8%) | 54 (40%) | 61 (45.2%)  |

* Analysis conducted using the number of evaluable results for trending analysis. Difference is 30.4% (95% CI: 19.7% to 40.2%)

A higher MIC reading trend was observed in the overall performance of *Pseudomonas aeruginosa* compared to the CLSI broth micro-dilution, which raises concerns for potential major errors. This trending and the potential for occurrence of major error(s) for Meropenem when testing clinical and challenge isolate results with Liofilchem MIC Test Strip (MTS), was addressed in the labeling by adding the following footnote under the performance characteristics Table:

The Liofilchem MIC Test Strip (MTS) Meropenem MIC values tended to be one or more doubling dilution higher when testing *P. aeruginosa* compared to the CLSI reference broth microdilution (for 135 *P. aeruginosa* isolates tested with evaluable MIC results for trending, 14.8% were one, two or more doubling dilutions lower, 40% were exact, and 61% were one, two or more dilution higher compared to the CLSI broth microdilution results).

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

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5. Expected values/Reference range:

Table 5: FDA Interpretive Criteria for Meropenem (μg/mL)

|  Organisms | S | I | R  |
| --- | --- | --- | --- |
|  Enterobacteriaceae | ≤1 | 2 | ≥4  |
|  Pseudomonas aeruginosa | ≤2 | 4 | ≥8  |

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.

---

**Source:** [https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K162854](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/JWY/K162854)

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