← Product Code [LRG](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LRG) · K101425

# MICROSCAN DRIED GRAM-NEGATIVE MIC/COMBO PANEL, B1017 PANEL SERIES (K101425)

_Siemens Healthcare Diagnostics · LRG · Sep 10, 2010 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LRG/K101425

## Device Facts

- **Applicant:** Siemens Healthcare Diagnostics
- **Product Code:** [LRG](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LRG.md)
- **Decision Date:** Sep 10, 2010
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1640
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

The MicroScan® Dried Gram-Negative MIC/Combo Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-negative bacilli. After inoculation, panels are incubated for 16 - 20 hours at 35°C +/- 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the Package Insert. This particular submission is for the addition of the antimicrobial Doripenem at concentrations of 0.008 to 32 mcg/ml to the test panel. The gram-negative organisms which may be used for Doripenem susceptibility testing in this panel are: Acinetobacter baumanii Escherichia coli Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa

## Device Story

MicroScan® Dried Gram-Negative MIC/Combo Panels contain dehydrated Mueller Hinton Broth and nutrients with micro-dilutions of antimicrobial agents. Panels are rehydrated and inoculated with bacterial suspensions prepared via turbidity or Prompt® methods. After 16-20 hours of incubation at 35°C in non-CO2, growth is assessed to determine the Minimum Inhibitory Concentration (MIC). Testing is performed in clinical laboratories. Results are obtained via visual observation or automated reading using MicroScan® WalkAway® or autoSCAN®-4 systems. Automated systems use optical detection to measure growth inhibition. MIC results and categorical interpretations (SIR) assist clinicians in selecting appropriate antimicrobial therapy for gram-negative infections.

## Clinical Evidence

Clinical efficacy testing conducted at three sites using 573 gram-negative isolates (535 intended for testing). Combined efficacy and challenge study results showed 97.0% Essential Agreement (EA) and 97.2% Category Agreement (CA). Reproducibility was >95% across all sites, days, and reading methods (manual, WalkAway, autoSCAN-4). No clinical sensitivity/specificity data required for AST systems; performance is based on comparison to reference broth dilution methods.

## Technological Characteristics

Dried micro-dilution panels containing Mueller Hinton Broth and nutrients. Growth-based detection principle. Inoculation via turbidity or Prompt® methods. Incubation 16-20 hours at 35°C. Automated reading via optical detection (WalkAway® or autoSCAN-4 systems). Complies with CLSI M07-A8 and M100-S19 standards.

## 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

- MicroScan Dried Gram-Negative MIC/Combo Panels- Ertapenem (k032706)

## 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.
>
> Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/).

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

A. 510(k) Number:
k101425

B. Purpose for Submission:
To add doripenem at concentrations of 0.008-32 µg/mL to the Microscan® Dried Gram-Negative MIC/Combo Panels.

C. Measurand:
Doripenem 0.008-32 µg/mL

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

E. Applicant:
Siemens Healthcare Diagnostics, Inc.

F. Proprietary and Established Names:
MicroScan® Dried Gram-Negative MIC/Combo Panels

G. Regulatory Information:
1. Regulation section:
866.1640 - Antimicrobial Susceptibility Test Powder
2. Classification:
Class II
3. Product code:
LRG- Instrument for Auto Reader & Interpretation of Overnight Antimicrobial Susceptibility Systems
JWY - Manual Antimicrobial Susceptibility Test Systems
LTT – Panels, Test, Susceptibility, Antimicrobial
4. Panel:
83 Microbiology

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H. Intended Use:

1. Intended use:

For use with MicroScan® Dried Gram Negative MIC/Combo Panels and Dried Gram Negative Breakpoint Combo Panels. MicroScan® panels are designed for use in determining antimicrobial agent susceptibility and/or identification to the species level of aerobic and facultative anaerobic gram-negative bacilli.

The MicroScan® Dried Gram Negative MIC/Combo Panels is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram negative bacilli.

2. Indication(s) for use:

The MicroScan® Dried Gram Negative MIC/Combo Panels is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram negative bacilli. After incubation, panels are incubated for 16-20 hours at 35°C +/- 1°C in a non-CO₂ incubator, and read either visually or with MicroScan instrumentation, according to the Package insert.

This particular submission is for the addition of Doripenem at concentrations 0.008 to 32μg/mL to the test panel.

The gram-negative organisms which may be used for Doripenem susceptibility testing in this panel are:

Acinetobacter baumannii
Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa

3. Special conditions for use statement(s):

- For prescription use only
- The Log and Stationary Inoculum methods should not be used with Doripenem.
- The Prompt™ method of inoculation is an alternate method of inoculation preparation that is supported in the methodology along with the turbidity method.

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4. Special instrument requirements:

MicroScan® WalkAway® System and MicroScan® autoSCAN®-4 are the alternate read methods for Doripenem

I. Device Description:

The MicroScan® Dried Gram-Negative MIC/Combo Panel contains micro-dilutions of each antimicrobial agent in various concentrations with Mueller Hinton Broth and various nutrients which are dehydrated and dried in panels. Each panel contains two control wells: a no-growth control well (contains water only/no nutrients or broth), and a growth control well (contains test medium without antibiotic). The panel is rehydrated and inoculated at the same time with 0.1 ml of suspension prepared by the turbidity method (inoculum prepared in water, then 0.1 ml transferred to 25 ml of inoculum water containing pluronic-D/F-a wetting solution). The Prompt® method of inoculation is also recommended as an alternate means of preparing the inoculum. The panels are incubated at 35°C in a non-CO₂ for 16-20 hours and read by visual observation for growth. Panels may also be read automatically with the WalkAway® and autoSCAN®-4 Systems.

J. Substantial Equivalence Information:

1. Predicate device name(s): MicroScan Dried Gram-Negative MIC/Combo Panels- Ertapenem
2. Predicate 510(k) number(s): k032706
3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Intended use | MicroScan® panels are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility and/or identification to the species level of colonies, grown on solid media, of rapidly growing aerobic and facultative anaerobic organisms | Same  |
|  Inoculum preparation | Inoculum prepared from isolated colonies using either the Turbidity method or Prompt® system | Same  |
|  Technology | Growth based after 16 hours | Same  |
|  Results | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) | Same  |
|  Instrument | autoSCAN®-4 or WalkAway® | Same  |
|  Differences  |   |   |

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|  Item | Device | Predicate  |
| --- | --- | --- |
|  Antibiotic | Doripenem at 0.008- 32 μg/mL | Ertapenem at 0.002- 32 μg/mL  |
|  Test organisms | Acinetobacter baumannii
Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa | Enterobacteriaceae  |

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

Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA”; Clinical and Laboratory Standards Institute (CLSI) M07-A8 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard”; M100-S19 “Performance Standards for Antimicrobial Susceptibility Testing”

## L. Test Principle:

After incubation in non-CO₂ incubator for 16-20 hours, the MIC for the test organisms are read by determining the lowest antimicrobial concentration showing inhibition of growth. The panels are read either visually or automatically with the WalkAway® and autoSCAN®-4, which uses an optics system with growth algorithms to directly measure organism growth.

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

1. Analytical performance:

a. Precision/Reproducibility:

Reproducibility was demonstrated using 10 isolates tested at three sites on three separate days in triplicate. The study included the testing of the following inoculum and reading variables; turbidity inoculum method and Prompt method of inoculation with reading performed manually, by WalkAway instrument and autoSCAN-4 instrument. All results were >95% reproducible.

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|  Difference in the number of dilutions between the mode of the MicroScan® result and the actual result with each inoculation method for between site reproducibility  |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Inoculation Method | Read Method | ≥Minus 2 dilutions | Minus 1 dilution | Exact | Plus 1 Dilution | ≥Plus 2 dilutions | % Reproducible  |
|  Prompt | Manual | 5 | 29 | 212 | 22 | 2 | 97.4  |
|  Prompt | WalkAway | 8 | 18 | 222 | 22 |  | 97.0  |
|  Prompt | autoScan4 |  | 4 | 229 | 35 | 2 | 99.3  |
|  Turbidity | Manual | 3 | 26 | 225 | 14 | 2 | 98.1  |
|  Turbidity | WalkAway |  | 7 | 235 | 24 | 4 | 98.5  |
|  Turbidity | autoScan4 |  | 6 | 238 | 22 | 4 | 98.5  |

There were more results in the minus category (one dilution lower) when reading manually with the Prompt or the turbidity inoculation methods; however, there were more results in the plus category when using the auto reader (WalkAway or autoScan). The same trend was also observed in the challenge study.

b. Linearity/assay reportable range:

Not Applicable

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

The recommended QC isolates, E.coli ATCC 25922 and  $P$  aeruginosa ATCC 27853 were tested a sufficient number of times with acceptable results most of the time with the reference method. Quality control results demonstrated the ability of the different reading parameters (manual, WalkAway, and autoScan) by Turbidity or Prompt inoculation methods to produce acceptable results.

The following table provides the frequency of the results in each concentration with the expected range stated.

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|   |   |   |   | Results  |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Organism | μg/mL | ref | Turbidity |   |   | Prompt  |   |   |
|  Doripenem |  |  | Manual | Walk Away | Auto Scan | Manual | Walk Away | Auto Scan  |
|  E. coli ATCC 25922
Expected range 0.015- 0.06 μg/mL | <=0.008 |  |  |  |  |  |  |   |
|   |  0.015 |  | 29 | 3 | 12 | 6 | 1 | 2  |
|   |  0.03 | 115 | 89 | 76 | 70 | 69 | 70 | 73  |
|   |  0.06 | 3 | 1 |  | 1 | 5 | 7 | 5  |
|   |  0.12 |  |  |  |  |  |  |   |
|   |  0.25 |  |  |  |  |  |  |   |
|   |  0.5 |  |  |  |  |  |  |   |
|   |  1 |  |  |  |  |  |  |   |
|   |  2 |  |  |  |  |  |  |   |
|   |  4 |  |  |  |  |  |  |   |
|   |  8 |  |  |  |  |  | 1 |   |
|  P. aeruginosa
ATCC 27853
Expected range
0.12- 0.5 μg/mL | 0.12 |  | 21 | 47 | 1 | 2 |  | 1  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  0.25 | 83 | 77 | 29 | 59 | 69 | 59 | 68  |
|   |  0.5 | 32 | 19 | 1 | 22 | 12 | 21 | 15  |
|   |  1 | 3 | 1 |  | 1 |  | 2 | 1  |
|   |  2 |  |  |  |  |  |  |   |
|   |  4 |  |  |  |  |  |  |   |
|   |  8 |  |  |  |  |  | 1 |   |

Inoculum density control: A turbidity meter was used for the turbidity inoculation method. Colony counts were performed weekly on *E. coli* ATCC 25922 for the Prompt inoculation method.

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 efficacy testing was conducted at three external sites using fresh isolates supplemented with stock isolates. The study included a total of 573 Gram-negative isolates, of which 535 were Intended for Testing (IFT) organisms. There were 538 fresh and 36 stock isolates. Of the 573 isolates

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tested, there were 74 Acinetobacter baumannii, 330 Enterobacteriaceae, 131 Pseudomonas aeruginosa. There were 75 challenge isolates tested and compared to the reference broth dilution result mode that was determined by previous testing of each isolate multiple times in the recommended reference panel. All isolates grew in the MicroScan panels.

Efficacy testing was performed using the turbidity inoculation method and read manually after incubation for 16-20 hours at 35°C +/- 1°C in a non-CO₂ incubator. A comparison to the reference method was provided with the following agreement.

Overall Performance Summary- Overnight Manual (Efficacy + Challenge)

|  Doripenem | EA Tot | EA # | EA % | Eval EA Tot | Eval EA # | Eval EA % | CA # | CA % | #NS | CA Err  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |   |   |   |   |   |   |   |  # | %  |
|  Efficacy | 535 | 522 | 97.6 | 510 | 499 | 97.8 | 522 | 97.6 | 91 | 13 | 2.4  |
|  Challenge | 75 | 70 | 93.3 | 70 | 66 | 94.3 | 71 | 94.7 | 16 | 4 | 5.3  |
|  Combined | 610 | 592 | 97.0 | 580 | 565 | 97.4 | 593 | 97.2 | 107 | 17 | 2.6  |

EA - Essential Agreement
CA - Category Agreement
NS - Not Susceptible

EA is when there is agreement between the reference method and the new method is within plus or minus one serial two-fold dilution of antibiotic. Category agreement (CA) is when the new method result interpretation agrees exactly with the reference panel result interpretation. Evaluable EA is when the MIC result is on scale for both the new method and the reference method and have on-scale EA.

There were thirteen categorical errors in the Efficacy study; eleven of which were from P. aeruginosa, one from A. baumannii, all were within EA and one dilution lower when comparing to the reference method. A limitation was included when testing P. aeruginosa with Doripenem.

A challenge set was tested at one site. The challenge set of organisms was tested using both Prompt and Turbidity inoculation methods and read either visually or with MicroScan instrumentation (autoSCAN-4, WalkAway). The table below demonstrated those that were in exact agreement with the reference method result and those that differed by one or more 2-fold dilutions:

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|  Difference in the number of dilutions between the expected reference result and the MicroScan® Result  |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|  Inoculation Method | Read Method | ≥Minus 2 dilutions | Minus 1 dilution | Exact | Plus 1 Dilution | ≥Plus 2 dilutions  |
|  Prompt | Manual | 2 | 12 | 45 | 10 | 1  |
|  Prompt | WA | 1 | 6 | 43 | 17 | 3  |
|  Prompt | AS4 |  | 7 | 43 | 17 | 3  |
|  Turbidity | Manual | 2 | 13 | 46 | 7 | 2  |
|  Turbidity | WA |  | 6 | 46 | 15 | 3  |
|  Turbidity | AS4 |  | 6 | 42 | 19 | 3  |

Overall EA in the challenge study was  $&gt;90\%$  by all reading methods with both Prompt and Turbidity inoculation methods, and they all were in similar exact agreement. However, there were more results in the plus category with the WA and AS4 reads in both inoculation methods. With the Manual reads, more results were in the minus category. The trend was consistent with the reproducibility study data.

The following table demonstrated the performance based on essential agreement (EA) and category agreement (CA) for the challenge set and the different inoculation and reading methods.

|   | Total | EA | CA Errors | Major Errors | Very Major Errors | CA  |
| --- | --- | --- | --- | --- | --- | --- |
|  Prompt/Manual | 75 | 71 (94.7%) | 2 (2.7%) | N/A | N/A | 73 (97.3%)  |
|  Prompt/WA | 75 | 70 (93.3%) | 2 (2.7%) | N/A | N/A | 73 (97.3%)  |
|  Prompt/AS4 | 75 | 71 (94.7%) | 2 (2.7%) | N/A | N/A | 73 (97.3%)  |
|  Turbidity/Manual | 75 | 70 (93.3%) | 4 (5.3%) | N/A | N/A | 71 (94.7%)  |
|  Turbidity/WA | 75 | 71 (94.7%) | 5 (6.7%) | N/A | N/A | 70 (93.3%)  |
|  Turbidity/AS4 | 75 | 71 (94.7%) | 5 (6.7%) | N/A | N/A | 70 (93.3%)  |

b. Matrix comparison: Not Applicable

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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:

Enterobacteriaceae ≤0.5
Pseudomonas aeruginosa ≤2
Acinetobacter baumannii ≤1

CLSI interpretive breakpoints have not been established when the Doripenem was submitted for review.

The current absence of resistant isolates precludes defining results other than Susceptible. Isolates yielding MIC results suggestive of Non-susceptible category should be submitted to a reference laboratory for further testing.

N. Proposed Labeling:

The expected value range, interpretive criteria and QC for gram negative panels are included in the package insert. The labeling is sufficient and 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.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LRG/K101425](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LRG/K101425)

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