← Product Code [LRG](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LRG) · K063101

# MICROSCAN MICROSTREP PLUS PANEL CEFOTAXIME (0.015 - 8 MCG/ML (K063101)

_Dade Behring, Inc. · LRG · Nov 1, 2006 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LRG/K063101

## Device Facts

- **Applicant:** Dade Behring, Inc.
- **Product Code:** [LRG](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LRG.md)
- **Decision Date:** Nov 1, 2006
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1640
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

The MicroScan MICroSTREP plus® Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of aerobic streptococci, including Streptococcus pneumoniae. After inoculation, panels are incubated for 20 - 24 hours at 35°C +/- 1°C in a non-CO2 incubator, and read visually according to the Package Insert. Additionally, the panels may be incubated in and read by a MicroScan® WalkAway instrument.

## Device Story

MicroScan® MICroSTREP plus® Panel is a 96-well plastic dish containing dehydrated microdilutions of Cefotaxime (0.015–8 µg/mL). Panels are rehydrated with Mueller-Hinton broth supplemented with 2–5% lysed horse blood and inoculated with standardized bacterial suspensions (approx. 5 × 10⁵ CFU/mL). After 20–24 hours incubation at 35°C, growth is assessed to determine the Minimum Inhibitory Concentration (MIC). The device supports both manual visual reading and automated reading via the MicroScan® WalkAway System, which utilizes optics light detection to measure growth. The automated system provides quantitative and qualitative susceptibility results, assisting clinicians in identifying appropriate antimicrobial therapy for streptococcal infections. The system is intended for use in clinical laboratory settings.

## Clinical Evidence

Bench testing only. Reproducibility was assessed using 10 isolates across 4 sites (360 results), demonstrating >95% reproducibility for both manual and automated methods. Performance was validated using 70 streptococcal challenge isolates (including 53 S. pneumoniae) compared to reference broth dilution. Essential Agreement (EA) was 92.9% for manual and 92.5% for automated reading. One very major discrepancy (vmj) was noted in the automated method (1/22, 4.5%) for meningitis breakpoints. No clinical efficacy studies were required as the manual method was previously established.

## Technological Characteristics

Miniaturized broth dilution susceptibility test system. Panels contain antimicrobial agents in concentrations bridging clinical interest. Rehydrated with Mueller-Hinton broth, 2-5% lysed horse blood, and 50 mM HEPES. Incubation at 35°C +/- 1°C. Automated reading via MicroScan WalkAway instrument. Regulatory class II, product codes LRG and LTT.

## 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 MICroSTREP plus® Panel ([K021111](/device/K021111.md))

## Submission Summary (Full Text)

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

A. 510(k) Number:
K063101

B. Purpose for Submission:
To add the option for automated reading of Cefotaxime at 0.015 – 8 µg/mL to the MICroSTREP plus® Panel on the MicroScan® WalkAway System

C. Measurand:
Cefotaxime at 0.015 – 8 µg/mL

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

E. Applicant:
Dade Behring Inc,
MicroScan®

F. Proprietary and Established Names:
MicroScan® MICroSTREP plus® Panel – Cefotaxime at 0.015 – 8 µg/mL

G. Regulatory Information:

1. Regulation section:
21 CFR 866.1640 – Antimicrobial Susceptibility Test Powder

2. Classification:
Class II

3. Product Code:
LRG – Instrument for Auto Reader & Interpretation of Overnight
Antimicrobial Susceptibility System
LTT – Panels, Test, Susceptibility, Antimicrobial

4. Panel:
83 Microbiology

H. Intended Use:

1. Intended use(s):
Cefotaxime at 0.015 – 8 µg/mL is for use with MICroSTREP plus® Panels.
MICroSTREP plus® Panels are designed for use in determining quantitative

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and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of aerobic streptococci, including *Streptococcus pneumoniae*.

2. **Indication(s) for use:**
This submission is for adding the option for automated reading of the antibiotic Cefotaxime at concentrations of 0.015 – 8 µg/mL to MICroSTREP *plus®* Panels on the MicroScan® WalkAway System for testing *Streptococcus pneumoniae*, *Streptococcus pyogenes*, and *Streptococcus* species.

3. **Special condition for use statement(s):**
Prescription Use Only
Turbidity method of inoculum preparation only

The absence of resistant strains of beta hemolytic streptococci precludes defining any results categories other than “susceptible”. For isolates yielding results suggestive of a “nonsusceptible” category, organism identification and antimicrobial susceptibility results should be confirmed.

4. **Special instrument Requirements:**
Not Applicable

I. **Device Description:**
The MicroScan® MICroSTREP *plus®* Panel is a 96-well plastic dish which contains microdilutions of each antimicrobic in various concentrations dried in aqueous solutions. The panel is rehydrated and inoculated at the same time with a Mueller-Hinton broth supplemented with lysed horse blood (2 – 5%). The target inoculum concentration for each well should be approximately 5 × 10⁵ colony forming units (CFU)/mL. Panels are incubated in a 35°C non-CO₂ incubator for 20-24 hours. After incubation, the panels are read manually for growth. Additionally, panels may be incubated in and read by a MicroScan® WalkAway instrument. Each panel contains a “growth” but it does not contain a “no growth” control well.

J. **Substantial Equivalence Information:**

1. **Predicate device name(s):**
MICroSTREP *plus®*

2. **Predicate K number(s):**
K021111

3. **Comparison with predicate:**

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Intended use | Determination of susceptibility to antimicrobics with aerobic streptococci including *Streptococcus pneumoniae* | Same  |

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|  Isolates | For use with aerobic streptococci including Streptococcus pneumoniae isolated colonies from culture | Same  |
| --- | --- | --- |
|  Results | Quantitative with qualitative interpretations | Same  |
|  Incubation | 20 – 24 hours | Same  |
|  Panels | Cefotaxime dried in aqueous solution | Same  |
|  Differences  |   |   |
|  Item | Device | Predicate  |
|  Technology | Growth based using algorithm with optics light detection | Growth based  |
|  Reading | Overnight method Manual or automated | Overnight method Manual read only  |
|  Instrument | MicroScan® WalkAway System or Microdilution viewer | Microdilution viewer  |

# 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-S16) "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard."

# L. Test Principle:

The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in water and dehydrated. Various antimicrobial agents are diluted in water, buffer or minute concentrations of broth to concentrations bridging the range of clinical interest. Panels are rehydrated with  $115~\mu \mathrm{L}$  Mueller-Hinton broth supplemented with  $2 - 5\%$  lysed horse blood (LHB), after inoculation of the broth with a standardized suspension of the organism. The target inoculum concentration for each well should be approximately  $5\times 10^{5}$  colony forming units (CFU)/mL. After incubation in a non- $\mathrm{CO}_{2}$  incubator for 20-24 hours, the minimum inhibitory concentration (MIC) for the test organisms is determined by observing the lowest antimicrobial concentration showing inhibition of growth. Panels can be read manually using indirect light or the panels can be read on the MicroScan® WalkAway instrument using optics light detection.

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

This submission is for the AST Panel only. The ID System was not reviewed.

The Reproducibility studies, QC performance data, and Challenge isolates evaluated by the manual and automated reading methods are required to demonstrate that there is no difference between manual reading and automated reading in the MicroScan®

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WalkAway System. The clinical efficacy performance was previously established using the manual read method and was therefore not required for this submission.

1. Analytical performance:

a. Precision/Reproducibility:
Reproducibility was demonstrated using 10 isolates tested at 4 sites on 3 separate days in triplicate, for a total of 360 results. The study included testing on the MicroScan® WalkAway System with automated reading at 20-24 hours, and manual readings at 20-24 hours incubation.

Both reading methods demonstrated >95% reproducibility, and no differences were observed.

b. Linearity/assay reportable range:
Not applicable

c. Traceability, Stability, Expected values (controls, calibrators, or method):
The recommended QC isolate S. pneumoniae ATCC 49619 was tested a sufficient number of times with acceptable results on all testing days with the reference method. Quality control results demonstrated the ability of the different reading parameters (manual and instrument) to produce acceptable results. The following table provides the frequency of results in each concentration with the expected range stated. Both reading methods produced the same mode as the reference method.

|  Organism | Concentration μg/mL | Reference results | MicroScan® WalkAway results  |   |
| --- | --- | --- | --- | --- |
|   |  |  | Manual Overnight | Instrument Overnight  |
|  S. pneumoniae ATCC 49619
Expected range 0.03 – 0.12 μg/mL | 0.03 |  |  | 1  |
|   |  0.06 | 52 | 45 | 49  |
|   |  0.12 | 31 | 44 | 39  |
|   |  0.25 |  |  |   |
|   |  0.5 |  |  |   |
|   |  1 |  |  |   |
|   |  2 |  |  |   |

Inoculum density control: A turbidity meter, which was verified each day of testing, was used for the turbidity inoculation method. Colony counts were performed weekly, on the ATCC S. pneumoniae with all results in the expected range of approximately 5 x 10⁵.

No trending was observed.

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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 with manual result reading was conducted in the previous submission (K021111). In this submission, Challenge isolates were evaluated by the manual and automated reading methods to demonstrate that there is no difference between manual reading and instrument reading on the MicroScan® WalkAway System. There were 70 streptococcal challenge isolates, including 53 Streptococcus pneumoniae strains from the CDC Challenge Set tested internally and compared to the reference broth dilution result, which was obtained prior to beginning the design validation. A comparison was done with readings on the instrument after 20 hours incubation, and also read manually when incubated for 20-24 hours. Performance by the automated reading method was acceptable with no differences or trends. The read method comparison results are displayed in the tables below.

The recommended CLSI reference method was followed with the exception of the use of a small amount (0.1%) of Pluronic (a wetting agent) in the final inoculum. A validation of the use of Pluronic in the frozen reference panel was conducted. QC was also performed with no difference apparent in the results.

Read method comparison of Streptococcus species and Cefotaxime

|  Non-meningitis breakpoints | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | #R | min | maj | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Challenge Manual | 70 | 65 | 92.9 | 61 | 56 | 91.8 | 13 | 8 | 0 | 0  |
|  Challenge Automated | 70 | 65 | 92.9 | 59. | 54 | 91.5 | 13 | 9 | 0 | 0  |
|  Meningitis breakpoints | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | #R | min | maj | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Challenge Manual | 70 | 65 | 92.9 | 61 | 56 | 91.8 | 23 | 6 | 0 | 1  |
|  Challenge Automated | 70 | 65 | 92.9 | 59 | 54 | 91.5 | 23 | 9 | 0 | 1  |

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EA-Essential Agreement
R-resistant isolates

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

Essential agreement (EA) is when the Microscan® MICroSTREP plus® panels agree with the reference test panel results exactly or within one doubling dilution of the reference method. Evaluable (Eval) are results that are within the test range and on scale.

Automated reading results were the same as the manual reading results with no trending.

There was one (1/22, 4.5%) vmj generated by one Streptococcus pneumoniae isolate with the automated reading method, evaluated with the Meningitis breakpoints. The same isolate produced a min error using the Nonmeningitis breakpoints with the automated reading method. The overall EA% of 92.9% and Eval EA% of 91.8% for the manual read and overall EA% of 92.5% and Eval EA% of 91.5% for the automated reading were both acceptable. No other differences or trending was observed between the manual and the automated reading method results. Therefore, the data are acceptable.

The test device had a growth rate of >95% for both the manual reading and the automated reading methods.

The comparison of the reading methods demonstrates that the manual reading method and the automated reading on the MicroScan® WalkAway System are no different. The efficacy data performed with the manual reading method would therefore be expected to have no differences.

The performance data currently documented in the package insert will not change.

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

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4. Clinical cut-off: Not applicable

5. Expected values/Reference range:

|  Cefotaxime | S | I | R  |
| --- | --- | --- | --- |
|  Streptococcus pneumoniae |   |   |   |
|  (nonmeningitis) | ≤ 1 | 2 | ≥ 4  |
|  Streptococcus pneumoniae |  |  |   |
|  (meningitis) | ≤ 0.5 | 1 | ≥ 2  |
|  Streptococcus spp. other than Streptococcus pneumoniae |   |   |   |
|  Beta hemolytic group* | ≤ 0.5 | --- | ---  |
|  Viridans group | ≤ 1 | 2 | ≥ 4  |

The expected value range, interpretive criteria and QC as recommended by CLSI are included in the package insert.

*The absence of resistant strains of beta hemolytic streptococci precludes defining any results categories other than “susceptible”. For isolates yielding results suggestive of a “nonsusceptible” category, organism identification and antimicrobial susceptibility results should be confirmed.

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.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LRG/K063101](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LRG/K063101)

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