← Product Code [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON) · K070860

# MICROSCAN SYNERGIES PLUS GRAM-POSITIVE MIC/COMBO PANELS WITH CLINDAMYCIN (K070860)

_Dade Behring, Inc. · LON · May 11, 2007 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K070860

## Device Facts

- **Applicant:** Dade Behring, Inc.
- **Product Code:** [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON.md)
- **Decision Date:** May 11, 2007
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1645
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Intended Use

The MicroScan® Synergies plus™ Gram-Positive 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-positive enterococci and staphylococci. After inoculation, panels are incubated for 4.5 - 18 hours at 35°C +/- 1°C, in a WalkAway® SI, or equivalent, and read by the MicroScan® Instrumentation. Additionally, the panels may be incubated in a non-CO2 incubator and the Antimicrobial Susceptibility Testing (AST) portions can be read visually, according to the Package Insert.

## Device Story

MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels are miniaturized broth dilution susceptibility tests. Panels contain dehydrated antimicrobial agents; rehydrated with Synergies plus™ Pos Broth after inoculation with standardized organism suspensions. Panels incubated in WalkAway® SI instrument (or equivalent) for 4.5-18 hours. Instrument reads minimum inhibitory concentration (MIC) by identifying lowest concentration showing growth inhibition. Used in clinical laboratories by trained personnel. Output provides quantitative/qualitative susceptibility data to assist clinicians in selecting appropriate antimicrobial therapy for patients with Gram-positive infections.

## Clinical Evidence

Clinical and challenge testing performed on 304 gram-positive isolates (268 fresh, 36 stock) and 75 challenge isolates. Primary endpoints: Essential Agreement (EA) and Category Agreement (CA) against CLSI reference broth dilution. Rapid read (<16h) method showed 98.0% EA and 99.1% CA for challenge sets; 98.3% EA and 99.3% CA for clinical sets. Major error rate 2.9% (challenge) and 0% (clinical). Reproducibility >95% across 3 sites. Bench testing confirmed performance of rapid read method.

## Technological Characteristics

Miniaturized broth dilution susceptibility test; dehydrated antimicrobial agents in multi-well panels. Rehydrated with Synergies plus™ Pos Broth. Incubation: 4.5-18 hours at 35°C. Readout: Automated via WalkAway® SI instrument or visual inspection. Connectivity: Compatible with WalkAway® SI system. Sterilization: Not specified.

## Regulatory 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

- MicroScan® Dried Gram-Positive and Gram-Negative MIC/Combo Panels (k862140, k020185)

## 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:
K070860

B. Purpose for Submission:
To add Clindamycin at 0.03 – 8 µg/mL (Long Dilution Sequence) and 0.12 – 2 µg/mL (5-Dilution Breakpoint [BP] Sequence) to the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels

C. Measurand:
Clindamycin at 0.03 – 8 µg/mL (Long Dilution Sequence) and 0.12 – 2 µg/mL (5-Dilution Breakpoint [BP] Sequence)

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® Synergies plus™ Gram-Positive MIC/Combo Panels

G. Regulatory Information:

1. Regulation section:
866.1645 - Fully automated short-term incubation cycle antimicrobial susceptibility system
866.1640 - Antimicrobial Susceptibility Test Powder

2. Classification:
Class II

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3. Product code:
LON – Automated AST system short incubation
LRG-Instrument for Auto Reader &amp; Interpretation of Overnight Antimicrobial Susceptibility Systems
JWY - Manual Antimicrobial Susceptibility Test Systems
LTT – Panels, Test, Susceptibility, Antimicrobial

4. Panel:
83 Microbiology

H. Intended Use:

1. Intended use(s):
The MicroScan® Synergies plus™ Gram Positive 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-positive enterococci and staphylococci. After inoculation, panels are incubated for 4.5 – 18 hours at 35°C ± 1°C, in a WalkAway® SI, or equivalent, and read by the MicroScan® Instrumentation. Additionally, the panels may be incubated in a non-CO₂ incubator and the Antimicrobial Susceptibility Testing (AST) portions can be read visually, according to the Package Insert.

2. Indication(s) for use:
The testing of Clindamycin at concentrations of 0.03 – 8 µg/mL (Long Dilution Sequence) and 0.12 – 2 µg/mL (5-Dilution Breakpoint [BP] Sequence) to the Gram-Positive MIC/Combo test panel is indicated for testing Staphylococcus aureus (penicillinase and non-penicillinase producing strains) and Staphylococcus epidermidis (penicillinase and non-penicillinase producing strains) at 4.5-16 hours or 16-20 hours for a overnight reading.

3. Special conditions for use statement(s):
- Turbidity method of inoculum preparation only.
- For prescription use only.

4. Special instrument requirements:
Not Applicable

I. Device Description:

Each panel contains two control wells: a negative control well, and a growth control well which contains test medium without antibiotic. Antibiotics are diluted in water, buffer, or minute concentrations of broth to selected concentrations prior to dehydration of the panels. The panel is rehydrated and inoculated at the same time with 0.1 ml of suspension prepared by the turbidity method (inoculum prepared in 0.4% saline with Pluronic® (a wetting agent), then 0.1 ml transferred to 25 ml of inoculum Synergies plus Pos Broth with Pluronic®) for a

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final inoculum concentration of 3-7 X 10⁵ CFU/ml. Panels are incubated in a Walk-Away® System and read periodically starting at 4.5 hours until sufficient growth to determine the MIC. Alternately the panels may be incubated at 35° C in a non-CO₂ for 16-24 hours and read by visual observation of growth.

J. Substantial Equivalence Information:

1. Predicate device name(s):

MicroScan® Dried Gram-Positive and Gram-Negative MIC/Combo Panels

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

k862140

k020185

1. 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  |
|  Specimen | Isolated colonies from culture used | Same  |
|  Inoculum | Inoculum density to 0.5 McFarland standard | Same  |
|  Incubation | <16 hours
16 – 24 hours | Same  |
|  Results | Quantitative with qualitative interpretations | Same  |
|  Technology | Growth based | Same  |

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|  Item | Device | Predicate  |
| --- | --- | --- |
|  Panels | Dried Clindamycin in water | Dried clindamycin or gentamycin in broth  |
|  Reading | Uses both a ≤ 16 hour read and overnight read method in the same system | Overnight system uses only the overnight reading method and <16 hour instruments use only the <16 hour read method.  |
|  Inoculum preparation | Turbidity method of inoculation only. | Inoculum prepared using either the Turbidity method or Prompt® system  |
|  Instrument | WalkAway® -SI System or equivalent | AutoScan® -4 or WalkAway®  |
|  Antibiotic | Clindamycin at 0.03 – 8 μg/mL (Long Dilution Sequence) and at 0.12 – 2 μg/mL (5-Dilution Breakpoint [BP] Sequence) | Different concentrations depending on the antibiotic  |

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) M7 (M100-S17) “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard”.

L. Test Principle:

The WalkAway® SI uses a Colorimetric Optics System consisting of a color wheel/lamp assembly and a Photosensor. There is an initial read at 2.5 hours with a possible final read at 4.5, 5.5, 6.5, 8, 12, 16/18 hours (overnight instrument readings, manual readings), or 24 hours depending on the growth rate of the organism being tested. No reading below 16 hours of incubation is reported. The time of final read is dependent on the user preference, the growth rate of the organism, and the sensitivity of the automatic reader since cell densities below $2 \times 10^{7}$ cells/ml are not detected.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Reproducibility was demonstrated using 360 isolates tested at 3 sites on 3 separate

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days in triplicate. The study included the testing on the WalkAway® SI read at &lt;16 hours, WalkAway® 16-18 hour readings and manual readings at 16-20 hours incubation. The Reproducibility total for the Rapid read method equaled 330 isolates. The WalkAway® SI had 30 results that were not readable at &lt;16 hours. All results were &gt;95% reproducible for the Long Dilution and the 5-Dilution Breakpoint Sequence for all read methods. Performance claims are based on the Rapid read method.

There was a trend for the Rapid read method to produce slightly more susceptible results.

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 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 &gt;95% of the time. The following tables provide the frequency of the results in each concentration with the expected range stated.

|  Results  |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|  Organism | Conc. in μg/mL | # reference | MicroScan®  |   |   |   |
|  Clindamycin
Long Dilution |  |  | Manual overnight | Instrument overnight | <16 h instrument  |   |
|  E. faecalis
ATCC 29212
Range
4 - >8 μg/mL | 0.5 |  |  |  |   |   |
|   |  1 |  |  |  |   |   |
|   |  2 |  |  |  |   |   |
|   |  4 |  |  |  | 12  |   |
|   |  8 | 52 | 46 | 54 | 72  |   |
|   |  >8 | 36 | 44 | 36 | 6  |   |
|  Results  |   |   |   |   |   |   |
|  Organism | Conc. in μg/mL | # reference | MicroScan®  |   |   |   |
|  Clindamycin
Long Dilution |  |  | Manual overnight | Instrument overnight | <16 h instrument  |   |
|  S. aureus
ATCC
Range
0.06 - 0.25 μg/mL | ≤0.03 |  |  |  | 2  |   |
|   |  0.06 |  | 4 | 8 | 14  |   |
|   |  0.12 | 87 | 81 | 84 | 77  |   |
|   |  0.25 | 8 | 9 | 1 | 3  |   |
|   |  0.5 |  | 1 | 1 |   |   |
|   |  ≥1 |  | 2 | 3 | 1  |   |

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|  Results  |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|  Organism | Conc. in μg/mL | # reference | MicroScan®  |   |   |   |
|  Clindamycin 5 BP Dilution |  |  | Manual overnight | Instrument overnight | <16 h instrument  |   |
|  E. faecalis ATCC 29212 Range >2 μg/mL | ≤0.12 |  |  |  |   |   |
|   |  0.25 |  |  |  |   |   |
|   |  0.5 |  |  |  |   |   |
|   |  1 |  |  |  |   |   |
|   |  2 |  |  |  |   |   |
|   |  >2 | 21 | 21 | 21 | 21  |   |
|  Results  |   |   |   |   |   |   |
|  Organism | Conc. in μg/mL | # reference | MicroScan®  |   |   |   |
|  Clindamycin 5 BP Dilution |  |  | Manual overnight | Instrument overnight | <16 h instrument  |   |
|  S. aureus ATCC 29213 Range <=≤0.12 - 0.25 μg/mL | ≤0.12 | 18 | 17 | 18 | 18  |   |
|   |  0.25 | 3 | 3 | 1 | 3  |   |
|   |  0.5 |  | 1 | 1 |   |   |
|   |  1 |  |  |  |   |   |
|   |  2 |  |  | 1 |   |   |
|   |  >2 |  |  |  |   |   |

There is a slight trend for the  $&lt; 16$  hour Long Dilution Sequence Rapid read method to produce QC results that were more susceptible than the reference result, if only by one dilution, for both the S. aureus ATCC 29213 and the E. faecalis ATCC 29212. This trend was not observed for the five Breakpoint Dilution Sequence QC results.

Inoculum density control: A turbidity meter was used for the turbidity inoculation method. Turbidity inoculum verification provided.

d. Detection limit:

Not Applicable

e. Analytical specificity:

Not Applicable

f. Assay cut-off:

Not Applicable

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2. Comparison studies:

a. Method comparison with predicate device:

Clinical testing was conducted at three sites using fresh isolates supplemented with stock isolates. A total of 304 gram-positive isolates were tested of which 268 were fresh isolates and 36 were stock isolates. Fourteen (14) Clinical isolates for the Long Dilution and the Breakpoint Dilution Sequences were reported at ≥16 hours and were not included as Rapid read results. There were 75 challenge isolates tested at one site 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. Fourteen (14) Challenge isolates for the Long Dilution and the Breakpoint Dilution Sequences were reported at ≥16 hours and were not included as Rapid read results.

The Synergies plus™ readings were obtained at times between 4.5 and 16 hours of incubation for &gt;95% of the results. An additional comparison was done with readings on the instrument after overnight incubation and also read manually when incubated 16 - 18 hours. Performance by these alternate reading methods was also acceptable with no apparent differences or trends.

The recommended CLSI reference method was followed with the exception of the use of a small amount (0.1%) Pluronic® in the final inoculum. A validation of the use of Pluronic® in the frozen reference panels was conducted. Similar calculations for the different reading methods were performed with very little difference. QC was also performed. There was a slight trend for the Rapid read method to produce more susceptible QC results than the reference method results, if only by one dilution. This trend was also observed in the Reproducibility studies.

The chart below demonstrates the performance of all three reading methods (Synergies plus™ readings at &lt;16 hours, overnight on the WalkAway® and manually read at 18 hours using the TouchScan®-SR) when compared to the reference method.

Clinical and Challenge Data – Read Method comparisons for Clindamycin

|   | Total | EA | %EA | Total Eval | EA of Eval | %EA of Eval | CA | %CA | #R | min | maj | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  <16 h
• Long
• 5 Dil. BP | 351 | 344 | 98.0 | 234 | 228 | 97.4 | 348 | 99.1 | 115 | 2 | 1 | 0  |
|   |  351 | NA | NA | NA | NA | NA | 348 | 99.1 | 115 | 2 | 1 | 0  |
|  Overnight instrument
• Long
• 5 Dil. BP | 379 | 375 | 98.9 | 253 | 251 | 99.2 | 373 | 98.4 | 124 | 4 | 1 | 1  |
|   |  379 | NA | NA | NA | NA | NA | 373 | 98.4 | 124 | 4 | 1 | 1  |
|  Overnight Manual
• Long
• 5 Dil. BP | 379 | 376 | 98.9 | 253 | 251 | 99.2 | 373 | 98.4 | 124 | 4 | 1 | 1  |
|   |  379 | NA | NA | NA | NA | NA | 373 | 98.4 | 124 | 4 | 1 | 1  |

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

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

NA – Essential Agreement result are not applicable for Breakpoint format

Essential agreement (EA) is when the MicroScan® Synergies plus panel agrees with the reference test panel results exactly or within one doubling dilution of the reference method. Category agreement (CA) is when the MicroScan® Synergies plus panel interpretation (S-I-R) agrees exactly with the reference panel interpretation. Evaluable (Eval) are results that are within the test range and on scale.

Of the 75 Challenge isolates tested, the expected results for 41 strains were Susceptible and 34 strains were Resistant. One very major error (1/7, 14.3%) occurred in the Challenge Set data. The vmj error was generated by one S. epidermidis (methicillin-resistant) by the Overnight Instrument and the Overnight Manual read methods in both the Long Dilution and the 5-Dilution Breakpoint Sequence data, but a vmj error was not detected by the Rapid read method, because the read time was &gt;16 hours. Although the expected result for this isolate was resistant, the reference result on the day of testing was susceptible and was in agreement with the Overnight Instrument and the Overnight Manual read methods results. The overall combined EA and the CA for the Challenge Set Data was &gt;95% for all read methods and dilution combinations. There was one (1) major error (6.7%, 1/15) produced by one S. aureus (methicillin-sensitive) generated by the Rapid read method only. The overall maj error rate of 2.9% (1/34) for the Challenge Set Data for all read methods was in the acceptable range. Therefore, the Challenge Set performance data are acceptable.

Clinical Data Read Method Comparison - Clindamycin

|   | Total | EA | %EA | Total Eval | EA of Eval | %EA of Eval | CA | %CA | #R | min | maj | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  <16 h
• Long
• 5 Dil BP | 290 | 285 | 98.3 | 200 | 196 | 98.0 | 288 | 99.3 | 88 | 2 | 0 | 0  |
|   |  290 | NA | NA | NA | NA | NA | 288 | 99.3 | 88 | 2 | 0 | 0  |
|  Overnight instrument
• Long
• 5 Dil BP | 304 | 301 | 99.0 | 211 | 209 | 99.1 | 300 | 98.7 | 90 | 3 | 1 | 0  |
|   |  304 | NA | NA | NA | NA | NA | 300 | 98.7 | 90 | 3 | 1 | 0  |
|  Overnight Manual
• Long
• 5 Dil BP | 304 | 301 | 99.0 | 211 | 209 | 99.1 | 300 | 98.7 | 90 | 3 | 1 | 0  |
|   |  304 | NA | NA | NA | NA | NA | 300 | 98.7 | 90 | 3 | 1 | 0  |

Performance claims (in bold) that will appear in the labeling and the procedural manual are based on the clinical Rapid read (&lt;16 hour) method results only. The table above displays the Clinical data results compared by reading method.

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The Clinical data Rapid read method EA of 98.3% and the CA of 99.3% are both very good. Overnight Instrument and Manual read methods EA and CA are both very similar to the Rapid read method results for the Long Dilution and the 5-Dilution Breakpoint Sequence data results.

There were no vmj errors generated by any of the read methods. There was 1 maj error (1/213, 0.5%) produced by the Overnight Instrument and the Overnight Manual read methods. This maj error was not observed in the Rapid read method results because the time-to-results was &gt;16 hours. Because of the number of off-scale results in the Clinical data results, no real trending was observed.

The overall error rates are within acceptable limits for all reading methods. The performance data are acceptable for both the Long Dilution and for the 5-Dilution Breakpoint Sequence results using the Rapid read (&lt;16 hour) method.

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:

Staphylococcus species Interpretive criteria: &lt;=≤0.5 (S), 1 – 2 (I), &gt;=≥ 4 (R)

The interpretative criteria and Quality Control Ranges values are included in the package insert.

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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/LON/K070860](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K070860)

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