MICROSCAN SYNERGIES PLUS GRAM-POSITIVE MIC/COMBO PANELS WITH VANCOMYCIN (0.25-64 UG/ML)

K060312 · Dade Behring, Inc. · LON · Mar 23, 2006 · Microbiology

Device Facts

• Record ID: K060312
• Device Name: MICROSCAN SYNERGIES PLUS GRAM-POSITIVE MIC/COMBO PANELS WITH VANCOMYCIN (0.25-64 UG/ML)
• Applicant: Dade Behring, Inc.
• Product Code: LON · Microbiology
• Decision Date: Mar 23, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1645
• Device Class: Class 2

Indications for Use

Vancomycin at concentrations of 0.25 to 64 µg/mL on the MicroScan® Synergies plus ™ Gram-Positive MIC/Combo Panel is intended for use with MicroScan® Synergies plus ™ Panels read on the WalkAway® -SI System (including upgraded WalkAway® -40 or WalkAway® -96 to meet WalkAway® SI equivalence). MicroScan® panels are designed for use in testing colonies, grown on solid media, of rapidly growing aerobic and facultative anaerobic gram-positive cocci; the panels also provide quantitative and/or qualitative antimicrobial agent susceptibility for staphylococci and enterococci.

Device Story

MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels are miniaturized broth dilution susceptibility tests; dehydrated antimicrobial agents are rehydrated with Synergies plus™ Pos Broth after inoculation with standardized organism suspensions. Panels are incubated in WalkAway® SI System (or equivalent) for 4.5–18 hours. Device uses rapid fluorogenic identification and dried overnight AST technologies. Instrumentation reads minimum inhibitory concentration (MIC) by determining lowest antimicrobial concentration showing growth inhibition. Used in clinical laboratories by trained personnel to guide antimicrobial therapy for gram-positive infections. Benefits include rapid, quantitative susceptibility results for vancomycin (0.25–64 µg/ml) to inform clinical decision-making.

Clinical Evidence

Bench testing only. Performance evaluated using fresh and stock efficacy isolates and challenge strains. Compared against frozen reference panel. Overall essential agreement >97% for vancomycin. Reproducibility and precision confirmed using turbidity inoculum preparation and WalkAway® SI System. Quality control testing yielded acceptable results.

Technological Characteristics

Miniaturized broth dilution panels; dehydrated antimicrobial agents in water/buffer/broth. Sensing principle: fluorogenic identification and growth inhibition detection. Energy source: electrical (WalkAway® system). Connectivity: compatible with WalkAway® instrumentation. Sterilization: not specified. Software: automated reading of MIC via instrumentation.

Indications for Use

Indicated for testing Staphylococcus and Enterococcus spp. using vancomycin at 0.25–64 µg/mL concentrations at <16 hours or >16 hours (overnight).

Regulatory Classification

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® Synergies plus™ Gram-Negative MIC/Combo Panels
• MicroScan® Dried Gram-Positive Panels

Submission Summary (Full Text)

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

A. 510(k) Number:
K060312

B. Purpose for Submission:
For addition of vancomycin on the MicroScan® Synergies plus™ Gram-Positive for testing appropriate Staphylococcus and Enterococcus spp

C. Measurand:
Vancomycin 0.25 – 64 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® 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

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:

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1. Intended use(s):

Vancomycin at concentrations of 0.25 to 64 µg/mL on the MicroScan® Synergies plus ™ Gram-Positive MIC/Combo Panel is intended for use with MicroScan® Synergies plus ™ Panels read on the WalkAway® -SI System (including upgraded WalkAway® -40 or WalkAway® -96 to meet WalkAway® SI equivalence).

MicroScan® panels are designed for use in testing colonies, grown on solid media, of rapidly growing aerobic and facultative anaerobic gram-positive cocci; the panels also provide quantitative and/or qualitative antimicrobial agent susceptibility for staphylococci and enterococci.

2. Indication(s) for use:

The addition of vancomycin at concentrations of 0.25 to 64 µg/mL to the gram-positive test panel for testing Staphylococcus and Enterococcus spp. at &lt; 16 hours or &gt;16 hours for an overnight reading.

3. Special conditions for use statement(s):

- S. aureus isolates with MICs of 8 – 16 µg/mL on MicroScan® Synergies plus ™ Gram-Positive MIC/Combo Panels will be incubated for 16-18 hours for overnight instrument or visual reporting of vancomycin.
- MicroScan® Synergies plus ™ Gram-Positive MIC/Combo Panel detects vancomycin resistance in the VRSA S. aureus strains available at the time of comparative testing. The ability of the MicroScan® Synergies plus ™ Gram-Positive MIC/Combo Panel to detect resistance in other S. aureus strains is unknown due to the limited number of resistant strains available for comparative testing.
- 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 (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®, then 0.1ml transferred to 25ml of inoculum Synergies plus Pos Broth with PLURONIC®) for a 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

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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

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 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 hours | Same |
| Results | Quantitative with qualitative interpretations | Same |
| Technology | Growth based | Same |
| Differences | | |
| Item | Device | Predicate |
| Panels | Dried vancomycin in water | Dried clindamycin or gentamicin in broth |
| Reading | Uses both an early read and overnight methods in the same system | Overnight system uses only the overnight reading methods and <16 hour instruments use only the <16 hour read methods. |
| Inoculum preparation | Turbidity method of inoculation only. | Inoculum prepared from isolated colonies using either the Turbidity method or Prompt® system |
| Instrument | WalkAway® -SI System or | autoScan® -4 or |
| | Inoculum with a single run | AutoScan® -4 or |
| Inoculum preparation | Turbidity method of inoculation only. | AutoScan® -4 or |
| Inoculum preparation | Turbidity method of inoculation | AutoScan® -4 or |

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| | equivalent | WalkAway® |
| --- | --- | --- |
| Antibiotic | Vancomycin 0.25 – 64 μg/mL | 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-S16) “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, or 18 hours (overnight instrument readings, manual readings) depending on the growth rate of the organism being tested. The time of final read is dependent on 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 10 isolates tested at 3 sites on 3 separate days in triplicate. The study included the testing on the WalkAway® SI read at &lt;16 hours, WalkAway® &gt;16 hour readings and manual readings at &gt;16 hour incubation. All results were &gt;95% reproducible.

b. Linearity/assay reportable range:

Not Applicable

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

The recommended QC isolates, S. aureus ATCC 29213 and E. faecalis ATCC 29212 were tested a sufficient number of times with acceptable results on all testing days with the reference method. The E. faecalis ATCC 29212 isolates grew in the range of 6.5 – 24 hours read times while all QC results of S. aureus ATCC 29213 grew in the 4.5-16 hour window on the Synergies Plus. Quality control results demonstrated the ability of the different reading parameters (manual and instrument) to produce acceptable results.

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

| Results | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Organism | Conc in μg/mL | # reference | MicroScan® | | | |
| | | | >16 Hour Manual overnight | | >16 Hour Instrument overnight | <16 Hour |
| | | | | | | |
| S. aureus ATCC 29213 | 0.5 | 30 | | | | |
| Expected Range: 0.25 – 1 μg/mL | 1 | 53 | 79 | | 82 | 84 |
| | 2 | 1 | 5 | | 2 | |
| | | | | | | |
| | | | | | | |
| E. faecalis ATCC 29212 | 2 | 84 | 47 | | 60 | 60 |
| Expected Range: 1 – 4 μg/mL | 4 | | 37 | | 24 | 24 |
| | | | | | | |
| | | | | | | |

Inoculum density control: A turbidity meter was used for the turbidity 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 testing was conducted at 3 sites using fresh isolates supplemented with stock isolates. A total of 549 gram positive Enterococci and Staphylococci were tested of which 476 were fresh isolates and 73 were stock isolates. There were 78 challenge isolates tested which included the 3 VRSA (Vancomycin Resistant S. aureus). All challenge isolates were tested at one site with the exception of the 3 VRSA (Vancomycin Resistant S. aureus) which were tested at a different site. These challenge isolates were compared to the reference broth dilution result mode that was determined by previous testing of each isolate multiple times in the recommended reference panel. The Synergies plus™ readings were obtained between 4.5 and 16 hours of incubation for &gt;90% of the results. An additional comparison was done with

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readings on the instrument after overnight incubation and also read manually when incubated &gt;16 hours. Performance by these alternate reading methods was also acceptable. 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. The test device had a no growth rate of &lt;10%.

The charts below demonstrated the performance of all three reading methods (Synergies plus™ readings at &lt;16 hours, &gt;16 hours on the WalkAway® and manually read at &gt;16 hours using the touchScan®-SR) with the long dilution sequence when compared to the reference method.

Performance Summary of the &lt;16 Hour Read Method

| | Total | EA | %EA | Total eval | EA of eval | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Efficacy | 507 | 497 | 98.0 | 443 | 435 | 98.2 | 501 | 98.8 | 59 | 2 | 4 | 0 |
| Challenge | 72 | 68 | 94.4 | 59 | 56 | 94.9 | 68 | 94.4 | 15 | 3 | 1 | 0 |
| Combined | 579 | 565 | 97.6 | 502 | 491 | 97.8 | 569 | 98.3 | 74 | 5 | 5 | 0 |

Performance Summary of the &gt;16 Hour Instrument Read

| | Total | EA | %EA | Total eval | EA of eval | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Efficacy | 549 | 540 | 98.4 | 486 | 478 | 98.4 | 546 | 99.5 | 61 | 1 | 2 | 0 |
| Challenge | 78 | 73 | 93.6 | 65 | 61 | 93.8 | 74 | 94.9 | 15 | 3 | 1 | 0 |
| Combined | 627 | 613 | 97.8 | 551 | 539 | 97.8 | 620 | 98.9 | 76 | 4 | 3 | 0 |

Performance Summary of the &gt;16 Hour Manual Read

| | Total | EA | %EA | Total eval | EA of eval | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Efficacy | 549 | 543 | 98.9 | 486 | 481 | 99.0 | 547 | 99.6 | 61 | 1 | 1 | 0 |
| Challenge | 78 | 73 | 93.6 | 65 | 61 | 93.8 | 73 | 93.6 | 15 | 4 | 1 | 0 |
| Combined | 627 | 616 | 98.2 | 551 | 542 | 98.4 | 620 | 98.9 | 76 | 5 | 2 | 0 |

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

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

Evaluable results are those that fall within the test range of the reference method and could also be on-scale with the new device if within the plus/minus one dilution variability. EA is when there is agreement between the reference method and the MicroScan® within plus or minus one serial two-fold dilution of antibiotic. CA is when the interpretation of the reference method agrees exactly with the interpretation of the MicroScan® result.

The &lt;16 Hour Read Method had 42 isolates that did not grow in 16 hours

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for a no growth rate of 7.7% (48/627) but provided results at &gt;16 hour. There appears to be a slight trend where the test device is more resistant than the reference device as reflected in the number of maj errors for each read method. This observation was also noted in the QC organisms where results are at the higher end of the expected range.

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 spp. ≤4 (S), 8–16 (I), ≥32 (R)

Enterococcus spp. ≤4 (S), 8–16 (I), ≥32 (R)

S. aureus comment only:

- S. aureus isolates with vancomycin MICs ≥4 μg/mL should alert the user that additional testing is advised and the isolate with confirmed, or potential, vancomycin resistance should be reported immediately through state and local health departments to the CDC

N. Proposed Labeling:

The interpretative criteria are the same as recommended by the FDA. All values are included in the package insert.

O. Conclusion:

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