MICROSCAN SYNERGIES PLUS GRAM POSITIVE MINIMUM INHIBITORY CONCENTRATION/COMBO PANELS - LEVOFLOXACIN

K051311 · Dade Behring, Inc. · LON · Jul 12, 2005 · Microbiology

Device Facts

• Record ID: K051311
• Device Name: MICROSCAN SYNERGIES PLUS GRAM POSITIVE MINIMUM INHIBITORY CONCENTRATION/COMBO PANELS - LEVOFLOXACIN
• Applicant: Dade Behring, Inc.
• Product Code: LON · Microbiology
• Decision Date: Jul 12, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1645
• Device Class: Class 2

Indications for 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 staphylococci and enterococci. After inoculation, panels are incubated for 4.5 - 18 hours at 35℃ +/- 1℃, in a WalkAway® SZ, 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. This particular submission is for the addition of the antimicrobial Levofloxacin, at concentrations of 0.03 to 16 ug/ml, to the test panel.

Device Story

MicroScan® Synergies plus™ panels are diagnostic tools for antimicrobial susceptibility testing (AST). Panels contain dehydrated antibiotics and control wells; rehydrated with bacterial suspension (turbidity method). System uses WalkAway®-SI instrument with colorimetric optics (lamp/photosensor) to monitor bacterial growth. Device measures growth kinetics to determine Minimum Inhibitory Concentration (MIC) at 4.5–16 hours or via overnight incubation (16–20 hours). Output is quantitative MIC and qualitative susceptibility interpretation. Used in clinical microbiology laboratories by technicians. Results assist clinicians in selecting appropriate antibiotic therapy for gram-positive infections.

Clinical Evidence

Bench testing only. Performance evaluated using fresh clinical isolates and stock challenge strains compared to a frozen reference panel. Essential Agreement for Levofloxacin was >98%. Reproducibility and precision were confirmed using the WalkAway® system and turbidity inoculum preparation. Quality control testing met acceptable standards.

Technological Characteristics

Miniaturized broth dilution susceptibility test; dehydrated antimicrobial agents in microtiter wells. Rehydrated with Pos Broth. Incubation 4.5-18 hours at 35°C. Compatible with WalkAway® instrumentation or visual reading. Connectivity via automated instrument interface.

Indications for Use

Indicated for testing levofloxacin (0.03–16 µg/mL) against Enterococcus and Staphylococcus species in gram-positive test panels. Requires 4.5–16 hours or 16–20 hours incubation. For prescription use only; turbidity method of inoculum preparation required.

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:
K051311

B. Purpose for Submission:
To add levofloxacin to the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels

C. Measurand:
Levofloxacin at 0.03 – 16 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

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LRG-Instrument for Auto Reader & Interpretation of Overnight Antimicrobial Susceptibility Systems
JWY - Manual Antimicrobial Susceptibility Test Systems
LTT – Panels, Test, Susceptibility, Antimicrobial
LTW – Susceptibility Test Cards, Antimicrobial

4. Panel:
83 Microbiology

H. Intended Use:

1. Intended use(s):

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 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 gram-positive cocci and Listeria.

2. Indication(s) for use:

The testing of levofloxacin at concentrations of 0.03 – 16 µg/mL to the gram-positive test panel for testing Enterococcus and Staphylococcus 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 (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 16-20 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 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 |
| Differences | | | |
| Item | Device | Predicate | |
| Panels | Dried levofloxacin 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 equivalent | AutoScan® -4 or WalkAway® | |
| Antibiotic | Levofloxacin at 0.03-16 μg/mL | Different concentrations depending on the antibiotic | |

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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-S15) “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 x 10⁷ 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® 16-18 hour readings and manual readings at 16-20 hours incubation. The WalkAway® SI had 10 results that were not readable at &lt;16 hours. All results were &gt;95% reproducible. Although reproducible results were obtained with all methods of reading the &lt;16 hour readings produced a slight trend for a more susceptible result if only by one dilution.

b. Linearity/assay reportable range:

Not Applicable

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

The recommended QC isolate was tested a sufficient number of times with acceptable results on all testing days with the reference method. There were no QC results that did not provide a result in the 4.5-16 hour window. 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 the results in each concentration tested with the expected range stated.

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| Results | | | | | |
| --- | --- | --- | --- | --- | --- |
| Organism | Conc in μg/mL | # reference | MicroScan® | | |
| | | | Manual overnight | Instrument overnight | <16h instrument |
| E. faecalis ATCC 29212
Range 0.25-2 μg/mL | ≤ 0.12 | | | | |
| | 0.25 | | | | |
| | 0.5 | 40 | 31 | 19 | 80 |
| | 1 | 44 | 52 | 65 | 4 |
| | 2 | | 1 | | |
| | 4 | | | | |
| | | | | | |
| S. aureus ATCC 29213
Range 0.06-0.5 μg/mL | ≤ 0.03 | | | | |
| | 0.6 | | | | |
| | 0.12 | 64 | 40 | 35 | 72 |
| | 0.25 | 19 | 43 | 48 | 12 |
| | 0.5 | 1 | 1 | 1 | |
| | 1 | | | | |

There is a tendency of the &lt;16 hours results to be one dilution more susceptible but still be in the acceptable range. This was observed in the reproducibility data as well.

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 three sites using fresh isolates supplemented with stock isolates. A total of 549 gram-positive isolates were tested of which 476 were fresh isolates. There were 75 challenge isolates tested at one site and compared to the reference broth dilution result mode that was determined by

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previous testing of each isolate multiple times in the recommended reference panel. 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%) of 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 with no difference apparent in the results.

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.

| | total | EA | %EA | Total evaluable | EA of evaluable | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| < 16h | 621 | 613 | 98.7 | 431 | 424 | 98.4 | 602 | 96.9 | 250 | 16 | 1 | 2 |
| Overnight instrument | 624 | 618 | 99.0 | 431 | 426 | 98.8 | 618 | 99.0 | 250 | 12 | 0 | 1 |
| Overnight manual | 624 | 619 | 99.2 | 430 | 426 | 99.1 | 609 | 97.6 | 250 | 14 | 0 | 1 |

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.

b. Matrix comparison:
Not Applicable

3. Clinical studies:
a. Clinical Sensitivity:
Not Applicable
b. Clinical specificity:

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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. and Enterococcus spp. interpretive criteria:

$\leq 2$ (Susceptible), 4 (Intermediate), $\geq 8$ (Resistant)

All values are included in the package insert.

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.