DRIED GRAM-POSITIVE MIC/COMBO PANELS

K051202 · Dade Behring, Inc. · JWY · Jun 23, 2005 · Microbiology

Device Facts

• Record ID: K051202
• Device Name: DRIED GRAM-POSITIVE MIC/COMBO PANELS
• Applicant: Dade Behring, Inc.
• Product Code: JWY · Microbiology
• Decision Date: Jun 23, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1640
• Device Class: Class 2

Indications for Use

To determine antimicrobial agent susceptibility.

Device Story

MicroScan® Dried Gram-Positive MIC/Combo Panels consist of dehydrated Mueller Hinton Broth and nutrients in microdilution wells. Device rehydrated and inoculated with bacterial suspension (turbidity or Prompt® method); incubated 16-24 hours at 35°C. Growth detection performed via visual observation or automated optics systems (autoSCAN® 4 or WalkAway®). System identifies minimum inhibitory concentration (MIC) and categorical interpretation (SIR). Used in clinical microbiology laboratories to determine susceptibility of gram-positive cocci to vancomycin. Output informs antibiotic selection and resistance monitoring, specifically aiding detection of vancomycin-resistant S. aureus (VRSA).

Clinical Evidence

Bench testing only. Performance evaluated using fresh/stock clinical isolates and challenge strains compared to CLSI frozen reference panels. Essential Agreement for vancomycin was >99%. Reproducibility and precision confirmed across multiple inoculum methods (Turbidity, Prompt) and instruments (autoSCAN-4, WalkAway). Quality control testing met acceptance criteria.

Technological Characteristics

Dried microdilution panels containing Mueller Hinton Broth and nutrients. Growth-based detection via optical systems. Inoculation via turbidity or Prompt® methods. Incubation 16-24 hours at 35°C. Compatible with autoSCAN® 4 and WalkAway® automated readers. Software utilizes growth algorithms for MIC determination.

Indications for Use

Indicated for determining quantitative/qualitative antimicrobial susceptibility of rapidly growing aerobic and facultative anaerobic gram-positive cocci, including Enterococcus spp., Staphylococcus spp. (including S. aureus and S. epidermidis), Streptococcus agalactiae, and Streptococcus bovis. For prescription use.

Regulatory Classification

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-Positive and Gram-Negative MIC/Combo Panels (k862140)

Submission Summary (Full Text)

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

A. 510(k) Number:
K051202

B. Purpose for Submission:
Use of a revised vancomycin formulation in the Dried Gram-Positive MIC/Combo panels for the removal of a limitation on testing of *Staphylococcus aureus* by improving the detection of vancomycin-resistant *S. aureus* (VRSA)

C. Measurand:
Vancomycin at 0.25 to 128 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® Dried Gram-Positive 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

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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® Dried Gram Positive MIC/Combo, Dried Gram Positive Breakpoint Combo and Dried Gram Positive ID Type 2 panels.
MicroScan® Positive panels are designed for use in determining antimicrobial agent susceptibility and/or identification to the species level of rapidly growing aerobic and facultatively gram-positive cocci, some fastidious aerobic gram positive cocci and *Listeria monocytogenes*. Refer to Limitation of Procedure Section for use with fastidious streptococci.

2. Indication(s) for use:
The MicroScan® Dried 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 cocci. This indication is for the addition of the antimicrobial vancomycin at concentrations of 0.25-128 µg/mL to the test panel.

3. Special conditions for use statement(s):
The Prompt® method of inoculation is an alternate method of inoculation preparation that is supported in the methodology along with the turbidity method. The stationary and log inoculum methods should not be used with this antibiotic.

4. Special instrument requirements:
These panels can be read at ≥ 16 hours of incubation either manually, automatically on the autoSCAN® 4, or with the WalkAway® instrument systems but for best detection of VRSA readings should be performed after 18 hours especially for the autoSCAN® 4 instrument read results.

I. Device Description:
The MicroScan® Dried Gram-Positive MIC/Combo Panel contains microdilutions 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

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turbidity method (inoculum prepared in water, then 0.1ml transferred to 25ml of inoculum water containing pluronic-D/F-a wetting solution) for a final inoculum concentration of 3-7 X 10⁵ CFU/ml. 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 16-24 hours and read by visual observation of growth. Panels may also be read automatically with the WalkAway® or the AutoSCAN®4.

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

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | See above | Same |
| Inoculum preparation | Inoculum prepared from isolated colonies using either the Turbidity method or Prompt® system | Same |
| Technology | Growth based after 16 hours incubation | Same |
| Results | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) | Same |
| Instrument | autoSCAN® -4 or WalkAway® | Same |
| Differences | | |
| Item | Device | Predicate |
| Antibiotic | Vancomycin | Different concentrations depending on the antibiotic |
| Test organism | Enterococcus, Staphylococcus and some Streptococcus | Varies according to the antibiotic |
| Limitations | Staphylococcus must read at ≥ 18 hour of incubation on the autoSCAN® 4 | None |

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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:

After incubation in a non-CO₂ incubator for 16-24 hours, the minimum inhibitory concentration (MIC) for the test organisms are read by determining the lowest antimicrobial concentration showing inhibition of growth. The panels are read either manually using a touchSCAN® SR, or with the autoSCAN® 4 or the WalkAway® instrument, which uses an optics systems with growth algorithms to directly measure organism growth.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Reproducibility was demonstrated using 5 isolates tested at 2 sites and included the three VRSA and two QC strains. Three reading methods and two inoculation methods were tested at one site and the other site tested in replicates of three with each inoculation method using the manual reading method only. The QC strains were additionally tested at 5 sites using all methods. The following table provides the overall results for all combinations of these variables. This represents the reproducibility of each method based on the mode of that method and not the expected value.

| Difference in the number of dilutions between the mode of the MicroScan® result and the actual result with each different variable | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Inoculation method | Read method | ≥ Minus 2 dilutions | Minus 1 dilution | Exact | Plus 1 dilution | ≥ Plus 2 dilutions |
| Turbidity | Manual(touchSCAN®) | | 8 | 160 | 28 | 2 |
| Turbidity | WalkAway® | | 11 | 158 | 17 | |
| Turbidity | autoSCAN®4 | | 30 | 150 | 9 | 1 |
| Prompt® | Manual(touchSCAN®) | 1 | 38 | 150 | | 3 |
| Prompt® | WalkAway® | | 44 | 146 | | 3 |
| Prompt® | autoSCAN® 4 | | 46 | 144 | | |

b. Linearity/assay reportable range:

Not Applicable

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

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Quality Control was performed daily with the turbidity method and with the Prompt® with the following results.

| Organism | Conc. In μg/mL | Reference result | Turbidity inoculation with Read methods | | | Prompt® inoculation with Read methods | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | Manual | Walk-Away® | Auto-SCAN® | Manual | Walk-Away® | Auto-SCAN® |
| | | | | | | | | |
| E. faecalis ATCC 29212 Expected range 1-4 μg/mL | ≤ 0.25 | | | | | | | |
| | 0.5 | | | | | | | |
| | 1 | | | | | 1 | | |
| | 2 | 95 | 8 | 11 | 30 | 13 | 15 | 15 |
| | 4 | 1 | 87 | 78 | 62 | 78 | 77 | 75 |
| | | | | | | | | |
| S. aureus ATCC 29213 Expected range 0.5-2 μg/mL | ≤ 0.25 | | | | | | | |
| | 0.5 | 1 | | | | | | |
| | 1 | 89 | 67 | 75 | 82 | 25 | 29 | 31 |
| | 2 | 7 | 27 | 16 | 9 | 66 | 63 | 63 |
| | 4 | | | | 1 | | | |
| | 8 | | | | | | | |
| | ≥ 128 | | | 1 | | | | |

Quality control results demonstrated the ability of all variables of the procedure (reading and inoculation) to produce acceptable results. There does appear to be slight trending in all of the methods for both QC strains to appear one dilution more resistant than the reference method result but still in the expected range an acceptable number of times. This is even more apparent with the Prompt® method of inoculation and the S. aureus QC strain.

Inoculum density control: A turbidity meter was used for the turbidity inoculation method. The Prompt® method of inoculation had colony counts performed periodically throughout the study to determine the average inoculum density since there is no visual check of the inoculum using this device. QC strains were also included in the colony count study. The inoculum with the Prompt® method of inoculation generally provides a higher number of CFU with more variability than a method using turbidity meter although the S. aureus did have more variability even in the turbidity method but the average was still in the acceptable range for the turbidity method but not for the Prompt®. There are limitations for the use of the Prompt® and certain antibiotics that are more sensitive to inoculum concentration and those are stated in the package insert. Vancomycin will require no such statement. The chart below shows the CFU study results.

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| Organism | Number tested and method of inoculation | Average CFU X 105 | Minimum CFU X 105 | Maximum CFU X 105 |
| --- | --- | --- | --- | --- |
| S. aureus | 51 Prompt® | 15 | 2.7 | 54 |
| S. aureus ATCC 29213 | 36 Prompt® | 15.5 | 0.56 | 50 |
| S. aureus ATCC 29213 | 18 Prompt® | 18 | 2.3 | 30 |
| S. aureus ATCC 29213 | 31 Turbidity | 3.8 | 0.8 | 54 |
| E. faecalis ATCC 29212 | 32 Prompt® | 4.8 | 0.5 | 12 |
| E. faecalis ATCC 29212 | 14 Prompt® | 4.47 | 3 | 6.8 |
| E. faecalis ATCC 29212 | 41 Turbidity | 1.85 | 0.37 | 4 |

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:

The study was conducted at 5 sites. One hundred seventy two clinical isolates were tested and 106 challenge isolates. Challenge set includes the CDC Enterococci challenge set which includes 11 Van A, 19 Van B, 5 Van C1 and 5 Van C2. Also included were 53 Staphylococci from the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) which have interpretations near the intermediate breakpoint. This set also included the three known VRSA strains tested at MicroScan®. The results were compared to the reference expected results. The following table demonstrates the performance based on essential agreement and category agreement for the overall performance of the clinical isolates and the challenge with the turbidity method of inoculation and manual readings. Similar calculations for the different inoculation and reading methods were performed with very little difference.

| | total | EA | %EA | Total evaluable | EA of evaluable | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Clinical | 172 | 172 | 100 | 161 | 161 | 100 | 172 | 100 | 10 | 0 | 0 | 0 |
| Challenge | 106 | 104 | 98.1 | 95 | 93 | 97.9 | 101 | 95.3 | 28 | 5 | 0 | 0 |
| Combined | 278 | 276 | 99.3 | 256 | 254 | 99.2 | 273 | 98.2 | 38 | 5 | 0 | 0 |

EA-Essential Agreement

maj-major discrepancies

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CA-Category Agreement
R-resistant isolates

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 table below demonstrates the clinical and challenge results that were in exact agreement with the reference method result and those that differed by one or more dilutions.

| Difference in the number of dilutions between the reference result and the MicroScan® Result | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Inoculation method | Read method | ≤ minus 2 dilutions | minus 1 dilution | Exact | Plus 1 dilution | ≥ Plus 2 dilutions |
| Turbidity | Manual | 1 | 24 | 201 | 51 | 1 |
| Turbidity | WalkAway ® | 0 | 11 | 210 | 56 | 1 |
| Turbidity | autoSCAN® 4 | 0 | 25 | 217 | 36 | 0 |
| Prompt® | Manual | 0 | 23 | 136 | 110 | 6 |
| Prompt® | WalkAway ® | 0 | 11 | 146 | 112 | 6 |
| Prompt® | autoSCAN® 4 | 2 | 21 | 154 | 95 | 3 |

There appears to be a slight trend of the MicroScan® to be more resistant than the reference method (more values in the plus category). This is even more exaggerated using the Prompt® method of inoculation but still in EA at >95% with all read methods. This trend to slightly more resistant results for the Prompt® method of inoculation is consistent with the reproducibility data and also the higher CFU/ml in the Prompt® inoculum.

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:

$$
\leq 4 \mu \mathrm{g} / \mathrm{mL} (\mathrm{S}), 8 - 16 \mu \mathrm{g} / \mathrm{mL} (\mathrm{I}), \geq 32 \mu \mathrm{g} / \mathrm{mL} (\mathrm{R})
$$

Streptococcus other than S. pneumoniae interpretive criteria

$$
\leq 1 (\mathrm{S})
$$

The interpretative criteria and Quality Control Ranges are the same as recommended in the FDA approved pharmaceutical package insert and the CLSI. 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.