MicroScan Dried Gram Positive MIC/Combo Panels - Vancomycin (0.25-64 ug/mL)

K152346 · Beckman Coulter, Inc. · JWY · Sep 16, 2015 · Microbiology

Device Facts

• Record ID: K152346
• Device Name: MicroScan Dried Gram Positive MIC/Combo Panels - Vancomycin (0.25-64 ug/mL)
• Applicant: Beckman Coulter, Inc.
• Product Code: JWY · Microbiology
• Decision Date: Sep 16, 2015
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.1640
• Device Class: Class 2

Indications 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 bacteria. After inoculation, panels are incubated for 16 - 20 hours at 35°C +/- 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the package insert.

Device Story

MicroScan Dried Gram-Positive MIC/Combo Panels are miniaturized broth dilution susceptibility tests. Device consists of dehydrated antimicrobial agents in broth. Clinical laboratory workflow: isolate colonies from solid media; prepare standardized organism suspension; inoculate panel; rehydrate with water; incubate 16-20 hours at 35°C in non-CO2 incubator. Output: Minimum Inhibitory Concentration (MIC) determined by lowest antimicrobial concentration inhibiting growth. Read visually or via MicroScan instrumentation (autoSCAN-4 or WalkAway). Results assist clinicians in selecting appropriate antibiotic therapy for gram-positive bacterial infections.

Clinical Evidence

Bench testing only. Validation study compared MicroScan Dried Gram-Positive Panel performance against CLSI frozen reference panels using fresh/stock efficacy isolates and stock challenge strains. Primary endpoint: Essential Agreement (EA). For Enterococcus spp., EA ranged from 97.6% to 99.0% across all inoculation and reading methods. Reproducibility and precision testing confirmed acceptable performance for Vancomycin using Turbidity and Prompt inoculation methods and autoSCAN-4/WalkAway instrumentation. Quality control testing yielded acceptable results.

Technological Characteristics

Miniaturized broth microdilution system; dehydrated antimicrobial agents in broth; rehydrated with water. Dimensions: multi-well panel format. Connectivity: compatible with autoSCAN-4 and WalkAway instrumentation. Incubation: 16-20 hours at 35°C +/- 1°C. Inoculation methods: Turbidity or Prompt. Analysis: visual or automated optical reading.

Indications for Use

Indicated for determining antimicrobial susceptibility of rapidly growing aerobic and facultative anaerobic gram-positive bacteria, specifically Enterococci (e.g., E. faecalis) and Staphylococci (e.g., S. aureus, S. epidermidis, including heterogeneous methicillin-resistant strains).

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 MIC/Combo Panels - Vancomycin (K150039)

Submission Summary (Full Text)

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SPECIAL 510(k): Device Modification OIR Decision Summary

To: THE FILE

RE: DOCUMENT NUMBER K152346

This 510(k) submission contains information/data on modifications made to the SUBMITTER'S own Class II, Class III or Class I devices requiring 510(k). The following items are present and acceptable (delete/add items as necessary):

1. The name and 510(k) number of the SUBMITTER'S previously cleared device.
Trade Name: K150039 - MicroScan Dried Gram Positive MIC/Combo Panels - Vancomycin

2. Submitter's statement that the INDICATION/INTENDED USE of the modified device as described in its labeling HAS NOT CHANGED along with the proposed labeling which includes instructions for use, package labeling, and, if available, advertisements or promotional materials.

3. A description of the device MODIFICATION(S), including clearly labeled diagrams, engineering drawings, photographs, user's and/or service manuals in sufficient detail to demonstrate that the FUNDAMENTAL SCIENTIFIC TECHNOLOGY of the modified device has not changed.

This change was for a modification to the recommended incubation time for isolates of Enterococcus species from 24 hours to 16 to 20 hours. The instructions in labeling of the previously cleared device indicates an incubation time of 24 hours is necessary for detection or resistance in isolates that have intermediate or susceptible MICs to vancomycin. This labeling change does not affect the intended use. There were no modifications to the device.

4. Comparison Information (similarities and differences) to applicant's legally marketed predicate device including, labeling, intended use, physical characteristics, and evaluation of results obtained during the clinical study for incubation times of 16 to 20 hours for Enterococcus species as compared to results obtained after 24 hours of incubation.

5. A Design Control Activities Summary which includes:

a) Identification of Risk Analysis method(s) used to assess the impact of the modification on the device and its components, and the results of the analysis
b) Based on the Risk Analysis, an identification of the verification and/or validation activities required, including methods or tests used and acceptance criteria to be applied

The labeling for this modified subject device has been reviewed to verify that the indication/intended use for the device is unaffected by the modification. In addition, the submitter's description of the particular modification(s) and the comparative information between the modified and unmodified devices demonstrate that the fundamental scientific technology has not changed. The submitter has provided the design control information as specified in The New 510(k) Paradigm and on this basis, I recommend the device be determined substantially equivalent to the previously cleared (or their preamendment) device.

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## Applicant:
Beckman Coulter

## 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 bacteria. After inoculation, panels are incubated for 16 - 20 hours at 35°C +/- 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the package insert.

This particular submission is for the addition of the reformulated antimicrobial Vancomycin at concentration of 0.25 to 64 µg/ml to the test panel. The gram positive organisms which may be used for Vancomycin susceptibility testing in this panel are:

Enterococcus spp (e.g., Enterococcus faecalis)

Staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis (including heterogeneous methicillin-resistant strains)

## Device Description:

The MicroScan Dried Gram Positive MIC/Combo Panel with vancomycin is used to determine the quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative gram-positive cocci. After inoculation panels are incubated for 16-20 hours at 35°C ± 1°C in a non-CO2 incubator and read either visually or with MicroScan instrumentation, according to the package insert "Accurate detection of resistance requires an incubation time of 24 hours for Enterococci isolates with vancomycin.

Primary inoculation Method: Turbidity, Alternate Inoculation Method: Prompt™

Primary Read Method: Manual, Alternate Read Methods: MicroScan WalkAway System and MicroScan autoSCAN-4

Table 1. Comparison with the Predicate

| Similarities | | |
| --- | --- | --- |
| Item | Device MicroScan® Dried Gram-Positive MIC/Combo Panels – Vancomycin | Predicate MicroScan® Dried Gram-Positive MIC/Combo Panels – Vancomycin (K150039) |
| Intended Use | Determination of susceptibility to vancomycin with gram-positive bacteria | Same |
| Technology | Overnight Microdilution MIC Susceptibility Tests | Same |

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| Similarities | | |
| --- | --- | --- |
| Item | Device MicroScan® Dried Gram-Positive MIC/Combo Panels – Vancomycin | Predicate MicroScan® Dried Gram-Positive MIC/Combo Panels – Vancomycin (K150039) |
| Components | Vancomycin 0.25 – 64 μg/mL | Same |
| Result Reported | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) | Same |
| MIC Interpretive Breakpoints | S. aureus : S≤ 2, I= 4-8, R≥16 Enterococci and Coagulase Negative Staphylococci: S≤4, I=8-16, R≥32 | Same |
| Read Methods | Manual and Automated | Same |
| Inoculation Methods | Turbidity and Prompt™ | Same |
| Instruments | autoSCAN® 4 or WalkAway® | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Incubation Times | 16 – 20 hours for Staphylococcus species and Enterococcus species | 16 – 20 hours for Staphylococcus species; 24 hours for detection of resistant Enterococcus species |

1. **Analytical performance:**
a. **Precision/Reproducibility:**
Reproducibility data for 5 isolates of Enterococcus species including one isolate of E. casseliflavus, two isolates of E. faecalis and two isolates of E. faecium was provided. Organism selection was based on the intended use of the antimicrobial agent. Each isolate was tested at each site in triplicate over three days using 2 inoculation methods (Turbidity and Prompt) and 3 reading methods (manual, WalkAway Instrument and autoSCAN-4 Instrument).

The mode of the test panel MIC results was determined for each isolate. MIC results were compared to the mode value for each isolate. Results were considered in agreement if the test panel MIC was equal to or within ± 1 dilution of the mode for that isolate. Agreement was calculated assuming any off-scale results were within one well from the mode (best case) and by assuming any off-scale results were greater than one well from the mode (worst case). Data were analyzed for all dilutions of Vancomycin (0.25-64 μg/mL).

For all sites combined, agreement within 1 ± dilution from the mode for all inoculation and reading methods was > 95% for best case and > 94.7% for worst case scenarios. For isolates tested using the Prompt inoculation method and interpreted using the WalkAway instrument, the mode MIC of one Enterococcus isolate was off scale.

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Reproducibility was determined using the remaining four Enterococcus isolates. The results of the reproducibility best and worst case scenarios are shown in Table 2 below. The reproducibility results are acceptable.

Table 2. Reproducibility of Vancomycin MIC Testing with Enterococcus spp. (All Sites Combined)

| | Inoculation Method | | | |
| --- | --- | --- | --- | --- |
| Reading Method | Turbidity | | Prompt | |
| | Best Casea | Worst Casea | Best Casea | Worst Casea |
| Manual | 98.7% | 95.6% | 99.6% | 95.1% |
| WalkAway | 99.1% | 94.7% | 99.4%b | 98.9%b |
| autoSCAN-4 | 99.1% | 98.2% | 97.8% | 96.9% |

a Percent of results within $\pm 1$ dilution of the mode
b Reproducibility determined using results obtained from four Enterococcus isolates.

b. Traceability, Stability, Expected values (controls, calibrators, or methods): The organism recommended in the FDA approved pharmaceutical drug label and the CLSI is Enterococcus faecalis ATCC 29212. This organism was tested against reformulated Vancomycin and interpreted after 16-20 hours of incubation. Quality control was performed at all sites using the Turbidity and the Prompt methods for inoculation, read by the manual, the WalkAway and the autoSCAN4reading methods. Table 3 below represents the frequency of the QC. The QC results read at 16-20 hours are acceptable for all reading methods.

Table 3. QC of Vancomycin with E. faecalis (Read at 16-20 hours)

| ORGANISM Enterococcus faecalis ATCC 29212 Expected range: 1-4 μg/ml | Conc. μg/ml | Reference Result (read at 24 hours) | Turbidity Inoculation | | | Prompt Inoculation | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | Manual Read | WalkAway Read | autoSCAN -4 Read | Manual Read | WalkAway Read | autoSCAN- 4 Read |
| 0.25 | | | | | 1 | | | |
| | | | | | | | | |
| | 0.5 | | | | | | | |
| | 1 | 1 | 1 | | | 1 | | |
| | 2 | 244 | 249 | 243 | 250 | 251 | 249 | 253 |
| | 4 | 1 | 1 | 1 | 1 | | | |
| | 8 | | | | | | | |
| 16 | | | 1 | | | | | |
| Total in Range (%) | | 246/246 (100) | 251/25 1 (100) | 244/245 (99.6) | 251/252 (99.6) | 252/25 2 (100) | 249/249 (100) | 253/253 (100) |

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## 2. Comparison studies:

**Method comparison with predicate device:**

This Special 510(k) application was submitted to demonstrate that MicroScan Dried Gram-Positive MIC/Combo panels with reformulated vancomycin (Test panels) are substantially equivalent to frozen CLSI reference panels (Reference panels) for the detection of resistant *Enterococcus* species after 16 – 20 hours of incubation. Device performance was evaluated using 16 – 20 hour incubation data that was also collected during the conduct of studies submitted to support the clearance of the original predicate device (K150039) which were based on 24 hour incubation for *Enterococcus* species.

Previously collected results from testing of a total of 40 *Enterococcus* spp. challenge isolates and 166 clinical isolates with the dried MicroScan panels incubated for 16 – 20 hours were evaluated. The results obtained with the dried panels were compared to the reference method or expected results.

Table 4 below demonstrates the performance for *Enterococcus* species based on essential agreement and category agreement for the overall performance of the clinical and challenge isolates. Data is shown for each inoculum preparation method (Turbidity and Prompt) and reading method (Overnight Manual, Walk-Away, and autoScan4). The results were comparable to those obtained at 24 hours with the reference method.

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Table 4. Performance of MicroScan Dried Gram-Positive Panels with Vancomycin; All Inoculation Methods and Reading Methods

| | Total | EA | %EA | Total eval | EA of eval | %EA eval | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Overnight Manual Read | | | | | | | | | | | | |
| Turbidity | | | | | | | | | | | | |
| Efficacy | 166 | 163 | 98.2 | 98 | 96 | 98.0 | 162 | 97.6 | 62 | 4 | 0 | 0 |
| Challenge | 40 | 40 | 100 | 28 | 28 | 100 | 37 | 92.5 | 16 | 3 | 0 | 0 |
| Combined | 206 | 203 | 98.5 | 126 | 124 | 98.4 | 199 | 96.6 | 78 | 7 | 0 | 0 |
| Prompt | | | | | | | | | | | | |
| Efficacy | 166 | 162 | 97.6 | 98 | 95 | 96.9 | 160 | 96.4 | 62 | 5 | 1 | 0 |
| Challenge | 40 | 40 | 100 | 27 | 27 | 100 | 37 | 92.5 | 16 | 3 | 0 | 0 |
| Combined | 206 | 202 | 98.1 | 125 | 122 | 97.6 | 197 | 95.6 | 78 | 8 | 1 | 0 |
| WalkAway | | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Turbidity | | | | | | | | | | | | |
| Efficacy | 166 | 164 | 98.8 | 99 | 98 | 99.0 | 163 | 98.2 | 62 | 3 | 0 | 0 |
| Challenge | 40 | 40 | 100 | 28 | 28 | 100 | 37 | 92.5 | 16 | 3 | 0 | 0 |
| Combined | 206 | 204 | 99.0 | 127 | 126 | 99.2 | 200 | 97.1 | 78 | 6 | 0 | 0 |
| Prompt | | | | | | | | | | | | |
| Efficacy | 166 | 161 | 97.0 | 99 | 95 | 96.0 | 160 | 96.4 | 62 | 6 | 0 | 0 |
| Challenge | 40 | 40 | 100 | 27 | 27 | 100 | 37 | 92.5 | 16 | 3 | 0 | 0 |
| Combined | 206 | 201 | 97.6 | 126 | 122 | 96.8 | 197 | 95.6 | 78 | 9 | 0 | 0 |
| autoScan4 | | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Turbidity | | | | | | | | | | | | |
| Efficacy | 166 | 163 | 98.2 | 98 | 96 | 98.0 | 162 | 97.6 | 62 | 4 | 0 | 0 |
| Challenge | 40 | 40 | 100 | 28 | 28 | 100 | 36 | 90.0 | 16 | 4 | 0 | 0 |
| Combined | 206 | 203 | 98.5 | 126 | 124 | 98.4 | 198 | 96.1 | 78 | 8 | 0 | 0 |
| Prompt | | | | | | | | | | | | |
| Efficacy | 166 | 162 | 97.6 | 98 | 95 | 96.9 | 160 | 96.4 | 62 | 6 | 0 | 0 |
| Challenge | 40 | 40 | 100 | 28 | 28 | 100 | 37 | 92.5 | 16 | 3 | 0 | 0 |
| Combined | 206 | 202 | 98.1 | 126 | 123 | 97.6 | 197 | 95.6 | 78 | 9 | 0 | 0 |

EA-Essential Agreement
min-minor discrepancies
CA-Category Agreement
maj-major discrepancies
R-Resistant Isolates
vmj-very major discrepancies

## 3. Risk Assessment

The risk associated with the modification of the incubation time was assessed by the sponsor as follows:

1. Risk of a false susceptible result as interpreted using the WalkAway or autoSCAN-4 instruments – Medium Risk, mitigated by use of manual read of the panels and risk file references.

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2. Risk of a false resistant result as interpreted using the WalkAway or autoSCAN-4 instruments – Low Risk, mitigated by use of manual read of the panels and risk file references.
3. Risk of a false susceptible result as interpreted using manual read, WalkAway or autoSCAN-4 instrument reads – Medium risk mitigated by design, protective measures and safety information.

## 4. Expected values/Reference range:

The FDA interpretative criteria were used to evaluate all performance data are shown in Table 5 below.

Table 5. FDA Interpretive Criteria for Vancomycin

| Organism | Interpretive Criteria (Vancomycin MIC in μg/mL) | | |
| --- | --- | --- | --- |
| | S | I | R |
| Enterococcus spp
Coagulase Negative
Staphylococcus spp | ≤4 | 8-16 | ≥32 |
| S. aureus | ≤2 | 4-8 | ≥16 |

## 5. Device Labeling Changes

The data included in this submission validates the sponsor's proposal to remove the following statements from the device instructions for use:

1. Removal of the following statement from the Summary and Principles section of the MicroScan Dried Gram-Positive Procedural Manual for vancomycin

Accurate detection of resistance requires extended incubation times for the following organism/antimicrobics:

24 hours Enterococci Vancomycin

2. Removal of the following statement from the Reading the Panels section of the MicroScan Dried Gram-Positive Procedural Manual for vancomycin:

Incubation 24 hours
Organisms Enterococci
Antimicrobics Vancomycin