MicroScan Dried Gram Positive MIC/Combo Panels with vancomycin (0.25-64 mcg/mL)

K150039 · Siemens Healthcare Diagnostics, Inc. · LTT · Jul 2, 2015 · Microbiology

Device Facts

• Record ID: K150039
• Device Name: MicroScan Dried Gram Positive MIC/Combo Panels with vancomycin (0.25-64 mcg/mL)
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: LTT · Microbiology
• Decision Date: Jul 2, 2015
• Decision: SESE
• Submission Type: Traditional
• 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; panels contain dehydrated antimicrobial agents. Clinical laboratory personnel inoculate panels with standardized bacterial suspensions; panels are rehydrated with water. Incubation occurs in non-CO2 incubators for 16-20 hours (24 hours for Enterococcus vancomycin resistance detection). Results are read visually or via automated MicroScan instrumentation (autoSCAN-4 or WalkAway). The device determines the Minimum Inhibitory Concentration (MIC) by identifying the lowest antimicrobial concentration inhibiting bacterial growth. This information assists clinicians in selecting appropriate antibiotic therapy for patients with gram-positive bacterial infections.

Clinical Evidence

Clinical and challenge study (n=1075 total isolates: 947 clinical, 128 challenge). Evaluated MRSA, MSSA, CNS, and Enterococcus spp. Primary endpoints: Essential Agreement (EA) and Category Agreement (CA) vs. CLSI reference method. Combined EA/CA consistently >90%. Performance data provided for turbidity and Prompt inoculation methods across manual, WalkAway, and autoSCAN-4 reading methods. Bench testing included reproducibility and QC studies.

Technological Characteristics

Miniaturized, dehydrated broth microdilution panels. Mueller-Hinton broth supplemented with calcium/magnesium. Vancomycin concentrations: 0.25–64 µg/ml. Inoculation: Turbidity or Prompt™ method. Incubation: 35°C, 16–24 hours. Read methods: Manual, WalkAway, or autoSCAN-4. Software: Automated interpretation of growth-based fluorescence.

Indications for Use

Indicated for determining quantitative/qualitative antimicrobial susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-positive bacteria, including Enterococcus spp. (e.g., E. faecalis) and Staphylococci (including S. aureus and S. epidermidis). Prescription use only.

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 – Ceftaroline (K123933)

Submission Summary (Full Text)

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

A. 510(k) Number:
K150039

B. Purpose for Submission:
To obtain a substantial equivalence determination for the addition of the reformulated vancomycin to the MicroScan Dried Gram-Positive MIC/Combo Panel at concentrations 0.25 to 64 µg/ml for testing Enterococci (e.g., *Enterococcus faecalis*), Staphylococci, including *Staphylococcus aureus* and *Staphylococcus epidermidis*

C. Measurand:
Vancomycin in the dilution range of 0.25 - 64 µg/ml

D. Type of Test:
Quantitative Antimicrobial Susceptibility Test (AST), growth based fluorescence.

E. Applicant:
Beckman Coulter

F. Proprietary and Established Names:
MicroScan® Dried Gram-Positive MIC/Combo Panels with Vancomycin (0.25 – 64 µg/ml)

G. Regulatory Information:
1. Regulation section:
21 CFR 866.1640 Antimicrobial Susceptibility Test Powder
2. Classification:
Class II
3. Product code(s):
JWY – Manual Antimicrobial Susceptibility Test Systems

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LRG – Instrument for Auto Reader & Interpretation of overnight susceptible 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 or 3 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 facultative gram-positive cocci, some fastidious aerobic gram-positive cocci and Listeria monocytogenes. Refer to Limitations 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 bacteria. After inoculation, panels are incubated for 16 - 24 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)

3. Special conditions for use statement(s):

For prescription use only

"The ability of the MicroScan Dried Gram Positive Panels to detect vancomycin resistant S. aureus strains is unknown due to the limited number of resistant strains tested. None of the isolates tested had an MIC of 16µg/mL."

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"The ability of the MicroScan Dried Gram Positive Panels to detect vancomycin intermediate or resistant coagulase negative Staphylococcus is unknown because intermediate or resistance strains were not encountered at the time of comparative clinical testing. Any coagulase negative Staphylococcus isolate for which the vancomycin MIC value is $\geq 8\ \mu\mathrm{g}/\mathrm{mL}$ should be sent to a reference laboratory."

4. Special instrument requirements:

MicroScan panels can be read either manually or automatically on the autoScan-4 or the WalkAway instrument systems.

I. 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 $35^{\circ}\mathrm{C} \pm 1^{\circ}\mathrm{C}$ 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 autoSCAN4

J. Substantial Equivalence Information:

1. Predicate device name(s):

MicroScan® Dried Gram-Positive MIC/Combo Panels – Vancomycin

2. Predicate $510(\mathrm{k})$ number(s):

K123933

3. Comparison with predicate:

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Table 1. Comparison with the Predicate Device

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Product Name | MicroScan® Dried Gram-Positive MIC/Combo Panels – Vancomycin | MicroScan® Dried Gram-Positive MIC/Combo Panels – Ceftaroline (K123933) |
| Technology | Overnight Microdilution MIC Susceptibility | Same |
| Result Reported | Report results as minimum inhibitory concentration (MIC) and categorical interpretation (SIR) | Same |
| Read Methods | Manual and Automated | Same |
| Inoculation Methods | Turbidity and Prompt™ | Same |
| Instruments | autoSCAN® 4 or WalkAway® | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | Determination of susceptibility to vancomycin with gram-positive bacteria | Determination of susceptibility to ceftaroline with gram positive bacteria |
| Antibiotic | Dried Vancomycin 0.25-64 μg/ml | Dried ceftaroline 0.06-16 μg/mL |
| MIC Interpretive Breakpoints | S. aureus: S≤2, I=4-8, R≥16 Enterococci and Coagulase Negative Staphylococci: S≤4, I=8-16, R≥32 | S≤1, -, - |
| Labeling Limitations | “The ability of the MicroScan Dried Gram Positive Panels to detect vancomycin resistance S. aureus strains is unknown due to the limited number of resistant strains tested. None of the isolates tested had an MIC of 16μg/mL.” “The ability of the MicroScan Dried Gram Positive Panels to detect vancomycin intermediate or resistant coagulase negative Staphylococcus is unknown because intermediate or resistance strains were not encountered at the time of comparative clinical testing. Any coagulase negative Staphylococcus isolate for which the vancomycin MIC value is ≥8 | The ability of the MicroScan Dried Gram Positive Panels to detect resistance to ceftaroline is unknown because resistant strains were not available at the time of comparative testing. Staphylococci colony counts may be elevated with the Prompt method and may be greater than the CLSI expected range. Elevated colony counts may adversely affect antibiotic results that are affected by inoculum, especially with |

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| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | μg/mL should be sent to a reference laboratory.” | staphylococci isolates. |

## K. Standard/Guidance Document Referenced (if applicable):

1. Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucmO71462.pdf

2. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, Approved Standard-9th Edition, Document M07-A9

3. Performance Standards for Antimicrobial Susceptibility Testing - 24th Informational Supplement, M100-S24 (QC parameters only)

## L. Test Principle:

The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test which have been dehydrated. Various antimicrobial agents are diluted in Mueller-Hinton broth supplemented with calcium and magnesium to concentrations bridging the rage of clinical interest. Breakpoint Combo panels use concentrations equivalent to the categorical breakpoints of FDA and/or CLSI. After inoculation and rehydration with a standardized suspension of organism and incubation of 35°C for a minimum of 16 hours, the minimum inhibitory concentration (MIC) for the test organism is determined by observing the lowest antimicrobial concentration showing inhibition of growth.

## M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Reproducibility data for 10 isolates including one *E. casseliflavus*, one *E. faecalis*, two *E. faecium*, three *S. aureus* (one MSSA and two MRSA), two *S. epidermidis* and one *S. haemolyticus* and one QC strain (*E. faecalis* ATCC 29212) were generated at 5 clinical trial sites. Organism selection was based on the intended use of the antimicrobial agent. Each strain 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).

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The mode of the test panel MIC results was determined for each isolate. MIC results at each site were compared to the mode value for each strain. Results were considered in agreement if the test panel MIC was equal to or within $\pm 1$ 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 $(0.25 - 64\mu \mathrm{g / mL})$ . The agreement was calculated for each site and for the five sites combined.

For all sites combined, agreement within $1 \pm$ dilution from the mode for all inoculation and reading methods was $>95\%$ for best case and for worst case scenarios. The reproducibility study results are acceptable. The results of the best case scenarios are shown in Table 2 below.

The results were acceptable.

Table 2. Reproducibility of Vancomycin MIC Testing with S. aureus (Methicillin-Susceptible and Methicillin-Resistant, Enterococcus spp (All Sites Combined) and Coagulase Negative Staphylococcus

| | Inoculation Method | |
| --- | --- | --- |
| Reading Method | Turbiditya | Prompta |
| Manual | 490/492 (99.6%) | 491/492 (99.8%) |
| WalkAway | 490/492 (97.6%) | 488/492 (99.2%) |
| autoSCAN-4 | 490/492 (99.6%) | 489/492 (99.4%) |

a Number of results within $\pm 1$ dilution of the mode/total number of result $(\%)$

b. Linearity/assay reportable range:

Not applicable

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

The organism recommended by the FDA (CDER) and the CLSI, Enterococcus faecalis ATCC 29212 and S. aureus ATCC 29213 were tested against reformulated Vancomycin. 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. Tables 3 and 4 below represents the frequency of the results and all results were in acceptable range.

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Table 3. QC Table of Vancomycin E. faecalis (Read at 18 and 24 hours)

| ORGANISM
Enterococcus faecalis
ATCC 29212
Expected range: 1-4 μg/ml | conc. (μg/ml) | Ref Result | Turbidity Inoculation with Read Methods | | | | | | Prompt™ Inoculation with Read Methods | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | Manual | | Walk Away® | | auto SCAN® | | Manual | | Walk Away® | | auto SCAN® | |
| | | | 18 hr | 24 hr | 18 hr | 24 hr | 18 hr | 24 hr | 18 hr | 24 hr | 18 hr | 24 hr | 18 hr | 24 hr |
| | ≤0.25 | | | | | | | | | | | | | |
| | 0.5 | | | | | | | | | | | | | |
| | 1 | 1 | 1 | 2 | | | | | 1 | | | | | |
| | 2 | 242 | 247 | 245 | 241 | 246 | 248 | 248 | 249 | 247 | 247 | 248 | 251 | 248 |
| | 4 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | | | | 1 | | |
| | 8 | | | | | | | | | | | | | |
| | 16 | | | | | | | | | | | 1 | | |

Table 4. QC Table of Vancomycin S. aureus (Reading 18 hours)

| ORGANISM
S. aureus
ATCC 29213
Expected Range: 0.5 – 2 μg/ml | conc. (μg/ml) | Ref. Result | Turbidity Inoculation with Read Methods | | | Prompt™ Inoculation with Read Methods | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | Manual | Walk Away® | Auto SCAN® | Manual | Walk Away® | Auto SCAN® |
| | ≤0.25 | | | | | | | |
| | 0.5 | 39 | 3 | 3 | 2 | | | |
| | 1 | 204 | 244 | 240 | 243 | 172 | 165 | 161 |
| | 2 | 4 | 2 | 1 | 4 | 78 | 85 | 86 |
| | 4 | | | | 1 | 1 | 1 | 1 |
| | 8 | | 1 | 1 | | | | |
| | 16 | | | | | | | |

Quality Control results for the MicroScan Dried Gram Positive MIC/Combo Panel using both inoculation methods and using either reading methods demonstrated that the system could produce the expected quality control results. The QC results were within the expected range > 95% with all reads and inoculation methods for all 5 sites combined.

The quality control results are acceptable.

d. Detection limit:

Not applicable

e. Analytical specificity:

Not applicable

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f. Assay cut-off:

Not applicable

## 2. Comparison studies:

a. Method comparison with predicate device:

This 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). Device performance was evaluated in a clinical trial that included gram-positive isolates.

A total of 128 challenge isolates were tested (40 Enterococcus spp, 15 MRSA, 21 MSSA, 17 CNS, 9 VRSA and 26 VISA). Of the 128 challenge isolates, the expected results for 71 strains were susceptible, and 25 strains were Resistant. The 9 VRSA strains were tested at an internal site, while the rest of the isolates were tested at external sites.

A total of 947 clinical isolates were tested (166 Enterococcus spp, 205 MRSA, 207 MSSA and 369 CNS). Six hundred eighty-seven (687) organisms were fresh and two hundred sixty (260) were stock isolates. The results were compared to the reference method or expected results. Of the 947 gram positive isolates tested, 882 were identified by the Reference panel to be Susceptible, and 62 isolates were identified as Resistant.

Tables 5-8 below demonstrate the performance for each group of isolates (MRSA, MSSA, CNS and 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 (Overnight Manual, Walk-Away, and autoScan4). Accurate detection of resistance requires extended incubation times of 24 hours for Enterococci. Staphylococci results were read after 16-20 hours incubation (18-20 h for autoSCAN-4 instrument reads). The results were comparable to those obtained at 24 hours with the reference method. The performance data for VRSA and VISA is shown in Tables 9 and 10, respectively. Table 11 shows the overall performance summary for all organisms.

Table 5. MicroScan Performance for testing Vancomycin against MRSA

| | Total | EA | %EA | Total eval | EA of eval | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Overnight Manual Read | | | | | | | | | | | |
| Turbidity | | | | | | | | | | | | |
| Efficacy | 205 | 204 | 99.5 | 205 | 204 | 99.5 | 204 | 99.5 | 0 | 1 | 0 | 0 |
| Challenge | 15 | 15 | 100 | 15 | 15 | 100 | 15 | 100 | 0 | 0 | 0 | 0 |
| Combined | 220 | 219 | 99.5 | 220 | 219 | 99.5 | 219 | 99.5 | 0 | 1 | 0 | 0 |
| Prompt | | | | | | | | | | | | |

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Table 6. Microscan Performance for testing Vancomycin against MSSA

| | Total | EA | %EA | Total eval | EA of eval | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Overnight Manual Read | | | | | | | | | | | |
| Turbidity | | | | | | | | | | | | |
| Efficacy | 207 | 206 | 99.5 | 206 | 205 | 99.5 | 207 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 21 | 21 | 100 | 21 | 21 | 100 | 21 | 100 | 0 | 0 | 0 | 0 |
| Combined | 228 | 227 | 99.6 | 227 | 226 | 99.6 | 228 | 100 | 0 | 0 | 0 | 0 |
| Prompt | | | | | | | | | | | | |
| Efficacy | 207 | 192 | 92.8 | 206 | 191 | 92.7 | 206 | 99.5 | 0 | 1 | 0 | 0 |
| Challenge | 21 | 21 | 100 | 21 | 21 | 100 | 20 | 95.2 | 0 | 1 | 0 | 0 |
| Combined | 228 | 213 | 93.4 | 227 | 212 | 93.4 | 226 | 99.1 | 0 | 2 | 0 | 0 |
| | WalkAway | | | | | | | | | | | |
| Turbidity | | | | | | | | | | | | |
| Efficacy | 207 | 206 | 99.5 | 206 | 205 | 99.5 | 207 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 21 | 21 | 100 | 21 | 21 | 100 | 21 | 100 | 0 | 0 | 0 | 0 |
| Combined | 228 | 227 | 99.6 | 227 | 226 | 99.6 | 228 | 100 | 0 | 0 | 0 | 0 |
| Prompt | | | | | | | | | | | | |
| Efficacy | 207 | 193 | 93.2 | 206 | 192 | 93.2 | 206 | 99.5 | 0 | 1 | 0 | 0 |
| Challenge | 21 | 21 | 100 | 21 | 21 | 100 | 21 | 100 | 0 | 0 | 0 | 0 |
| Combined | 228 | 214 | 93.9 | 227 | 213 | 93.8 | 227 | 99.6 | 0 | 1 | 0 | 0 |
| | autoScan4 | | | | | | | | | | | |
| Turbidity | | | | | | | | | | | | |
| Efficacy | 207 | 205 | 99.0 | 206 | 204 | 99.0 | 207 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 21 | 21 | 100 | 21 | 21 | 100 | 20 | 95.2 | 0 | 1 | 0 | 0 |
| Combined | 228 | 226 | 99.1 | 227 | 225 | 99.1 | 227 | 99.6 | 0 | 1 | 0 | 0 |
| Prompt | | | | | | | | | | | | |
| Efficacy | 207 | 193 | 93.2 | 206 | 192 | 93.2 | 207 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 21 | 21 | 100 | 21 | 21 | 100 | 20 | 95.2 | 0 | 1 | 0 | 0 |

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Table 7. Microscan Performance for testing Vancomycin against CNS

| | Total | EA | %EA | Total eval | EA of eval | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Overnight Manual Read | | | | | | | | | | | |
| Turbidity | | | | | | | | | | | | |
| Efficacy | 369 | 368 | 99.7 | 357 | 356 | 99.7 | 369 | 369 | 0 | 0 | 0 | 0 |
| Challenge | 17 | 17 | 100 | 17 | 17 | 100 | 17 | 100 | 0 | 0 | 0 | 0 |
| Combined | 386 | 385 | 99.7 | 374 | 373 | 99.7 | 386 | 100 | 0 | 0 | 0 | 0 |
| Prompt | | | | | | | | | | | | |
| Efficacy | 369 | 369 | 100 | 359 | 359 | 100 | 369 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 17 | 17 | 100 | 17 | 17 | 100 | 17 | 100 | 0 | 0 | 0 | 0 |
| Combined | 386 | 386 | 100 | 376 | 376 | 100 | 386 | 100 | 0 | 0 | 0 | 0 |
| | WalkAway | | | | | | | | | | | |
| Turbidity | | | | | | | | | | | | |
| Efficacy | 369 | 368 | 99.7 | 357 | 356 | 99.7 | 369 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 17 | 17 | 100 | 17 | 17 | 100 | 17 | 100 | 0 | 0 | 0 | 0 |
| Combined | 386 | 385 | 99.7 | 374 | 373 | 99.7 | 386 | 100 | 0 | 0 | 0 | 0 |
| Prompt | | | | | | | | | | | | |
| Efficacy | 369 | 368 | 99.7 | 359 | 359 | 100 | 369 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 17 | 17 | 100 | 17 | 17 | 100 | 17 | 100 | 0 | 0 | 0 | 0 |
| Combined | 386 | 385 | 99.7 | 376 | 376 | 100 | 386 | 100 | 0 | 0 | 0 | 0 |
| | autoScan4 | | | | | | | | | | | |
| Turbidity | | | | | | | | | | | | |
| Efficacy | 369 | 367 | 99.5 | 352 | 350 | 99.4 | 369 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 17 | 17 | 100 | 17 | 17 | 100 | 17 | 100 | 0 | 0 | 0 | 0 |
| Combined | 386 | 384 | 99.5 | 369 | 367 | 99.5 | 386 | 100 | 0 | 0 | 0 | 0 |
| Prompt | | | | | | | | | | | | |
| Efficacy | 369 | 369 | 100 | 357 | 357 | 100 | 369 | 100 | 0 | 0 | 0 | 0 |
| Challenge | 17 | 17 | 100 | 17 | 17 | 100 | 17 | 100 | 0 | 0 | 0 | 0 |
| Combined | 386 | 386 | 100 | 374 | 374 | 100 | 386 | 100 | 0 | 0 | 0 | 0 |

Table 8. MicroScan Performance for testing Vancomycin against Enterococcus spp.

| | Total | EA | %EA | Total eval | EA of eval | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Overnight Manual Read | | | | | | | | | | | |
| Turbidity | | | | | | | | | | | | |
| Efficacy | 166 | 164 | 98.8 | 100 | 99 | 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 | 128 | 127 | 99.2 | 200 | 97.1 | 78 | 6 | 0 | 0 |
| Prompt | | | | | | | | | | | | |
| Efficacy | 166 | 161 | 97.0 | 100 | 96 | 96.0 | 161 | 97.0 | 62 | 4 | 1 | 0 |
| Challenge | 40 | 40 | 100 | 27 | 27 | 100 | 37 | 92.5 | 16 | 3 | 0 | 0 |
| Combined | 206 | 201 | 97.6 | 127 | 123 | 96.9 | 198 | 96.1 | 78 | 7 | 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 |

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Table 9. Microscan Performance for testing Vancomycin against VRSA Challenge

| | Total | EA | %EA | Total eval | EA of eval | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Overnight Manual Read | | | | | | | | | | | |
| Turbidity | 9 | 8 | 88.9 | 1 | 1 | 100 | 9 | 100 | 9 | 0 | 0 | 0 |
| Prompt | 9 | 8 | 88.9 | 1 | 1 | 100 | 9 | 100 | 9 | 0 | 0 | 0 |
| | WalkAway | | | | | | | | | | | |
| Turbidity | 9 | 8 | 88.9 | 1 | 1 | 100 | 9 | 100 | 9 | 0 | 0 | 0 |
| Prompt | 9 | 8 | 88.9 | 1 | 1 | 100 | 9 | 100 | 9 | 0 | 0 | 0 |
| | autoScan4 | | | | | | | | | | | |
| Turbidity | 9 | 8 | 88.9 | 1 | 1 | 100 | 9 | 100 | 9 | 0 | 0 | 0 |
| Prompt | 9 | 8 | 88.9 | 1 | 1 | 100 | 9 | 100 | 9 | 0 | 0 | 0 |

Table 10. Microscan Performance of Vancomycin against VISA Challenge

| | Total | EA | %EA | Total eval | EA of eval | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Overnight Manual Read | | | | | | | | | | | |
| Turbidity | 26 | 26 | 100 | 26 | 26 | 100 | 24 | 92.3 | 0 | 2 | 0 | 0 |
| Prompt | 26 | 25 | 96.2 | 26 | 25 | 96.2 | 24 | 92.3 | 0 | 2 | 0 | 0 |
| | WalkAway | | | | | | | | | | | |
| Turbidity | 26 | 26 | 100 | 26 | 26 | 100 | 24 | 92.3 | 0 | 2 | 0 | 0 |
| Prompt | 26 | 26 | 100 | 26 | 26 | 100 | 25 | 96.2 | 0 | 1 | 0 | 0 |
| | autoScan4 | | | | | | | | | | | |
| Turbidity | 26 | 26 | 100 | 26 | 26 | 100 | 24 | 92.3 | 0 | 2 | 0 | 0 |
| Prompt | 26 | 26 | 100 | 26 | 26 | 100 | 25 | 96.2 | 0 | 1 | 0 | 0 |

Table 11. Overall Performance Summary Clinical and Challenge for all organisms

| | Total | EA | %EA | Total eval | EA of eval | %EA | CA | %CA | #R | min | maj | vmj |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Overnight Manual Read | | | | | | | | | | | |
| Clinically | 947 | 942 | 99.5 | 868 | 864 | 99.5 | 943 | 99.6 | 62 | 4 | 0 | 0 |
| Challenge Total | 128 | 127 | 99.2 | 108 | 108 | 100 | 123 | 96.1 | 25 | 5 | 0 | 0 |
| Combined | 1075 | 1069 | 99.4 | 976 | 972 | 99.6 | 1066 | 99.2 | 87 | 9 | 0 | 0 |
| Prompt | | | | | | | | | | | | |
| Clinical Total | 947 | 910 | 96.1 | 870 | 834 | 95.9 | 940 | 99.3 | 62 | 6 | 1 | 0 |
| Challenge Total | 128 | 126 | 98.4 | 107 | 106 | 99.1 | 122 | 95.3 | 25 | 6 | 0 | 0 |
| Combined | 1075 | 1036 | 96.4 | 977 | 940 | 96.2 | 1062 | 98.8 | 87 | 12 | 1 | 0 |

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EA-Essential Agreement CA-Category Agreement R-Resistant Isolates

min-minor discrepancies maj-major discrepancies vmj-very major 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 plus/minus one dilution. Essential Agreement (EA) occurs when there is agreement between the result of the reference method and that of MicroScan® within plus or minus one serial two-fold dilution of the antibiotic. Category Agreement (CA) occurs when the interpretation of the result of the reference method agrees exactly with the interpretation of the MicroScan® result.

The overall combined %EA and %CA consistently meet the acceptance criteria of greater than or equal to 90%.

## MIC Trend Analysis:

Using the data provided by the sponsor in the diagonal table format recommended in the AST Guidance, an analysis was conducted to check for trending in MIC values.

As summarized in Table 12 below, a lower reading trend was observed in the overall performance of Coagulase negative Staphylococcus for the turbidity inoculation method in the three reading methods (overnight manual, WalkAway and autoScan4) compared to the CLSI broth micro-dilution method, which raises concerns for potential very major errors.

Table 12. Trending of Results by Turbidity Method in Combined Clinical and Challenge Study

| Organism | Difference in MIC as Compared to the CLSI Reference Method | | | | |
| --- | --- | --- | --- | --- | --- |
| | -2 | -1 | 0 | +1 | +2 |
| Overnight Manual Read | | | | | |
| CoNS combined | 0% (1/386) | 50.5% (195/386) | 47.9% (185/386) | 1.3% (5/386) | 0 |
| WalkAway | | | | | |
| CoNS combined | 0% (1/386) | 49.2% (190/386) | 49.2% (190/386) | 1.3% (5/386) | 0 |
| AutoScan4 | | | | | |
| CoNS combined | 0.5% (2/386) | 52% (201/386) | 46.4% (179/386) | 1% (4/386) | 0 |

Based on our analysis, the overall performance of S. aureus (MRSA, MSSA) for the prompt inoculation method, demonstrates a trend towards higher reading compared to the CLSI broth micro-dilution method for all reading methods. This information is summarized in Table 13 below.

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Table 13. Trending of Results by Prompt Method in Combined Clinical and Challenge Study

| Organism | Difference in MIC as Compared to the CLSI Reference Method | | | | |
| --- | --- | --- | --- | --- | --- |
| | -2 | -1 | 0 | +1 | +2 |
| Overnight Manual Read | | | | | |
| MRSA combined | 0 | 3.6% (8/221) | 46.2% (102/221) | 42.5% (94/221) | 7.7% (17/221) |
| MSSA combined | 0 | 1.8% (4/228) | 44.7% (102/228) | 46.9% (107/228) | 6.6% (15/228) |
| WalkAway | | | | | |
| MRSA combined | 0 | 5.7% (14/245) | 49.8% (122/245) | 36.3% (89/245) | 8.2% (20/245) |
| MSSA combined | 0 | 1.8% (4/228) | 44.7 (102/228) | 47.4% (108/228) | 6.1% (14/228) |
| AutoScan4 | | | | | |
| MRSA combined | 0 (1/221) | 4% (9/221) | 45% (100/221) | 43% (94/221) | 8% (17/221) |
| MSSA combined | 0 | 1% (3/228) | 45% (102/228) | 48% (109/228) | 6% (14/228) |

This trending and the potential for occurrence of major and very major errors(s) for Vancomycin when testing Coagulase negative S. aureus and MRSA and MSSA was also addressed by adding the following footnotes in the in labeling:

Footnote 1:

"MicroScan vancomycin MIC values tended to be one doubling dilution lower when testing coagulase negative Staphylococcus by the turbidity inoculation method using manual, WalkAway and autoScan4 reading methods compared to reference broth micro-dilution.

Footnote 2:

"MicroScan vancomycin MIC values tended to be one doubling dilution higher when testing S. aureus (MR and MS) by the Prompt inoculation method using manual, WalkAway and AutoScan-4 reading methods compared to reference broth micro-dilution.

# Growth Rate:

All isolates tested during the clinical (efficacy) trials grew in both the frozen reference panel and the dried MicroScan panels.

# Prompt Hold Study:

An external study was performed to determine the agreement of results obtained with the Prompt inoculation method using hold times of 0 hours and 4 hours prior to inoculation of the panels. Results of 4-hour holds were compared to 0-hour hold using the same inoculum and with expected results as determined by the reference method. Testing was performed with all three read methods (WA, AS4 and manually). The results showed that there is no statistical difference in the Vancomycin dried result between 4 hours and 0 hours to all read. There is no statistical

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difference in the Vancomycin dried results compared to the frozen results at 0 hour and 4 hour hold time for all read methods. The performance was acceptable for all organisms tested. No major or very major errors were noted with each method inoculated after extended hold times. Only minor errors were observed.

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:

The FDA interpretative criteria were used to evaluate all performance data are shown in Table 14 below.

Table 14. FDA Interpretive Criteria for Vancomycin

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

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.