VITEK 2 AST-Gram Positive Moxifloxacin (=0.25 - =8 µg/ml), VITEK 2 AST-GP Moxifloxacin (=0.25 - =8 µg/mL), VITEK 2 AST-GP Moxifloxacin

{0} FDA U.S. FOOD & DRUG ADMINISTRATION # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY ## I Background Information: A 510(k) Number K220803 B Applicant bioMerieux, Inc C Proprietary and Established Names VITEK 2 AST-Gram Positive Moxifloxacin (≤ 0.25 - ≥ 8 μg/ml), VITEK 2 AST-GP Moxifloxacin (≤ 0.25 - ≥ 8 μg/mL), VITEK 2 AST-GP Moxifloxacin D Regulatory Information | Product Code(s) | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | LON | Class II | 21 CFR 866.1645 - Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System | MI - Microbiology | | LTT | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology | | LTW | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology | ## II Submission/Device Overview: ### A Purpose for Submission: To update the VITEK 2 AST Gram-Positive Moxifloxacin device labeling to include updated, species-specific FDA-recognized interpretive criteria (i.e., breakpoints) for Staphylococcus spp. and Enterococcus faecalis, as published in the FDA STIC website. Previously obtained QC and reproducibility data is applicable to this reevaluation. Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} B Measurand: Moxifloxacin (≤ 0.25 - ≥ 8 μg/mL) C Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test III Intended Use/Indications for Use: A Intended Use(s): See Indications for Use below. B Indication(s) for Use: VITEK 2 AST-Gram Positive Moxifloxacin is designed for antimicrobial susceptibility testing of Gram positive microorganisms and is intended for use with the VITEK 2 and VITEK 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK 2 AST-Gram Positive Moxifloxacin is a quantitative test. Moxifloxacin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active both in vitro and in clinical infections: Enterococcus faecalis Staphylococcus aureus In vitro data are available, but their clinical significance is unknown: Staphylococcus epidermidis The VITEK 2 Gram-positive Susceptibility Card is intended for use with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Staphylococcus spp., Enterococcus spp., and S. agalactiae to antimicrobial agents when used as instructed. C Special Conditions for Use Statement(s): Rx - For Prescription Use Only D Special Instrument Requirements: VITEK 2 and VITEK 2 Compact Systems using 9.04 software K220803 - Page 2 of 12 {2} K220803 - Page 3 of 12 # IV Device/System Characteristics: ## A Device Description: The VITEK 2 AST card is a miniaturized, abbreviated and automated version of the doubling dilution technique for determining the minimum inhibitory concentration (MIC). Each VITEK 2 AST card contains 64 wells. A control well(s) which contain only nutrient medium is resident on all cards. The remaining wells contain premeasured portions of antimicrobials combined with the nutrient media. The isolate to be tested is diluted to a standardized concentration with 0.45% to 0.50% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK 2 System will automatically (or allow operator to manually) dilute the bacterial suspension to prepare an inoculum for susceptibility cards. Then, the VITEK 2 will fill, seal and place the card into the incubator/reader. The VITEK 2 Compact has a manual filling, sealing, and loading operation. The VITEK 2 Systems monitor the growth of each well in the card over a defined period of time. The analysis program determines when a well demonstrates growth based on attenuation of light measured by an optical scanner. This data is used to determine the minimum inhibitory concentration or "MIC" values for the antimicrobial agent. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card. VITEK 2 AST-GP Moxifloxacin has the following concentrations of Telavancin in the card: 0.25, 2 and 8 µg/mL (equivalent standard method concentration by efficacy in µg/mL). The MIC result range for the VITEK 2 AST-GP Telavancin is ≤0.25 to ≥8 µg/mL. For all species, the MIC result range indicates that the VITEK 2 system is capable of producing the following MIC results: ≤0.25, 0.5, 1, 2, 4 and ≥8 µg/mL for the AST Gram-Positive Moxifloxacin test. ## B Principle of Operation: The VITEK 2 and VITEK 2 Compact Systems utilize automated growth-based detection using attenuation of light measured by an optical scanner. The optics in the systems use visible light to directly measure organism growth within each of the 64 micro-wells. Transmittance optics is based on an initial light reading of a well before significant growth has begun. Every 15 minutes throughout the incubation cycle (defined period of time based on the VITEK 2 card), light transmittance readings of each well determine organism growth by the amount of light that is prevented from passing through the well. At the completion of the incubation period, the MIC values and their associated interpretive category results for each antimicrobial on the test card are displayed in an automatically generated report. # V Substantial Equivalence Information: ## A Predicate Device Name(s): Vitek 2 Gram Positive Moxifloxacin ## B Predicate 510(k) Number(s): K032399 {3} C Comparison with Predicate(s): | Device & Predicate Device(s): | Device: K220803 | Predicate: K032399 | | --- | --- | --- | | Device Trade Name | VITEK 2 AST-GP Moxifloxacin (≤ 0.25 - ≥ 8 μg/mL) | VITEK 2 AST-GP Moxifloxacin (≤ 0.25 - ≥ 8 μg/mL) | | General Device Characteristic Similarities | | | | Intended Use/Indications For Use | VITEK 2 AST-Gram Positive Moxifloxacin is designed for antimicrobial susceptibility testing of Gram-positive microorganisms and is intended for use with the VITEK 2 and VITEK 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK 2 AST-Gram Positive Moxifloxacin is a quantitative test. Moxifloxacin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active both in vitro and in clinical infections: Enterococcus faecalis Staphylococcus aureus In vitro data are available, but their clinical significance is unknown: Staphylococcus epidermidis The VITEK 2 Gram-positive Susceptibility Card | VITEK 2 AST-Gram Positive Moxifloxacin is designed for antimicrobial susceptibility testing of Staphylococcus aureus (methicillin-susceptible strains only). It is intended for use with the VITEK 2 System as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. The VITEK 2 Gram-positive Susceptibility Card is intended for use with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Staphylococcus spp., Enterococcus spp., and S. agalactiae to antimicrobial agents when used as instructed in the Online Product Information. | K220803 - Page 4 of 12 {4} | | is intended for use with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Staphylococcus spp., Enterococcus spp., and S. agalactiae to antimicrobial agents when used as instructed. | | | --- | --- | --- | | Test Methodology | Automated quantitative antimicrobial susceptibility test for use with the VITEK 2 and VITEK 2 Compact Systems to determine the in vitro susceptibility of microorganisms. | Same | | Antimicrobial Agent | Moxifloxacin | Same | | Concentrations | 0.25, 2, and 8 | Same | | Inoculum | Saline suspension of organism | Same | | Test Card | Gram-Positive (AST-GP) Susceptibility Card | Same | | Analysis Algorithms | Discriminant Analysis | Same | | Instrument | VITEK 2 and VITEK 2 Compact Systems | Same | | General Device Characteristic Differences | | | | Breakpoints | Enterococcus faecalis S ≤1, I 2, R ≥4 | Staphylococcus spp. S ≤2, I 4, R ≥8 | | | Staphylococcus spp. S ≤0.5, I 1, R ≥2 | | VI Standards/Guidance Documents Referenced: - CLSI M07-A11: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard – 11th Edition (January 2018) - CLSI M100-S30: Performance Standards for Antimicrobial Susceptibility Testing; 30th Informational Supplement (January 2020) - FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) K220803 - Page 5 of 12 {5} K220803 - Page 6 of 12 # VII Performance Characteristics (if/when applicable): ## A Analytical Performance: 1. **Precision/Reproducibility:** Reproducibility testing for the VITEK 2 AST Gram-Positive Moxifloxacin was conducted at three external sites using a panel of twenty-five Gram positive organisms consistent with the indications for use (i.e., six isolates of *S. aureus*, one isolate of *S. epidermidis*, thirteen isolates of *E. faecium*, three isolates of *E. faecalis* and two isolates of *E. casseliflavus*). Each isolate was tested in triplicate, using separate inocula, over three days for a total of 75 data points. Inocula were prepared using both the autodilution and manual dilution methods for testing with the VITEK 2 System. The mode of MIC values was determined for each isolate and the reproducibility was calculated based on the number of MIC values that fell within ± 1 doubling dilution of the mode. All MIC results were on-scale and within one doubling dilution from the modal MIC value; therefore, only best-case results are reported. The testing resulted in an overall reproducibility of 100% (75/75) when testing with the VITEK 2 System (autodilution and manual dilution methods). 2. **Linearity:** Not Applicable 3. **Analytical Specificity/Interference:** Not Applicable 4. **Assay Reportable Range:** Not Applicable 5. **Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):** The CLSI recommended QC strains for moxifloxacin, *E. faecalis* ATCC 29212 and *S. aureus* ATCC 29213, were tested a sufficient number of time (i.e., at least 20 times/site) at each testing site using both the VITEK 2 card and broth microdilution reference methods. Both the automatic dilution and manual dilution methods were used for the VITEK 2 system. In summary, QC organisms recommended by both the FDA and CLSI, namely *E. faecalis* ATCC 29212 and *S. aureus* ATCC 29213, were tested using the reference broth microdilution (BMD) method and the VITEK 2 GP-AST Moxifloxacin during the clinical study as summarized in Table 1. The overall QC results for both the reference and VITEK 2 were acceptable. The BMD dilution range (≤0.0625 - ≥16 μg/mL) covered the full expected result range of *E. faecalis* ATCC 29212 (expected range of 0.06-0.5 μg/mL) and *S. aureus* {6} ATCC 29213 (expected range of $0.016 - 0.12\mu \mathrm{g / mL}$ ); however, the VITEK 2 Moxifloxacin card ( $\leq 0.25 - \geq 8\mu \mathrm{g / mL}$ ) resulted in off-scale MIC values for E. faecalis ATCC 29212 and S. aureus ATCC 29213. An E. faecalis ATCC 29212 MIC value of $\leq 0.25\mu \mathrm{g / mL}$ (with VITEK 2) was considered as an indication that the quality control test results were acceptable. A S. aureus ATCC 29213 MIC value of $\leq 0.0625\mu \mathrm{g / mL}$ (with BMD) and $\leq 0.25\mu \mathrm{g / mL}$ (with VITEK 2) was considered as an indication that the quality control test results were acceptable. To address the expected off-scale QC results when testing E. faecalis ATCC 29212 and S. aureus ATCC 29213, the device labeling reviewed in the current submission includes the following footnote under the Quality Control Table: "Does not include the full CLSI/FDA recommended dilution range for QC testing with this organism". Table 1: Quality Control Results for VITEK 2 (AutoDilution and Manual Dilution Methods) | QC Organisms (All sites) | Expected Range (Moxifloxacin, μg/mL) | Concentration (μg/mL) | VITEK 2 Auto Dilution Frequency | | VITEK 2 Manual Dilution Frequency | | | --- | --- | --- | --- | --- | --- | --- | | | | | Test | Reference | Test | Reference | | Enterococcus faecalis ATCC 29212 | 0.06-0.5 | ≤0.0625 | | 1 | | 1 | | | | 0.125 | | 77 | | 52 | | | | 0.25 | | 11 | | 10 | | | | ≤0.25* | 90 | | 64 | | | | | 0.5 | | 1 | | 1 | | | | 1 | | | | | | | | 2 | | | | | | | | 4 | | | | | | | | 8 | | | | | | | | ≥16 | | | | | | Staphylococcus aureus ATCC 29213 | 0.016-0.12 | ≤0.0625 | | 88 | | 63 | | | | 0.125 | | 2 | | 2 | | | | 0.25 | | | | | | | | ≤0.25* | 90 | | 65 | | | | | 0.5 | | | | | | | | 1 | | | | | | | | 2 | | | | | | | | 4 | | | | | | | | 8 | | | | | | | | ≥16 | | | | | $^{1}$ VITEK 2 Card range for Moxifloxacin is $\leq 0.25 - \geq 8~\mu \mathrm{g / mL}$ and does not include the full CLSI/FDA-recommended dilution range for QC testing of E. faecalis ATCC 29212 and S.s aureus ATCC 29213. The lowest concentration of the VITEK 2 Moxifloxacin MIC range is $0.25~\mu \mathrm{g / mL}$ . Obtaining a value of $\leq 0.25~\mu \mathrm{g / mL}$ was considered an indication that the quality control test results were acceptable. Similarly, the lowest concentration of the BMD Moxifloxacin MIC range is $0.0625~\mu \mathrm{g / mL}$ . Obtaining a value of $\leq 0.0625~\mu \mathrm{g / mL}$ was considered an indication that the quality control test results were acceptable. $^{2}$ BMD: CLSI reference broth microdilution. Inoculum Density Check: The DensiCheck Plus was used to standardize the inoculum to a 0.5 McFarland standard. The instrument was standardized weekly with all results recorded at each site. Calibration values were within the expected range. K220803 - Page 7 of 12 {7} Device Failure: During the performance of the comparative study, there were several instrument processing errors that resulted in loss of AST cards with the VITEK 2 System. All isolates affected by these errors were retested in accordance with the testing protocol. Growth Failure Rate: There were no growth failures with VITEK 2 automatic or manual dilution or with VITEK 2 Compact. Purity Check: Purity plates were prepared from the inoculum suspensions. AST results were only reported for pure isolates. 6. Detection Limit: Not Applicable 7. Assay Cut-Off: Not Applicable B Comparison Studies: 1. Method Comparison with Predicate Device: The performance of the VITEK 2 AST-Gram Positive Moxifloxacin was evaluated using existing data collected in support of K032399 using the new interpretative criteria currently recognized by FDA. Testing of moxifloxacin was performed at four external sites. Results obtained with VITEK 2 AST-Gram Positive Moxifloxacin were compared to results obtained with the CLSI agar dilution reference panel. The MIC result range for the VITEK 2 AST-Gram Positive Moxifloxacin is ≤0.25 to ≥8 μg/mL for all species. The testing conditions for the reference method consisted of the following: - Medium: Cation Adjusted Mueller Hinton Agar - Inoculum: 1 mL of organism suspension standardized to approximate a McFarland 0.5 standard - Incubation: 35 ± 2°C; 16-20 hours The VITEK 2 cards were inoculated with test organisms using the auto-dilution method and manual dilution method. All test inocula used for the VITEK 2 AST cards and the reference method were standardized using the DensiCHEK Plus instrument. For the current submission, additional testing was done to assess performance: 20 S. epidermis clinical isolates. All testing was performed with the autodilution method at a single external clinical site. A total of 457 clinical isolates were evaluated using the VITEK 2 autodilution method. Of these isolates, 89.7% were contemporary isolates (tested within fourteen days from isolation) and 10.3% were stock isolates (no specific time from isolation). A total of 73 challenge isolates were evaluated using VITEK 2 autodilution and manual dilution methods. K220803 - Page 8 of 12 {8} The results obtained using the VITEK 2 autodilution and manual dilution methods of the from the 530 total isolates (457 clinical isolates and 73 challenge isolates) are summarized in Table 2. To support testing of $E$ faecalis using the VITEK 2 COMPACT system, the sponsor provided COMPACT data from an equivalency study that evaluated $E$ faecalis challenge in Levofloxacin and Norfloxacin which demonstrated acceptable essential agreement values. The provided performance data of $E$ faecalis evaluated in the VITEK 2 Compact equivalency study, in combination with the low risk assessment of the specified organism/ drug combination, was satisfactory to conclude that VITEK 2 AST-Gram Positive Moxifloxacin can be run on either the VITEK 2 system of the VITEK 2 Compact system with an equivalent level of safety and effectiveness. Table 2. Overall VITEK 2 Automatic and Manual Dilution Performance Data with Clinical and Challenge Isolates. | | Tot | # EA | % EA | Eval Tot | # Eval EA | % Eval EA | CA Tot | % CA | # R | # Vmj | # Maj | # Min | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | VITEK 2 Moxifloxacin Automatic Dilution- Clinical and Challenge | | | | | | | | | | | | | | Enterococcus faecalis (Breakpoints (μg/mL): ≤1 S, 2 I, ≥4 R) | | | | | | | | | | | | | | Clinical | 131 | 130 | 99.2 | 36 | 35 | 97.2 | 130 | 99.2 | 43 | 0 | 0 | 1 | | Challenge | 23 | 22 | 95.7 | 13 | 12 | 92.3 | 23 | 100 | 0 | 0 | 0 | 0 | | Total | 154 | 152 | 98.7 | 49 | 47 | 95.9 | 153 | 99.4 | 43 | 0 | 0 | 1 | | | | | | | | | | | | | | | | Staphylococcus aureus (Breakpoints (μg/mL): ≤0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 202 | 201 | 99.5 | 70 | 69 | 98.6 | 190 | 94.1 | 96 | 0 | 0 | 12 | | Challenge | 37 | 37 | 100 | 3 | 3 | 100 | 36 | 97.3 | 2 | 0 | 0 | 1 | | Total | 239 | 238 | 99.6 | 73 | 72 | 98.6 | 226 | 94.6 | 98 | 0 | 0 | 13 | | Staphylococcus epidermis (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 79 | 78 | 98.7 | 38 | 37 | 97.4 | 75 | 94.9 | 53 | 1 | 0 | 3 | | Challenge | 13 | 13 | 100 | 0 | 0 | - | 13 | 100 | 1 | 0 | 0 | 0 | | Total | 92 | 91 | 98.9 | 38 | 37 | 97.4 | 88 | 95.7 | 54 | 1 | 0 | 3 | | Coagulase negative Staphylococcus (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 14 | 14 | 100 | 5 | 5 | 100 | 14 | 100 | 5 | 0 | 0 | 0 | | Staphylococcus auricularis (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 1 | 1 | 100 | 0 | 0 | - | 1 | 100 | 0 | 0 | 0 | 0 | | Staphylococcus capitis (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 4 | 4 | 100 | 0 | 0 | - | 4 | 100 | 0 | 0 | 0 | 0 | | Staphylococcus cohnii (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 1 | 1 | 100 | 1 | 1 | 100 | 1 | 100 | 0 | 0 | 0 | 0 | | Staphylococcus haemolyticusi (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 12 | 12 | 100 | 6 | 6 | 100 | 12 | 100 | 8 | 0 | 0 | 0 | | Staphylococcus hominus (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 100 | 0 | 0 | 0 | 0 | | Staphylococcus lugdunensis (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 1 | 1 | 100 | 0 | 0 | - | 1 | 100 | 0 | 0 | 0 | 0 | | Staphylococcus saprophyticus (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 4 | 4 | 100 | 2 | 2 | 100 | 3 | 75 | 1 | 0 | 0 | 1 | | Staphylococcus sciuri (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | K220803 - Page 9 of 12 {9} | Clinical | 3 | 3 | 100 | 0 | 0 | - | 3 | 100 | 1 | 0 | 0 | 0 | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Staphylococcus simulans (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 2 | 2 | 100 | 0 | 0 | - | 2 | 100 | 1 | 0 | 0 | 0 | | Staphylococcus warneri (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Clinical | 2 | 2 | 100 | 1 | 1 | 100 | 2 | 100 | 0 | 0 | 0 | 0 | | Staphylococcus spp. (all) | | | | | | | | | | | | | | Clinical | 457 | 453 | 99.1 | 160 | 156 | 97.5 | 439 | 96.1 | 208 | 1 | 0 | 17 | | Challenge | 73 | 72 | 98.6 | 16 | 15 | 93.8 | 72 | 98.6 | 3 | 0 | 0 | 1 | | Total | 530 | 525 | 99.1 | 176 | 171 | 97.2 | 511 | 96.4 | 211 | 1 | 0 | 18 | | VITEK 2 Moxifloxacin Manual Dilution- Challenge | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Tot | # EA | % EA | Eval Tot | # Eval EA | % Eval EA | CA Tot | % CA | # R | # Vmj | # Maj | # Min | | Enterococcus faecalis (Breakpoints (μg/mL): ≤1 S, 2 I, ≥4 R) | | | | | | | | | | | | | | Challenge | 23 | 23 | 100 | 11 | 11 | 100 | 23 | 100 | 0 | 0 | 0 | 0 | | | | | | | | | | | | | | | | Staphylococcus aureus (Breakpoints (μg/mL): ≤0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Challenge | 37 | 37 | 100 | 3 | 3 | 100 | 36 | 97.3 | 2 | 0 | 0 | 1 | | Staphylococcus epidermis (Breakpoints (μg/mL): 0.5 S, 1 I, ≥2 R) | | | | | | | | | | | | | | Challenge | 13 | 13 | 100 | 0 | 0 | - | 13 | 100 | 1 | 0 | 0 | 0 | | Staphylococcus spp. (all) | | | | | | | | | | | | | | Total | 50 | 50 | 100 | 3 | 3 | 100 | 49 | 98 | 3 | 0 | 0 | 1 | ## Trending A trending analysis was conducted using the combined data (clinical and challenge) obtained from the VITEK 2 autodilution method for each species. This trending calculation analyzes device MIC values that are determined to be one or more doubling dilutions lower or higher than the reference method. MIC values that are off-scale for both the reference and device are not considered in the trending analysis. Species for which the difference between the percentage of isolates with higher or lower MIC values was $\geq 30\%$ with a statistically significant confidence interval were considered to have evidence of trending and is addressed in the labeling. Table 3. Trending Analysis | Trending Analysis VITEK 2 Moxifloxacin (Clinical and Challenge Isolates) Automatic Dilution | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | Organism | Total Evaluable for Trending | ≥1 Dilution lower No. (%) | Exact No. (%) | ≥1 Dilution Higher No. (%) | Percent Difference (CI) | Trending Noted | | Enterococcus faecalis | 54 | 6 (11.1%) | 20 (37.0%) | 28 (51.9%) | 40.7% (23.7%, 54.8%) | Yes | | Staphylococcus aureus | 94 | 2 (2.1%) | 38 (40.4%) | 54 (57.5%) | 55.3% (43.9%, 65.0) | Yes | | Staphylococcus epidermidis | 38 | 8 (21.0%) | 15 (39.5%) | 15 (39.5%) | 18.4% (-2.2%, 37.1%) | No | K220803 - Page 10 of 12 {10} A trend toward higher MIC values was observed for E. faecalis and S. aureus (Table 3). To address the observed trending, the following footnote was included by the sponsor to the performance table in the device labeling: VITEK 2 AST-GP Moxifloxacin MIC values tended to be in exact agreement or at least one doubling dilution higher when testing Enterococcus faecalis and Staphylococcus aureus compared to the CLSI reference agar dilution method. 2. Matrix Comparison: Not Applicable C Clinical Studies: 1. Clinical Sensitivity: Not Applicable 2. Clinical Specificity: Not Applicable 3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Not Applicable D Clinical Cut-Off: Not Applicable E Expected Values/Reference Range: The FDA and CLSI susceptibility interpretive criteria for Moxifloxacin are as listed in Table 4. Table 4. FDA Recognized Interpretive Criteria for Moxifloxacin | | Minimum Inhibitory Concentrations (μg/mL)a | | | | --- | --- | --- | --- | | Organisms | S | I | R | | Enterococcus faecalis | ≤1 | 2 | ≥4 | | Staphylococcus spp. | ≤0.5 | 1 | ≥2 | S = Susceptible; I = Intermediate; R = Resistant aAccording to CLSI M60-Ed2 and FDA STIC Website https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm410971.htm VIII Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. K220803 - Page 11 of 12 {11} IX Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. To support the implementation of changes to FDA-recognized susceptibility test interpretive criteria (i.e., breakpoints), this submission included a breakpoint change protocol that was reviewed and accepted by FDA. This protocol addresses future revisions to device labeling in response to breakpoint changes that are recognized on the FDA STIC webpage (https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm410971.htm). The protocol outlined the specific procedures and acceptance criteria that bioMérieux intends to use to evaluate the VITEK 2 AST-GP Moxifloxacin when revised breakpoints for telavancin are published on the FDA STIC webpage. The breakpoint change protocol included with the submission indicated that if specific criteria are met, bioMérieux will update the telavancin device label to include (1) the new breakpoints, (2) an updated performance section after re-evaluation of data in this premarket notification with the new breakpoints, and (3) any new limitations as determined by their evaluation. K220803 - Page 12 of 12