VITEK 2 AST-Gram Negative Omadacycline (<=0.25 - >=16 µg/mL)

{0} FDA U.S. FOOD &amp; DRUG ADMINISTRATION # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY ## I Background Information: A 510(k) Number K213931 B Applicant bioMérieux, Inc. C Proprietary and Established Names VITEK 2 AST-Gram Negative Omadacycline (≤0.25 - ≥16 μg/mL) 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 | ## II Submission/Device Overview: A Purpose for Submission: To obtain a substantial equivalence determination for omadacycline for testing of Gram-negative bacilli on the VITEK 2 and VITEK 2 Compact Antimicrobial Susceptibility Test (AST) Systems B Measurand: Omadacycline ≤0.25 – ≥16 μg/mL C Type of Test: Automated quantitative or qualitative antimicrobial susceptibility test for omadacycline Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} III Intended Use/Indications for Use: A Intended Use(s): See Indications for Use below. B Indication(s) for Use: VITEK 2 AST-Gram Negative Omadacycline is designed for antimicrobial susceptibility testing of Gram negative bacilli 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 Negative Omadacycline is a quantitative test. Omadacycline has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active *in vitro* and in clinical infections: For Acute Bacterial Skin and Skin Structure Infections (ABSSSI): *Enterobacter cloacae* *Klebsiella pneumoniae* For Community Acquired Bacterial Pneumonia (CABP): *Klebsiella pneumoniae* The VITEK 2 Gram-Negative Susceptibility Card is intended for use with the VITEK 2 Systems in clinical laboratories as an *in vitro* test to determine the susceptibility of clinically significant aerobic Gram-negative bacilli 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, VITEK 2 Systems (PC) version 9.04 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 K213931 - Page 2 of 12 {2} 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-Gram Negative Omadacycline has the following concentrations in the card: 0.5, 2, 8 and 16 µg/mL (equivalent standard method concentration by efficacy in µg/mL). ## 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 AST-Gram Negative Eravacycline (≤0.12 - ≥4 µg/mL) ## B Predicate 510(k) Number(s): K191766 ## C Comparison with Predicate(s): | Device & Predicate Device(s): | Device: K213931 | Predicate: K191766 | | --- | --- | --- | | Device Trade Name | Vitek 2 AST-Gram Negative Omadacycline (≤0.25 – ≥16 µg/mL) | Vitek 2 AST-Gram Negative Eravacycline (≤0.12 – ≥4 µg/mL) | | General Device Characteristic Similarities | | | | Intended Use | VITEK 2 AST-Gram Negative Omadacycline is designed for antimicrobial susceptibility testing of Gram negative bacilli and is intended for use with the VITEK 2 and VITEK 2 Compact Systems as a laboratory aid in the | VITEK 2 AST-Gram Negative Eravacycline is designed for antimicrobial susceptibility testing of Gram negative bacilli and is intended for use with the VITEK 2 and VITEK 2 Compact Systems as a laboratory aid in the | K213931 - Page 3 of 12 {3} K213931 - Page 4 of 12 | | determination of in vitro susceptibility to antimicrobial agents. VITEK 2 AST-Gram Negative Omadacycline is a quantitative test. The VITEK 2 Gram-Negative Susceptibility Card is intended for use with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant aerobic Gram-negative bacilli to antimicrobial agents when used as instructed. | determination of in vitro susceptibility to antimicrobial agents. VITEK 2 AST-Gram Negative Eravacycline is a quantitative test. The VITEK 2 Gram-Negative Susceptibility Card is intended for use with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant aerobic Gram-negative bacilli 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 | | Inoculum | Saline suspension of organism | Same | | Test Card | Gram Negative (AST-GN) Susceptibility Card | Same | | Instrument | VITEK 2 and VITEK 2 Compact Systems | Same | | General Device Characteristic Differences | | | | Antimicrobial Agent | Omadacycline | Eravacycline | | Concentrations | 0.5, 2, 8, 16 μg/mL | 0.25, 1, 2, 4 μg/mL | | Reporting Range | ≤0.5 - ≥16 μg/mL | ≤0.12 - ≥4 μg/mL | | Indicated Organisms | Omadacycline has been shown to active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: For ABSSSI: Enterobacter cloacae Klebsiella pneumoniae For CABP: | Eravacycline has been shown to active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial. Active in vitro and in clinical infections: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca | {4} VI Standards/Guidance Documents Referenced: - FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009) - CLSI M07-A11 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Eleventh Edition” Vol. 38 No. 2 (January 2018) - CLSI M100-M30, “Performance Standards for Antimicrobial Susceptibility Testing”; Thirtieth Edition (January 2020) VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: Reproducibility testing for the VITEK 2 AST-GN card with Omadacycline was conducted at three clinical sites using a panel of ten Gram-negative bacilli consistent with the indications for use (i.e., eight K. pneumoniae pneumoniae, one K. pneumoniae and one E. cloacae isolates). Each isolate was tested in triplicate over three days for a total of 270 data points. Inocula were prepared using both the auto-dilution and manual dilution methods for testing in the VITEK 2 System. In addition, the inocula were prepared by the manual dilution method for use with the VITEK 2 Compact. 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 MIC value. The majority of data points were on-scale and within ± one doubling dilution agreement as compared to the mode MIC. The data was analyzed taking into consideration best-case and worst-case scenarios as described in the Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems. The reproducibility performance is shown in Table 1. Table 1: Reproducibility Performance | | VITEK 2 | | VITEK 2 Compact | | --- | --- | --- | --- | | | Auto-Dilution | Manual Dilution | Manual Dilution | | Best Case | 100% | 99.63% | 100% | | Worst Case | 99.26% | 99.26% | 99.63% | K213931 - Page 5 of 12 {5} 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 strain, namely Escherichia coli ATCC 25922 was tested a sufficient number of times (i.e., at least 20/site) at each testing site using both the VITEK 2 AST-GN Omadacycline and Broth Microdilution (BMD) reference method. Both the automatic dilution and manual dilution methods were used for the VITEK 2 and the manual dilution method was used for the VITEK 2 Compact. The results are summarized in Table 2 below. Both the auto-dilution and the manual dilution methods for VITEK 2 and the manual dilution for VITEK 2 Compact QC results were within the expected range &gt;95% of the time, which is acceptable. Because the VITEK card reporting range (≤0.25 - ≥ 16 μg/mL) does not include the full CLSI/FDA-recommended dilution range for QC testing, the sponsor included a footnote in labeling to indicate that the device does not include the full CLSI/FDA-recommended dilution range for QC testing. Table 2: Quality Control Results for Omadacycline: VITEK 2 (Auto-Dilution and Manual Dilution Methods) and VITEK 2 Compact (Manual Dilution Method) | Organism | VITEK 2 Result Range | BMD Result Range (μg/mL) | VITEK 2 Auto-Dilution | BMD | VITEK 2 Manual Dilution | BMD | VITEK 2 Compact Manual Dilution | BMD | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Escherichia coli ATCC 25922 | | ≤0.03 | | | | | | | | | | 0.06 | | | | | | | | | | 0.12 | | | | | | | | | ≤0.25 | 0.25 | | 6 | | 4 | | 4 | | | 0.5 | 0.5 | 183 | 86 | 93 | 47 | 94 | 49 | | | 1 | 1 | 20 | 104 | 4 | 42 | 6 | 42 | | | 2 | 2 | 1 | 7 | | 4 | | 4 | | | 4 | 4 | | | | | | | | | 8 | 8 | | | 1 | | | | | | ≥16 | 16 | | 1 | | 1 | | 1 | | | | ≥32 | | | | | | | BMD: broth microdilution K213931 - Page 6 of 12 {6} Both the auto-dilution and the manual dilution methods for VITEK 2 and the manual dilution for VITEK 2 Compact QC results were within the expected range &gt;95% of the time, which is acceptable. Two ancillary quality control organisms were tested throughout comparative testing by broth microdilution reference method only. This was done to perform further quality control of the broth microdilution panels. The organisms tested were Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212. QC results for the broth microdilution method were within the expected result range &gt;95% of the time. S. aureus ATCC 29213 was within range 100% (207/207) and E. faecalis ATCC 29212 was within range 100% (206/206). ## Inoculum Density Control: The DensiCHEK Plus was used to standardize the inoculum to a 0.5 McFarland standard. The instrument was standardized daily with all results recorded at each site. Calibration values were within the expected range. ## Purity Check: A purity check of all organisms was performed on the dilution tube used to prepare the VITEK 2 card inoculum. Only those cultures that were pure were evaluated in the study. ## Growth Failure Rate: A total of 460 clinical and challenge isolates were tested by VITEK 2 AST-GN Omadacycline. No growth failure was recorded and all 460 isolates have VITEK 2 AST results available. 6. Detection Limit: Not applicable 7. Assay Cut-Off: Not applicable ## B Comparison Studies: 1. Method Comparison with Predicate Device: Testing of omadacycline on the VITEK 2 AST-Gram Negative card was performed at five clinical sites. There were 371 (IFU and non-IFU) clinical isolates and 89 challenge isolates tested for a total of 460 isolates. Results obtained with the VITEK 2 AST-Gram Negative card with omadacycline were compared to results obtained with the CLSI broth microdilution (BMD) reference panel. The MIC result range for the VITEK 2 AST-Gram Negative Omadacycline is ≤0.25 to ≥16 μg/mL for all species. The testing conditions for the reference method consisted of the following: - Medium: Mueller Hinton broth with the appropriate dilutions of antimicrobial solution added. - Inoculum: Direct colony suspension - Incubation: 35°C; 16-24 hours K213931 - Page 7 of 12 {7} The VITEK 2 AST cards were inoculated with test organisms using the auto-dilution method (VITEK 2) and manual dilution method (VITEK 2 and VITEK 2 Compact). All test inocula used for the VITEK 2 AST cards were standardized using the DensiCHEK Plus instrument. A total of 371 clinical isolates were evaluated at four sites: 59.3% were considered contemporary isolates (isolated from clinical specimen and tested within 6 months) and 40.7% were stock isolates. Complete test results were available for all clinical isolates from 330 indicated species: 300 Klebsiella pneumoniae, 27 Enterobacter cloacae, and 3 Enterobacter cloacae complex isolates. Results were available from an additional 41 non-indicated clinical isolates and those were as follows: 2 Citrobacter freundii, 3 Citrobacter koseri, 3 Enterobacter aerogenes, 27 Escherichia coli, 3 Klebsiella oxytoca, and 3 Serratia marcescens. All clinical isolates were tested with the auto-dilution option of the VITEK 2. A total of 89 challenge isolates were evaluated at one site. They included: 35 Enterobacter cloacae, 5 Enterobacter cloacae complex, 7 Klebsiella pneumoniae pneumoniae, and 42 Klebsiella pneumoniae. The challenge set was tested with the auto-dilution and manual dilution options of the VITEK 2 and with the manual dilution method on the VITEK 2 Compact. ## Clinical and Challenge Data – VITEK 2 Auto-Dilution VITEK 2 AST-GN Omadacycline performance was determined with 460 isolates (371 clinical isolates and 89 challenge isolates) and evaluated based on susceptibility testing interpretive criteria (breakpoints) established for the clinical indication, Acute Bacterial and Skin Structure Infections (ABSSSI). A subset of results (from 419 K. pneumoniae and E. cloacae isolates) obtained using the auto-dilution method of the VITEK 2 were evaluated using the breakpoints established for ABSSSI as applicable to these indicated species according to FDA STIC Website (Table 3). Table 3: Performance of All Clinical and Challenge Isolates with ABSSSI Breakpoints for Omadacycline: VITEK 2 Auto-Dilution | Organism Type | EA Tot | EA N | EA % | Eval. EA Tot | Eval. EA N | Eval. EA % | CA N | CA % | #R | #S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Enterobacteriaceae [Breakpoints (μg/mL): ≤4 (S), 8 (I), ≥16 (R)] | | | | | | | | | | | | | | | Clinical | 371 | 360 | 97.0 | 362 | 351 | 97.0 | 352 | 94.9 | 14 | 342 | 18 | 0 | 1 | | Challenge | 89 | 89 | 100 | 55 | 55 | 100 | 84 | 94.4 | 37 | 42 | 5 | 0 | 0 | | Combined | 460 | 449 | 97.6 | 417 | 406 | 97.4 | 436 | 94.8 | 51 | 384 | 23 | 0 | 1 | | K. pneumoniae and E. cloacae [Breakpoints (μg/mL): ≤4 (S), 8 (I), ≥16 (R)] | | | | | | | | | | | | | | | Clinical | 330 | 321 | 97.3 | 321 | 312 | 97.2 | 311 | 94.2 | 14 | 301 | 18 | 0 | 1 | | Challenge | 89 | 89 | 100 | 55 | 55 | 100 | 84 | 94.4 | 37 | 42 | 5 | 0 | 0 | | Combined | 419 | 410 | 97.9 | 376 | 367 | 97.6 | 395 | 94.3 | 51 | 343 | 23 | 0 | 1 | EA – Essential Agreement CA – Category Agreement EVAL – Evaluable isolates R – Resistant isolates min – minor errors maj – major errors vmj – very major errors S – Susceptible isolates The overall performance of Enterobacteriaceae is acceptable with an EA of 97.6% and a CA of 94.8%. There was no major errors and one very major error (1/51 = ~2.0%). K213931 - Page 8 of 12 {8} A subset of results (from 349 K. pneumoniae and K. pneumoniae pneumoniae isolates) obtained using the auto-dilution method of the VITEK 2 were evaluated using the breakpoints established for Community Acquired Bacterial Pneumonia (CABP) as applicable to this indicated species according to FDA STIC Website (Table 4). Table 4: Performance of Clinical and Challenge K. pneumoniae Isolates with CABP Breakpoints for Omadacycline: VITEK 2 Auto-Dilution | Organism Type | EA Tot | EA N | EA % | Eval. EA Tot | Eval. EA N | Eval. EA % | CA N | CA % | #R | #S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | K. pneumoniae [Breakpoints (μg/mL): ≤4 (S), 8 (I), ≥16 (R)] | | | | | | | | | | | | | | | Clinical | 300 | 293 | 97.7 | 293 | 286 | 97.6 | 282 | 94.0 | 11 | 274 | 17 | 0 | 1 | | Challenge | 49 | 49 | 100 | 26 | 26 | 100 | 45 | 91.8 | 26 | 16 | 4 | 0 | 0 | | Combined | 349 | 342 | 98.0 | 319 | 312 | 97.8 | 327 | 93.7 | 37 | 290 | 21 | 0 | 1 | EA – Essential Agreement CA – Category Agreement EVAL – Evaluable isolates R – Resistant isolates min – minor errors maj – major errors vmj – very major errors S – Susceptible isolates When using the auto-dilution method of the VITEK 2, data was analyzed to determine performance with breakpoints established for CABP for K. pneumoniae. There were no major errors and one very major error (1/37 = 2.7%). This VMJ error rate was considered acceptable as this was due to a single K. pneumoniae isolate among this smaller subset that was evaluated using the same breakpoints (CABP and ABSSSI). Collectively, the overall performance of K. pneumoniae was acceptable with an EA of 98.0% and a CA of 93.7% acceptable. ## Challenge Data – VITEK 2 and VITEK 2 Compact Manual Dilution The 89 challenge isolates were also tested at one site with the manual dilution option for the VITEK 2 and VITEK 2 Compact systems and evaluated based on clinical indication: ABSSSI (Table 5). All results for the 89 isolates tested with the manual dilution method of the VITEK 2 and VITEK 2 Compact were evaluated using breakpoints established for ABSSSI (Table 5). Table 5: Performance of Challenge Isolates with ABSSSI Breakpoints for Omadacycline: VITEK 2 Manual Dilution | System | EA Tot | EA N | EA % | Eval. EA Tot | Eval. EA N | Eval. EA % | CA N | CA % | #R | #S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Enterobacteriaceae [Breakpoints (μg/mL): ≤4 (S), 8 (I), ≥16 (R)] | | | | | | | | | | | | | | | VITEK 2 | 89 | 88 | 98.9 | 56 | 55 | 98.2 | 81 | 91.0 | 37 | 42 | 8 | 0 | 0 | | VITEK 2 Compact | 89 | 89 | 100 | 55 | 55 | 100 | 82 | 92.1 | 37 | 42 | 7 | 0 | 0 | The overall performance of Enterobacteriaceae is acceptable with an EA of 98.9% and a CA of 91.0% for the VITEK 2 System and an EA of 100% and a CA of 92.1% for the VITEK 2 Compact system. There were no major or very major errors. K213931 - Page 9 of 12 {9} A subset of results (from 42 K. pneumoniae and 7 K. pneumoniae pneumoniae isolates) obtained using the manual dilution method of the VITEK 2 and VITEK 2 Compact systems were evaluated using the breakpoints established for CABP as applicable to this species according to FDA STIC Website (Table 6). Table 6: Performance of K. pneumoniae Challenge Isolates with CABP Breakpoints for Omadacycline: VITEK 2 Manual Dilution | System | EA Tot | EA N | EA % | Eval. EA Tot | Eval. EA N | Eval. EA % | CA N | CA % | #R | #S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | K. pneumoniae [Breakpoints (μg/mL): ≤4 (S), 8 (I), ≥16 (R)] | | | | | | | | | | | | | | | VITEK 2 | 49 | 49 | 100 | 26 | 26 | 100 | 45 | 91.8 | 26 | 16 | 4 | 0 | 0 | | VITEK 2 Compact | 49 | 49 | 100 | 25 | 25 | 100 | 44 | 89.8 | 26 | 16 | 5 | 0 | 0 | The overall performance of K. pneumoniae is acceptable with an EA of 100% and a CA of 91.8% for the VITEK 2 System. There were no major or very major errors. While the performance for the VITEK 2 Compact system was &lt;90% for CA (89.8%), the EA was 100% and there were no major or very major errors. Taken together, the overall performance of K. pneumoniae is acceptable for the VITEK 2 Compact system. To address testing and reporting of non-indicated species, the following statement is included in the Precautions section of the device labeling: Per the FDA-Recognized Susceptibility Test Interpretive Criteria website, the safety and efficacy of antimicrobial drugs, for which antimicrobial susceptibility is tested by this AST device, may or may not have been established in adequate and well-controlled clinical trials for treating clinical infections due to microorganisms outside of those found in the indications and usage in the drug label. The clinical significance of susceptibility information in those instances is unknown. The approved labeling for specific antimicrobial drugs provides the uses for which the antimicrobial drug is approved. ## Resistance Mechanism Characterization Omadacycline was active in vitro against Enterobacteriaceae expressing the TetB efflux pump and one K. pneumoniae challenge isolate expressing tet(B) was included in the evaluation. K213931 - Page 10 of 12 {10} # MIC Trends A trending analysis was conducted using the combined data (clinical and challenge) obtained from the VITEK 2 auto-dilution method for each indicated organism species (Table 7). 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. Table 7. Trending Species (clinical and challenge isolates) | VITEK 2 Auto-Dilution | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | Organism | Total Evaluable for Trending | ≥1 dil. Lower # (%) | Exact # (%) | ≥1 dil. Higher # (%) | Percent Difference (95% CI) | Trending Noted | | E. cloacae* | 57 | 5 (8.77) | 27 (47.37) | 25 (43.86) | 35.09% (1.63 to 14.52) | Yes (High) | | K. pneumoniae** | 319 | 46 (14.42) | 213 (66.77) | 60 (18.81) | 4.39% (-1.41 to 10.17) | No | *E. cloacae and E. cloacae complex were consolidated into a single group, E. cloacae **K. pneumoniae and K. pneumoniae pneumoniae were consolidated into a single group, K. pneumoniae A trend toward higher MIC values was observed for $E$ cloacae. The following footnote to the performance table is included in the package insert to address the trending observed for VITEK 2 AST-Gram Negative Omadacycline: VITEK 2 AST-Gram Negative Omadacycline MIC values tended to be in exact agreement or at least one doubling dilution higher when testing E. cloacae compared to the CLSI reference broth microdilution 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): K213931 - Page 11 of 12 {11} Not applicable # D Clinical Cut-Off: Not applicable # E Expected Values/Reference Range: The FDA-recognized susceptibility interpretative criteria for Omadacycline are listed in Tables 8 and 9. Table 8. FDA-Recognized Interpretative Criteria for Omadacycline for Acute Bacterial Skin and Skin Structure Infections $(\mu \mathrm{g} / \mathrm{mL})^{\mathrm{a}}$ | Organism | Susceptible | Intermediate | Resistant | | --- | --- | --- | --- | | Enterobacteriaceaeb | ≤4 | 8 | ≥16 | a According to FDA STIC Website b Klebsiella pneumoniae and Enterobacter cloacae only Table 9. FDA-Recognized Interpretative Criteria for Omadacycline for Community Acquired Bacterial Pneumonia $(\mu \mathrm{g} / \mathrm{mL})^{\mathrm{a}}$ | Organism | Susceptible | Intermediate | Resistant | | --- | --- | --- | --- | | Enterobacteriaceaeb | ≤4 | 8 | ≥16 | a According to FDA STIC Website b Klebsiella pneumoniae only # VIII Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. # 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-GN Omadacycline when revised breakpoints for delafloxacin 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 delafloxacin 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. K213931 - Page 12 of 12