Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Omadacycline in the dilution range of 0.03-32ug/ml

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K183033 B. Purpose for Submission: To obtain a substantial equivalence determination for the addition of Omadacycline at concentrations of 0.03 – 32 µg/mL to the Sensititre 18-24-hour MIC or Breakpoint Susceptibility System for testing gram negative or gram positive non-fastidious isolates C. Measurand: Omadacycline in the dilution range of 0.03 – 32 µg/mL. D. Type of Test: Quantitative Antimicrobial Susceptibility Test (AST), growth-based detection E. Applicant: ThermoFisher Scientific F. Proprietary and Established Names: Sensititre 18 – 24 hour MIC or Breakpoint Susceptibility System with Omadacycline in the dilution range of 0.03 – 32 µg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code: JWY – Manual Antimicrobial Susceptibility Test System {1} LRG – Instrument for Auto Reader and Instrumentation of Overnight Susceptibility Systems LTT – Panels, Test, Susceptibility, Antimicrobial 4. Panel: 83, Microbiology H. Intended Use: 1. Intended use(s): The Sensititre MIC and Breakpoint Susceptibility system is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious gram negative isolates comprising of Enterobacteriaceae, Pseudomonas aeruginosa and other non-Enterobacteriaceae and of non-fastidious gram positive isolates, comprising of Staphylococcus sp., Enterococcus sp., and Beta hemolytic Streptococci other than S. pneumoniae. 2. Indication(s) for use: The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious isolates. This 510(k) is for Omadacycline in the dilution range of 0.03 – 32 µg/mL for testing non-fastidious gram positive and gram negative organisms on the Sensititre 18-24 hour MIC panel. Omadacycline has been shown to be active both clinically and in vitro against the following organisms according to the FDA drug label: Gram negative bacteria Klebsiella pneumoniae Enterobacter cloacae Gram positive bacteria Enterococcus faecalis Staphylococcus lugdunensis Staphylococcus aureus Omadacycline has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug approved label: Gram negative bacteria Citrobacter koseri Citrobacter freundii 2 {2} Klebsiella (Enterobacter) aerogenes Escherichia coli Klebsiella oxytoca 3. Special conditions for use statement(s): For prescription use only The following limitations are included in the labeling: The testing of Omadacycline with Gram-negative and Gram-positive organisms was performed using the autoreader (OptiRead) and Vizion reading methods only. The use of an alternative reading method when testing Omadacycline has not been evaluated. Studies of Omadacycline with gram negative and gram positive non-fastidious organisms were performed using the AIM autoinoculator. The use of an alternative inoculation system when testing meropenem/vaborbactam has not been evaluated. The ability of the Sensititre system to detect resistance to Omadacycline in the following species is unknown because resistant strains were not available at the time of comparative testing: S. aureus (MRSA and MSSA), Enterococcus faecalis and S. lugdunensis. Isolates yielding omadacyline MIC results suggestive of a resistant interpretive category should be submitted to a reference laboratory for further testing. Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the Sensititre Omadacycline for non-fastidious gram-negative and gram-positive organisms is unknown for organisms harboring the following resistance mechanisms: tetB, tetK, tetL, tetM. The safety and efficacy of Omadacycline in treating Acute Bacterial Skin and Skin Structure infections (ABSSSI) due to organisms other than K. pneumoniae and E. cloacae or Community Acquired Bacterial Pneumoniae (CABP) due to organisms other than K. pneumoniae may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. The safety and efficacy of Omadacycline in treating Acute Bacterial Skin and Skin Structure infections (ABSSSI) due to organisms other than S. aureus (MRSA and MSSA, S. lugdunensis and E. faecalis or Community Acquired Bacterial Pneumoniae (CABP) due to organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. 3 {3} 4. Special instrument requirements: Sensititre AIM for device inoculation Sensititre VIZION or OptiRead for plate reading I. Device Description: Sensititre MIC Susceptibility MIC panels are multi-well microtiter plates, dosed with dried, stabilized antimicrobials. It is a miniaturized version of the classic broth dilution method and can provide both qualitative and quantitative susceptibility results. After inoculation, plates are sealed with an adhesive seal, incubated at 34 – 36 °C for 18 – 24 hours and examined for bacterial growth. Antimicrobial susceptibility test results can be determined by reading growth using the digital device (VIZION) or automatically on an autoreader (OptiRead) using fluorescence. J. Substantial Equivalence Information: 1. Predicate device name(s): Sensititre 18-24 hour Susceptibility System, Cefepime 2. Predicate 510(k) number(s): K962867 3. Comparison with predicate: 4 {4} Table 1. Comparison with the Predicate Device | Similarities | | | | --- | --- | --- | | Item | Device K183033 Sensititre 18-24 hour Susceptibility System Omadacycline | Predicate K962867 Sensititre 18-24 Hour Susceptibility System Cefepime | | Intended Use | The Sensititre MIC and Breakpoint Susceptibility system is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious gram negative isolates, comprising of Enterobacteriaceae, Pseudomonas aeruginosa, and other non-Enterobacteriaceae and of non-fastidious gram positive isolates, comprising of Staphylococcus sp., Enterococcus sp., and Beta hemolytic Streptococci other than S. pneumoniae. | Same | | Test Panel | 96 well plate is dosed with selected antimicrobial agents and substrate for the fluorescent reads, then dried. The bacterial suspension in the appropriate broth is used to rehydrate the plate | Same | | Test Organism | Non-fastidious gram-positive and gram-negative isolates | Same | | Reading Methods | Results can be read using the following methods:1) Automatically with the OptiRead (fluorescent substrate technology)2) On the VIZION (digital viewing device) | Same | {5} | Differences | | | | --- | --- | --- | | Item | Device | Predicate | | Antimicrobial Agent | Omadacycline | Cefepime | | Incubation | 18 hours, 35 ± 1° C | 18-24 hours, 35 ± 1°C | ## K. Standard/Guidance Document Referenced (if applicable): Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. CLSI M100-S027: Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Seventh Informational Supplement CLSI M7-A10: Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Tenth Edition ## L. Test Principle: The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System includes multi-well plastic microtiter plates that contain doubled dilution of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read by the digital device, VIZION, or by use of an automated reader (OptiRead). The VIZION allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to manually determine MIC results. The Sensititre OptiRead utilizes fluorescence technology to read the microbroth dilution plates after 18 to 24 hours incubation. The technology involves the detection of bacterial growth by monitoring the activity of specific surface enzymes produced by the test organism. Growth is determined by generating a fluorescent product from a fluorogenic substrate. The substrate is prepared by conjugating a fluorescent compound to the specific enzyme substrates with a bond which prevents fluorescence. The enzymatic action of the bacterial surface enzymes on the substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The substrate can be added to the inoculum broth which is dispensed into the test plate at the same time as the test organism, or, the plates can be prepared with the substrate already added to each micro-well. {6} M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was performed at four sites using a panel comprised of 12 strains of Enterobacteriaceae: (K. pneumoniae (four isolates), E. cloacae (one isolate), E. coli (five isolates) and K. oxytoca (two isolates). Thirteen gram positive isolates from indicated species were evaluated including S. aureus MSSA (five isolates), S. aureus MRSA (five isolates) and E. faecalis (three isolates). In addition, one non-indicated gram positive species was tested. All isolates were tested in triplicate over three days with each read method (i.e., VIZION and OptiRead). The Sensititre Aim inoculator was used for plate inoculation. The mode MIC value was determined and the reproducibility was calculated based on MIC values falling within ±1 dilution of the mode MIC value. Reproducibility was greater than 95% for both read methods with both gram-positive and gram-negative organisms and was considered to be acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality control strains recommended by the CLSI were tested with Omadacycline at four sites. The QC organisms tested were E. coli ATCC 25922, S. aureus ATCC 29213 and E. faecalis ATCC 29212. The QC strains were tested a minimum of 20 times per site and read using the VIZION and OptiRead. The results demonstrate that the Sensititre 18-24 hour MIC or Breakpoint panel with Omadacycline produced quality control results in the recommended range >95% of the time (Table 2). 7 {7} Table 2. Quality Control Results for Sensititre 18 – 24 hour MIC or Breakpoint Susceptibility System with Omadacycline with the VIZION and OptiRead Methods. | QC Organism | Omadacycline Range (μg/mL) | Concentration (μg/mL) | Reference | Sensititre | | | --- | --- | --- | --- | --- | --- | | | | | | Read method | | | | | | | VIZION | OptiRead | | E. coli ATCC 25922 | 0.25 - 2 | 0.12 | 0 | 0 | 0 | | | | 0.25 | 26 | 4 | 1 | | | | 0.5 | 53 | 75 | 76 | | | | 1 | 1 | 1 | 3 | | | | 2 | 0 | 0 | 0 | | | | 4 | 0 | 0 | 0 | | S. aureus ATCC 29213 | 0.12 - 1 | 0.06 | 0 | 0 | 0 | | | | 0.12 | 4 | 3 | 3 | | | | 0.25 | 71 | 58 | 71 | | | | 0.5 | 3 | 20 | 7 | | | | 1 | 0 | 0 | 0 | | | | 2 | 0 | 0 | 0 | | | | | | | | | E. faecalis ATCC 29212 | 0.06 – 0.5 | 0.03 | 0 | 0 | 0 | | | | 0.06 | 12 | 0 | 3 | | | | 0.12 | 52 | 41 | 71 | | | | 0.25 | 14 | 39 | 7 | | | | 0.5 | 0 | 1 | 0 | | | | 1 | 0 | 0 | 0 | Inoculum Density. Inoculum density checks were performed a sufficient number of times; all organism suspensions were in the acceptable range. Purity checks. Purity checks were performed on all isolates following plate inoculation. Only results from pure cultures were evaluated. Growth Failure: All gram-negative and gram-positive isolates tested showed growth in the Sensititre panels. d. Detection limit: Not applicable e. Analytical specificity: Not applicable {8} f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Results obtained with Sensititre 18 – 24 hour MIC or Breakpoint Susceptibility System with Omadacycline were compared to results obtained with the CLSI broth microdilution reference panel. Drug dilutions were prepared using fresh Mueller Hinton broth as indicated in CLSI M100, 28th ed. Clinical testing was performed at four sites, three of which were in the U.S. A total of 365 clinical Enterobacteriaceae isolates were tested comprised of the following species: K. pneumoniae (96 isolates), E. cloacae (41 isolates), E. coli (108 isolates), Citrobacter spp. (57 isolates), K. aerogenes (20 isolates), and K oxytoca (43 isolates). A total of 390 gram positive clinical isolates were tested comprised of the following species: S. aureus (MSSA, 201 isolates, MRSA 199 isolates), S. lugdunensis (20 isolates), and E. faecalis (60 isolates). All of the clinical isolates tested were fresh isolates. During the course of the clinical trial, all Sensititre dried MIC panels were inoculated using the Sensititre Autoinoculator (AIM) and the same panel was read on both the VIZION (manual read) and the OptiRead in a blinded manner. The sponsor added the following limitations to the device labeling to reflect these inoculation and read methods: Studies of Omadacycline with gram positive and gram negative organisms were performed using the AIM autoinoculator. The use of an alternative inoculation system when testing Omadacycline has not been evaluated. The testing of Omadacycline with Gram-negative and Gram-positive organisms was performed using the autoreader (OptiRead) and VIZION reading methods only. The use of an alternative reading method when testing Omadacycline has not been evaluated. A total of 194 challenge isolates were tested at a single site. Species tested included K. pneumoniae (28 isolates), E. cloacae (11 isolates), E. coli (16 isolates), Citrobacter spp. (8 isolates), K. aerogenes (7 isolates), K. oxytoca (5 isolates), S. aureus (MSSA, 50 isolates, MRSA 50 isolates), S. lugdunensis (14 isolates), and E. faecalis (5 isolates). For the Enterobacteriaceae, results were evaluated for essential agreement (EA) and category agreement (CA). For CA evaluation, the same breakpoints for both Community Acquired Bacterial Pneumonia (CABP) and Acute Bacterial Skin and Skin Structure Infections (ABSSSI) (≤4, 8, ≥16) were used as noted on the FDA-Recognized Susceptibility Test Interpretive Criteria Website (STIC) (https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm575163.htm). The results from clinical and challenge testing determined with the 9 {9} 10 VIZION demonstrated a combined EA of 100% and CA of 96.6%. A total of 438 isolates were determined to have evaluable results; the EA of evaluable results was 100% (Table 3). Clinical and challenge isolate results for the Enterobacteriaceae determined with OptiRead demonstrated a combined EA of 99.8% and CA of 96.6%. A total of 438 isolates were determined to have evaluable results; the EA of evaluable results was 99.8% (Table 5). For S. aureus (MSSA) results were evaluated for essential agreement (EA) and category agreement (CA). For CA evaluation, the STIC-recognized breakpoints for CABP, the combined MIC results from clinical and challenge testing determined with the VIZION demonstrated EA of 100% and CA 90.4%; EA of evaluable results was 100% (Table 4). For MIC results determined with OptiRead, the combined results from clinical and challenge testing demonstrated an EA of 99.2% and CA of 100%; EA of evaluable results was 99.2% (Table 6). For S. aureus (MSSA and MRSA) evaluated using the STIC-recognized breakpoints for ABSSSI, combined MIC results of clinical and challenge testing read using VIZION demonstrated an EA of 99.4% and CA of 97.8%; EA of evaluable results was 99.4% (Table 4). Using OptiRead, results demonstrated an EA of 98.4% and CA of 98.8%; EA of evaluable result was 98.4% (Table 6). MIC results for isolates of S. lugdunensis were evaluated using STIC-recognized breakpoints for ABSSSI only and showed 100% EA and CA for results read on both VIZION and OptiRead (Tables 4 and 6). MIC results for isolates of E. faecalis were evaluated using STIC-recognized breakpoints for ABSSSI only. Results obtained using VIZION demonstrated an EA of 93.8% and CA of 92.3%; EA of evaluable was 97.7% (Table 4). For results obtained using OptiRead, EA was 95.9% and CA was 93.8%; EA of evaluable was 100% (Table 6). For all gram-positive organisms, an insufficient number of resistant strains were encountered during the clinical evaluation. The sponsor included the following limitation in the device labeling: The ability of the Sensititre system to detect resistance to Omadacycline in the following species is unknown because resistant strains were not available at the time of comparative testing: S. aureus (MRSA and MSSA), Enterococcus faecalis and S. lugdunensis. Isolates yielding omadacyline MIC results suggestive of a resistant interpretive category should be submitted to a reference laboratory for further testing. {10} Table 3. Performance of Gram Negative Clinical and Challenge Isolates, ABSSSI and CABP Breakpoints, Read Using VIZION | | Tot | EA N | EA % | Eval Tot | Eval EA N | Eval EA % | CA Tot | CA % | No. R | No. S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Enterobacteriaceae ABSSSI and CABP breakpoints (≤4, 8, ≥16)a | | | | | | | | | | | | | | | Clinical | 365 | 365 | 100.0 | 363 | 363 | 100.0 | 353 | 96.7 | 18 | 333 | 12 | 0 | 0 | | Challenge | 75 | 75 | 100.0 | 75 | 75 | 100.0 | 72 | 96.0 | 8 | 54 | 3 | 0 | 0 | | Total | 440 | 440 | 100.0 | 438 | 438 | 100.0 | 425 | 96.6 | 26 | 387 | 15 | 0 | 0 | a Includes K. pneumoniae, E. cloacae, E. coli, Citrobacter spp., K. aerogenes and K. oxytoca EA - Essential Agreement (+/- 1 dilution) CA - Category Agreement EVAL - Evaluable isolates R - Resistant isolates min - minor discrepancies maj - major discrepancies vmj - very major discrepancies Essential agreement (EA) occurs when the result of the reference method and that of the Sensititre panel are within plus or minus one serial two-fold dilution of the antibiotic. Evaluable results are those that are on scale for both the reference method and the Sensititre panel. Category agreement (CA) occurs when the interpretation of the result of the reference method agrees exactly with the interpretation of the Sensititre panel. Table 4. Performance of Gram Positive Clinical and Challenge Isolates, CABP and ABSSSI Breakpoints, Read Using VIZION | | Tot | EA N | EA % | Eval Tot | Eval EA N | Eval EA % | CA Tot | CA % | No. R | No. S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Staphylococcus aureus (MSSA) - CABP breakpoints (≤0.25, 0.5, ≥1) | | | | | | | | | | | | | | | Clinical | 201 | 201 | 100.0 | 200 | 200 | 100.0 | 178 | 88.6 | 1 | 191 | 23 | 0 | 0 | | Challenge | 50 | 50 | 100.0 | 50 | 50 | 100.0 | 49 | 98.0 | 0 | 50 | 0 | 0 | 0 | | Total | 251 | 251 | 100.0 | 250 | 250 | 100.0 | 227 | 90.4 | 1 | 241 | 23 | 0 | 0 | | | | | | | | | | | | | | | | | Staphylococcus aureus (MSSA) - ABSSSI breakpoints (≤0.5, 1, ≥2) | | | | | | | | | | | | | | | Clinical | 201 | 201 | 100.0 | 200 | 200 | 100.0 | 200 | 99.5 | 0 | 200 | 1 | 0 | 0 | | Challenge | 50 | 50 | 100.0 | 50 | 50 | 100.0 | 50 | 100.0 | 0 | 50 | 0 | 0 | 0 | | Total | 251 | 251 | 100.0 | 250 | 250 | 100.0 | 250 | 99.6 | 0 | 250 | 1 | 0 | 0 | | | | | | | | | | | | | | | | | Staphylococcus aureus (MRSA) - ABSSSI breakpoints (≤0.5, 1, ≥2) | | | | | | | | | | | | | | | Clinical | 199 | 197 | 99.0 | 199 | 197 | 99.0 | 192 | 96.6 | 2 | 184 | 7 | 0 | 0 | | Challenge | 50 | 49 | 98.0 | 50 | 49 | 98.0 | 47 | 94.0 | 0 | 48 | 3 | 0 | 0 | | Total | 249 | 246 | 98.8 | 249 | 246 | 98.8 | 239 | 96.0 | 2 | 232 | 10 | 0 | 0 | | | | | | | | | | | | | | | | | Staphylococcus aureus (MSSA and MRSA) - ABSSSI breakpoints (≤0.5, 1, ≥2) | | | | | | | | | | | | | | | Clinical | 400 | 398 | 99.5 | 399 | 397 | 99.5 | 392 | 98.0 | 2 | 384 | 8 | 0 | 0 | | Challenge | 100 | 99 | 99.0 | 100 | 99 | 99.0 | 97 | 97.0 | 0 | 98 | 3 | 0 | 0 | | Total | 500 | 497 | 99.4 | 499 | 496 | 99.4 | 489 | 97.8 | 2 | 482 | 11 | 0 | 0 | | | | | | | | | | | | | | | | | Staphylococcus lugdunensis ABSSSI breakpoints - (≤0.12, 0.25, ≥0.5) | | | | | | | | | | | | | | | Clinical | 20 | 20 | 100.0 | 20 | 20 | 100.0 | 20 | 100.0 | 0 | 20 | 0 | 0 | 0 | | Challenge | 14 | 14 | 100.0 | 14 | 14 | 100.0 | 14 | 100.0 | 3 | 11 | 0 | 0 | 0 | | Total | 34 | 34 | 100.0 | 34 | 34 | 100.0 | 34 | 100.0 | 3 | 31 | 0 | 0 | 0 | | | | | | | | | | | | | | | | | Enterococcus faecalis - ABSSSI breakpoints (≤0.25, 0.5, ≥1) | | | | | | | | | | | | | | | Clinical | 60 | 56 | 93.3 | 55 | 53 | 96.4 | 55 | 91.7 | 1 | 58 | 5 | 0 | 0 | | Challenge | 5 | 5 | 100.0 | 5 | 5 | 100.0 | 5 | 100.0 | 1 | 4 | 0 | 0 | 0 | {11} Table 5. Performance of Gram Negative Clinical and Challenge Isolates, Read Using OptiRead | | Tot | EA N | EA % | Eval Tot | Eval EA N | Eval EA % | CA Tot | CA % | No. R | No. S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Enterobacteriaceae ABSSSI and CABP breakpoints (≤4, 8, ≥16) | | | | | | | | | | | | | | | Clinical | 365 | 364 | 99.7 | 364 | 363 | 99.7 | 348 | 95.3 | 18 | 333 | 16 | 1 | 0 | | Challenge | 75 | 75 | 100.0 | 75 | 75 | 100.0 | 67 | 89.3 | 8 | 54 | 8 | 0 | 0 | | Total | 440 | 439 | 99.8 | 439 | 438 | 99.8 | 415 | 94.3 | 26 | 387 | 24 | 1 | 0 | Table 6. Performance of Gram Positive Clinical and Challenge Isolates, CABP and ABSSSI Breakpoints, Read Using OptiRead | | Tot | EA N | EA % | Eval Tot | Eval EA N | Eval EA % | CA Tot | CA % | No. R | No. S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Staphylococcus aureus (MSSA) - CABP breakpoints (≤0.25, 0.5, ≥1) | | | | | | | | | | | | | | | Clinical | 201 | 199 | 99.0% | 200 | 198 | 99.0% | 187 | 93.0% | 1 | 191 | 14 | 0 | 0 | | Challenge | 50 | 50 | 100.0% | 50 | 50 | 100.0% | 50 | 100.0% | 0 | 50 | 0 | 0 | 0 | | Total | 251 | 249 | 99.2% | 250 | 248 | 99.2% | 237 | 94.4% | 1 | 241 | 14 | 0 | 0 | | | | | | | | | | | | | | | | | S. aureus (MSSA) - ABSSSI breakpoints (≤0.5, 1 ≥2) | | | | | | | | | | | | | | | Clinical | 201 | 199 | 99.0 | 200 | 198 | 99.0 | 201 | 100.0 | 0 | 200 | 0 | 0 | 0 | | Challenge | 50 | 50 | 100.0 | 50 | 50 | 100.0 | 50 | 100.0 | 0 | 50 | 0 | 0 | 0 | | Total | 251 | 249 | 99.2 | 250 | 248 | 99.2 | 251 | 100.0 | 0 | 250 | 0 | 0 | 0 | | | | | | | | | | | | | | | | | S. aureus (MRSA) - ABSSSI breakpoints (≤0.5, 1 ≥2) | | | | | | | | | | | | | | | Clinical | 199 | 195 | 98.0 | 199 | 195 | 98.0 | 195 | 98.0 | 2 | 184 | 4 | 0 | 0 | | Challenge | 50 | 48 | 96.0 | 50 | 48 | 96.0 | 48 | 96.0 | 0 | 48 | 2 | 0 | 0 | | Total | 249 | 243 | 97.6 | 249 | 243 | 97.6 | 243 | 97.6 | 2 | 232 | 6 | 0 | 0 | | | | | | | | | | | | | | | | | S. aureus (MSSA and MRSA) - ABSSSI breakpoints (≤0.5, 1 ≥2) | | | | | | | | | | | | | | | Clinical | 400 | 394 | 98.5 | 399 | 393 | 98.5 | 396 | 99.0 | 2 | 384 | 4 | 0 | 0 | | Challenge | 100 | 98 | 98.0 | 100 | 98 | 98.0 | 98 | 98.0 | 0 | 98 | 2 | 0 | 0 | | Total | 500 | 492 | 98.4 | 499 | 491 | 98.4 | 494 | 98.8 | 2 | 482 | 6 | 0 | 0 | | | | | | | | | | | | | | | | | S. lugdunensis - ABSSSI breakpoints (≤0.12, 0.25, ≥0.5) | | | | | | | | | | | | | | | Clinical | 20 | 20 | 100.0 | 20 | 20 | 100.0 | 20 | 100.0 | 0 | 20 | 0 | 0 | 0 | | Challenge | 14 | 14 | 100.0 | 14 | 14 | 100.0 | 14 | 100.0 | 3 | 11 | 0 | 0 | 0 | | Total | 34 | 34 | 100.0 | 34 | 34 | 100.0 | 34 | 100.0. | 3 | 31 | 0 | 0 | 0 | | | | | | | | | | | | | | | | | E. faecalis - ABSSSI breakpoints (≤0.25, 0.5, ≥1) | | | | | | | | | | | | | | | Clinical | 60 | 58 | 96.7 | 55 | 55 | 100.0 | 56 | 93.3 | 1 | 58 | 4 | 0 | 0 | | Challenge | 5 | 5 | 100.0 | 5 | 5 | 100.0 | 5 | 100.0 | 1 | 4 | 0 | 0 | 0 | | Total | 65 | 63 | 96.9 | 60 | 60 | 100.0 | 61 | 93.8 | 2 | 62 | 4 | 0 | 0 | {12} To address the testing of non-indicated species the following footnotes were included in the device labeling: The safety and efficacy of Omadacycline in treating Acute Bacterial Skin and Skin Structure infections (ABSSSI) due to organisms other than K. pneumoniae and E. cloacae or Community Acquired Bacterial Pneumoniae (CABP) due to organisms other than K. pneumoniae may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. The safety and efficacy of Omadacycline in treating Acute Bacterial Skin and Skin Structure infections (ABSSSI) due to organisms other than S. aureus (MRSA and MSSA, S. lugdunensis and E. faecalis or Community Acquired Bacterial Pneumoniae (CABP) due to organisms other than S. aureus (MSSA only) may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. ## Resistance Mechanisms Challenge isolates harboring the resistance mechanisms against which Omadacycline has been shown to be active were not tested. The sponsor added the following limitation to the device labeling: Resistance mechanism characterization was not available for all organisms at the time of comparative testing, and therefore the performance of the Sensititre Omadacycline for non-fastidious gram-negative and gram-positive organisms is unknown for organisms harboring the following resistance mechanisms: tetB, tetK, tetL, tetM. ## MIC Trending An analysis of trending was conducted using the combined clinical and challenge data for each organism group. This trending calculation takes into account MIC values that are determined to be one or more doubling dilutions lower or higher compared to the reference method irrespective of whether the device MIC values are on-scale or not. Trending results are shown in Table 7 for Enterobacteriaceae and for gram positive organisms in Table 8. Results for Enterobacteriaceae were also stratified by species to determine if particular trends were observed. The acceptable percent difference between higher and lower dilution readings is <30%. 13 {13} # Gram-negative Table 7. Trending in Enterobacteriaceae, Clinical and Challenge Isolates | Read Method | Organism | Total evaluable for trending | ≥1 dilution lower No. (%) | Exact No (%) | ≥1 dilution higher No (%) | | --- | --- | --- | --- | --- | --- | | VIZION | K. pneumoniae^{a} | 122 | 11(9.0) | 77 (63.1) | 34 (27.9) | | | E. cloacae^{b} | 52 | 3 (5.8) | 41 (78.9) | 8 (15.4) | | | K. oxytoca^{c} | 48 | 2 (4.2) | 39 (81.3) | 7 (14.6) | | | K. aerogenes^{d} | 27 | 2 (7.4) | 22 (81.5) | 3 (11.1) | | | Citrobacter spp.^{e} | 65 | 2 (3.1) | 34 (52.3) | 29 (44.6) | | | E. coli^{f} | 124 | 14 (11.3) | 73 (58.9) | 37 (29.8) | | | All Enterobacteriaceae^{g} | 438 | 34 (7.8) | 286 (65.3) | 118 (26.9) | | OptiRead | K. pneumoniae^{h} | 123 | 17 (13.8) | 71 (57.7) | 35 (28.5) | | | E. cloacae^{i} | 52 | 5 (9.6) | 40 (76.9) | 7 (13.5) | | | K. oxytoca^{j} | 48 | 5 (10.4) | 35 (72.9) | 8 (16.7) | | | K. aerogenes^{k} | 27 | 3 (11.1) | 22 (81.5) | 2 (7.4) | | | Citrobacter spp.^{l} | 65 | 6 (9.2) | 29 (44.6) | 30 (46.2) | | | E. coli^{m} | 124 | 23 (18.6) | 71 (57.3) | 30 (24.2) | | | All Enterobacteriaceae^{n} | 439 | 59 (13.4) | 268 (61.1) | 112 (25.5) | a Difference between the higher and lower dilutions for K. pneumoniae is:18.9% b Difference between the higher and lower dilutions for E. cloacae is: 9.6% c Difference between the higher and lower dilutions for K. oxytoca is: 10.4% d Difference between the higher and lower dilutions for K. aerogenes is: 3.7% e Difference between the higher and lower dilutions for Citrobacter spp. is 41.5% f Difference between the higher and lower dilutions for E. coli is 18.6% g Difference between the higher and lower dilutions for Enterobacteriaceae (Manual Read) is 19.2% h Difference between the higher and lower dilutions for K. pneumoniae is: 14.6% i Difference between the higher and lower dilutions for E. cloacae is:3.9% j Difference between the higher and lower dilutions for K oxytoca is 6.2% k Difference between the higher and lower dilutions for K. aerogenes is -3.7% l Difference between the higher and lower dilutions for Citrobacter spp. is 36.9% m Difference between the higher and lower dilutions for E. coli is 5.7% n Difference between the higher and lower dilutions for Enterobacteriaceae (Auto Read) is 12.1% {14} # Gram-positive Table 8. Trending in Staphylococcus spp. and E. faecalis | Read Method | Organism | Total evaluable for trending | ≥ 1 dilution lower No. (%) | Exact No (%) | ≥ 1 dilution higher No (%) | | --- | --- | --- | --- | --- | --- | | Vizion | S. aureus (MSSA)^{a} | 250 | 18 (7.2) | 132 (52.8) | 100 (40.0) | | | S. aureus (MRSA)^{b} | 249 | 12 (4.8) | 142 (57.0) | 95 (38.2) | | | S. aureus^{c} | 499 | 30 (6.0) | 274 (54.9) | 195 (39.1) | | | S. lugdunensis^{d} | 34 | 2 (5.9) | 24 (70.6) | 8 (23.5) | | | E. faecalis^{e} | 60 | 0 | 33 (55.0) | 27 (45.0) | | | | | | | | | OptiRead | S. aureus (MSSA)^{f} | 250 | 34 (13.6) | 138 (55.2) | 78 (31.2) | | | S. aureus (MRSA)^{g} | 249 | 24 (9.6) | 137 (55.0) | 88 (35.3) | | | S. aureus^{h} | 499 | 58 (11.6) | 275 (55.1) | 166 (33.3) | | | S. lugdunensis^{i} | 34 | 16 (47.1) | 17 (50.0) | 1 (2.9) | | | E. faecalis^{j} | 60 | 8 (13.3) | 36 (60.0) | 16 (26.7) | a Difference between the higher and lower dilutions for S. aureus (MSSA) is: 32.8% b Difference between the higher and lower dilutions for S. aureus (MRSA) is: 33.3% c Difference between the higher and lower dilutions for S. aureus (MSSA and MRSA) is: 33.1% d Difference between the higher and lower dilutions for S. lugdunensis is: 17.7% e Difference between the higher and lower dilutions for E. faecalis is: 45.0% f Difference between the higher and lower dilutions for S. aureus (MSSA) is: 17.6% g Difference between the higher and lower dilutions for S. aureus (MRSA) is: 25.7% h Difference between the higher and lower dilutions for S. aureus (MSSA and MRSA) is: 22.6% i Difference between the higher and lower dilutions for S. lugdunensis is: -44.1% j Difference between the higher and lower dilutions for E. faecalis is: 13.3% A trend toward higher MIC readings was observed for Citrobacter spp with both Vizion and OptiRead. A trend toward higher MIC readings was observed for S. aureus (MRSA and MSSA and E. faecalis with Vizion; a trend toward lower MIC readings was observed for S. lugdunensis with OptiRead. The sponsor included the following footnotes to the performance table to address the trending observed for Omadacycline. Omadacycline MIC values tended to be in exact agreement or at least one dilution higher when testing Citrobacter spp. with OptiRead compared to the CLSI reference broth microdilution. MIC values tended to be in exact agreement or one dilution lower when testing S. lugdunensis. Omadacycline MIC values tended to be in exact agreement or at least one dilution higher when testing Citrobacter spp., S. aureus (MRSA and MSSA) and E. faecalis with Vizion compared to the CLSI reference broth microdilution. {15} 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 16 {16} 5. Expected values/Reference range: Table 9. Interpretive Criteria for Omadacycline | Organism | Infection Type | FDA Interpretive Criteria for Omadacycline MIC (μg/mL) | | | | --- | --- | --- | --- | --- | | | | S | I | R | | Enterobacteriaceaea | CABP and ABSSSI | ≤4 | 8 | ≥18 | | S. aureus (MSSA only) | CABP | ≤0.25 | 0.5 | ≥1 | | S. aureus (MSSA and MRSA) | ABSSSI | ≤0.5 | 1 | ≥2 | | S. lugdunensis | ABSSSI | ≤0.12 | 0.25 | ≥0.5 | | E. faecalis | ABSSSI | ≤0.25 | 0.5 | ≥1 | N. Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision.