The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Amikacin in the dilution range of 0.25-256 ug/mL

{0} FDA U.S. FOOD & DRUG ADMINISTRATION # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY ## I Background Information: A 510(k) Number K252014 B Applicant Thermo Fisher Scientific C Proprietary and Established Names The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Amikacin in the dilution range of 0.25-256 µg/mL D Regulatory Information | Product Code(s) | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | JWY | Class II | 21 CFR 866.1640 - Antimicrobial Susceptibility Test Powder | MI - Microbiology | | LRG | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology | | LTT | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology | ## II Submission/Device Overview: ### A Purpose for Submission: To obtain substantial equivalence determination for The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Amikacin in the dilution range of 0.25-256 µg/mL with updated FDA-recognized breakpoints for Acinetobacter spp., Enterobacterales, and Pseudomonas aeruginosa and modified dilution range from that cleared in K860753. ### B Measurand: Amikacin in the dilution range of 0.25 to 256 µg/mL Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} C Type of Test: Quantitative antimicrobial susceptibility test (AST) growth-based detection III Intended Use/Indications for Use: A 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 Acinetobacter species, Enterobacterales, Pseudomonas aeruginosa, and other non-Enterobacterales and of non-fastidious Gram positive isolates, comprising of Staphylococcus spp., Enterococcus spp., and beta-haemolytic Streptococci other than S. pneumoniae. B 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 amikacin in the dilution range of 0.25-256 µg/mL for testing non-fastidious gram-negative isolates on The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System. Testing is indicated for Acinetobacter spp., Enterobacterales, and Pseudomonas aeruginosa, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC) webpage. The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Amikacin in the dilution range of 0.25-256 µg/mL demonstrated acceptable performance with the following organisms: Acinetobacter spp. (Acinetobacter baumannii) Enterobacterales (Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marcescens) Pseudomonas aeruginosa C Special Conditions for Use Statement(s): Rx - For Prescription Use Only The following limitation was applied to amikacin testing in the appropriate section of the device labeling that references other drugs: Studies of the following drugs were performed with the AIM Autoinoculator and read using the ARIS HiQ/OptiRead and Vizion. The use of an alternative inoculation system or alternative read methods has not been evaluated. Due to the insufficient number of resistant of C. freundii, C. koseri, E. cloacae complex, E. coli, K. aerogenes, K. oxytoca, M. morganii, P. vulgaris, and S. marcescens isolates evaluated, the following limitation was applied to amikacin testing in the appropriate section of the device labeling that references other drugs: K252014 - Page 2 of 14 {2} The ability of the Sensititre system to detect resistance or non-susceptibility to antimicrobics as shown below is unknown because an insufficient number of resistant or non-susceptible strains were available at the time of comparative testing. If such a strain is observed, it should be submitted to a reference laboratory. ## D Special Instrument Requirements: - Sensititre AIM for device inoculation - Sensititre Vizion digital viewing device - Sensititre ARIS HiQ/OptiRead automated plate reader ## IV Device/System Characteristics: ### A Device Description: The Sensititre 18-24 hour MIC or Breakpoint Susceptibility Plate System is an antimicrobial susceptibility test. Each plate is dosed with dried, stabilized antimicrobial agents at appropriate dilutions. It is a micro-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. ### B Principle of Operation: The Sensititre 18-24 hour MIC Susceptibility plates are multi-well plastic microtiter plates that contain doubled dilutions of antibacterial agents. Each plate includes antimicrobial agents at appropriate dilutions. Results can be read using the digital viewing device (Vizion) or by use of an automated plate reader (ARIS HiQ/OptiRead). The Sensititre Vizion digital viewing device allows the panel image to be displayed on a touch screen directly from a video camera and allows the user to visually 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 non-fluorescent 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 bound non-fluorescent substrate cleaves the bond releasing fluorescence. The amount of fluorescence detected is directly related to the activity of bacterial growth. The MIC is determined by observing the lowest dilution of antimicrobial agent that inhibits growth of the organism. The non-fluorescent (fluorogenic) 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. Sensititre 18-24 hour MIC plates can either be read automatically on an ARIS HiQ/OptiRead using fluorescence or by visual reading of growth on the Vizion digital viewing device. K252014 - Page 3 of 14 {3} V Substantial Equivalence Information: A Predicate Device Name(s): The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Lefamulin in the dilution range of 0.008-16 µg/mL B Predicate 510(k) Number(s): K192729 C Comparison with Predicate(s): | Device & Predicate Device(s): | Device K252014 | Predicate K192729 | | --- | --- | --- | | Device Trade Name | The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Amikacin in the dilution range of 0.25-256 µg/mL | The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Lefamulin in the dilution range of 0.008-16 µg/mL | | General Device Characteristic Similarities | | | | Intended Use | The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious bacterial isolates. | Same | | Test panel | Each 96 well plate is precision 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 | | Incubation | 18-24 hours | Same | | Read Method | Results can be read using fluorescence with the ARIS HiQ/OptiRead or by visual reading of growth with the Vizion. | Same | | General Device Characteristic Differences | | | | Antibiotic and Dilution Range | Amikacin 0.25-256 µg/mL | Lefamulin 0.008-16 µg/mL | | Test Organisms | Acinetobacter spp. (Acinetobacter baumannii) Enterobacterales (Citrobacter freundii, Citrobacter koseri, Enterobacter cloacae complex, | Staphylococcus aureus (methicillin-susceptible isolates) | K252014 - Page 4 of 14 {4} | | Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marcescens) Pseudomonas aeruginosa | | | --- | --- | --- | VI Standards/Guidance Documents Referenced: CLSI M07, "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard - Eleventh Edition", (January 2018) CLSI M100, "Performance Standards for Antimicrobial Susceptibility Testing; 34th Edition", (March 2024) Guidance for Industry and FDA: Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems, August 28, 2009 VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: A reproducibility study of The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Amikacin was performed at three sites using a panel of twenty-five (25) gram-negative isolates from species indicated for use with the device (six Escherichia coli, five Klebsiella pneumoniae, four Pseudomonas aeruginosa, three Serratia marcescens, two Enterobacter cloacae, two Acinetobacter baumannii, one Citrobacter koseri, one Proteus mirabilis, and one Providencia stuartii). All isolates were tested in triplicate over three days for a total of 252 data points with each read method (i.e., automatically with the ARIS HiQ/OptiRead and visually with the Vizion). The Sensititre AIM Autoinoculator was used for Sensititre plate inoculation. The mode MIC value was determined, and the reproducibility was calculated based on MIC values falling within $\pm 1$ doubling dilution of the mode MIC value. The reproducibility studies for both the ARIS HiQ/OptiRead and Vizion read methods demonstrated acceptable performance of $\geq 95\%$. 2. Linearity: Not applicable. 3. Analytical Specificity/Interference: K252014 - Page 5 of 14 {5} Not applicable. 4. Assay Reportable Range: Not applicable. 5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods): The CLSI-recommended quality control (QC) strains *E. coli* ATCC 25922 and *P. aeruginosa* ATCC 27853 were tested at three sites. The QC strains were tested a minimum of 20 times per site and read automatically with the ARIS HiQ/OptiRead and visually with the Vizion. The QC strains were also tested with the reference method. The results demonstrate that The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Amikacin produced quality control results within the recommended range >95% of the time (Table 1). Table 1. Quality Control Results for *E. coli* and *P. aeruginosa* with Amikacin with the Reference Method, ARIS HiQ/OptiRead, and Vizion | QC Organism | Expected Range (μg/mL) | Concentration (μg/mL) | Reference | ARIS HiQ/OptiRead | Vizion | | --- | --- | --- | --- | --- | --- | | Escherichia coli ATCC 25922 | 0.5-4 μg/mL | ≤0.25 | - | - | - | | | | 0.5 | - | - | - | | | | 1 | 6 | 11 | 6 | | | | 2 | 66 | 94 | 95 | | | | 4 | 12 | 9 | 13 | | | | ≥8 | - | - | - | | Pseudomonas aeruginosa ATCC 27853 | 1-4 μg/mL | ≤0.5 | - | - | - | | | | 1 | 4 | 11 | 1 | | | | 2 | 75 | 103 | 108 | | | | 4 | 5 | - | 5 | | | | ≥8 | - | - | - | Inoculum Density: Inoculum density checks were performed for all QC, reproducibility, challenge, and clinical isolates tested. Only results from cultures with appropriate inoculum densities were reported. Purity Checks: Purity checks were performed for all QC, reproducibility, challenge, and clinical isolates tested. Only results from pure cultures were reported. Growth Failure: There were no growth failures. ARIS HiQ/OptiRead Invalid (No fluorescence): There were no invalids for *Acinetobacter* spp., Enterobacterales, or *P. aeruginosa* that did not produce adequate fluorescence by the ARIS HiQ/OptiRead. 6. Detection Limit: K252014 - Page 6 of 14 {6} Not applicable. 7. Assay Cut-Off: Not applicable. ## B Comparison Studies: ### 1. Method Comparison with Predicate Device: Testing of The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Amikacin was performed at three external sites. Results were compared to those obtained with the CLSI broth microdilution reference method. Sensititre panels were inoculated using only the AIM Autoinoculator and results were read automatically by the ARIS HiQ/OptiRead and visually by the Vizion. Reference panels were inoculated according to recommendations in the M07 CLSI document and results were read manually using a mirrored reader. No inoculation system other than the AIM Autoinoculator and no read methods other than ARIS HiQ/OptiRead and Vizion was used in the comparative study. To address the inoculation method and read method limitation, the following limitation was applied to amikacin testing in the appropriate section of the device labeling that references other drugs: Studies of the following drugs were performed with the AIM Autoinoculator and read using the ARIS HiQ/OptiRead and Vizion. The use of an alternative inoculation system or alternative read methods has not been evaluated. The testing conditions for the reference method consisted of the following: - Media: per CLSI M07 guidelines for Acinetobacter spp., Enterobacterales and Pseudomonas aeruginosa - Inoculum: Inoculated per CLSI M07 guidelines - Incubation: 34-36°C in a non-CO₂ incubator for 20-24 hours (Acinetobacter spp.) or 16-20 hours (Enterobacterales and Pseudomonas aeruginosa) Inoculation and incubation procedure for Acinetobacter spp., Enterobacterales (excluding Proteus spp., Providencia spp., and Morganella spp.) and Pseudomonas aeruginosa - Media: cation-adjusted Mueller Hinton broth with TES buffer (CAMHBT) - Inoculum: A suspension approximating a 0.5 McFarland standard was prepared in 5 mL sterile water. Ten (10) μL of the standardized suspension was transferred to 11 mL of CAMHBT. Susceptibility plates were inoculated with 50 μL of the final organism suspension using the Sensititre AIM Autoinoculator. - Incubation: 34-36°C in a non-CO₂ incubator for 18-24 hours (20-24 hours for Acinetobacter spp.) Inoculation and incubation procedure for Proteus spp., Providencia spp., and Morganella spp. - Media: cation-adjusted Mueller Hinton broth with TES buffer (CAMHBT) - Inoculum: A suspension approximating a 0.5 McFarland standard was prepared in 5 mL sterile water. One (1.0) μL of the standardized suspension was transferred to 11 mL of K252014 - Page 7 of 14 {7} CAMHBT. Susceptibility plates were inoculated with 50 μL of the final organism suspension using the Sensititre AIM Autoinoculator. - Incubation: 34-36°C in a non-CO₂ incubator for 18-24 hours # ARIS HiQ/OptiRead: A total of 686 gram-negative clinical isolates comprised of A. baumannii (60 isolates), Enterobacterales (30 C. freundii, 45 C. koseri, 60 E. cloacae complex, 75 E. coli, 60 K. aerogenes, 25 K. oxytoca, 65 K. pneumoniae, 30 M. morganii, 40 P. mirabilis, 36 P. rettgeri, 34 P. stuartii, 36 P. vulgaris, and 30 S. marcescens isolates), and P. aeruginosa (60 isolates), as well as 193 challenge isolates comprised of A. baumannii, (24 isolates), Enterobacterales (6 C. freundii, 5 C. koseri, 20 E. cloacae complex, 25 E. coli, 12 K. aerogenes, 5 K. oxytoca, 26 K. pneumoniae, 3 M. morganii, 10 P. mirabilis, 7 P. rettgeri, 7 P. stuartii, 4 P. vulgaris, and 11 S. marcescens isolates) and P. aeruginosa (28 isolates) were evaluated with the ARIS HiQ/OptiRead and the results are provided in Table 2. For Acinetobacter spp. read using the ARIS HiQ/OptiRead, the combined clinical and challenge isolates (84 isolates) were acceptable at 97.6% and 91.7% for EA and CA, respectively. There were seven minor errors and no major errors or very major errors. For Enterobacterales read using the ARIS HiQ/OptiRead, the combined clinical and challenge isolates (707 isolates) were acceptable at 96.3% and 98.9% for EA and CA, respectively. There were seven minor errors, no major errors, and one very major error (1/31 = 3.2%). When evaluating by individual species, the one very major error was due to an E. coli isolate (1/2 = 50%). Due to the lack of resistant isolates evaluated, the very major error is considered random, and the following performance footnote was included in the device labeling: The 1 very major error observed was considered a random error due to the limited number of resistant isolates tested for E. coli. For P. aeruginosa read using the ARIS HiQ/OptiRead, the combined clinical and challenge isolates (88 isolates) were acceptable at 96.6% and 95.5% for EA and CA, respectively. There were four minor errors and no major errors or very major errors. Table 2. Amikacin Performance of Acinetobacter spp., Enterobacterales, and P. aeruginosa Read by ARIS HiQ/OptiRead | | Tot | EA No. | EA % | Eval Tot | Eval EA No. | Eval EA % | CA Tot | CA % | No. R | No. S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Acinetobacter spp. [≤16 (S), 32 (I), ≥64 (R)] | | | | | | | | | | | | | | | Clinical | 60 | 58 | 96.7 | 48 | 46 | 95.8 | 59 | 98.3 | 16 | 44 | 1 | 0 | 0 | | Challenge | 24 | 24 | 100 | 24 | 24 | 100 | 18 | 75.0 | 8 | 10 | 6 | 0 | 0 | | Total | 84 | 82 | 97.6 | 72 | 70 | 97.2 | 77 | 91.7 | 24 | 54 | 7 | 0 | 0 | | Enterobacterales [≤16 (S), 32 (I), ≥64 (R)] | | | | | | | | | | | | | | | Clinical | 566 | 546 | 96.5 | 547 | 527 | 96.3 | 561 | 99.1 | 18 | 546 | 4 | 0 | 1 | | Challenge | 141 | 135 | 95.7 | 131 | 125 | 95.4 | 138 | 98.9 | 13 | 121 | 3 | 0 | 0 | | Total | 707 | 681 | 96.3 | 678 | 652 | 96.2 | 699 | 98.9 | 31 | 667 | 7 | 0 | 1 | | P. aeruginosa [≤16 (S), 32 (I), ≥64 (R)] | | | | | | | | | | | | | | K252014 - Page 8 of 14 {8} | | Tot | EA No. | EA % | Eval Tot | Eval EA No. | Eval EA % | CA Tot | CA % | No. R | No. S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Clinical | 60 | 58 | 96.7 | 59 | 57 | 96.6 | 59 | 98.3 | 2 | 57 | 1 | 0 | 0 | | Challenge | 28 | 27 | 96.4 | 28 | 27 | 96.4 | 25 | 89.3 | 4 | 21 | 3 | 0 | 0 | | Total | 88 | 85 | 96.6 | 87 | 84 | 96.6 | 84 | 95.5 | 6 | 78 | 4 | 0 | 0 | EA - Essential Agreement CA - Category Agreement S - Susceptible R - Resistant EVAL - Evaluable MICs 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 or those in which an off-scale result is at least two doubling dilutions from the on-scale result. Category agreement (CA) occurs when the interpretation of the result of the reference method agrees exactly with the interpretation of the Sensititre panel. ## Vizion: A total of 686 gram-negative clinical isolates comprised of A. baumannii (60 isolates), Enterobacterales (30 C. freundii, 45 C. koseri, 60 E. cloacae complex, 75 E. coli, 60 K. aerogenes, 25 K. oxytoca, 65 K. pneumoniae, 30 M. morganii, 40 P. mirabilis, 36 P. rettgeri, 34 P. stuartii, 36 P. vulgaris, and 30 S. marcescens isolates), and P. aeruginosa (60 isolates), as well as 193 challenge isolates comprised of A. baumannii, (24 isolates), Enterobacterales (6 C. freundii, 5 C. koseri, 20 E. cloacae complex, 25 E. coli, 12 K. aerogenes, 5 K. oxytoca, 26 K. pneumoniae, 3 M. morganii, 10 P. mirabilis, 7 P. rettgeri, 7 P. stuartii, 4 P. vulgaris, and 11 S. marcescens isolates) and P. aeruginosa (28 isolates) were evaluated with the Vizion and the results are provided in Table 3. For Acinetobacter spp. read using the Vizion, the combined clinical and challenge isolates (84 isolates) were acceptable at 95.2% for both EA and CA. There were four minor errors and no major errors or very major errors. For Enterobacterales read using the Vizion, the combined clinical and challenge isolates (707 isolates) were acceptable at 95.6% and 98.7% for EA and CA, respectively. There were eight minor errors, no major errors, and one very major error (1/31 = 3.2%). When evaluating by individual species, the one very major error was due to an E. coli isolate (1/2 = 50%). Due to the lack of resistant isolates evaluated, the very major error is considered random, and the following performance footnote was included in the device labeling: The 1 very major error observed was considered a random error due to the limited number of resistant isolates tested for E. coli. For P. aeruginosa read using the Vizion, the combined clinical and challenge isolates (88 isolates) were acceptable at 97.7% for both EA and CA. There were two minor errors and no major errors or very major errors. Table 3. Amikacin Performance of Acinetobacter spp., Enterobacterales, and P. aeruginosa Read by Vizion K252014 - Page 9 of 14 {9} | | Tot | EA No. | EA % | Eval Tot | Eval EA No. | Eval EA % | CA Tot | CA % | No. R | No. S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Acinetobacter spp., [≤16 (S), 32 (I), ≥64 (R)] | | | | | | | | | | | | | | | Clinical | 60 | 56 | 93.3 | 48 | 44 | 91.7 | 59 | 98.3 | 16 | 44 | 1 | 0 | 0 | | Challenge | 24 | 24 | 100 | 24 | 24 | 100 | 21 | 87.5 | 8 | 10 | 3 | 0 | 0 | | Total | 84 | 80 | 95.2 | 72 | 68 | 94.4 | 80 | 95.2 | 24 | 54 | 4 | 0 | 0 | | Enterobacterales [≤16 (S), 32 (I), ≥64 (R)] | | | | | | | | | | | | | | | Clinical | 566 | 540 | 95.4 | 547 | 521 | 95.3 | 561 | 99.1 | 18 | 546 | 4 | 0 | 1 | | Challenge | 141 | 136 | 96.5 | 131 | 126 | 96.2 | 137 | 97.2 | 13 | 121 | 4 | 0 | 0 | | Total | 707 | 676 | 95.6 | 678 | 647 | 95.4 | 698 | 98.7 | 31 | 667 | 8 | 0 | 1 | | P. aeruginosa [≤16 (S), 32 (I), ≥64 (R)] | | | | | | | | | | | | | | | Clinical | 60 | 59 | 98.3 | 59 | 58 | 98.3 | 59 | 98.3 | 2 | 57 | 1 | 0 | 0 | | Challenge | 28 | 27 | 96.4 | 28 | 27 | 96.4 | 27 | 96.4 | 4 | 21 | 3 | 0 | 0 | | Total | 88 | 86 | 97.7 | 87 | 85 | 97.7 | 86 | 97.7 | 6 | 78 | 2 | 0 | 0 | EA - Essential Agreement CA - Category Agreement S - Susceptible R - Resistant EVAL - Evaluable MICs 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 or those in which an off-scale result is at least two doubling dilutions from the on-scale result. Category agreement (CA) occurs when the interpretation of the result of the reference method agrees exactly with the interpretation of the Sensititre panel. Due to the insufficient number of $C$ freundii, $C$ koseri, $E$ cloacae complex, $E$ coli, $K$ aerogenes, $K$ oxytoca, $M$ morganii, $P$ vulgaris, and $S$ marcescens resistant isolates evaluated, the following limitation was applied to amikacin testing in the appropriate section of the device labeling that references other drugs: The ability of the Sensititre system to detect resistance or non-susceptibility to antimicrobics as shown below is unknown because an insufficient number of resistant or non-susceptible strains were available at the time of comparative testing. If such a strain is observed, it should be submitted to a reference laboratory. # MIC Trending A trending analysis was conducted using the combined data (clinical and challenge) obtained for both the ARIS HiQ/OptiRead and the Vizion for Acinetobacter spp., Enterobacterales, and $P$ . aeruginosa. This trending calculation takes into account MIC values that are determined to be one or more doubling dilutions lower or higher than the reference method irrespective of whether the device MIC values are on-scale or not. Species for which the difference between the percentage of isolates with higher vs. lower readings was $>30\%$ and for which the confidence interval was determined to be statistically significant were considered to show evidence of trending. Trending that shows higher or lower MIC values compared to the reference is addressed in the labeling. Evaluation of results for A. baumannii., species within Enterobacterales, and P. aeruginosa with amikacin using the ARIS HiQ/OptiRead and Vizion are summarized in Table 4. A trend toward K252014 - Page 10 of 14 {10} lower MIC values was observed for $P.$ mirabilis, $P.$ stuartii, and $P.$ vulgaris using the ARIS/HiQ/OptiRead when compared to the CLSI broth microdilution reference method. A trend toward lower MIC values was observed for $P.$ mirabilis, $P.$ stuartii, and $P.$ vulgaris using the Vizion when compared to the CLSI broth microdilution reference method. To address the MIC trending, the sponsor included the following footnotes in the performance table: For ARIS HiQ/OptiRead: Amikacin MIC values tended to be in exact agreement or at least one doubling dilution lower when testing P. mirabilis, P. stuartii, and P. vulgaris with the ARIS HiQ/OptiRead compared to the CLSI broth microdilution reference method. For Vizion: Amikacin MIC values tended to be in exact agreement or at least one doubling dilution lower when testing P. mirabilis, P. stuartii, and P. vulgaris with the Vizion compared to the CLSI broth microdilution reference method. Table 4. Amikacin Trending Analysis for Acinetobacter spp., Enterobacterales, and $P$ . aeruginosa with ARIS HiQ/OptiRead and Vizion | Read Method | Organism | Total Evaluable for Trending | ≥1 Dilution Lower No. (%) | Exact No. (%) | ≥1 Dilution Higher No. (%) | Percent Difference (95% CI) | Trending Noted | | --- | --- | --- | --- | --- | --- | --- | --- | | ARIS HiQ/OptiRead | A. baumannii | 72 | 20, (27.8) | 36 | 16, (22.2) | -6% (-19% to 9%) | No | | | C. freundii | 35 | 7, (20.0) | 22 | 6, (17.1) | -3% (-21% to 16%) | No | | | C. koseri | 50 | 19, (38.0) | 24 | 7, (14.0) | -24% (-40% to -7%) | No | | | E. cloacae complex | 79 | 16, (20.3) | 59 | 4, (5.1) | -15% (-26% to -25%) | No | | | E. coli | 99 | 20, (20.2) | 65 | 14, (14.1) | -6% (-17% to 5%) | No | | | K. aerogenes | 72 | 19, (26.4) | 46 | 7, (9.7) | -17% (-29% to -4%) | No | | | K. oxytoca | 30 | 6, (20.0) | 23 | 1, (3.3) | -17% (-34% to 0%) | No | | | K. pneumoniae | 76 | 9, (11.8) | 49 | 18, (23.7) | 12% (0% to 24%) | No | | | M. morganii | 33 | 11, (33.3) | 18 | 4, (12.4) | -21% (-40% to -1%) | No | | | P. mirabilis | 48 | 20, (41.7) | 23 | 5, (10.4) | -31% (-46% go -14%) | Yes, low | | | P. rettgeri | 41 | 15, (36.6) | 22 | 4, (9.8) | -27% (-43% to -9%) | No | | | P. stuartii | 39 | 17, (43.6) | 17 | 5, (12.8) | -31% (-48% to -11%) | Yes, low | | | P. vulgaris | 40 | 23, (57.5) | 17 | 0, (0.0) | -57% (-71% to -40%) | Yes, low | | | S. marcescens | 41 | 8, (19.5) | 27 | 6, (14.4) | -5% (-21% to 12%) | No | | | P. aeruginosa | 87 | 25, (28.7) | 58 | 4, (4.6) | -24% (-35% to -13%) | No | | | A. baumannii | 72 | 14, (19.4) | 39 | 19, (26.4) | 7% | No | K252014 - Page 11 of 14 {11} | Read Method | Organism | Total Evaluable for Trending | ≥1 Dilution Lower No. (%) | Exact No. (%) | ≥1 Dilution Higher No. (%) | Percent Difference (95% CI) | Trending Noted | | --- | --- | --- | --- | --- | --- | --- | --- | | Vizion | | | | | | (-7% to 20%) | | | | C. freundii | 35 | 4, (11.4) | 20 | 11, (31.4) | 20% (1% to 38%) | No | | | C. koseri | 50 | 15, (30.0) | 21 | 14, (28.0) | -2% (-19% to 15%) | No | | | E. cloacae complex | 79 | 8, (10.1) | 61 | 10, (12.7) | 3% (-8% to 13%) | No | | | E. coli | 99 | 17, (17.2) | 57 | 25, (25.3) | 8% (-8% to 19%) | No | | | K. aerogenes | 72 | 14, (19.4) | 46 | 12, (16.7) | -3% (-15% to 10%) | No | | | K. oxytoca | 30 | 5, (16.7) | 19 | 6, (20.0) | 3% (-17% to 23%) | No | | | K. pneumoniae | 76 | 6, (7.9) | 48 | 22, (29.0) | 21% (9% to 33%) | No | | | M. morganii | 33 | 4, (12.1) | 24 | 5, (15.2) | 3% (-14% to 20%) | No | | | P. mirabilis | 48 | 20, (41.7) | 23 | 5, (10.4) | -31% (-46% to -14%) | Yes, low | | | P. rettgeri | 41 | 13, (31.7) | 21 | 7, (17.1) | -15% (-32% to 4%) | No | | | P. stuartii | 39 | 17, (43.6) | 18 | 4, (10.3) | -33% (-50% to -14%) | Yes, low | | | P. vulgaris | 40 | 19, (47.5) | 21 | 0, (0.0) | -48% (-63% to -31%) | Yes, low | | | S. marcescens | 41 | 5, (12.2) | 24 | 12, (29.3) | 17% (-1% to 34%) | No | | | P. aeruginosa | 87 | 6, (6.9) | 66 | 15, (17.2) | 10% (1% to 20%) | No | ## Testing/Reporting MICs for Species Not Listed in the Indications for Use For this review, the interpretive criteria are applied to the organisms/organism groups according to the FDA STIC website. As required under 511A(2)(2)(B) of the Federal Food, Drug and Cosmetic Act, the following statement is included in the Warnings and Precautions section of the device labeling to address testing and reporting of non-indicated species: 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. ## 2. Matrix Comparison: Not applicable. K252014 - Page 12 of 14 {12} # 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: Table 5: FDA-Recognized Interpretive Criteria for Amikacin | | Minimum Inhibitory Concentrations (μg/mL)a | | | | --- | --- | --- | --- | | Organisms | Susceptible | Intermediate | Resistant | | Acinetobacter spp. | ≤16 | 32 | ≥64 | | Enterobacterales | ≤16 | 32 | ≥64 | | Pseudomonas aeruginosa | ≤16 | 32 | ≥64 | aAccording to FDA STIC Webpage, https://www.fda.gov/drugs/development-resources/fda-recognized-antimicrobial-susceptibility-test-interpretive-criteria # 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 predetermined change control plan (PCCP) with a breakpoint change protocol that was reviewed and accepted by FDA in submission K231994 cleared on August 25, 2023. 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 Thermo Fisher Scientific intends to use to evaluate The Sensititre 18-24 hour MIC or Breakpoint Susceptibility K252014 - Page 13 of 14 {13} System with Amikacin when revised breakpoints for amikacin are published on the FDA STIC webpage. The breakpoint change protocol included with the submission indicated that if specific criteria are met, Thermo Fisher Scientific will update the amikacin 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. K252014 - Page 14 of 14