SENSITITRE HAEMOPHILUS/STREPTOCOCCUS PNEUMONIAE (HP) MIC AND SUSCEPTIBILITY PLATES

{0} 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k062841 B. Purpose for Submission: To add additional organism groups to the antibiotic daptomycin on the Sensititre® Haemophilus influenzae / Streptococcus species MIC Susceptibility Plates C. Measurand: Daptomycin at 0.03-32 µg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test (AST) growth based fluorescence E. Applicant: TREK Diagnostic Systems, Inc. F. Proprietary and Established Names: Sensititre® Haemophilus influenzae / Streptococcus species MIC Susceptibility plates G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY-manual readings of AST testing of >16 hour incubation LRG Automated readings of AST of >16 hour incubation. 4. Panel: 83 Microbiology H. Intended Use: {1} 2 1. Intended use(s): The Sensititre® Haemophilus influenzae/Streptococcus species plates are in vitro diagnostic products for quantitatively and or qualitative susceptibility testing of isolated colonies of Haemophilus influenzae and Streptococcus species from clinical specimens. Plates can either be read manually or automatically on the Sensititre Autoreader and/or ARIS with Streptococcus species and manually with H.influenzae. 2. Indication(s) for use: This application is for the addition of testing Streptococcus species (spp.) with daptomycin at 0.03-32 µg/mL) for use with the Sensititre® Haemophilus influenzae/Streptococcus species Susceptibility Plates. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: Automated readings may be performed on the Sensititre® AutoReader or Sensititre® ARIS®. I. Device Description: Sensititre® MIC Susceptibility plate MIC panels are multi-well plastic microtitre plates, precision dosed with antimicrobial agents at appropriate dilutions and then dried. This is similar to the micro broth dilution methods and can provide both qualitative and quantitative susceptibility results. The medium required for testing Streptococcus is Sensititre® Mueller-Hinton (MH) broth with 2 – 5% lysed horse blood with a final organism density of 5 X 10⁵ colony forming units (CFU/mL). This is then incubated in a non CO₂ incubator for 20 – 24 hours and read manually for growth or automatically on the Sensititre® Autoreader and/or ARIS. J. Substantial Equivalence Information: 1. Predicate device name(s): Pasco MIC and MIC/ID Panels 2. Predicate 510(k) number(s): K032518 {2} 3 Comparison with predicate: | Similarities | | | | --- | --- | --- | | Item | Device | Predicate | | Intended use | an in vitro diagnostic product for clinical susceptibility testing of Streptococcus species | Same | | Inoculum | Prepared from colonies using the direct inoculation method | Same | | Growth medium | Mueller – Hinton (MH) broth with 2 – 5% lysed horse blood | Same | | Inoculation method | Direct equated to a 0.5 McFarland | Same | | Differences | | | | Item | Device | Predicate | | Type panel | Dried antibiotics | 100 μl/well frozen | | Incubation | 20 - 24 hours | 16-24 hours | | Technology | Fluorescence detection of growth | Turbidity detection of growth | | Reading method | Visual growth and Auto read by instrumentation | Visual detection of growth | K. Standard/Guidance Document Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test Systems; Guidance for Industry and FDA”; CLSI M7 (M100-S16) “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard.” L. Test Principle: The Sensititre® Autoread System utilizes fluorescence technology to read 20 -24 hour Streptococcus spp. plates. 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 non-fluorescent (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 fluorophore, is then said to be quenched. The substrate is added to the inoculum broth and dispensed into the test plates at the same time as the test organism or the plates can be prepared with the substrate already added to the plate. Enzymatic action of the bacterial surface enzymes on the specific substrates, cleave this bond releasing the fluorophore, which is now capable of 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 or automatically for the detection of fluorescence. {3} M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: A reproducibility study was performed on 25 Streptococcus spp. These isolates were tested once for each antimicrobial at each of the three sites on the automated and manual read method demonstrating >95% reproducibility for both read methods. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolate, S. pneumoniae 49619 was tested daily with acceptable results. Quality control was also performed at all sites using both manual and autoread methods. The Sensititre® results demonstrated that the system can produce QC results in the recommended range for both manual and automated read methods. The mode difference between the reference method and the two read methods demonstrates a slight trend for the Sensititre® to produce a result reading of slightly more susceptible. The reference method was in range for every day tested. The Table below includes the frequency of each result in the range tested. | Antimicrobial | ORGANISM | Conc ug/ml. | Sensititre® Autoread | Sensititre® manual | Reference | | --- | --- | --- | --- | --- | --- | | | | | | | | | Daptomycin | S. pneumoniae ATCC 49619 Exp. Range: 0.6 – 0.5 ug/ml | 0.03 | | | | | | | 0.06 | | | | | | | 0.12 | 45 | 50 | 20 | | | | 0.25 | 8 | 7 | 40 | | | | 0.5 | 7 | 3 | | | | | 1 | | | | Nephelometer was used at each site to standardize the inoculum and it was calibrated each time it was switched on. Colony counts from QC isolates were performed using the direct inoculum method with acceptable results. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable {4} 5 2. Comparison studies: a. Method comparison with predicate device: Comparison was performed to the broth dilution reference panel prepared according to the CLSI recommendation. Clinical testing included both fresh and stock clinical isolates of *Streptococcus* species and a set of challenge organisms. The broth reference panel for *Streptococcus* spp. was set up using MH supplemented with 2% to 5% lysed horse blood as recommended by CLSI and incubated in a non CO₂ incubator for 20 – 24 hours. The Sensititre® plate was read both manually and using the Sensititre Autoreader between 20 and 24 hour. The comparison resulted in the performance evaluations as reflected below. The Autoreader results and the manual results were very similar with acceptable results for both. A slight trend to more susceptible results was also noted with both read methods as compared to the reference result but still providing good essential agreement. Both methods produced similar results so only one method is presented below. Since there is only a susceptible category there are no major, minor or very major discrepancies. All isolates tested were detected in the susceptible category. Summary Table for *Streptococcus* spp. other than *S. pneumoniae* | | EA Tot | EA N | EA % | Eval EA Tot | Eval EA N | Eval EA % | CA % | | --- | --- | --- | --- | --- | --- | --- | --- | | Clinical isolates | 297 | 293 | 98.7 | 273 | 269 | 98.5 | 100 | | Challenge isolates | 50 | 50 | 100 | 46 | 46 | 100 | 100 | | Combined | 347 | 343 | 98.8 | 319 | 315 | 98.7 | 100 | EA-Essential Agreement CA-Category Agreement EA is when there is agreement between the reference method and the Sensititre® panel within plus or minus one serial two-fold dilution of antibiotic. Category agreement (CA) is when the Sensititre® panel result interpretation agrees exactly with the reference panel result interpretation. Evaluable EA is when the MIC result is on scale for both the Sensititre® and the reference and have on-scale EA. The EA% is acceptable when compared to the reference method as described in the FDA guidance document, “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA”. The charts above demonstrated that the performance for *Streptococcus* spp. other than *S. pneumoniae* was very good for both methods of reading. In this study the growth rate for *Streptococcus* spp. was greater than 95%. b. Matrix comparison: Not Applicable 3. Clinical studies: {5} a. Clinical Sensitivity: Not Applicable b. Clinical specificity: Not Applicable c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable 4. Clinical cut-off: Not Applicable 5. Expected values/Reference range: | Antibiotic | Organism | Interpretative Criteria | | --- | --- | --- | | Daptomycin | Streptococcus spp. other than S. pneumoniae | ≤1 (S)* | * For some organism/antimicrobial agent combinations, the absence or rare occurrence of resistant strains precludes defining any results categories other than "susceptible." For strains yielding results suggestive of a "nonsusceptible" category, organism identification and antimicrobial susceptibility test results should be confirmed. Subsequently, the isolates should be saved and submitted to a reference laboratory that will confirm results using a CLSI reference dilution method. # N. Proposed Labeling: The expected value range, interpretive criteria and QC are included in the package insert. The labeling is sufficient and satisfies the requirements of 21 CFR Part 809.10. # O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision.