MICROSCAN SYNERGIES PLUS GRAM POSITIVE MIC/COMBO PANELS NEW ANTIMICROBIAL-STREPTOMYCIN SYNERGY SCREEN

{0} 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K071316 B. Purpose for Submission: To add a Streptomycin Synergy Screen to the MicroScan® Synergies plus™ Gram-Positive for testing Enterococcus spp C. Measurand: Streptomycin 1000 µg/mL, 1- Dilution Breakpoint Sequence D. Type of Test: Qualitative growth based detection algorithm using optics light detection E. Applicant: Dade Behring Inc, MicroScan® F. Proprietary and Established Names: MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels G. Regulatory Information: 1. Regulation section: 866.1645 - Fully automated short-term incubation cycle antimicrobial susceptibility system 866.1640 - Antimicrobial Susceptibility Test Powder 2. Classification: Class II 3. Product code: LON – Automated AST system short incubation LRG-Instrument for Auto Reader &amp; Interpretation of Overnight Antimicrobial Susceptibility Systems {1} JWY - Manual Antimicrobial Susceptibility Test Systems LTT – Panels, Test, Susceptibility, Antimicrobial 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-positive enterococci and staphylococci. After inoculation, panels are incubated for 4.5 – 18 hours at 35°C +/- 1°C in a WalkAway® - SI or equivalent and read by the MicroScan® Instrument System. Additionally the panels may be incubated in a non-CO₂ incubator and the Antimicrobial Susceptibility Testing (AST) portions can be read visually, according to the Package Insert. 2. Indication(s) for use: This submission is for the addition of the antimicrobial Streptomycin Synergy Screen at a concentration of 1000 µg/mL for testing Enterococcus spp at 4.5-16 hours or 16-20 hours for an overnight reading. 3. Special conditions for use statement(s): - E. faecium with the Rapid Read Method - hold Susceptible (&lt;1000 µg/mL) results to overnight/manual reads (16-20 hours). - E. faecalis with the Overnight Read Method - If E. faecalis overnight (16-20 hr) reads are critical to patient care verify with WalkAway Instrument read (footnote in the Instructions for Use Manual). - Turbidity method of inoculum preparation only. - For prescription use only. 4. Special instrument requirements: Not Applicable I. Device Description: Each panel contains two control wells: a negative control well, and a growth control well (contains test medium without antibiotic). Antibiotics are diluted in water, buffer, or minute concentrations of broth to selected concentrations prior to dehydration of the panels. The panel is rehydrated and inoculated at the same time with 0.1 ml of suspension prepared by the turbidity method (inoculum prepared in 0.4% saline with Pluronic® - a wetting agent, then 0.1 ml transferred to 25 ml of {2} inoculum Synergies plus Pos Broth with Pluronic®) for a final inoculum concentration of $3 - 7\mathrm{X}10^{5}$ CFU/ml. Panels are incubated in a Walk-Away® System and read periodically starting at 4.5 hours until there is sufficient growth to determine the MIC. Alternately the panels may be incubated at $35^{\circ}\mathrm{C}$ in a non- $\mathrm{CO}_{2}$ for 16-24 hours and read by visual observation of growth. # J. Substantial Equivalence Information: 1. Predicate device name(s): MicroScan® Dried Gram-Positive and Gram-Negative MIC/Combo Panels 2. Predicate 510(k) number(s): k862140 k020185 3. Comparison with predicate: | Similarities | | | | --- | --- | --- | | Item | Device | Predicate | | Intended use | MicroScan® panels are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility and/or identification to the species level of colonies, grown on solid media, of rapidly growing aerobic and facultative anaerobic organisms | Same | | Specimen | Isolated colonies from culture used | Same | | Inoculum | Inoculum density to 0.5 McFarland standard | Same | | Incubation | Fully automated short-term (<16 hours) Incubation Cycle Microdilution MIC Susceptibility Tests Overnight Microdilution MIC Susceptibility tests | Same | | Technology | Growth based | Same | | Differences | | | | Item | Device | Predicate | | Panels | Dried streptomycin Synergy Screen | Dried clindamycin or gentamicin in broth | | Reading | Uses both a ≤ 16 h read and overnight read method in the same system | Overnight system uses only the overnight reading method and <16 hour instruments use only the <16 hour read method. | | Inoculum preparation | Turbidity method of inoculation only. | Inoculum prepared using either the Turbidity method or Prompt® system | | Results | Qualitative interpretations | Quantitative with qualitative interpretations | | Instrument | WalkAway® -SI System or equivalent | autoScan® -4 or WalkAway® | | Antibiotic | Streptomycin at 1000 μg/mL | Different concentrations depending on the antibiotic | {3} K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: “Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA”; Clinical and Laboratory Standards Institute (CLSI) M7 (M100-S17) “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard”. L. Test Principle: The WalkAway® SI uses a Colorimetric Optics System consisting of a color wheel/lamp assembly and a Photosensor. There is an initial read at 2.5 hours with a possible final read at 4.5, 5.5, 6.5, 8, 12, 16/18 hours (overnight instrument readings, manual readings), or 24 hours depending on the growth rate of the organism being tested. The time of final read is dependent on the user customization, the growth rate of the organism, and the sensitivity of the automatic reader since cell densities below $2 \times 10^{7}$ cells/ml are not detected. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility was demonstrated using ten isolates tested at three sites on three separate days in triplicate. The study included the testing on the WalkAway® SI read at less than (&lt;) 16 hours, WalkAway® 16-18 hour readings and manual readings at 16-20 hours incubation. Acceptable reproducibility (95%) was demonstrated with only category agreement (S, R) since that is all that is detected. b. Linearity/assay reportable range: Not Applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC Enterococcus faecalis ATCC 29212 and Enterococcus faecalis ATCC 51299 were tested a sufficient number of times with acceptable results most of the time with the reference method. Both of the QC isolates grow in the 4.5-18 hour window. Quality control results demonstrated the ability of the different reading parameters (manual and instrument) to produce acceptable results of greater than (&gt;) 95%. The following table provides the frequency of the results in each concentration with the expected range stated. {4} Quality Control Table | | | | Results | | | | --- | --- | --- | --- | --- | --- | | Organism | Conc in μg/mL | # reference | MicroScan® | | | | Streptomycin Synergy Screen | | | Manual overnight | Instrument overnight | <16 hrs instrument | | E. faecalis ATCC 29212 | ≤1000 | 62 | 62 | 62 | 61 | | Range ≤ 1000 μg/mL | >1000 | | | | 1 | | | | | | | | | | | | | | | | Organism | Conc in μg/mL | # reference | MicroScan® | | | | --- | --- | --- | --- | --- | --- | | Streptomycin Synergy Screen | | | Manual overnight | Instrument overnight | <16 hrs instrument | | E. faecalis ATCC 51299 | ≤1000 | | | 1 | 1 | | Range >1000 μg/mL | >1000 | 64 | 64 | 63 | 63 | | | | | | | | | | | | | | | Inoculum density control: A turbidity meter was used for the turbidity inoculation method. Turbidity inoculum verification provided. d. Detection limit: Not Applicable e. Analytical specificity: Not Applicable f. Assay cut-off: Not Applicable 2. Comparison studies: a. Method comparison with predicate device: Clinical testing was conducted at three sites using Enterococci and the MicroScan® Synergies plus™ Gram-Positive panel with Streptomycin Synergy Screen (Test Panel) compared with a frozen reference panel. A total of 374 gram-positive isolates were tested of which 297 were fresh isolates and 68 were stock isolates. Nine isolates were reported at greater than or equal to $(\geq)$ 16 hours and were not included as Rapid read results. Therefore, of the 374 isolates tested, 365 Rapid read isolates were analyzed. There were 83 challenge isolates selected from CDC challenge strains and stock organisms tested at one site and compared to the reference broth dilution result mode that {5} were determined by previous testing of each isolate multiple times in the recommended reference panel. Four challenge isolates were reported at $\geq 16$ hours and were not included as Rapid read results. There were 68 isolates from the verification testing which were tested in house. These isolates were primary clinical isolates collected over time. A qualitative comparison only was performed. The Synergies plus™ readings were obtained at times between 4.5 and 16 hours of incubation for &gt;95% of the results. An additional comparison was done with readings on the instrument after overnight incubation and also read manually when incubated 16-18 hours. The recommended CLSI reference method was followed with the exception of the use of a small amount (0.1%) Pluronic® in the final inoculum. A validation of the use of Pluronic® in the frozen reference panels was conducted. Similar calculations for the different reading methods were performed with very little difference. The charts below demonstrates the performance of all three reading methods Rapid (WalkAway® SI, &lt;16 hours) Overnight Instrument (&gt;16 hours on the WalkAway® SI, 16/18 hours) and Overnight Manual (manual/visual read, 16 - 20) with the one dilution breakpoint when compared to the reference method. Performance Summary | | Total | CA | %CA | #R | #S | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Rapid Read Method Combined | 444 | 438 | 98.6 | 175 | 269 | N/A | 2 | 4 | | Overnight Instrument Read Combined | 457 | 448 | 98.0 | 179 | 278 | N/A | 6 | 3 | | Overnight Manual Read Combined | 457 | 448 | 98.0 | 179 | 278 | N/A | 6 | 3 | CA-Category Agreement maj-major discrepancies R-resistant isolates vmj-very major discrepancies CA is when the interpretation of the reference method agrees exactly with the interpretation of the MicroScan® result. N/A - Min errors are not applicable since only S or R results are possible The no growth rate was 2.9% (9/374) in the efficacy study and 5.0% (4/79) in the challenge study with the &lt;16 hour read method. E. faecium had a higher than expected vmj discrepancy rate of 3.3% (3/90) with the Rapid read. A limitation has been included in the package insert. E. faecalis had a vmj discrepancy rate of 2.7% (2/75) with the overnight {6} manual read. A footnote has been included in the Instruction for Use Manual. 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 5. Expected values/Reference range: Enterococcus spp. interpretive criteria: ≤1000 (S), &gt;1000 (R) 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.