← Product Code [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON) · K063365 # SYNERGIES PLUS GRAM-POSITIVE MIC/COMBO PANELS WITH GENTAMICIN (0.06-32MG/ML LONG DILUTION SEQUENCE (K063365) _Dade Behring, Inc. · LON · Dec 8, 2006 · Microbiology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K063365 ## Device Facts - **Applicant:** Dade Behring, Inc. - **Product Code:** [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON.md) - **Decision Date:** Dec 8, 2006 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 866.1645 - **Device Class:** Class 2 - **Review Panel:** Microbiology ## Indications for Use The 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℃ +/- 1℃, in a WalkAway® SI, or equivalent, and read by the MicroScan® Instrumentation. 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. This particular submission is for the addition of the antimicrobial gentamicin, at concentrations of 0.06 to 32 µg/ml Long Dilution Sequence for staphylococci, to the test panel. ## Device Story MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels are miniaturized broth dilution susceptibility tests. Panels contain dehydrated antimicrobial agents; rehydrated with Synergies plus™ Pos Broth after inoculation with standardized organism suspension. Incubated in WalkAway® SI instrument (or equivalent) for 4.5-18 hours. Instrument reads minimum inhibitory concentration (MIC) by identifying lowest concentration inhibiting growth. Used in clinical microbiology laboratories by technicians. Output provides quantitative/qualitative susceptibility data to clinicians for antibiotic selection and treatment optimization. ## Clinical Evidence Clinical study evaluated 301 Gram-positive isolates (267 fresh, 34 stock) and 75 challenge isolates across 3 sites. Primary endpoint was Essential Agreement (EA) and Category Agreement (CA) compared to CLSI reference broth dilution. Rapid read (<16h) method achieved 94.6% EA and 97.0% CA. Overnight instrument read achieved 97.7% EA and 96.7% CA. Reproducibility was >95% across all methods. Two very major (vmj) errors (5%) were observed in the rapid read method, attributed to specific isolate antibiograms rather than systemic failure. ## Technological Characteristics Miniaturized broth dilution susceptibility test; dehydrated antimicrobial agents in panel wells. Rehydrated with Pos Broth. Incubation 4.5-18 hours at 35°C. Automated reading via WalkAway® SI instrument or visual reading. Connectivity via instrument integration. Class II device (Product codes: LON, LRG, JWY, LTT). ## Regulatory Identification A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases. ## Special Controls *Classification.* Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.” ## Predicate Devices - MicroScan® Synergies plus™ Gram-Negative MIC/Combo Panels - MicroScan® Dried Gram-Positive Panels ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K063365 B. Purpose for Submission: To add gentamicin at concentrations of 0.06 to 2 µg/mL to the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panels C. Measurand: Gentamicin at 0.06 – 2 µg/mL D. Type of Test: Quantitative and 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 & Interpretation of Overnight Antimicrobial Susceptibility Systems JWY - Manual Antimicrobial Susceptibility Test Systems LTT – Panels, Test, Susceptibility, Antimicrobial {1} 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): MicroScan® Synergies plus™ Gram-Positive panels, with gentamicin, are intended for determination of susceptibility of Gram-positive enterococci and staphylococci to the antimicrobial gentamicin. For use with MicroScan® Synergies plus™ Panels read on the WalkAway® -SI System (including upgraded WalkAway® -40 or WalkAway® -96 to meet WalkAway® SI equivalence). 2. Indication(s) for use: 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. The testing of gentamicin at concentrations of 0.06 – 2 µg/mL on the MicroScan® Synergies plus™ Gram-Positive MIC/Combo Panel is indicated for testing staphylococci at 4.5-16 hours or 16-20 hours for an overnight reading. The Gram-positive organisms which may be tested on this panel are Staphylococcus species (coagulase-positive and coagulase-negative). 3. Special conditions for use statement(s): 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 a very small amount (0.1%) of Pluronic®--a wetting agent), then 0.1 mL transferred to 25 mL of inoculum Synergies plus Pos Broth with Pluronic® for a final inoculum concentration of 3-7 X 10⁵ CFU/mL. Panels are incubated in a Walk-Away® System and read periodically starting at 4.5 hours until sufficient growth to determine the MIC (Minimum Inhibitory Concentration). Alternately, the panels may be incubated at 35°C in a non-CO₂ for 16-24 hours and read by visual observation of growth. 2 {2} J. Substantial Equivalence Information: 1. Predicate device name(s): MicroScan® Dried Gram-Positive MIC/Combo Panels and MicroScan® Synergies plus™ 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 | <16 hours 16 – 24 hours | Same | | Results | Quantitative with qualitative interpretations | Same | | Technology | Growth based | Same | | Differences | | | | Item | Device | Predicate | | Panels | Dried gentamicin in water | Dried clindamycin or gentamicin in broth | | Reading | Uses both a ≤ 16 hour 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 | | Instrument | WalkAway® -SI System or equivalent | autoScan® -4 or WalkAway® | | Antibiotic | Gentamicin at 0.06 –2 μg/mL | Different concentrations depending on the antibiotic | {3} 4 K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Guidance for Industry and FDA”; Clinical and Laboratory Standards Institute (CLSI) M7 (M100-S16) “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 or 18 hours (overnight instrument readings, manual readings) 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): Data on the gram-positive panel for Gentamicin at $0.06 - 2\ \mu\mathrm{g/mL}$ were evaluated. The Synergies plus™ readings were obtained at times between 4.5 and 16 hours of incubation (Rapid read method). An additional comparison was done with readings on the instrument after 16 – 18 hours incubation for the Overnight Instrument read method, and also for the Overnight Manual read method, when incubated 16- 18 hours and read visually. This submission is for the AST Panel only. The ID System was not reviewed. 1. Analytical performance: a. Precision/Reproducibility: Reproducibility was demonstrated using 10 isolates tested at 3 sites on 3 separate days in triplicate. The study included the testing on the WalkAway® SI read at <16 hours, WalkAway® 16-18 hour readings and manual readings at 16-20 hours incubation. All results were >95% reproducible for all reading methods. There appears to be a slight trend for the Rapid read method to produce more resistant results. b. Linearity/assay reportable range: Not Applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): The recommended QC isolate was tested a sufficient number of times with acceptable results on most testing days with the reference method. The percent QC results that did not grow in the 4.5-16 hour window was $0\%$ for the *E. faecalis* ATCC 29212 and $2\%$ for the *S. aureus* ATCC 29213. {4} Quality control results demonstrated the ability of the different reading parameters (manual and instrument) to produce acceptable results >95% of the time for the Rapid Read Method. The following table provides the frequency of the results in each concentration with the expected range stated. | Results | | | | | | | | --- | --- | --- | --- | --- | --- | --- | | Organism | Conc in μg/mL | # reference | MicroScan® | | | | | | | | Manual overnight | Instrument overnight | < 16 hours instrument | | | E. faecalis ATCC 29212 Range 4—16 μg/mL | 1 | | | | | | | | 2 | | | | | | | | 4 | 1 | 55 | | 6 | | | | 8 | 39 | 56 | 110 | 99 | | | | 16 | 65 | 1 | 1 | 5 | | | | 32 | | | | 1 | | | | >32 | | | | | | | Results | | | | | | | | Organism | Conc in μg/mL | # reference | MicroScan® | | | | | | | | Manual overnight | Instrument overnight | < 16 hours instrument | | | S. aureus ATCC 29213 Range 0.12—1 μg/mL | 0.12 | | | | | | | | 0.25 | 2 | 2 | 1 | 1 | | | | 0.5 | 46 | 86 | 84 | 88 | | | | 1 | 47 | 9 | 8 | 7 | | | | 2 | | 1 | 2 | 2 | | | | 4 | | 2 | 3 | 1 | | | | 8 | | | 1 | 1 | | | | 16 | | | | | | | | 32 | | | | | | | | >32 | | | 1 | | | E. faecalis ATCC 29212 QC performance: The modes each of the reading methods for the Microscan results are more susceptible than the mode for the reference method result, if only by one dilution. S. aureus ATCC 29213 QC performance: The modes each of the reading methods for the Microscan results are more susceptible than the mode for the reference method result, if only by one dilution. There were 93.8% (92/99) test panel in range results for the Instrument Overnight reading method due to "skipped wells", which were verified manually. The test panel in range results for the Rapid read method and the Manual Overnight read method were both >95% acceptable, respectively. No QC trending was observed. Inoculum density control: A turbidity meter was used for the turbidity inoculation {5} 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 3 sites. A total of 301 Clinical Gram-positive isolates were tested of which 267 were fresh isolates and 34 were stock isolates. Four (4) isolates were reported at >= 16 hours and were not included as Rapid read results. Therefore, of the 301 isolates tested, 297 Rapid read Long Dilution isolates were analyzed. There were 75 challenge isolates tested at one site and compared to the reference broth dilution result mode that was determined by previous testing of each isolate multiple times in the recommended reference panel. The Synergies plus™ readings were obtained at times between 4.5 and 16 hours of incubation for >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. Performance by these alternate reading methods was also acceptable with no apparent differences or trends. The recommended CLSI reference method was followed with the exception of the use of a small amount (0.1%) Pluronic® (a wetting agent) 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. QC was also performed with no difference apparent in the results. The chart below demonstrates the performance of all three reading methods (Synergies plus™ readings at <16 hours, overnight on the WalkAway® and manually read at 18 hours using the touchScan®-SR) when compared to the reference method. Clinical and Challenge Data – Read Method comparison for Gentamicin | | Total | EA | %EA | Total evaluable | EA of evaluable | Eval % EA | CA | %CA | #R | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | <16 hr Rapid | 370 | 351 | 94.9 | 285 | 271 | 95.1 | 357 | 96.5 | 73 | 11 | 0 | 2 | | Overnight instrument | 376 | 367 | 97.6 | 287 | 279 | 97.2 | 364 | 96.8 | 73 | 11 | 1 | 0 | | Overnight Manual | 376 | 369 | 98.1 | 290 | 284 | 97.9 | 370 | 98.4 | 73 | 6 | 0 | 0 | {6} EA-Essential Agreement CA-Category Agreement R-resistant isolates maj-major discrepancies vmj-very major discrepancies min- minor discrepancies Essential agreement (EA) is when the MicroScan® Synergies plus panel agrees with the reference test panel results exactly or within one doubling dilution of the reference method. Category agreement (CA) is when the MicroScan® Synergies plus panel interpretation agrees exactly with the reference panel interpretation. Evaluable (Eval) are results that are within the test range and on scale. The device had a growth rate of >95%. Of the 75 Challenge isolates tested, the expected results for 39 strains were Susceptible, 3 strains were Intermediate, and 33 strains were Resistant. There were 4 minor errors (4/73, 5.5%) generated in the Challenge Set data, using the <16 hr Rapid reading method, but there were no vmj or maj errors produced. The overall combined EA and the CA for the Clinical and Challenge Set data were >90% for all read methods, and the overall performance data are acceptable. Performance claims (in bold) that will appear in the labeling and the procedural manual are based on the Clinical data Rapid read (<16 hour) method results only. The table below displays the clinical data results compared by reading method. Clinical Data Read Method comparison - Gentamicin | | Total | EA | %EA | Total evaluable | EA of evaluable | Eval % EA | CA | %CA | #R | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | <16 hr Rapid | 297 | 281 | 94.6 | 244 | 233 | 95.5 | 288 | 97.0 | 40 | 7 | 0 | 2 | | Overnight instrument | 301 | 294 | 97.7 | 244 | 237 | 97.1 | 291 | 96.7 | 40 | 10 | 0 | 0 | | Overnight Manual | 301 | 296 | 98.3 | 247 | 242 | 98.0 | 296 | 98.3 | 40 | 5 | 0 | 0 | The Clinical data Rapid read method EA of 94.6% and the CA of 97.0% are both very good. Overnight Instrument and Manual read methods EA and CA are both similar to the Rapid read method results for the Long Dilution data. The 2 vmj (2/40, 5%) were generated by two S. aureus isolates tested at two different sites generated by the Rapid read method. Because of the low number of resistant isolates, the overall vmj error rate appears to be elevated. Further analysis of these 2 isolates demonstrated that there appeared to be a problem with the entire antibiogram. There appears to be a slight trend for the device to produce more susceptible results as compared to the reference method. This trend was not noted in the reproducibility data, where the results for the <16 hour readings were slightly more resistant. {7} 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: Staphylococcus spp. interpretive criteria: <= 4 (S), 8 (I), >= 16 (R) The interpretative criteria and Quality Control Ranges values are included in the package insert. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. Performance characteristic claims that will be added to the Procedural Manual and to the labeling were based on the clinical data Rapid read (<16 hour) method results only. O. Conclusion: The submitted information in this premarket notification is complete and does support a substantial equivalence decision. --- **Source:** [https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K063365](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K063365) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. 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