← Product Code [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON) · K031602 # MICROSCAN SYNERGIES PLUS GRAM NEGATIVE MIC/COMBO PANELS WITH NITROFURANTOIN (1-256 UG/ML) (K031602) _Dade Behring, Inc. · LON · Jul 31, 2003 · Microbiology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K031602 ## Device Facts - **Applicant:** Dade Behring, Inc. - **Product Code:** [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON.md) - **Decision Date:** Jul 31, 2003 - **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-Negative 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-negative bacilli. 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® Instrumentation. Additionally, the panels may be incubated in a non-CO2 incubator and the AST portions can be read visually, according to the Package Insert. ## Device Story MicroScan Synergies plus Gram-Negative MIC/Combo Panels are miniaturized broth dilution susceptibility tests. Panels contain dehydrated antimicrobial agents in Mueller-Hinton broth. Clinical laboratory technicians inoculate panels with standardized bacterial suspensions; panels are rehydrated with water. Incubation occurs in WalkAway SI system or equivalent (4.5-18 hours at 35°C). Device determines Minimum Inhibitory Concentration (MIC) by identifying the lowest antimicrobial concentration inhibiting bacterial growth. Results are read via MicroScan instrumentation or visual inspection. Data assists clinicians in selecting appropriate antibiotic therapy for gram-negative infections, potentially improving patient outcomes by ensuring effective treatment. ## Clinical Evidence Bench testing only. Study compared MicroScan results to NCCLS M7 reference broth dilution method using 531 clinical isolates and 60 challenge organisms. Primary endpoints were Essential Agreement (EA) and Category Agreement (CA). Combined <16-hour results showed 99% EA and 87.1% CA. Reproducibility study across three sites showed >95% reproducibility. No major or very major errors observed in overnight (≥16h) readings. Minor errors noted near interpretive cutoffs. ## Technological Characteristics Miniaturized broth microdilution panels; dehydrated antimicrobial agents in Mueller-Hinton broth; rehydrated with water. Incubation at 35°C +/- 1°C. Compatible with WalkAway SI automated instrumentation or visual reading. Analyzes gram-negative bacilli susceptibility to Nitrofurantoin (1-256 µg/ml). ## 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® rapID/S plus™ Gram Negative MIC/Combo Panels -gentamicin ([K020185](/device/K020185.md)) ## 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} 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY DEVICE ONLY TEMPLATE A. 510(k) Number: k031602 B. Analyte: Nitrofurantoin 1-256 ug/ml AST C. Type of Test: Quantitative <16 hour growth based with Colorimetric Optics System D. Applicant: Dade Behring Inc. E. Proprietary and Established Names: MicroScan® rapID/S plus™ Gram-Negative MIC/Combo Panels F. Regulatory Information: 1. Regulation section: 866.1645 Short-Term Antimicrobial Susceptibility Test System 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product Code: LON System, Test, Automated, Antimicrobial Susceptibility, Short Incubation JWY Manual Antimicrobial Susceptibility Test Systems LRG Instrument for auto reader & Interpretation of Overnight Susceptibility System 4. Panel: 83 Microbiology G. Intended Use: 1. Intended use(s): For use with MicroScan rapID/S plus™ panels read on the WalkAway® -SI System or equivalent (upgraded WalkAway® -40 or WalkAway® -96). 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 gram-negative bacilli. (Enterobacteriaceae, glucose non-fermenters, and non-Enterobacteriaceae glucose fermenters). 2. Indication(s) for use: The MicroScan® rapID/S plus™ Gram-Negative 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-negative bacilli. After inoculation, panels are incubated for 4.5-18 hours at 35°C +/- 1°C, in a WalkAway SI or equivalent, and read by MicroScan® Instrumentation. Additionally panels may be incubated in a non-CO² incubator and the AST portions can be read visually according to the Package Insert. Nitrofurantoin at concentrations of 1-256 ug/ml will be added {1} Page 2 of 5 to the gram negative test panel for testing Enterobacteriaceae at less than (<)16 hours or greater than (>)16 hours for an overnight reading. 3. Special condition for use statement(s): A comment will follow for all appropriate organism that states “Due to expected natural resistance to Nitrofurantoin, Rapid and Overnight MIC and interpretive results with Morganella morganii, Proteus spp., Providencia spp. or Serratia spp. will not be reported in the Software or patient reports”. 4. Special instrument Requirements: H. Device Description: The MicroScan® rapID/S plus™ Panel contains microdilutions of each antimicrobic in various concentrations on dehydrated and dried panels with Mueller Hinton Broth and various nutrients. Each panel contains two control wells: a no-growth control well (contains water only/no nutrients or broth), and a growth control well (contains test medium without antibiotic). The panel is rehydrated and inoculated at the same time with 0.1 ml of suspension prepared by the turbidity method (inoculum prepared in water, then 0.1ml transferred to 25ml of inoculum water containing pluronic-D/F-a wetting solution). I. Substantial Equivalence Information: 1. Predicate device name(s): MicroScan® rapID/S plus™ Gram Negative MIC/Combo Panels -gentamicin 2. Predicate K number(s): K020185 3. Comparison with predicate: | Similarities | | | | --- | --- | --- | | Item | Device | Predicate | | specimen | Isolated colonies from culture used | Isolated colonies from culture used | | Inoculum | Inoculum density to 0.5 McFarland standard | Inoculum density to 0.5 McFarland standard | | Incubation | <16 hours instrument read ≥ 16 hours instrument read or manual read | < 16 hours instrument read ≥ 16 hours instrument read or manual read | | results | Quantitative with qualitative interpretations | Quantitative with qualitative interpretations | | Differences | | | | Item | Device | Predicate | | panels | Dried nitrofurantoin at 1-256 ug/ml | Dried gentamicin at 0.12-32 ug/ml | J. Standard/Guidance Document Referenced (if applicable): “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA”; NCCLS M7 (M100-S13) {2} Page 3 of 5 "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard" ## K. 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, 10, 12, 16, or 18 hours (overnight instrument readings, manual readings) depending on the growth rate of the organism being tested. The initial read is subtracted from the final read to minimize variations from all components of the system. The time of final read is dependent on 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. Reading considerations are built into the reading for faster growing and slower growing organisms. Organisms that do not reach a specific threshold at 4.5 hours have the minimum threshold raised at 5.5 hours. This allows for fermenters (faster grower organisms) to be read at 4.5, 5.5 or 6.5 hours and delay the reading of non-fermenters (slow growing) to 8, 10, 12 and up to 16 hours. If there is insufficient amount of growth at 16 hours the panels will be held an additional amount of time to determine an overnight reading. ## L. Performance Characteristics (if/when applicable): ### 1. Analytical performance: a. Precision/Reproducibility: A study was conducted on twenty five on-scale organisms tested one time at three different sites. These were read on the MicroScan® rapID/S plus™ Gram-Negative MIC panels at <16 hours, overnight (>16 hours) read manually or on the WalkAway SI system. All results were >95% reproducible with the mode of the test result. b. Linearity/assay reportable range: Not applicable c. Traceability (controls, calibrators, or method): The recommended QC isolate was tested with acceptable results on all testing days with the reference method. The percent of E. coli ATCC 25922 that did not grow in time for the <16 hour reading was 2.7%. The results for the manual readings (Man) and the overnight instrument (≥ 16) readings were all acceptable. | ORGANISM | | RESULTS | | | | | --- | --- | --- | --- | --- | --- | | | Conc in ug/ml | # reference | MicroScan | | | | | | | Man | ≥16 h | <16h | | E. coli ATCC 25922 Range 4-16 | 2 | | | | | | | 4 | | | | 4 | | | 8 | 108 | 109 | 110 | 105 | | | 16 | 1 | 3 | 2 | | | | 32 | | | | | Inoculum Density checks were controlled using turbidity meter. Colony counts were also performed weekly. {3} 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: Broth dilution reference panels prepared according to the recommendations of the NCCLS M7. Clinical testing was performed at three sites on 531 isolates using the turbidity inoculum method for testing. This group had a "no growth" rate of $1.5\%$ at $< 16$ hour read time but were available at a later read time. The table below presents the results of the remaining Enterobacteriaceae after excluding the organisms listed in the limitation statement that MicroScan does not claim for testing with nitrofurantoin. The $< 16$ hour results demonstrated trending with more values one well more susceptible when compared to the reference method. A set of sixty challenge organisms were tested at one site. The performance of those that read at $< 16$ hours is included in the table below. There were a large number of minor errors which is reflected by the large number of results that are near the interpretive cutoffs (evaluable results). These have very good essential agreement (plus or minus one well of the reference method) but most of the minor errors had a MIC on the MicroScan® rapID/S plus™ more susceptible than the reference by one serial dilution of nitrofurantoin. The summary chart of $< 16$ hour readings of Enterobacteriaceae | | total | EA | %EA | Total evaluable | EA of evaluable | %EA | CA | %CA | #R | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Clinical | 523 | 519 | 99.2 | 514 | 512 | 99.6 | 457 | 87.4 | 64 | 66 | 0 | 0 | | Challenge | 60 | 58 | 96.7 | 60 | 58 | 96.7 | 51 | 85 | 6 | 9 | 0 | 0 | | Combined | 583 | 577 | 99 | 574 | 570 | 99.3 | 508 | 87.1 | 70 | 75 | 0 | 0 | EA-Essential Agreement CA-Category Agreement R-resistant isolates maj-major discrepancies vmj-very major discrepancies min-minor discrepancies The challenge set of organisms were also evaluated with the $\geq 16$ hour readings performed on the WalkAway and also manual readings. This performance was at least as good as the $< 16$ hour readings with no major or very major errors. The comparison to the expected result demonstrated that although there was very good essential agreement for all reading methods the $< 16$ hour readings were read as more susceptible as compared to the expected result than any other method. The chart below demonstrates that when the same isolates are tested on all three reading methods the rapid results more frequently produce a more susceptible result while still performing in essential agreement to the expected reference method result. The table below demonstrates that the $\geq 16$ hour {4} Page 5 of 5 instrument readings and the $\geq 16$ hour manual readings were in exact agreement with the expected about $80\%$ and $87\%$ of the time respectively while the $<16$ hour readings were in exact agreement about $63\%$ of the time with the rest of the result falling in the more susceptible range. | | Two dilution more susceptible | One dilution more susceptible | Exact agreement with reference method | One dilution more resistant | | --- | --- | --- | --- | --- | | <16 hour | 2 | 20 | 38 | | | ≥ 16 hour | | 5 | 48 | 7 | | ≥ manual | | 6 | 52 | 2 | 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): 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: $\leq 32$ (S); $64$ (I); $\geq 128$ (R) These interpretive criteria, the quality control organisms and their expected value range are the same as that recommended in the NCCLS M7 and will be included in the package insert. M. Conclusion: This demonstrates that the MicroScan® rapID/S plus™ gram negative panels with nitrofurantoin at 1-256 ug/ml are substantially equivalent to the predicate when compared to the reference method as recommended in the “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA” --- **Source:** [https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K031602](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K031602) **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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