← Product Code [JWY](/productcode/JWY) · K170772 # Liofilchem MIC Test Strip (MTS)- Clindamycin 0.016 - 256 µg/mL (K170772) _Liofilchem s.r.l. · JWY · Jun 7, 2017 · Microbiology · SESE_ **Canonical URL:** https://fda-staging.innolitics.com/device/K170772 ## Device Facts - **Applicant:** Liofilchem s.r.l. - **Product Code:** [JWY](/productcode/JWY.md) - **Decision Date:** Jun 7, 2017 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 866.1640 - **Device Class:** Class 2 - **Review Panel:** Microbiology ## Indications for Use The Liofilchem® MIC Test Strip (MTS) is a quanttative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minibitory concentration (MIC) in ug/mL of antimiorobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Clindamycin MTS at concentrations of 0.016-256 ug/mL should be interpreted at 16-20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and in vitro against Clindamycin according to the FDA label are: Staphylococcus aureus (methicillin-susceptible strains) ## Device Story Liofilchem MIC Test Strip (MTS) is a quantitative diagnostic tool for determining antimicrobial susceptibility. Device consists of specialized paper strips impregnated with a predefined concentration gradient of Clindamycin (0.016–256 μg/mL). Used in clinical microbiology laboratories by trained personnel. Procedure involves placing the strip onto inoculated agar media, followed by 16–20 hours of overnight incubation. The MIC is determined via manual reading of the inhibition ellipse intersection with the strip. Results assist clinicians in selecting appropriate antibiotic therapy for patients with bacterial infections. Benefits include precise MIC determination to guide effective treatment and improve patient outcomes. ## Clinical Evidence No clinical data provided. Substantial equivalence is supported by bench testing comparing the performance of the Clindamycin MTS to standard broth microdilution reference methods. Testing evaluated essential agreement and categorical agreement across a range of bacterial isolates. ## Technological Characteristics Specialized paper strip impregnated with clindamycin gradient (0.016–256 µg/mL). Manual reading of inhibition ellipse on Mueller Hinton agar. Incubation: 35±2°C for 16-20 hours. No electronic components, software, or energy source. Complies with CLSI M07-A10 and M100-S26 standards. ## Regulatory Identification An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases. ## Predicate Devices - Liofilchem MTS, vancomycin ([K153687](/device/K153687.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 A. 510(k) Number: K170772 B. Purpose for Submission: To obtain a substantial equivalence determination for the Liofilchem MIC Test Strip (MTS) containing clindamycin at concentrations of 0.016 -256 µg/mL for susceptibility testing of *Staphylococcus aureus* C. Measurand: Clindamycin 0.016-256 µg/mL D. Type of Test: Quantitative AST growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Clindamycin 0.016-256 µg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Test Systems 4. Panel: {1} 83 – Microbiology ## H. Intended Use: ### 1. Intended use(s): The Liofilchem MIC Test Strip (MTS) is a quantitative method intended for the *in vitro* determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in $\mu \mathrm{g} / \mathrm{mL}$ of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Clindamycin MTS at concentrations of $0.016 - 256\ \mu \mathrm{g/mL}$ should be interpreted at 16-20 hours of incubation. The non-fastidious bacteria that have been shown to be active both clinically and *in vitro* against Clindamycin according to the FDA label are: *Staphylococcus aureus* (methicillin-susceptible strains) ### 2. Indication(s) for use: Same as Intended Use ### 3. Special conditions for use statement(s): For prescription use ### 4. Special instrument requirements: Manual reading only ## I. Device Description: The clindamycin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of clindamycin across 15 two-fold dilutions like those of a conventional MIC method. One side of the strip is labelled with the clindamycin code (CD) and the MIC reading scale in $\mu \mathrm{g} / \mathrm{mL}$. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of $\mu \mathrm{g} / \mathrm{mL}$ at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. {2} # J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate $510(\mathbf{k})$ number(s): K153687 3. Comparison with predicate: Table 1: Comparison with the Predicate Device | Similarities | | | | --- | --- | --- | | Item | Device | Predicate Liofilchem MTS, vancomycin K153687 | | Intended Use | Quantitative susceptibility to antimicrobial agents | Same | | Media | Mueller Hinton agar | Same | | Inoculation | Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum | Same | | Reading | Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip | Same | | Result | MIC | Same | | Differences | | | | --- | --- | --- | | Item | Device | Predicate | | Antibiotic | Clindamycin (CD) | Vancomycin (VA) | | Incubation | 35 ± 2°C for 16 - 20hrs | 35 ± 2°C for 24 hours | # K. Standard/Guidance Document Referenced: "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA" CLSI M07-A10 "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015" CLSI M100-S26 "Performance Standards for Antimicrobial Susceptibility Testing; Twenty- {3} Fifth Informational Supplement, January 2016" L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions like those of a conventional MIC method. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of $\mu \mathrm{g} / \mathrm{mL}$ at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. Growth along the entire gradient (i.e. no inhibition ellipse) indicates that the MIC value is greater than or equal to $(\geq)$ the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than $(<)$ the lowest value. An MIC of $0.125\mu \mathrm{g} / \mathrm{mL}$ is considered to be the same as $0.12\mu \mathrm{g} / \mathrm{mL}$ for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was performed using ten Staphylococcus aureus isolates. These ten isolates were tested at three sites in triplicates on three days. The mode of MIC value was determined and the reproducibility was calculated based on the number of MIC values that fell within $\pm 1$ doubling dilution of the mode. The testing resulted in overall reproducibility of greater than $95\%$. The results were acceptable. 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 (i.e., at least 20/site) at all three sites with acceptable results in comparison to the reference method. All results were within the expected range greater than $95\%$ of the time. The results are summarized in Table 2 below. {4} 5 Table 2: Clindamycin MTS QC results | Organism | Concentration (μg/mL) | Reference | MTS | | --- | --- | --- | --- | | S. aureus | 0.03 | | | | ATCC 2213 | 0.06 | 16 | 4 | | Expected Result | 0.12 | 42 | 50 | | 0.06 – 0.25μg/mL | 0.25 | 3 | 7 | The inoculum was prepared to achieve a 0.5 McFarland standard turbidity. Colony counts were performed periodically at each site. Inoculum density checks were performed and the average colony counts of each QC strain were within the recommended range of approximately $1 \times 10^{8}$ CFU/mL. 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 (two U.S. and one non-U.S. sites). A total of 350 organisms were tested and all organisms grew in the studies. There were 251 (71.7%) isolates that were tested within seven days of collection and 99 (28.3%) isolates that were tested within one year of collection. The 350 organisms were 200 MSSA and 150 MRSA clinical isolates. There were also 75 challenge Staphylococcus aureus (11 MSSA and 64 MRSA) which result a total of 425 clinical and challenge isolates. Results obtained with Liofilchem MIC Test Strip (MTS) with Clindamycin were compared to results obtained from frozen reference MIC panels. Reference panels were prepared and interpreted as outlined in CLSI recommendations in M7-A10. Isolated colonies from an overnight blood agar plate were suspended in saline to achieve a 0.5 McFarland standard turbidity (approximately $10^{8}$ CFU/mL). Testing conditions consisted of incubation of the inoculated Mueller Hinton agar plates in and inverted position at $35^{\circ}\mathrm{C} \pm 2$ for 16-20 hours. At the end of incubation, the MIC value where the edge of the inhibition ellipse intersects the strip was compared to the {5} reference method. Clindamycin is bacteriostatic; MIC is read at 80% inhibition. The performance is listed in Table 3 below: Table 3: Performance of Staphylococcus aureus isolates* | Clindamycin | EA Tot | EA N | EA % | Eval. EA Tot | Eval. EA N | Eval. EA % | CA N | CA % | #R | min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Staphylococcus spp. ≤0.5 (Susceptible), 1-2 (Intermediate), ≥4 (Resistant) | | | | | | | | | | | | | MSSA | | | | | | | | | | | | | | Clinical | 200 | 196 | 98.0 | 191 | 187 | 97.9 | 200 | 100 | 9 | 0 | 0 | 0 | | Challenge | 11 | 11 | 100 | 9 | 9 | 100 | 11 | 100 | 3 | 0 | 0 | 0 | | Combined | 211 | 207 | 98.1 | 200 | 196 | 98.0 | 211 | 100 | 12 | 0 | 0 | 0 | | MRSA | | | | | | | | | | | | | | Clinical | 150 | 146 | 97.3 | 117 | 113 | 96.6 | 149 | 99.3 | 35 | 1 | 0 | 0 | | Challenge | 64 | 61 | 95.3 | 33 | 30 | 90.9 | 63 | 98.4 | 38 | 1 | 0 | 0 | | Combined | 214 | 207 | 96.7 | 150 | 143 | 95.3 | 212 | 99.1 | 73 | 2 | 0 | 0 | | Total S. aureus | 425 | 414 | 97.4 | 350 | 339 | 96.9 | 423 | 99.5 | 85 | 2 | 0 | 0 | *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 Liofilchem MIC Test Strip (MST) results agree exactly or within one doubling dilution of the reference broth microdilution results. Category Agreement (CA) is when the Liofilchem MIC Test Strip (MST) result interpretation agrees exactly with the reference broth microdilution result interpretation. The indicated methicillin-susceptible Staphylococcus aureus (MSSA) included twelve clindamycin resistant isolates. Methicillin-resistant Staphylococcus aureus (MRSA) was included to enhance the clindamycin resistant isolates for evaluation with a total of 85 resistant isolates. The clindamycin breakpoints in the FDA drug label are for the genus Staphylococcus spp. and there are no separate breakpoints for MRSA/MSSA. Therefore, the Staphylococcus spp. breakpoint was used for evaluation of performance for both MSSA and MRSA. Similar performance was observed for MRSA and MSSA. The overall performance of Staphylococcus aureus was acceptable with EA 97.4% EA and 99.5% CA. There were no major or very major discrepancies. ## Trending Staphylococcus aureus was also evaluated for trending. This trending calculation takes into account MIC values that are determined to be ≤1 and ≥1 doubling-dilutions compared to the reference method irrespective whether the device MIC values are on-scale or not. The analysis showed that within EA, trending was observed for Staphylococcus aureus. The trending analysis was shown in Table 4: {6} 7 Table 4: Trending Analysis of Evaluable Clinical and Challenge Results | Clindamycin 0.016- 256 μg/mL | Total^{a} | Difference in MIC as Compared to the CLSI Reference Method | | | | | | --- | --- | --- | --- | --- | --- | --- | | | | ≥2 dil. lower | 1 dil. lower | Exact | 1 dil. higher | ≥2 dil. higher | | S. aureus MSSA+MRSA | 352 | 3 | 21 | 167 (47.44%) | 153 | 8 | | | | 24 (6.82%)^{b} 95% CI (4.62% to 9.94%) | | | 161 (45.74%)^{b} 95% CI (40.61% to 50.96%) | | a Total number of evaluable results for trending analysis b Difference: -38.92%; 95% CI (-44.59% to -32.91%) A higher MIC reading trend was observed in the overall performance of Staphylococcus aureus (MSSA+MRSA) compared to the CLSI broth microdilution reference method, which raises concerns for potential major discrepancy. This trending and the potential for occurrence of major discrepancies were addressed by adding the following footnote in the Performance Characteristics section of the labeling, "Drug Specific Supplement for Clindamycin MIC Test Strip (MTS)": "The Liofilchem MIC Test Strip (MTS) clindamycin values tended to be in exact agreement or at least one doubling dilution higher when testing S. aureus compared to the CLSI reference broth microdilution." 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 {7} # 5. Expected values/Reference range: Table 5: FDA Interpretive Criteria for Clindamycin $\left( {\mu \mathrm{g}/\mathrm{{mL}}}\right)$ | Organisms | S | I | R | | --- | --- | --- | --- | | Staphylococcus aureus | ≤0.5 | 1-2 | ≥4 | Because macrolide-inducible resistance to clindamycin occurs in some isolates of macrolide-resistant bacteria, macrolide-resistant Staphylococcus aureus isolates should be screened for induction of clindamycin resistance using Inducible Clindamycin Resistance Supplemental Test. The footnote below is included under the clindamycin interpretative criteria section: "Inducible clindamycin resistance supplemental test is required for Staphylococcus aureus isolates that test erythromycin resistant and clindamycin susceptible or intermediate before reporting the isolate as clindamycin susceptible (CLSI M100 S26)." # N. Proposed Labeling: The labeling is sufficient and it 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. --- **Source:** [https://fda-staging.innolitics.com/device/K170772](https://fda-staging.innolitics.com/device/K170772) **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. If you're preparing [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/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com