VITEK 2 GRAM POSITIVE ERYTHROMYCIN FOR STREPTOCOCCUS PNEUMONIAE

{0} 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY DEVICE ONLY TEMPLATE A. 510(k) Number: k083383 B. Purpose of Submission: Addition of Erythromycin intermediate category to the VITEK®2 and VITEK®2 Compact Systems Antimicrobial Susceptibility Test (AST) System C. Measurand Erythromycin ≤ 0.25 - ≥ 1 µg/mL D. Type of Test: Qualitative growth based detection algorithm using predetermined growth thresholds E. Applicant: bioMerieux, Inc. F. Proprietary and Established Names: VITEK®2 Gram Positive Erythromycin G. Regulatory Information: 1. Regulation section: 866.1645 Short-Term Antimicrobial Susceptibility Test System 2. Classification: II 3. Product Code: LON System, Test, Automated, Antimicrobial Susceptibility, Short Incubation 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): The VITEK®2 Antimicrobial Susceptibility Test is intended to be used with the VITEK®2 System for the automated quantitative or qualitative susceptibility testing of isolated colonies for most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus agalactiae, and S. pneumoniae. The VITEK®2 Gram Positive Susceptibility Card is intended for use with the VITEK®2 system in clinical laboratories as an in vitro test to determine the susceptibility of Streptococcus pneumoniae to antimicrobial agents when used as instructed in the Online Product Information. {1} 2. Indication(s) for use: VITEK® 2 Gram Positive Erythromycin for *Streptococcus pneumoniae* is designed for antimicrobial susceptibility testing of gram positive *Streptococcus pneumoniae* and is intended for use with the VITEK® 2 and the VITEK® 2 Compact Systems as a laboratory aid in the determination of *in vitro* susceptibility to antimicrobial agents. VITEK® 2 Gram Positive Erythromycin for *Streptococcus pneumoniae* is a qualitative test. This submission is for the addition of intermediate interpretive criteria to the VITEK® 2 Gram Positive Erythromycin for *Streptococcus pneumoniae* at a concentration of 0.06, 0.125, and 0.25 µg/mL and a calling range of ≤0.25, and ≥ 1 µg/mL which includes an intermediate breakpoint with a discrete call of 0.5. 3. Special condition for use statement(s): Prescription use only The ability of the VITEK® 2 system to detect intermediate isolates of *Streptococcus pneumoniae* with erythromycin is unknown because intermediate organisms were not available at the time of comparative testing. Intermediate strains for *Streptococcus pneumoniae*/Erythromycin are very rare. 4. Special instrument Requirements: Not applicable I. Device Description: The VITEK® 2 AST card containing the test is inoculated with a standardized organism suspension. The card is incubated within the instrument and optically monitored throughout the incubation cycle. Results are automatically calculated once a predetermined growth threshold is reached and a report is generated that contains the final result. J. Substantial Equivalence Information: 1. Predicate device name(s): VITEK® 2 Gram Positive Telithromycin for *Streptococcus pneumoniae* 2. Predicate K number(s): k053186 3. Comparison with predicate {2} | Similarities | | | | --- | --- | --- | | Item | Device | Predicate | | Intended Use | Determine antimicrobial susceptibility to antimicrobial agents | Same | | Instrument | VITEK®2 System | Same | | Test Card | VITEK®2 card, including the base broth | Same | | Test organism | Colonies of Gram-Positive cocci | Same | | Differences | | | | Item | Device | Predicate | | Antibiotic | Erythromycin at specific concentrations | Telithromycin at specific concentrations | | Reading algorithm | Unique for erythromycin | Unique for telithromycin | # K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA"; CLSI M7 (M100-S18) "Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard". # L. Test Principle: The VITEK®2's Optics systems use visible light to directly measure organism growth. This transmittance optics is based on an initial light reading of a well before significant growth has begun. Periodic light transmittance samplings of the same well measure organism growth by how much light is prevented from going through the well. An interpretive call is made between 4 and 16 hours for a "rapid" read but may be extended to 18 hours in some instances. The VITEK®2 Susceptibility Card test is based on the microdilution minimum inhibitory concentration technique with concentrations equivalent to standard method concentrations. Several parameters based on the growth characteristics observed are used to provide appropriate input for the MIC calculations. Discriminate analysis is used to develop the algorithm that determines the susceptibility result for all antimicrobials on the VITEK®2 system. The MIC result must be linked to organism identification in order to determine a category interpretation. A category interpretation (SIR) will be reported along with a MIC. # M. Performance Characteristics (if/when applicable): # 1. Analytical performance: The data included in this submission were acquired during the clinical studies performed at multiple sites. There have been no changes to the AST formulation or intended use since the VITEK®2 Gram Positive Erythromycin for S. pneumoniae test was cleared under k063492. The analysis was modified to conform to standard practice of reporting results for all available {3} FDA breakpoints for an antibiotic/organism combination. The clinical trial data submitted as part of k063492 was re-analyzed using the modified algorithm analysis. The Reproducibility, QC and clinical studies was performed in the previous submission (k063492) and was not performed for this submission because the drug formulation has not changed. a. Precision/Reproducibility: Ten strains of Streptococcus pneumoniae were tested at three sites in triplicate on three days with the VITEK®2 AST-GP Erythromycin. This testing was performed using both the manual dilution and also the automatic dilution method. Acceptable reproducibility was demonstrated with only category agreement (S, R) since that is all that is detected. b. Linearity/assay reportable range: Not applicable c. Traceability (controls, calibrators, or method): The recommended QC isolate was tested on every test occasion with the reference method and the VITEK®2. The reference method QC results were in range for every day tested. The VITEK®2 was tested a sufficient number of times to demonstrate that the system can produce QC results in the recommended range. Quality Control was performed during the studies using both the auto-dilution and the manual method of diluting the organisms. Results demonstrated that methods were comparable with the same mode. | ORGANISM | VITEK®2 Conc. (ug/mL) | VITEK®2 AUTO-DIL | VITEK®2 MAN-DIL | Reference Conc. (ug/mL) | Reference | | --- | --- | --- | --- | --- | --- | | | | | | | | | S. pneumoniae | ≤0.25 | 79 | 79 | ≤0.03125 | 41 | | ATCC 49619 | | | | 0.0625 | 19 | | Expected Range: | | | | 0.125 | 19 | | 0.03125 – 0.125 μg/mL | | | | | | | | | | | | | Inoculum density control was monitored using the DensiChek instrument. This was standardized weekly with all results recorded and in the expected range. Verification was performed during internal testing. d. Detection limit: {4} Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable ## 2. Comparison studies: a. Method comparison with predicate device: A clinical study was conducted at three sites using the VITEK®2 gram positive cards with erythromycin and the broth microdilution method using Mueller Hinton (MH) broth with lysed horse blood prepared as recommended by CLSI. Inoculum was prepared with direct colony suspension. The testing included both fresh clinical isolates and stock isolates along with a challenge set with known results. Two methods of inoculation (manual and automated) were evaluated. Clinical testing was performed using the automated method of inoculation and the challenge set was tested using both the manual and the automated method. The test device had a growth rate of >90%. Essential agreement was not calculated because the VITEK®2 card contained <5 dilutions of erythromycin. A comparison was provided to the reference method with the following agreement. Summary Table for S. pneumoniae | | CA Tot | CA N | CA % | #R | Min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | | Clinical | 379 | 373 | 98.4 | 99 | 4 | 1 | 1 | | Challenge | 58 | 57 | 98.3 | 16 | 1 | 0 | 0 | | Combined | 437 | 430 | 98.4 | 115 | 5 | 1 | 1 | CA-Category Agreement Min-min discrepancies R-resistant isolates maj-major discrepancies vmj-very major discrepancies Category Agreement is when the interpretation (SIR) of the reference method agrees exactly with the interpretation (SIR) of the VITEK®2 results. ## Manual Dilution: The challenge set of organisms was also tested at one site using the manual method of inoculation with the following performance that demonstrated that there is minimal difference between the two inoculation methods. Summary Table for S. pneumoniae | | CA Tot | CA N | CA % | #R | Min | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | | Challenge | 58 | 56 | 96.6 | 16 | 2 | 0 | 0 | b. Matrix comparison: {5} 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: S. pneumoniae ≤0.25 (S), 1 (I), ≥2 (R) N. 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 information submitted in this premarket notification is complete and supports a substantial equivalence decision.