(98 days)
VITEK® 2 AST-Gram Positive Daptomycin is designed for antimicrobial susceptibility testing of Gram positive microorganisms and is intended for use with the VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 AST-Gram Positive Daptomycin is a quantitative test. Daptomycin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.
Active both in vitro and in clinical infections: Enterococcus faecalis (vancomycin-susceptible isolates only) Staphylococcus aureus (including methicillin-resistant isolates)
In vitro data are available, but their clinical significance is unknown: Enterococcus faecalis (vancomycin-resistant isolates)
The VITEK® 2 Gram-positive Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Staphylococcus spp., Enterococcus spp., and S. agalactiae to antimicrobial agents when used as instructed.
The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh(1) and Gerlach(2). The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique(3).
Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.
VITEK® 2 AST-GP Daptomycin has the following concentrations in the card: 0.5, 1, 2, 4, and 8 ug/mL (equivalent standard method concentration by efficacy in ug/mL).
The provided document describes the VITEK® 2 AST-GP Daptomycin system, an antimicrobial susceptibility test, and its performance evaluation.
Here's an analysis of the acceptance criteria and the study proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for antimicrobial susceptibility test (AST) systems in the US are generally defined by the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems. While specific numerical targets for Essential Agreement (EA) and Category Agreement (CA) are usually outlined in this guidance, the summary states the device demonstrated substantially equivalent performance when compared with the broth microdilution reference method, as defined in the FDA Class II Special Controls Guidance Document.
The reported performance of the VITEK® 2 AST-GP Daptomycin is provided in "Table 2: VITEK® 2 AST-GP Daptomycin Performance".
| Metric | Staphylococcus aureus | Enterococcus faecalis | Overall (implied from text) |
|---|---|---|---|
| Acceptance Criteria | (As per FDA Guidance, typical minimums for new ASTs are usually >90% for EA and >90% for CA with specific limits on VME/ME/mE) | ||
| Essential Agreement (%EA) | (183/194) 94.3% | (262/270) 97.0% | 95.9% |
| Very Major Errors (VME) | N/A | (1/8) 12.5% | |
| Major Errors (ME) | (2/185) 1.1% | (0/219) 0.0% | |
| Minor Errors (mE) | N/A | (41/270) 15.2% | |
| Category Agreement (%CA) | (192/194) 99.0% | (228/270) 84.4% | 90.5% |
Note on VME/ME/mE for Staphylococcus aureus: The document lists "N/A" for VME and mE for Staphylococcus aureus and "0.0%" for ME for Enterococcus faecalis. This might indicate that no specific VME/ME/mE were observed or reported in those categories, or that the formatting of the table in the document itself uses N/A for cases where a specific error type threshold wasn't relevant or wasn't met to be explicitly calculated. However, for a complete picture, the FDA guidance document would provide the specific acceptance thresholds for these error types. The (1/8) 12.5% VME for Enterococcus faecalis and (41/270) 15.2% mE for Enterococcus faecalis would likely be subject to specific acceptance criteria limits in the FDA guidance; for example, VMEs are typically expected to be ≤ 1.5% and MEs ≤ 3.0%, while mEs generally have a higher tolerance but still a limit. The document states a 90.5% overall Category Agreement, which for Enterococcus faecalis alone is 84.4%, falling below the typical 90% threshold for CA. This discrepancy might be addressed in a larger context within the full premarket notification, or perhaps the overall performance across all tested species met the required threshold despite one species being lower.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Staphylococcus aureus: 194 isolates
- Enterococcus faecalis: 270 isolates
- Total Clinical Isolates in Performance Study: 194 + 270 = 464 isolates.
- The study also used a "set of challenge strains" in addition to fresh and stock clinical isolates, but the exact number of challenge strains is not specified in this summary.
- Data Provenance:
- "An external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This suggests a prospective or a mix of prospective and retrospective collection from external sources (likely clinical laboratories).
- The document does not specify the country of origin for the data.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
- The ground truth was established by the CLSI broth microdilution reference method. This method is a standardized laboratory procedure, not reliant on human expert interpretation in the same way as, for example, image reading. Therefore, "number of experts" and "qualifications of experts" are not directly applicable in the context of establishing ground truth for this type of antimicrobial susceptibility testing.
4. Adjudication Method for the Test Set
- The reference method itself (CLSI broth microdilution) serves as the "ground truth" or "adjudication." No separate human adjudication process (e.g., 2+1, 3+1 consensus) is applicable or mentioned for this type of in vitro diagnostic device study. The device's results are directly compared to the results of the reference method.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study design is typically used for AI-powered diagnostic imaging devices where human readers interpret images with or without AI assistance. This device is an automated in vitro diagnostic system for antimicrobial susceptibility testing, not requiring human interpretation of complex visual data for its primary function.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, the performance study effectively evaluates the "standalone" performance of the VITEK® 2 AST-GP Daptomycin system. The system automatically processes the samples and generates MIC values and interpretive categories, which are then compared directly to the CLSI broth microdilution reference method. There is no human intervention in the device's determination of susceptibility.
7. The Type of Ground Truth Used
- The ground truth used was the CLSI broth microdilution reference method, which is a highly standardized and accepted laboratory method for determining antimicrobial susceptibility. This is essentially a "gold standard" laboratory method.
8. The Sample Size for the Training Set
- The document does not provide information on the training set size. This type of premarket notification summary focuses on the performance evaluation of the final device, not typically on the specific dataset used for algorithm development or training. The "Discriminant Analysis" mentioned under "Analysis Algorithms" implies a statistical model was used, which would have been developed/trained on a dataset, but details of this dataset are not included in this summary.
9. How the Ground Truth for the Training Set Was Established
- As the training set details are not provided, the method for establishing its ground truth is also not described in this summary. It would logically be established using a similar or identical reference method to the test set, but this is not confirmed.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo in blue. Underneath the FDA logo is the word "ADMINISTRATION".
July 5, 2023
BioMerieux, Inc Jared Bronson Regulatory Affairs Specialist 595 Anglum Rd. Hazelwood, Missouri 63042
Re: K230864
Trade/Device Name: VITEK 2 AST-Gram Positive Daptomycin (<=0.12 ->=8 ug/mL), VITEK 2 AST-GP Daptomycin (<=0.12 - >=8 µg/mL), VITEK 2 AST-GP Daptomycin Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System Regulatory Class: Class II Product Code: LON, LTW, LTT Dated: March 22, 2023 Received: March 29, 2023
Dear Jared Bronson:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part
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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ribhi Shawar -S
Ribhi Shawar, Ph.D. (ABMM) Branch Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known)
Device Name
VITEK® 2 AST-GP Daptomycin (≤0.12 - ≥8 µg/mL)
Indications for Use (Describe)
VITEK® 2 AST-Gram Positive Daptomycin is designed for antimicrobial susceptibility testing of Gram positive microorganisms and is intended for use with the VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 AST-Gram Positive Daptomycin is a quantitative test. Daptomycin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.
Active both in vitro and in clinical infections: Enterococcus faecalis (vancomycin-susceptible isolates only) Staphylococcus aureus (including methicillin-resistant isolates)
In vitro data are available, but their clinical significance is unknown: Enterococcus faecalis (vancomycin-resistant isolates)
The VITEK® 2 Gram-positive Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Staphylococcus spp., Enterococcus spp., and S. agalactiae to antimicrobial agents when used as instructed.
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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Image /page/3/Picture/0 description: The image shows the logo for bioMérieux, a French multinational biotechnology company. The logo is a circle with the top half in dark blue and the bottom half in yellow-green. The company name, "BIOMÉRIEUX", is written in white, sans-serif font in the center of the blue portion of the circle.
510(k) SUMMARY
VITEK® 2 AST-GP Daptomycin (≤ 0.121 -> 8 µg/mL)
510(k) Submission Information:
| Submitter's Name: | bioMérieux, Inc. |
|---|---|
| Address: | 595 Anglum RoadHazelwood, MO 63042 |
| Contact Person: | Jared BronsonRegulatory Affairs Specialist |
| Phone Number: | 314-201-8799 |
| Fax Number: | 314-731-8689 |
| Date of Preparation: | June 12, 2020 |
| B. Device Name: | |
| Formal/Trade Name: | VITEK® 2 AST-GP Daptomycin (≤0.12 - ≥8 µg/mL) |
| Classification Name: | 21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code: LON, LTT, LTW |
| Common Name: | VITEK® 2 AST-GP Daptomycin |
| C. Predicate Device: | VITEK® 2 AST-GP Daptomycin (≤0.12 - ≥8 µg/mL)(K091126) |
D. Device Description:
The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh(1) and Gerlach(2). The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique(3).
Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured
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Image /page/4/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle with the top half in dark blue and the bottom half in yellow and green. The word "BIOMÉRIEUX" is written in white letters in the center of the blue portion of the circle.
portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.
VITEK® 2 AST-GP Daptomycin has the following concentrations in the card: 0.5, 1, 2, 4, and 8 ug/mL (equivalent standard method concentration by efficacy in ug/mL).
E. Substantial Equivalence Information:
The similarities and differences of the VITEK® 2 AST-GP Daptomycin when compared to the predicate device, VITEK®2 AST-GP Daptomycin (K091126), are described in the following table. There is no difference between the new device and the predicate device.
| Device and Predicate Device(s): | Device: | Predicate Device: K091126 |
|---|---|---|
| Device Trade Name | VITEK® 2 AST-GP Daptomycin(≤0.12 - ≥8 µg/mL) | VITEK® 2 AST-GP Daptomycin(≤0.12 - ≥8 µg/mL) |
| Intended Use/Indications for Use | VITEK® 2 AST-GP Daptomycin is designed for antimicrobial susceptibility testing of Gram-positive microorganisms and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 AST-GP Daptomycin is a quantitative test. Daptomycin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.The VITEK® 2 Gram Positive Susceptibility Card is intended for use with the VITEK® 2 Systems in | Same |
Table 1: Substantial Equivalence
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Image /page/5/Picture/0 description: The image shows the logo for bioMérieux. The logo consists of a blue circle on top and a green circle on the bottom. The word "BIOMÉRIEUX" is written in white letters in the center of the blue circle.
| clinical laboratories as an in vitro testto determine the susceptibility ofEnterococcus spp., Staphylococcusspp., and Streptococcus agalactiae toantimicrobial agents when used asinstructed. | ||
|---|---|---|
| Test Methodology | Automated quantitative antimicrobialsusceptibility test for use with theVITEK® 2 and VITEK® 2 CompactSystems to determine the in vitrosusceptibility of microorganisms | Same |
| Antimicrobial Agent | Daptomycin | Same |
| Inoculum | Saline suspension of organism | Same |
| Test Card | Gram-positive (AST-GP) SusceptibilityCard | Same |
| Instrument | VITEK® 2 and VITEK® 2 CompactSystems | Same |
| Analysis Algorithms | Discriminant Analysis | Same |
| Type of Test | Quantitative | Same |
| Concentrations | 0.5, 1, 2, 4, 16 | Same |
| General Device Characteristic Differences | ||
| Breakpoints | Staphylococcus aureus(S/I/R) $\leq$ 1 / - / - | Staphylococcus aureus(S/I/R) $\leq$ 1 / - / - |
| Enterococcus faecalis(S/I/R) $\leq$ 2 / 4 / > 8 | Enterococcus faecalis(S/I/R) $\leq$ 4 / - / - | |
| Indicated Organisms | Active both in vitro and in clinicalinfections:Enterococcus faecalis (vancomycin-susceptible isolates only)Staphylococcus aureus (includingmethicillin-resistant isolates)In vitro data are available. but theirclinical significance is unknown:Enterococcus faecalis (vancomycin-resistant isolates) | Active both in vitro and in clinicalinfections:Enterococcus faecalis (vancomycin-susceptible isolates only)Staphylococcus aureus (includingmethicillin-resistant isolates) |
F. Intended Use:
VITEK® 2 AST-GP Daptomycin is designed for antimicrobial susceptibility testing of Gram positive microorganisms and is intended for use with the VITEK® 2 and VITEK® 2 COMPACT Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents.
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Image /page/6/Picture/0 description: The image shows the logo for bioMérieux. The logo consists of a blue circle on top and a yellow-green circle on the bottom, separated by a white line. The word "BIOMÉRIEUX" is written in white letters in the center of the blue circle.
VITEK® 2 AST-GP Daptomycin is a quantitative test. Daptomycin has been shown to be active against the microorganisms listed below, according to the FDA label for this antimicrobial.
Active both in vitro and in clinical infections: Enterococcus faecalis (vancomycin-susceptible isolates only) Staphylococcus aureus (including methicillin-resistant isolates)
In vitro data are available, but their clinical significance is unknown: Enterococcus faecalis (vancomycin-resistant isolates)
The VITEK® 2 AST-GP Daptomycin Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Enterococcus spp., Staphylococcus spp., and Streptococcus agalactiae to antimicrobial agents when used as instructed.
G. Performance Overview and Conclusion:
VITEK® 2 AST-GP Daptomycin demonstrated substantially equivalent performance when compared with the broth microdilution reference method, as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009).
The Premarket Notification (PMA) presents data in support of VITEK® 2 AST-GP Daptomycin. An external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains. The external evaluations were designed to confirm the acceptability of VITEK® 2 AST-GP Daptomycin by comparing its performance with the CLSI broth microdilution reference method incubated at 16-20 hrs. The data is representative of performance on both the VITEK® 2 Compact instrument platforms.
VITEK® 2 AST-GP Daptomycin (<0.12 - ≥8 µg/mL) demonstrated acceptable performance of 95.9% overall Essential Agreement and 90.5% overall Category Agreement with the reference method. Reproducibility and Quality Control demonstrated acceptable results. as presented in Table 2 below:
Table 2: VITEK® 2 AST-GP Daptomycin Performance
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Image /page/7/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle that is split into two halves. The top half is blue and contains the word "BIOMÉRIEUX" in white, sans-serif font. The bottom half is yellow and green, with the yellow fading into green.
| Group | % Error | % Error | ||||||
|---|---|---|---|---|---|---|---|---|
| %EA | VME | ME | mE | %CA | VME | ME | mE | |
| Staphylococcusaureus | (183/194)94.3 | N/A | N/A | N/A | (192/194)99.0 | (0/9)0.0 | (2/185)1.1 | N/A |
| Enterococcusfaecalis. | (262/270)97.0% | N/A | N/A | N/A | (228/270)84.4% | (1/8)12.5% | (0/219)0.0% | (41/270)15.2% |
Reproducibility and Quality Control demonstrated acceptable results.
H. References:
-
- MacLowry, J.D. and Marsh, H.H., Semi-automatic Microtechnique for Serial Dilution Antibiotic Sensitivity Testing in the Clinical laboratory, Journal of Laboratory Clinical Medicine, 72:685-687, 1968.
-
- Gerlach, E.H., Microdilution 1: A Comparative Study, p. 63-76. Current Techniques for Antibiotic Susceptibility Testing. A. Balows (ed.), Charles C. Thomas, Springfield, IL, 1974.
- Barry, A.L., The Antimicrobic Susceptibility Test, Principles and Practices, Lea and Febiger, 3. Philadelphia, PA, 1976.
§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.
(a)
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.(b)
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.”