(53 days)
VITEK® 2 AST-Gram Negative Polymyxin B is designed for antimicrobial susceptibility testing of Gram Negative bacilli 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-Gram Negative Polymyxin B is a quantitative test. Polymyxin B has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.
Active in vitro and in clinical infections: Pseudomonas aeruginosa
The VITEK® 2 Gram-Negative Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant aerobic Gram-negative bacilli 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-GN Polymyxin B has the following concentrations in the card: 0.125, 0.5, 2 and 8 ug/mL (equivalent standard method concentration by efficacy in ug/mL).
The acceptance criteria and study proving the device meets them are described below:
Acceptance Criteria and Device Performance
| Metric | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Overall Essential Agreement | ≥ 90% | 93.9% |
| Overall Category Agreement | ≥ 90% | 96.6% |
Note: The acceptance criteria are based on the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009). The specific percentage thresholds for "acceptable performance" are derived from this guidance, although the exact numerical thresholds are not explicitly stated within the provided text, they are commonly 90% or higher for both essential and category agreement in AST systems.
Study Information
2. Sample size used for the test set and the data provenance:
- Test Set Size: Not explicitly stated as a single number for each component (clinical isolates, stock clinical isolates, challenge strains). The document mentions an "external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains." The combined total number of isolates for the test set is not provided.
- Data Provenance: Not explicitly stated (e.g., country of origin). The study used "fresh and stock clinical isolates, as well as a set of challenge strains," suggesting a mix of retrospectively collected and specifically curated (challenge) strains.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable. The ground truth was established using a reference laboratory method, not expert consensus.
4. Adjudication method for the test set:
- Not applicable. The ground truth was established using a reference laboratory method (CLSI broth microdilution), not through expert adjudication of results from the device.
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 device is an automated antimicrobial susceptibility testing system, not an AI-assisted diagnostic device for human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, a standalone performance study was done. The VITEK® 2 AST-GN Polymyxin B system, an "Automated quantitative antimicrobial susceptibility test," was compared against the CLSI broth microdilution reference method. The device operates automatically to determine susceptibility.
7. The type of ground truth used:
- Expert consensus, pathology, outcomes data, etc.: The ground truth was established using a CLSI broth microdilution reference method, specifically "the CLSI broth microdilution reference method incubated at 16-20 hours."
8. The sample size for the training set:
- Not explicitly stated. The document describes a performance evaluation (test set) but does not provide details on a separate training set used for developing the algorithm. The VITEK® 2 system's underlying "Growth Pattern Analysis" algorithms would have been developed and trained using diverse microbiological data, but specific sample sizes for this training are not detailed in this 510(k) summary.
9. How the ground truth for the training set was established:
- Not explicitly stated. Given the nature of the device (antimicrobial susceptibility testing), it can be inferred that the ground truth for any training would also have been established using a standardized reference method like broth microdilution, similar to how the test set ground truth was established.
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February 14, 2020
BioMerieux, Inc. Esther Hernandez Regulatory Affairs Specialist 595 Anglum Road Hazelwood, Missouri 63042
Re: K193567
Trade/Device Name: VITEK 2 AST- Gram Negative Polymyxin B (<=0.25 - >=16 ug/mL) 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: December 20, 2019 Received: December 23, 2019
Dear Esther Hernandez:
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 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR
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- 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, Ph.D. (ABMM) Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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510(k) SUMMARY
VITEK® 2 AST-GN Polymyxin B
A. 510(k) Submission Information:
| Submitter's Name: | bioMérieux, Inc. |
|---|---|
| Address: | 595 Anglum RoadHazelwood, MO 63042 |
| Contact Person: | Esther HernandezRegulatory Affairs Specialist |
| Phone Number: | 314-731-8841 |
| Fax Number: | 314-731-8689 |
| Date of Preparation: | December 19, 2019 |
| Device Name: | |
| Formal/Trade Name: | VITEK® 2 AST- Gram Negative Polymyxin B (≤0.25 - ≥ 16 µg/mL) |
| Classification Name: | 21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code LON |
| Common Name: | VITEK® 2 AST-GN Polymyxin B |
| Predicate Device: | VITEK® 2 AST-GN Delafloxacin (K183524) |
D. Device Description:
B.
C.
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
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Image /page/3/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle with a blue top half and a green and yellow gradient bottom half. The word "BIOMÉRIEUX" is written in white letters in the blue portion of the circle.
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-GN Polymyxin B has the following concentrations in the card: 0.125, 0.5, 2 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-GN Polymyxin B when compared to the predicate device, VITEK 2 AST-GN Delafloxacin (K183524), are described in the following table.
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| Item | Device:VITEK® 2 AST-GN Polymyxin B | Predicate:VITEK® 2 AST-G NDelafloxacin (K183524) |
|---|---|---|
| Similarities | ||
| Intended Use | VITEK® 2 AST-Gram NegativePolymyxin B is designed forantimicrobial susceptibility testing ofGram negative bacilli and is intendedfor use with the VITEK® 2 and VITEK®2 Compact Systems as a laboratoryaid in the determination of in vitrosusceptibility to antimicrobial agents.VITEK® 2 AST-Gram NegativePolymyxin B is a quantitative test.Polymyxin B has been shown to beactive against most strains of themicroorganisms listed below,according to the FDA label for thisantimicrobial.Active in vitro and in clinicalinfections:PseudomonasaeruginosaThe VITEK® 2 Gram-NegativeSusceptibility Card is intended for usewith the VITEK® 2 Systems inclinical laboratories as an in vitro testto determine the susceptibility ofclinically significant Gram-negative bacilli to antimicrobialagents when used as instructed. | VITEK® 2 AST-Gram NegativeDelafloxacin is designed forantimicrobial susceptibility testing ofGram negative bacilli and is intendedfor use with the VITEK®2 andVITEK® 2 Compact Systems as alaboratory aid in the determination ofin vitro susceptibility to antimicrobialagents. VITEK® 2 AST-GramNegative Delafloxacin is a quantitativetest.Delafloxacin has been shown to beactive against most strains of themicroorganisms listed below, accordingto the FDA label for this antimicrobial.Active in vitro and in clinical infections:Escherichia coliEnterobacter cloacaeKlebsiella pneumoniaePseudomonasaeruginosaThe VITEK® 2 Gram-negativeSusceptibility Card is intended for usewith the VITEK® 2 Systems in clinicallaboratories as an in vitro test to determinethe susceptibility of clinically significantGram-negative bacilli toantimicrobial agents when used asinstructed. |
| TestMethodology | Automated quantitative antimicrobialsusceptibility test for use with theVITEK® 2 and VITEK® 2 CompactSystems to determine the in vitrosusceptibility of Gram negative bacilli | Same |
| Inoculum | Saline suspension of organism | Same |
| Test Card | VITEK® 2 Gram Negative SusceptibilityTest Card | Same |
| Instrument | VITEK® 2 and VITEK® 2Compact Systems | Same |
| AnalysisAlgorithms | Growth Pattern Analysis | Same |
| Differences | ||
| AntimicrobialAgent | Polymyxin B | Delafloxacin |
| AntimicrobialConcentration | 0.125, 0.5, 2, 8 | 0.06, 0.25, 0.5, 2 |
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Image /page/5/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle with a blue upper half and a yellow-green lower half. The word "BIOMÉRIEUX" is written in white letters in the blue half of the circle.
F. Intended Use:
VITEK® 2 AST-Gram Negative Polymyxin B is designed for antimicrobial susceptibility testing of Gram Negative bacilli 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-Gram Negative Polymyxin B is a quantitative test. Polymyxin B has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.
Active in vitro and in clinical infections: Pseudomonas aeruginosa
The VITEK® 2 Gram-Negative Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant aerobic Gram-negative bacilli to antimicrobial agents when used as instructed.
F. Performance Overview and Conclusion:
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VITEK® 2 AST-GN Polymyxin B demonstrated substantially equivalent performance when compared with the CLSI 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 (510[k]) presents data in support of VITEK® 2 AST- GN Polymyxin B. 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-GN Polymyxin B by comparing its performance with the CLSI broth microdilution reference method incubated at 16-20 hours. The data is representative of performance on both the VITEK® 2 and VITEK® 2 Compact instrument platforms.
VITEK® 2 AST-GN Polymyxin B demonstrated acceptable performance of 93.9% overall Essential Agreement and 96.6% overall Category Agreement with the reference method. Reproducibility and Quality Control demonstrated acceptable results.
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, 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.”