(81 days)
VITEK® 2 AST-Gram Negative Imipenem/Relebactam 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 Imipenem/Relebactam is a quantitative test. Imipenem/Relebactam 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: Klebsiella (Enterobacter) aerogenes Enterobacter cloacae Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa Citrobacter freundii Klebsiella oxytoca
In vitro data are available, but clinical significance is unknown Citrobacter koseri Enterobacter asburiae
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 () 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 Imipenem/Relebactam has the following concentrations in the card: 0.25/4, 1/4, 4/4 and 16/4 ug/mL (equivalent standard method concentration by efficacy in ug/mL).
The provided text describes the 510(k) summary for VITEK® 2 AST-Gram Negative Imipenem/Relebactam, an automated antimicrobial susceptibility testing system. The study aims to demonstrate substantial equivalence to a predicate device and adherence to CLSI broth microdilution reference methods.
Here's a breakdown of the requested information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the FDA Class II Special Controls Guidance Document (August 28, 2009) and assessed through Essential Agreement and Category Agreement. The specific numerical acceptance criteria are not explicitly stated as "acceptance criteria" but are reported as performance metrics that demonstrate acceptability.
| Performance Metric | Acceptance Criteria (Implied by FDA Guidance and acceptable performance) | Reported Device Performance (Enterobacteriaceae & P. aeruginosa Combined) |
|---|---|---|
| Essential Agreement (EA) | Not explicitly stated as a numerical threshold, but 90% or greater is typical for AST devices (implied by acceptable "95.6% EA") | 95.6% |
| Category Agreement (CA) | Not explicitly stated as a numerical threshold, but 90% or greater is typical for AST devices (implied by acceptable "98.0% CA") | 98.0% |
Note on Acceptance Criteria: While the text states "acceptable performance of 95.3% Essential Agreement and 98.9% Category Agreement for Enterobacteriaceae and 96.2% Essential Agreement and 95.5% Category Agreement for P. aeruginosa," it doesn't explicitly state the pre-defined acceptance criteria (e.g., "EA must be >= 90%"). However, these reported values are presented as demonstrating "substantially equivalent performance" and "acceptable performance," strongly implying they met the underlying criteria.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: The text mentions an "external evaluation... with fresh and stock clinical isolates, as well as a set of challenge strains." However, the exact numerical sample size (total number of isolates tested in the external evaluation) is not provided in the given text.
- Data Provenance: The text states the study was an "external evaluation" using "fresh and stock clinical isolates" and "challenge strains." This suggests the data is likely retrospective (using existing collections of isolates) and potentially prospective if fresh clinical isolates were collected during the study period. The country of origin of the data is not specified.
3. Number of Experts Used to Establish Ground Truth and Qualifications
This information is not provided in the text. The ground truth was established by the CLSI broth microdilution reference method, which is a standardized laboratory procedure, not typically relying on expert interpretation in the same way as, for example, image analysis.
4. Adjudication Method for the Test Set
This information is not applicable in the context of this study. The ground truth was established by a reference laboratory method (CLSI broth microdilution), not by human interpretation requiring adjudication.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of Human Improvement
- MRMC Comparative Effectiveness Study: No, an MRMC comparative effectiveness study was not done. This study is evaluating the performance of an automated AST system against a reference method, not the impact of AI assistance on human readers.
- Effect Size of Human Improvement: Therefore, this information is not applicable.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, a standalone performance study was done. The VITEK® 2 AST-GN Imipenem/Relebactam is an automated system described as a "quantitative test" that "automatically fills, seals and places the card into the incubator/reader" and "monitor[s] the growth of each well... At the completion of the incubation cycle, a report is generated." The reported performance metrics (Essential Agreement and Category Agreement) are for the device's output compared to the reference method, indicating standalone performance.
7. The Type of Ground Truth Used
The type of ground truth used was the CLSI broth microdilution reference method. This is a consensus-based, standardized laboratory method for determining antimicrobial susceptibility.
8. The Sample Size for the Training Set
This information is not provided in the text. As this is an automated system based on growth pattern analysis (not explicitly a machine learning model that requires a distinct "training set" in the common sense for AI, though it would have been developed and validated on internal data), there isn't a "training set" as might be described for a deep learning algorithm. The provided text describes the performance evaluation of the developed system.
9. How the Ground Truth for the Training Set Was Established
This information is not provided in the text. For a system like VITEK, the underlying "ground truth" for its development would be established through extensive correlation with standard laboratory methods, similar to the CLSI broth microdilution method used for its performance evaluation.
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March 13, 2020
BioMerieux, Inc. Jolyn Tenllado Regulatory Affairs Expert 595 Anglum Road Hazelwood, Missouri 63042
Re: K193572
Trade/Device Name: VITEK 2 AST-Gram Negative Imipenem/Relebactam (<0.25/4 - ≥16/4 μg/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 Jolyn Tenllado:
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/cfpmp/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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see
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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 medical devices and radiation-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 Imipenem/Relebactam
A. 510(k) Submission Information:
| Submitter's Name: | bioMérieux, Inc. |
|---|---|
| Address: | 595 Anglum RoadHazelwood, MO 63042 |
| Contact Person: | Jolyn TenlladoRegulatory Affairs Expert |
| Phone Number: | 314-731-8386 |
| Fax Number: | 314-731-8689 |
| Date of Preparation: | December 20, 2019 |
| B. Device Name: | |
| Formal/Trade Name: | VITEK® 2 AST- Gram NegativeImipenem/Relebactam (≤ 0.25/4 - ≥ 16/4 µg/mL) |
| Classification Name: | 21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code LON |
| Common Name: | VITEK® 2 AST-GN Imipenem/Relebactam |
| C. Predicate Device: | VITEK® 2 AST-GN Imipenem (K183415) |
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 () 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 bottom half. The word "BIOMÉRIEUX" is written in white letters in the center of the blue half 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 Imipenem/Relebactam has the following concentrations in the card: 0.25/4, 1/4, 4/4 and 16/4 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 Imipenem/Relebactam when compared to the predicate device, VITEK 2 AST-GN Imipenem (K183415), are described in the following table.
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Image /page/4/Picture/0 description: The image shows the logo for bioMerieux. The logo is a circle that is split into two halves. The top half is blue and contains the word "BIOMERIEUX" in white letters. The bottom half of the circle is yellow and green.
| Item | Device:VITEK® 2 AST-GNImipenem/Relebactam | Predicate:VITEK® 2 AST-GN Imipenem(K183415) |
|---|---|---|
| Similarities | ||
| Intended Use | VITEK® 2 AST-Gram NegativeImipenem/Relebactam is designed forantimicrobial susceptibility testing ofGram negative bacilli and is intended foruse with the VITEK® 2 and VITEK® 2Compact Systems as a laboratory aid inthe determination of in vitro susceptibilityto antimicrobial agents. VITEK® 2 AST-Gram Negative Imipenem/Relebactam isa quantitative test.Imipenem/Relebactam has been shown tobe active against most strains of themicroorganisms listed below, accordingto the FDA label for this antimicrobial.Active in vitro and in clinical infections:Klebsiella (Enterobacter) aerogenesEnterobacter cloacaeEscherichia coliKlebsiella pneumoniaePseudomonas aeruginosaCitrobacter freundiiKlebsiella oxytocaIn vitro data are available, but clinicalsignificance is unknownCitrobacter koseriEnterobacter asburiae | VITEK® 2 AST-Gram NegativeImipenem is designed for antimicrobialsusceptibility testing of Gram negativebacilli and is intended for use with theVITEK® 2 and VITEK® 2 CompactSystems as a laboratory aid in thedetermination of in vitro susceptibility toantimicrobial agents. VITEK® 2 AST-Gram Negative Imipenem is aquantitative test. Imipenem has beenshown to be active against most strains ofthe microorganisms listed below,according to the FDA label for thisantimicrobial.Active in vitro and in clinical infections:Acinetobacter spp.Citrobacter spp.Enterobacter spp. (excluding E.aerogenes)Escherichia coliKlebsiella spp.Pseudomonas aeruginosaThe VITEK® 2 Gram-NegativeSusceptibility Card is intended for usewith the VITEK® 2 Systems in clinicallaboratories as an in vitro test todetermine the susceptibility of clinicallysignificant aerobic Gram-negative bacillito antimicrobial agents when used asinstructed. |
| Item | Device:VITEK® 2 AST-GNImipenem/Relebactam | Predicate:VITEK® 2 AST-GN Imipenem(K183415) |
| Similarities | ||
| Intended Use(Cont.) | The VITEK® 2 Gram-NegativeSusceptibility Card is intended for usewith the VITEK® 2 Systems in clinicallaboratories as an in vitro test todetermine the susceptibility of clinicallysignificant aerobic Gram-negative bacillito antimicrobial 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 | Imipenem/Relebactam | Imipenem |
| AntimicrobialConcentration | 0.25/4, 1/4, 4/4, 16/4 | 0.5, 2, 8, 16 |
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Image /page/5/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 letters. The bottom half is yellow and green.
F. Intended Use:
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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 green circle on the bottom. The word "BIOMÉRIEUX" is written in white letters in the center of the blue circle.
VITEK® 2 AST-Gram Negative Imipenem/Relebactam 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 Imipenem/Relebactam is a quantitative test. Imipenem/Relebactam 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: Klebsiella (Enterobacter) aerogenes Enterobacter cloacae Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa Citrobacter freundii Klebsiella oxytoca
In vitro data are available, but clinical significance is unknown Citrobacter koseri Enterobacter asburiae
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:
VITEK® 2 AST-GN Imipenem/Relebactam 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 Imipenem/Relebactam. 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 Imipenem/Relebactam by comparing its performance with the CLSI broth microdilution reference method incubated at 16-20
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hours. The data is representative of performance on both the VITEK® 2 and VITEK® 2 Compact instrument platforms.
VITEK® 2 AST-GN Imipenem/Relebactam demonstrated acceptable performance of 95.3% Essential Agreement and 98.9% Category Agreement for Enterobacteriaceae and 96.2% Essential Agreement and 95.5% Category Agreement for P. aeruginosa with the reference method. Overall performance for Enterobacteriaceae and P. aeruginosa combined was 95.6% Essential Agreement and 98.0% Category Agreement. 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.”