(210 days)
VITEK® 2 AST-Gram Negative Fosfomycin is designed for antimicrobial susceptibility testing of Gram negative bacilli 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 Negative Fosfomyoin is a quantitative test. Fosfomycin 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:
Escherichia coli
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 sigmificant 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(0). 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 Fosfomycin (≤4 - ≥256 ug/mL) has the following concentrations in the card: 2, 8, 16 and 64 ug/mL (equivalent standard method concentration by efficacy in ug/mL).
The provided text describes the performance of the VITEK® 2 AST-GN Fosfomycin device for antimicrobial susceptibility testing. Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance:
The document refers to the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)" for acceptance criteria. While the specific numerical acceptance criteria (e.g., minimum percentage for %EA and %CA, maximum percentage for VME, ME, mE) are not explicitly stated in the provided text, the reported device performance is given in Table 2.
| Metric | Acceptance Criteria (Implicit from FDA Guidance) | Reported Device Performance (Enterobacterales - E. coli) |
|---|---|---|
| %EA (Essential Agreement) | Not explicitly stated, but device demonstrated acceptable performance | 99.2% (377/380) |
| VME (Very Major Errors) | Not explicitly stated, but device demonstrated acceptable performance | 0.0% (0/14) |
| ME (Major Errors) | Not explicitly stated, but device demonstrated acceptable performance | 0.0% (0/365) |
| mE (Minor Errors) | Not explicitly stated, but device demonstrated acceptable performance | 0.3% (1/380) |
| %CA (Category Agreement) | Not explicitly stated, but device demonstrated acceptable performance | 99.7% (379/380) |
2. Sample Size Used for the Test Set and Data Provenance:
- Test Sample Size: 380 isolates for Escherichia coli (Enterobacterales). The reported performance values (e.g., 377/380 for %EA, 379/380 for %CA) confirm this.
- Data Provenance: The study was an "external evaluation conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This indicates a prospective study using a mix of clinical and challenge strains. The country of origin is not specified.
3. Number of Experts Used to Establish Ground Truth and Qualifications:
This information is not provided in the given text.
4. Adjudication Method for the Test Set:
This information is not provided in the given text.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No MRMC study was done, as this is an antimicrobial susceptibility testing system, not a device that involves human readers interpreting cases.
6. Standalone Performance:
Yes, a standalone performance study was done. The VITEK® 2 AST-GN Fosfomycin demonstrated performance by comparing its results with the "CLSI agar dilution reference method." This indicates the algorithm (device) performed the susceptibility testing independently.
7. Type of Ground Truth Used:
The ground truth used was the CLSI agar dilution reference method. This is considered a gold standard for antimicrobial susceptibility testing.
8. Sample Size for the Training Set:
The document does not explicitly state the sample size for a training set. The study focuses on the "external evaluation" of the device's performance against a reference method. AST systems like VITEK 2 typically rely on established microbiological principles rather than machine learning models requiring large training sets in the same way an image analysis AI might.
9. How the Ground Truth for the Training Set Was Established:
As there's no mention of a separate training set in the context of machine learning, this information is not applicable/provided. If a "training set" were to be conceptualized for an AST system, it would relate to the initial development and calibration of the system's algorithms against established reference methods, which is part of the overall design and development process for such devices. The "CLSI agar dilution reference method" serves as the benchmark against which the device's accuracy is continually validated.
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March 9, 2023
bioMerieux SA, Inc. Craig Buehler Sr. Regulatory Affairs Specialist 595 Anglum Road Hazelwood, Missouri 63042
Re: K222430
Trade/Device Name: VITEK 2 AST-Gram Negative Fosfomycin (≤4 - ≥256 µg/mL), VITEK 2 AST-GN Fosfomycin (≤4 - ≥256 µg/mL), VITEK 2 AST-GN Fosfomycin 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: August 10, 2022 Received: August 11, 2022
Dear Craig Buehler:
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
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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 https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) 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) K222430
Device Name VITEK® 2 AST-GN Fosfomycin (<4 - >256 ug/mL)
Indications for Use (Describe)
VITEK® 2 AST-Gram Negative Fosfomycin is designed for antimicrobial susceptibility testing of Gram negative bacilli 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 Negative Fosfomyoin is a quantitative test. Fosfomycin 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:
Escherichia coli
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 sigmificant aerobic Gram-negative bacilli 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. The logo is a circle with a blue top half and a gradient bottom half that transitions from yellow to green. The word "BIOMÉRIEUX" is written in white, sans-serif font across the center of the blue portion of the circle.
510(k) SUMMARY
B.
C.
VITEK® 2 AST-Gram Negative Fosfomycin (≤4 - ≥256 µg/mL)
510(k) Submission Information:
| Submitter's Name: | bioMérieux, Inc. |
|---|---|
| Address: | 595 Anglum RoadHazelwood, MO 63042 |
| Contact Person: | Craig BuehlerSenior Regulatory Affairs Specialist |
| Phone Number: | 314-731-8358 |
| Fax Number: | 314-731-8689 |
| Date of Preparation: | August 9, 2022 |
| Device Name: | |
| Formal/Trade Name: | VITEK® 2 AST-Gram Negative Fosfomycin (≤4 - ≥256 µg/mL) |
| Classification Name: | 21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code: LON, LTW, LTT |
| Common Name: | VITEK® 2 AST-GN Fosfomycin (≤4 - ≥256 µg/mL) |
| Predicate Device: | VITEK® 2 AST-GN Eravacycline (≤ 0.12 - ≥ 4 µg/mL) (K191766) |
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(0). 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
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Image /page/4/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle with a blue semi-circle at the top and a yellow-green gradient semi-circle at the bottom. The word "BIOMÉRIEUX" is written in white letters in the blue semi-circle.
VITEK® 2 AST-GN Fosfomycin Traditional 510(k) Submission
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 Fosfomycin (≤4 - ≥256 ug/mL) has the following concentrations in the card: 2, 8, 16 and 64 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 Fosfomycin (≤4 - ≥256 µg/mL) when compared to the predicate device, VITEK® 2 AST-GN Eravacycline (≤ 0.12 ->24 ug/mL), are described in the Table 1 below.
| Item | Device:VITEK® 2 AST-Gram NegativeFosfomycin( $\leq$ 4 - $\geq$ 256 µg/mL) | Predicate:VITEK® 2 AST-GNEravacycline( $\leq$ 0.12 - $\geq$ 4 µg/mL)(K191766) |
|---|---|---|
| Similarities | ||
| Intended Use | VITEK® 2 AST-Gram NegativeFosfomycin 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 toantimicrobial agents. VITEK® 2AST-Gram Negative Fosfomycin isa quantitative test.The VITEK® 2 Gram-NegativeSusceptibility Card is intended foruse with the VITEK® 2 Systems inclinical laboratories as an in vitrotest to determine the susceptibility ofclinically significant aerobic Gramnegative bacilli to antimicrobial | VITEK® 2 AST-Gram NegativeEravacycline is designed forantimicrobial susceptibility testingof Gram negative bacilli and isintended for use with the VITEK®2 and VITEK® 2 Compact Systemsas a laboratory aid in thedetermination of in vitrosusceptibility to antimicrobialagents. VITEK® 2 AST-GramNegative Eravacycline is aquantitative test.The VITEK® 2 Gram-NegativeSusceptibility Card is intended foruse with the VITEK® 2 Systems inclinical laboratories as an in vitrotest to determine the susceptibilityof clinically significant aerobic |
| Item | Device:VITEK® 2 AST-Gram NegativeFosfomycin( $<=4 - >=256$ µg/mL) | Predicate:VITEK® 2 AST-GNEravacycline( $<= 0.12 -> 4$ µg/mL)(K191766) |
| Similarities | ||
| agents when used as instructed. | Gram negative bacilli toantimicrobial agents when used asinstructed. | |
| Test Methodology | Automated quantitativeantimicrobial susceptibility test foruse with the VITEK® 2 and VITEK®2 Compact Systems to determine thein vitro susceptibility ofmicroorganisms | Same |
| Inoculum | Saline suspension of organism | Same |
| Test Card | Gram Negative (AST-GN)Susceptibility Card | Same |
| Instrument | VITEK® 2 and VITEK® 2 CompactSystems | Same |
| Differences | ||
| AntimicrobialAgent | Fosfomycin | Eravacycline |
| Concentrations | 2, 8, 16, 64 | 0.25, 1, 2, 4 |
| Indications for use | Fosfomycin has been shown to beactive against most strains of themicroorganisms listed below,according to the FDA label for thisantimicrobial. | Eravacycline 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:Escherichia coli | Active in vitro and in clinicalinfections:Citrobacter freundiiEnterobacter cloacaeEscherichia coliKlebsiella oxytocaKlebsiella pneumoniaeIn vitro data are available, butclinical significance is unknown:Citrobacter koseriKlebsiella (Enterobacter)aerogenes |
Table 1: Substantial Equivalence
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Image /page/5/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle divided 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.
VITEK® 2 AST-GN Fosfomycin Traditional 510(k) Submission
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Image /page/6/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 a gradient from yellow to green. The company name, "BIOMÉRIEUX", is written in white, sans-serif font across the center of the blue portion of the circle.
F. Intended Use:
VITEK® 2 AST-Gram Negative Fosfomycin 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 Fosfomycin in is a quantitative test. Fosfomycin 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:
Escherichia coli
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.
G. Performance Overview and Conclusion:
VITEK® 2 AST-GN Fosfomycin demonstrated substantially equivalent performance when compared with the CLSI agar dilution 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 Fosfomycin. 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 Fosfomycin by comparing its performance with the CLSI agar dilution reference method incubated at 16-24 hrs. The data is representative of performance on both the VITEK® 2 Compact instrument platforms.
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Image /page/7/Picture/0 description: The image shows the logo for bioMérieux, a French multinational biotechnology company. The logo is a circle with a blue upper half and a yellow-green lower half. The company name, "BIOMÉRIEUX", is written in white, sans-serif font in the center of the blue portion of the circle.
VITEK® 2 AST-GN Fosfomycin Traditional 510(k) Submission
The VITEK® 2 AST-GN Fosfomycin demonstrated acceptable performance as presented in Table 2 below:
| %EA | VME | ME | mE | %CA | VME | ME | mE | |
|---|---|---|---|---|---|---|---|---|
| PerformanceforEnterobacterales (E. coli) | (377/380)99.2 | N/A | N/A | N/A | (379/380)99.7 | (0/14)0.0 | (0/365)0.0 | (1/380)0.3 |
Table 2: VITEK® 2 AST-GN Fosfomycin Performance
Reproducibility and Quality Control demonstrated acceptable results.
H. References:
- MacLowry, J.D. and Marsh, H.H., Semi-automatic Microtechnique for Serial Dilution Antibiotic 1. 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 2. 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.”