VITEK® 2 Streptococcus Tetracycline is designed for antimicrobial susceptibility testing of Streptococcus species 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 Streptococcus Tetracycline is a quantitative test. Tetracycline has been shown to be active against the microorganisms listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections: Streptococcus pneumoniae Streptococcus pyogenes*

*The VITEK® 2 Streptococcus Susceptibility Card also reports the susceptibility of the following additional organisms as listed on the FDA Susceptibility Test Interpretative Criteria website (STIC): Streptococcus spp. B-Hemolytic Group (other than S. pyogenes).

The VITEK® 2 Streptococcus Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Streptococcus pneumoniae, beta-hemolytic Streptococcus, and Viridans Streptococcus to antimicrobial agents when used as instructed.

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 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 Streptococcus Tetracycline has the following concentrations in the card: 0.125, 0.5, 1, and 4 ug/mL (equivalent standard method concentration by efficacy in ug/mL).

AI/ML Overview

Here's an analysis of the acceptance criteria and study proving the device meets those criteria, based on the provided text:

Device: VITEK® 2 Streptococcus Tetracycline (≤0.25 - ≥16 µg/mL)
Intended Use: Antimicrobial susceptibility testing of Streptococcus species, as a laboratory aid in determining in vitro susceptibility to antimicrobial agents. Specifically for Streptococcus pneumoniae and Streptococcus pyogenes, with additional reporting for Beta-hemolytic Streptococcus (other than S. pyogenes).

Acceptance Criteria and Reported Device Performance

The study compared the VITEK® 2 Streptococcus Tetracycline performance against the CLSI broth microdilution reference method. The acceptance criteria are implicitly defined by the guidance document cited: "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)."

Acceptance Metric	Requirement (Implied by FDA Guidance and Overall Performance)	Reported Device Performance
Overall Essential Agreement (EA)	Generally, >90% (industry standard for AST systems)	98.3%
Overall Category Agreement (CA)	Generally, >90% (industry standard for AST systems)	97.9%
Very Major Errors (VME) for S. pneumoniae	N/A (Not Applicable - typically assessed for Resistant to Susceptible mismatches, but the table shows N/A)	0.0%
Major Errors (ME) for S. pneumoniae	N/A (Not Applicable - typically assessed for Susceptible to Resistant mismatches)	0.0%
Minor Errors (mE) for S. pneumoniae	Low (e.g., <10%, depending on specific guidance)	0.3%
Very Major Errors (VME) for S. pyogenes	N/A	0.0%
Major Errors (ME) for S. pyogenes	N/A	0.0%
Minor Errors (mE) for S. pyogenes	Low	0.0%
Very Major Errors (VME) for Beta-hemolytic Streptococcus (other than S. pyogenes)	Low (e.g., <1.5%)	0.6%
Major Errors (ME) for Beta-hemolytic Streptococcus (other than S. pyogenes)	Low (e.g., <3%)	0.6%
Minor Errors (mE) for Beta-hemolytic Streptococcus (other than S. pyogenes)	Low (e.g., <10%)	3.4%
Reproducibility	Acceptable	Demonstrated acceptable results
Quality Control	Acceptable	Demonstrated acceptable results

Note on N/A for VME/ME: The table explicitly states "N/A" for VME and ME for S. pneumoniae and S. pyogenes. This often happens when there are no resistant isolates in the sample set or too few to reliably calculate these error rates, or if the "N/A" rather indicates that essential and categorical agreements are sufficient and the specific error rates are not the primary metrics for that specific organism set. However, for Beta-hemolytic Streptococcus, VME, ME, and mE percentages are provided, suggesting these metrics were relevant for that group.

Study Details

Sample sizes used for the test set and the data provenance:
- Test Set Sample Sizes:
  - Streptococcus pneumoniae: 289 isolates
  - Streptococcus pyogenes: 308 isolates
  - Beta-hemolytic Streptococcus (other than S. pyogenes): 530 isolates
- Total Isolates: 289 + 308 + 530 = 1127 isolates
- Data Provenance: The study involved an "external evaluation" conducted with "fresh and stock clinical isolates, as well as a set of challenge strains." The document does not specify the country of origin of the data or whether the study was retrospective or prospective. Typically, clinical isolates imply prospective collection from various clinical labs in the country where the study was primarily conducted (likely the US, given FDA submission).
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable in this context. The ground truth for antimicrobial susceptibility testing (AST) is established by a standardized, physical reference method, not by expert consensus on interpretations of images or signals. The reference method used was the CLSI broth microdilution reference method.
Adjudication method for the test set:
- Not applicable. As the ground truth is established by a standardized laboratory method (broth microdilution), there's no need for human adjudication of results in the traditional sense. The comparison is between the device's output and the reference method's output.
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:
- Not applicable. This is not an AI/imaging device. It's an automated antimicrobial susceptibility testing system. The "readers" are the instruments (VITEK® 2 and VITEK® 2 Compact Systems) which produce quantitative results (MIC) and interpretive categories (Susceptible, Intermediate, Resistant).
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, the performance listed in Table 2 (Essential Agreement and Category Agreement) represents the standalone performance of the VITEK® 2 system compared to the reference method. The device is designed to provide automated results.
The type of ground truth used:
- Reference Method: The ground truth was established using the CLSI broth microdilution reference method, incubated at 16-24 hrs. This is a well-established and standardized laboratory method for determining minimum inhibitory concentrations (MICs) of antimicrobials.
The sample size for the training set:
- The document implies that the study described is a validation study used to support regulatory submission, not a study that involved a training phase for a machine learning model. Therefore, a "training set" in the context of AI is not relevant here. The device uses "Discriminant Analysis" algorithms, which would have been developed and validated internally during the device's original development, not as part of this specific 510(k) submission. No training set size is provided for the algorithms themselves.
How the ground truth for the training set was established:
- Not applicable, as this is not an AI/ML development study presented in the document. The "ground truth" for developing the underlying discriminant analysis algorithms (mentioned as the "Analysis Algorithms") would have traditionally been established using similar reference methods during the initial R&D phase of the VITEK® 2 system itself.

Summary

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February 3, 2023

bioMérieux, Inc Jared Bronson Regulatory Affairs Specialist 595 Anglum Rd. Hazelwood, Missouri 63042

Re: K223481

Trade/Device Name: VITEK 2 Streptococcus Tetracycline (<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 Dated: November 17, 2022 Received: November 18, 2022

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 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 -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)

K223481

Device Name

VITEK® 2 Streptococcus Tetracycline (≤0.25 ->16 ug/mL)

Indications for Use (Describe)

Active in vitro and in clinical infections: Streptococcus pneumoniae Streptococcus pyogenes*

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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510(k) SUMMARY

VITEK® 2 Streptococcus Tetracycline (≤ 0.25 -> 16 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:	314-731-8799
Fax Number:	314-731-8689
Date of Preparation:	February 02, 2023
B. Device Name:
Formal/Trade Name:	VITEK® 2 Streptococcus Tetracycline (≤ 0.25 - ≥ 16µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code: LON
Common Name:	VITEK® 2 Streptococcus Tetracycline
C. Predicate Device:	VITEK® 2 Streptococcus Tetracycline (≤ 0.25 - ≥ 16µg/mL) (K111893)

D. Device Description:

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VITEK® 2 Streptococcus Tetracycline has the following concentrations in the card: 0.125, 0.5, 1, and 4 ug/mL (equivalent standard method concentration by efficacy in ug/mL).

E. Substantial Equivalence Information:

The similarities and differences of the VITEK® 2 Streptococcus Tetracycline when compared to the predicate device, VITEK® 2 Streptococcus Tetracycline (K111893), are described in the following table. The differences between both devices include the addition of Streptococcus pneumoniae and Beta hemolytic streptococcus spp. breakpoints and removal of Streptococcus spp. breakpoint, as well as narrowing the indications for use to Streptococcus pneumoniae and Streptococcus pyogenes.

Device and PredicateDevice(s):	Device:	Predicate Device: K111893
Device Trade Name	VITEK® 2 Streptococcus Tetracycline(≤ 0.25 – ≥ 16 µg/mL)	VITEK® 2 Streptococcus Tetracycline
Intended Use	VITEK® 2 Streptococcus Tetracycline isdesigned for antimicrobialsusceptibility testing of Streptococcusspecies and is intended for use with theVITEK® 2 and VITEK® 2 CompactSystems as a laboratory aid in thedetermination of in vitro susceptibilityto antimicrobial agents. VITEK® 2Streptococcus Tetracycline is aquantitative test. Tetracycline has beenshown to be active against most strainsof the microorganisms listed below,according to the FDA label for thisantimicrobial.	VITEK® 2 Streptococcus Tetracycline isdesigned for antimicrobial susceptibilitytesting of Streptococcus species.VITEK® 2 Streptococcus Tetracycline isa quantitative test intended for use withthe VITEK® 2 and the VITEK® 2Compact Systems as a laboratory aid inthe determination of in vitrosusceptibility to antimicrobial agents.Tetracycline has an antimicrobial activityagainst the microorganisms listed below,according to the FDA label for thisantimicrobial.
	The VITEK® 2 StreptococcusSusceptibility Card is intended for usewith the VITEK® 2 Systems in clinicallaboratories as an in vitro test todetermine the susceptibility ofStreptococcus pneumoniaeStreptococcus pneumoniae , beta-hemolytic Streptococcus , andViridans Streptococcus toantimicrobial agents when used asinstructed.	The VITEK® 2 AntimicrobialSusceptibility Test (AST) is intended tobe used with the VITEK® 2 System forthe automated quantitative or qualitativesusceptibility testing of isolated coloniesfor the most clinically significant aerobicgram-negative bacilli, Staphylococcusspp., Enterococcus spp., Streptococcusspp. and clinically significant yeast.
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	Tetracycline	Same
Inoculum	Saline suspension of organism	Same
Test Card	Streptococcus (AST-ST) SusceptibilityCard	Same
Analysis Algorithms	Discriminant Analysis	Same
Instrument	VITEK® 2 and VITEK® 2 CompactSystems	Same
Concentrations	0.125, 0.5, 1, 4	Same
	General Device Characteristic Differences
Breakpoints	Streptococcus pneumoniae$S ≤ 1$ , I 2, $R ≥ 4$Beta hemolytic Streptococcus species(including S. pyogenes )$S ≤ 2$ , I 4, $R ≥ 8$	Streptococcus spp.$S ≤ 4$ , I 8, $R ≥ 16$
Indications for Use	Active in vitro and in clinicalinfections :Streptococcus pneumoniaeStreptococcus pyogenes **The VITEK® 2 StreptococcusSusceptibility Card also reports thesusceptibility of the followingadditional organisms as listed on theFDA Susceptibility TestInterpretative Criteria website	Active in vitro and in clinical infections :Streptococcus pneumoniaeStreptococcus pyogenesViridans group streptococci

Table 1: Substantial Equivalence

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VITEK® 2 Streptococcus Tetracycline

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(STIC): Streptococcus spp. ß-
Hemolytic Group (other than S.
pyogenes).

F. Intended Use:

VITEK® 2 Streptococcus Tetracycline is designed for antimicrobial susceptibility testing of Streptococcus species 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 Streptococcus Tetracycline is a quantitative test. Tetracycline 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:

Streptococcus pneumoniae Streptococcus pyogenes*

G. Performance Overview and Conclusion:

VITEK® 2 Streptococcus Tetracycline 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 (510[k]) presents data in support of VITEK® 2 Streptococcus Tetracycline. 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 Streptococcus Tetracycline by comparing its performance with the CLSI broth

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microdilution reference method incubated at 16-24 hrs. The data is representative of performance on both the VITEK® 2 and VITEK® 2 Compact instrument platforms.

VITEK® 2 Streptococcus Tetracycline (≤0.25 - ≥16 µg/mL) demonstrated acceptable performance of 98.3% overall Essential Agreement and 97.9% overall Category Agreement with the reference method as presented in Table 2 below:

Antimi-crobial	Comment	Essential Agreement Category				Category Agreement
		% Error				% Error
		%EA	VME	ME	mE	%CA	VME	ME	mE
Tetracycline	Streptococcus pneumoniae.	(284/289)98.3%	N/A	N/A	N/A	(288/289)99.7%	(0/83)0.0%	(0/206)0.0%	(1/289)0.3%
	Streptococcus pyogenes.	(307/308)99.7%	N/A	N/A	N/A	(308/308)100.0%	(0/28)0.0%	(0/280)0.0%	(0/308)0.0%
	Beta-hemolytic Streptococcus (Other than Streptococcus pyogenes).	(518/530)97.7%	N/A	N/A	N/A	(509/530)96.0%	(2/348)0.6%	(1/166)0.6%	(18/530)3.4%

Table 2: VITEK® 2 Streptococcus Tetracycline Performance

Reproducibility and Quality Control demonstrated acceptable results.

H. The performance data presented in the submission support a substantial equivalence decision. VITEK® 2 AST-Streptococcus Tetracycline (≤0.25 ->16 µg/mL) is substantially equivalent to VITEK® 2 AST Streptococcus Tetracycline (K111893).

G. References:

1. 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.

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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.

Regulation Number and Section

§ 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.”