VITEK® 2 AST-Streptococcus Cefotaxime is designed for antimicrobial susceptibility testing of Streptococcus spp. 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- Streptococcus Cefotaxime is a quantitative test. Cefotaxime 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 (Group A beta-hemolytic streptococci)*
Streptococcus spp. (Viridans group streptococci)

*The VITEK® 2 Streptococus Susceptibility Card also reports the susceptibility of the following additional organisms as listed on the FDA Susceptibility Test Interia 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 S. 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(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 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.

AI/ML Overview

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for VITEK® 2 AST-Streptococcus Cefotaxime:

1. Table of Acceptance Criteria and Reported Device Performance:

The document references "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)" for defining acceptable performance. While the specific numerical acceptance criteria from this guidance are not explicitly called out in the provided text, the reported performance (Table 2) implicitly indicates that these criteria were met for the device to be deemed substantially equivalent. The table below presents the reported performance directly from the document.

Antimicrobial	Indicated Organism (with Notes)	Essential Agreement (EA) %	Very Major Error (VME) %	Major Error (ME) %	Minor Error (mE) %	Category Agreement (CA) %	% Reproducibility
Cefotaxime*	Streptococcus pneumoniae (meningitis)	98.6% (346/351)	0.0% (0/54)	0.8% (2/243)	10.0% (35/351)	89.5% (314/351)	N/A
	Streptococcus pneumoniae (non-meningitis)	98.6% (346/351)	0.0% (0/23)	0.3% (1/297)	10.0% (35/351)	89.7% (315/351)	N/A
	Streptococcus pyogenes (Group A β-Hemolytic Group) NS	100.0% (310/310)	0.0% (0/0)	0.0% (0/310)	N/A	100.0% (310/310)	100.0
	Streptococcus spp. β-Hemolytic Group (other than S. pyogenes) NS	100.0% (554/554)	0.0% (0/0)	0.0% (0/554)	N/A	100.0% (554/554)	N/A
	Streptococcus spp. Viridans Group	97.3% (397/408)	0.0% (0/12)	0.0% (0/381)	2.9% (12/408)	97.1% (396/408)	N/A

Note on Acceptance Criteria: While not explicitly stated, FDA guidance for AST systems typically requires:

Essential Agreement (EA): Generally ≥ 90%
Category Agreement (CA): Generally ≥ 90%
Major Error (ME) Rate: Generally ≤ 3%
Very Major Error (VME) Rate: Generally ≤ 1.5%

Based on the reported performance, the device appears to meet these implied criteria. However, there's a specific note for Streptococcus pneumoniae (both meningitis and non-meningitis) where Minor Error (mE) is 10.0%, which is higher than typical acceptance for mE. For Streptococcus spp. Viridans Group, the EA is 97.3% and CA is 97.1%.

A note states: "The VITEK 2 Cefotaxime MIC values for Streptococcus spp Viridans Group tended to be at least one dilution lower than the reference method and may contribute to the occurrence of very major errors." However, the reported VME for this group is 0.0%.

2. Sample Size and Data Provenance:

The study involved an "external evaluation" with various types of isolates.

Test Set Sample Sizes (from Table 2):
- Streptococcus pneumoniae (meningitis): 351 isolates
- Streptococcus pneumoniae (non-meningitis): 351 isolates
- Streptococcus pyogenes (Group A β-Hemolytic Group) NS: 310 isolates
- Streptococcus spp. β-Hemolytic Group (other than S. pyogenes) NS: 554 isolates
- Streptococcus spp. Viridans Group: 408 isolates
Data Provenance: The document states the external evaluation was "conducted with contemporary and stock clinical isolates, as well as a set of challenge strains." This suggests a mix of prospective (contemporary clinical isolates) and retrospective (stock clinical isolates and challenge strains) data. There is no explicit mention of the country of origin of the data.

3. Number of Experts and Qualifications for Ground Truth:

This information is not provided in the document. The ground truth (reference method) for the test set was established by the CLSI broth microdilution reference method; however, the involvement and qualifications of human experts in interpreting or reviewing these results are not detailed.

4. Adjudication Method for the Test Set:

This information is not provided in the document. For AST systems, the ground truth is typically the CLSI broth microdilution, which is a standardized laboratory procedure, so traditional adjudication methods like "2+1" or "3+1" used in imaging studies between human readers are not directly applicable here. The comparison is between the device's output and the reference method's output.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

No, an MRMC comparative effectiveness study was not done. This device is an automated antimicrobial susceptibility test system, meaning it directly outputs results (MIC values and interpretive categories). It does not involve human readers interpreting images or data that would then be compared with and without AI assistance. The performance comparison is solely between the automated system and a laboratory reference method.

6. Standalone (Algorithm Only) Performance:

Yes, a standalone performance evaluation was done. The entire study describes the performance of the VITEK® 2 AST-Streptococcus Cefotaxime system (which includes the algorithm for analysis) against the CLSI broth microdilution reference method. There is no human element in the interpretation of the VITEK® 2 system's results for this evaluation; it's the device's output being compared directly.

7. Type of Ground Truth Used:

The ground truth used was the CLSI broth microdilution reference method, which is a standardized laboratory procedure considered the gold standard for determining antimicrobial susceptibility.

8. Sample Size for the Training Set:

The document does not specify the sample size used for the training set. It only describes the "external evaluation" which serves as the validation or test set.

9. How the Ground Truth for the Training Set was Established:

Since the training set sample size is not specified, the method for establishing its ground truth is also not explicitly stated. However, given the nature of the device and the validation method, it's highly probable that if a training set was used for algorithm development, its ground truth would also have been established using the CLSI broth microdilution reference method, similar to the test set.

Summary

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October 28, 2021

bioMérieux, Inc Cherece L Jones Staff Regulatory Affairs Specialist 595 Anglum Rd. Hazelwood, Missouri, 63042 USA.

Re: K210287

Trade/Device Name: VITEK 2 AST- Streptococcus Cefotaxime (<0.125 - >8 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: January 29, 2021 Received: February 2, 2021

Dear Cherece Jones:

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 post marketing 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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Indications for Use

510(k) Number (if known)

K210287

Device Name

VITEK® 2 AST- Streptococcus Cefotaxime (≤0.125 - ≥8 µg/mL)

Indications for Use (Describe)

Active in vitro and in clinical infections:

Streptococcus pneumoniae Streptococcus pyogenes (Group A beta-hemolytic streptococci)* Streptococcus spp. (Viridans group streptococci)

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 AST-Streptococcus Cefotaxime (≤0.125 - ≥8 µg/mL)

A. 510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Cherece L. JonesStaff Regulatory Affairs Specialist
Phone Number:	314 -731-8684
Fax Number:	314-731-8689
Date of Preparation:	January 29, 2021
B. Device Name:
Formal/Trade Name:	VITEK® 2 AST- Streptococcus Cefotaxime (≤0.125 - ≥8µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code: LON
Common Name:	VITEK® 2 AST-ST Cefotaxime (≤0.125 - ≥8 µg/mL)
C. Predicate Device:	VITEK® 2 AST-Streptococcus Cefotaxime (≤0.125 -≥8 µg/mL) (K121863)

D. Device Description:

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E. Substantial Equivalence Information:

The similarities and differences of the VITEK® 2 AST- Streptococcus Cefotaxime (≤0.125 - ≥8 ug/mL) when compared to the predicate device, VITEK® 2 AST-Streptococcus Cefotaxime (<0.125 - ≥8 µg/mL) (K121863), are described in Table 1 below.

Item	Device:VITEK® 2 AST- StreptococcusCefotaxime (≤0.125 - ≥8 µg/mL)(K210287)	Predicate:VITEK® 2 AST-StreptococcusCefotaxime (≤0.125 - ≥8 µg/mL)(K121863)
General Device Characteristic Similarities
IntendedUse/Indications for Use	VITEK® 2 AST-StreptococcusCefotaxime is designed forantimicrobial susceptibility testing ofStreptococcus spp. 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-Streptococcus Cefotaxime is aquantitative test.	Same
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	Cefotaxime	Same
Inoculum	Saline suspension of organism	Same
Test Card	Streptococcus (AST-ST)Susceptibility Card	Same
Analysis Algorithms	Discriminate Analysis	Same
Instrument	VITEK® 2 and VITEK® 2 CompactSystems	Same

Table 1: Substantial Equivalence

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	Device:	Predicate:
Item	VITEK® 2 AST- StreptococcusCefotaxime (≤0.125 - ≥8 µg/mL)(K210287)	VITEK® 2 AST-StreptococcusCefotaxime (≤0.125 - ≥8 µg/mL)(K121863)
Concentrations	0.25, 0.5, 1, 2	Same
General Device Characteristic Differences
Indicated Organisms	Cefotaxime 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:Streptococcus pneumoniaeStreptococcus pyogenes (Group Abeta-hemolytic streptococci)Streptococcus spp. (Viridans groupstreptococci)The VITEK® 2 StreptococcusSusceptibility Card also reports thesusceptibility of the followingadditional organisms aslisted on the FDA Susceptibility TestInterpretative Criteria website(STIC): Streptococcus spp. ß-Hemolytic Group (other than S.pyogenes ).The VITEK® 2 StreptococcusSusceptibility Card is intended foruse with the VITEK® 2 Systems inclinical laboratories as an in vitro testto determine the susceptibility of S.pneumoniae , beta-hemolyticStreptococcus , and ViridansStreptococcus to antimicrobial agentswhen used as instructed	Cefotaxime has been shown to beactive against most strains of themicroorganism listed below, accordingto the FDA label for this antimicrobial.Active in vitro and in clinicalinfections:Streptococcus pneumoniae ,Streptococcus pyogenes (Group Abeta-hemolytic streptococci),Streptococcus spp.The VITEK® 2 AntimicrobialSusceptibility Test (AST) is intendedto be used with the VITEK® 2 andVITEK 2 Compact Systems for theautomated quantitative or qualitativesusceptibility testing of isolatedcolonies for the most clinicallysignificant aerobic gram-negativebacilli, Staphylococcus spp.,Enterococcus spp., Streptococcusagalactiae , and S. pneumoniae .

F. Performance Overview and Conclusion:

VITEK® 2 AST-ST Cefotaxime (≤0.125 - ≥8 µg/mL) 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).

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The Premarket Notification (510|k]) presents data in support of VITEK® 2 AST-ST Cefotaxime. An external evaluation was conducted with contemporary and stock clinical isolates, as well as a set of challenge strains. The external evaluations were designed to confirm the acceptability of AST-ST Cefotaxime by comparing its performance with the CLSI broth microdilution reference method incubated at 20-24 hrs (i.e. Streptococcus). The data is representative of performance on both the VITEK® 2 and VITEK® 2 Compact instrument platforms.

The VITEK® 2 AST-ST Cefotaxime (≤0.125 - ≥8 µg/mL) demonstrated acceptable performance as presented in Table 2 below:

Antimicrobial	AntimicrobialCode	AntibioticVersion	Bp1	Comment2	Essential Agreement Category				Category Agreement				% Repr du cibilit
					% Error				% Error
					%EA	VME	ME	mE	%CA	VME	ME	mE
Cefotaxime*	CTX	(ctx01n)	FDA(CLSI)	#, EStreptococcuspneumoniae(meningitis)	(346/351)98.6	N/A	N/A	N/A	(314/351)89.5	(0/54)0.0	(2/243)0.8	(35/351)10.0
				#, EStreptococcuspneumoniae(non -meningitis)	(346/351)98.6	N/A	N/A	N/A	(315/351)89.7	(0/23)0.0	(1/297)0.3	(35/351)10.0
				#, EStreptococcuspyogenes(Group A β-HemolyticGroupNS	(310/310)100.0	N/A	N/A	N/A	(310/310)100.0	(0/0)0.0	(0/310)0.0	N/A	100.0
				#, EStreptococcusspp. β-HemolyticGroup (otherthan S.pyogenes) NS	(554/554)100.0	N/A	N/A	N/A	(554/554)100.0	(0/0)0.0	(0/554)0.0	N/A
				#, EStreptococcusspp. ViridansGroup	(397/408)97.3	N/A	N/A	N/A	(396/408)97.1	(0/12)0.0	(0/381)0.0	(12/408)2.9

Toble 21 VITEV® 2 AST ST Cafatoximo Porformonea

The VITEK 2 Cefotaxime MC values for Streptococus spp Viridans Group ended to be at least one than the reference method and may contibute to the occurrence of very major errors.

NS - The current absence of resistant isolates defining any results other than susceptible. Isolates pieding MC results suggestive of Nonsuceptible category should be submitted to a reference laboratory for further testing.

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*For specific information regarding succession and associaed test methods and quality contriss standards recognized by FDA for his drug, pleas sec https://www.fda.gov/STIC

Kev: # = US Food and Drug Administration 510(k) cleared E = External performance data

Quality Control demonstrated acceptable results.

G. Limitations:

The ability of the AST card to detect resistance with the following combination(s) is unknown because resistant strains were either not available or an insufficient number were encountered at the time of comparative testing:

Cefotaxime (ctx01n): Streptococcus pyogenes (Group A ß-hemolytic streptococci) and ● Streptococcus spp ß-Hemolytic Group (other than S. pyogenes)

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.

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.”