VITEK® 2 AST-Gram Positive Delafloxacin is designed for antimicrobial susceptibility testing of Gram positive microorganisms 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 Positive Delafloxacin is a quantitative test. Delafloxacin 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: Acute Bacterial Skin and Skin Structure Infections (ABSSSI):
Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible isolates) Streptococcus agalactiae Enterococcus faecalis

Community-Acquired Bacterial Pneumonia (CABP):
Staphylococcus aureus (methicillin-susceptible isolates only)

The VITEK® 2 Gram-positive Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Staphylococcus spp., Enterococcus spp., and S. agalactiae 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() 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 study details based on the provided document:

Acceptance Criteria and Device Performance for VITEK® 2 AST-Gram Positive Delafloxacin

The device, VITEK® 2 AST-Gram Positive Delafloxacin, is an antimicrobial susceptibility testing system. Its performance was compared against the CLSI broth microdilution reference method.

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) as the definition for acceptable performance. While the specific numerical acceptance criteria from this guidance are not explicitly stated in the provided text, the table below presents the reported device performance, which the document states "demonstrated acceptable performance."

Performance Metric	Target/Acceptance Criteria (Implicitly met based on "acceptable performance")	Reported Device Performance (Delafloxacin)
Percentage Essential Agreement (%EA)
ABSSSI (Overall)	N/A (implicitly >X%)	96.6% (737/763)
ABSSSI (E. faecalis)	N/A (implicitly >X%)	95.0% (342/360)
ABSSSI (MSSA+MRSA)	N/A (implicitly >X%)	98.2% (320/326)
ABSSSI (S. agalactiae)	N/A (implicitly >X%)	97.4% (75/77)
CABP (MSSA)	N/A (implicitly >X%)	99.4% (169/170)
Percentage Category Agreement (%CA)
ABSSSI (Overall)	N/A (implicitly >X%)	94.0% (717/763)
ABSSSI (E. faecalis)	N/A (implicitly >X%)	94.4% (340/360)
ABSSSI (MSSA+MRSA)	N/A (implicitly >X%)	92.0% (300/326)
ABSSSI (S. agalactiae)	N/A (implicitly >X%)	100.0% (77/77)
CABP (MSSA)	N/A (implicitly >X%)	97.1% (165/170)
Very Major Errors (VME)	N/A (implicitly <X%)
ABSSSI (Overall)	N/A (implicitly <X%)	1.5% (2/136)
ABSSSI (E. faecalis)	N/A (implicitly <X%)	2.0% (2/98)
ABSSSI (MSSA+MRSA)	N/A (implicitly <X%)	0.0% (0/36)
ABSSSI (S. agalactiae)	N/A (implicitly <X%)	0.0% (0/2)
CABP (MSSA)	N/A (implicitly <X%)	0.0% (0/7)
Major Errors (ME)	N/A (implicitly <X%)
ABSSSI (Overall)	N/A (implicitly <X%)	0.5% (3/594)
ABSSSI (E. faecalis)	N/A (implicitly <X%)	0.4% (1/252)
ABSSSI (MSSA+MRSA)	N/A (implicitly <X%)	0.7% (2/267)
ABSSSI (S. agalactiae)	N/A (implicitly <X%)	0.0% (0/75)
CABP (MSSA)	N/A (implicitly <X%)	0.0% (0/155)
Minor Errors (mE)	N/A (implicitly <X%)
ABSSSI (Overall)	N/A (implicitly <X%)	5.4% (41/763)
ABSSSI (E. faecalis)	N/A (implicitly <X%)	4.7% (17/360)
ABSSSI (MSSA+MRSA)	N/A (implicitly <X%)	7.4% (24/326)
ABSSSI (S. agalactiae)	N/A (implicitly <X%)	0.0% (0/77)
CABP (MSSA)	N/A (implicitly <X%)	2.9% (5/170)
% Reproducibility	N/A (implicitly >X%)	100.0% (for Delafloxacin - unspecified organism type)

2. Sample Size Used for the Test Set and Data Provenance

Test Set Organisms: The document states that "An external evaluation was conducted with contemporary and stock clinical isolates, as well as a set of challenge strains." Specific numbers for each organism type tested within the overall categories are provided in the performance table (e.g., 763 isolates for ABSSSI Overall, 360 for E. faecalis, 326 for MSSA+MRSA, 77 for S. agalactiae, 170 for CABP MSSA).
Data Provenance: The document explicitly mentions "contemporary and stock clinical isolates." This suggests a mix of retrospective (stock isolates) and potentially prospective (contemporary clinical isolates) data. The country of origin is not specified.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

This information is not provided in the document. The ground truth was established by the CLSI broth microdilution reference method, which is a standardized laboratory procedure, not typically an expert consensus based on individual interpretation.

4. Adjudication Method for the Test Set

This information is not applicable for this type of test (Antimicrobial Susceptibility Testing). Adjudication methods like 2+1 or 3+1 are typically used in image-based diagnostic studies where multiple human readers are involved and their interpretations need to be reconciled. In AST, the reference method provides a direct, quantitative result.

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

A MRMC comparative effectiveness study was not done. This type of study assesses the performance of human readers, sometimes with and without AI assistance. This document describes the performance of an automated AST device against a reference method, not human interpretation.

6. Standalone (Algorithm Only) Performance

Yes, a standalone performance study was done. The entire evaluation described in the "Performance Overview and Conclusion" section focuses on the performance of the VITEK® 2 AST-Gram Positive Delafloxacin system (algorithm only) against the CLSI broth microdilution reference method, without human intervention in the result determination by the VITEK system.

7. Type of Ground Truth Used

The ground truth used was the CLSI broth microdilution reference method. This is a laboratory-based, standardized, quantitative method for determining minimum inhibitory concentrations (MICs) of antimicrobial agents.

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 appears to be the test set.

9. How the Ground Truth for the Training Set Was Established

The document does not specify how the ground truth for any potential training set was established. However, given that the external evaluation used the CLSI broth microdilution reference method, it is highly probable that any training data would have also been benchmarked against a similar gold standard reference method.

Summary

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April 28, 2020

bioMerieux, Inc Cherece Jones Staff Regulatory Affairs Specialist 595 Anglum Rd. Hazelwood, Missouri 63042

Re: K200590

Trade/Device Name: VITEK 2 AST-Gram Positive Delafloxacin (≤0.015 - ≥1 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, LTT, LTW Dated: March 4, 2020 Received: March 6, 2020

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 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-Gram Positive Delafloxacin (≤0.015-≥1 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:	March 4, 2020
B. Device Name:
Formal/Trade Name:	VITEK® 2 AST-Gram Positive Delafloxacin (≤0.015 - ≥1 µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code: LON
Common Name:	VITEK® 2 AST-GP Delafloxacin (≤0.015 - ≥1 µg/mL)
C. Predicate Device:	VITEK® 2 AST-Gram Positive Dalbavancin (≤0.015 -≥1 µg/mL) (K190616)
D. Device Description:

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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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.

E. Substantial Equivalence Information:

The similarities and differences of the VITEK® 2 AST-GP Delafloxacin (≤0.015-≥1 µg/mL) when compared to the predicate device, VITEK® 2 AST-Gram Positive Dalbavancin (≤0.015 ->1 ug/mL), are described in the Table 1 below.

Item	Device:VITEK® 2 AST-GP Delafloxacin(≤0.015 - ≥1 µg/mL)	Predicate:VITEK® 2 AST-Gram PositiveDalbavancin (≤0.015 - ≥1 µg/mL)(K190616)
	Similarities
Intended Use	VITEK® 2 AST-Gram PositiveDelafloxacin is designed forantimicrobial susceptibility testing ofGram positive microorganisms and isintended for use with the VITEK® 2and VITEK® 2 Compact Systems asa laboratory aid in the determinationof in vitro susceptibility toantimicrobial agents. VITEK® 2AST-Gram Positive Delafloxacin is aquantitative test. Delafloxacin hasbeen shown to be active against moststrains of the microorganisms listedbelow, according to the FDA labelfor this antimicrobial.Active in vitro and in clinicalinfections:Acute Bacterial Skin and SkinStructure Infections (ABSSSI):Staphylococcus aureus (includingmethicillin-resistant and methicillin-susceptible isolates)Streptococcus agalactiaeEnterococcus faecalisCommunity-Acquired Bacterial	VITEK® 2 AST-Gram PositiveDalbavancin is designed forantimicrobial susceptibility testing ofGram positive microorganisms and isintended for use with the VITEK® 2and VITEK® 2 Compact Systems as alaboratory aid in the determination ofin vitro susceptibility to antimicrobialagents. VITEK® 2 AST-Gram PositiveDalbavancin is a quantitative test.Dalbavancin has been shown to beactive against most strains of themicroorganisms listed below,according to the FDA label for thisantimicrobial.Active both in vitro and in clinicalinfectionsStaphylococcus aureus (includingmethicillin-resistant isolates)Enterococcus faecalis (vancomycin-susceptible isolates only)Streptococcus agalactiaeThe VITEK® 2 Gram-positiveSusceptibility Card is intended for usewith the VITEK® 2 Systems in clinical

Table 1: Substantial Equivalence

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Item	Device:VITEK® 2 AST-GP Delafloxacin(≤0.015 - ≥1 µg/mL)	Predicate:VITEK® 2 AST-Gram PositiveDalbavancin (≤0.015 - ≥1 µg/mL)(K190616)
Similarities
	Pneumonia (CABP):Staphylococcus aureus (methicillin-susceptible isolates only)The VITEK® 2 Gram-positiveSusceptibility Card is intended foruse with the VITEK® 2 Systems inclinical laboratories as an in vitro testto determine the susceptibility ofStaphylococcus spp., Enterococcusspp., and S. agalactiae toantimicrobial agents when used asinstructed.	laboratories as an in vitro test todetermine the susceptibility ofStaphylococcus spp., Enterococcusspp., and S. agalactiae toantimicrobial agents when used asinstructed.
Test Methodology	Automated quantitative antimicrobialsusceptibility test for use with theVITEK® 2 and VITEK® 2 CompactSystems to determine the in vitrosusceptibility of microorganisms	Same
Inoculum	Saline suspension of organism	Same
Test Card	Gram Positive (AST-GP)Susceptibility Card	Same
Analysis Algorithms	Growth Pattern Analysis	Same
Instrument	VITEK® 2 and VITEK® 2 CompactSystems	Same
Differences
Antimicrobial Agent	Delafloxacin	Dalbavancin
Concentrations	0.008, 0.03, 0.06, 0.25	0.0625, 0.125, 0.25, 0.5

F. Indications for Use:

Active in vitro and in clinical infections: Acute Bacterial Skin and Skin Structure Infections (ABSSSI):

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Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible isolates) Streptococcus agalactiae Enterococcus faecalis

Community-Acquired Bacterial Pneumonia (CABP):

Staphylococcus aureus (methicillin-susceptible isolates only)

G. Performance Overview and Conclusion:

VITEK® 2 AST-Gram Positive Delafloxacin 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-Gram Positive Delafloxacin. 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 VITEK® 2 AST-Gram Positive Delafloxacin by comparing its performance with the CLSI broth microdilution reference method incubated at 16-20 hrs for Staphylococci and Enterococci and 20-24 hrs for Streptococci. The data is representative of performance on both the VITEK® 2 Compact instrument platforms.

The VITEK® 2 AST-Gram Positive Delafloxacin demonstrated acceptable performance as presented in Table 2 below:

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Antimicrobial	Comment	Essential Agreement Category				Category Agreement				% Reproducibility
		%EA	VME	ME	mE	%CA	VME	ME	mE
	#, EABSSSI(Overall)	(737/763)96.6%	N/A	N/A	N/A	(717/763)94.0%	(2/136)1.5%	(3/594)0.5%	(41/763)5.4%
	#, EABSSSI (E.faecalis)	(342/360)95.0%	N/A	N/A	N/A	(340/360)94.4%	(2/98)2.0%	(1/252)0.4%	(17/360)4.7%
Delafloxacin	#, EABSSSI(MSSA+MRSA)	(320/326)98.2%	N/A	N/A	N/A	(300/326)92.0%	(0/36)0.0%	(2/267)0.7%	(24/326)7.4%	100.0
	#, EABSSSI(S.agalactiae)	(75/77)97.4%	N/A	N/A	N/A	(77/77)100%	(0/2)0.0%	(0/75)0.0%	(0/77)0.0%
	#, ECABP(MSSA)	(169/170)99.4%	N/A	N/A	N/A	(165/170)97.1%	(0/7)0.0%	(0/155)0.0%	(5/170)2.9%
NOTE: VITEK® 2 AST-Gram Positive Delafloxacin MIC values tended to be in exact agreement or at least one doubling dilution higherwhen testing Staphylococcus aureus compared to the CLSI reference broth microdilution method.
NOTE: When evaluating performance of the challenge isolates on the manual dilution option for the VITEK® 2 and VITEK® 2 Compact,testing with MRSA isolates yielded an EA of 85% (17/20) and an CA of 80% (16/20). For challenge isolates on the auto dilution option forthe VITEK® 2, testing with MRSA isolates yielded an EA of 85% (17/20) and an CA of 85% (17/20). All categorical errors wereconsidered minor

Toblo 21 VITEY® 2 AST Crom Pocitive Dolofloxacin Parfarmon

Key: #= US Food and Drug Administration 510(k) cleared

E = External performance data

Quality Control demonstrated acceptable results.

H. 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.
1. 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.

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1. Barry, A.L., The Antimicrobic Susceptibility Test, Principles and Practices, Lea and Febiger, 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.”