VITEK® MS is a mass spectrometry system using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) for the identification of microorganisms cultured from human specimens.

The VITEK® MS system is a qualitative in vitro diagnostic device indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial, yeast and mould infections.

Device Description

The VITEK® MS v3.0 system is a system consisting of kit reagents (VITEK® MS-CHCA, VITEK® MS-FA, VITEK® MS Mycobacterium/Nocardia Kit, VITEK® MS Mould Kit), VITEK® MS-DS target slides, and the VITEK® MS (original equipment VITEK® MS Prep Station, Knowledge Base v3.2.0, software, and the VITEK" MS (original eq

AI/ML Overview

This document focuses on the VITEK® MS system, a mass spectrometry system for microorganism identification, and its performance characteristics. It outlines the acceptance criteria and details of the study conducted to prove the device meets these criteria.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the reported performance targets which show very high agreement rates for identification. The primary performance metric is the "Total Correct Genus ID (One Choice and Low Discrimination)".

Here's a table summarizing criteria derived from the reported performance, reflecting typical expectations for such devices, and the observed performance for different organism groups.

Organism Group	Acceptance Criteria (Implied) - Total Correct Genus ID	Reported Device Performance (Total Correct Genus ID)
Gram-positive bacteria	>95%	95.8% (3594/3750)
Gram-negative bacteria	>95%	95.2% (5788/6079)
Gram-negative bacteria (Brucella only)	>90%	91.7% (220/240)
Yeasts	>95%	96.8% (1316/1360)
Moulds	>90%	92.7% (1398/1508)
Mycobacterium	>95%	96.5% (777/805)
Nocardia	>95%	97.9% (374/382)
Overall (All Organisms Total)	>95%	95.4% (13247/13884)

Note: The reported performance also details "One Choice Correct" and "Low Discrimination Correct" breakouts, as well as discordant and no-ID rates, providing a comprehensive view of the device's accuracy. For example, for "All" clinical bacteria and yeast isolates tested, the agreement with reference identification was 98.8% (4189/4241).

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

Test Set Sample Size:

Overall Performance (Routine fresh and stock strains): 13,884 samples across various organism groups.
Clinical Studies (Clinical isolates): 4,241 test results.
Brucella specific testing (ATCC): 240 strains for clinical trial, 180 for reproducibility, 45 for challenge testing.

Data Provenance:
The data was collected from:

Routine fresh and stock strains from patient cultures in clinical microbiology laboratories and bioMérieux laboratories in the United States and France. This indicates a mix of prospective and retrospective (stock strains) data and geographic diversity.
Clinical isolates were tested at "one external clinical trial site and one internal site" for bacteria (other than Brucella) and yeasts.
For Brucella, clinical trial, reproducibility, and challenge testing were performed at "one external clinical trial site" (specifically, ATCC is mentioned for Brucella testing). This suggests a focus on specific, well-characterized strains for Brucella.

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

The document does not explicitly state the number of experts used or their specific qualifications (e.g., "radiologist with 10 years of experience"). However, it mentions that "Samples were sequenced by the appropriate reference laboratory, and if needed, additional analysis was performed internally to obtain a reference identification (GenBank, dendrogram analysis)."

This implies that the ground truth was established by:

Personnel at "appropriate reference laboratories" (implying qualified microbiologists/scientists).
Internal personnel at bioMérieux.
The use of "proficiency panels tested by all participating technologists at the external sites" for the clinical trial suggests that the individuals performing the tests were trained and qualified.

While specific numbers and detailed qualifications of individual experts are not provided, the methodology points to reliance on established laboratory practices and reference techniques for accurate identification.

4. Adjudication Method for the Test Set

The document does not explicitly describe a formal adjudication method (like 2+1 or 3+1 for human readers of images). For microbiological identification, the "adjudication" is inherent in the ground truth establishment process:

Reference methods (DNA sequencing analysis, supplemental testing) are considered the gold standard.
If sequencing was insufficient, "additional analysis was performed internally to obtain a reference identification (GenBank, dendrogram analysis)." This suggests a process where discrepancies or difficult identifications are resolved by deeper, more definitive, and comparative analysis rather than a simple consensus among multiple readers.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done in the traditional sense of comparing human readers with and without AI assistance for interpretation tasks. This device is an automated system for identifying microorganisms, not an AI for image interpretation that assists human diagnosticians. The study focuses on the accuracy of the automated system against a definitive reference method.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)

Yes, the study primarily evaluates the standalone performance of the VITEK® MS system. The reported performance metrics (e.g., "Total Correct Genus ID") reflect the accuracy of the device's algorithm in identifying microorganisms when presented with samples.

While the "Interpretation of results and use of the VITEK® MS system require a competent laboratorian" is mentioned in the device description, the performance tables quantify the output of the machine itself compared to the ground truth, effectively reporting its standalone accuracy.

7. The Type of Ground Truth Used

The ground truth for microorganism identification was established using:

DNA sequencing analysis: This is the primary reference method.
Supplemental testing (when necessary): This could include biochemical tests, serology, or other definitive microbiological techniques.
Previously well-characterized strains (ATCC or equivalent): For certain challenge or quality control tests, established strains were used, for which the identity is already known and highly reliable.
GenBank and dendrogram analysis: Used for additional internal analysis to obtain reference identification when sequencing was not fully conclusive, reinforcing the ground truth.

This indicates a robust, multi-faceted approach to ground truth establishment, relying on genetic and phenotypic gold standards.

8. The Sample Size for the Training Set

The document does not explicitly state the sample size used for the training set for the VITEK® MS Knowledge Base (KB) v3.2.0. It mentions that the "Knowledge Base includes data representing 1316 species and 1158 taxa displayed" and "1095 species of bacteria" and "232 species of fungi." This describes the content of the database used for identification, which is analogous to the "training data" that built the system's ability to recognize these species. However, the exact number of samples or spectra used to build this database is not provided in this excerpt.

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

The document describes the "Knowledge Base" as having been "developed from spectra of a number of microbial species." While it doesn't detail the training process or the ground truth establishment for the training set specifically, it's highly implied that the same rigorous methods used for the test set (DNA sequencing, supplemental testing, well-characterized strains) would have been used to curate the reference spectra within the Knowledge Base. This ensures that the foundational data used by the device for identification is accurate and reliable. The continuous updates to the "Knowledge Base v3.2.0" suggest an ongoing process of incorporating new and validated spectral data.

Summary

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December 21, 2018

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: a seal on the left and the FDA acronym with the agency's full name on the right. The seal features an eagle emblem surrounded by text, while the FDA acronym is in blue, followed by "U.S. FOOD & DRUG ADMINISTRATION" in a sans-serif font, also in blue.

bioMerieux, Inc. Jennifer Jines Regulatory Affairs Specialist 595 Anglum Rd. Hazelwood, Missouri 63042

Re: K181412

Trade/Device Name: Vitek MS Regulation Number: 21 CFR 21 CFR 866.3378 Regulation Name: Clinical Mass Spectrometry Microorganism Identification and Differentiation System Regulatory Class: Class II Product Code: QBN Dated: May 29, 2018 Received: May 30, 2018

Dear Jennifer Jines:

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 mav, 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 avare 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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Uwe Scherf -S

Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K181412

Device Name VITEK® MS

Indications for Use (Describe)

(See Attached for 'List of Claimed Organisms')

Type of Use (Select one or both, as applicable)

| X | Prescription Use (Part 21 CFR 801 Subpart D)

| | | Over-The-Counter Use (21 CFR 801 Subpart C)

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Indications for Use Attachment

Gram Negative / Positive Bacteria & Yeast

Abiotrophia defectiva Achromobacter denitrificans Achromobacter xylosoxidans Acinetobacter baumannii Acinetobacter calcoaceticus Acinetobacter haemolyticus Acinetobacter johnsonii Acinetobacter junii Acinetobacter lwoffii Acinetobacter nosocomialis Acinetobacter pittii Actinomyces bovis Actinomvces israelii Actinomvces meveri Actinomyces naeslundii Actinomyces neuii Actinomyces odontolyticus Actinotignum schaalii Aerococcus viridans Aeromonas hydrophila Aeromonas jandaei Aeromonas punctata (caviae) Aeromonas sobria Aggregatibacter actinomycetemcomitans Aggregatibacter aphrophilus Aggregatibacter segnis Alcaligenes faecalis ssp faecalis Bacteroides caccae Bacteroides eggerthii Bacteroides fragilis Bacteroides ovatus / xylanisolvens Bacteroides pyogenes Bacteroides stercoris Bacteroides thetaiotaomicron Bacteroides uniformis Bacteroides vulgatus Bifidobacterium spp Bilophila wadsworthia Bordetella avium Bordetella bronchiseptica Bordetella parapertussis Bordetella pertussis Brevundimonas diminuta Brevundimonas vesicularis Brucella spp

Burkholderia cenocepacia Burkholderia cepacia Burkholderia contaminans Burkholderia gladioli Burkholderia multivorans Burkholderia vietnamiensis Campylobacter coli Campvlobacter jejuni Campylobacter rectus Candida albicans Candida auris Candida dubliniensis Candida duobushaemulonii Candida famata Candida glabrata Candida guilliermondii Candida haemulonii Candida inconspicua Candida intermedia Candida kefyr Candida krusei Candida lambica Candida lipolytica Candida lusitaniae Candida metapsilosis Candida norvegensis Candida orthopsilosis Candida parapsilosis Candida pelliculosa Candida rugosa Candida tropicalis Candida utilis Candida zeylanoides Cedecea davisae Cedecea lapagei Cedecea neteri Chryseobacterium gleum Chryseobacterium indologenes Citrobacter amalonaticus Citrobacter braakii Citrobacter farmeri Citrobacter freundii Citrobacter koseri Citrobacter youngae Clostridium baratii Clostridium beijerinckii Clostridium butyricum Clostridium cadaveris

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Clostridium clostridioforme Clostridium difficile Clostridium innocuum Clostridium novvi Clostridium perfringens Clostridium ramosum Clostridium septicum Clostridium sporogenes Clostridium tertium Clostridium tetani Comamonas testosteroni Corynebacterium jeikeium Cronobacter muytjensii Cronobacter sakazakii Cronobacter turicensis Cryptococcus gattii Cryptococcus neoformans Curtobacterium flaccumfaciens Delftia acidovorans Edwardsiella hoshinae Edwardsiella tarda Eikenella corrodens Elizabethkingia anophelis Elizabethkingia meningoseptica Elizabethkingia miricola Enterobacter aerogenes Enterobacter asburiae Enterobacter cancerogenus Enterobacter cloacae Enterobacter hormaechei Enterobacter kobei Enterobacter ludwigii Enterococcus avium Enterococcus casseliflavus Enterococcus durans Enterococcus faecalis Enterococcus faecium Enterococcus gallinarum Enterococcus hirae Escherichia coli Escherichia fergusonii Escherichia hermannii Escherichia vulneris Ewingella americana Finegoldia magna Fusobacterium mortiferum Fusobacterium necrophorum Fusobacterium nucleatum Fusobacterium periodonticum Gardnerella vaginalis

Gemella haemolysans Gemella morbillorum Granulicatella adiacens Haemophilus influenzae Haemophilus parahaemolyticus Haemophilus parainfluenzae Hafnia alvei Hathewaya histolytica Kingella denitrificans Kingella kingae Klebsiella oxytoca Klebsiella pneumoniae Klebsiella variicola Kluyvera ascorbata Kluyvera cryocrescens Kluyvera intermedia Kocuria rhizophila Kodamaea ohmeri Lactococcus garvieae Lactococcus lactis Leclercia adecarboxylata Legionella pneumophila Lelliottia amnigena Leuconostoc mesenteroides Leuconostoc pseudomesenteroides Listeria monocytogenes Malassezia furfur Malassezia pachydermatis Mannheimia haemolytica Micrococcus luteus Mobiluncus curtisii Moraxella catarrhalis Moraxella lacunata Moraxella nonliquefaciens Moraxella osloensis Morganella morganii Myroides spp Neisseria cinerea Neisseria gonorrhoeae Neisseria meningitidis Neisseria mucosa / sicca Ochrobactrum anthropi Oligella ureolytica Oligella urethralis Paeniclostridium sordellii Pantoea agglomerans Pantoea dispersa

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Paraclostridium bifermentans Parvimonas micra Pasteurella aerogenes Pasteurella multocida Pediococcus acidilactici Peptoniphilus asaccharolyticus Peptostreptococcus anaerobius Plesiomonas shigelloides Pluralibacter gergoviae Porphyromonas asaccharolytica / uenonis Porphyromonas gingivalis Prevotella bivia Prevotella buccae Prevotella denticola Prevotella intermedia Prevotella loescheii Prevotella melaninogenica Prevotella oralis Prevotella oris Propionibacterium acidipropionici Propionibacterium acnes Propionibacterium avidum Propionibacterium granulosum Propionibacterium propionicum Proteus mirabilis Proteus penneri Proteus vulgaris Providencia alcalifaciens Providencia rettgeri Providencia rustigianii Providencia stuartii Pseudomonas aeruginosa Pseudomonas alcaligenes Pseudomonas fluorescens Pseudomonas luteola Pseudomonas mendocina Pseudomonas oryzihabitans Pseudomonas putida Pseudomonas stutzeri Ralstonia pickettii Raoultella ornithinolytica Raoultella planticola Raoultella terrigena Rhizobium radiobacter Rhodotorula mucilaginosa Rothia mucilaginosa Saccharomyces cerevisiae Salmonella enterica ssp enterica Saprochaete capitata Serratia ficaria

Serratia fonticola Serratia grimesii Serratia liquefaciens Serratia marcescens Serratia odorifera Serratia plymuthica Serratia proteamaculans Serratia quinivorans Serratia rubidaea Shewanella putrefaciens Sphingobacterium multivorum Sphingobacterium spiritivorum Sphingomonas paucimobilis Staphylococcus aureus Staphylococcus auricularis Staphylococcus capitis Staphylococcus chromogenes Staphylococcus cohnii ssp cohnii Staphylococcus cohnii ssp urealvticus Staphylococcus epidermidis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus hyicus Staphylococcus intermedius Staphylococcus kloosii Staphylococcus lentus Staphylococcus lugdunensis Staphylococcus pseudintermedius Staphylococcus saprophyticus Staphylococcus schleiferi Staphylococcus sciuri Staphylococcus simulans Staphylococcus warneri Staphylococcus xylosus Stenotrophomonas maltophilia Streptococcus agalactiae Streptococcus alactolyticus Streptococcus anginosus Streptococcus canis Streptococcus constellatus Streptococcus cristatus Streptococcus dysgalactiae ssp dysgalactiae Streptococcus dysgalactiae ssp equisimilis Streptococcus equi ssp equi Streptococcus equi ssp zooepidemicus Streptococcus equinus Streptococcus gallolyticus ssp gallolyticus Streptococcus gallolyticus ssp pasteurianus Streptococcus gordonii

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Streptococcus infantarius ssp coli (Str.lutetiensis) Streptococcus infantarius ssp infantarius Streptococcus intermedius Streptococcus mitis / Streptococcus oralis Streptococcus mutans Streptococcus parasanguinis Streptococcus pneumoniae Streptococcus pseudoporcinus Streptococcus pyogenes Streptococcus salivarius ssp salivarius Streptococcus sanguinis Streptococcus sobrinus Streptococcus suis Streptococcus uberis Streptococcus vestibularis Tannerella forsythia Veillonella dispar Vibrio alginolyticus Vibrio cholerae Vibrio fluvialis Vibrio metschnikovii Vibrio mimicus Vibrio parahaemolyticus Vibrio vulnificus Yersinia aldovae Yersinia enterocolitica Yersinia frederiksenii Yersinia intermedia Yersinia kristensenii Yersinia pseudotuberculosis Yersinia ruckeri

Mycobacterium

Mycobacterium abscessus Mycobacterium avium Mycobacterium chelonae Mycobacterium fortuitum group Mvcobacterium gordonae Mycobacterium haemophilum Mycobacterium immunogenum Mycobacterium intracellulare Mycobacterium kansasii Mycobacterium lentiflavum Mycobacterium malmoense Mycobacterium marinum Mycobacterium mucogenicum Mycobacterium scrofulaceum Mycobacterium simiae

Mycobacterium smegmatis Mycobacterium szulgai Mycobacterium tuberculosis complex Mycobacterium xenopi

Nocardia

Nocardia abscessus Nocardia africana / nova Nocardia asteroides Nocardia brasiliensis Nocardia cvriacigeorgica Nocardia farcinica Nocardia otitidiscaviarum Nocardia paucivorans Nocardia pseudobrasiliensis Nocardia transvalensis Nocardia veterana Nocardia wallacei

Mould

Acremonium sclerotigenum Alternaria alternata Aspergillus brasiliensis Aspergillus calidoustus / ustus Aspergillus flavus / oryzae Aspergillus fumigatus Aspergillus lentulus Aspergillus nidulans Aspergillus niger complex Aspergillus sydowii Aspergillus terreus complex Aspergillus versicolor Blastomyces dermatitidis Cladophialophora bantiana Coccidioides immitis / posadasii Curvularia hawaiiensis Curvularia spicifera Epidermophyton floccosum Exophiala dermatitidis Exophiala xenobiotica Exserohilum rostratum Fusarium oxysporum complex Fusarium proliferatum Fusarium solani complex Histoplasma capsulatum Lecythophora hoffmannii Lichtheimia corymbifera Microsporum audouinii

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Microsporum canis Microsporum gypseum Mucor racemosus complex Paecilomyces variotii complex Penicillium chrysogenum Pseudallescheria boydii Purpureocillium lilacinum Rasamsonia argillacea complex Rhizopus arrhizus complex Rhizopus microsporus complex Sarocladium kiliense Scedosporium apiospermum
Scedosporium prolificans Sporothrix schenckii complex Trichophyton interdigitale Trichophyton rubrum Trichophyton tonsurans Trichophyton verrucosum Trichophyton violaceum Trichosporon asahii Trichosporon dermatis / mucoides Trichosporon inkin

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510(k) SUMMARY

VITEK® MS

A. 510(k) Number: K181412

B. Purpose for Submission: Update to the VITEK® MS clinical Knowledge Base v3.2.0 to add new indications for use to the previously cleared device K162950 and DEN130013 (K124067)

C. Measurand: See Intended Use

D. Type of Test: A mass spectrometer system for clinical use for the identification of microorganisms is a qualitative in vitro diagnostic device intended for the identification of microorganisms cultured from human specimens. The device is comprised of an ionization source, a mass analyzer and a spectral database. The device is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infections.

E. Applicant:

Submitter's Name:	bioMérieux, Inc. on behalf of bioMérieux, SA
Address:	bioMérieux SA3 Route de Port Michaud.La Balme les Grottes, 38390 (France)
Contact Person:	Jennifer JinesRegulatory Affairs Specialist
Phone Number:	314 -731-8352
Fax Number:	314-731-8689
Date of Preparation:	May 18, 2018

F. Proprietary and Established Names:

Formal/Trade Name:	VITEK® MS
Common Name:	VITEK® MS, VITEK MS

G. Regulatory Information:

1. Regulation Section:	21 CFR 866.3378
2. Classification Name:	Clinical mass spectrometry microorganism identification anddifferentiation system
3. Product Code:	QBN
4. Panel:	Microbiology

H. Intended Use:

1. Intended use(s):
  VITEK® MS is a mass spectrometry system using matrix-assisted laser desorption/ionization – time of flight mass spectrometry (MALDI-TOF MS) for the identification of microorganisms cultured from human specimens.

The VITEK® MS is a qualitative in vitro diagnostic device indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial, yeast and mould infections.

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2. Indication(s) for use:

The following organisms are claimed:

Gram Negative / Positive Bacteria & Yeast

Abiotrophia defectiva Achromobacter denitrificans Achromobacter xylosoxidans Acinetobacter baumannii Acinetobacter calcoaceticus Acinetobacter haemolyticus Acinetobacter johnsonii Acinetobacter junii Acinetobacter lwoffii Acinetobacter nosocomialis Acinetobacter pittii Actinomyces bovis Actinomyces israelii Actinomyces meyeri Actinomyces naeslundii Actinomyces neuii Actinomyces odontolyticus Actinotignum schaalii Aerococcus viridans Aeromonas hydrophila Aeromonas jandaei Aeromonas punctata (caviae) Aeromonas sobria Aggregatibacter actinomycetemcomitans Aggregatibacter aphrophilus Aggregatibacter segnis Alcaligenes faecalis ssp faecalis Bacteroides caccae Bacteroides eggerthii Bacteroides fragilis Bacteroides ovatus / xylanisolvens Bacteroides pyogenes Bacteroides stercoris Bacteroides thetaiotaomicron Bacteroides uniformis Bacteroides vulgatus Bifidobacterium spp Bilophila wadsworthia Bordetella avium Bordetella bronchiseptica Bordetella parapertussis Bordetella pertussis Brevundimonas diminuta Brevundimonas vesicularis Brucella spp

Burkholderia cenocepacia Burkholderia cepacia Burkholderia contaminans Burkholderia gladioli Burkholderia multivorans Burkholderia vietnamiensis Campylobacter coli Campylobacter jejuni Campylobacter rectus Candida albicans Candida auris Candida dubliniensis Candida duobushaemulonii Candida famata Candida glabrata Candida guilliermondii Candida haemulonii Candida inconspicua Candida intermedia Candida kefyr Candida krusei Candida lambica Candida lipolytica Candida lusitaniae Candida metapsilosis Candida norvegensis Candida orthopsilosis Candida parapsilosis Candida pelliculosa Candida rugosa Candida tropicalis Candida utilis Candida zeylanoides Cedecea davisae Cedecea lapagei Cedecea neteri Chryseobacterium gleum Chryseobacterium indologenes Citrobacter amalonaticus Citrobacter braakii Citrobacter farmeri Citrobacter freundii Citrobacter koseri Citrobacter youngae Clostridium baratii Clostridium beijerinckii Clostridium butyricum Clostridium cadaveris

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Serratia fonticola Serratia grimesii Serratia liquefaciens Serratia marcescens Serratia odorifera Serratia plymuthica Serratia proteamaculans Serratia quinivorans Serratia rubidaea Shewanella putrefaciens Sphingobacterium multivorum Sphingobacterium spiritivorum Sphingomonas paucimobilis Staphylococcus aureus Staphylococcus auricularis Staphylococcus capitis Staphylococcus chromogenes Staphylococcus cohnii ssp cohnii Staphylococcus cohnii ssp urealyticus Staphylococcus epidermidis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus hyicus Staphylococcus intermedius Staphylococcus kloosii Staphylococcus lentus Staphylococcus lugdunensis Staphylococcus pseudintermedius Staphylococcus saprophyticus Staphylococcus schleiferi Staphylococcus sciuri Staphylococcus simulans Staphylococcus warneri Staphylococcus xylosus Stenotrophomonas maltophilia Streptococcus agalactiae Streptococcus alactolyticus Streptococcus anginosus Streptococcus canis Streptococcus constellatus Streptococcus cristatus Streptococcus dysgalactiae ssp dysgalactiae Streptococcus dysgalactiae ssp equisimilis Streptococcus equi ssp equi Streptococcus equi ssp zooepidemicus Streptococcus equinus Streptococcus gallolyticus ssp gallolyticus Streptococcus gallolyticus ssp pasteurianus Streptococcus gordonii

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Mycobacterium

Mycobacterium abscessus Mycobacterium avium Mycobacterium chelonae Mycobacterium fortuitum group Mycobacterium gordonae Mycobacterium haemophilum Mycobacterium immunogenum Mycobacterium intracellulare Mycobacterium kansasii Mycobacterium lentiflavum Mycobacterium malmoense Mycobacterium marinum Mycobacterium mucogenicum Mycobacterium scrofulaceum Mycobacterium simiae

Mycobacterium smegmatis Mycobacterium szulgai Mycobacterium tuberculosis complex Mycobacterium xenopi

Nocardia

Nocardia abscessus Nocardia africana / nova Nocardia asteroides Nocardia brasiliensis Nocardia cyriacigeorgica Nocardia farcinica Nocardia otitidiscaviarum Nocardia paucivorans Nocardia pseudobrasiliensis Nocardia transvalensis Nocardia veterana Nocardia wallacei

Mould

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Microsporum canis Microsporum gypseum Mucor racemosus complex Paecilomyces variotii complex Penicillium chrysogenum Pseudallescheria boydii Purpureocillium lilacinum Rasamsonia argillacea complex Rhizopus arrhizus complex Rhizopus microsporus complex Sarocladium kiliense Scedosporium apiospermum
Scedosporium prolificans Sporothrix schenckii complex Trichophyton interdigitale Trichophyton rubrum Trichophyton tonsurans Trichophyton verrucosum Trichophyton violaceum Trichosporon asahii Trichosporon dermatis / mucoides Trichosporon inkin

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Image /page/14/Picture/1 description: The image shows the logo for bioMerieux. The logo is a blue circle with the word "BIOMERIEUX" in white letters. The bottom half of the circle is green and yellow.

3. Special conditions for use statement(s):

The VITEK MS is for prescription use only in accordance with 21 CFR 801.109

4. Special instrument requirements:

VITEK® MS: Shimadzu AXIMA® Assurance mass spectrometer VITEK® MS Prep Station VITEK® MS-DS Target Slides

Reagents:

VITEK® MS-CHCA (Alpha-cyano-4-hydroxy-cinnamic acid) solution VITEK® MS-FA (Formic acid) reagent VITEK® MS MYCOBACTERIUM/NOCARDIA KIT VITEK® MS LIQUID MYCO SUPPLEMENTAL KIT VITEK® MS MOULD KIT

Database:

VITEK® MS v3.2.0 Knowledge Base (KB)

Software:

VITEK® MS Sample Prep Station software
VITEK® MS Acquisition Station
VITEK® MS Analysis Server / Software
VITEK® MS Computation Engine Myla® Middleware

I. Device Description:

The VITEK® MS v3.0 system is a system consisting of kit reagents (VITEK® MS-CHCA, VITEK® MS-FA, VITEK® MS Mycobacterium/Nocardia Kit, VITEK® MS Mould Kit), VITEK® MS-DS target slides, 17, 11 Er 115 Myobbaterialines and the VTEEN MO Modia Rith, The US Criginal equipment
VITEK® MS Prep Station, Knowledge Base v3.2.0, software, and the VITEK" MS (original eq

Reagent Description:

VITEK® MS-CHCA (Alpha-cyano-4-hydroxy-cinnamic acid) is the solution that serves as a matrix which will crystalize with the microbial sample on the target slide spot. 1.0 µl of the matrix is added to the spot with the sample and allowed to dry forming crystals.

The VITEK® MS-FA (Formic acid) reagent is used to pre-treat yeast in order to extract protein before the VITEK MS-CHCA matrix is added to the spot containing the sample.

VITEK® MS-DS target slides are single-use disposables which contain 3 acquisition groups of 16 sample spots. Each group includes 1 calibration spot. Target slides are for single use only.

VITEK® MS MYCOBACTERIUM/NOCARDIA KIT includes ethanol and vials with glass beads to inactivate mycobacteria and nocardia by disrupting the cells. The kit also includes formic acid and acetonitrile to complete the extraction of proteins.

VITEK® MS LIQUID MYCO SUPPLEMENTAL KIT includes the additional consumables (i.e., 5 mL conical bottom tubes and safety backed absorbent pads) needed to process samples for mycobacterium with liquid media.

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VITEK® MS MOULD KIT provides ethanol, formic acid and acetonitrile to inactivate moulds and extract their proteins.

Knowledge Base:

The reference database for the VITEK® MS system includes data representing 1316 species and 1158 taxa displayed. VITEK® MS Knowledge Base v3.2.0 includes 1095 species of bacteria (863 single species and 77 groups including 232 species of fungi (195 single species and 12 groups including 26 species).

Additional laboratory tests as determined by Microbiology laboratory protocols for low discrimination results or non-clinically validated organisms are necessary for the completion of the organism identification. Non-clinically validated organisms are displayed as (@ in the report.

Testing of non-clinically validated species or species not found in the database may result in an unidentified result or a misidentification.

Note: Interpretation of results and use of the VITEK® MS system require a competent laboratorian who should judiciously make use of experience, specimen information, and other pertinent procedures before reporting the identification of test organisms. Additional information known to the user, such as Gram stain reaction, colonial and cellular morphology, and growth aerobically or in CO2 should be considered when accepting VITEK® MS results.

Software:

The VITEK® MS system consists of a suite of applications that perform the overall system function. The system functions as a kiosk, not allowing the end-user to access any operating system functions. The end-user cannot access the native operating system configuration panels. The software application contains several processes that include handling all network activity, communication, and synchronization with the all the components. The VITEK® MS system software is comprised of four software components and MYLA middleware.

VITEK® MS Sample Prep Station software: The VITEK MS Prep Station is used to prepare 1. VITEK® MS-DS target slides. It consists of a computer workstation equipped with a barcode reader, Touch Screen and Virtual Keyboard.
VITEK® MS acquisition station: The Acquisition Station Software controls the VITEK MS to 2. acquire spectral data from each sample in turn and displays the spectra for the operator to review. The Acquisition Station displays the spectra and peak lists and transfers the peak lists to the VITEK MS Analysis Server.
VITEK® MS Analysis Server / Software: The VITEK MS Analysis Server is the software that 3. manages the VITEK MS workflow and computes VITEK MS identification results. It is a software component that resides on the Myla Server (PC).
VITEK® MS Computation Engine: The VITEK MS analysis server sends to the computation 4. enqine that calculates the identification results. The algorithms and mapping files required for identification are contained within the computation engine.
1. Myla® Middeware: Myla is a computer application ("Middleware"), based on Web technology, which allows data related to the laboratory workflow, laboratory instruments, Laboratory Information System (LIS), analysis results, etc. to be grouped together. Myla® interfaces between the bioMérieux instruments connected to the application (e.g., VITEK MS) and the Laboratory Information System (LIS). Myla® is the user interface for the review and approval of the VITEK® MS identification results.

VITEK® MS:

bioMérieux's VITEK® MS. is the same instrument as the Shimadzu Axima Assurance MALDI TOF spectrometer. The VITEK MS is manufactured for bioMérieux by Kratos Analytical (a Shimadzu subsidiary) in Manchester, UK. The VITEK MS contains a Class 1 laser product containing a Class 3b invisible-light laser. The laser is a 337 nm nitrogen laser, fixed focus. This speed depends on the mass of the ions with heavier molecules having a higher moment

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of inertia resulting in a lower velocity. The time of transit is measured precisely by the ions' arrival at a particle detector. Based on the time of flight, the m/z ratio of each particle can be determined, and a mass spectrum of the sample mixture is generated. The recorded signal is processed by the Acquisition Station software and presented as a spectrum of intensity versus mass in Daltons (Da).

J. Substantial Equivalence Information:

1. Predicate Device Name:
  MALDI Biotyper CA System
1. Predicate Device De Novo Submission Number:
  DEN170081
1. Comparison with predicate:

Similarities
Characteristic	New DeviceVITEK® MS v3 / KB v3.2.0	Predicate DeviceMALDI Biotyper CA System(DEN170081)
Classification	Classification Name: MassSpectrometry, Maldi Tof,Microorganism Identification,Cultured isolatesRegulation Number: 21 CFR866.3378	Classification Name: MassSpectrometry, Maldi Tof,Microorganism Identification,Cultured isolatesRegulation Number: 21 CFR866.3378
Product Code	QBN	QBN
Intended Use	VITEK® MS is a massspectrometry system using matrix-assisted laser desorption/ionization - time of flight massspectrometry (MALDI-TOF MS) forthe identification ofmicroorganisms cultured fromhuman specimens.The VITEK® MS is a qualitative invitro diagnostic device indicatedfor use in conjunction with otherclinical and laboratory findings toaid in the diagnosis of bacterial,yeast and mould infections.	The MALDI Biotyper CA System is amass spectrometer system usingmatrix-assisted laser desorption/ionization - time of flight (MALDI-TOF) for the identification anddifferentiation of microorganismscultured from human specimens.The MALDI Biotyper CA System is aqualitative in vitro diagnostic deviceindicated for use in conjunction withother clinical and laboratory findingsto aid in the diagnosis of bacterialand fungal infections
Sample Type	Isolated colony from a patientsample source, from mediaincluding:- BacT/ALERT® MP (liquidculture media bottle)- Brucella agar base- Buffered charcoal yeastextract- Campylosel agar- Chocolate polyvitex agar- chromID CPS- Coletsos	Isolated colony from any patientsample source.Acceptable media:-Columbia blood agar with 5%sheep blood (Gram-negativebacteria)-Columbia CNA agar with 5%sheep blood (Gram-positivebacteria)-Trypticase soy agar with 5%sheep blood (Gram-negative

	- Columbia blood agar with5% sheep blood- Lowenstein-Jensen- MacConkey agar- MGITTM (liquid culturemedia bottle)- Middlebrook 7H10 agar- Middlebrook 7H11 agar- Modified Sabourauddextrose agar (glucose:20 g/l - pH: 6.1)- Potato dextrose agar- Sabouraud dextrose agar(glucose: 40 g/l - pH: 5.6)- Sabouraud dextrose agarwith Gentamicin &Chloramphenicol- Trypticase soy agar- Trypticase soy agar with5% sheep blood- Trypticase soy agar withneutralizers- BacT/ALERT® MP- Campylosel agar- chromID CPS- Coletsos- Lowenstein-Jensen- MGITTM- Middlebrook 7H10 agar- Middlebrook 7H11 agar- Modified Sabourauddextrose agar (glucose:20 g/l - pH: 6.1)- Potato dextrose agar- Sabouraud dextrose agarwith Gentamicin &Chloramphenicol- Trypticase soy agar withneutralizers* Non-bioMérieux mediaNote: Some media are differentthan the media for the predicatedevice.	- bacteria, Gram-positivebacteria, yeasts)- Chocolate agar (Gram-negativebacteria, Gram-positivebacteria)- MacConkey Agar (Gram-negative bacteria)- Brucella Agar with 5% horseblood (Gram-negative anaerobicbacteria, Gram-positiveanaerobic bacteria)- Sabouraud-Dextrose Agar(Yeasts)- CDC anaerobe Agar with 5%sheep blood (Gram-negativeanaerobic bacteria, Gram-positive anaerobic bacteria)- CDC anaerobe 5% sheepblood Agar with phenylethylalcohol (Gram-negativeanaerobic bacteria, Gram-positive anaerobic bacteria)- CDC anaerobe laked sheepblood Agar with kanamycin andvancomycin (Gram-negativeanaerobic bacilli)- Bacteroides bile esculin Agarwith amikacin (Bacteroidesspecies)- Clostridium difficile Agar with7% sheep blood (Clostridiumdifficile)- Brain Heart Infusion Agar(Yeasts)- Campylobacter Agar with 5Antimicrobics and 10% SheepBlood (Campylobacter species)- Bordet Gengou Agar with 15%sheep blood (Bordetellaspecies)
Type of Test	Automated Mass SpectrometrySystem	Automated Mass SpectrometrySystem
Matrix	alpha-cyano-4-hydroxy-cinnamicacid	alpha-cyano-4-hydroxy-cinnamicacid
Method of Testing	The sample prep for bacteria andyeast is direct testing from isolatedcolonies. Inactivation of thesample occurs during the additionof the CHCA Matrix.For sample prep of Mycobacteria,Nocardia and mould, aninactivation and extraction processis required prior to spotting thesample to the VITEK® MS-DSTarget Slide.	Bacteria & Yeast: Direct testingIf after initial analysis the log(score)is reported at <2.00, organisms maybe processed using the Extraction(Ext) procedure or extended DirectTransfer (eDT, 70% aqueous formicacid). If eDT method still yieldslog(score) <2.0, organism may beprocessed via Ext procedure.

Result Reporting	For Brucella sample prep, aninactivation process is requiredprior to spotting the sample to theVITEK® MS-DS Target Slide.	Organism identification is reportedwith high confidence if thelog(score) is >2.0. An organismidentification is reported with lowconfidence if the log(score) isbetween 1.70 and <2.00.
	To detect microbial growth, theVITEK MS System uses aknowledge base developed fromspectra of a number of microbialspecies. The resulting spectrafrom the VITEK MS / AcquisitionStation are evaluated against thisknowledge.Identification are displayed, with aconfidence value when anorganism or organism group isidentified. Low-discriminationidentifications are displayed whenmore than one, but not more thanfour identifications, are made.When more than fouridentifications are made, or whenno match is found, the organism isconsidered unidentified.Data analysis is performed usingsoftware embedded on the MYLA®Server.

Algorithm	An algorithm process known as"mass binning" is used for thedifferentiation of the speciesincluded in the knowledge base.	Calculates matches by comparing anew spectrumagainst each single reference entryof a reference database.
Recorded MassRange	2,000 - 20,000 m/z	2,000 - 20,000 m/z
Laser	Class 1 Laser Product - 337 nmfixed focus, nitrogen laser	Class 1 Laser product (class 4 withsafety cover opened) - 337 nm fixedfocus, nitrogen laser

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Differences
Characteristic	New DeviceVITEK® MS v3 / KB v3.2.0	Predicate DeviceMALDI Biotyper CA System(DEN170081)
Knowledge Baseand Indicationsfor Use	VITEK® MS v3.2 Knowledge Base	MALDI Biotyper Reference Libraryfor Clinical Applications (MBT-CA)
MALDI-TOF MSinstrument	Shimadzu AXIMA® Assurance MS	Bruker microflex LT/SH (benchtop)Bruker microflex LT/SH smart(benchtop)
SystemComponents,Software,Reagents	The VITEK® MS system consists of anumber of components,- a Prep Station- the MS Instrument- an Acquisition Station- software/middleware solutionsincluding,	The MBT-CA System consists ofthe microflex LT/SH massspectrometer, reference library, kitreagents, US IVD 48 Spot Targetor MBT Biotarget 96 US IVD plate,and software.Software:

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BIOMÉRIEUX

	Acquisition Station Software, an Analysis Server, a Computation Engine, MYLA® - disposables/consumables the VITEK® MS-DS Target Slides, CHCA Matrix, Formic Acid, VITEK® MSMycobacetium/Nocardia Kit, VITEK® MS Mould Kit	MBT-CA System Software Package: MBT-CA System client software displaying the user interface, MBT-CA System Server, and MBT-CA System DB Server flexControl Software Package: GTPS firmware and flexControl acquisition software Reagents:• US IVD Bacterial Test Standard (BTS)• US IVD HCCA portioned (α-Cyano-4-hydroxycinnamic acid)
Calibration	E. coli ATCC 8739	Bruker US IVD Bacterial Test Standard

K. Standard/Guidance Document Referenced (if applicable):

. FDA/CDRH/ODE Evaluation of Automatic Class III Designation, Guidance for Industry and CDRH Staff (February 19, 1998)
. FDA Guidance Document, "Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable" (April 25, 2006)
. Statistical Guidance on Reporting Results From Studies Evaluation Diagnostic Tests (March 13, 2007)
CLSI C50-A Mass Spectrometry in the Clinical Laboratory: General Principles and Guidance; Approved Guideline, 1st edition (October 29, 2007)
CLSI MM09-A Nucleic Acid Sequencing Methods in Diagnostic Laboratory Medicine; . Approved Guideline, 2nd edition (August 14, 2015)
CLSI MM18-A Interpretive Criteria for Identification of Bacteria and Fungi by DNA Target Sequencing; Approved Guideline, 1st edition (April 28, 2008)
CLSI M35-A2 Abbreviated Identification of Bacteria and Yeast, Approved Guideline, 200 . edition (November 24, 2008)
. CLSI EP09-A3 Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline, 30 edition (August 30, 2013)
CLSI EP12-A2 User Protocol for Evaluation of Qualitative Test Performance; Approved . Guideline, 2nd edition (January 25, 2008)

L. Test Principle:

The VITEK MS system is based on a matrix-assisted laser desorption ionization-time of flight mass spectrometer (MALDI-TOF MS). The colony is mixed with a saturated matrix solution and forms crystals. The ionization of this mixture by the laser induces the desorption and transfer of protons from photo-excited matrix to analyte to form a protonated molecule. During the analysis process, proteins are ionized without fragmentation by the coordinated

M. Performance Characteristics (if/when applicable):

Performance Characteristics:

The following performance characteristics were obtained by testing routine fresh and stock

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strains from patient cultures in clinical microbiology laboratories and bioMérieux laboratories in the United States and France. The strains included:

Gram-positive bacteria ●
. Gram-negative bacteria (including Brucella)
. Yeasts
. Moulds
Mycobacterium
Nocardia ●

VITEK® MS IDENTIFICATION
Organism Group	Total CorrectGenus ID (OneChoice and LowDiscrimination)	One ChoiceCorrect: Species ID or Group/Complex ID		Low DiscriminationCorrect: Genus ID		Discordant ID 3	No ID 4
		One choicereferenceresult	Multiplechoicereferenceresult 1	One choicereferenceresult	Multiplechoicereferenceresult 2
Gram-positive bacteria	95.8%(3594/3750)95% CI [95.2 ; 96.5]%	89.9%(3372/3750)	1.9%(29/1494)	5.0%(188/3750)	0.3%(5/1494)	0.4%(14/3750)	3.8%(142/3750)
Gram-negative bacteria	95.2%(5788/6079)95% CI [94.6 ; 95.7]%	88.9%(5407/6079)	0.1%(2/2543)	6.2%(379/6079)	0.0%(0/2543)	1.0%(60/6079)	3.8%(231/6079)
Gram-negativebacteria (Brucella only)	91.7%(220/240)95% CI [87.4 ; 94.8]%	91.7%(220/240)	0.0%(0/240)	0.0%(0/240) 5	0.0%(0/240)	0.0%(0/240)	8.3%(20/240) 6
Yeasts	96.8%(1316/1360)95% CI [95.7 ; 97.6]%	95.9%(1304/1360)	0.5%(1/204)	0.8%(11/1360)	0.0%(0/204)	0.1%(2/1360)	3.1%(42/1360)
Moulds	92.7%(1398/1508)95% CI [91.3 ; 94.0]%	91.2%(1376/1508)	N/A	1.5%(22/1508)	N/A	0.9%(13/1508)	6.4%(97/1508)
Mycobacterium	96.5%(777/805)95% CI [95.0 ; 97.7]%	96.5%(777/805)	N/A	0.0%(0/805)	N/A	0.4%(3/805)	3.1%(25/805)
Mycobacterium Solid	97.4%(713/732)95% CI [96.0 ; 98.4]%	97.4%(713/732)	N/A	0.0%(0/732)	N/A	0.1%(1/732)	2.5%(18/732)
Mycobacterium Liquid	87.7%(64/73)95% CI [77.9 ; 94.2]%	87.7%(64/73)	N/A	0.0%(0/73)	N/A	2.7%(2/73)	9.6%(7/73)
Nocardia	97.9%(374/382)95% CI [95.9 ; 99.1]%	89.3%(341/382)	N/A	8.6%(33/382)	N/A	0.8%(3/382)	1.3%(5/382)
Total	95.4%(13247/13884)95% CI [95.1 ; 95.8]%	90.6%(12577/13884)	0.8%(32/4241)	4.6%(633/13884) 7	0.1%(5/4241) 7	0.7%(95/13884)	3.9%(542/13884)

1 = Reference ID represents multiple related species that cannot be resolved by sequencing rDNA and the VITEK® MS result matches one of these reference results. Only reference results to a species level were included for V2.0 and V3.0 claimed organisms are designated by N/A in the Muliple Choice Reference Result column in the performance tables.

2 = Reference ID represents correct Genus with multiple reated species that cannot be resolved by sequencing rDNA and he VITEK® MS result matches the reference result at a Genus level to a species level were included for Y2.0 and V30 claimed organisms, and
these organisms are designated by N/A in the Multipl

s = Includes single choice incorrect identification results wih >1 choice in the same genus but the genus does not match the reference genus.

4 = Includes Low Discrimination with multiple genera or No ID (Bad Spectra, Not Enough Peaks (Bad spectrum), or No ID (Good spectrum)).

s = On occasions the VITEK® MS result for Brucella spp will report as a low discrimination result of Brucella spp, even though it is a single choice correct identification of Brucella spp. This will be corrected in a future software release.

6 = Of the 240 Brucella spp strains tested in he cinical trial, 20 (8.3%) resulted in No ID. Samples suspected of Brucelled accordingly.

7 = Of the 707 low discrimination same genus results, 689 (97.5%) had the correct species present and 18 (2.5%) did not have the correct species present.

Clinical studies:

The objective of the clinical trial is to evaluate the percent agreement of the VITEK® MS to identify microorganisms in a clinical setting as compared to the reference method [DNA sequencing analysis and supplemental testing when necessary, or previously well characterized strains (ATCC or equivalent)]. Samples were sequenced by the appropriate reference laboratory, and if needed,

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additional analysis was performed internally to obtain a reference identification (GenBank, dendrogram analysis). Organisms tested during the clinical trial included aerobic gram positive and gram negative bacteria, including Brucella, and yeasts.

The VITEK® MS KB v3.2.0 clinical trial consisted of quality control and clinical testing of bacteria (other than Brucella) and yeasts at one external clinical trial site and one internal site. For Brucella, clinical trial testing consisted of quality control, reproducibility, challenge and clinical testing at one external clinical trial site. Prior to initiation of the clinical trial, a proficiency panel was tested by all participating technologists at the external sites to ensure adequate training.

A total of 4,241 test results are included in the performance data.

Performance was determined by comparing the VITEK® MS identification to a one choice or multiple choice (more than one species) reference identification.

The VITEK® MS v3 / KB v3.2.0 release demonstrated high performance at 98.8% (4189/4241) agreement for clinical isolates tested, with a very low number of discordant (0.3%) and no identification (0.9%) results obtained. When excluding No ID results, performance improves to 99.7% (4189/4201) agreement with the same low discordant rate of 0.3%.

Overall performance for all organisms tested from all sites combined:

Organism Classification	N	Number ofUniqueIsolates	Total Correct GENUS ID(One Choice and Low Discrim.)	One ChoiceCorrect: Genus IDCorrect: Species ID or Group/Complex ID		Low DiscriminationCorrect: Genus ID		Discordant ID	No ID
				One choicereference result	Multiple choice reference result1	One choicereference result	Multiple choice reference result2
Gram + Bacteria	Aerobic	801	281	99.4% (796/801)	86.1% (690/801)	0.5% (4/801)	12.1% (97/801)	0.6% (5/801)	0.0% (0/801)	0.6% (5/801)
Gram + Bacteria	Anaerobic	693	205	99.3% (688/693)	95.5% (662/693)	3.6% (25/693)	0.1% (1/693)	0.0% (0/693)	0.0% (0/693)	0.7% (5/693)
Gram + Bacteria	Total	1494	486	99.3% (1484/1494)	90.5% (1352/1494)	1.9% (29/1494)	6.6% (98/1494)	0.3% (5/1494)	0.0% (0/1494)	0.7% (10/1494)
Gram - Bacteria	Aerobic	2119	570	98.2% (2080/2119)	92.5% (1960/2119)	0.1% (2/2119)	5.6% (118/2119)	0.0% (0/2119)	0.6% (12/2119)	1.3% (27/2119)
Gram - Bacteria	Anaerobic	424	72	99.5% (422/424)	99.3% (421/424)	0.0% (0/424)	0.2% (1/424)	0.0% (0/424)	0.0% (0/424)	0.5% (2/424)
Gram - Bacteria	Total	2543	642	98.4% (2502/2543)	93.6% (2381/2543)	0.1% (2/2543)	4.7% (119/2543)	0.0% (0/2543)	0.5% (12/2543)	1.1% (29/2543)
Yeasts	Total	204	44	99.5% (203/204)	99.0% (202/204)	0.5% (1/204)	0.0% (0/204)	0.0% (0/204)	0.0% (0/204)	0.5% (1/204)
-All-	Grand Total	4241	1172	98.8% (4189/4241)	92.8% (3935/4241)	0.8% (32/4241)	5.1% (217/4241)	0.1% (5/4241)	0.3% (12/4241)	0.9% (40/4241)

Reference ID represents multip e re ated spec es that cannot be resolved by sequencing rDNA and the VITEK MS resut matches one of these reference resuts

²Reference ID represents correct Genus w th multiple related species that cannot be resolved by sequencing rDNA and the VITEK MS resut matches the reference result at a Genus level

98.8% (4189/4241) agreement, 95% Cl [98.3%, 99.0%], was obtained for all clinical bacteria and veast isolates tested (correct one choice identification plus a low discrimination correct genus result) from all sites combined, with 12 (0.3%) misidentifications and 40 (0.9%) No ID results.

Overall performance for all orqanisms tested from all sites combined excluding No ID results:

	VITEK MS KB 3.2 Overall Performance for All Sites Combined - Excluding No ID Results
	VITEK MS IDENTIFICATION
Organism Classification		N	Number ofUniqueIsolates	Total Correct GENUS ID(One Choice and Low Discrim.)	One ChoiceCorrect: Genus IDCorrect: Species ID or Group/Complex ID		Low DiscriminationCorrect: Genus ID		Discordant ID
					One choicereference result	Multiple choice reference result1	One choicereference result	Multiple choice reference result2
Gram + Bacteria	Aerobic	796	278	100.0% (796/796)	86.7% (690/796)	0.5% (4/796)	12.2% (97/796)	0.6% (5/796)	0.0% (0/796)
Gram + Bacteria	Anaerobic	688	203	100.0% (688/688)	96.2% (662/688)	3.6% (25/688)	0.1% (1/688)	0.0% (0/688)	0.0% (0/688)
Gram + Bacteria	Total	1484	481	100.0% (1484/1484)	91.1% (1352/1484)	2.0% (29/1484)	6.6% (98/1484)	0.3% (5/1484)	0.0% (0/1484)
Gram - Bacteria	Aerobic	2092	561	99.4% (2080/2092)	93.7% (1960/2092)	0.1% (2/2092)	5.6% (118/2092)	0.0% (0/2092)	0.6% (12/2092)
Gram - Bacteria	Anaerobic	422	70	100.0% (422/422)	99.8% (421/422)	0.0% (0/422)	0.2% (1/422)	0.0% (0/422)	0.0% (0/422)
Gram - Bacteria	Total	2514	631	99.5% (2502/2514)	94.7% (2381/2514)	0.1% (2/2514)	4.7% (119/2514)	0.0% (0/2514)	0.5% (12/2514)
Yeasts	Total	203	43	100.0% (203/203)	99.5% (202/203)	0.5% (1/203)	0.0% (0/203)	0.0% (0/203)	0.0% (0/203)
~~All~~	Grand Total	4201	1155	99.7% (4189/4201)	93.7% (3935/4201)	0.8% (32/4201)	5.2% (217/4201)	0.1% (5/4201)	0.3% (12/4201)

Reference ID represents multiple related speces that cannot be resolved by sequencing rDNA and the VITEK MS resut matches one of these reference resuts

*Reference ID represents correct Genus with mutiple re ated spec es that cannot be resolved by sequencing rDNA and the VITEK MS result matches the reference result at a Genus

99.7% (4189/4201) agreement, 95% Cl [99.5%, 99.8%], was obtained for all clinical bacteria and yeast isolates tested (correct one choice identification plus a low discrimination correct genus result) from all sites combined when excluding No ID results, with 12 (0.3%) misidentifications.

Overall performance of Brucella organisms tested at ATCC:

VITEK MS KB 3.2 Overall Performance for ATCC
VITEK MS IDENTIFICATION Site: ATCC
Organism Classification		N	Number ofUniqueIsolates	Total Correct GENUS ID(One Choice and Low Discrim.)	One ChoiceCorrect: Genus IDCorrect: Species ID or Group/Complex ID		Low DiscriminationCorrect: Genus ID		Discordant ID	No ID
					One choicereference result	Multiple choice reference result1	One choicereference result	Multiple choice reference result2
Brucella	Total	240	50	91.7% (220/240)	91.7% (220/240)	0.0% (0/240)	0.0% (0/240)	0.0% (0/240)	0.0% (0/240)	8.3% (20/240)

¹Reference D represents mu tiple related species that cannot be resolved by sequencing rDNA and the VITEK MS result ma ches one of these reference resul s

²Reference D represents correct Genus with mutinereated species that cannot be resolved by sequencing rDNA and the VITEK MS result matches the reference resut at a Genus level

Reference: Drepresents correct Genus & in multiple species that cannot be resolved by sequencing rDNA and the VITEK MS result matches the reference result at a Genus level
Note: On occasion the VITEK MS result for Brucella spp will report as a low discrimination result of Brucella spp / Brucella spp, even though it is a single choice correct identification of Brucella spp. This will be corrected in a future software release.

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91.7% (220/240) agreement, 95% Cl [87.4%, 94.8%], was obtained for all Brucella isolates tested at ATCC, with 20 (8.3%) No ID results and no misidentifications.

Overall performance of Brucella organisms tested at ATCC excluding No ID results:

Organism Classification		N	Number ofUniqueIsolates	Total Correct GENUS ID(One Choice and Low Discrim.)	VITEK MS IDENTIFICATION Site: ATCCOne ChoiceCorrect: Genus IDCorrect: Species ID or Group/Complex ID		Low DiscriminationCorrect: Genus ID		Discordant ID
					One choicereference result	Multiple choice reference result1	One choicereference result	Multiple choice reference result2
Brucella	Total	220	45	100.0% (220/220)	100.0% (220/220)	0.0% (0/220)	0.0% (0/220)	0.0% (0/220)	0.0% (0/220)
1Reference ID represents multiple related species that cannot be resolved by sequencing rDNA and the VITEK MS result matches one of these reference results.2Reference ID represents correct Genus w th multiple related species that cannot be resolved by sequencing rDNA and the VITEK MS result matches the reference result at a Genus level.

100% (220/220) agreement, 95% Cl [98.3%, 100.0%], was obtained for all Brucella isolates tested at ATCC when excluding No ID results, with no misidentifications.

Overall performance of Brucella reproducibility testing:

VITEK MS KB 3.2 REPRODUCIBILITY
Sample	Organism	Day					Total (%)	95% CI
		1	2	3	4	5
R1	Brucella abortus	12/12	12/12	12/12	12/12	12/12	60/60 (100.0%)	[94.0, 100.0]%
R2	Brucella melitensis	12/12	12/12	12/12	12/12	12/12	60/60 (100.0%)	[94.0, 100.0]%
R3	Brucella suis	12/12	12/12	12/12	12/12	12/12	60/60 (100.0%)	[94.0, 100.0]%
All	All	36/36	36/36	36/36	36/36	36/36	180/180 (100.0%)	[98.0, 100.0]%

NOTE: Reproducibility results display the Brucella species tested (Brucella melitensis and Brucella suis). However, the VITEK MS will only provide a genus level identification of Brucella spp in Myla. 100% agreement was obtained with the Brucella reproducibility strains tested at ATCC.

Overall performance of Brucella challenge testing:

VITEK MS KB3.2 BRUCELLA CHALLENGE
		VITEK MS IDENTIFICATION
Organism Classification		N	Number ofUniqueIsolates	Total Correct GENUS ID(One Choice and Low Discrim.)	One ChoiceCorrect: Genus IDCorrect: Species ID or Group/Complex ID		Low DiscriminationCorrect: Genus ID		Discordant ID	No ID
					One choicereference result	Multiple choice reference result1	One choicereference result	Multiple choice reference result2
Brucella spp	Total	15	45	64.4% (29/45)	64.4% (29/45)	0.0% (0/45)	0.0% (0/45)	0.0% (0/45)	0.0% (0/45)	35.6% (16/45)
1Reference Drepresents multiple related species that cannot be resolved by sequencing rDNA and the VITEK MS result matches one of these reference results2Reference Drepresents correct Genus with multiple related species that cannot be resolved by sequencing rDNA and the VITEK MS result matches the reference result at a Genus levelNote: On occasion the VITEK MS result for Brucella spp will report as a low discrimination result of Brucella spp / Brucella spp, even though it is a single choice correct den ification of Brucella spp. This will be corrected in a future software release.

Organism Classification	N	Number of	Total Correct GENUS ID	VITEK MS IDENTIFICATIONOne Choice		Low Discrimination		Discordant ID
	Total			One choice	Multiple choice reference result	One choice	Multiple choice reference result²
Brucella spp	12	29	100.0% (29/29)	100.0% (29/29)	0.0% (0/29)	0.0% (0/29)	0.0% (0/29)	0.0% (0/29)
Reference D represents multiple related species that cannot be resolved by sequencing rDNA and the VITEK MS result matches one of these reference results
²Reference D represents correct Genus with multiple related species that cannot be resolved by sequencing rDNA and the VITEK MS result matches the reference result at a Genus evel

64.4% (29/45) agreement was obtained for the 15 Brucella challenge strains tested at ATCC in triplicate, with 16 (35.6%) No ID results and no misidentifications.100% (29/29) agreement was obtained when excluding No ID results.

Overall performance of quality control testing:

VITEK MS KB 3.2 QUALITY CONTROL
		Correct ID/Total (%) Per Site
Organism Identification	ATCC	CCF	LBM	All SitesCombined
*Brucella melitensis	48/48 (100.0%)			48/48 (100.0%)
Candida glabrata		27/27 (100.0%)	24/24 (100.0%)	51/51 (100.0%)
Enterobacter aerogenes		47/47 (100.0%)	47/47 (100.0%)	94/94 (100.0%)
Negative Control	51/51 (100.0%)	48/48 (100.0%)	49/49 (100.0%)	148/148 (100.0%)

Quality control result displays as Brucella melitensis . However, the VITEK MS will only provide a genus level identification of Brucella spp in Myla.

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100% agreement was obtained with the all quality control strains tested at all sites.

N. Instrument Name:

VITEK® MS

Regulation Number and Section

§ 866.3378 Clinical mass spectrometry microorganism identification and differentiation system.

(a)
Identification. A clinical mass spectrometry microorganism identification and differentiation system is a qualitative in vitro diagnostic device intended for the identification and differentiation of microorganisms from processed human specimens. The system acquires, processes, and analyzes spectra to generate data specific to a microorganism(s). The device is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infection.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use statement must include a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended, when applicable.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt with an indication for in vitro diagnostic use.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology and all pre-analytical methods for processing of specimens, and algorithm used to generate a final result. This must include a description of validated inactivation procedure(s) that are confirmed through a viability testing protocol, as applicable.
(ii) Performance characteristics for all claimed sample types from clinical studies with clinical specimens that include prospective samples and/or, if appropriate, characterized samples.
(iii) Performance characteristics of the device for all claimed sample types based on analytical studies, including limit of detection, inclusivity, reproducibility, interference, cross-reactivity, interfering substances, carryover/cross-contamination, sample stability, and additional studies regarding processed specimen type and intended use claims, as applicable.
(iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing.
(4) The device's labeling must include a prominent hyperlink to the manufacturer's website where the manufacturer must make available their most recent version of the device's labeling required under § 809.10(b) of this chapter, which must reflect any changes in the performance characteristics of the device. FDA must have unrestricted access to this website, or manufacturers must provide this information to FDA through an alternative method that is considered and determined by FDA to be acceptable and appropriate.
(5) Design verification and validation must include:
(i) Any clinical studies must be performed with samples representative of the intended use population and compare the device performance to results obtained from an FDA-accepted reference method and/or FDA-accepted comparator method, as appropriate. Documentation from the clinical studies must include the clinical study protocol (including predefined statistical analysis plan, if applicable), clinical study report, and results of all statistical analyses.
(ii) Performance characteristics for analytical and clinical studies for specific identification processes for the following, as appropriate:
(A) Bacteria,
(B) Yeasts,
(C) Molds,
(D) Mycobacteria,
(E) Nocardia,
(F) Direct sample testing (
e.g., blood culture),(G) Antibiotic resistance markers, and
(H) Select agents (
e.g., pathogens of high consequence).(iii) Documentation that the manufacturer's risk mitigation strategy ensures that their device does not prevent any device(s) with which it is indicated for use, including incorporated device(s), from achieving their intended use (
e.g., safety and effectiveness of the functions of the indicated device(s) remain unaffected).(iv) A detailed device description, including the following:
(A) Overall device design, including all device components and all control elements incorporated into the testing procedure.
(B) Algorithm used to generate a final result from raw data (
e.g., how raw signals are converted into a reported result).(C) A detailed description of device software, including validation activities and outcomes.
(D) Acquisition parameters (
e.g., mass range, laser power, laser profile and number of laser shots per profile, raster scan, signal-to-noise threshold) used to generate data specific to a microorganism.(E) Implementation methodology, construction parameters, and quality assurance protocols, including the standard operating protocol for generation of reference entries for the device.
(F) For each claimed microorganism characteristic, a minimum of five reference entries for each organism (including the type strain for microorganism identification), or, if there are fewer reference entries, a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, for why five reference entries are not needed.
(G) DNA sequence analysis characterizing all type strains and at least 20 percent of the non-type strains of a species detected by the device, or, if there are fewer strain sequences, then a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, must be provided for the reduced number of strains sequenced.
(H) As part of the risk management activities, an appropriate end user device training program, which must be offered as an effort to mitigate the risk of failure from user error.