The MBT Sepsityper is a qualitative in vitro diagnostic device consisting of a MBT-CA (Sepsityper) software extension and a reagent kit (MBT Sepsityper Kit US IVD) for use in conjunction with other clinical and laboratory findings to aid in the early diagnosis of bacterial and yeast infections from positively flagged blood cultures using the MALDI Biotyper CA System.

The MBT Sepsityper Kit US IVD is a disposable blood culture processing device that includes associated reagents that are intended to concentrate and purify microbial cells from blood culture samples identified as positive by a continuous monitoring blood culture system and confirmed to demonstrate the presence of a single organism as determined by Gram stain. This sample preparation manual method is performed by laboratory health a clinical diagnostic setting.

Subculturing of positive blood cultures is necessary to recover organisms for identification of organisms not identified by the MBT-CA System, for susceptibility testing and for differentiation of mixed growth.

Positive MBT Sepsityper results do not rule out co-infection with organisms that may not be detected by the MBT-CA System. Results of the MBT Sepsityper should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Results of the MBT Sepsityper should be correlated with Gram stain results and used in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and yeast bloodstream infections.

Device Description

The MBT Sepsityper is a qualitative in vitro diagnostic device consisting of a MBT-CA (Sepsityper) software extension and a reagent kit (MBT Sepsityper Kit US IVD). The MBT Sepsityper Kit US IVD is a disposable blood culture processing device that includes associated reagents that are intended to concentrate and purify microbial cells from blood culture samples identified as positive by a continuous monitoring blood culture system and confirmed to demonstrate the presence of a single organism as determined by Gram stain. This sample preparation manual method is performed by laboratory health a clinical diagnostic setting.

AI/ML Overview

The provided text is related to an FDA 510(k) clearance for a medical device (MBT Sepsityper) and primarily describes its indications for use, regulatory classification, and the types of organisms it can identify. It does NOT contain the detailed information necessary to fully address all parts of your request regarding acceptance criteria and the study proving the device meets those criteria.

Specifically, the document does not include:

A table of acceptance criteria and reported device performance.
Sample sizes used for test and training sets, or data provenance.
Information on expert ground truth establishment (number of experts, qualifications, adjudication).
Details about MRMC comparative effectiveness studies or standalone algorithm performance.
Specifics on how ground truth was established for training or test sets (e.g., pathology, outcomes data).

Therefore, I can only address the parts for which information is implicitly or explicitly available in the provided text.

Based on the provided information, here's what can be gathered:

1. A table of acceptance criteria and the reported device performance:

This information is not provided in the document. The document is an FDA clearance letter, which typically summarizes the outcome of the review rather than providing the raw performance data or the detailed acceptance criteria used in the validation study.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):

This information is not provided in the document. The document mentions that the device is "for use in conjunction with other clinical and laboratory findings to aid in the early diagnosis of bacterial and yeast infections from positively flagged blood cultures." It also lists a wide range of bacteria and yeasts the device is intended to identify, implying that a significant amount of data was used for validation, but specific sample sizes and provenance are absent.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):

This information is not provided in the document. For in vitro diagnostic microbiology devices like this, ground truth is typically established by definitive laboratory methods (e.g., sequencing, advanced biochemical tests) rather than expert human interpretation of images, but the specifics are not detailed here.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

This information is not provided in the document. Adjudication methods are typically relevant for studies involving human interpretation of complex medical images, which is not the primary function of this device.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

This information is not provided in the document. MRMC studies are generally applicable to imaging devices where human interpretation plays a significant role. This device is an in vitro diagnostic system for microorganism identification using mass spectrometry, not an AI-assisted diagnostic imaging tool.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

The device is described as "a qualitative in vitro diagnostic device consisting of a MBT-CA (Sepsityper) software extension and a reagent kit." This implies that the software performs the identification based on mass spectrometry data, making it a standalone algorithm in terms of the identification process itself. However, the clearance states it is "for use in conjunction with other clinical and laboratory findings," and that "results should not be used as the sole basis for diagnosis," indicating that human oversight and integration with other clinical data are required downstream. The document does not explicitly state if standalone performance metrics (e.g., sensitivity, specificity) of the algorithm alone were evaluated as a distinct part of the study, separate from its overall clinical utility.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

While not explicitly stated in detail, for an in vitro diagnostic device identifying microorganisms, the ground truth would almost certainly be established by definitive microbiological methods, such as:

Reference culture methods: Gold standard growth and biochemical identification.
Molecular methods: DNA sequencing (e.g., 16S rRNA gene sequencing for bacteria, ITS region sequencing for fungi) which provides highly accurate species-level identification.
The document lists specific organisms the device can identify, implying that the ground truth for these organisms was established by such highly accurate methods.

8. The sample size for the training set:

This information is not provided in the document.

9. How the ground truth for the training set was established:

This information is not provided in the document, but similar to point 7, it would logically be established by definitive microbiological or molecular methods.

Summary

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December 27, 2020

Bruker Daltonik GmbH Peter Trinder Regulatory Affairs Director Fahrenheitstrasse 4 Bremen. 28359 De

Re: K193419

Trade/Device Name: MBT Sepsityper Regulation Number: 21 CFR 866.3378 Regulation Name: Clinical Mass Spectrometry Microorganism Identification and Differentiation System Regulatory Class: Class II Product Code: ONJ Dated: December 2, 2019 Received: December 9, 2019

Dear Peter Trinder:

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 (reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (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 medical devices and radiation-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,

Kristian M. Roth -S

Kristian Roth, Ph.D. Branch Chief Bacterial Respiratory and Medical Countermeasures 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) K193419

Device Name MBT Sepsityper

Indications for Use (Describe)

Organisms recovered from positive blood culture bottles that are suitable for identification using the MBT Sepsity per Kit US IVD and MBT-CA Systems are:

Bacteria: Abiotrophia defectiva Achromobacter xylosoxidans Acinetobacter baumannii / nosocomialis group Acinetobacter calcoaceticus Acinetobacter haemolyticus Acinetobacter johnsonii Acinetobacter junii Acinetobacter lwoffii Acinetobacter pittii Acinetobacter radioresistens Acinetobacter ursingii Actinomyces europaeus Actinomyces funkei Actinomyces graevenitzii Actinomyces hyovaginalis Actinomyces meyeri Actinomyces neuii Actinomyces odontolyticus

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Actinomyces oris Actinomyces radingae Actinomyces turicensis Actinomyces urogenitalis Actinotignum schaalii group Aerococcus sanguinicola Aerococcus urinae Aerococcus viridans Aeromonas hydrophila / caviae group Aeromonas salmonicida Aggregatibacter actinomycetemcomitans Aggregatibacter aphrophilus Aggregatibacter segnis Alcaligenes faecalis Alloiococcus otitis Alloscardovia omnicolens Anaerococcus murdochii Anaerococcus vaginalis Arthrobacter cumminsii Bacteroides caccae Bacteroides fragilis Bacteroides nordii Bacteroides ovatus group Bacteroides pyogenes Bacteroides salyersiae Bacteroides stercoris group Bacteroides thetaiotaomicron group Bacteroides uniformis Bacteroides vulgatus group Bifidobacterium breve Bordetella hinzii Bordetella pertussis / bronchiseptica / parapertussis Brevibacterium casei Brevundimonas diminuta group Burkholderia cepacia complex Burkholderia gladioli Burkholderia multivorans Campylobacter coli Campylobacter jejuni Campylobacter ureolyticus Capnocytophaga ochracea Capnocytophaga sputigena Chryseobacterium gleum Chryseobacterium indologenes Citrobacter amalonaticus complex Citrobacter freundii complex Citrobacter koseri Clostridium beijerinckii Clostridium bifermentans Clostridium butyricum Clostridium clostridioforme group Clostridium difficile Clostridium innocuum Clostridium paraputrificum

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Clostridium perfringens Clostridium ramosum Clostridium septicum Clostridium sordellii Clostridium sporogenes / Clostridium botulinum (group I) Clostridium tertium Corynebacterium accolens Corynebacterium afermentans group Corynebacterium amycolatum Corynebacterium aurimucosum group Corynebacterium bovis Corynebacterium coyleae Corynebacterium diphtheriae Corynebacterium freneyi Corynebacterium glucuronolyticum Corynebacterium glutamicum Corynebacterium jeikeium Corynebacterium kroppenstedtii Corynebacterium macginleyi Corynebacterium minutissimum Corynebacterium mucifaciens / ureicelerivorans group Corynebacterium propinquum Corynebacterium pseudodiphtheriticum Corynebacterium pseudotuberculosis Corynebacterium resistens Corynebacterium riegelii Corynebacterium striatum group Corynebacterium tuberculostearicum Corynebacterium ulcerans Corynebacterium urealyticum Corynebacterium xerosis Cronobacter sakazakii group Cupriavidus pauculus group Delftia acidovorans group Dermabacter hominis Dermacoccus nishinomiyaensis Edwardsiella tarda Eikenella corrodens Elizabethkingia meningoseptica group Enterobacter aerogenes Enterobacter amnigenus Enterobacter cloacae complex Enterococcus avium Enterococcus casseliflavus Enterococcus durans Enterococcus faecalis Enterococcus faecium Enterococcus gallinarum Enterococcus hirae Enterococcus mundtii Enterococcus raffinosus Escherichia coli Escherichia hermannii Escherichia vulneris

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Ewingella americana Facklamia hominis Finegoldia magna Fluoribacter bozemanae Fusobacterium canifelinum Fusobacterium necrophorum Fusobacterium nucleatum Gardnerella vaginalis Gemella haemolysans Gemella morbillorum Gemella sanguinis Granulicatella adiacens Haemophilus haemolyticus Haemophilus influenzae Haemophilus parahaemolyticus group Haemophilus parainfluenzae Hafnia alvei Helcococcus kunzii Kingella denitrificans Kingella kingae Klebsiella oxytoca / Raoultella ornithinolytica Klebsiella pneumoniae Klebsiella variicola Kocuria kristinae Kytococcus sedentarius Lactobacillus gasseri Lactobacillus jensenii Lactobacillus rhamnosus Lactococcus garvieae Lactococcus lactis Leclercia adecarboxylata Legionella longbeachae Legionella pneumophila Leuconostoc citreum Leuconostoc mesenteroides Leuconostoc pseudomesenteroides Listeria monocytogenes Macrococcus caseolyticus Mannheimia haemolytica group Micrococcus luteus Micrococcus lylae Mobiluncus curtisii Moraxella sg Branhamella catarrhalis* Moraxella sg Moraxella nonliquefaciens* Moraxella sg Moraxella osloensis* Morganella morganii Myroides odoratimimus Myroides odoratus Neisseria bacilliformis Neisseria cinerea Neisseria elongata Neisseria flavescens / subflava group Neisseria gonorrhoeae Neisseria lactamica

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Neisseria meningitidis Neisseria sicca group Neisseria weaveri Nocardia brasiliensis Nocardia cyriacigeorgica Nocardia farcinica group Nocardia nova Nocardia otitidiscaviarum Ochrobactrum anthropi Oligella ureolytica Oligella urethralis Pantoea agglomerans Parabacteroides distasonis Parabacteroides goldsteinii Parabacteroides johnsonii / merdae group Parvimonas micra Pasteurella multocida Pediococcus acidilactici Pediococcus pentosaceus Peptoniphilus harei group Peptostreptococcus anaerobius Plesiomonas shigelloides Pluralibacter gergoviae Porphyromonas gingivalis Porphyromonas somerae Prevotella bivia Prevotella buccae Prevotella denticola Prevotella intermedia Prevotella melaninogenica Propionibacterium acnes Proteus mirabilis Proteus vulgaris group Providencia rettgeri Providencia stuartii Pseudomonas aeruginosa Pseudomonas fluorescens group Pseudomonas oryzihabitans Pseudomonas putida group Pseudomonas stutzeri Ralstonia pickettii Rhizobium radiobacter Rothia aeria Rothia dentocariosa Rothia mucilaginosa Salmonella sp** Serratia fonticola Serratia liquefaciens Serratia marcescens Serratia odorifera Serratia plymuthica Serratia rubidaea Sphingobacterium multivorum Sphingobacterium spiritivorum

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Sphingomonas paucimobilis group Staphylococcus aureus Staphylococcus auricularis Staphylococcus capitis Staphylococcus caprae Staphylococcus carnosus Staphylococcus cohnii Staphylococcus delphini Staphylococcus epidermidis Staphylococcus equorum Staphylococcus felis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus intermedius Staphylococcus lentus Staphylococcus lugdunensis Staphylococcus pasteuri Staphylococcus pettenkoferi Staphylococcus pseudintermedius Staphylococcus saccharolyticus Staphylococcus saprophyticus Staphylococcus schleiferi Staphylococcus sciuri Staphylococcus simulans Staphylococcus vitulinus Staphylococcus warneri Staphylococcus xylosus Stenotrophomonas maltophilia Streptococcus agalactiae Streptococcus anginosus Streptococcus canis Streptococcus constellatus Streptococcus dysgalactiae Streptococcus equi Streptococcus gallolyticus Streptococcus gordonii Streptococcus intermedius Streptococcus lutetiensis Streptococcus mitis / oralis group Streptococcus mutans Streptococcus parasanguinis Streptococcus pneumoniae Streptococcus pyogenes Streptococcus salivarius / vestibularis group Streptococcus sanguinis Streptococcus sobrinus Streptococcus thermophilus Sutterella wadsworthensis Trueperella bernardiae Turicella otitidis Vagococcus fluvialis Veillonella parvula group Vibrio parahaemolyticus Vibrio vulnificus

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Weeksella virosa Yersinia enterocolitica Yersinia frederiksenii Yersinia intermedia Yersinia kristensenii Yersinia pseudotuberculosis sg* = subgenus sp** = species

Yeasts:

Candida albicans Candida auris Candida boidinii Candida dubliniensis Candida duobushaemulonii Candida famata Candida glabrata Candida guilliermondii Candida haemulonis Candida inconspicua Candida intermedia Candida kefyr Candida krusei Candida lambica Candida lipolytica Candida lusitaniae Candida metapsilosis Candida norvegensis Candida orthopsilosis Candida parapsilosis Candida pararugosa Candida pelliculosa Candida tropicalis Candida valida Candida zeylanoides Cryptococcus gattii Cryptococcus neoformans var grubii* Cryptococcus neoformans var neoformans* Cyberlindnera jadinii Geotrichum candidum Geotrichum capitatum Kloeckera apiculata Malassezia furfur Malassezia pachydermatis Pichia ohmeri Rhodotorula mucilaginosa Saccharomyces cerevisiae Trichosporon asahii Trichosporon inkin Trichosporon mucoides group * = variety

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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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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.