MALDI Biotyper CA System

K142677 · Bruker Daltonics, Inc. · PEX · Mar 27, 2015 · Microbiology

Device Facts

• Record ID: K142677
• Device Name: MALDI Biotyper CA System
• Applicant: Bruker Daltonics, Inc.
• Product Code: PEX · Microbiology
• Decision Date: Mar 27, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3361
• Device Class: Class 2

Intended Use

The Bruker Daltonics, Inc. MALDI Biotyper CA System is a mass spectrometer system using matrix-assisted laser desorption/ionization – time-of-flight (MALDI-TOF) for the identification of microorganisms cultured from human specimens. The MALDI Biotyper CA 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 and yeast infections.

Device Story

The MALDI Biotyper CA System is a benchtop MALDI-TOF mass spectrometer used in clinical laboratories for microbial identification. It processes isolated colonies from various culture media. The system uses a 'soft' ionization technique where a laser irradiates a matrix-sample composite, releasing positively charged proteins (primarily ribosomal) into a flight tube. The time-of-flight is measured to determine molecular mass, creating a characteristic spectral fingerprint. The system software transforms spectra into peak lists and compares them against a reference database using a biostatistical algorithm to generate a log(score) (0.00–3.00). A log(score) ≥2.00 indicates high-confidence identification; 1.70–1.99 indicates low-confidence. Results are reviewed by a microbiologist alongside Gram staining, morphology, and growth characteristics to inform clinical decision-making. The device benefits patients by providing rapid, accurate identification of bacterial and yeast pathogens, facilitating timely targeted therapy.

Clinical Evidence

Clinical performance was evaluated using 4,395 fresh and stored isolates across six US clinical sites. The study compared MBT-CA results against a reference algorithm. For bacteria, high-resolution species identification accuracy was 97.47% (≥2.0 log score). For yeast, high-resolution species identification accuracy was 91.03%. Reproducibility and precision were confirmed across multiple operators, instruments, and sites, with 94% of reproducibility panel organisms correctly identified. Bench testing confirmed stability of samples on target plates for up to 24 hours and media compatibility.

Technological Characteristics

MALDI-TOF mass spectrometer (Bruker microflex benchtop). Mass range: 2,000–20,000 m/z. Matrix: α-Cyano-4-hydroxycinnamic acid. Sample preparation: Direct Transfer (DT), extended Direct Transfer (eDT) with 70% formic acid, or Extraction (Ext). Connectivity: Standalone system. Software: MBT-CA for data acquisition and biostatistical analysis. Calibration: Bruker US IVD Bacterial Test Standard (BTS). Target: 48-spot reusable steel target.

Indications for Use

Indicated for the identification of cultured bacterial and yeast microorganisms from human specimens to aid in the diagnosis of infections. Intended for use by trained laboratory personnel.

Regulatory Classification

Identification

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.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software. (2) Premarket notification submissions must include database implementation methodology, construction parameters, and quality assurance protocols. (3) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling. (4) As part of the risk management activities performed under 21 CFR 820.10(c) design and development, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument. (5) Premarket notification submissions must include details on the appropriate end user device training program that will be offered while marketing the device.

Predicate Devices

• Vitek MS (K124067)
• Bruker Daltonics, Inc. MBT-CA System (K130831)

Submission Summary (Full Text)

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

BRUKER DALTONICS, INC MARKUS KOSTRZEWA VICE PRESIDENT CLINICAL MASS SPECTROMETRY R&D FAHRENHEILSTRASSE-4 BREMEN 28359 DE

March 27, 2015

Re: K142677 Trade/Device Name: MALDI Biotyper CA System Regulation Number: 21 CFR 866.3361 Regulation Name: Mass spectrometer system for clinical use for the identification of microorganisms Regulatory Class: II Product Code: PEX Dated: February 27, 2015 Received: March 2, 2015

Dear Dr. Kostrzewa:

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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Uwe Scherf - S for

Sally Hojvat, M.Sc., PhD. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known) K142677

#### Device Name

MALDI Biotyper CA System

#### Indications for Use (Describe)

The Bruker Daltonics, Inc. MALDI Biotyper CA System is a mass spectrometer system using matrix-assisted laser desorption/ionization – time-of-flight (MALDI-TOF) for the identification of microorganisms cultured from human specimens.

The MALDI Biotyper CA 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 and yeast infections.

#### BACTERIA

Achromobacter xylosoxidans Acinetobacter baumannii complex [4] Acinetobacter haemolyticus Acinetobacter johnsonii Acinetobacter junii Acinetobacter lwoffii Acinetobacter radioresistens Acinetobacter ursingii Actinomyces meyeri Actinomyces neuii Actinomyces odontolyticus Actinomyces oris Aerococcus urinae Aerococcus viridans Aeromonas salmonicida Aeromonas sp[7] Alcaligenes faecalis Anaerococcus vaginalis Bacteroides fragilis Bacteroides ovatus group Bacteroides thetaiotaomicron group Bacteroides uniformis Bacteroides vulgatus group Bordetella group[3] Bordetella hinzii Brevibacterium casei Brevundimonas diminuta group Burkholderia cepacia complex [13] Burkholderia gladioli Burkholderia multivorans Campylobacter coli Campylobacter jejuni Campylobacter ureolyticus Capnocytophaga ochracea Capnocytophaga sputigena

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Chryseobacterium gleum Chryseobacterium indologenes Citrobacter amalonaticus complex Citrobacter freundii complex Citrobacter koseri Clostridium difficile Clostridium perfringens Corynebacterium amycolatum Corynebacterium aurimucosum group Corynebacterium bovis Corynebacterium diphtheriae Corynebacterium glucuronolyticum Corynebacterium jeikeium Corynebacterium kroppenstedtii Corynebacterium macginleyi Corynebacterium minutissimum Corynebacterium propinquum Corynebacterium pseudodiphtheriticum Corynebacterium riegelii Corynebacterium striatum group Corynebacterium tuberculostearicum Corynebacterium ulcerans Corynebacterium urealyticum Corynebacterium xerosis Cronobacter sakazakii group Cupriavidus pauculus group Delftia acidovorans group Dermacoccus nishinomiyaensis Edwardsiella tarda Eikenella corrodens Elizabethkingia meningoseptica group Enterobacter aerogenes Enterobacter amnigenus Enterobacter cloacae complex Enterococcus avium group Enterococcus casseliflavus Enterococcus faecalis Enterococcus faecium Enterococcus gallinarum Enterococcus hirae Escherichia coli Finegoldia magna Fusobacterium canifelinum Fusobacterium necrophorum Fusobacterium nucleatum Gardnerella vaginalis Gemella haemolysans Gemella sanguinis Granulicatella adiacens Haemophilus haemolyticus Haemophilus influenzae Haemophilus parahaemolyticus group Haemophilus parainfluenzae Hafnia alvei

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Kingella kingae Klebsiella oxytoca / Raoultella ornithinolytica Klebsiella pneumoniae Kocuria kristinae Kytococcus sedentarius Lactococcus garvieae Lactococcus lactis Leuconostoc mesenteroides Macrococcus caseolyticus Micrococcus luteus Moraxella sg Branhamella catarrhalis Moraxella sg Moraxella nonliquefaciens Moraxella sg Moraxella osloensis Morganella morganii Myroides odoratimimus Myroides odoratus Oligella ureolytica Oligella urethralis Pantoea agglomerans Parabacteroides distasonis Pasteurella multocida Pediococcus pentosaceus Peptoniphilus harei group Peptostreptococcus anaerobius Plesiomonas shigelloides Porphyromonas gingivalis 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 Rhizobium radiobacter Rothia aeria Rothia dentocariosa Rothia mucilaginosa Salmonella sp Serratia liquefaciens Serratia marcescens Serratia plymuthica Serratia rubidaea Staphylococcus aureus Staphylococcus auricularis Staphylococcus capitis Staphylococcus caprae

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Staphylococcus carnosus Staphylococcus cohnii Staphylococcus epidermidis Staphylococcus equorum Staphylococcus felis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus lugdunensis Staphylococcus pasteuri Staphylococcus pettenkoferi Staphylococcus pseudintermedius Staphylococcus saccharolyticus Staphylococcus saprophyticus Staphylococcus schleiferi Staphylococcus simulans Staphylococcus vitulinus Staphylococcus warneri Stenotrophomonas maltophilia Streptococcus agalactiae Streptococcus anginosus Streptococcus constellatus Streptococcus dysgalactiae Streptococcus gallolyticus Streptococcus gordonii Streptococcus intermedius Streptococcus lutetiensis Streptococcus mitis / oralis group Streptococcus mutans Streptococcus pneumoniae Streptococcus pyogenes Streptococcus salivarius Sutterella wadsworthensis Vibrio parahaemolyticus Vibrio vulnificus Yersinia enterocolitica Yersinia pseudotuberculosis

#### YEAST

Candida albicans Candida boidinii Candida dubliniensis Candida duobushaemulonii Candida famata Candida glabrata Candida guilliermondii Candida haemulonis Candida inconspicua Candida kefyr Candida krusei Candida lambica Candida lipolytica Candida lusitaniae Candida metapsilosis Candida norvegensis

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Candida orthopsilosis Candida parapsilosis Candida pararugosa Candida pelliculosa Candida tropicalis Candida valida Cryptococcus gattii Cryptococcus neoformans var grubii Cryptococcus neoformans var neoformans Geotrichum candidum Geotrichum capitatum Kloeckera apiculata Pichia ohmeri Saccharomyces cerevisiae Trichosporon asahii

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

> Prescription Use (Part 21 CFR 801 Subpart D)

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

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# 510(k) SUMMARY

| Date of Summary: | March 27, 2015 |
|----------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Product Name | MBT-CA System |
| Sponsor | Bruker Daltonics, Inc.<br>40 Manning Road,<br>Billerica, MA 01821 |
| Correspondent | Bruker Daltonik GmbH<br>Markus Kostrzewa, Vice President Clinical Mass Spectrometry R&D<br>Fahrenheitstrasse 4<br>Bremen, 28359<br>Phone: [phone]Fax: [phone]<br>Email: [e-mail] |
| Device Identification | |
| Trade or Proprietary Name: | MALDI Biotyper CA System |
| Common or Usual Name: | System, mass spectrometry, maldi tof, microorganism identification,<br>cultured isolates |
| Product Code: | DEV |

| Product Code: | PEX |
|---------------------|-----------------|
| Regulation Section: | 21 CFR 866.3361 |
| Device Class: | Class II |
| Panel: | Microbiology |

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## Substantial Equivalency

The Bruker Daltonics, Inc. MBT-CA System is substantially equivalent to the MS (K124067) and the Bruker Datonics, Inc. MBT-CA System (K13083). Table 1 compares the characteristics of the MBT-CA System (New Device) and the Vitek MS (Predicate Device).

### Table 1. Substantial Equivalency Table

| Similarities | | | |
|--------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | NEW DEVICE | PRIMARY PREDICATE DEVICE | PREDICATE DEVICE |
| Characteristic | Bruker Daltonics, Inc. MBT-CA System | Vitek® MS | Bruker Daltonics, Inc. MBT-CA |
| | (TBD) | (K124067) | System (K130831) |
| Product Codes | PEX | PEX | PEX |
| Intended use | The Bruker Daltonics, Inc. MALDI Biotyper CA System is a mass<br>spectrometer system using matrix-assisted laser<br>desorption/ionization - time-of-flight (MALDI-TOF) for the<br>identification of microorganisms cultured from human<br>specimens.<br>The MALDI Biotyper CA System is a qualitative <i>in vitro</i><br>diagnostic device indicated for use in conjunction with other<br>clinical and laboratory findings to aid in the diagnosis of<br>bacterial and yeast infections. | The Vitek® MS is a mass spectrometer system<br>using matrix-assisted laser<br>desorption/ionization-time-of- flight (MALDI-<br>TOF) for the identification of microorganisms<br>cultured from human specimen.<br>The VITEK MS is a qualitative <i>in vitro</i> diagnostic<br>device indicated for use in conjunction with<br>other clinical and laboratory findings to aid in<br>the diagnosis of bacterial and yeast infections. | See "Differences" |
| Sample type | Isolated colony from any patient sample source.<br>Acceptable media:<br>• Columbia blood agar with 5% sheep blood<br>• Trypticase soy agar with 5% sheep Blood<br>• Chocolate agar<br>• MacConkey Agar<br>• Columbia CNA agar with 5% sheep blood<br>• Brucella Agar with 5% horse blood<br>• CDC anaerobe Agar with 5% sheep blood<br>• CDC anaerobe 5% sheep blood Agar with phenylethyl alcohol<br>• CDC anaerobe laked sheep blood Agar with kanamycin and<br>vancomycin<br>• Bacteroides bile esculin Agar with amikacin<br>• Clostridium difficile Agar with 7% sheep blood<br>• Sabouraud-Dextrose Agar<br>• Brain Heart Infusion Agar<br>• Campylobacter Agar with 5 Antimicrobics and 10% Sheep<br>Blood<br>• Bordet Gengou Agar with 15% sheep blood | Isolated colony from any patient sample<br>source.<br>Acceptable media:<br>• Columbia blood agar with 5% sheep blood<br>• Trypitcase soy agar with 5% sheep Blood<br>• Chocolate polyvitex agar<br>• Campylosel agar<br>• MacConkey Agar<br>• Modified Sabouraud dextrose Agar<br>• ChromID CPS | Isolated colony from any patient sample<br>source.<br>Acceptable media:<br>• Columbia blood agar with 5% sheep<br>blood<br>• Trypticase soy agar with 5% sheep<br>Blood<br>• Chocolate agar<br>• MacConkey Agar |
| Type of Test | Automated Mass Spectrometry System | Automated Mass Spectrometry System | Automated Mass Spectrometry System |
| Similarities | | | |
| Characteristic | NEW DEVICE<br>Bruker Daltonics, Inc. MBT-CA System<br>(TBD) | PRIMARY PREDICATE DEVICE<br>Vitek® MS<br>(K124067) | PREDICATE DEVICE<br>Bruker Daltonics, Inc. MBT-CA<br>System (K130831) |
| Matrix | α-Cyano-4-hydroxycinnamic acid | α-Cyano-4-hydroxycinnamic acid | α-Cyano-4-hydroxycinnamic acid |
| Method of<br>Testing | Bacteria & Yeast: Direct testing<br>If after initial analysis the log(score) is reported at <2.00,<br>organisms may be processed using the Extraction (Ext)<br>procedure or extended Direct Transfer (eDT, 70% aqueous<br>formic acid) procedure. If eDT procedure still yields log(score)<br><2.00, organism may be processed via Ext procedure. | Bacteria & Yeast: Direct testing | Bacteria: Direct testing<br>If after initial analysis the log(score) is<br>reported at <2.00, organisms are<br>processed using the Extraction procedure. |
| Result Reporting | Organism identification is reported with high confidence if the<br>log(score) is ≥2.00.<br>An organism identification is reported with low confidence if<br>the log(score) is between 1.70 and <2.00. | A single identification is displayed, with a<br>confidence value from 60.0 to 99.9, when one<br>significant organism or organism group is<br>retained.<br>"Low-discrimination" identifications are<br>displayed when more than one but not more<br>than four significant organisms or organism<br>groups are retained.<br>When more than four organisms or organism<br>groups are found, or when no match is found,<br>the organism is considered unidentified. | Organism identification is reported with<br>high confidence if the log(score) is ≥2.00.<br>An organism identification is reported with<br>low confidence if the log(score) is between<br>1.70 and <2.00. |
| Matching<br>Algorithm | Calculates matches by comparing a new spectrum against each<br>single reference entry of a reference database. | Uses a proprietary process called "mass<br>binning." In this process, the spectrum<br>between 3,000 and 17,000 Daltons are divided<br>into 1300 pre-defined<br>intervals called "bins". Next, an algorithm<br>based on supervised machine learning known<br>as the "Advanced Spectrum Classifier", is used<br>to determine how<br>informative each bin was in differentiating that<br>species from all other species in the database. | Calculates matches by comparing a new<br>spectrum against each single reference<br>entry of a reference database. |
| Recorded mass<br>range | 2,000 - 20,000 m/z | 2,000 - 20,000 m/z | 2,000 - 20,000 m/z |
| Similarities | | | |
| Characteristic | NEW DEVICE<br>Bruker Daltonics, Inc. MBT-CA System<br>(TBD) | PRIMARY PREDICATE DEVICE<br>Vitek® MS<br>(K124067) | PREDICATE DEVICE<br>Bruker Daltonics, Inc. MBT-CA System (K130831) |
| Calibration | Bruker US IVD Bacterial Test Standard (BTS) | See "Differences" | Bruker US IVD Bacterial Test Standard (BTS) |
| MALDI Target Plate | US IVD 48 Spot Target<br>• 48 positions reusable steel targets | See "Differences" | US IVD 48 Spot Target<br>• 48 positions reusable steel targets |
| MALDI-TOF MS instruments | Bruker microflex (benchtop) | See "Differences" | Bruker microflex (benchtop) |
| Database | MALDI Biotyper for Clinical Applications (MBT-CA) | See "Differences" | MALDI Biotyper for Clinical Applications (MBT-CA) |

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| Differences | | | |
|----------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------|-----------------------------------------------------------------------|
| Characteristic | NEW DEVICE<br>Bruker Daltonics, Inc. MBT-CA System<br>(TBD) | PREDICATE DEVICE<br>Vitek® MS<br>(K124067) | PREDICATE DEVICE<br>Bruker Daltonics, Inc. MBT-CA System<br>(K130831) |
| Culture Age | Bacteria and yeasts growth should be between<br>18h to 48h (+12h storage at RT)<br>Specific requirements:<br>• Bordetella: Incubation on BG agar should<br>not be longer than 24h (+12h storage at RT).<br>• Campylobacter: Incubation can be<br>prolonged to 72h (+12h storage at RT).<br>• Streptococcus pneumoniae: Incubation<br>should not be longer than 24h (+12h storage<br>at RT) due to possible autolysis. | Bacteria and yeast growth should be<br>between 24 to 72 hours. | Bacteria growth should be between 18h to 36h |
| Calibration | Bruker US IVD Bacterial Test Standard (BTS) | E. coli ATCC 8739 | See "Similarities" |
| MALDI Target | US IVD 48 Spot Target | VITEK MS-DS Target Slides | See "Similarities" |
| Plate | • 48 positions reusable steel targets | • 48 positions disposable plastic targets | See "Similarities" |
| MALDI-TOF MS | Bruker microflex | Shimadzu AXIMA® Assurance MS | See "Similarities" |
| instruments | (benchtop) | (floor standing) | See "Similarities" |
| Database | MALDI Biotyper for Clinical Applications (MBT-<br>CA) | VITEK® MS V2.0 Knowledge Base | See "Similarities" |

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Image /page/11/Picture/0 description: The image shows the logo for Bruker Corporation. The logo features the word "BRUKER" in bold, sans-serif font, with the "B" slightly larger than the other letters. Above the word, there is a stylized graphic of an atom, with two intersecting elliptical orbits around a central point, representing the nucleus. The orbits and the central point are in a light blue color.

| Differences | | | |
|----------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Characteristic | NEW DEVICE<br>Bruker Daltonics, Inc. MBT-CA System<br>(TBD) | PREDICATE DEVICE<br>Vitek® MS<br>(K124067) | PREDICATE DEVICE<br>Bruker Daltonics, Inc. MBT-CA System<br>(K130831) |
| Intended Use | The Bruker Daltonics, Inc. MALDI Biotyper CA System is a mass spectrometer system using matrix-assisted<br>laser desorption/ionization - time-of-flight (MALDI-<br>TOF) for the identification of microorganisms cultured<br>from human specimens.<br><br>The MALDI Biotyper CA System is a qualitative <i>in vitro</i><br>diagnostic device indicated for use in conjunction with<br>other clinical and laboratory findings to aid in the<br>diagnosis of bacterial and yeast infections. | See "Similarities" | The Bruker Daltonics, Inc. MALDI Biotyper CA<br>System is a qualitative <i>in vitro</i> diagnostic mass<br>spectrometer system for the identification of Gram-<br>negative bacterial colonies cultured from human<br>specimens using matrix-assisted laser<br>desorption/ionization - time-of-flight (MALDI-TOF)<br>mass spectrometry technology.<br><br>The MALDI Biotyper CA System is indicated for use<br>in conjunction with other clinical and laboratory<br>findings to aid in the diagnosis of Gram-negative<br>bacterial infections. |

These differences do not affect substantial equivalence of the MBT-CA System and MBT-CA System (K130831). All systems are mass spectrometers using matrix-assisted laser desorption – time-of-flight (MALDI-TOF) for the identification of microorganisms cultured from human specimens. The differences noted above do not impact the intended use and do not raise questions as to the safectiveness of the test (new) device.

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### Intended Use

The Bruker Daltonics, Inc. MALDI Biotyper CA System is a mass spectrometer system using matrix-assisted laser desorption/ionization – time-of-flight (MALDI-TOF) for the identification of microorganisms cultured from human specimens.

The MALDI Biotyper CA 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 and yeast infections.

The following organisms are claimed:

### Bacteria:

| Achromobacter xylosoxidans | Cupriavidus pauculus group | Propionibacterium acnes | |
|-------------------------------------|--------------------------------------|---------------------------------|--|
| Acinetobacter haemolyticus | Delftia acidovorans group | Proteus mirabilis | |
| Acinetobacter johnsonii | Dermacoccus nishinomiyaensis | Proteus vulgaris group | |
| Acinetobacter junii | Edwardsiella tarda | Providencia rettgeri | |
| Acinetobacter lwoffii | Eikenella corrodens | Providencia stuartii | |
| Acinetobacter radioresistens | Elizabethkingia meningoseptica group | Pseudomonas aeruginosa | |
| Acinetobacter ursingii | Enterobacter aerogenes | Pseudomonas fluorescens group | |
| Acinetobacter baumannii complex [4] | Enterobacter amnigenus | Pseudomonas oryzihabitans | |
| Actinomyces meyeri | Enterobacter cloacae complex | Pseudomonas putida group | |
| Actinomyces neuii | Enterococcus casseliflavus | Pseudomonas stutzeri | |
| Actinomyces odontolyticus | Enterococcus faecalis | Rhizobium radiobacter | |
| Actinomyces oris | Enterococcus faecium | Rothia aeria | |
| Aerococcus urinae | Enterococcus gallinarum | Rothia dentocariosa | |
| Aerococcus viridans | Enterococcus hirae | Rothia mucilaginosa | |
| Aeromonas salmonicida | Enterococcus avium group | Salmonella sp | |
| Aeromonas sp[7] | Escherichia coli | Serratia liquefaciens | |
| Alcaligenes faecalis | Finegoldia magna | Serratia marcescens | |
| Anaerococcus vaginalis | Fusobacterium canifelinum | Serratia plymuthica | |
| Bacteroides fragilis | Fusobacterium necrophorum | Serratia rubidaea | |
| Bacteroides uniformis | Fusobacterium nucleatum | Staphylococcus aureus | |
| Bacteroides ovatus group | Gardnerella vaginalis | Staphylococcus auricularis | |
| Bacteroides thetaiotaomicron group | Gemella haemolysans | Staphylococcus capitis | |
| Bacteroides vulgatus group | Gemella sanguinis | Staphylococcus caprae | |
| Bordetella group[3] | Granulicatella adiacens | Staphylococcus carnosus | |
| Bordetella hinzii | Haemophilus haemolyticus | Staphylococcus cohnii | |
| Brevibacterium casei | Haemophilus influenzae | Staphylococcus epidermidis | |
| Brevundimonas diminuta group | Haemophilus parainfluenzae | Staphylococcus equorum | |
| Burkholderia gladioli | Haemophilus parahaemolyticus group | Staphylococcus felis | |
| Burkholderia multivorans | Hafnia alvei | Staphylococcus haemolyticus | |
| Burkholderia cepacia complex [13] | Kingella kingae | Staphylococcus hominis | |
| Campylobacter coli | Klebsiella pneumoniae | Staphylococcus lugdunensis | |
| Campylobacter jejuni | Klebsiella oxytoca / | Staphylococcus pasteuri | |
| Raoultella ornithinolytica | | | |
| Campylobacter ureolyticus | Kocuria kristinae | Staphylococcus pettenkoferi | |
| Capnocytophaga ochracea | Kytococcus sedentarius | Staphylococcus pseudintermedius | |
| Capnocytophaga sputigena | Lactococcus garvieae | Staphylococcus saccharolyticus | |

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Image /page/13/Picture/0 description: The image shows the logo for Bruker. The logo consists of the word "BRUKER" in a bold, sans-serif font, with a stylized atom symbol to the right. The atom symbol is made up of three overlapping circles, with a small dot in the center of each circle. The logo is simple and modern, and the atom symbol suggests that the company is involved in science or technology.

| Chryseobacterium gleum | Lactococcus lactis | Staphylococcus saprophyticus |
|-----------------------------------------|-------------------------------------------|------------------------------------|
| Chryseobacterium indologenes | Leuconostoc mesenteroides | Staphylococcus schleiferi |
| Citrobacter amalonaticus complex | Macrococcus caseolyticus | Staphylococcus simulans |
| Citrobacter koseri | Micrococcus luteus | Staphylococcus vitulinus |
| Citrobacter freundii complex | Moraxella sg Branhamella catarrhalis | Staphylococcus warneri |
| Clostridium difficile | Moraxella sg Moraxella<br>nonliquefaciens | Stenotrophomonas maltophilia |
| Clostridium perfringens | Moraxella sg Moraxella osloensis | Streptococcus agalactiae |
| Corynebacterium amycolatum | Morganella morganii | Streptococcus anginosus |
| Corynebacterium bovis | Myroides odoratimimus | Streptococcus constellatus |
| Corynebacterium diphtheriae | Myroides odoratus | Streptococcus dysgalactiae |
| Corynebacterium glucuronolyticum | Oligella ureolytica | Streptococcus gallolyticus |
| Corynebacterium jeikeium | Oligella urethralis | Streptococcus gordonii |
| Corynebacterium kroppenstedtii | Pantoea agglomerans | Streptococcus intermedius |
| Corynebacterium macginleyi | Parabacteroides distasonis | Streptococcus lutetiensis |
| Corynebacterium minutissimum | Pasteurella multocida | Streptococcus mutans |
| Corynebacterium propinquum | Pediococcus pentosaceus | Streptococcus pneumoniae |
| Corynebacterium<br>pseudodiphtheriticum | Peptoniphilus harei group | Streptococcus pyogenes |
| Corynebacterium riegelii | Peptostreptococcus anaerobius | Streptococcus salivarius |
| Corynebacterium tuberculostearicum | Plesiomonas shigelloides | Streptococcus mitis / oralis group |
| Corynebacterium ulcerans | Porphyromonas gingivalis | Sutterella wadsworthensis |
| Corynebacterium urealyticum | Prevotella bivia | Vibrio parahaemolyticus |
| Corynebacterium xerosis | Prevotella buccae | Vibrio vulnificus |
| Corynebacterium aurimucosum group | Prevotella denticola | Yersinia enterocolitica |
| Corynebacterium striatum group | Prevotella intermedia | Yersinia pseudotuberculosis |
| Cronobacter sakazakii group | Prevotella melaninogenica | |

### Yeast:

- Candida albicans Candida boidinii Candida dubliniensis Candida duobushaemulonii Candida glabrata Candida famata Candida guilliermondii Candida haemulonis Candida inconspicua 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 Cryptococcus gattii Cryptococcus neoformans_var_grubii Cryptococcus neoformans var neoformans Geotrichum candidum Geotrichum capitatum Kloeckera apiculata Pichia ohmeri Saccharomyces cerevisiae Trichosporon asahii

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Image /page/14/Picture/0 description: The image shows the logo for Bruker Corporation. The logo consists of the word "BRUKER" in bold, black letters. Above the word is a blue atom symbol with two electrons orbiting the nucleus. The atom symbol is stylized and has a modern look.

## Methodology

Biochemical methods are currently the most commonly used methods for the identification of microorganisms. Organisms are tested against a range of reagents and organism identification is based on a microorganism's reaction to these reagents.

The MBT-CA System uses a different methodology for organism identification based on unique protein patterns of the microorganisms obtained from mass spectrometry. The test organism's spectrum (a pattern of mass peaks) is compared with a reference spectra library (database). Using biostatistical analysis, a probability ranking of the organism identification is generated. The probability ranking is represented as a log(score) between 0.00 and 3.00. Organism identification is reported with high confidence if the log(score) is ≥2.00. An organism identification is reported with low confidence if the log(score) is between 1.70 and <2.00.

Some MBT-CA identifications displayed are non-clinically validated organisms. In the interest of public health, these organisms are displayed but are grayed out in the MBT-CA report as a means of directing the required additional laboratory testing. These results are not reported; identifications must be confirmed using alternate laboratory methods. Results for non-clinically validated organisms cannot be transmitted from the MBT-CA to the laboratory information system.

Organisms to be identified with the MBT-CA System should be isolated for purity on appropriate isolation media.

Direct Transfer (DT): An individual colony from a subculture plate is transferred to a selected position on an US IVD 48 Spot Target plate (target) and overlaid with US IVD HCCA portioned (matrix). The standard solvent (50% acetonitrile / 47.5% H2O / 2.5% trifluoroacetic acid) in the matrix solution extracts proteins (mainly ribosomal proteins, which are present in high concentration) from the microorganisms. When dried matrix crystallizes, the inoculated target is ready to be analyzed on the MBT-CA System. If after initial analysis the log(score) is reported as <2.00, organisms can be processed using the extended Direct Transfer (eDT) procedure or the Extraction (Ext) procedure and analysis repeated. If eDT is employed and log(score) is reported as <2.00, reanalysis via the Extraction procedure may be used.

## extended Direct Transfer (eDT):

If DT analysis yields a (log(score) <2.00) result, an individual colony from a subculture plate may be transferred to a selected position on a target and overlaid with 70% aqueous formic acid solution. The target is air-dried and then matrix is overlaid. When dried matrix crystallizes, the inoculated target is ready to be analyzed on the MBT-CA System. If a high confidence result is not achieved (log(score) is reported at <2.00), organisms can be processed using the Extraction procedure and analysis repeated.

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Image /page/15/Picture/0 description: The image shows the logo for Bruker. The logo consists of the word "BRUKER" in bold, black letters. Above the word is a blue graphic that resembles an atom with electrons orbiting around it. The atom graphic is stylized with curved lines and blue dots.

Extraction procedure (Ext): If after initial analysis and eDT procedure the log(score) is reported at <2.00, organisms are processed using the Extraction procedure and analysis repeated. For this purpose, isolated colonies from the subculture plate are extracted in accordance with MBT-CA System user manual. Afterwards they are transferred to the target and treated as described above.

## MALDI-TOF Analysis:

Samples are analyzed using MALDI (matrix-assisted laser desorption/ionization) TOF (time-offlight) mass spectrometry. The matrix transfers protons onto the extracted proteins and absorbs UV light. A laser in the MALDI- TOF mass spectrometer irradiates the matrix sample composite, causing evaporation and release of positively charged intact proteins and peptides ("soft" ionization technique). These ions are electrostatically accelerated over a short distance and arrive in the flight tube at a mass-dependent speed. As different proteins/peptides have different masses, ions arrive at the detector at different times (time-of-flight). The system measures the time (in the nanosecond range) between pulsed acceleration and the corresponding detector signal, the speed is converted into an exact molecular mass. The massto-charge ratio of an ion is proportional to the square of its drift time.

Highly abundant microbial proteins (mainly ribosomal proteins) result in a mass spectrum with characteristic mass and intensity distribution. It is specific for many bacteria and is interpreted as a molecular fingerprint to identify the test organism.

Data acquisition is controlled with MBT-CA Software. The spectrum of the unknown organism is first transformed into a peak list. Using a biostatistical algorithm, this peak list is compared to the reference peak lists of organisms in the reference library (database) and a log(score) is generated. A higher log(score) indicates a higher degree of similarity to the organism in the reference library. Organism identification is reported with high confidence if the log(score) is ≥2.00. An organism identification is reported with low confidence if the log(score) is between 1.70 and <2.00.

The log(score) ranges, defined in the MBT-CA System, are indicative of the probability of organism identification. Results should be reviewed by a trained microbiologist and final organism identification should be based on all relevant information available. This information includes but is not limited to: Gram staining, colony morphology, growth characteristics, sample matrix, etc.

## Performance Data

## Precision/Repeatability:

Validation of the whole MALDI Biotyper CA System was performed on six (6) working days with two (2) runs/day following manufacturer's instructions for use. Ten (10) test organisms were tested in triplicate via Direct Transfer (DT) and extended Direct Transfer (eDT) in each run. If a replicate yielded a log(score) <2.00, the test organism was repeated in triplicate via Extraction. The study also tested multiple sources of system variability including two (2) test operators, two

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Image /page/16/Picture/0 description: The image shows the logo for Bruker. The logo consists of the word "BRUKER" in bold, sans-serif font. Above the word is a blue graphic that resembles an atom with two orbiting electrons. The graphic is stylized and abstract, with the electrons forming a circular path around the central nucleus.

(2) microflex LT/SH instruments and two (2) target plates. Overall results from the precision/repeatability study are presented below.

| | # samples | # samples | # samples | # samples ≥2.0 ID |
|----------------------------|-----------|--------------|---------------|-------------------|
| Test organism | measured | ≥2.0 ID (DT) | ≥2.0 ID (eDT) | (DT/eDT+Ext) |
| Brevibacterium casei | 36 | 36 (100%) | 36 (100%) | 36 (100%) |
| Enterococcus faecalis | 36 | 34 (94%) | 36 (100%) | 36 (100%) |
| Micrococcus luteus | 36 | 21 (58%) | 36 (100%) | 36 (100%) |
| Staphylococcus aureus | 36 | 36 (100%) | 36 (100%) | 36 (100%) |
| Staphylococcus epidermidis | 36 | 36 (100%) | 36 (100%) | 36 (100%) |
| Streptococcus agalactiae | 36 | 34 (94%) | 36 (100%) | 36 (100%) |
| Candida albicans | 36 | 18 (50%) | 30 (83%) | 36 (100%) |
| Candida parapsilosis | 36 | 6 (17%) | 32 (89%) | 36 (100%) |
| Candida tropicalis | 36 | 34 (94%) | 35 (97%) | 36 (100%) |
| Saccharomyces cerevisiae | 36 | 20 (56%) | 27 (75%) | 36 (100%) |

## Table 2: Overall Precision per Test Organism

Based upon the data presented, the study confirms repeatability and precision of the MALDI Biotyper CA System independent from:

- System Operators
- microflex LT/SH instruments
- Target plates

## Limit of Detection/Dynamic Range:

The Limit of Detection study was conducted to estimate the dynamic range (in terms of sample amount) of Gram-positive bacteria and yeasts to be identified on the MALDI Biotyper CA System. Six (6) frequently occurring clinically relevant test organisms [three (3) Gram-positive and three (3) yeast] were chosen for this study. [NOTE: Due to the nature of yeast organisms, dynamic range studies using known yeast concentration was not feasible for the Direct Transfer procedure].

Turbidity measurements of stock suspensions containing microbial material were performed at a wavelength of 600 nm. To determine the amount of cfu/μL the stock suspensions of each testorganism were diluted in a series of 1:10 dilutions resulting in a final dilution of 10′ (Grampositive bacteria) and 10° (yeasts). 10 µL from the final diluted test-suspensions were transferred to TSA isolation media plates and incubated for 18-24h at (37±2)°C for Gram-positive bacteria and at (29±2)°C for yeasts, respectively. To account for random errors, the determination of each suspension's concentration in cfu/μL containing microbial material was done in triplicate. All suspensions were tested in replicates of eight (8) via each testing methodology (DT, eDT, Ext). Study results concluded that the estimated dynamic range for the Direct, extended Direct and Extraction procedure are as follows:

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Image /page/17/Picture/0 description: The image shows the logo for Bruker. The logo consists of the word "BRUKER" in bold, black letters. Below the word, there is a blue atom-like graphic with three elliptical orbits intersecting each other. The orbits are connected by small blue dots.

| | DT | | eDT | | EXT | |
|--------------------------|-------------------------|-------------------------|-------------------------|-------------------------|-------------------------|-------------------------|
| Test Organism | Lower limit<br>[cfu/µL] | Upper limit<br>[cfu/µL] | Lower limit<br>[cfu/µL] | Upper limit<br>[cfu/µL] | Lower limit<br>[cfu/µL] | Upper limit<br>[cfu/µL] |
| Enterococcus faecalis | 1.2 x 106 | 6.0 x 107 | 3.6 x 106 | 1.8 x 108 | 3.6 x 106 | 1.8 x 108 |
| Enterococcus faecium | 4.5 x 107 | 4.5 x 107 | 2.1 x 106 | 1.1 x 108 | 2.1 x 106 | 1.1 x 108 |
| Staphylococcus aureus | 3.5 x 105 | 1.8 x 108 | 4.1 x 104 | 2.1 x 108 | 4.1 x 105 | 2.1 x 108 |
| Candida albicans | N/A | N/A | 2.0 x 105 | 2.0 x 106 | 2.0 x 106 | 1.0 x 107 |
| Candida parapsilosis | N/A | N/A | 2.5 x 105 | 2.5 x 106 | 2.5 x 106 | 1.3 x 107 |
| Saccharomyces cerevisiae | N/A | N/A | 1.5 x 105 | 1.5 x 106 | 1.5 x 105 | 7.5 x 106 |

### Media and Colony Stability

With the inclusion of Gram-negative microaerophilic, Gram-negative anaerobic, Gram-positive aerobic and anaerobic and yeast organisms, a study on the following media was conducted to confirm acceptability of the recommended agar and the stability of the colony for up to 12 hours at room temperatur…