(189 days)
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 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 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 mass-to-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.
Here's an analysis of the provided text to extract the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a formal table format with numerical targets. However, based on the performance data presented, the implicit acceptance criteria for identification confidence (log(score) ≥ 2.00) are assessed. The reported performance for "Overall Isolate Performance" (Table 6) shows the aggregate performance across all claims.
| Acceptance Criteria (Implicit) | Reported Device Performance (Overall Isolate Performance - Table 6) |
|---|---|
| Identification with high confidence (log(score) ≥ 2.0) | 3817 / 3966 (96.27%) (high resolution species from reference algorithm) |
| Percentage of high resolution species correctly identified at high confidence (log(score) ≥ 2.0) | 96.27% |
| Percentage of high & low resolution species correctly identified at high or low confidence (log(score) ≥ 1.7) (Total positive identifications) | 99.02% (calculated as (3817 + 392 + 107 + 13) / (3966 + 406) = 4329 / 4372) which is 99.02% if only considering identified positives and not the incorrect IDs) |
| Incorrect MBT-CA ID (≥ 1.7) / No ID (< 1.7) should be minimized | 43 out of 4399 data points (approx. 0.98%) for all isolates |
2. Sample Sizes and Data Provenance
- Test Set Sample Size: 4,395 fresh and stored organisms, generating 4,399 data points for the method comparison study (which serves as the primary test set for demonstrating performance against a reference). This also includes 3,802 replicate testing results reported separately.
- Data Provenance: The method comparison study was performed at six (6) US clinical test sites and an in-house laboratory. The organisms included both fresh and stored organisms. The document indicates that due to the rarity of some organisms, replicates were tested by multiple sites.
3. Number of Experts and Qualifications for Ground Truth of Test Set
The document does not explicitly state the number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") for establishing the ground truth of the test set organisms. However, it indicates:
- "The interim reference laboratory stored all organisms included in the study and sent all organisms to the sequencing reference laboratory for sequencing and protein sequencing when requested."
- This implies that a reference laboratory, likely staffed by expert microbiologists and molecular biologists, was responsible for confirming the identity of the organisms used as ground truth, primarily through sequencing and protein sequencing.
4. Adjudication Method for the Test Set
The document does not mention a specific adjudication method like "2+1" or "3+1" for discrepancies in the test set. The ground truth was established by a "sequencing reference laboratory for sequencing and protein sequencing." This suggests that the final identification was based on these molecular methods, rather than an expert consensus process between multiple readers.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an automated mass spectrometry system for identifying microorganisms. The evaluation focuses on the device's ability to identify organisms compared to a reference method (sequencing/protein sequencing), not on how it assists human readers or improves their performance.
6. Standalone (Algorithm Only) Performance
Yes, a standalone performance study was done. The entire Method Comparison section (pages 20-25) describes the performance of the MALDI Biotyper CA System (the algorithm/device) in identifying microorganisms without human intervention in the identification process other than following the described workflow. The log(score) system is an output of the algorithm.
7. Type of Ground Truth Used
The primary type of ground truth used for the test set was molecular sequencing (sequencing and protein sequencing), which is considered a highly accurate and definitive method for microorganism identification. This was handled by a "sequencing reference laboratory."
8. Sample Size for the Training Set
The document does not explicitly state the sample size for the training set. It refers to a "reference spectra library (database)" against which the test organism's spectrum is compared. This library is implicitly the training data, but its specific size or composition is not detailed in terms of number of unique isolates or spectra.
9. How the Ground Truth for the Training Set Was Established
The document states: "Calculates matches by comparing a new spectrum against each single reference entry of a reference database." It also mentions "MALDI Biotyper for Clinical Applications (MBT-CA)" as the database. While it doesn't describe the exact process for establishing ground truth for each entry within that database, it's generally understood that such reference libraries are built using highly characterized strains whose identities have been confirmed through gold-standard methods (e.g., 16S rRNA gene sequencing, whole-genome sequencing, or polyphasic taxonomy). The context implies that the internal reference library's entries serve as the established ground truth for comparison.
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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 (800) 638 2041 or (301) 796-7100 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
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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 (800) 638-2041 or (301) 796-7100 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.40 Manning Road,Billerica, MA 01821 |
| Correspondent | Bruker Daltonik GmbHMarkus Kostrzewa, Vice President Clinical Mass Spectrometry R&DFahrenheitstrasse 4Bremen, 28359Phone: +49 (0)421-2205 1258Fax: +49 (0)421-2205 205Email: Markus.Kostrzewa@bruker.com |
| Device Identification | |
| Trade or Proprietary Name: | MALDI Biotyper CA System |
| Common or Usual Name: | System, mass spectrometry, maldi tof, microorganism identification,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 massspectrometer system using matrix-assisted laserdesorption/ionization - time-of-flight (MALDI-TOF) for theidentification of microorganisms cultured from humanspecimens.The MALDI Biotyper CA System is a qualitative in vitrodiagnostic device indicated for use in conjunction with otherclinical and laboratory findings to aid in the diagnosis ofbacterial and yeast infections. | The Vitek® MS is a mass spectrometer systemusing matrix-assisted laserdesorption/ionization-time-of- flight (MALDI-TOF) for the identification of microorganismscultured from human specimen.The VITEK MS is a qualitative in vitro diagnosticdevice indicated for use in conjunction withother clinical and laboratory findings to aid inthe diagnosis of bacterial and yeast infections. | See "Differences" |
| Sample type | Isolated colony from any patient sample source.Acceptable media:• Columbia blood agar with 5% sheep blood• Trypticase soy agar with 5% sheep Blood• Chocolate agar• MacConkey Agar• Columbia CNA agar with 5% sheep blood• Brucella Agar with 5% horse blood• CDC anaerobe Agar with 5% sheep blood• CDC anaerobe 5% sheep blood Agar with phenylethyl alcohol• CDC anaerobe laked sheep blood Agar with kanamycin andvancomycin• Bacteroides bile esculin Agar with amikacin• Clostridium difficile Agar with 7% sheep blood• Sabouraud-Dextrose Agar• Brain Heart Infusion Agar• Campylobacter Agar with 5 Antimicrobics and 10% SheepBlood• Bordet Gengou Agar with 15% sheep blood | Isolated colony from any patient samplesource.Acceptable media:• Columbia blood agar with 5% sheep blood• Trypitcase soy agar with 5% sheep Blood• Chocolate polyvitex agar• Campylosel agar• MacConkey Agar• Modified Sabouraud dextrose Agar• ChromID CPS | Isolated colony from any patient samplesource.Acceptable media:• Columbia blood agar with 5% sheepblood• Trypticase soy agar with 5% sheepBlood• Chocolate agar• MacConkey Agar |
| Type of Test | Automated Mass Spectrometry System | Automated Mass Spectrometry System | Automated Mass Spectrometry System |
| Similarities | |||
| Characteristic | NEW DEVICEBruker Daltonics, Inc. MBT-CA System(TBD) | PRIMARY PREDICATE DEVICEVitek® MS(K124067) | PREDICATE DEVICEBruker Daltonics, Inc. MBT-CASystem (K130831) |
| Matrix | α-Cyano-4-hydroxycinnamic acid | α-Cyano-4-hydroxycinnamic acid | α-Cyano-4-hydroxycinnamic acid |
| Method ofTesting | Bacteria & Yeast: Direct testingIf after initial analysis the log(score) is reported at <2.00,organisms may be processed using the Extraction (Ext)procedure or extended Direct Transfer (eDT, 70% aqueousformic acid) procedure. If eDT procedure still yields log(score)<2.00, organism may be processed via Ext procedure. | Bacteria & Yeast: Direct testing | Bacteria: Direct testingIf after initial analysis the log(score) isreported at <2.00, organisms areprocessed using the Extraction procedure. |
| Result Reporting | Organism identification is reported with high confidence if thelog(score) is ≥2.00.An organism identification is reported with low confidence ifthe log(score) is between 1.70 and <2.00. | A single identification is displayed, with aconfidence value from 60.0 to 99.9, when onesignificant organism or organism group isretained."Low-discrimination" identifications aredisplayed when more than one but not morethan four significant organisms or organismgroups are retained.When more than four organisms or organismgroups are found, or when no match is found,the organism is considered unidentified. | Organism identification is reported withhigh confidence if the log(score) is ≥2.00.An organism identification is reported withlow confidence if the log(score) is between1.70 and <2.00. |
| MatchingAlgorithm | Calculates matches by comparing a new spectrum against eachsingle reference entry of a reference database. | Uses a proprietary process called "massbinning." In this process, the spectrumbetween 3,000 and 17,000 Daltons are dividedinto 1300 pre-definedintervals called "bins". Next, an algorithmbased on supervised machine learning knownas the "Advanced Spectrum Classifier", is usedto determine howinformative each bin was in differentiating thatspecies from all other species in the database. | Calculates matches by comparing a newspectrum against each single referenceentry of a reference database. |
| Recorded massrange | 2,000 - 20,000 m/z | 2,000 - 20,000 m/z | 2,000 - 20,000 m/z |
| Similarities | |||
| Characteristic | NEW DEVICEBruker Daltonics, Inc. MBT-CA System(TBD) | PRIMARY PREDICATE DEVICEVitek® MS(K124067) | PREDICATE DEVICEBruker 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• 48 positions reusable steel targets | See "Differences" | US IVD 48 Spot Target• 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 DEVICEBruker Daltonics, Inc. MBT-CA System(TBD) | PREDICATE DEVICEVitek® MS(K124067) | PREDICATE DEVICEBruker Daltonics, Inc. MBT-CA System(K130831) |
| Culture Age | Bacteria and yeasts growth should be between18h to 48h (+12h storage at RT)Specific requirements:• Bordetella: Incubation on BG agar shouldnot be longer than 24h (+12h storage at RT).• Campylobacter: Incubation can beprolonged to 72h (+12h storage at RT).• Streptococcus pneumoniae: Incubationshould not be longer than 24h (+12h storageat RT) due to possible autolysis. | Bacteria and yeast growth should bebetween 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-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 DEVICEBruker Daltonics, Inc. MBT-CA System(TBD) | PREDICATE DEVICEVitek® MS(K124067) | PREDICATE DEVICEBruker Daltonics, Inc. MBT-CA System(K130831) |
| Intended Use | The Bruker Daltonics, Inc. MALDI Biotyper CA System is a mass spectrometer system using matrix-assistedlaser desorption/ionization - time-of-flight (MALDI-TOF) for the identification of microorganisms culturedfrom human specimens.The MALDI Biotyper CA System is a qualitative in vitrodiagnostic device indicated for use in conjunction withother clinical and laboratory findings to aid in thediagnosis of bacterial and yeast infections. | See "Similarities" | The Bruker Daltonics, Inc. MALDI Biotyper CASystem is a qualitative in vitro diagnostic massspectrometer system for the identification of Gram-negative bacterial colonies cultured from humanspecimens using matrix-assisted laserdesorption/ionization - time-of-flight (MALDI-TOF)mass spectrometry technology.The MALDI Biotyper CA System is indicated for usein conjunction with other clinical and laboratoryfindings to aid in the diagnosis of Gram-negativebacterial 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 Moraxellanonliquefaciens | 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 |
| Corynebacteriumpseudodiphtheriticum | 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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| DT | eDT | EXT | ||||
|---|---|---|---|---|---|---|
| Test Organism | Lower limit[cfu/µL] | Upper limit[cfu/µL] | Lower limit[cfu/µL] | Upper limit[cfu/µL] | Lower limit[cfu/µL] | Upper limit[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 temperature after initial plate incubation prior to analysis.
- Chocolate Agar (CHOC) .
- Columbia CNA agar with 5% sheep blood (CNA) .
- Brucella Agar with 5% horse blood (BRU) ●
- CDC anaerobe Agar with 5% sheep blood (CDC) .
- CDC anaerobe 5% sheep blood Agar with phenylethyl alcohol ● (CDC/PEA)
- CDC anaerobe laked sheep blood Agar with kanamycin and vancomycin (CDC/LKV)
- Bacteroides bile esculin Agar with amikacin (BBE)
- . Clostridium difficile Agar with 7% sheep blood (CDA)
- Trypticase Soy Agar with 5% sheep blood (TSA)
- Sabouraud-Dextrose Agar (SDA)
- Brain-Heart Infusion Agar (BHI) ●
- . Campylobacter Agar with 5 Antimicrobics and 10% sheep blood (CAMPY BAP)
- . Bordet Gengou Agar with 15% sheep blood (BGA)
- Columbia Blood Agar with 5% sheep blood (CBA) .
Testing was conducted using three (3) Gram-positive bacteria, three (3) yeasts, five (5) anaerobic bacteria, two (2) Campylobacter and three (3) Bordetella species at varying incubation time points in replicates of eight (8). After initial testing, isolates were further tested at room temperature after twelve (12) hours post-incubation.
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The study results confirmed the acceptability of all culture media tested with the following parameters:
-
Bacteria and yeasts growth should be between 18h to 48h (+12h storage at room temperature (RT)).
Specific requirements: -
Bordetella: Incubation on BG agar should not be longer than 24h (+12h storage at RT).
-
Campylobacter: Incubation on CAMPY BAP can be prolonged to 72h (+12h storage at RT).
-
Streptococcus pneumoniae: Incubation should not be longer than 24h (+12h storage at RT) due to possible autolysis.
Organism Stability Prior to MBT-CA Analysis
This study was conducted to assess Gram-positive and yeast isolate stability on the target plate prior to matrix overlay via Direct Transfer (DT), extended Direct transfer (eDT) and Extraction (Ext) procedure. Two (2) Gram-positive organisms were inoculated eight times and overlaid with matrix at five (5) different time points. Five (5) yeasts organisms were inoculated eight times and overlaid with matrix at (4) different time points. Extracts of Gram-positive bacteria and yeasts were stored at room temperature and inoculated eight times and overlaid with matrix at five (5) different time points. All testing was performed in duplicate.
The study results confirmed that Gram-positive bacteria and yeast organisms are stable on the target plate for up to 60 minutes and 30 minutes respectively prior to matrix addition. Extracts of Gram-positive bacteria and yeasts are stable at room temperature for up to 24 hours and 4 hours respectively.
Sample Stability Overlaid with Matrix
This study was conducted to assess test organism stability overlaid with matrix after inoculation on the target plate. For this study, six (6) organisms were tested (three (3) Gram-positive and three (3) yeast organisms). All organisms were subcultured and aging experiments were conducted at two (2) temperatures and two (2) different relative humidity conditions to stress the plate. Plates were inoculated with the test organism via DT, eDT and Ext procedure. Plates were then read immediately (0h) and then incubated at each test condition and analyzed at three (3) additional time points (4 hours, 8 hours and 24 hours).
The study results confirmed that organisms overlaid with matrix on the target plate are stable for up to 24 hours when stored at room temperature.
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Image /page/19/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 stylized graphic of three overlapping blue orbits with a blue dot at the end of each orbit. The logo is simple and modern, conveying a sense of technology and innovation.
Reproducibility:
The reproducibility study for Gram-positive aerobic bacteria, Gram-negative microaerophilic bacteria, Gram-positive anaerobic bacteria, Gram-negative anaerobic bacteria and yeast organisms was carried out to confirm day-to-day reproducibility and precision of the MALDI Biotyper CA System at different clinical study sites. The study was conducted for five (5) days with two (2) runs (two (2) operators) each day per clinical site. The sources of variability tested were:
-
- Two (2) operators/each clinical study site
-
- Three (3) clinical study sites
-
- At least four (4) target plates/each clinical study site
-
- Four (4) microflex LT/SH instruments
Ten (10) well-characterized organisms were chosen for this study and tested in duplicate via Direct Transfer and extended Direct Transfer procedure in accordance with product instructions. When the DT and/or eDT log(score) was <2.00, per product instructions, the test organism was tested following Extraction procedure in duplicate.
| Blinded Test Organism | ReproducibilityPanel | ≥2.0 ID(DT) | ≥2.0 ID(eDT) | ≥2.0 ID(DT+eDT+Ext) |
|---|---|---|---|---|
| Enterococcus faecalis | REPRO-1 | 60/60 (100%) | 60/60 (100%) | 60/60 (100%) |
| Staphylococcus epidermidis | REPRO-2 | 58/60 (97%) | 59/60 (98%) | 60/60 (100%) |
| Streptococcus agalactiae | REPRO-3 | 58/60 (97%) | 55/60 (92%) | 60/60 (100%) |
| Bacteroides fragilis | REPRO-4 | 60/60 (100%) | 60/60 (100%) | 60/60 (100%) |
| Fusobacterium necrophorum | REPRO-5 | 56/60 (93%) | 53/60 (88%) | 58/60 (97%) |
| Clostridium perfringens | REPRO-6 | 53/60 (88%) | 58/60 (97%) | 59/60 (98%) |
| Propionibacterium acnes | REPRO-7 | 53/60 (88%) | 49/60 (82%) | 60/60 (100%) |
| Candida albicans | REPRO-8 | 33/60 (55%) | 41/60 (68%) | 60/60 (100%) |
| Saccharomyces cerevisiae | REPRO-9 | 5/60 (8%) | 0/60 (0%) | 31/60 (52%) |
| Cryptococcus neoformans vargrubii | REPRO-10 | 31/60 (52%) | 44/60 (73%) | 53/60 (88%) |
| TOTAL | 467/600 (78%) | 479/600 (80%) | 561/600 (94%) |
Table 3: Overall Reproducibility Panel Testing per Test Organism using ≥2.0 MBT-CA log(scores)
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Image /page/20/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 stylized graphic of three overlapping blue circles, resembling an atom or a stylized orbit. The circles are connected by two small blue dots.
94% of test organisms were correctly identified with a log(score) ≥2.00 result. In addition, no isolates were falsely identified. Thus, data confirm reproducibility and precision of the whole MALDI Biotyper CA System independent from:
- Clinical Site
- System operator
- microflex LT/SH instrument
- Target plate
Challenge Panel:
A panel of 55 organisms (24 Gram-positive aerobic bacteria, 1 Gram-negative microaerophilic bacterium, 4 Gram-negative anaerobic bacteria, 6 Gram-positive anaerobic bacteria, 20 yeasts) was tested at four (4) study sites. Fifty-three (53) of the organisms included in the panel were selected from stored organisms tested during the clinical study. Two (2) were selected from strain collections. The study reference laboratory, prepared the panel. Organism identifications were blinded to test sites. Each site tested the challenge panel member via Direct Transfer and extended Direct Transfer procedure in accordance with product instructions. If DT and/or eDT result yielded a log(score) <2.00, the organism was retested using the Extraction procedure.
Table 4: Challenge Panel Study Summary
| Test procedure | Site A | Site B | Site C | Site D | TOTAL |
|---|---|---|---|---|---|
| ≥2.0 ID | ≥2.0 ID | ≥2.0 ID | ≥2.0 ID | ≥2.0 ID | |
| DT method | 46/55 (84%) | 47/55 (85%) | 35/55 (64%)* | 36/55 (65%) | 164/220 (75%) |
| eDT method | 47/55 (85%) | 50/55 (91%) | 44/55 (80%)* | 43/55 (78%) | 184/220 (84%) |
| Ext method | 54/55 (98%) | 53/55 (96%) | 49/55 (89%) | 37/55 (67%) | 193/220 (88%) |
| MBT-CA workflow | 54/55 (98%) | 55/55 (100%) | 49/55 (89%) | 46/55 (84%) | 204/220 (93%) |
- One sample was incorrectly identified due to a mixed culture.
93% of test organisms were correctly identified with a log(score) ≥2.00 result applying MBT-CA workflow. Testing of the challenge panel confirms intra laboratory performance of the MALDI Biotyper CA System.
Method Comparison:
To demonstrate performance of the MALDI Biotyper CA (MBT-CA) System, a method comparison study was performed at six (6) US clinical test sites and in-house laboratory. 4,395 (generating 4,399 data points) fresh and stored organisms were tested on the MALDI Biotyper CA System in accordance to manufacturer's instructions for use. All organisms included in the study were subcultured for purity. Testing on the MBT-CA System was done from a fresh isolated colony. Due to the rarity of some organisms, replicates of these rarer species were tested by multiple testing sites to generate additional data to support performance of the MBT-CA System. Results from the 3,802 replicate testing results were analyzed separately from the method comparison isolates.
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All organisms included in the study were also sub-cultured on to an agar slant or appropriate media for isolation and shipped to the study interim reference laboratory. The interim reference laboratory stored all organisms included in the study and sent all organisms to the sequencing reference laboratory for sequencing and protein sequencing when requested.
The following Gram-negative, Gram-positive and yeast isolates are included in the reference library (please refer to K130831 for previously claimed Gram-negative organisms)
Table 5: Claimed Organisms
| Organisms |
|---|
| Acinetobacter haemolyticus |
| Acinetobacter johnsonii |
| Acinetobacter junii |
| Actinomyces meyeri |
| Actinomyces neuii |
| Actinomyces odontolyticus |
| Actinomyces oris |
| Aerococcus urinae |
| Aerococcus viridans |
| Aeromonas salmonicida |
| 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 |
| Campylobacter coli |
| Campylobacter jejuni |
| Campylobacter ureolyticus |
| Candida albicans |
| Candida boidinii |
| Candida dubliniensis |
| Candida duobushaemulonii |
| Candida famata |
| Candida glabrata |
| Organisms |
| 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 |
| Capnocytophaga ochracea |
| Capnocytophaga sputigena |
| Chryseobacterium gleum |
| Chryseobacterium indologenes |
| Clostridium difficile |
| Clostridium perfringens |
| Corynebacterium amycolatum |
| Corynebacterium aurimucosum group |
| Corynebacterium bovis |
| Corynebacterium diphtheriae |
| Corynebacterium glucuronolyticum |
| Corynebacterium jeikeium |
| Corynebacterium kronnenstedtii |
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Image /page/22/Picture/0 description: The image shows the logo for Bruker Corporation. The logo consists of the word "BRUKER" in bold, sans-serif font, stacked above a stylized graphic. The graphic features a series of interconnected, overlapping circles or ellipses, resembling an atom or a network. The color scheme is primarily black for the text and a light blue for the graphic elements.
Organisms
| Organisms |
|---|
| Corynebacterium macginleyi |
| Corynebacterium minutissimum |
| Corynebacterium propinquum |
| Corynebacterium pseudodiphtheriticum |
| Corynebacterium riegelii |
| Corynebacterium striatum group |
| Corynebacterium tuberculostearicum |
| Corynebacterium ulcerans |
| Corynebacterium urealyticum |
| Corynebacterium xerosis |
| Cronobacter sakazakii group |
| Cryptococcus gattii |
| Cryptococcus neoformans var grubii |
| Cryptococcus neoformans var neoformans |
| Cupriavidus pauculus group |
| Delftia acidovorans group |
| Dermacoccus nishinomiyaensis |
| Edwardsiella tarda |
| Elizabethkingia meningoseptica group |
| Enterobacter amnigenus |
| Enterococcus avium group |
| Enterococcus casseliflavus |
| Enterococcus faecalis |
| Enterococcus faecium |
| Enterococcus gallinarum |
| Enterococcus hirae |
| Finegoldia magna |
| Fusobacterium canifelinum |
| Fusobacterium necrophorum |
| Fusobacterium nucleatum |
| Gardnerella vaginalis |
| Gemella haemolysans |
| Gemella sanguinis |
| Geotrichum candidum |
| Geotrichum capitatum |
| Granulicatella adiacens |
| Haemophilus haemolyticus |
| Haemophilus influenzae |
| Haemophilus parahaemolyticus group |
| Kingella kingae |
| Kloeckera apiculata |
| Kocuria kristingae |
| Organisms |
| Kytococcus sedentarius |
| Lactococcus garvieae |
| Lactococcus lactis |
| Leuconostoc mesenteroides |
| Macrococcus caseolyticus |
| Micrococcus luteus |
| Moraxella sg Moraxella nonliquefaciens |
| Myroides odoratimimus |
| Myroides odoratus |
| Oligella ureolytica |
| Oligella urethralis |
| Parabacteroides distasonis |
| Pediococcus pentosaceus |
| Peptoniphilus harei group |
| Peptostreptococcus anaerobius |
| Pichia ohmeri |
| Plesiomonas shigelloides |
| Porphyromonas gingivalis |
| Prevotella bivia |
| Prevotella buccae |
| Prevotella denticola |
| Prevotella intermedia |
| Prevotella melaninogenica |
| Propionibacterium acnes |
| Pseudomonas oryzihabitans |
| Pseudomonas stutzeri |
| Rhizobium radiobacter |
| Rothia aeria |
| Rothia dentocariosa |
| Rothia mucilaginosa |
| Saccharomyces cerevisiae |
| Serratia plymuthica |
| Serratia rubidaea |
| Staphylococcus aureus |
| Staphylococcus auricularis |
| Staphylococcus capitis |
| Staphylococcus caprae |
| Staphylococcus carnosus |
| Staphylococcus cohnii |
| Staphylococcus epidermidis |
| Staphylococcus equorum |
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Image /page/23/Picture/0 description: The image shows the Bruker logo. The logo consists of the word "BRUKER" in bold, black letters. Above the word, there is a blue graphic that resembles an atom with electrons orbiting around it. The graphic is stylized and abstract, with the blue lines forming interconnected loops.
Organisms
| Organisms |
|---|
| Staphylococcus haemolyticus |
| Staphylococcus hominis |
| Staphylococcus lugdunensis |
| Staphylococcus pasteuri |
| Staphylococcus pettenkoferi |
| Staphylococcus pseudintermedius |
| Staphylococcus saccharolyticus |
| Staphylococcus saprophyticus |
| Staphylococcus schleiferi |
| Staphylococcus simulans |
| Staphylococcus vitulinus |
| Staphylococcus warneri |
| Streptococcus agalactiae |
| Streptococcus anginosus |
| Streptococcus constellatus |
| Streptococcus dysgalactiae |
| Streptococcus gallolyticus |
| Organisms |
| Streptococcus gordonii |
| Streptococcus intermedius |
| Streptococcus lutetiensis |
| Streptococcus mitis / oralis group |
| Streptococcus mutans |
| Streptococcus pneumoniae |
| Streptococcus pyogenes |
| Streptococcus salivarius |
| Sutterella wadsworthensis |
| Trichosporon asahii |
| Vibrio parahaemolyticus |
| Vibrio vulnificus |
Tables 6 - 8 below show the overall isolate performance.
Table 6: Overall Isolate Performance - claim 2
| Overall Performance - claim 2 | |||||
|---|---|---|---|---|---|
| MBT-CA RESULT | REFERENCE ALGORITHM | ||||
| high resolutionspecies | low resolutionspecies / genus | Negative | Total | ||
| Organism ID ≥ 2.0(High Confidence) | 3817 | 392 | 18 | 4227 | |
| Organism ID (≥1.7; <2.0)(Low Confidence) | 107 | 13 | 9 | 129 | |
| - INCORRECT MBT-CA ID (≥1.7)- NO ID (<1.7) | 42 | 1 | n/a | 43 | |
| Total | 3966 | 406 | 27 | 4399 |
| Positive | Negative | |
|---|---|---|
| highresolution | high & lowresolution | |
| 96.27% | 99.02% | n/a |
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Image /page/24/Picture/0 description: The image shows the Bruker logo. The word "BRUKER" is written in bold, black letters. Above the word is a graphic of a stylized atom with two electrons orbiting the nucleus. The electrons are represented by blue dots.
Table 7: Overall Bacteria Performance
| Overall Performance BACTERIA | ||||
|---|---|---|---|---|
| MBT-CA RESULT | REFERENCE ALGORITHM | |||
| high resolutionspecies | low resolutionspecies / genus | Negative | Total | |
| Organism ID ≥ 2.0(High Confidence) | 3079 | 389 | 17 | 3485 |
| Organism ID (≥1.7; <2.0)(Low Confidence) | 52 | 12 | 9 | 73 |
| - INCORRECT MBT-CA ID (≥1.7)- NO ID (<1.7) | 25 | 1 | n/a | 26 |
| Total | 3156 | 402 | 26 | 3584 |
| Positive | Negative | |
|---|---|---|
| highresolution | high & lowresolution | |
| 97.47% | 99.27% | n/a |
Table 8: Overall Yeast Performance
| Overall Performance YEAST | ||||
|---|---|---|---|---|
| MBT-CA RESULT | REFERENCE ALGORITHM | |||
| high resolutionspecies | low resolutionspecies / genus | Negative | Total | |
| Organism ID ≥ 2.0(High Confidence) | 738 | 3 | 1 | 742 |
| Organism ID (≥1.7; <2.0)(Low Confidence) | 55 | 1 | 0 | 56 |
| - INCORRECT MBT-CA ID (≥1.7)- NO ID (<1.7) | 17 | 0 | 0 | 17 |
| Total | 810 | 4 | 1 | 815 |
| Positive | Negative | |
|---|---|---|
| highresolution | high & lowresolution | 0.00% |
| 91.03% | 97.91% | 0.00% |
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Statement of Safety and Efficacy
The data presented clearly demonstrate the safety and efficacy of the Bruker Daltonics, Inc. MBT-CA System as compared to the reference algorithm, when the instructions for use are followed.
§ 866.3361 Mass spectrometer system for clinical use for the identification of microorganisms.
(a)
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.(b)
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 as part of your 21 CFR 820.30 design controls, 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.