(203 days)
No
The device uses a 1:1 comparison of unknown spectra against a reference library and sorts results based on a calculated score. This is a deterministic algorithm based on pre-defined reference patterns, not a system that learns or adapts from data. The document explicitly states "The addition of new reference entries does not influence the already included entries." and "If no reference entries are removed within a library update the log(score) calculation remains unchanged for the same MALDI spectra," which is contrary to how typical ML models function. There is no mention of training or inference in the context of AI/ML.
No
The device is an in vitro diagnostic device used to identify and differentiate microorganisms to aid in the diagnosis of bacterial and fungal infections. It does not provide any treatment or therapeutic benefit.
Yes
The "Intended Use / Indications for Use" section explicitly states, "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 fungal infections." This direct statement confirms its diagnostic purpose.
No
The device description explicitly states that the system consists of hardware components including a mass spectrometer, kit reagents, target plates, and firmware, in addition to the software.
Yes, this device is an IVD (In Vitro Diagnostic).
The document explicitly states in the "Intended Use / Indications for Use" section:
"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 fungal infections."
This statement directly identifies the device as an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
The MALDI Biotyper CA System is a mass spectrometer system using matrix-assisted laser desorption/ionization - time of flight (MALDI-TOF) for the identification and differentiation 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 fungal infections.
Product codes (comma separated list FDA assigned to the subject device)
QBN
Device Description
- The MBT-CA System consists of the Microflex LT/SH mass spectrometer, reference library, kit reagents (US IVD HCCA, US IVD Bacterial Test Standard), US IVD 48 Spot Target or MBT Biotarget 96 US IVD plate, and software. The MALDI Biotyper CA System with closed safety covers is a Class 1 Laser product. With the safety cover opened it becomes a Class 4 Laser product.
- The MALDI Biotyper CA System reference library was established by analyzing the type strain from each claimed species combined with 4 to ~30 additional strains from the same species provided by clinical laboratories or commercial strain collections. Currently a total of 3029 strains (covering 334 species / groups with 294 bacteria plus 40 yeasts) are contained in the clinically validated MBT-CA library.
- Implementation methodology, construction parameters and quality assurance protocols use a standard operating protocol for generation of reference entries and all testing parameters are the same.
- MBT-CA microorganism identification is based on isolate MALDI spectra using Bruker reference libraries with a 1:1 comparison of unknown MALDI spectra against each single entry of a given reference library. During a single identification event, an unknown MALDI spectra is compared against each single reference entry producing individual log(score) results. This number of log(scores) is sorted based on their value and the highest one is used to generate the final result. The addition of new reference entries does not influence the already included entries. If no reference entries are removed within a library update the log(score) calculation remains unchanged for the same MALDI spectra.
- MALDI Biotyper CA System client software displays a user-interface which guides the user through the MALDI Biotyper CA System workflow. The MALDI Biotyper CA System client also interfaces to the flexControl software for automated acquisition of mass spectra on the microflex LT/SH instrument.
- The MALDI Biotyper CA System server communicates with the MALDI Biotyper CA System client and the MBT-DB server. It performs preprocessing on acquired spectra, and matches peak lists against the Main Spectrum (reference pattern, (MSP)) for matching and calculates the score value (log (score)).
- The MBT-DB server stores all information for the MALDI Biotyper CA System. The MBT-DB maintains spectra data (creation information and mass/intensity lists), project data (results of defined and executed runs), method data (parameter lists for spectra preprocessing and identification), user management data, reference patterns and other peak lists plus additional maintenance data.
- GTPS firmware communicates with the flexControl PC software, controls and monitors the vacuum, moves the sample carrier and performs the docking of the target plate, controls and monitors high voltages in the ion source, generates trigger signals, and monitors instrument status.
- The flexControl acquisition software communicates with the MALDI Biotyper CA System client, loads automatic run jobs, communicates with the GTPS firmware, communicates with the laser in the microflex LT/SH instrument, sets the acquisition parameters in the digitizer and reads the acquired data from the digitizer, performs automated data acquisition, evaluates acquired spectra, adjusts the laser power during automatic data acquisition, performs a re-calibration of the time-of-flight to mass transformation, stored acquired spectra on disk and performs source cleaning. The flexControl software does not display a user interface.
- The optional Honeywell (Hyperion 1300g) Barcode Reader USB cable is connected to the MALDI Biotyper CA System computer. The barcode reader scans the unique ten-digit target ID which appears in the Target ID box on the target plate. After the target ID has been entered, the a new Run page opens and the ten-digit target ID appears as the Plate ID and is appended to the Run name. Sample identifications are entered into the computer corresponding to the target plate position for that run.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
For in vitro diagnostic use only
The MALDI Biotyper CA System is for prescription use only.
Description of the training set, sample size, data source, and annotation protocol
The MALDI Biotyper CA System reference library was established by analyzing the type strain from each claimed species combined with 4 to ~30 additional strains from the same species provided by clinical laboratories or commercial strain collections. Currently a total of 3029 strains (covering 334 species / groups with 294 bacteria plus 40 yeasts) are contained in the clinically validated MBT-CA library.
Description of the test set, sample size, data source, and annotation protocol
A panel of Candida auris isolates and nine (9) other yeast species related to C. auris or commonly misidentified as C. auris were obtained from the CDC & FDA Antibiotic Resistance Isolate Bank (https://wwwn.cdc.gov/arisolatebank/). Additional C. auris isolates were obtained from (b) (4) (9), (b) (4) (8), (b) (4) (1). Isolates are summarized in Table 1 below.
Twenty-eight (28) C. auris isolates as well as the nine (9) additional yeast species of the CDC panel were used for this study. Each isolate was cultured on sabourauddextrose agar, and spotted 8 times using DT, eDT and Ext sample preparation techniques. and measured on the MALDI instrument. Mass spectra acquisition and MBT-CA System identification were performed using FDA-cleared MBT-CA System software (client version 3.2.12). 888 spectra (37 strains * 3 sample preparations * 8 spots = 888) were used for identification and compared against the:
- cleared validated MBT-CA library.
- non-clinically validated MBT-CA library,
- cleared plus non-clinically validated MBT-CA libraries, and
- cleared validated MBT-CA library plus the six (6) new C. auris reference entries.
All 37 isolates used in this study were identified successfully using DT, eDT and Ext sample preparation techniques. Six (6) strains were used for reference library generation and 28 strains of C. auris were analyzed. All 28 strains were used for performance evaluation but only 22 strains were used for generating the truth tables; the six (6) strains used for reference entries were excluded from truth table counting (See Tables 2 and 3).
The ITS sequence was determined for all six strains used for the new reference library entries.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
- Addition of C. auris to MBT-CA reference library
- Study Type: Analytical Performance
- Sample Size: 888 spectra (37 strains * 3 sample preparations * 8 spots)
- Key Results: All 37 isolates identified successfully using DT, eDT and Ext.
- Analytical Specificity - In silico evaluation
- Study Type: Analytical Specificity
- Sample Size: 0 spectra (6822 log(scores))
- Key Results: Cross-validation showed 100% identical results.
- Analytical Specificity - Wet testing of claimed organisms
- Study Type: Analytical Specificity
- Sample Size: 360 spectra / log(scores)
- Key Results: All organisms could be identified. No influence of new C. auris reference entries and no cross-identification was observed.
- Analytical Specificity - Wet testing of RUO organisms
- Study Type: Analytical Specificity
- Sample Size: (0) pectra / log(scores)
- Key Results: None of the RUO organisms were (fified with the MBT-CA libraries. No influence of the new C. auris reference entries and no cross-identification was observed.
- Reproducibility: See K130831, K142677 and K163536.
- Linearity/assay Reportable Range: Not applicable, qualitative assay.
- Traceability, Stability, Expected Values (controls, calibrators, or methods):
- Calibrator: See K130831, K142677 and K163536.
- Controls: See K130831, K142677 and K163536.
- Sample Stability after Matrix Overlay: Validation previously reported in 510(k) K130831 (Gram-negative) and K142677 (Gram-positive and yeasts).
- US IVD Bacterial Test Standard (BTS) Stability: Established and described in 510(k) K130831.
- HCCA portioned (Matrix) Stability: Established and described in 510(k) K130831.
- Target plates stability: Established and described in 510(k) K142677.
- Organism Stability: See K130831, K142677 and K163536.
- Detection Limit:
- Influence of Agar Media: Validation previously performed and reported in 510(k) K130831.
- Carry-Over/ Cross-Contamination: Previously performed and reported in K130831.
- Assay Cut-off: Unchanged from K130831.
- Comparison Studies:
- Method comparison with predicate device: Not applicable.
- Matrix comparison: Not applicable.
- Clinical Studies: See K130831, K142677 and K163536.
- Clinical cut-off: See Assay Cut-Off.
- Expected values/Reference range: See L.1.i.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
| MBT-CA Result | Reference Algorithm | Total |
|---|---|---|
| Positive Organism ID; (High Confidence); log(score) $\ge$ 2.0 | 22 (High resolution species) | 22 |
| Positive Organism ID; (Low Confidence); log(score) $\ge$ 1.7 - |
§ 866.3378 Clinical mass spectrometry microorganism identification and differentiation system.
(a)
Identification. A clinical mass spectrometry microorganism identification and differentiation system is a qualitative in vitro diagnostic device intended for the identification and differentiation of microorganisms from processed human specimens. The system acquires, processes, and analyzes spectra to generate data specific to a microorganism(s). The device is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infection.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use statement must include a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended, when applicable.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt with an indication for in vitro diagnostic use.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology and all pre-analytical methods for processing of specimens, and algorithm used to generate a final result. This must include a description of validated inactivation procedure(s) that are confirmed through a viability testing protocol, as applicable.
(ii) Performance characteristics for all claimed sample types from clinical studies with clinical specimens that include prospective samples and/or, if appropriate, characterized samples.
(iii) Performance characteristics of the device for all claimed sample types based on analytical studies, including limit of detection, inclusivity, reproducibility, interference, cross-reactivity, interfering substances, carryover/cross-contamination, sample stability, and additional studies regarding processed specimen type and intended use claims, as applicable.
(iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing.
(4) The device's labeling must include a prominent hyperlink to the manufacturer's website where the manufacturer must make available their most recent version of the device's labeling required under § 809.10(b) of this chapter, which must reflect any changes in the performance characteristics of the device. FDA must have unrestricted access to this website, or manufacturers must provide this information to FDA through an alternative method that is considered and determined by FDA to be acceptable and appropriate.
(5) Design verification and validation must include:
(i) Any clinical studies must be performed with samples representative of the intended use population and compare the device performance to results obtained from an FDA-accepted reference method and/or FDA-accepted comparator method, as appropriate. Documentation from the clinical studies must include the clinical study protocol (including predefined statistical analysis plan, if applicable), clinical study report, and results of all statistical analyses.
(ii) Performance characteristics for analytical and clinical studies for specific identification processes for the following, as appropriate:
(A) Bacteria,
(B) Yeasts,
(C) Molds,
(D) Mycobacteria,
(E) Nocardia,
(F) Direct sample testing (
e.g., blood culture),(G) Antibiotic resistance markers, and
(H) Select agents (
e.g., pathogens of high consequence).(iii) Documentation that the manufacturer's risk mitigation strategy ensures that their device does not prevent any device(s) with which it is indicated for use, including incorporated device(s), from achieving their intended use (
e.g., safety and effectiveness of the functions of the indicated device(s) remain unaffected).(iv) A detailed device description, including the following:
(A) Overall device design, including all device components and all control elements incorporated into the testing procedure.
(B) Algorithm used to generate a final result from raw data (
e.g., how raw signals are converted into a reported result).(C) A detailed description of device software, including validation activities and outcomes.
(D) Acquisition parameters (
e.g., mass range, laser power, laser profile and number of laser shots per profile, raster scan, signal-to-noise threshold) used to generate data specific to a microorganism.(E) Implementation methodology, construction parameters, and quality assurance protocols, including the standard operating protocol for generation of reference entries for the device.
(F) For each claimed microorganism characteristic, a minimum of five reference entries for each organism (including the type strain for microorganism identification), or, if there are fewer reference entries, a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, for why five reference entries are not needed.
(G) DNA sequence analysis characterizing all type strains and at least 20 percent of the non-type strains of a species detected by the device, or, if there are fewer strain sequences, then a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, must be provided for the reduced number of strains sequenced.
(H) As part of the risk management activities, an appropriate end user device training program, which must be offered as an effort to mitigate the risk of failure from user error.
0
EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR
DECISION MEMORANDUM
A. DEN Number:
DEN 170081
B. Purpose for Submission:
De Novo request for evaluation of automatic class III designation for the MALDI Biotyper CA System
C. Measurands:
See Indications for Use
D. Type of Test:
A mass spectrometer system for clinical use for the identification and differentiation of microorganisms is a qualitative in vitro diagnostic device intended for the identification and differentiation of microorganisms cultured from human specimens. The device is comprised of an ionization source, a mass analyzer and a spectral database. The system acquires, processes and analyzes spectra to generate data specific to a microorganism(s). The device is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infections.
E. Applicant:
Bruker Daltonik GmbH
F. Proprietary and Established Names:
Trade Name: MALDI Biotyper CA System
Common Names: MALDI Biotyper CA (MBT-CA) System, MBT-CA
G. Regulatory Information:
-
- Regulation section:
21 CFR 866.3378
- Regulation section:
-
- Classification:
1
Class II (Special Controls)
-
- Product code(s):
QBN
- Product code(s):
-
- Panel:
83- Microbiology
- Panel:
H. Indications for Use:
-
- Indications for use:
The MALDI Biotyper CA System is a mass spectrometer system using matrix-assisted laser desorption/ionization - time of flight (MALDI-TOF) for the identification and differentiation of microorganisms cultured from human specimens.
- Indications for use:
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 fungal infections.
| Bacteria: | |
|---|---|
| Abiotrophia defectiva | Achromobacter xylosoxidans |
| Acinetobacter baumannii / nosocomialis group | Acinetobacter calcoaceticus |
| Acinetobacter haemolyticus | Acinetobacter johnsonii |
| Acinetobacter junii | Acinetobacter lwoffii |
| Acinetobacter pittii | Acinetobacter radioresistens |
| Acinetobacter ursingii | Actinomyces europaeus |
| Actinomyces funkei | Actinomyces graevenitzii |
| Actinomyces hyovaginalis | Actinomyces meyeri |
| Actinomyces neuii | Actinomyces odontolyticus |
| Actinomyces oris | Actinomyces radingae |
| Actinomyces turicensis | Actinomyces urogenitalis |
| Actinotignum schaalii group | Aerococcus sanguinicola |
| Aerococcus urinae | Aerococcus viridans |
| Aeromonas salmonicida | Aeromonas hydrophila / caviae group |
| Aggregatibacter actinomycetemcomitans | Aggregatibacter aphrophilus |
| Aggregatibacter segnis | Alcaligenes faecalis |
| Alloiococcus otitis | Alloscardovia omnicolens |
| Bacteria: | |
| Anaerococcus murdochii | Anaerococcus vaginalis |
| Arthrobacter cumminsii | Bacteroides caccae |
| Bacteroides fragilis | Bacteroides nordii |
| Bacteroides ovatus group | Bacteroides pyogenes |
| Bacteroides salyersiae | Bacteroides stercoris group |
| Bacteroides thetaiotaomicron group | Bacteroides uniformis |
| Bacteroides vulgatus group | Bifidobacterium breve |
| Bordetella pertussis bronchiseptica | |
| parapertussis | Bordetella hinzii |
| Brevibacterium casei | Brevundimonas diminuta group |
| Burkholderia cepacia complex | Burkholderia gladioli |
| Burkholderia multivorans | Campylobacter coli |
| Campylobacter jejuni | Campylobacter ureolyticus |
| Capnocytophaga ochracea | Capnocytophaga sputigena |
| Chryseobacterium gleum | Chryseobacterium indologenes |
| Citrobacter amalonaticus complex | Citrobacter freundii complex |
| Citrobacter koseri | Clostridium beijerinckii |
| Clostridium bifermentans | Clostridium butyricum |
| Clostridium clostridioforme group | Clostridium difficile |
| Clostridium innocuum | Clostridium paraputrificum |
| Clostridium perfringens | Clostridium ramosum |
| Clostridium septicum | Clostridium sordellii |
| Clostridium sporogenes / | |
| Clostridium botulimim (group I) | Clostridium tertium |
| Corynebacterium accolens | Corynebacterium afermentans group |
| Corynebacterium amycolatum | Corynebacterium aurimucosum group |
| Corynebacterium bovis | Corynebacterium coyleae |
| Corynebacterium diphtheriae | Corynebacterium frenevi |
| Corynebacterium glucuronolyticum | Corynebacterium glutamicum |
| Corynebacterium jeikeium | Corynebacterium kroppenstedtii |
| Corynebacterium macginleyi | Corynebacterium minutissimum |
| Corynebacterium mucifaciens / | |
| ureicelerivorans group | Corynebacterium propinquum |
| Corynebacterium pseudodiphtheriticum | Corynebacterium pseudotuberculosis |
| Bacteria: | |
| Corynebacterium resistens | Corynebacterium riegelii |
| Corynebacterium striatum group | Corynebacterium tuberculostearicum |
| Corynebacterium ulcerans | Corynebacterium urealyticum |
| Corynebacterium xerosis | Cronobacter sakazakii group |
| Cupriavidus pauculus group | Delftia acidovorans group |
| Dermabacter hominis | Dermacoccus nishinomiyaensis |
| Edwardsiella tarda | Eikenella corrodens |
| Elizabethkingia meningoseptica group | Enterobacter aerogenes |
| Enterobacter amnigenus | Enterobacter cloacae complex |
| Enterococcus avium | Enterococcus casseliflavus |
| Enterococcus durans | Enterococcus faecalis |
| Enterococcus faecium | Enterococcus gallinarum |
| Enterococcus hirae | Enterococcus mundtii |
| Enterococcus raffinosus | Escherichia coli |
| Escherichia hermannii | Escherichia vulneris |
| Ewingella americana | Facklamia hominis |
| Finegoldia magna | Fluoribacter bozemanae |
| Fusobacterium canifelinum | Fusobacterium necrophorum |
| Fusobacterium nucleatum | Gardnerella vaginalis |
| Gemella haemolysans | Gemella morbillorum |
| Gemella sanguinis | Gramulicatella adiacens |
| Haemophilus haemolyticus | Haemophilus influenzae |
| Haemophilus parahaemolyticus group | Haemophilus parainfluenzae |
| Hafnia alvei | Helcococcus kunzii |
| Kingella denitrificans | Kingella kingae |
| Klebsiella oxytoca Raoultella | |
| ornithinolytica | Klebsiella pneumoniae |
| Klebsiella variicola | Kocuria kristinae |
| Kytococcus sedentarius | Lactobacillus gasseri |
| Lactobacillus jensenii | Lactobacillus rhamnosus |
| Lactococcus garvieae | Lactococcus lactis |
| Leclercia adecarboxylata | Legionella longbeachae |
| Bacteria: | |
| Legionella pneumophila | Leuconostoc citreum |
| Leuconostoc mesenteroides | Leuconostoc pseudomesenteroides |
| Listeria monocytogenes | Macrococcus caseolyticus |
| Mannheimia haemolytica group | Micrococcus luteus |
| Micrococcus lylae | Mobiluncus curtisii |
| Moraxella sg Branhamella catarrhalis* | |
| Moraxella sg Moraxella osloensis* | Moraxella sg Moraxella nonliquefaciens* |
| Morganella morganii | |
| Myroides odoratimimus | Myroides odoratus |
| Neisseria bacilliformis | Neisseria cinerea |
| Neisseria elongata | Neisseria flavescens / subflava group |
| Neisseria gonorrhoeae | Neisseria lactamica |
| Neisseria meningitidis | Neisseria sicca group |
| Neisseria weaveri | Nocardia brasiliensis |
| Nocardia cyriacigeorgica | Nocardia farcinica group |
| Nocardia nova | Nocardia otitidiscaviarum |
| Ochrobactrum anthropi | Oligella ureolytica |
| Oligella urethralis | Pantoea agglomerans |
| Parabacteroides distasonis | Parabacteroides goldsteinii |
| Parabacteroides johnsonii / merdae group | Parvimonas micra |
| Pasteurella multocida | Pediococcus acidilactici |
| Pediococcus pentosaceus | Peptoniphilus harei group |
| Peptostreptococcus anaerobius | Plesiomonas shigelloides |
| Pluralibacter gergoviae | Porphyromonas gingivalis |
| Porphyromonas somerae | Prevotella bivia |
| Prevotella buccae | Prevotella denticola |
| Prevotella intermedia | Prevotella melaninogenica |
| Propionibacterium acnes | Proteus mirabilis |
| Proteus vulgaris group | Providencia rettgeri |
| Providencia stuartii | Pseudomonas aeruginosa |
| Pseudomonas fluorescens group | Pseudomonas oryzihabitans |
| Pseudomonas putida group | Pseudomonas stutzeri |
| Ralstonia pickettii | Rhizobium radiobacter |
| Bacteria: | |
| Rothia aeria | Rothia dentocariosa |
| Rothia mucilaginosa | Salmonella sp** |
| Serratia fonticola | Serratia liquefaciens |
| Serratia marcescens | Serratia odorifera |
| Serratia plymuthica | Serratia rubidaea |
| Sphingobacterium multivorum | Sphingobacterium spiritivorum |
| Sphingomonas paucimobilis group | Staphylococcus aureus |
| Staphylococcus auricularis | Staphylococcus capitis |
| Staphylococcus caprae | Staphylococcus carnosus |
| Staphylococcus cohnii | Staphylococcus delphini |
| Staphylococcus epidermidis | Staphylococcus equorum |
| Staphylococcus felis | Staphylococcus haemolyticus |
| Staphylococcus hominis | Staphylococcus intermedius |
| Staphylococcus lentus | Staphylococcus lugdunensis |
| Staphylococcus pasteuri | Staphylococcus pettenkoferi |
| Staphylococcus pseudintermedius | Staphylococcus saccharolyticus |
| Staphylococcus saprophyticus | Staphylococcus schleiferi |
| Staphylococcus sciuri | Staphylococcus simulans |
| Staphylococcus vitulinus | Staphylococcus warneri |
| Staphylococcus xylosus | Stenotrophomonas maltophilia |
| Streptococcus agalactiae | Streptococcus anginosus |
| Streptococcus canis | Streptococcus constellatus |
| Streptococcus dysgalactiae | Streptococcus equi |
| Streptococcus gallolyticus | Streptococcus gordonii |
| Streptococcus intermedius | Streptococcus lutetiensis |
| Streptococcus mitis / oralis group | Streptococcus mutans |
| Streptococcus parasanguinis | Streptococcus pneumoniae |
| Streptococcus pyogenes | Streptococcus salivarius / vestibularis group |
| Streptococcus sanguinis | Streptococcus sobrinus |
| Streptococcus thermophilus | Sutterella wadsworthensis |
| Trueperella bernardiae | Turicella otitidis |
| Vagococcus fluvialis | Veillonella parvula group |
2
3
4
5
6
Bacteria:
Vibrio parahaemolyticus
Weeksella virosa
Yersinia frederiksenii
Yersinia kristensenii
- = subgenus
sp** = species
- Yeasts:
| Candida albicans | Candida auris |
|---|---|
| Candida boidinii | Candida dubliniensis |
| Candida duobushaemulonii | Candida famata |
| Candida glabrata | Candida guilliermondii |
| Candida haemulonis | Candida inconspicua |
| Candida intermedia | Candida kefyr |
| Candida krusei | Candida lambica |
| Candida lipolytica | Candida lusitaniae |
| Candida metapsilosis | Candida norvegensis |
| Candida orthopsilosis | Candida parapsilosis |
| Candida pararugosa | Candida pelliculosa |
| Candida tropicalis | Candida valida |
| Candida zeylanoides | Cryptococcus gattii |
| Cryptococcus neoformans var grubii* | Cryptococcus neoformans var neoformans* |
| Cyberlindnera jadinii | Geotrichum candidum |
| Geotrichum capitatum | Kloeckera apiculata |
| Malassezia furfur | Malassezia pachydermatis |
| Pichia ohmeri | Rhodotorula mucilaginosa |
| Saccharomyces cerevisiae | Trichosporon asahii |
| Trichosporon inkin | Trichosporon mucoides group |
| * = variety |
Vibrio vulnificus
Yersinia enterocolitica
Yersinia pseudotuberculosis
Yersinia intermedia
-
- Special conditions for use statement(s):
For in vitro diagnostic use only
- Special conditions for use statement(s):
7
The MALDI Biotyper CA System is for prescription use only.
Special instrument requirements:
Microflex LT/SH mass spectrometer
Database: MALDI Biotyper for Clinical Applications (MBT-CA)
Software:
- MBT-CA System Software Package:
- MBT-CA System client software displaying the user interface ●
- MBT-CA System Server ●
- MBT-CA System DB Server ●
- flexControl Software Package (GTPS firmware, flexControl acquisition software) ●
Honeywell (Hyperion 1300g) Barcode Reader (optional)
I. Device Description:
- The MBT-CA System consists of the Microflex LT/SH mass spectrometer, reference library, ● kit reagents (US IVD HCCA, US IVD Bacterial Test Standard), US IVD 48 Spot Target or MBT Biotarget 96 US IVD plate, and software. The MALDI Biotyper CA System with closed safety covers is a Class 1 Laser product. With the safety cover opened it becomes a Class 4 Laser product.
- The MALDI Biotyper CA System reference library was established by analyzing the type . strain from each claimed species combined with 4 to ~30 additional strains from the same species provided by clinical laboratories or commercial strain collections. Currently a total
- of 3029 strains (covering 334 species / groups with 294 bacteria plus 40 yeasts) are P contained in the clinically validated MBT-CA library.
- Implementation methodology, construction parameters and quality assurance protocols use a standard operating protocol for generation of reference entries and all testing parameters are the same.
- MBT-CA microorganism identification is based on isolate MALDI spectra using Bruker ● reference libraries with a 1:1 comparison of unknown MALDI spectra against each single entry of a given reference library. During a single identification event, an unknown MALDI spectra is compared against each single reference entry producing (b) (4) individual log(score) results. This number of log(scores) is sorted based on their value and the highest one is used to generate the final result. The addition of new reference entries does not influence the already included entries. If no reference entries are removed within a library update the log(score) calculation remains unchanged for the same MALDI spectra.
- MALDI Biotyper CA System client software displays a user-interface which guides the user through the MALDI Biotyper CA System workflow. The MALDI Biotyper CA System client also interfaces to the flexControl software for automated acquisition of mass spectra on the microflex LT/SH instrument.
- The MALDI Biotyper CA System server communicates with the MALDI Biotyper CA ● System client and the MBT-DB server. It performs preprocessing on acquired spectra, and
8
matches peak lists against the Main Spectrum (reference pattern, (MSP)) for matching and calculates the score value (log (score)).
- The MBT-DB server stores all information for the MALDI Biotyper CA System. The MBT-DB maintains spectra data (creation information and mass/intensity lists), project data (results of defined and executed runs), method data (parameter lists for spectra preprocessing and identification), user management data, reference patterns and other peak lists plus additional maintenance data.
- GTPS firmware communicates with the flexControl PC software, controls and monitors the vacuum, moves the sample carrier and performs the docking of the target plate, controls and monitors high voltages in the ion source, generates trigger signals, and monitors instrument status.
- The flexControl acquisition software communicates with the MALDI Biotyper CA System client, loads automatic run jobs, communicates with the GTPS firmware, communicates with the laser in the microflex LT/SH instrument, sets the acquisition parameters in the digitizer and reads the acquired data from the digitizer, performs automated data acquisition, evaluates acquired spectra, adjusts the laser power during automatic data acquisition, performs a re-calibration of the time-of-flight to mass transformation, stored acquired spectra on disk and performs source cleaning. The flexControl software does not display a user interface.
- The optional Honeywell (Hyperion 1300g) Barcode Reader USB cable is connected to the MALDI Biotyper CA System computer. The barcode reader scans the unique ten-digit target ID which appears in the Target ID box on the target plate. After the target ID has been entered, the a new Run page opens and the ten-digit target ID appears as the Plate ID and is appended to the Run name. Sample identifications are entered into the computer corresponding to the target plate position for that run.
Required Materials Supplied by Bruker
- US IVD 48 Spot Target [P/N: 8604532] ●
- US IVD BTS (Bacterial Test Standard) [P/N: 8604530] ●
- US IVD HCCA portioned [P/N: 8604531] ●
Required Materials that are Not Supplied by Bruker
The following solvents and chemicals are not supplied by Bruker but are required to perform the analysis. For best results, use freshly prepared solutions and chemicals of (b) (4) or MALDI (b) (4) solvents). compatible grade (for example,
- Standard Solvent (acetonitrile 50%, water 47.5% and trifluoroacetic acid 2.5%) ● [Vendor: (b) (4) or equivalent]
- Acetonitrile ●
- (b) (4) water ●
- Formic acid (FA)
- (b) (4) Ethanol (EtOH) ●
- Trifluoroacetic acid (TFA)
- Sterile Colony Transfer Device ●
- . Sterile (b) inoculation loops
- (b) (4) pipette tips ●
- Suitable pipettes for volumes from ●
(b) (4)
(b) (4)
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Image /page/9/Figure/0 description: The image shows a list of laboratory equipment. The list includes plastic tubes, screw-cap micro tubes, a bench-top microcentrifuge, a vortex mixer, and standard laboratory equipment. Some of the text in the image is redacted.
J. Standard/Guidance Document Referenced (if applicable):
Not applicable
K. Test Principle:
Organisms to be identified with the MALDI Biotyper CA System are isolated using the appropriate isolation media. Users are instructed to first test the organism using the direct transfer technique (unless specified to perform extraction in the product labeling). If results are less than Micrococcus flavus | |
| | Aerobe | Rothia terrae | |
| bacteria | Anaerobe | Clostridium magnum | |
| | Anaerobe | Paenibacillus durus | |
| Yeasts | | Candida solani | |
- c. Reproducibility: See K130831, K142677 and K163536.
- d. Linearity/assay Reportable Range: Not applicable, qualitative assay.
- Traceability, Stability, Expected Values (controls, calibrators, or methods): e.
Calibrator: See K130831, K142677 and K163536.
Controls: See K130831, K142677 and K163536.
Sample Stability after Matrix Overlay: The sample stability study on target plates for Gram-negative bacteria was previously validated and reported in 510(k) K130831. The sample stability on target plates for Gram-positive bacteria and yeasts was validated and reported in 510(k) K142677.
US IVD Bacterial Test Standard (BTS) Stability: BTS Stability was established and described in 510(k) K130831.
HCCA portioned (Matrix) Stability: CCA portioned (Matrix) Stability was established and described in 510(k) K130831.
Target plates stability: Target plate stability was established and described in 510(k) K142677.
Organism Stability: For FDA-cleared media organism stability studies see K130831, K142677 and K163536.
- f. Detection Limit:
The Limit of Detection/Dynamic Range study for Gram-negative bacteria was previously performed and reported in K130831. The Limit of Detection/Dynamic Range study for Gram-positive bacteria and yeasts was performed and reported in 510(k) K142677.
g. Influence of Agar Media
The validation of sample preparation of test organism to demonstrate that culture media inoculated onto US IVD 48 spot targets with or without an organism present does not interfere with system performance was previously performed and reported in 510(k) K130831.
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h. Carry-Over/ Cross-Contamination
The carry-over, cross-contamination and target cleaning study was previously performed and reported in K130831. -
Assay Cut-off i.
The assay cut-off remains unchanged as established in K130831. Using statistical 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 (direct or extracted) is reported with high confidence if the log(score) is ≥ 2.00. If a direct transfer organism identification log(score) is