(240 days)
The Bruker Daltonics, Inc MALDI Biotyper CA System is a qualitative in vitro diagnostic mass spectrometer system for the identification of Gram-negative bacterial colonies cultured from human specimens using matrix-assisted laser desorption/ ionization - time of flight (MALDI-TOF) mass spectrometry technology.
The MALDI Biotyper CA System is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of Gram negative bacterial infections.
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.
The provided text describes the acceptance criteria and a detailed study for the MALDI Biotyper CA System, a mass spectrometer used for identifying Gram-negative bacterial colonies.
Here's the breakdown of the information requested:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally implied throughout the performance studies, aiming for high correct identification rates and low false identification/no identification rates for organisms within the claim, and "No Identification" for organisms outside the claim.
| Acceptance Criteria Category | Specific Acceptance Criteria (Implied from Study Goals) | Reported Device Performance |
|---|---|---|
| Precision/Repeatability | Consistent and reproducible organism identification across multiple operators, instruments, target lots, and matrix lots, with high log(scores). | - Overall Reliability: 100% of samples passed (identified) after Direct Transfer + Extraction for all 10 tested organisms. Most organisms achieved high identification rates (≥97.2%) with Direct Transfer alone. - Average log(score): All tested organisms in DT+Ext method showed high average log(scores) well above the 2.0 threshold (ranging from 2.138 to 2.587), with low standard deviations. - Conclusion: Study confirms repeatability and precision independent of system operators, microflex instruments, target lots, matrix lots, and BTS lots. |
| Limit of Detection | Ability to correctly identify organisms (log(score) ≥2.00) within a specified dynamic range of cell concentrations for both Direct Transfer (DT) and Extraction (Ext) methods. | - Dynamic Range (DT): Lower limit: 6.3x10³-1.4x10⁴ cells/µL, Upper limit: 1.4x10⁶- ≥ 6.5x10⁷ cells/µL. - Dynamic Range (Ext): Lower limit: 9.0x10³-1.3x10⁵ cells/µL, Upper limit: 1.1x10⁷- ≥ 6.9x10⁷ cells/µL. - Conclusion: The device successfully identified organisms within these estimated dynamic ranges. |
| Specificity | - Organisms not included in the reference library should be reported as "No Identification" (Phase 1). - Closely related species not in the reference library should not produce incorrect identifications. (Phase 1) - Closely related claimed species should be uniquely identified (Phase 2). | - Phase 1 (Non-claimed organisms): 100% (2/2 for all tested strains) of Anaerobes, Mycobacteria, Gram-Negative (not claimed), Gram-Positive, and Yeast organisms returned "No Identification" with zero false identifications. - Phase 2 (Closely related claimed species): 100% (2/2 for all tested strains) of Burkholderia cepacia, B. multivorans, and B. gladioli were correctly identified with zero false identifications. - Conclusion: High confidence in specificity, demonstrating non-claimed organisms are not falsely identified and closely related species are differentiated. |
| Mixed Culture | No false identifications when a mixed culture is analyzed, even with varying concentrations of target and non-target organisms. (Users are still instructed to test single isolated colonies). | - Performance: 0/32 false identifications across all tested conditions (100% target, 75% target/25% non-target, 50% target/50% non-target, 25% target/75% non-target). - Conclusion: No false results were obtained, and the impact on final test results is "greatly reduced" compared to biochemical methods. |
| Media and Colony Stability | - Acceptability of specified culture media (TSA, CBA, MAC, CHOC). - Colony stability for up to 12 hours post-incubation at room temperature. | - Media Acceptability: All four media (TSA, CBA, MAC, CHOC) showed high identification rates (263/288 to 288/288) with 0/288 false identifications for both DT and Ext methods. - Colony Stability: Confirmed stability for up to 12 hours post-incubation. |
| Influence of Agar Media | - Agar media alone should not generate mass spectra leading to false identification (100% "No ID" for agar alone). - Agar media should not interfere with MBT-CA performance or organism identification when present with the isolate. | - Agar Alone: 100% (12/12) of agar only replicates resulted in "No ID". - Target + Agar: 100% (10/12 to 12/12, depending on media) of target organism + agar replicates showed 0% false identifications. - Conclusion: Media do not interfere with performance or identification and do not generate false identifications on their own. |
| Organism Stability prior to MBT-CA Analysis | - Isolate stability on the target plate (prior to matrix overlay) for up to 60 minutes via DT and Ext. - Stability of extracted material (prior to target plate inoculation) for up to 24 hours at room temperature. | - Isolate on Target (DT/Ext): 100% correct identification (24/24 or 6/6) at all time points up to 120 minutes for DT and 60 minutes for Ext, with 0 false identifications. - Extracted Material Stability: 100% correct identification (24/24) for up to 24 hours when stored at room temperature, with 0 false identifications. - Conclusion: Samples are stable on the target plate for up to 60 minutes, and extracts are stable for up to 24 hours at room temperature. |
| Sample Stability overlaid with Matrix | - Stability of test organisms on the spotted target plate after matrix addition for up to 24 hours across various temperature and humidity conditions. - Matrix alone should not interfere or influence identification (should result in "No Peaks Found"). | - Organism Stability: Mostly 100% correct identification across various temperature/humidity conditions and time points up to 24 hours. A few instances showed 23/24 or 18/24 correct identifications at 8 hours under specific stressed conditions, but the 24-hour mark returned to 24/24, suggesting good overall stability. - Matrix Alone: 100% "No Peaks Found" for matrix alone across all conditions and time points. - Conclusion: Inoculated test organisms overlaid with matrix are stable for up to 24 hours at room temperature, and matrix alone does not interfere. |
| Bacterial Test Standard (BTS) Stability | - BTS stability for 3 weeks at 37±2ºC (accelerated/shipping). - BTS stability for 12 months at < 18°C (real-time). - Reconstituted BTS stability for 5 months (in-use). | - Accelerated/Shipping: All average log(scores) remained high (2.332 to 2.391) across 3 weeks at 37±2ºC. - Real-Time: All average log(scores) remained high (2.250 to 2.414) across 18 months at < 18°C. - In-Use (Reconstituted): All average log(scores) remained high (2.240 to 2.413) across 6 months. - Conclusion: BTS is stable for 3 weeks (accelerated), 18 months (real-time), and 5 months (in-use reconstituted). |
| HCCA portioned (Matrix) Stability | - Matrix stability for 16 weeks at 37±2ºC (accelerated/shipping). - Matrix stability for 18 months at 2-8℃ (real-time). - Reconstituted matrix stability for 1 week at 20-25℃ (in-use). - Reconstituted matrix stability for 12 hours at 15±1°C and 30±1°C (stressed). | - Accelerated/Shipping: 100% (16/16) correct identifications, 0 false identifications, for up to 16 weeks at 37±2ºC. - Real-Time: 100% (16/16) correct identifications, 0 false identifications, for up to 18 months at 2-8℃. - In-Use (Controlled Room Temp): 100% (24/24) correct identifications, 0 false identifications, for up to 7 days. Matrix alone showed 100% "no peaks found". - In-Use (Stressed Temps): 100% (24/24) correct identifications, 0 false identifications, for up to 12 hours at 15±1°C and 30±1°C. Matrix alone showed 100% "no peaks found". - Conclusion: Matrix stability confirmed for accelerated/shipping (16 wks), real-time (18 mos), in-use at controlled room temp (1 wk), and in-use at stressed temps (12 hrs). |
| Carry-Over and Cross Contamination | No cross-contamination (microbial sample convergence between adjacent target spots) and no carry-over (target contamination due to insufficient target cleaning). | - Performance: Across 5 cycles and multiple runs for two target plates, 100% "no peaks found" for matrix-only spots, and 100% (16/16) correct identifications for test organisms with 0 false identifications. - Conclusion: The study confirmed neither cross-contamination nor carry-over effects. |
| Proficiency/Familiarity | Intended operators should be able to illustrate reproducible results using both testing methods (DT and Ext). | - Performance: Across 4 sites and multiple operators, high rates of "samples passed" (25/25, 29/30, 30/31, etc.) for both DT and Ext methods. Only a few instances had 1 missed sample out of 25-35. - Conclusion: Confirmed that operators can achieve reproducible results. |
| Reproducibility | 100% correct identification of blinded test organisms at the species level across different clinical sites, operators, instruments, and target plates. | - Performance: 100% of all blinded test organisms were correctly identified at the species level at each clinical test site (80/80 after DT+Ext). Initial DT results were also very high (e.g., 95-100%). - Conclusion: Data confirm reproducibility and precision independent of clinical site, system operators, microflex instruments, and target plates. |
| Challenge Panel | Intra-laboratory performance with high rates of correct identification (≥96%) for a panel of diverse organisms. | - Performance: Combined DT and Ext methods yielded high identification rates across five sites (99%, 99%, 99%, 97%, 99%). - Conclusion: Confirms intra-laboratory performance. |
| Method Comparison (Overall) | - High percentage of correct organism identifications (High Confidence: log(score) ≥2.0). - Very low rate of misidentification or "No Identification" across fresh and stored isolates. | - Positive Organism ID (High Confidence): 2174/2263 (96.07%) - Positive Organism ID (Low Confidence): 48/2263 (2.12%) - Correct Genus/Species/Group/Complex ID (Combined High & Low Confidence): 2222/2263 (98.19%) - Wrong Genus ID: 3/2263 (0.13%) - No ID: 25/2263 (0.09%) - Overall Safety and Efficacy: The data demonstrate safety and efficacy compared to the reference method (16s bi-directional sequencing). |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Precision/Repeatability: 10 test organisms, 72 samples measured per organism (total 720 samples). Data provenance is not specified, but the study was performed in the US (implied by "Bruker US IVD Bacterial Test Standard (BTS)"). It appears to be prospective, laboratory-controlled testing.
- Limit of Detection: 7 frequently occurring clinically relevant test organisms. Each cell stock was diluted to a minimum of 5 concentrations and tested in duplicate (minimum 70 measurements). Data provenance is not specified, likely laboratory.
- Specificity (Phase 1): 16 strains of organisms not in the library, each tested in duplicate (DT + Ext), so 32 direct transfer and 32 extraction tests for identification (total 64). Data provenance is not specified, likely laboratory.
- Specificity (Phase 2): 6 strains of closely related organisms, each tested in duplicate (DT + Ext), so 12 direct transfer and 12 extraction tests for identification (total 24). Data provenance is not specified, likely laboratory.
- Mixed Culture: 1 target organism (Pseudomonas aeruginosa) with 4 non-target organisms. Tested at 4 concentration conditions, 32 measurements per condition (total 128 tests). Data provenance is not specified, likely laboratory.
- Media and Colony Stability: 7 Gram-negative organisms, 2 incubation time points (18h, 24h), 2 temperatures (18°C, 25°C), 4 media types. Each condition likely involves multiple replicates. The table shows totals of 288 tests per media type (DT) and 288 per media type (Ext). (Total 2304 tests displayed). Data provenance is not specified, likely laboratory.
- Influence of Agar Media: 4 agar media types, each inoculated alone (12 replicates), with target organism alone (12 replicates), and with target organism + agar (10-12 replicates). This involves 3 frequently occurring Enterobacteriacea and non-fermenting Gram Negative Bacteria (36 total replicates for agar alone. 36 replicates for target organism alone. ~36 replicates for target organism + agar). Data provenance is not specified, likely laboratory.
- Organism Stability Prior to MBT-CA Analysis: 3 common gram-negative bacteria. DT: 8 replicates per organism, 5 time points (120 tests). Ext: 6 replicates per time point for 5 time points (30 tests). Extracted Material: 2 extracts, 24 replicates per extract, 5 time points (240 tests). Data provenance is not specified, likely laboratory.
- Sample Stability overlaid with Matrix: 3 gram negative target organisms. Multiple conditions (temperature, humidity), 4 time points. Each condition involved 4 target spots of directly transferred, 4 spots of extracted, and 8 spots of matrix solution alone. (e.g., 24/24 or 18/24 for organisms, 8/8 for matrix). Data provenance is not specified, likely laboratory.
- Bacterial Test Standard (BTS) Stability:
- Accelerated/Shipping: 3 lots of BTS, 8 vials/lot. Tested at 3 time intervals (1, 2, 3 weeks). Each time interval, 2 vials/lot reconstituted, 16 target plate positions + 3 cross-joint positions spotted (approx. 19 tests * 3 lots * 3 timepoints + initial = 171 tests).
- Real-Time: 3 lots of BTS. Tested at 5 time intervals (3, 6, 9, 12, 18 months). (approx. 19 tests * 3 lots * 5 timepoints + initial = 285 tests).
- In-Use: 1 lot, 4 vials. Tested at 6 time points (1-6 months). (approx. 8 replicates * 6 timepoints + initial = 56 tests).
- Data provenance is not specified, likely laboratory.
- HCCA portioned (Matrix) Stability:
- Accelerated/Shipping: 1 lot matrix. Tested at 6 time intervals (1, 2, 4, 7, 16 weeks). Each interval, 16 replicates of ID (DT/EXT methods) for two targets (32 total), plus matrix alone.
- Real-Time: 3 lots matrix. Tested at 5 time intervals (3, 6, 9, 12, 18 months). 16 replicates of ID per target (32 total).
- In-Use (Controlled RT): 3 lots matrix. Tested at 3 time intervals (1, 3, 7 days). 24 replicates of ID per target (48 total) plus 8 matrix alone.
- In-Use (Stressed Temps): 1 lot matrix. Tested at 2 time intervals (6, 12 hours). 24 replicates of ID per target (48 total) plus 8 matrix alone.
- Data provenance is not specified, likely laboratory.
- Carry-Over and Cross Contamination: 2 target plates. 2 frequently occurring Gram negative bacteria. Each target inoculated 4x via DT and Ext in alternating patterns. All sample positions overlaid with matrix, remaining unused positions as blanks. Repeated 4 times on each target plate (5 cycles total). Results show 16 test organisms per run and 26-27 matrix-only spots per run (approx. 240 organism identification tests and 265 matrix blanks across the summary tables). Data provenance is not specified, likely laboratory.
- Proficiency/Familiarity: 4 US study sites, multiple operators (16 operators shown in table). Each operator tested 5 QC organisms. The # samples passed varies per operator (e.g., 25/25, 30/31, 32/32), indicating varying numbers of replicates for these 5 QC organisms (ranging from 25 to 35 samples per operator for each method, DT and Ext).
- Reproducibility: 4 clinical study sites, 2 operators/site, 10 well-characterized organisms. Tested in duplicate via direct transfer. 80 samples per organism (4 sites * 2 operators * 5 days * 2 runs/day * 2 replicates = 80 per organism) (Total 800 tests for 10 organisms). Data provenance is US clinical sites.
- Challenge Panel: 100 organisms (80 from clinical study, 20 from strain collections). Tested at 5 study sites. Site E only received 87 samples. (4 sites * 100 organisms, 1 site * 87 organisms = 487 organism identifications). Data provenance is US clinical sites for some organisms, and strain collections for others.
- Method Comparison: 2263 fresh and stored isolates (Gram-negatives) tested in total. Performance compared to sequencing and biochemical identification. Data from 4 clinical test sites and Bruker (Bremen, Germany). Provenance is a mix of fresh (498 never frozen) and stored isolates, from clinical test sites (US) and potentially other sources. Appears to be prospective (fresh isolates) and retrospective (stored isolates).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
The ground truth for the method comparison study (the primary clinical performance study) was established by:
- Sequencing: Specifically, "16s bi-directional sequencing" and "protein sequencing."
- Biochemical identification: "Vitek 2".
- The text does not specify the number or qualifications of experts who performed or interpreted these ground truth methods. It only mentions that the isolates were sent to a "sequencing reference laboratory" for sequencing in accordance with "MM-18 A guidelines" (which are CLSI M-18 guidelines for bacterial identification systems using nucleic acid sequencing).
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The text does not describe an adjudication method for disagreements in ground truth or between the device and ground truth. It states that performance was "compared to sequencing and when necessary to biochemical identification (i.e: Vitek 2) and protein sequencing." There's no mention of a human review or adjudication process for conflicting results between these reference methods or between the device and the reference.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- No, an MRMC comparative effectiveness study was not done.
- This device is an automated mass spectrometry system for identifying microorganisms. It does not involve human "readers" or "AI assistance" in the typical sense applied to medical imaging or diagnostics where human interpretation is enhanced by AI. The device itself performs the identification based on mass spectrometry data and a biostatistical algorithm comparing to a reference library.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, a standalone (algorithm only) performance study was done. The entire performance section (Precision, LOD, Specificity, Mixed Culture, Media/Colony Stability, Organism Stability, Matrix Stability, Carry-Over, Challenge Panel, Reproducibility, and Method Comparison) describes the performance of the MALDI Biotyper CA System itself, which is an automated system generating organism IDs with a log(score).
- The "Performance Data" and "Method Comparison" sections explicitly evaluate the device's ability to identify organisms compared to reference methods. The system reports an organism identification with high confidence if the log(score) is ≥ 2.00 and low confidence if the log(score) is between 1.70 and <2.00. This is the "algorithm only" performance.
- While the text mentions that "Results should be reviewed by a trained microbiologist and final organism identification should be based on all relevant information available," the reported performance metrics (e.g., 96.07% high confidence ID rate in method comparison) reflect the device's standalone output before any human review or integration with other clinical findings.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth used for the method comparison study (the central performance evaluation) was a combination of:
- 16s bi-directional sequencing (primary molecular method)
- Biochemical identification (Vitek 2) (conventional phenotypic method, used "when necessary")
- Protein sequencing (another molecular method, used "when necessary")
This constitutes a robust, laboratory-based reference standard for microbial identification.
8. The sample size for the training set
The document does not explicitly state the size of the training set used to build the MALDI Biotyper CA System's reference library (database). It mentions that 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)."
The method comparison study states, "In total, 2263 fresh and stored isolates were tested to support the initial reference library claim." This phrasing suggests these 2263 isolates might have been used for validation of the library's performance, but not necessarily for its training or development, as the library would presumably exist prior to this validation study. The content does not elaborate on the training data used to create the specific reference library ("MALDI Biotyper for Clinical Applications (MBT-CA)") or the database itself.
9. How the ground truth for the training set was established
Since the size and specific details of the training set are not provided, the method for establishing its ground truth is also not explicitly detailed in this summary. However, it's reasonable to infer that the reference library would have been built using well-characterized microbial strains, with their identities confirmed by gold-standard methods similar to, or even more comprehensive than, those used for the test set (e.g., definitive sequencing and classical microbiological techniques). The primary ground truth for the system's performance validation relies on 16s bi-directional sequencing, biochemical methods, and protein sequencing.
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510(k) SUMMARY
| Date of Summary: | October 28, 2013 |
|---|---|
| Product Name | MBT-CA System |
| Sponsor: | Bruker Daltonics, Inc40 Manning Road,Billerica, MA 01821 |
| Correspondent | MDC Associates, LLCFran White, Regulatory Consultant180 Cabot StreetBeverly, MA 01915 |
| Device Identification | |
| Trade or Proprietary Name: | MALDI Biotyper CA System |
| Common or Usual Name: | Mass spectrometer for clinical multiplex test systems |
| Product Code: | PEX |
| Regulation Section: | 21 CFR 862.3361 Instrumentation for clinical multiplex test sys |
21 CFR 862.3361 Instrumentation for clinical multiplex test systems Class II (special controls) Microbiology
Substantial Equivalency
Device Class:
Panel:
The Bruker Daltonics, Inc MBT-CA System is substantially equivalent to the Vitek® MS MALDI-TOF mass spectrometer system (K124067). Table 1 compares the characteristics of the MBT-CA System (New Device) and the Vitek® MS (predicate device).
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Comparison of New Device with Predicate Device
TABLE 1: Substantial Equivalency Table
| Similarities | ||
|---|---|---|
| Characteristic | NEW DEVICEBruker Daltonics, Inc MBT-CA System(K130831) | PREDICATE DEVICEVitek® MS(K124067) |
| Product Codes | PEX | PEX |
| Intended use | The Bruker Daltonics, Inc MALDI BiotyperCA System is a qualitative in vitrodiagnostic mass spectrometer system forthe identification of Gram-negativebacterial colonies cultured from humanspecimens using matrix-assisted laserdesorption/ ionization - time of flight(MALDI-TOF) mass spectrometrytechnology.The MALDI Biotyper CA System isindicated for use in conjunction withother clinical and laboratory findings toaid in the diagnosis of Gram negativebacterial infections. | The Vitek® MS is a mass spectrometersystem using matrix-assisted laserdesorption/ionization-time to flight(MALDI-TOF) for the identification ofmicroorganisms cultured from humanspecimen.The VITEK MS is a qualitative in vitrodiagnostic device indicated for use inconjunction with other clinical andlaboratory findings to aid in the diagnosisof bacterial and yeast infections. |
| Sample type | Isolated colony from any patient samplesource.Acceptable media:• Columbia blood agar with 5% sheepblood• Trypticase soy agar with 5% sheepBlood• Chocolate agar• MacConkey Agar | Isolated colony from any patient samplesource.Acceptable media:• Columbia blood agar with 5% sheepblood• Trypticase soy agar with 5% sheepBlood• Chocolate polyvitex agar• Campylosel agar• MacConkey Agar• Modified Sabouraud dextrose Agar• ChromID CPS |
| Type of Test | Automated Mass Spectrometry System | Automated Mass Spectrometry System |
| Matrix | α-Cyano-4-hydroxycinnamic acid | α-Cyano-4-hydroxycinnamic acid |
| Method ofTesting | Bacteria: Direct testingIf after initial analysis the log(score) isreported at < 2.00, organisms areprocessed using the extractionprocedure. | Bacteria: Direct testing |
| Similarities | ||
| Characteristic | NEW DEVICEBruker Daltonics, Inc MBT-CA System(K130831) | PREDICATE DEVICEVitek® MS(K124067) |
| ResultReporting | Organism identification is reported withhigh confidence if the log(score) is $\ge$ 2.00.An organism identification is reported with low confidence if the log(score) isbetween 1.70 and <2.00. | A single identification is displayed, with aconfidence value from 60.0 to 99.9, whenone significant organism or organismgroup is retained."Low-discrimination" identifications aredisplayed when more than one but notmore than four significant organisms ororganism groups are retained.When more than four organisms ororganism groups are found, or when nomatch is found, the organism isconsidered unidentified. |
| MatchingAlgoritm | Calculates matches by comparing a newspectrum against each single referenceentry of a reference database. | Uses a proprietary process called "massbinning." In this process, the spectrumbetween 3,000 and 17,000 Daltons aredivided into 1300 pre-definedintervals called "bins". Next, an algorithmbased on supervised machine learningknown as the "Advanced SpectrumClassifier", is used to determine howinformative each bin was indifferentiating that species from all otherspecies in the database. |
| Recorded massrange | 2,000 - 20,000 m/z | 2,000 - 20,000 m/z |
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| Differences | |||
|---|---|---|---|
| Characteristic | NEW DEVICEBruker Daltonics, Inc MBT-CA System(K130831) | PREDICATE DEVICEVitek® MS(K124067) | |
| Culture Age | Bacteria growth should be between 18h to36h | Bacteria and yeast growth should be between24 to 72 hours. | |
| Calibration | Bruker US IVD Bacterial Test Standard (BTS) | E. coli ATCC 8739 | |
| MALDI Target | US IVD 48 Spot Target | VITEK MS-DS Target Slides | |
| Plate | 48 positions reusable steel targets | • 48 positions disposable plastic targets | |
| MALDI-TOF MS | Bruker microflex | Shimadzu AXIMA® Assurance MS | |
| instruments | (benchtop) | (floor standing) | |
| Database | MALDI Biotyper for Clinical Applications(MBT-CA) | VITEK MS V2.0 Knowledge Base |
These differences do not affect substantial equivalence of the MBT-CA System and Vitek® MS system. Both systems are mass spectrometer systems using matrix-assisted laser desorption/ionization-time to 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 safety and effectiveness of the test (new) device.
Intended Use
The Bruker Daltonics, Inc MALDI Biotyper CA System is a qualitative in vitro diagnostic mass spectrometer system for the identification of Gram-negative bacterial colonies cultured from human specimens using matrix-assisted laser desorption/ ionization - time of flight (MALDI-TOF) mass spectrometry technology.
The MALDI Biotyper CA System is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of Gram negative bacterial infections.
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.
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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 an overnight subculture plate is transferred to a selected position on an US IVD 48 Spot Target plate (target). The target is air dried and US IVD HCCA portioned (matrix) is added. The standard solvent (50% acetonitrile / 47.5% HzO / 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 at < 2.00, organisms can be processed using the extraction procedure and analysis repeated.
Extraction Procedure (Ext): If after initial analysis 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 overnight subculture plate are extracted using ethanol / formic acid procedure. 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-of-flight) 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 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 species-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.
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Performance Data
Precision/Repeatability:
Validation of the whole MALDI Biotyper CA System was performed on twelve (12) working days with two (2) runs/day following manufacturer's instructions for use. Ten (10) test organisms were tested in triplicate in each run. The study also tested multiple sources of system variability including three (3) test operators, three (3) microflex LT/SH instruments, three (3) target lots, three (3) BTS lots and three (3) Matrix lots. As triplicates of each test organism were prepared and tested in each run, a total of 72 MALDI Biotyper CA System identifications were carried out for each test organism. Overall results from the precision/repeatability study are presented below.
| Test Organism | # samples measured | # samples passed(DT) | # samples passed(DT+Ext) |
|---|---|---|---|
| Acinetobacter baumannii | 72 | 62 (86.1%) | 72 (100%) |
| Pseudomonas aeruginosa | 72 | 70 (97.2%) | 72 (100%) |
| Stenotrophomonas maltophilia | 72 | 70 (97.2%) | 72 (100%) |
| Enterobacter cloacae | 72 | 70 (97.2%) | 72 (100%) |
| Escherichia coli | 72 | 71 (98.6%) | 72 (100%) |
| Hafnia alvei | 72 | 72 (100%) | 72 (100%) |
| Proteus mirabilis | 72 | 72 (100%) | 72 (100%) |
| Brevundimonas diminuta* | 72 | 72 (100%) | 72 (100%) |
| Haemophilus influenzae | 72 | 72 (100%) | 72 (100%) |
| Moraxella catarrhalis | 72 | 72 (100%) | 72 (100%) |
Table 2: Overall Precision per Test Organism
- Brevundimonas diminuta was tested but is not included in the claim.
Table 3: Overall Precision per Test Organism Average log(score)
| Test Organism | # samples measured | Average log(score) [DT+Ext] |
|---|---|---|
| Acinetobacter baumannii | 72 | 2.172 ± 0.113 |
| Pseudomonas aeruginosa | 72 | 2.368 ± 0.121 |
| Stenotrophomonas maltophilia | 72 | 2.364 ± 0.078 |
| Enterobacter cloacae | 72 | 2.138 ± 0.064 |
| Escherichia coli | 72 | 2.385 ± 0.097 |
| Hafnia alvei | 72 | 2.452 ± 0.095 |
| Proteus mirabilis | 72 | 2.587 ± 0.079 |
| Brevundimonas diminuta* | 72 | 2.489 ± 0.045 |
| Haemophilus influenzae | 72 | 2.344 ± 0.118 |
| Moraxella catarrhalis | 72 | 2.523 ± 0.080 |
- Brevundimonas dimiuta was tested but is not included in the claim.
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 Production Lots
- Matrix Lots ●
- BTS Lots
{6}------------------------------------------------
Limit of Detection/Dynamic Range:
The Limit of Detection study was designed to establish the estimated dynamic range of sample size for both the Direct Transfer (DT) and Extraction method (Ext) procedure. Seven (7) frequently occurring clinically relevant test organisms were chosen for this study. Cell density and cell concentration were estimated by measuring the optical density of the suspension at a wavelength of 600nm. Approximately 3x10° cells/mL were reported to correspond to an optical density of OD600 = 1 according to the commonly used McFarland Standard. All suspensions were tested in duplicate. Each cell stock was diluted to a minimum five (5) concentrations and tested in duplicate. A cell concentration was considered within the dynamic range if the MBT-CA correctly identified the organism for both replicates with a log(score) of ≥2.00.
Study results concluded that the estimated dynamic range for the direct and extracted method is as follows:
| Technique | Lower limit[cells/µL] | Upper limit[cells/µL] |
|---|---|---|
| Direct Transfer | 6.3x103-1.4x104 | 1.4x106- $\geq$ 6.5x107 |
| Extraction | 9.0x103-1.3x105 | 1.1x107- $\geq$ 6.9x107 |
Specificity:
The goal of the specificity study was to validate the performance of the proposed MALDI Biotyper CA System reference library by ensuring that organisms not included in the reference library would not yield an incorrect identification and would be reported as "No Identification." Additionally, the study was designed to further demonstrate that the MALDI Biotyper CA System identification is not impacted when closely related species not included in the reference library are run on the system.
The study was conducted in two phases. In phase one, organisms currently not included in the initial system reference library were tested via Direct Transfer and extraction method to ensure that the organisms would not be falsely identified by the MALDI Biotpyer CA system. Organisms tested fell into the following five groupings:
- Anaerobe bacteria ।
- -Mycobacteria
- Gram-Negative bacteria (not currently claimed within the library) ।
- -Gram-Positive bacteria
- -Yeast species
Results from this phase are presented below:
| Table 4: Phase 1: Summary Results | ||
|---|---|---|
| ----------------------------------- | -- | -- |
| Organism | Strain | # of "No Identification" | # of falseidentification | |
|---|---|---|---|---|
| DT | Ext | |||
| Bacteroides fragilis | DSM 2151 | 2 / 2 | 2 / 2 | 0 |
| Bacteroides fragilis | DSM 9669 | 2 / 2 | 2 / 2 | 0 |
| Prevotella copri | DSM 18205T | 2 / 2 | 2 / 2 | 0 |
| Prevotella buccae | DSM 19025T | 2 / 2 | 2 / 2 | 0 |
| Mycobacterium fortuitum ssp.fortuitum | DSM 43477 | 2 / 2 | 2 / 2 | 0 |
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| Organism | Strain | # of “No Identification”DT | # of “No Identification”Ext | # of falseidentification |
|---|---|---|---|---|
| Mycobacterium fortuitum ssp.fortuitum | DSM 46621T | 2 / 2 | 2 / 2 | 0 |
| Neisseria gonorrhoeae | DSM 9188T | 2 / 2 | 2 / 2 | 0 |
| Neisseria gonorrhoeae | DSM 15130 | 2 / 2 | 2 / 2 | 0 |
| Erwinia tasmaniensis | DSM 17949 | 2 / 2 | 2 / 2 | 0 |
| Erwinia tasmaniensis | DSM 17950 | 2 / 2 | 2 / 2 | 0 |
| Vagococcus fluvialis | DSM 5731T | 2 / 2 | 2 / 2 | 0 |
| Vagococcus fluvialis | DSM 21402 | 2 / 2 | 2 / 2 | 0 |
| Facklamia hominis | CCUG 59179 | 2 / 2 | 2 / 2 | 0 |
| Facklamia hominis | CCUG 49614 | 2 / 2 | 2 / 2 | 0 |
| Guehomyces pullulans | CBS 2532T | 2 / 2 | 2 / 2 | 0 |
| Guehomyces pullulans | CBS 2542 | 2 / 2 | 2 / 2 | 0 |
| Cyberlindnera mississippiensis | CBS 7023T | 2 / 2 | 2 / 2 | 0 |
| Cyberlindnera mississippiensis | CBS 7027 | 2 / 2 | 2 / 2 | 0 |
In phase two of the study testing, Burkholderia cepacia/multivorans/gladioli were investigated via Direct transfer and extraction method to ensure that closely related organisms can be differentiated when tested on the MALDI Biotyper CA System. Results from this phase of testing are reported below:
| Organism | Strain | # of CorrectIdentifications | # of falseidentification | |
|---|---|---|---|---|
| DT | Ext | |||
| Burkholderia cepacia | DSM 9241 | 2 / 2 | 2 / 2 | 0 |
| Burkholderia cepacia | DSM 50181 | 2 / 2 | 2 / 2 | 0 |
| Burkholderia multivorans | 1A112372344v MVD | 2 / 2 | 2 / 2 | 0 |
| Burkholderia multivorans | H480 MCRF | 2 / 2 | 2 / 2 | 0 |
| Burkholderia gladioli | DSM 8361 | 2 / 2 | 2 / 2 | 0 |
| Burkholderia gladioli | LMG 6956 | 2 / 2 | 2 / 2 | 0 |
Table 5: Phase 2: Summary Results
Phase 1 data demonstrates with high confidence that Anaerobes, Mycobacteria, Gram-negative, Grampositive and Yeast organisms not included in the MALDI Biotyper CA database are not identified confirming the specificity of the MALDI Biotyper CA reference library when following product instructions for use for both DT and extraction method. Phase 2 data confirms that closely related species can be unambiguously identified by the MALDI Biotyper CA System.
Mixed Culture:
Although MALDI Biotyper CA System users will be instructed to select only a single isolated colony for identification on the MALDI Biotyper CA System this study was conducted to assess the effect of testing a mixed culture on MALDI Biotyper CA identification. Pseudomonas aeruginosa, a frequently occurring Gram negative bacterium was chosen as the target organism for this study. Four (4) non-target organisms consisting of gram-negative and gram-positive bacteria where introduced with the target organism at varying concentrations to determine the affect a mixed culture would have on
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MBT-CA identification.
| Condition | Target OrganismAmount | Non-Target OrganismAmount | # of MALDI Biotyper CAFalse Identifications |
|---|---|---|---|
| A | 100% | 0% | 0/32 |
| B | 75% | 25% | 0/32 |
| C | 50% | 50% | 0/32 |
| D | 25% | 75% | 0/32 |
Table 6: Summary of Mixed Culture Study
Although system users will be instructed to test a single isolated colony on the MALDI Biotyper CA System, it is important to note that when a mixed culture is analyzed on the system, no false results are obtained and the impact on final test results is greatly reduced when compared to the issues observed with alternative biochemical methods.
Media and Colony Stability
In accordance with product instructions for use, customers are advised that primary or secondary isolation plates of recommended media [Trypticase Soy Agar with 5% sheep blood (TSA), Columbia Blood Agar with 5% sheep blood (CBA), MacConkey Agar (MAC), and Chocolate Agar (Choc)] may be held for up to 12 hours at room temperature prior to testing on the MALDI Biotyper CA System. This study was conducted to confirm the acceptability of the recommended agar/media and stability of the colony for up to 12 hours prior to analysis.
Testing was conducted using seven (7) gram-negative organisms at two different incubation time points (18h, 24h). After initial incubation, isolates were further tested at two (2) temperatures (18°C, 25°C) for 12 hours post-incubation.
| Media | ≥2.0 Identification(DT) | False Identification(DT) | ≥2.0 Identification(Ext) | False Identification(Ext) |
|---|---|---|---|---|
| TSA | 288/288 | 0/288 | 288/288 | 0/288 |
| CBA | 284/288 | 0/288 | 288/288 | 0/288 |
| MAC | 263/288 | 0/288 | 288/288 | 0/288 |
| CHOC | 288/288 | 0/288 | 288/288 | 0/288 |
Table 7: Summary of Media and Colony Stability Study
The study results confirm that the following culture media can be used on the MALDI Biotyper CA System:
- · Trypticase Soy Agar with 5% sheep blood (TSA)
- Columbia Blood Agar with 5% sheep blood (CBA)
- · MacConkey Agar (MAC)
- · Chocolate Agar (CHOC)
Study results conclude that sample colony is stable for up to 12 hours post-incubation.
Influence of Agar Media
This study was completed in order to demonstrate that impurities such as salts, peptides or carbohydrates introduced from culture media do not interfere with MALDI Biotyper CA identification. In
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addition, the study set-out to prove that isolation media alone would not generate mass spectra leading to false identification on the MBT-CA system. TSA, CBA, MAC and CHOC agars were tested by the following methods:
- Each agar media was inoculated using the Direct Transfer (DT) and Extraction (Ext) method alone (6) six times each.
- -Three (3) frequently occurring Enterobacteriacea and non-fermenting Gram Negative Bacteria were transferred to the target plate in duplicate via DT and Ext method to serve as a control.
- -Each target organism was then inoculated in duplicate via DT and Ext method such that a sample agar media was included with the isolate.
A summary of results obtained is provided below:
| Agar Alone | Target Organism Alone | Target Organism + Agar | ||||
|---|---|---|---|---|---|---|
| Media | # replicates | % No ID | # replicates | % False ID | # replicates | % False ID |
| TSA | 12/12 | 100 | 12/12 | 0 | 10/12 | 0 |
| CBA | 12/12 | 100 | 12/12 | 0 | 12/12 | 0 |
| MAC | 12/12 | 100 | 12/12 | 0 | 12/12 | 0 |
| CHOC | 12/12 | 100 | 12/12 | 0 | 12/12 | 0 |
Table 8: Summary of Influence of Agar Media Study
The study confirms that the media recommended for use on the MALDI Biotyper CA System do not interfere with MBT-CA performance or organism identification.
Organism Stability prior to MALDI Biotyper CA System Analysis
This study was conducted to assess isolate stability on the target plate prior to matrix overlay via Direct Transfer (DT) and Extraction (Ext) method. In addition, the study set out to confirm the stability of extracted material prior to target plate inoculation.
To test for isolate stability on the target plate prior to matrix overlay via DT, three (3) common gram negative bacteria were inoculated eight times and overlaid with matrix at five (5) different time points. After matrix overlay, isolates were tested in accordance with product instructions. For the Ext method, colonies were prepared following the extraction technique per product instructions for use. Extracts were overlaid with matrix at five (5) different time points and tested per product instructions. For the third phase of testing, the three (3) gram negative isolates were extracted twice. The extracts were stored at controlled room temperature for up to 24 hours and tested at five (5) time points in replicates of eight.
A summary of results obtained is provided below:
| Test Phase | Testing Condition | Measurands | Correct Identification | False Identification |
|---|---|---|---|---|
| Direct Transfer (DT) | 0 min | 24 | 24/24 | 0/24 |
| Direct Transfer (DT) | 15 min | 24 | 24/24 | 0/24 |
| Direct Transfer (DT) | 30 min | 24 | 24/24 | 0/24 |
| Direct Transfer (DT) | 60 min | 24 | 24/24 | 0/24 |
| Direct Transfer (DT) | 120 min | 24 | 24/24 | 0/24 |
Table 9: Summary of Organism Stability Prior to MBT-CA Analysis Study
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| Test Phase | Testing Condition | Measurands | Correct Identification | False Identification |
|---|---|---|---|---|
| Extraction Method (Ext) | 0 min | 6 | 6/6 | 0/6 |
| 10 min | 6 | 6/6 | 0/6 | |
| 20 min | 6 | 6/6 | 0/6 | |
| 30 min | 6 | 6/6 | 0/6 | |
| 60 min | 6 | 6/6 | 0/6 | |
| Extract #1 | 0 hour | 24 | 24/24 | 0/24 |
| 1 hour | 24 | 24/24 | 0/24 | |
| 4 hours | 24 | 24/24 | 0/24 | |
| 8 hours | 24 | 24/24 | 0/24 | |
| 24 hours | 24 | 24/24 | 0/24 | |
| Extract #2 | 0 hour | 24 | 24/24 | 0/24 |
| 1 hour | 24 | 24/24 | 0/24 | |
| 4 hours | 24 | 24/24 | 0/24 | |
| 8 hours | 24 | 24/24 | 0/24 | |
| 24 hours | 24 | 24/24 | 0/24 |
Study results confirm that samples are stable on the target plate when tested via DT or Ext method for up to sixty (60) minutes prior to analysis. In addition, extracts are stable for up to 24 hours when stored at room temperature.
Sample Stability overlaid with Matrix
This study was conducted to prove the stability of test organisms on the spotted target plate following matrix addition at various temperature and relative humidity conditions. In addition, the study served to prove that matrix alone will not influence MBT-CA identification. Three (3) gram negative target organisms were cultured on Columbia Blood Agar (CBA) and aging experiments were done at two (2) different temperature and relative humidity testing condition, two (2) target plates were inoculated and each contained four target spots of directly transferred test organism, four spots of extracted test organism and eight spots of matrix solution alone. All spots containing test organism were then overlaid with matrix in accordance with product instructions for use and tested immediately and then stored at one of the testing conditions and retested at 4±1 hour, 8±1 hour and 24±1 hour.
The results of the testing are summarized below:
| Test Condition | Test Age | Test Organism Correct Identification | Matrix “No Peaks Found” |
|---|---|---|---|
| DT20 ± 1°C, 40 ± 5% | 0 hour | 24/24 | 8/8 |
| 4 hours | 24/24 | 8/8 | |
| 8 hours | 24/24 | 8/8 | |
| 24 hours | 24/24 | 8/8 | |
| Ext20 ± 1°C, 40 ± 5% | 0 hour | 24/24 | 8/8 |
| 4 hours | 24/24 | 8/8 | |
| 8 hours | 24/24 | 8/8 | |
| 24 hours | 24/24 | 8/8 |
Table 10: Summary of Sample Stability overlaid with Matrix
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| Test Condition | Test Age | Test Organism Correct Identification | Matrix "No Peaks Found" |
|---|---|---|---|
| DT20 ± 1°C, 70 ± 5% | 0 hour | 24/24 | 8/8 |
| DT20 ± 1°C, 70 ± 5% | 4 hours | 24/24 | 8/8 |
| DT20 ± 1°C, 70 ± 5% | 8 hours | 23/24 | 8/8 |
| DT20 ± 1°C, 70 ± 5% | 24 hours | 24/24 | 8/8 |
| Ext20 ± 1°C, 70 ± 5% | 0 hour | 24/24 | 8/8 |
| Ext20 ± 1°C, 70 ± 5% | 4 hours | 24/24 | 8/8 |
| Ext20 ± 1°C, 70 ± 5% | 8 hours | 24/24 | 8/8 |
| Ext20 ± 1°C, 70 ± 5% | 24 hours | 24/24 | 8/8 |
| DT25 ± 1°C, 30 ± 5% | 0 hour | 24/24 | 8/8 |
| DT25 ± 1°C, 30 ± 5% | 4 hours | 24/24 | 8/8 |
| DT25 ± 1°C, 30 ± 5% | 8 hours | 24/24 | 8/8 |
| DT25 ± 1°C, 30 ± 5% | 24 hours | 24/24 | 8/8 |
| Ext25 ± 1°C, 30 ± 5% | 0 hour | 24/24 | 8/8 |
| Ext25 ± 1°C, 30 ± 5% | 4 hours | 24/24 | 8/8 |
| Ext25 ± 1°C, 30 ± 5% | 8 hours | 24/24 | 8/8 |
| Ext25 ± 1°C, 30 ± 5% | 24 hours | 24/24 | 8/8 |
| DT25 ± 1°C, 70 ± 5% | 0 hour | 24/24 | 8/8 |
| DT25 ± 1°C, 70 ± 5% | 4 hours | 24/24 | 8/8 |
| DT25 ± 1°C, 70 ± 5% | 8 hours | 18/24 | 8/8 |
| DT25 ± 1°C, 70 ± 5% | 24 hours | 24/24 | 8/8 |
| Ext25 ± 1°C, 70 ± 5% | 0 hour | 24/24 | 8/8 |
| Ext25 ± 1°C, 70 ± 5% | 4 hours | 24/24 | 8/8 |
| Ext25 ± 1°C, 70 ± 5% | 8 hours | 23/24 | 8/8 |
| Ext25 ± 1°C, 70 ± 5% | 24 hours | 24/24 | 8/8 |
All study results confirmed that inoculated test organisms once overlaid with matrix are stable for up to 24 hours at room temperature. In addition, matrix alone does not interfere or influence MBT-CA identification.
Bacterial Test Standard (BTS) Stability
The Bruker Bacterial Test Standard is an in vitro diagnostic product for mass spectrum calibration and optimization as well as a performance control for the identification of microorganisms with the MBT-CA System. The testing summarized below was done to determine the stability of unreconstituted and reconstituted BTS material.
In one study, accelerated and shipping stability of BTS was assessed using three (3) lots of BTS material. Shipping and accelerated stability conditions were simulated by storing eight (8) vials of each BTS lot in a climate controlled chamber at 37±2ºC for one (1), two (2) and three (3) weeks. At each time interval, two (2) vials of each BTS lot were removed, allowed to acclimate to room temperature, reconstituted and spotted on sixteen (16) target plate positions (each vial) and three (3) cross-joint positions. Target plates were then analyzed in accordance with product instructions for use.
{12}------------------------------------------------
In the second study, real-time stability of BTS was assessed using three (3) lots of BTS material. The three lot of material were maintained at recommended storage conditions per product instructions (< 18°C) and tested at 3, 6, 9, 12 and 18 months following the same process as described above.
In the third and final study, in-use (reconstituted) stability of BTS was assessed using four vials of a single lot of BTS reagent. All four vials were reconstituted in accordance with product instructions for use. Two (2) vials each were then pooled. Testing was carried out in replicates of eight (8) immediately following reconstitution then frozen and retested at 1, 2, 3, 4, 5 and 6 months.
The summary of the results of the three (3) studies are provided below:
| Study | Test Age | av. log(score)Lot# 1, Vial 1 | av. log(score)Lot# 1, Vial 2 | av. log(score)Lot# 2, Vial 1 | av. log(score)Lot# 2, Vial 2 | av. log(score)Lot# 3, Vial 1 | av. log(score)Lot# 3, Vial 2 |
|---|---|---|---|---|---|---|---|
| Accelerated/ShippingStability | No Aging | 2.334 ± 0.027 | 2.353 ± 0.023 | 2.344 ± 0.024 | 2.351 ± 0.019 | 2.370 ± 0.031 | 2.345 ± 0.023 |
| 1 week | 2.385 ± 0.030 | 2.362 ± 0.042 | 2.337 ± 0.034 | 2.364 ± 0.039 | 2.372 ± 0.034 | 2.353 ± 0.023 | |
| 2 weeks | 2.384 ± 0.021 | 2.365 ± 0.043 | 2.344 ± 0.054 | 2.381 ± 0.034 | 2.372 ± 0.021 | 2.349 ± 0.026 | |
| 3 weeks | 2.391 ± 0.022 | 2.372 ± 0.027 | 2.369 ± 0.031 | 2.347 ± 0.037 | 2.332 ± 0.031 | 2.349 ± 0.033 | |
| Real-Time Stability | No Aging | 2.293 ± 0.030 | 2.276 ± 0.038 | 2.333 ± 0.057 | 2.320 ± 0.031 | 2.274 ± 0.041 | 2.250 ± 0.031 |
| 3 months | 2.391 ± 0.049 | 2.387 ± 0.042 | 2.358 ± 0.050 | 2.380 ± 0.036 | 2.296 ± 0.027 | 2.303 ± 0.019 | |
| 6 months | 2.318 ± 0.035 | 2.340 ± 0.036 | 2.349 ± 0.035 | 2.338 ± 0.024 | 2.298 ± 0.029 | 2.296 ± 0.027 | |
| 9 months | 2.361 ± 0.037 | 2.346 ± 0.027 | 2.356 ± 0.029 | 2.348 ± 0.028 | 2.348 ± 0.028 | 2.320 ± 0.023 | |
| 12 months | 2.310 ± 0.024 | 2.327 ± 0.020 | 2.292 ± 0.033 | 2.292 ± 0.022 | 2.262 ± 0.028 | 2.284 ± 0.026 | |
| 18 months | 2.414 ± 0.026 | 2.410 ± 0.043 | 2.338 ± 0.027 | 2.346 ± 0.014 | 2.340 ± 0.034 | 2.344 ± 0.026 |
Table 11: Summary of BTS Stability
| Study | Test Age | av. log(score)Lot# 1, Vial 1 | av. log(score)Lot# 1, Vial 2 |
|---|---|---|---|
| In-UseStability | No Aging | 2.413 ± 0.038 | 2.392 ± 0.022 |
| 1 month | 2.396 ± 0.030 | 2.353 ± 0.054 | |
| 2 months | 2.331 ± 0.020 | 2.360 ± 0.020 | |
| 3 months | 2.365 ± 0.022 | 2.371 ± 0.034 | |
| 4 months | 2.359 ± 0.017 | 2.362 ± 0.025 | |
| 5 months | 2.332 ± 0.024 | 2.292 ± 0.044 | |
| 6 months | 2.293 ± 0.023 | 2.240 ± 0.044 |
The shipping/accelerated stability study confirmed that BTS is stable for three (3) weeks at temperatures up to 37±2°C. Two of these weeks account for the shipping and one for the long-term storage. Realtime stability testing confirms that BTS is stable for up to 18 months when stored in accordance with product claims. (Bruker only claims stability for 12 months, though.) Lastly, in-use stability confirms that reconstituted BTS is stable for five (5) months when stored in accordance with product claims.
HCCA portioned (Matrix) Stability
HCCA portioned (Matrix) is used when processing test organisms for identification on the MBT-CA system. Matrix must be reconstituted prior to use. These studies were conducted to determine the stability of unreconstituted matrix as well as in-use (reconstituted) matrix.
{13}------------------------------------------------
In one study, accelerated/shipping stability was assessed using a single lot of matrix. Shipping conditions were simulated by storing the matrix at 37±2ºC for two (2) weeks while accelerated stability studies conducted subsequently at the same temperature for 14 weeks. All testing was done using a common gram negative organism. At each time interval, matrix was removed, allowed to acclimate to room temperature, reconstituted and testing was done via direct transfer (DT) and extraction (Ext) method using two (2) targets in replicates of eight (8) in accordance with product instructions for use.
A second study assessed the real time stability of HCCA matrix using three (3) lots of material. All test lots were stored at the recommended storage condition per product instructions 2-8℃. All three lots were tested on two (2) target plates in replicates of eight (8) and tested at 3, 6, 9, 12 and 18 months in keeping with the process described for accelerated/shipping stability.
A third study assessed the recommended stability of reconstituted matrix for one (1) week at controlled room temperature (20-25℃). Three (3) lots of matrix material were reconstituted in accordance with product instructions for use and stored in a climate controlled chamber at 20±1ºC for seven (7) days. Testing was conducted at day one (1), three (3) and seven (7) using three (3) common gram negative bacteria on two (2) target plates, in replicates of eight. In addition, matrix alone was inoculated onto eight (8) positions at each time point.
A fourth study was conducted to assess the stability of reconstituted matrix at stressed temperatures for up to twelve (12) hours. A single lot of matrix material was reconstituted in accordance with product instructions for use and stored in a climate controlled chamber at 15±1ºC and 30±1ºC for twelve (12) hours. Testing was conducted at 6±1 hours and 12±1 hours using three (3) common gram negative bacteria on two (2) target plates, in replicates of eight. In addition, matrix alone was inoculated onto eight (8) positions at each time point.
The results of the four (4) studies are summarized below:
| Study | Test Condition | Test Age | # MBT-CA ID ≥2.0,(Target 1) | # "no ID",(Target 1) | # "false ID",(Target 1) | # MBT-CA ID ≥2.0,(Target 2) | # "no ID",(Target 2) | # "false ID",(Target 2) |
|---|---|---|---|---|---|---|---|---|
| Accelerated/ShippingStability | Matrix Lot #1 | No Aging | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 |
| 1 week | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 2 weeks | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 4 weeks | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 7 weeks | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 16 weeks | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| Real-TimeStability | Matrix Lot #1 | No Aging | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 |
| 3 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 6 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 9 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 12 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 18 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| Matrix Lot #2 | No Aging | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | |
| 3 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 6 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 9 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 12 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| Study | Test Condition | Test Age | # MBT-CA ID ≥2.0, (Target 1) | # "no ID", (Target 1) | # "false ID" (Target 1) | # MBT-CA ID ≥2.0, (Target 2) | # "no ID", (Target 2) | # "false ID", (Target 2) |
| Matrix Lot #3 | 18 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | |
| No Aging | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 3 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 6 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 9 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 12 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| 18 months | 16/16 | 0/16 | 0/16 | 16/16 | 0/16 | 0/16 | ||
| In-UseStability atControlledRoomTemperature | Matrix Lot #1;20±1°C | No Aging | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 |
| 1 day | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| 3 days | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| 7 days | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| Matrix Lot #1;25±1°C | No Aging | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | |
| 1 day | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| 3 days | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| 7 days | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| Matrix Lot #2;20±1°C | No Aging | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | |
| 1 day | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| 3 days | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| 7 days | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| Matrix Lot #3;20±1°C | No Aging | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | |
| 1 day | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| 3 days | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| 7 days | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| In-UseStability atControlledRoomTemperature | Matrix Lot #1;Matrix Only | No Aging | # "no peaks found ID", (Target 1); T=20°C8/8 | # "no peaks found ID", (Target 2); T=20°C8/8 | ||||
| 1 day | 8/8 | 8/8 | ||||||
| 3 days | 8/8 | 8/8 | ||||||
| 7 days | 8/8 | 8/8 | ||||||
| Matrix Lot #2;Matrix Only | No Aging | # "no peaks found ID", (Target 1); T=25°C8/8 | # "no peaks found ID", (Target 2); T=25°C,8/8 | |||||
| 1 day | 8/8 | 8/8 | ||||||
| 3 days | 8/8 | 8/8 | ||||||
| 7 days | 8/8 | 8/8 | ||||||
| Matrix Lot #3;Matrix Only | No Aging | 8/8 | 8/8 | |||||
| 1 day | 8/8 | 8/8 | ||||||
| 3 days | 8/8 | 8/8 | ||||||
| 7 days | 8/8 | 8/8 | ||||||
| In-UseStability atStressedTemperatures | Matrix Lot #1;15±1°C | No Aging | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 |
| 6 hours | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| 12 hours | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| Matrix Lot #1;30±1°C | No Aging | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | |
| 6 hours | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| 12 hours | 24/24 | 0/24 | 0/24 | 24/24 | 0/24 | 0/24 | ||
| Test Condition | Test Age | # "no peaks found ID",(Target 1) T=15°C | # "no peaks found ID",(Target 2) T=15°C | # "no peaks found ID",(Target 1) T=30°C | # "no peaks found ID",(Target 2) T=30°C, | |||
| Matrix Lot #1;Matrix Only | No Aging | 8/8 | 8/8 | 8/8 | 8/8 | |||
| 1 day | 8/8 | 8/8 | 8/8 | 8/8 | ||||
| 3 days | 8/8 | 8/8 | 8/8 | 8/8 |
Table 12: Summary of Matrix Stability
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Shipping/accelerated stability studies confirm that matrix is stable for sixteen (16) weeks at temperatures up to 37±2℃. Real-time stability studies confirm that matrix is stable for up to 18 months when stored in accordance with product instructions for use. In addition, in-use (reconstituted) stability testing confirmed that reconstituted matrix is stable for one (1) week when stored at controlled room temperature and for 12 hours when stressed by temperatures up to 15℃ or 30℃.
Carry-Over and Cross Contamination:
This study was conducted to determine the effect of cross-contamination, defined as microbial sample convergence between adjacent target spots and carry-over defined as target contamination due to insufficient target cleaning after MALDI Biotyper CA organism identification. Two targets and two (2) frequently occurring Gram negative bacteria were chosen for this testing. Each target was inoculated with test organism four (4) times via Direct Transfer and extraction method in an alternating pattern. All sample positions were overlaid with matrix solution including the remaining unused target positions to serve as blank measurements. Testing then proceeded in accordance with product instructions for use. Targets were then cleaned in accordance with the Target Cleaning procedure and organism prepared in a similar fashion but in the reverse pattern. The test cycle described above was repeated four (4) times on each target plate. Results of this study are presented below.
| Test procedure | Matrix only | Test Organism | |||
|---|---|---|---|---|---|
| "no peaks found" | # of MALDIBiotyper CA ID | # of "no ID" | # of "false ID" | ||
| ≥2.0 | |||||
| 1st cycle | 1st run | 26 / 26 (100%) | 16/16 | 0/16 | 0/16 (0%) |
| 2nd run | 27 / 27 (100%) | 16/16 | 0/16 | 0/16 (0%) | |
| 2nd cycle | 1st run | 26 / 26 (100%) | 16/16 | 0/16 | 0/16 (0%) |
| 2nd run | 27 / 27 (100%) | 16/16 | 0/16 | 0/16 (0%) | |
| 3rd cycle | 1st run | 26 / 26 (100%) | 16/16 | 0/16 | 0/16 (0%) |
| 2nd run | 27 / 27 (100%) | 16/16 | 0/16 | 0/16 (0%) | |
| 4th cycle | 1st run | 26 / 26 (100%) | 16/16 | 0/16 | 0/16 (0%) |
| 2nd run | 27 / 27 (100%) | 16/16 | 0/16 | 0/16 (0%) | |
| 5th cycle | 1st run | 26 / 26 (100%) | 16/16 | 0/16 | 0/16 (0%) |
| 2nd run | 27 / 27 (100%) | 16/16 | 0/16 | 0/16 (0%) |
Table 13: Target #1 (SN 00004) Summary Data
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| Test procedure | Matrix only | Test Organism | |||
|---|---|---|---|---|---|
| "no peaks found" | # of MBT-CA ID≥2.0 | # of "no ID" | # of "false ID" | ||
| 1st cycle | 1st run | 26 / 26 (100%) | 16/16 | 0/16 | 0/16 (0%) |
| 2nd run | 27 / 27 (100%) | 16/16 | 0/16 | 0/16 (0%) | |
| 2nd cycle | 1st run | 26 / 26 (100%) | 16/16 | 0/16 | 0/16 (0%) |
| 2nd run | 27 / 27 (100%) | 16/16 | 0/16 | 0/16 (0%) | |
| 3rd cycle | 1st run | 26 / 26 (100%) | 16/16 | 0/16 | 0/16 (0%) |
| 2nd run | 27 / 27 (100%) | 16/16 | 0/16 | 0/16 (0%) | |
| 4th cycle | 1st run | 26 / 26 (100%) | 16/16 | 0/16 | 0/16 (0%) |
| 2nd run | 27 / 27 (100%) | 16/16 | 0/16 | 0/16 (0%) | |
| 5th cycle | 1st run | 26 / 26 (100%) | 16/16 | 0/16 | 0/16 (0%) |
| 2nd run | 27 / 27 (100%) | 16/16 | 0/16 | 0/16 (0%) |
Table 14: Target #2 (SN 00012) Summary Data
The study confirmed that there are neither cross-contamination nor carry-over effects in the automated MALDI Biotyper CA identification process.
Proficiency/Familiarity
Prior to method comparison study initiation, each intended study operator from the four (4) US Study sites underwent a proficiency/familiarity period to ensure that each operator was familiar with all aspects of instrument operation. Each intended operator was asked to test five (5) QC organisms using both the Direct Transfer (DT) and Extraction (Ext) method following product instructions for use.
| Site | Operator | Test Organism [Correct Identifications ≥2.0] | |
|---|---|---|---|
| # Samples Passed (DT) | # Samples Passed (Ext) | ||
| #1 | #1 | 25/25 | 25/25 |
| #2 | 30/31 | 30/30 | |
| #3 | 32/32 | 30/35 | |
| #2 | #1 | 25/25 | 25/25 |
| #2 | 29/30 | 30/30 | |
| #3 | #1 | 25/26 | 25/25 |
| #2 | 25/25 | 25/25 | |
| #3 | 25/25 | 25/25 | |
| #4 | 25/25 | 25/25 | |
| #5 | 30/32 | 30/30 | |
| #6 | 25/25 | 25/25 | |
| #4 | #1 | 25/25 | 25/25 |
| #2 | 25/25 | 25/25 | |
| #3 | 25/26 | 25/25 | |
| #4 | 29/30 | 30/30 | |
| #5 | 25/25 | 25/25 |
Table 15: Proficiency/Reproducibility Study Summary
All testing confirmed that, though the MBT-CA technology is of a higher complexity, intended operators are able to illustrate reproducible results using both testing methods.
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Reproducibility:
The reproducibility study was conducted to confirm day-to-day reproducibility and precision of the MALDI Biotyper CA System on different clinical study was conducted for five (5) days with two (2) runs each day/each clinical site. The sources of variability tested were:
-
- Two (2) operators/each clinical study site
-
- Four (4) clinical study sites
-
- Four (4) Target plates each clinical study sites
-
- Four (4) microflex LT/SH instruments
Ten (10) well-characterized organisms were chosen for this study and tested in duplicate via direct transfer method in accordance with product instructions. When the DT log(score) was <2.0, per product instructions, the test organism was tested following extraction method.
| Blinded Test Organism | Reproducibility Panel | # samples passed(DT) | # samples passed(DT+Ext) |
|---|---|---|---|
| Stenotrophomonas maltophilia | REPRO-1 | 77/80 (96%) | 80/80 (100%) |
| Citrobacter koseri | REPRO-2 | 80/80 (100%) | 80/80 (100%) |
| Enterobacter aerogenes | REPRO-3 | 77/80 (96%) | 80/80 (100%) |
| Escherichia coli | REPRO-4 | 78/80 (98%) | 80/80 (100%) |
| Klebsiella pneumoniae | REPRO-5 | 76/80 (95%) | 80/80 (100%) |
| Morganella morganii | REPRO-6 | 80/80 (100%) | 80/80 (100%) |
| Pasteurella multocida | REPRO-7 | 79/80 (99%) | 80/80 (100%) |
| Proteus mirabilis | REPRO-8 | 80/80 (100%) | 80/80 (100%) |
| Pseudomonas aeruginosa | REPRO-9 | 78/80 (98%) | 80/80 (100%) |
| Salmonella sp | REPRO-10 | 78/80 (98%) | 80/80 (100%) |
Table 16: Reproducibility Study Summary
100% of all blinded test organisms were correctly identified on the species level at each clinical test site. Thus, data confirm reproducibility and precision of the whole MALDI Biotyper CA System independent from:
- Clinical Site
- System operators
- microflex LT/SH instruments
- Target plates
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Challenge Panel:
A panel of 100 organisms was tested at five (5) study sites. Eighty (80) of the Organisms included in the panel were selected from stored organisms tested during the clinical study. Twenty (20) 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 method in accordance with product instructions. If DT result yielded a log(score) <2.00, the organism was retested using the extraction method.
| Test procedure | Site A | Site B | Site C | *Site D | **Site E |
|---|---|---|---|---|---|
| Direct Transfer | 99/100(99%) | 98/100(98%) | 99/100(99%) | 96/100(96%) | 86/87 (99%) |
| Extraction Transfer onlyorganisms withlog(Score) <2.0. | 99/100(99%) | 99/100(99%) | 99/100(99%) | 97/100(97%) | 86/87 (99%) |
Table 17: Challenge Panel Study Summary
- One sample was incorrectly identified due to a site error, while another sample was not exclude from the study because of mixed culture.
** The number of test organisms was reduced as 13 samples were not received.
Testing of the challenge panel confirms intra laboratory performance of the MALDI Biotyper CA System.
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Method Comparison:
To demonstrate performance of the MALDI Biotyper CA (MBT-CA) System, a method comparison study was performed at four (4) clinical test sites and Bruker (Bremen, Germany). Fresh and frozen organisms were tested on the MALDI Biotyper CA System in accordance with 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.
At the time of testing on the MBT-CA, the test organism was subcultured onto a TSA Agar slant and shipped to the study reference laboratory. The reference laboratory, transferred the isolate to a sequencing reference laboratory for sequencing in accordance with MM-18 A guidelines.
Performance of the MBT-CA was compared to sequencing and when necessary to biochemical identification (i.e: Vitek 2) and protein sequencing.
In total, 2263 fresh and stored isolates were tested to support the initial reference library claim. An overall performance table is presented below:
| REFERENCE ALGORITHM | |||
|---|---|---|---|
| All Isolates - ALL SITES | Positive | Negative | Total |
| Positive Organism ID; (High Confidence); log(score) ≥2.0 | 2174 | 16 | 2190 |
| Positive Organism ID; (Low Confidence); log(score) ≥1.7; <2.0 | 48 | 23 | 71 |
| Negative | 2 | n/a | 2 |
| Total | 2224 | 39 | 2263 |
Table 18: Method Comparison Summary Table (Fresh & Stored Isolates)
| Gramnegatives | Correct:Genus IDSpecies ID orGroup ID orComplex ID | Correct: Genus IDWrong: Species ID orGroup ID orComplex ID | Wrong: Genus ID | no ID | |||
|---|---|---|---|---|---|---|---|
| ALLSITES | highconfidencelog(score)≥2.0 | lowconfidencelog(score)≥1.7 ... <2.0 | highconfidencelog(score)≥2.0 | lowconfidencelog(score)≥1.7 ... <2.0 | highconfidencelog(score)≥2.0 | lowconfidencelog(score)≥1.7 ... <2.0 | log(score)<2.0 |
| IDs | 2174 / 226396.07% | 48 / 22632.12% | 141) / 22630.62% | 222) / 22630.97% | 23) / 22630.09% | 14) / 22630.04% | 25) / 22630.09% |
| CombinedIDs | 2222 / 226398.19% | 36 / 22631.59% | 3 / 22630.13% | n/a |
Of the 2263 isolates included in the initial reference library claim, one hundred fifty-seven (157) samples required extraction for an overall sample extraction rate of 6.9% (157/2263). Of the 193 Quality Control runs conducted during the course of the method comparison study, there were five (5) instances where
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a Quality Control organism failed to yield an expected result. As a result, all isolates included in that plate run were repeated using a fresh QC organism transfer. The overall plate repeat rate was 2.6% (5/193).
In addition, it is important to note that of the 2263 isolates, 498 were "fresh" meaning that the isolates were never frozen. The performance of these isolates is provided below:
| vul 19911 autilillaSingle of the state of the state of the state of the state of the state of the state of the station of the state of the state of the state of the state of the state of the s | ||||
|---|---|---|---|---|
| REFERENCE ALGORITHM | ||||
| All Isolates | Positive | Negative | Total | |
| Positive Organism ID ≥ 2.0 | 488 | O | 488 | |
| Positive Organism (Low Discrimination) | 9 | 10 | ||
| Negative | O | O | O | |
| Total | 497 | 1 | 498 |
Table 19: Method Comparison Summary Table (Fresh Isolates)
| Positive | Negative | |
|---|---|---|
| highdiscrimination | high & lowdiscrimination | 0.00% |
| 98.0% | 99.8% | 0.00% |
Statement of Safety and Efficacy
The data presented clearly demonstrate the safety and efficacy of the Bruker Daltonic, Inc MBT-CA System as compared to the reference method, 16s bi-directional sequencing, 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.