(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
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
§ 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.