(150 days)
The COBAS TaqMan Analyzer is a fully automated amplification and detection system for nucleic acids using 5' nuclease technology. The COBAS TaqMan Analyzer is intended to be used by laboratory professionals trained in laboratory techniques and on the use of the analyzer.
The COBAS TaqMan Analyzer is a flexible, automated batch analyzer that automates the real-time kinetic amplification and detection steps of the Polymerase Chain Reaction (PCR) process. The COBAS TaqMan Analyzer combines the operations of automated handling of reaction tubes (K-Tubes), thermal cycling, controlled temperature incubation, real-time photometric detection at each cycle and result reporting into a single automated analyzer. The instrument consists of four major sub-components: (1) a thermal cycler module; (2) a robotic transfer unit; (3) a photometer module and (4) a workstation, which together with an on-board real-time processor controls and monitors the major components including system and run control, results calculation, and system diagnostic tests and provides the user interface.
Here's an analysis of the COBAS TaqMan™ Analyzer based on the provided 510(k) summary, aiming to address your specific questions about acceptance criteria and study details.
Important Note: The provided document is a 510(k) summary for a device (the analyzer itself), not a specific assay that runs on the analyzer. Therefore, the acceptance criteria and performance data presented are for the instrument's capabilities as a whole, often in comparison to a predicate instrument, rather than clinical performance metrics (like diagnostic sensitivity/specificity for a disease). Clinical performance metrics would typically be found in the 510(k) for the specific assays validated for use on the analyzer.
Acceptance Criteria and Reported Device Performance
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria Category | Specific Metric (Implied) | Predicate Device (COBAS AMPLICOR Analyzer) Performance (Implied) | COBAS TaqMan Analyzer Performance (Reported) | Device Meets Criteria? (Based on "substantially equivalent" claims) |
|---|---|---|---|---|
| Linearity | Comparable linearity across dynamic range | (Not explicitly quantified, but established) | Comparable to COBAS AMPLICOR Analyzer | Yes |
| Dynamic Range | Ability to amplify over a specific range without dilution | 3 - 4 log dynamic range | 7 - 8 log dynamic range (enhanced by 3 orders of magnitude), 50 - 2x10^7 IU/mL | Yes (Exceeds predicate) |
| Precision | Reproducibility of results | (Not explicitly quantified, but established) | Substantially equivalent | Yes |
| Sensitivity | Lower limit of quantitation | (Not explicitly quantified for comparison) | Lower limit of quantitation: 50 IU/mL (Improved over predicate) | Yes (Exceeds predicate) |
| Specificity | Ability to correctly identify negative specimens | (Not explicitly quantified for comparison) | Initial: 96.87% (93/96) for EIA sero-negative specimens; Recalculated: 98.9% (93/94) after retesting | Yes (Improved over predicate) |
| Carryover | Absence of contamination from high-concentration samples | (Not explicitly quantified, but established) | Substantially equivalent | Yes |
| Correlation | Agreement of results with predicate device | (Not explicitly quantified, but correlation expected) | Substantially equivalent | Yes |
| Thermal Cycling | Heating performance and tolerances | Established operational characteristics | Meets or exceeds operational characteristics of COBAS AMPLICOR Analyzer | Yes |
| Detection Timing | Precision of detection procedure | Precisely timed | Precisely times detection procedure | Yes |
Explanation of 'Implied' Performance: For a 510(k) for an instrument, the "acceptance criteria" are generally that the new device performs as well as or better than the legally marketed predicate device for the functions it performs. The document states that the COBAS TaqMan Analyzer was "substantially equivalent to the COBAS AMPLICOR Analyzer in all non-clinical performance studies." Where specific improvements are noted (e.g., dynamic range, sensitivity, specificity), these indicate that the new device exceeded the predicate's performance, which is also an acceptable outcome for equivalence.
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size for Test Set:
- For specificity, 96 EIA sero-negative specimens were initially tested, with 3 subsequently retested, resulting in a final count of 94 for the recalculated specificity.
- No other specific sample sizes are provided for linearity, dynamic range, precision, carryover, or correlation studies. These are described in a general comparative sense.
- Data Provenance: Not explicitly stated (e.g., country of origin). The studies are described as "non-clinical performance studies." It's not specified if they were retrospective or prospective, but given they are performance evaluations of an instrument, they would typically involve prospective testing of prepared samples.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
- This information is not provided in the summary. For an instrument 510(k), experts typically wouldn't establish "ground truth" in the same way they would for a diagnostic assay's clinical performance study. The ground truth for instrument performance (e.g., linearity, precision) would be based on known concentrations of analytes in controls or characterized samples. For the specificity evaluation, the "EIA sero-negative specimens" served as a reference, and the "manual HCV AMPLICOR Test" was used for retesting and confirmation.
4. Adjudication Method:
- Not applicable/Not described in the context of this instrument performance study. Adjudication methods (like 2+1 or 3+1) are typically used in clinical studies where multiple human readers interpret results, and disagreement needs a resolution mechanism. Here, the instrument's performance is being evaluated against known standards or a predicate device. The retesting of three samples for specificity could be considered a form of "adjudication" or re-evaluation to refine the ground truth for those specific cases.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, an MRMC study was not done. This type of study focuses on human reader performance, often with or without AI assistance, which is not relevant for the evaluation of this automated instrument.
6. Standalone Performance Study (Algorithm Only Without Human-in-the-Loop):
- Yes, a standalone performance study was done. The entire "Non-Clinical Performance" section (Section 7.1) describes the standalone performance of the COBAS TaqMan Analyzer. The analyzer is described as "fully automated" and provides "interpretative qualitative or quantitative result" without direct human intervention once samples are loaded. The entire evaluation compares "the analyzer comparing it to the predicate device (COBAS AMPLICOR Analyzer)."
7. Type of Ground Truth Used:
- The ground truth varied depending on the performance metric:
- Linearity, Dynamic Range, Precision: Likely based on known concentrations of control materials or highly characterized samples.
- Sensitivity (Lower Limit of Quantitation): Determined by testing serially diluted samples with known analyte concentrations.
- Specificity: Initially referenced against EIA serology results ("EIA sero-negative specimens"). For discrepant results (TaqMan positive/EIA negative), a manual HCV AMPLICOR Test was used as a confirmatory "ground truth."
- Correlation: Comparison against the COBAS AMPLICOR Analyzer's results on the same samples.
8. Sample Size for the Training Set:
- Not applicable/Not provided. This device is a molecular diagnostic instrument, not an AI/machine learning algorithm that requires a separate "training set" in the conventional sense. Its "training" is in its engineering and calibration. If it contained internal algorithms, those would be part of the instrument's design and fixed, not adjusted via a training set.
9. How the Ground Truth for the Training Set Was Established:
- Not applicable. As stated above, there is no "training set" in the context of this device.
§ 862.2170 Micro chemistry analyzer for clinical use.
(a)
Identification. A micro chemistry analyzer for clinical use is a device intended to duplicate manual analytical procedures by performing automatically various steps such as pipetting, preparing filtrates, heating, and measuring color intensity. The distinguishing characteristic of the device is that it requires only micro volume samples obtainable from pediatric patients. This device is intended for use in conjunction with certain materials to measure a variety of analytes.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.