(133 days)
In vitro test for the quantitative determination of carbamazepine in serum and plasma on Roche/Hitachi cobas c systems.
Measurements obtained are used in monitoring levels of carbamazepine to help ensure appropriate therapy.
The ONLINE TDM Carbamazepine Gen. 4 assay is for the quantitative determination of carbamazepine in human serum or plasma on automated clinical chemistry analyzers. It is a homogeneous microparticle agglutination immunoassay based on the kinetic interaction of microparticles in solution (KIMS). Biotinylated drug hapten serves as the binding partner to anticarbamazepine antibody and streptavidin coated latex beads. A competitive reaction to a limited amount of specific anti-carbamazepine antibody takes place between the hapten and free carbamazepine in the sample. A decrease in the apparent signal produced by the microparticle agglutination is proportional to the amount of drug present in the sample.
Here's an analysis of the provided text, focusing on acceptance criteria and the study proving the device meets them:
Device Name: ONLINE TDM Carbamazepine Gen.4
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria Category | Specific Criteria/Metric | Reported Device Performance |
|---|---|---|
| Detection Limit | Limit of Blank (LoB) | 0.3 µg/mL (Claimed: 0.5 µg/mL) |
| Limit of Detection (LoD) | 0.5 µg/mL (Claimed: 1.0 µg/mL) | |
| Limit of Quantitation (LoQ) | 1.4 µg/mL (Claimed: 2.0 µg/mL) | |
| Precision | Repeatability (CV%) | TDM Control 1: 2.2% |
| TDM Control 2: 1.4% | ||
| TDM Control 3: 1.3% | ||
| Human Serum 1: 2.7% | ||
| Human Serum 2: 2.1% | ||
| Human Serum 3: 1.8% | ||
| Human Serum 4: 1.3% | ||
| Human Serum 5: 1.4% | ||
| Intermediate Precision (CV%) | TDM Control 1: 2.8% | |
| TDM Control 2: 2.3% | ||
| TDM Control 3: 1.8% | ||
| Human Serum 1: 3.3% | ||
| Human Serum 2: 2.9% | ||
| Human Serum 3: 2.6% | ||
| Human Serum 4: 2.4% | ||
| Human Serum 5: 2.9% | ||
| Linearity | Pearson correlation coefficient (R) | Serum: 0.997 |
| K2-EDTA, Plasma: 0.999 | ||
| Measuring Range | Claimed Measuring Range | 2.0 to 20.0 µg/mL |
| Matrix Comparison | Correlation (r) | Serum vs. Serum Gel Separation: 0.989 |
| Serum vs. Li-heparin: 0.991 | ||
| Serum vs. Na-heparin: 0.990 | ||
| Serum vs. K2-EDTA: 0.988 | ||
| Serum vs. K3-EDTA: 0.994 | ||
| Interferences (Endogenous) | Hemolysis (H index) | Up to 1000 (approx. Hgb 1000 mg/dL) |
| Icterus (I index) | Up to 50 (approx. bilirubin 50 mg/dL) | |
| Lipemia (L index) | Up to 2000 (approx. triglyceride 1000 mg/dL) | |
| Cholesterol | Up to 600 mg/dL | |
| Rheumatoid Factor | Up to 1200 IU/mL | |
| Total Protein | Up to 13 g/dL | |
| Interferences (Drugs) | Non-interference at specific concentrations for 16 common drugs | (See Table 7 in document for specific concentrations) |
| Cross-reactivity | % Cross reactivity at 3 µg/mL and 12 µg/mL for various compounds | (See Table 8 in document for specific values for 27 compounds) |
| Method Comparison to Predicate | Deming Regression (r) | 0.993 |
2. Sample Size Used for the Test Set and Data Provenance:
- Detection Limit (LoB): 60 measured values (10-fold determinations per run on one instrument, 6 runs over 3 days).
- Detection Limit (LoD): 36 determinations (5 samples, 2-fold determination per run, 6 runs over 3 days).
- Detection Limit (LoQ): Not explicitly stated, but "Nine samples are prepared... tested in two aliquots over at least three days on one analyzer, 2 runs per day for 3 lots." This implies a significant number of data points.
- Precision: "Two runs per day for ≥ 21 days on the same analyzer." This amounts to at least 42 runs for each sample type. Numerous samples were tested (TDM Controls 1, 2, 3 and Human Serums 1-5).
- Linearity: "Eleven levels (including the high concentration pool and diluent)." Tested for both human serum and plasma.
- Matrix Comparison: "33 full tubes" of paired serum and plasma samples from single donors.
- Interferences (Endogenous): Two human sample pools, varying concentrations of interfering substances.
- Interferences (Drugs): Two human sample pools, spiked with 16 different drugs.
- Cross-reactivity: Two carbamazepine concentrations (3 µg/mL and 12 µg/mL) tested against 27 different compounds.
- Method Comparison to Predicate: "One hundred single native human samples of patients taking carbamazepine."
Data Provenance: The document does not explicitly state the country of origin for the samples. It mentions "human serum," "human serum sample pool," and "single native human samples of patients." It is implied to be a retrospective analysis of samples collected for the purpose of testing, but it's not explicitly stated as retrospective or prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
Not applicable. This device is an in-vitro diagnostic (IVD) for quantitative determination of a drug concentration. The "ground truth" for these tests is established by reference methods, calibrators, and known concentrations, not by expert interpretation of images or clinical cases. For example, LoQ uses LC/MS as the expected/target value.
4. Adjudication Method for the Test Set:
Not applicable. As this is an IVD for quantitative measurement, there is no subjective interpretation requiring adjudication among experts. The "ground truth" is determined by analytical methods with known accuracy and precision (e.g., LC/MS for LoQ).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:
No, an MRMC study was not done. This type of study is relevant for imaging devices or tests where human readers interpret results, often with and without AI assistance. This device is an automated quantitative assay, so human reader involvement in the primary measurement is not a factor.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
Yes, the entire performance evaluation presented is a standalone (algorithm/device-only) performance assessment. The device quantifies carbamazepine levels directly from samples. The results are compared against established analytical standards and a predicate device.
7. The Type of Ground Truth Used:
The ground truth for the performance studies is established by:
- Reference Methods: For LoQ, LC/MS (Liquid Chromatography/Mass Spectrometry) is explicitly stated as the method for determining the expected or target value.
- Known Concentrations: Samples with known concentrations of carbamazepine are used for various tests like detection limits, precision, linearity, and interference studies.
- Predicate Device Comparison: The reference standard for the "Method Comparison to Predicate" is the results obtained from the predicate device (ONLINE TDM Carbamazepine, K031902) on the cobas c 501.
- USP Reference Standards: The traceability for the assay calibration is stated as being standardized against USP reference standards.
8. The Sample Size for the Training Set:
Not applicable. This device is an immunoassay (KIMS technology), not a machine learning or AI-based algorithm that requires a "training set" in the conventional sense. The "training" of such a system would involve optimizing assay reagents and parameters during development, not a data-driven training dataset for an AI model.
9. How the Ground Truth for the Training Set Was Established:
Not applicable for the same reasons as point 8. The device's "training" is in its chemical and biological design, optimization, and manufacturing, rather than data-driven ground truth establishment for a training set.
§ 862.3645 Neuroleptic drugs radioreceptor assay test system.
(a)
Identification. A neuroleptic drugs radioceptor assay test system is a device intended to measure in serum or plasma the dopamine receptor blocking activity of neuroleptic drugs and their active metabolites. A neuroleptic drug has anti-psychotic action affecting principally psychomotor activity, is generally without hypnotic effects, and is a tranquilizer. Measurements obtained by this device are used to aid in determining whether a patient is taking the prescribed dosage level of such drugs.(b)
Classification. Class II.