(357 days)
The Carbamazepine is intended for the quantitative in vitro diagnostic determination of the carbamazepine concentration in human serum using T60 Clinical Chemistry Analyzers. Measurements are used in the diagnosis and treatment of carbamazepine overdose and in monitoring levels of carbamazepine to help ensure proper therapy.
The Valproic Acid is intended for the quantitative in vitro diagnostic determination of the valproic acid concentration in human serum using T60 Clinical Chemistry Analyzers. Measurements are used in the diagnosis and treatment of valproic acid overdose and in monitoring levels of valproic acid to help ensure proper therapy.
TDM Calibration set B is intended for in vitro diagnostic use as a calibrator in the quantitative measurement of the kit code 981645 Carbamazepine and kit code 981650 Valproic acid assays on T60 Analyzer.
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The provided text describes the 510(k) submission for Thermo Fisher Scientific Oy's Carbamazepine and Valproic Acid test systems and TDM Calibration set B. The document outlines the intended use, indications for use, and a comparison with predicate devices to establish substantial equivalence.
Here's an analysis of the acceptance criteria and study information, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria provided are primarily in comparison to a predicate device, focusing on similar performance characteristics. The document presents performance data for "New device #1" (Thermo Fisher Scientific Oy's device) and "Predicate device #1" (Microgenics Corporation CEDIA® Carbamazepine II/Valproic Acid II).
Carbamazepine Assay:
| Attribute | Acceptance Criteria (Predicate Device #1) | Reported Device Performance (New Device #1) |
|---|---|---|
| Intended Use | For quantitation of carbamazepine in human serum or plasma using automated clinical chemistry analyzers, for diagnosis and treatment of overdose and monitoring levels to ensure proper therapy. | For quantitative determination of carbamazepine concentration in human serum on T60 analyzer, for diagnosis and treatment of overdose and monitoring levels to help ensure proper therapy. |
| Indications for Use | Same as Intended Use. | For quantitative in vitro diagnostic determination of carbamazepine concentration in human serum using T60 Clinical Chemistry Analyzers, for diagnosis and treatment of overdose and monitoring levels to help ensure proper therapy. |
| Assay Protocol | Recombinant DNA technology (US Patent no. 4708929) to produce a unique homogeneous enzyme immunoassay system. | Recombinant DNA technology (US Patent no. 4708929) to produce a unique homogeneous enzyme immunoassay system. |
| Traceability/Standardization | Calibration values traceable to USP reference materials prepared gravimetrically to drug-free human serum. | Calibration values are traceable to USP reference materials prepared gravimetrically to drug-free human serum. |
| Sample Type | Serum or plasma (Na or Li heparin, Na EDTA). | Human Serum. |
| Reagent Storage | Store at 2-8 °C. Do not freeze. Stability of unopened components indicated on labels. | Unopened reagents stable at 2-8 °C until expiration date. DO NOT FREEZE. |
| Expected Values (Therapeutic Range for adults) | Ranges such as 5-12 µg/ml, 8-12 µg/ml, 3-12 µg/ml, 6-10 µg/ml, 4-10 µg/ml, 4-8 µg/ml, 4-12 µg/ml. | Suggested ranges: 4 - 12 µg/ml or 17 - 51 µmol/l (1); 4 - 10 µg/ml or 17 - 42 µmol/l (2). |
| Measuring Range | Between 0.5 µg/ml and approximately 20 µg/ml. | From 1.0 µg/ml to 19.0 µg/ml. |
| Precision | Within run: Level 4.2 µg/ml (SD=0.06, CV=1.5%), Level 10.6 µg/ml (SD=0.08, CV=0.8%), Level 16.8 µg/ml (SD=0.12, CV=0.7%). Total: Level 4.2 µg/ml (SD=0.15, CV=3.5%), Level 10.6 µg/ml (SD=0.21, CV=2.0%), Level 16.8 µg/ml (SD=0.29, CV=1.7%). | Within run: Level 3.0 µg/ml (SD=0.09, CV=2.8%), Level 9.5 µg/ml (SD=0.14, CV=1.5%), Level 15.0 µg/ml (SD=0.16, CV=1.1%). Between run: Level 3.0 µg/ml (SD=0.07, CV=2.4%), Level 15.0 µg/ml (SD=0.14, CV=0.9%). Total: Level 3.0 µg/ml (SD=0.19, CV=6.3%), Level 9.5 µg/ml (SD=0.32, CV=3.3%), Level 15.0 µg/ml (SD=0.42, CV=2.8%). |
| Method Comparison (Deming Regression) | Y = 1.04x - 0.04; r = 0.999; Sy.x = 0.26; Range 1.3 - 19.8 µg/ml; N = 103 (vs. previous CEDIA Carbamazepine assay). | y = 0.98 x + 0.02; r = 0.993; Range 1.9 - 19.6 µg/ml; N = 134. |
| Limitations (Interference) | Hemoglobin up to 1000 mg/dl, Bilirubin up to 66 mg/dl, Triglyceride up to 1000 mg/dl, Total protein up to 12 g/dl, Rheumatoid factor up to 180 IU/ml. | No interference found: Hemoglobin up to 1000 mg/dl, Bilirubin up to 58 mg/dl, Lipemia up to 1000 mg/dl of Intralipid®. |
Valproic Acid Assay:
| Attribute | Acceptance Criteria (Predicate Device #1) | Reported Device Performance (New Device #1) |
|---|---|---|
| Intended Use | For quantitation of valproic acid in human serum or plasma using automated clinical chemistry analyzers, for diagnosis and treatment of overdose and monitoring levels to ensure proper therapy. | For quantitative determination of valproic acid concentration in human serum on T60 instrument, for diagnosis and treatment of overdose and monitoring levels to help ensure proper therapy. |
| Indications for Use | Same as Intended Use. | For quantitative in vitro diagnostic determination of valproic acid concentration in human serum using T60 Clinical Chemistry Analyzers, for diagnosis and treatment of overdose and monitoring levels to help ensure proper therapy. |
| Assay Protocol | Recombinant DNA technology (US Patent no. 4708929) to produce a unique homogeneous enzyme immunoassay system. | Recombinant DNA technology (US Patent no. 4708929) to produce a unique homogeneous enzyme immunoassay system. |
| Traceability/Standardization | Calibration values traceable to USP reference materials prepared gravimetrically to drug-free human serum. | Calibration values are traceable to USP reference materials prepared gravimetrically to drug-free human serum. |
| Sample Type | Serum or plasma (Na or Li heparin, Na EDTA). | Human Serum. |
| Reagent Storage | Store at 2-8 °C. Do not freeze. Stability of unopened components indicated on labels. | Unopened reagents stable at 2-8 °C until expiration date. DO NOT FREEZE. |
| Expected Values (Therapeutic range for adults) | Ranges such as 50-100 µg/ml, 40-90 µg/ml. Toxic >100 µg/ml. | 50 - 100 µg/ml or 347 - 693 µmol/l (1,2). |
| Measuring Range | Between 3.0 µg/ml and approximately 150 µg/ml. | From 3.0 µg/ml to 142.5 µg/ml. |
| Precision | Within run: Level 24.4 µg/ml (SD=0.59, CV=2.4%), Level 95.0 µg/ml (SD=1.43, CV=1.5%), Level 136.8 µg/ml (SD=1.81, CV=1.3%). Total: Level 24.4 µg/ml (SD=0.83, CV=3.4%), Level 95.0 µg/ml (SD=1.93, CV=2.0%), Level 136.8 µg/ml (SD=2.48, CV=1.8%). | Within run: Level 35.0 µg/ml (SD=0.43, CV=1.2%), Level 81.1 µg/ml (SD=0.81, CV=1.0%), Level 113.6 µg/ml (SD=1.01, CV=0.9%). Between run: Level 35.0 µg/ml (SD=0.61, CV=1.8%), Level 81.1 µg/ml (SD=1.08, CV=1.3%), Level 113.6 µg/ml (SD=1.07, CV=0.9%). Total: Level 35.0 µg/ml (SD=1.90, CV=5.4%), Level 81.1 µg/ml (SD=3.15, CV=3.9%), Level 113.6 µg/ml (SD=3.11, CV=2.7%). |
| Method Comparison (Deming Regression) | Y = 1.08x - 0.61; r = 0.972; Sy.x = 7.042; Range 2.6 - 119.8 µg/ml; N = 77 (vs. commercially available fluorescence polarization immunoassay). | y = 0.996 x + 1.4; r = 0.993; Range 3.2 - 143.4 µg/ml; N = 136. |
| Limitations (Interference) | Hemoglobin up to 1000 mg/dl, Bilirubin up to 60 mg/dl, Triglyceride up to 1000 mg/dl, Total protein up to 10 g/dl, IgA up to 790 mg/dl, IgG up to 4300 mg/dl, IgM up to 840 mg/dl, Rheumatoid factor up to 200 IU/ml. | No interference found: Hemoglobin up to 1000 mg/dl, Bilirubin up to 58 mg/dl, Lipemia up to 1000 mg/dl of Intralipid®. |
2. Sample sizes used for the test set and the data provenance
- Carbamazepine:
- Method Comparison (test set): N = 134 samples (Carbamazepine).
- Provenance: Not explicitly stated, but clinical chemistry assays typically use de-identified human serum samples. The document doesn't specify if the data is retrospective or prospective, or the country of origin.
- Valproic Acid:
- Method Comparison (test set): N = 136 samples (Valproic Acid).
- Provenance: Not explicitly stated, but clinical chemistry assays typically use de-identified human serum samples. The document doesn't specify if the data is retrospective or prospective, or the country of origin.
- Precision (Carbamazepine & Valproic Acid): Tested at multiple levels (3 for each assay). The number of replicates or runs to achieve the reported SD and CV values is not explicitly stated in this summary but is typically part of the full validation report.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not provided in the document. For these types of quantitative in vitro diagnostic devices, "ground truth" is typically established by comparing the device's measurements against a recognized reference method or a predicate device that has established accuracy, rather than expert consensus on a clinical diagnosis. The predicate device's performance data is used as the comparative "truth" for demonstrating substantial equivalence.
4. Adjudication method for the test set
This is not applicable/provided as the study focuses on quantitative measurement comparison rather than diagnostic interpretation requiring adjudication. The method comparison studies for both Carbamazepine and Valproic Acid used Deming regression to compare the new device's measurements against the predicate device's measurements.
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
This is not applicable. This document describes an in vitro diagnostic device (a laboratory test for drug levels) and not an imaging or interpretive AI-driven diagnostic system that would involve human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This document describes a standalone in vitro diagnostic system (reagents and an analyzer) which performs quantitative measurements of drug concentrations. The results are then used by healthcare professionals for diagnosis and treatment. In this context, the "standalone" performance refers to the analytical performance of the device itself (precision, measuring range, method comparison) as detailed in the tables. There isn't an "algorithm only" component in the sense of a software-AI device, but rather a chemical assay coupled with an automated analyzer.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The "ground truth" for the method comparison studies was the measurements obtained from the predicate devices (CEDIA® Carbamazepine II and a commercially available fluorescence polarization immunoassay for Valproic Acid). For precision studies, "truth" is established by the known concentrations of quality control materials. The overall goal is to demonstrate that the new device's measurements correlate closely with these established methods.
8. The sample size for the training set
This information is not provided in the summary. For in vitro diagnostic assays, "training set" is usually not explicitly defined in the same way as for AI/ML models. Assay development and optimization involve extensive testing with various samples, but this isn't typically presented as a distinct "training set" in 510(k) summaries for traditional IVDs.
9. How the ground truth for the training set was established
This information is not provided for the reasons mentioned in point 8.
§ 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.