(81 days)
The SERADYN QMS™ / MULTIGENT™ VALPROIC ACID assay is used for the quantitation of valproic acid in human serum or plasma on the Abbott AEROSET® System. Valproic acid is a broad-spectrum anticonvulsant drug used solely or in combination with other anticonvulsant drugs for the treatment of absence seizures. It also has demonstrated effectiveness in the management of generalized tonic-clonic and myoclonic seizures, as well as atypical absence, simple and complex partial and mixed grand mal and petit mal seizures. The capability of treating many types of seizures with a single anticonvulsant has resulted in the wide-spread use of valproic acid, particularly in children in whom tonic-clonic and myclonic seizures are most prevalent. Valproic acid has proven effective in the treatment of many patients otherwise refractory to other anticonvulsant treatments. Most patients receiving valproic acid do not develop a tolerance to its anticonvulsant effects. Monitoring serum valproic acid levels combined with other clinical data can provide the physician with useful information to aid in adjusting patient dosage and achieving optimal therapeutic effect while avoiding useless sub-therapeutic or harmful toxic dosage levels.
The Seradyn QMS™ / MULTIGENT™ Valproic Acid Assay is a homogeneous Particle Enhanced Turbidimetric Immunoassay used for the quantitation of valproic acid in serum or plasma. The assay is intended for use on the Abbott AEROSET® System, using the Seradyn QMS™ / MULTIGENT™ Valproic Acid Calibrators. The reagent system components are 1) Valproic acid coated microparticle reagent, and 2) the antibody reagent which consists of a mouse monoclonal antibody specific for valproic acid. The technology is based on competition between the valproic acid in the sample and valproic acid coated onto the microparticles, for the antibody-binding sites of the anti-Valproic Acid antibody reagent. In the absence of valproic acid in the sample, the specific antibody in the antibody reagent binds the valoroic acid on the particle, and results in rapid agglutination of the microparticles. In the presence of valproic acid in the sample, the valproic acid in the sample competes for antibody binding sites of the specific antibody in the antibody reagent, and partially inhibits the agglutination of the microparticles. The rate of agglutination (turbidity) is directly proportional to the rate in absorbance change of incident light and is measured spectrophotometrically by the Abbott AEROSET® System at a wavelength of 604 nm. A six level Seradyn QMS™ / MULTIGENT™ Valproic Acid Calibrator set, with known valproic acid concentrations is used to quantitate the assay. An internal concentrationdependent calibration curve is generated by the AEROSET® System, by measuring the rate of absorbance change of each calibrator level. Maximum absorbance rate is at the lowest valproic acid concentration and the lowest absorbance rate at the highest valproic acid concentration. By monitoring the change in rate of a specimen with unknown valproic acid concentration, and comparing to the internal calibration curve, a sample's concentration can readily be obtained and reported as valproic acid concentration in either ug/mL or umol/L.
Here's a breakdown of the Seradyn QMS™/MULTIGENT™ Valproic Acid assay's acceptance criteria and the studies performed to demonstrate its performance:
1. Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Specificity (Cross-Reactivity) | No explicit overall acceptance criteria stated, but individual cross-reactivity percentages are evaluated. | For major metabolites and related compounds, most show very low or negative cross-reactivity: 3-keto-valproic acid: 4.80%2-N-Propylglutaric Acid: 6.63%2-N-Propyl-4-pentenoic Acid: 31.13%2-Ethyl-2-phenylmalonamide: -0.63%Carbamazepine: -0.77%Ethosuximide: 0.06%Phenobarbital: 0.76%Phenytoin: 0.22%Carbamazepine-10,11-epoxide: -0.41%Primidone: -0.20%Salicylate: -1.49% |
| Accuracy by Recovery | 100 ± 10% of theoretical value | 100% (at 144.51 µg/mL target): 100%50% (at 72.25 µg/mL target): 102.6%25% (at 36.13 µg/mL target): 104.7% |
| Sensitivity (Least Detectable Dose) | Not explicitly stated but comparison is made to predicate device. | 3.0 µg/mL (20.79 µmol/L) |
| Accuracy & Linearity by Dilution | 100 ± 10% of theoretical value (for recovery) | Recovery: Neat (150 µg/mL): 96.8%80% (120 µg/mL): 95.5%60% (90 µg/mL): 99.2%40% (60 µg/mL): 100.2%20% (30 µg/mL): 109.3%10% (15 µg/mL): 98.0%2.5% (3.75 µg/mL): 98.9% |
| Linearity: y = 0.9569x + 1.688; R = 0.999 | ||
| Precision | Not explicitly stated, but results are provided for various levels of precision. | Sample 1 (Mean 32.81 µg/mL): Within Run CV(%) 1.10%, Between Day CV(%) 1.56%, Run to Run CV(%) 0.00%, Total CV(%) 1.91% |
| Sample 2 (Mean 70.56 µg/mL): Within Run CV(%) 1.03%, Between Day CV(%) 0.90%, Run to Run CV(%) 0.27%, Total CV(%) 1.40% | ||
| Sample 3 (Mean 116.40 µg/mL): Within Run CV(%) 1.90%, Between Day CV(%) 1.37%, Run to Run CV(%) 1.30%, Total CV(%) 2.68% | ||
| Method Comparison | Not explicitly stated, but statistical comparison against predicate device is provided. | Correlation Coefficient (R) = 0.986, Slope = 0.955, y-intercept = 3.58 |
| Interfering Substances | Recoveries of 100 ±10% for hemoglobin, bilirubin, and lipids. | Bilirubin (20 mg/dL): 99.5% recoveryHemoglobin (1,000 mg/dL): 100% recoveryIntralipid (2,000 mg/dL): 99% recovery |
| HAMA Interference | Recovery of 100 ±10% | Control: 100% recoveryHAMA 1: 93% recoveryHAMA 2: 96% recovery |
| Instrument On-board Stability | N/A (demonstrated to be acceptable for claim) | Acceptable data for a claim of 54 days (one re-calibration required). |
| Instrument Calibration Stability | N/A (demonstrated to be acceptable for claim) | Acceptable data for a claim of 27 days. |
2. Sample Sizes and Data Provenance for Test Set
- Specificity (Cross-Reactivity): Each substance was tested in triplicate using control sera and spiked samples. The precise number of unique control sera or spiked samples is not specified beyond "control sera and spiked samples."
- Accuracy by Recovery: Tested at three different concentrations of valproic acid added to human serum. The number of samples for each concentration is not specified beyond "human serum."
- Sensitivity (Least Detectable Dose): Not explicitly stated, derived from statistical analysis of low concentration measurements.
- Accuracy & Linearity by Dilution: A 150.0 µg/mL VPA Calibrator was diluted to 80%, 60%, 20%, 10%, and 2.5%. Each diluted sample, as well as the undiluted calibrator, was analyzed in duplicate.
- Precision: A tri-level human serum-based commercial control was assayed in duplicate twice a day for twenty days. This means 80 measurements (3 levels * 2 duplicates/day * 20 days / 3 levels = 80 measurements per sample level).
- Method Comparison: 53 clinical specimens. Data provenance is not specified (e.g., country of origin, retrospective/prospective), but they are "clinical specimens," suggesting they are from real patients.
- Interfering Substances: For each interferent (bilirubin, hemoglobin, Intralipid), a human serum pool containing valproic acid was tested with and without the interferent. The interferent concentrations were tested twice (n=2 in the table).
- HAMA Interference: A normal human serum pool (control), and HAMA type 1 and HAMA type 2 samples were spiked with valproic acid. Each sample was assayed in duplicate.
Data Provenance: The studies appear to be laboratory-based analytical performance studies conducted by the device manufacturer (Seradyn, Inc.). The document does not specify countries of origin for samples or whether data was retrospective or prospective, but the nature of the tests suggests prospective analytical validation.
3. Number of Experts and Qualifications for Ground Truth
Not applicable. This device is an in-vitro diagnostic test for quantifying a chemical compound (valproic acid) in patient samples. The "ground truth" for the test set is established by known concentrations of valproic acid in controls, calibrators, or spiked samples, or by comparison to a legally marketed predicate device (Abbott AxSYM® Valproic Acid assay) which itself has established analytical accuracy. It does not involve human interpretation like in medical imaging.
4. Adjudication Method for Test Set
Not applicable for chemical assays. Ground truth is established by the known concentrations of calibrators, controls, or by direct comparison to a reference method or predicate device, not by expert consensus or adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is an automated in-vitro diagnostic assay for quantitative measurement. It does not involve human readers interpreting cases or AI assistance in human interpretation.
6. Standalone (Algorithm Only) Performance
Yes, the studies reported are for the standalone analytical performance of the Seradyn QMS™/MULTIGENT™ Valproic Acid assay on the Abbott AEROSET® System. There is no human-in-the-loop performance described for this type of device.
7. Type of Ground Truth Used
The ground truth for the analytical validation studies was primarily established by:
- Known concentrations: For accuracy (recovery, linearity by dilution), precision, and sensitivity, valproic acid concentrations were either precisely known (e.g., calibrators, spiked samples).
- Comparison to a predicate device: For method comparison, the results were compared against the Abbott AxSYM® Valproic Acid assay, which is a legally marketed device cleared under K941615, establishing the "truth" for equivalency.
8. Sample Size for the Training Set
Not applicable. This device is an analytical assay, not an AI/ML model that undergoes a "training set" development phase in the conventional sense. Its performance is based on the inherent chemical and optical properties of the reagents and the instrument, which are developed and optimized through traditional analytical chemistry and engineering principles, not machine learning.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of AI/ML for this type of chemical assay. The assay's "calibration" is performed using a six-level Seradyn QMS™/MULTIGENT™ Valproic Acid Calibrator set with known valproic acid concentrations. An internal concentration-dependent calibration curve is generated by the AEROSET System using these calibrators. This is standard practice for quantitative analytical assays.
§ 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.