(189 days)
The Abbott Phenobarbital assay is for in vitro diagnostic use for the quantitative measurement of phenobarbital in human serum or plasma on the ARCHITECT cSystems. The measurements obtained are used in the diagnosis and treatment of phenobarbital overdose and in monitoring levels of phenobarbital to help ensure appropriate therapy.
The Phenobarbital Assay kit is supplied ready-to-use in liquid form, for storage at 2 to 8°C. Each Phenobarbital Assay kit is packaged in a rectangular cardboard box divided into three sections. One section will contain three bottles of Antibody Reagent (R1), one section will contain three bottles of Microparticle Reagent (R2), and the last section will contain the package insert. Each kit is sufficient for 300 tests.
The Abbott Phenobarbital Assay demonstrated substantial equivalence to the predicate device (Abbott Aerosett Phenobarbital Assay (K993031)) through a series of performance studies. The studies assessed various analytical characteristics of the device to ensure it meets its intended use for the quantitative measurement of phenobarbital in human serum or plasma.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Limit of Quantitation (LOQ) | Inter-assay precision ≤ 7% CV or 0.7 µg/mL SD; Bias ≤ 10% or 1.0 µg/mL | LOQ is 2.0 µg/mL, meeting design acceptance criteria. |
| Precision | Total run %CV ≤ 6.7% | Total run %CV was less than or equal to 6.7%, meeting design acceptance criteria. |
| Spike Recovery | Recover within ±10% or ±1.0 µg/mL error of HPLC results | All samples recovered within ±10% or ±1.0 µg/mL error of the HPLC results. |
| Method Comparison (vs. HPLC) | Correlate well with HPLC (specific metrics implied but not explicitly stated as acceptance criteria, but shown to be strong) | y = 0.933x + 0.68, R = 0.9887, n=108. (Strong correlation observed) |
| Specificity (Cross-Reactivity) | Minimal to no cross-reactivity to other medications; Minimal to no interference from endogenous substances | Showed minimal to no cross-reactivity to other potentially administered medications. Showed minimal to no interference to endogenous substances up to the concentrations tested. |
| Linearity | Linear performance throughout the assay range (2.0 to 80 µg/mL) | Demonstrated linear performance from 2.0 to 80 µg/mL. |
| Onboard Stability | Stable for a specified period | Reagents stable onboard for up to 45 days. |
| Standard Curve Calibration Stability | Stable for a specified period | Standard curve calibration stable for up to 14 days. |
| Reagent Shelf Life Stability | Stable for a specified period | Reagents will be stable at 2-8°C for 24 months. |
2. Sample Size Used for the Test Set and Data Provenance
- Limit of Quantitation (LOQ): The text indicates the LOQ was measured "over an extended period" but does not specify the exact number of samples or runs.
- Precision: Not explicitly stated, but the study followed a CLSI protocol, which typically involves multiple samples tested over several runs and days.
- Spike Recovery: "Negative serum samples were spiked with phenobarbital at concentrations across the assay range." The exact number of samples is not stated.
- Method Comparison: 108 samples (n=108) were tested.
- Matrix Comparison: The following matrices were tested: serum in glass, serum in plastic, serum separator tube (SST) in plastic, plasma with sodium fluoride/potassium oxalate in plastic, plasma with sodium heparin in plastic and glass, plasma with lithium heparin in plastic with or without gel, plasma with K3 EDTA in glass and plastic, plasma with K2 EDTA in plastic, and sodium citrate in plastic and glass. The number of samples for each matrix is not specified.
- Specificity (Cross-Reactivity/Interference): Not explicitly stated, but implies multiple substances were tested across various concentrations.
- Linearity: "Samples were tested to demonstrate linearity throughout the assay range." The exact number of samples is not specified.
- Onboard Stability, Standard Curve Calibration Stability, Reagent Shelf Life Stability: These studies involve testing over time with an unspecified number of samples or replicates.
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of in vitro diagnostic device testing for regulatory submission, it is typically prospective, controlled laboratory studies using prepared samples (spiked, diluted, or well-characterized patient samples).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of submission for an in vitro diagnostic assay does not typically involve expert clinical readers or radiologists. The "ground truth" for the test set is established by:
- Reference Methods: For method comparison, High-Performance Liquid Chromatography (HPLC) results are used as the reference method ("gold standard") for phenobarbital concentration. This approach does not involve human expert interpretation in the same way imaging studies might.
- Known Concentrations: For studies like linearity, spike recovery, LOQ, and precision, samples are prepared with known, precisely measured concentrations of phenobarbital.
- CLSI Protocols: The reference to CLSI protocols indicates established laboratory standards are followed for experimental design and data analysis, ensuring the rigor of the "ground truth" establishment through standardized procedures.
Therefore, there are no "experts" in the clinical interpretation sense involved in establishing the ground truth; rather, the ground truth is analytically derived.
4. Adjudication Method for the Test Set
Not applicable. As described above, the ground truth is established through analytical reference methods or known sample compositions, not through human adjudication of clinical findings.
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
Not applicable. This device is an in vitro diagnostic assay for quantitative measurement, not an AI-assisted diagnostic imaging or clinical decision support tool that involves human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
The entire performance evaluation is inherently a "standalone" or "algorithm-only" assessment in the context of an automated IVD assay. The Abbott Phenobarbital Assay, once calibrated, quantifies phenobarbital concentration based on its reaction kinetics. The performance studies detailed are evaluating this standalone analytical performance.
7. The Type of Ground Truth Used
The ground truth used in these studies is primarily:
- Reference Method Assays: For method comparison, HPLC (High-Performance Liquid Chromatography) served as the reference method for confirming phenobarbital concentrations.
- Known Concentrations: For precision, linearity, LOQ, and spike recovery, samples were prepared with known, established concentrations of phenobarbital.
8. The Sample Size for the Training Set
The document describes performance testing for a finished device. It does not provide information about a "training set" in the context of machine learning, as this is a chemical assay, not an AI/ML device. Therefore, the concept of a training set as understood in AI/ML is not applicable here. The assay is "trained" or optimized during its development phase through iterative experimentation, but the data for this is not detailed in a 510(k) summary (which focuses on verification and validation).
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the AI/ML sense. The "ground truth" for the development and optimization of the assay would have been established through precisely prepared samples with known phenobarbital concentrations and comparisons to established analytical methods during the research and development phases of the assay.
§ 862.3660 Phenobarbital test system.
(a)
Identification. A phenobarbitol test system is a device intended to measure phenobarbital, an antiepileptic and sedative-hypnotic drug, in human specimens. Measurements obtained by this device are used in the diagnosis and treatment of phenobarbital use or overdose and in monitoring levels of phenobarbital to ensure appropriate therapy.(b)
Classification. Class II.