(143 days)
For in vitro diagnostic and laboratory professional use.
VITROS Chemistry Products PHBR Slides quantitatively measure phenobarbital (PHBR) concentration in serum and plasma (lithium heparin) using the automated VITROS 5600 Integrated System.
Measurements obtained by this device are used as an aid in the diagnosis and treatment of phenobarbital use or overdose and in monitoring levels of phenobarbital to help ensure appropriate therapy.
The VITROS PHBR Slide is a multilayered, analytical element coated on a polyester support. The phenobarbital assay is based on an enzymatic heterogeneous, competitive immunoassay format. Immobilized anti-phenobarbital antibody and phenobarbital-peroxidase conjugate are present in the spreading layer.
A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Phenobarbital in the sample competes with the phenobarbitalperoxidase conjugate for a limited number of antibody binding sites during Incubation 1. The subsequent addition of 12 µL of VITROS Immuno-Wash Fluid to the slide removes unbound phenobarbital-peroxidase conjugate from the read area, while also providing a substrate for the enzyme mediated oxidation of leuco dye.
The rate of dye formation, as monitored by reflectance spectrophotometry for Incubation 2, is inversely proportional to the phenobarbital concentration in the sample. To determine if an adequate wash has occurred, a wash detection dye is read at 540 nm during Incubation 2.
Here's an analysis of the provided FDA 510(k) summary, specifically focusing on the acceptance criteria and study proving the device meets those criteria, formatted as requested:
Device: VITROS Chemistry Products PHBR Slides
Device Type: In vitro diagnostic device for quantitative measurement of phenobarbital (PHBR) concentration in serum and plasma.
1. Table of Acceptance Criteria and Reported Device Performance
The FDA 510(k) summary outlines several analytical performance characteristics that serve as acceptance criteria for the VITROS Chemistry Products PHBR Slides. The document doesn't explicitly state "acceptance criteria" for all metrics in the form of numerical thresholds before the study results, but rather presents the study results as meeting acceptable performance for substantial equivalence. For some, like LoQ, a specific goal is mentioned.
| Performance Characteristic | Acceptance Criterion (Implicit/Explicit) | Reported Device Performance |
|---|---|---|
| Method Comparison | Demonstrate substantial equivalence to predicate device (ARCHITECT iPhenobarbital Assay) via Passing-Bablok Regression. Implied criteria for acceptable slope and correlation coefficient close to 1, and low intercept. | N=142 samples. Slope: 0.92, Correlation Coefficient: 0.983, Intercept: -2.0 µg/mL, Sv.x: 2.6. Range of Samples: 5.6 - 76.1 µg/mL. |
| Precision | Demonstrate acceptable repeatability and within-lab precision (low %CV and SD). No explicit numerical criterion stated, but implied to be within industry standards for clinical chemistry assays of this type for therapeutic drug monitoring. | Repeatability: PHBR conc. (µg/mL) / SD / %CV |
| 5.0 / 0.20 / 3.9% | ||
| 9.1 / 0.27 / 2.9% | ||
| 11.0 / 0.30 / 2.7% | ||
| 23.0 / 0.50 / 2.2% | ||
| 25.1 / 0.59 / 2.4% | ||
| 38.1 / 0.79 / 2.1% | ||
| 59.3 / 1.50 / 2.5% |
Within Lab: PHBR conc. (µg/mL) / SD / %CV
5.0 / 0.25 / 5.0%
9.1 / 0.33 / 3.6%
11.0 / 0.44 / 4.0%
23.0 / 0.65 / 2.8%
25.1 / 0.81 / 3.2%
38.1 / 1.09 / 2.9%
59.3 / 2.11 / 3.6% |
| Detection Limits (LoD) | Demonstrate a limit of detection low enough for clinical utility. No explicit numerical criterion stated prior to reporting. | LoD: 1.3 µg/mL |
| Detection Limits (LoQ) | Allowable error goal for LoQ: ≤ 1.5 µg/mL. | Claimed LoQ: 3.0 µg/mL. The study found the claimed LoQ to be acceptable within the ≤ 1.5 µg/mL total error goal. |
| Linearity | Deviation from linearity within allowable limits: ± 1.3 µg/mL at phenobarbital concentrations 10 µg/mL. | Demonstrated linearity over the measuring range of 3.0 - 80.0 µg/mL. LLLI: 0.5 µg/mL, ULLI: 83.5 µg/mL. Reported deviation from linearity was within the specified allowable deviations. |
| Specificity (Interference) | Bias > 1.8 µg/mL at approx. 15 µg/mL PHBR or bias > 5.2 µg/mL at approx. 50 µg/mL PHBR considered significant interference. Implied acceptance: most common substances should not interfere, or known interferences clearly identified and characterized. | Nine (9) substances showed interference (bias exceeding criteria) at specified concentrations relative to PHBR concentrations of 15 µg/mL or 50 µg/mL. Sixty-one (61) other test substances did not cause significant bias. |
| Cross-Reactivity | Characterize the cross-reactivity of structurally related compounds and common co-prescribed drugs. Implied acceptance: cross-reactivity is understood and characterized. | Cross-reactivity of 12 substances (e.g., amobarbital, mephobarbital, phenytoin) was evaluated. Results are provided for reference in the customer instructions for use (specific numerical results not provided in this summary). |
| Measuring Range | 3.0 – 80.0 µg/mL | 3.0 – 80.0 µg/mL |
2. Sample Sizes and Data Provenance
- Method Comparison: 142 serum samples.
- Precision: 88 observations (2 replicates per run, 2 runs per day over 22 days) using patient pools and quality control materials.
- Linearity: Fourteen proportionally related admixtures of low and high concentration fluids were tested, each in duplicate.
- Specificity (Interference) & Cross-Reactivity: Number of individual samples tested for each interferent/cross-reactant not explicitly stated, but the studies describe adding substances to serum samples.
- Training Set Sample Size: Not applicable based on the provided document. This is an IVD device measuring analyte concentration, not an AI/ML device requiring a training set for algorithm development in the traditional sense. The phrase "training set" is typically used for machine learning models.
- Data Provenance: Not specified in the provided text (e.g., country of origin, retrospective/prospective). Standard laboratory validation protocols (CLSI guidelines listed) imply controlled, often prospective, collection for such studies.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- Not applicable. The "ground truth" for this device (a quantitative diagnostic for phenobarbital concentration) is established by direct chemical measurement in the form of a reference method (the predicate device) or by known concentrations of prepared standards/controls. It does not involve expert interpretation or consensus in the way a diagnostic imaging AI might.
4. Adjudication Method for the Test Set
- Not applicable. This specific study does not involve human readers or interpretations that would require adjudication. Measurements are quantitative and compared to a reference method or known concentrations.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No. An MRMC study is typically performed for AI-assisted diagnostic imaging or similar scenarios where human readers make subjective interpretations. This document describes the analytical performance of an in vitro diagnostic device for measuring a chemical analyte, which is not subject to human reader variability in the same way.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- Yes, indirectly. The entire document describes the standalone analytical performance of the VITROS Chemistry Products PHBR Slides on the VITROS 5600 Integrated System. The device provides a quantitative measurement directly, without human interpretation in the loop that would alter the result itself. The measurements obtained are then used by laboratory professionals to aid in diagnosis and treatment, but the device's performance itself is evaluated as a standalone analytical instrument.
7. Type of Ground Truth Used
- Reference Method / Known Concentrations:
- For Method Comparison, the ground truth is established by the results from the legally marketed predicate device (ARCHITECT iPhenobarbital Assay) on the same patient samples.
- For Precision, Detection Limits, Linearity, Specificity, and Cross-Reactivity, the ground truth is established by using prepared samples with known, controlled concentrations of phenobarbital and/or interfering/cross-reacting substances.
8. Sample Size for the Training Set
- Not applicable. As explained in section 2, this is an IVD device for quantitative measurement, not an AI/ML device that requires a "training set" for algorithm development.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. No training set in the AI/ML sense. For analytical validation, ground truth is established by precisely prepared standards and controls, or by comparison to a validated reference method (like the predicate device).
§ 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.