(35 days)
The Access Free T4 assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of free thyroxine levels in human serum and plasma (heparin) for the diagnosis and treatment of thyroid diseases using the Access Immunoassay Systems.
Assay type: two-step, competitive
The Access Free T4 assay is a two-step enzyme immunoassay. The Access Free T4 assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access Free T4 reagent pack, Access Free T4 calibrators, along with Wash Buffer II are designed for use with the Access Immunoassay Systems in a clinical laboratory setting.
The Access Free T4 contains the following components:
- R1a: Dynabeads paramagnetic particles coated with streptavidin and mouse monoclonal anti-Thyroxine (T4) coupled to biotin; preservative
- R1b: TRIS buffered saline with protein (avian), surfactant, preservative
- R1c: TRIS buffered saline with protein (avian), surfactant, preservative.
- R1d: Triiodothyronine-alkaline phosphatase (bovine) conjugate in a TRIS buffer with protein (avian), surfactant, preservative.
- R1e: TRIS buffer with protein (avian and murine), surfactant, preservative
The provided 510(k) summary describes the Access Free T4 assay, a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of free thyroxine levels in human serum and plasma for the diagnosis and treatment of thyroid diseases.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The document outlines acceptance criteria and performance for several studies.
| Study Type | Acceptance Criteria | Reported Device Performance (Access 2 / Dxl 9000 Immunoassay Analyzer) |
|---|---|---|
| Method Comparison | Slope 1.00 ± 0.12 | Access 2: Slope = 1.02 (95% CI: 1.00 to 1.04), Correlation Coefficient R = 0.98. Dxl 9000: Slope = 1.02 (95% CI: 0.99 to 1.05), Correlation Coefficient R = 0.95. Both devices met the acceptance criteria. |
| Imprecision | Within-laboratory (total) %CV ≤ 10.0% for values ≥ 0.61 ng/dL. Within-laboratory (total) SD ≤ 0.06 for concentrations =0.61 ng/dL, but it is below 0.61 ng/dL so the SD criteria applies, and 0.05 is below 0.06).** Samples 2-5 (0.92 - 4.3 ng/dL): Within-lab %CVs 3.3% - 4.6%. Overall, the performance seems to meet the criteria for all samples based on the appropriate metric (SD for low conc., %CV for high conc). | |
| Linearity | The assay should demonstrate linearity across the measuring interval. Measuring interval: Access 2: 0.40 - 6.0 ng/dL. Dxl 9000: 0.32 - 6.0 ng/dL. | A study based on CLSI EP06-Ed2 determined the assay demonstrated linearity across the measuring interval for both instruments. No specific quantitative linearity results (e.g., coefficient of determination) are provided, but the statement indicates success. |
| Analytical Specificity | Change in concentration between control and test sample within specified percentages for various cross-reactants (e.g., D-T4: ≤ 100%, L-T3: ≤ 2%, R-T3: ≤ 25%, etc.). | Testing was performed with various cross-reactants. The document states that the observed changes in concentration met the specified acceptance criteria for all tested cross-reactants. |
| Interference (Common Substances) | Change in concentration between the control sample and the test sample within ± 10%. | No significant interference (± 10%) was observed for any of the tested interferents at their highest concentrations (e.g., Albumin, Aspirin, Bilirubin, Biotin, Hemoglobin, Lipemia, Methimazole, Phenylbutazone, Phenytoin, Prealbumin, Sodium Salicylate, Thiouracil, Thyroxine Binding Globulin). The specific concentration for Biotin interference was 3,510 ng/mL (previous device was ≤ 10 ng/mL). |
| Sample Type Comparison | For determination of equivalency between sample types, the results should be comparable. (Implied acceptance based on Passing-Bablok regression with slopes near 1 and tight CIs). | Access 2 (Serum vs. LiHep Plasma): N=41, Estimate (slope) = 0.99, 95% CI: 0.94 - 1.04. Dxl 9000 (Serum vs. LiHep Plasma): N=43, Estimate (slope) = 0.97, 95% CI: 0.93 - 0.99. Both instruments show good agreement between serum and lithium heparin plasma. |
| Detection Capability (LoB, LoD, LoQ) | Established limits based on CLSI guideline EP17-A2. | Access 2: LoB = 0.25 ng/dL, LoD = 0.40 ng/dL, LoQ = 0.40 ng/dL. Dxl 9000: LoB = 0.25 ng/dL, LoD = 0.32 ng/dL, LoQ = 0.32 ng/dL. The results are listed and implicitly met the established limits for these studies. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Method Comparison: 163 serum samples.
- Imprecision: For both Access 2 and Dxl 9000, "multiple samples" were tested in duplicate in 2 runs per day for a minimum of 20 days. The tables show
Nvalues per sample type ranging from 80 to 84 (representing the total number of replicates over the 20+ days for each control sample). - Detection Capability (LoB, LoD, LoQ): "multiple reagent lots and 3 instruments over a minimum of 3 days" (LoB) and "multiple reagent lots and 3 instruments over a minimum of 5 days" (LoD, LoQ).
- Analytical Specificity: Serum samples with two concentrations of Free T4, tested in replicates of six each.
- Interference: Patient serum samples with two levels of Free T4, with 6 to 12 replicates tested for each control sample preparation.
- Sample Type Comparison: A minimum of 40 matched sets of patient samples were tested with each reagent lot. Specifically, 41 matched sets for Access 2 and 43 matched sets for Dxl 9000 were reported.
Data Provenance: The document does not explicitly state the country of origin of the data or whether it was retrospective or prospective. Given the nature of these clinical performance studies for an in vitro diagnostic device, it is typically prospective, involving controlled testing in a laboratory setting with collected human samples. The term "patient serum samples" suggests human origin.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This section is not applicable to this type of device (in vitro diagnostic immunoassay). The "ground truth" for an immunoassay is typically established by reference methods, consensus methods, or highly characterized samples, not by expert human readers. The predicate device itself acts as a comparative standard in the method comparison study.
4. Adjudication Method
This section is not applicable for this type of device as there is no human interpretation or decision-making process that would require adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
This section is not applicable. This device is an automated immunoassay for quantitative determination of a specific analyte (Free T4), not an imaging or diagnostic device that relies on human reader interpretation (with or without AI assistance).
6. Standalone Performance Study
Yes, the entire set of studies described (Method Comparison, Imprecision, Detection Capability, Linearity, Analytical Specificity, Interference, Sample Type Comparison) represents the standalone performance of the modified device (Access Free T4) when compared against the predicate device or a recognized standard (e.g., CLSI guidelines). The performance metrics provided (slope, correlation, %CV, SD, LoB, LoD, LoQ, % difference) quantify the device's accuracy, precision, and analytical characteristics.
7. Type of Ground Truth Used
The ground truth used depends on the specific study:
- Method Comparison: The predicate device (Access Free T4 Assay on the Access Immunoassay Analyzer K982250) served as the comparator or "reference" for comparison.
- Imprecision: Statistical methods define precision (e.g., repeatability, within-laboratory variability). Control samples with known target values serve as the basis for evaluation.
- Detection Capability (LoB, LoD, LoQ): These limits are derived statistically from measurements of blank samples and low-concentration samples.
- Linearity: Expected proportional changes in analyte concentration across a range are compared against measured values.
- Analytical Specificity and Interference: Known concentrations of potential cross-reactants or interferents added to serum samples with known Free T4 levels are used. The "true" effect is zero interference/cross-reactivity.
- Sample Type Comparison: Matched patient samples (serum vs. plasma) are used, where the expectation is agreement between results from different sample matrices from the same individual.
8. Sample Size for the Training Set
This document only describes analytical performance studies for the modified device. There is no mention of a "training set" in the context of machine learning or AI, as this is an immunoassay device, not a software algorithm that would typically undergo a training phase.
9. How the Ground Truth for the Training Set Was Established
This is not applicable as there is no training set for this type of device.
§ 862.1695 Free thyroxine test system.
(a)
Identification. A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(b)
Classification. Class II.