(116 days)
The Access 25(OH) Vitamin D Total assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of total 25-hydroxyvitamin D [25(OH) vitamin D] levels in human serum and plasma using the UniCel DxI Immunoassay Systems. Results are to be used as an aid in the assessment of vitamin D sufficiency.
The Access 25(OH) Vitamin D Total Calibrators are intended to calibrate the Access 25(OH) Vitamin D Total assay for the quantitative determination of total 25-hydroxyvitamin D [25(OH) vitamin D] levels in human serum and plasma using the UniCel DxI Immunoassay Systems.
The Access 25(OH) Vitamin D Total for use on the UniCel DxI Immunoassay System, The Access 25(OH) Vitamin D Total Calibrators for use on the UniCel DxI Immunoassay System, and the UniCel DxI Immunoassay analyzer comprise the Access Immunoassay System for the quantitative determination of total 25-hydroxyvitamin D [25(OH) vitamin D] levels in human serum and plasma.
The Access 25(OH) Vitamin D Total assay is a two-step sequential competitive binding immunoenzymatic assay. In the initial incubation, sample is added to a reaction vessel with a vitamin D binding protein (DBP) releasing agent and paramagnetic particles coated with sheep monoclonal anti-25(OH) vitamin D antibody. 25(OH) vitamin D is released from DBP and binds to the immobilized monoclonal anti-25(OH) vitamin D on the solid phase. Subsequently, a 25(OH) vitamin D analogue-alkaline phosphatase conjugate is added which competes for binding to the immobilized monoclonal anti-25(OH) vitamin D. After a second incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate Lumi-Phos 530 is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is inversely proportional to the concentration of 25(OH) vitamin D in the sample. The amount of analyte in the sample is determined from a stored, multi-point calibration curve.
The provided text describes the Beckman Coulter Access 25(OH) Vitamin D Total assay, an in vitro diagnostic immunoassay system cleared by the FDA through the 510(k) pathway. This pathway establishes substantial equivalence to a predicate device, rather than proving a new device meets specific acceptance criteria based on established ground truth in the same way a de novo or PMA would. Therefore, the information provided focuses on comparative performance against a predicate and a reference method, rather than pre-defined acceptance criteria against a clinical ground truth.
Here's an interpretation of the available information regarding acceptance criteria and supporting studies, framed as closely as possible to your request:
1. Table of Acceptance Criteria and Reported Device Performance
Since this is a 510(k) submission, the "acceptance criteria" are implied by the need to demonstrate substantial equivalence to the predicate device and acceptable analytical performance. The document doesn't explicitly state "acceptance criteria" numerical targets in the same way a clinical trial might, but rather describes the results of analytical studies showing performance characteristics.
| Performance Metric | Implied "Acceptance Criteria" (Demonstrate equivalence / acceptable analytical performance) | Reported Device Performance (Access 25(OH) Vitamin D Total) |
|---|---|---|
| Method Comparison (vs. Predicate) | Strong correlation with predicate device | Correlation coefficient of 0.88 (Passing-Bablok analysis) |
| Method Comparison (vs. Reference Method) | Strong correlation with Reference Measurement Procedure (RMP) | Slope of 0.99 and correlation coefficient of 0.94 (vs. NIST-Ghent ID-LC-MS/MS RMP) |
| Imprecision (Total CV) | ≤ 10.0% for concentrations > 15.0 ng/mL | Ranged from 4.2% to 9.3% |
| Imprecision (Total SD) | ≤ 1.5 ng/mL for concentrations ≤ 15.0 ng/mL | Ranged from 0.7 to 1.3 ng/mL |
| Linearity | Demonstrate linearity across the measuring range | Demonstrated linearity from 7.0 ng/mL to 120 ng/mL |
| Limit of Blank (LoB) | Established LoB for assay | 1.50 ng/mL (Highest observed with no analyte: 0.98 ng/mL) |
| Limit of Detection (LoD) | Established LoD for assay | 2.00 ng/mL (Lowest detectable with 95% probability: 1.47 ng/mL) |
| Limit of Quantitation (LoQ) | Established LoQ for assay (e.g., %CV of 20%) | 7.0 ng/mL (Lowest quantifiable with 20% CV: 4.4 ng/mL) |
| Analytical Specificity (Interference) | No significant interference from normal blood constituents/common medications | No interference from normal human blood constituents and common medications; Hemoglobin up to 0.5 g/L without interference |
| Cross Reactivity | Limited or acceptable cross-reactivity | Paricalcitol caused falsely elevated results; other cross-reactants did not cause interference |
2. Sample Size and Data Provenance
- Test Set for Method Comparison (vs. Predicate): 278 samples
- Test Set for Method Comparison (vs. Reference Method): 110 samples
- Test Set for Imprecision: Specific sample numbers not explicitly stated, but "representative studies" were performed with multiple concentrations.
- Test Set for LoB, LoD, LoQ, Linearity, Analytical Specificity, Cross Reactivity: Not explicitly stated as "test sets" with distinct sample counts, but rather as results from specific analytical experiments.
- Population Observation Group (for typical concentration range): 367 apparently healthy male and female adults.
- Data Provenance: The document does not explicitly state the country of origin for the samples. The studies are described as analytical validation studies performed by the manufacturer (Beckman Coulter). The reference method (NIST-Ghent ID-LC-MS/MS) suggests an international reference, but the origin of the samples used in comparison to it is not specified. The context of a US FDA submission suggests the intent for US regulatory compliance. The studies are prospective in nature, as they involve testing the device's performance characteristics.
3. Number of Experts and their Qualifications for Ground Truth
- For Method Comparison (vs. Predicate): The "ground truth" is effectively the results obtained from the predicate device (DiaSorin LIAISON 25 OH Vitamin D Total Assay). This predicate device's performance would have been established previously, but no expert review of its results is mentioned for this study.
- For Method Comparison (vs. Reference Method): The "ground truth" is the NIST-Ghent ID-LC-MS/MS Reference Measurement Procedure (RMP). This is a highly accurate and standardized analytical method, a "gold standard" in laboratory measurement, and does not involve human expert interpretation in the diagnostic sense (like a radiologist reading an image). It's a laboratory-based, instrumental reference method.
- For other analytical studies (Imprecision, Linearity, LoB, LoD, LoQ, Specificity, Cross-reactivity): The "ground truth" is defined by the experimental setup and the known concentrations or characteristics of the samples used (e.g., control samples with known concentrations, samples spiked with interferents). No human experts are used to establish ground truth in this context.
4. Adjudication Method for the Test Set
Not applicable. Diagnostic immunoassay studies for 510(k) clearance typically do not involve human adjudication in the way clinical studies for imaging or histology might. The "ground truth" is based on the performance of a reference method or predetermined analytical characteristics.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This type of study (MRMC, human-in-the-loop performance) is not applicable to an automated immunoassay device. The device provides a quantitative numerical result, not an interpretation that radiologists or other human readers would perform.
6. Standalone (Algorithm Only) Performance
Yes, the studies described are standalone performance evaluations of the Access 25(OH) Vitamin D Total assay. The device itself performs the measurement and produces the result without human intervention for interpretation beyond operating the instrument and collecting the sample.
7. Type of Ground Truth Used
- Predicate Device Performance: For the primary substantial equivalence comparison.
- Reference Measurement Procedure (RMP): Specifically, the NIST-Ghent ID-LC-MS/MS for the 25(OH) Vitamin D ID LC-MS/MS (a highly accurate and standardized laboratory method). This is considered a highly reliable analytical "ground truth".
- Known Sample Characteristics: For analytical characteristics like linearity, limits of detection/quantitation, specificity, and cross-reactivity, ground truth is established by using control materials, spiked samples, or samples with otherwise analytically verified characteristics.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI. This immunoassay system is a hardware-based diagnostic device with chemical reagents, and its "training" refers to its analytical calibration and development, not algorithm training.
The closest analogy would be the samples used to develop and refine the assay's performance characteristics and define its calibration curve. However, specific numbers for this purpose are not provided. The development process would involve numerous samples, but these are distinct from a "training set" as understood in a machine learning context.
9. How the Ground Truth for the Training Set was Established
As discussed above, an explicit "training set" with ground truth in the AI sense is not applicable. The assay is based on established chemiluminescent immunoassay principles. The "calibration curve" for the device is established using calibrators with known concentrations of 25(OH) Vitamin D. These calibrator concentrations would be precisely determined through highly accurate reference methods, likely similar to the NIST-Ghent ID-LC-MS/MS RMP. The document states "The Access 25(OH) Vitamin D Total Calibrators are intended to calibrate the Access 25(OH) Vitamin D Total assay," and list 6 calibrator levels (0, 6, 17, 37, 87, and 210 ng/mL) containing human serum with 25(OH) vitamin D. The ground truth for these calibrators would be established through a rigorous metrological chain to a primary reference standard.
§ 862.1825 Vitamin D test system.
(a)
Identification. A vitamin D test system is a device intended for use in clinical laboratories for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). Vitamin D test systems must comply with the following special controls:(1) Labeling in conformance with 21 CFR 809.10 and
(2) Compliance with existing standards of the National Committee on Clinical Laboratory Standards.