(62 days)
The DiaSorin LIAISON® Vitamin B12 assay uses chemiluminescent immunoassay (CLIA) technology for the quantitative determination of Vitamin B12 in human serum, SST serum and lithium heparin plasma. Measurements obtained by this device are used in the diagnosis and treatment of anemia's of gastrointestinal malabsorption. Assay results should be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions.
The assay must be performed on the LIAISON® XL Analyzer.
The LIAISON® Vitamin B12 assay is a competitive chemiluminescence immunoassay (CLIA) for quantitative determination of Vitamin B12 is serum. SST serum and lithium heparin plasma. During the first incubation, Vitamin B12 is dissociated from its binding protein. After the initial incubation of 10.5 minutes. Vitamin B12 binds to an intrinsic factor on the solid phase. After a second incubation of 10.5 minutes, a Vitamin B12 linked to an isoluminol derivative is added to compete with the Vitamin B12 in the sample. After a third incubation of 5.25 minutes, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added to initiate a flash chemiluminescent reaction. The light signal is measured by a photomultiplier as relative light units (RLU) and is inversely proportional to the concentration of Vitamin B12 present in calibrators, controls, or samples.
Here is the information about the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a tabulated format with specific pass/fail thresholds for each performance characteristic. Instead, it describes various performance studies and their results. The "reported device performance" below summarizes the key findings from these studies. It is implied that these findings meet the FDA's requirements for substantial equivalence.
| Performance Characteristic | Reported Device Performance |
|---|---|
| Method Comparison | LIAISON® Vitamin B12 = 0.97 (Reference Method) + 6.25; R = 0.985 (N=155). This indicates strong agreement with a commercially available reference method. |
| Sample Matrix Equivalence | SST serum vs. Serum (N=48): Constant Bias = 8.21 (95% CI: 2.14 to 16.56), Proportional Bias = 0.97 (95% CI: 0.94 to 0.99), R² = 0.996. |
| Lithium Heparin vs. Serum (N=48): Constant Bias = 14.78 (95% CI: 1.09 to 29.87), Proportional Bias = 1.10 (95% CI: 1.05 to 1.15), R² = 0.988. These results demonstrate equivalence across different sample types. | |
| Reference Range | Observed Range (N=166, US population): 107.2 pg/mL – 653.3 pg/mL (2.5th to 97.5th Percentile). Median: 318.5 pg/mL. Establishes expected values for a healthy population. |
| Precision | Intra-Run %CVs: Ranged from 3.4% to 5.2%. |
| Total %CVs: Ranged from 6.7% to 10.0% across 8 samples/controls with varying mean concentrations (240 pg/mL to 1262 pg/mL). Indicates good reproducibility and repeatability. | |
| Linearity | Serum: Observed Vitamin B12 = 1.076x + 6.896; R = 0.998 |
| SST Serum: Observed Vitamin B12 = 1.009x + 0.224; R = 0.999 | |
| Lithium Heparin plasma: Observed Vitamin B12 = 1.029x - 0.095; R = 0.996. Shows linearity across the measuring range. | |
| Recovery | Mean Recovery: 100% (Individual sample recoveries ranged from 95% to 106% across 5 high/low concentration pairs). Demonstrates accurate recovery of Vitamin B12. |
| Analytical Specificity (Cross-Reactivity) | Dicyanocobinamide (10,000 pg/mL): -0.19% Cross Reactivity. Shows minimal cross-reactivity with a related substance. |
| Analytical Specificity (Interference) | No interference demonstrated at specified high concentrations for Hemoglobin (300 mg/dL), Bilirubin (40 mg/dL), Triglycerides (3,000 mg/dL), Cholesterol (500 mg/dL), Albumin (12 g/dL), Human IgG (12 g/dL), HAMA (1387.5 ng/mL), Rheumatoid Factor (1035 IU/mL), Acetaminophen (20 mg/dL), Acetylsalicylic Acid (65 mg/dL), Ibuprofen (50 mg/dL), Biotin (2 mg/mL). |
| Limit of Blank (LoB) | ≤ 38.7 pg/mL |
| Limit of Detection (LoD) | 51.2 pg/mL |
| Limit of Quantitation (LoQ) | 55 pg/mL |
| Stability | Reagent Integral Open vial on system: 42 days |
| Reagent Integral Open vial 2-8°C: 28 days | |
| Calibration curve: 21 days | |
| Traceability | Traceable to an in-house standard preparation (pg/mL). |
2. Sample Sizes Used for the Test Set and Data Provenance
- Method Comparison: 155 samples. Data provenance not explicitly stated (e.g., country of origin) but implied to be patient samples. Retrospective or prospective is not specified, but typically method comparison uses existing samples.
- Sample Matrix Comparison: 48 matched patient sets (serum, SST serum, lithium heparin plasma samples). Data provenance not specified.
- Reference Range: 166 prospectively collected serum samples from apparently healthy adults aged 21-59. Provenance: United States; mixed ethnic backgrounds (30% Caucasian, 31% African Americans, 39% Hispanics). Prospective.
- Precision: Six (6) serum samples and two (2) kit controls.
- Linearity: One (1) high sample of each specimen type (serum, lithium heparin plasma).
- Recovery Study: Five (5) high concentration serum samples and five (5) low concentration serum samples.
- Cross-Reactivity Studies: Controlled spiked samples.
- Interference Studies: Controlled spiked samples.
- Limit of Blank, Limit of Detection, Limit of Quantitation: Not explicitly stated, typically involves multiple replicates of blank and low-concentration samples.
The document refers to various CLSI (Clinical and Laboratory Standards Institute) guidelines, which are commonly used for prospective, standardized studies in laboratory settings.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The concept of "experts" to establish "ground truth" as typically understood in AI/imaging studies (e.g., radiologists interpreting images) does not apply directly here. The ground truth for this device (a Vitamin B12 assay) is established through:
- Measurement by a commercially available reference method: For method comparison studies, the predicate device's results serve as a reference.
- Defined concentrations / spiking: For linearity, recovery, analytical specificity, and LoD/LoQ studies, the ground truth is based on accurately prepared samples with known concentrations.
- Clinical criteria: For the reference range study, healthy status was determined by inclusion/exclusion criteria related to medical history, medication use, and fasting status. These criteria are established by medical consensus, not by individual experts "adjudicating" each case.
Therefore, the number and qualifications of experts in the traditional sense are not applicable here.
4. Adjudication Method for the Test Set
Not applicable. As this is an in-vitro diagnostic (IVD) assay quantifying a biomarker, the "ground truth" is determined by established analytical methods, reference materials, or clinical definitions, rather than human interpretation requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for diagnostic imaging devices where human readers interpret medical images with and without AI assistance. This document describes an in-vitro diagnostic device that measures a biomarker in a laboratory setting, not an imaging device.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies described are standalone (algorithm/device only) performance studies. The entire document focuses on the analytical performance of the LIAISON® Vitamin B12 assay itself, without any human interpretation of its results being part of the primary performance evaluation. The device generates quantitative values for Vitamin B12, and its accuracy, precision, linearity, etc., are evaluated directly.
7. The Type of Ground Truth Used
The ground truth used varies by study:
- Method Comparison: "Reference Method" (another commercially available Vitamin B12 assay, the predicate device, Beckman Coulter Access Vitamin B12 assay, K140496).
- Sample Matrix Comparison: Comparison against its own measurement in serum, which is considered the reference matrix.
- Reference Range: Clinical criteria for "apparently healthy adults" (absence of anemias, B12 deficiency, IBD, celiac disease, malabsorption, specific medication use, pregnancy, etc.).
- Precision, Linearity, Recovery, Analytical Specificity (Cross-Reactivity & Interference), LoB, LoD, LoQ: Defined concentrations in spiked or diluted samples, or blank samples. These are established through gravimetric/volumetric preparation of standards and controls.
8. The Sample Size for the Training Set
The document does not provide information about a "training set" in the context of machine learning. This device is a chemiluminescent immunoassay (CLIA), which is a traditional laboratory analytical method, not an AI/machine learning algorithm that requires training data in the same way. The assay development would involve optimizing reagents and protocols, but this is a different process than "training" an algorithm.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as this device does not utilize a training set in the machine learning sense. The "ground truth" (i.e., known concentrations) during the development and optimization of such an assay would be established through primary analytical methods, reference materials, and standardized analytical practices during the assay's R&D phase.
§ 862.1810 Vitamin B
12 test system.(a)
Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.(b)
Classification. Class II.