(297 days)
Reagent: for in vitro diagnostic use in the quantitative determination of β2-microglobulin in human serum or plasma (lithium heparin and potassium EDTA) on ADVIA® 1650 Chemistry systems. The ADVIA 1650 Chemistry 32-Microglobulin (B2M) assay aids in the diagnosis of active rheumatoid arthritis and kidney disease.
Calibrators: for in vitro diagnostic use in the calibration of ADVIA® Chemistry systems for the ADVIA Chemistry β2-Microglobulin method.
The ADVIA 1650 Chemistry 32-Microglobulin (B2M) assay sample is diluted and reacted with a buffer that contains latex particles coated with antibody specific for ß2microglobulin. The formation of the antibody-antigen complex during the reaction results in an increase in turbidity, the extent of which is measured as the amount of light absorbed at 545 nm. The ß2-Microglobulin concentration in a sample is determined by constructing a standard curve from the absorbance of a reagent blank and a single-level calibrator.
The ADVIA Chemistry B2-Microglobulin Calibrator is a single analyte, lyophilized, buffer based product containing bovine serum albumin and human ß2-Microglobulin. The kit consists of 3 vials of a single level calibrator. The calibrator requires reconstitution with 1 mL of distilled water prior to use.
Here's an analysis of the provided text regarding the acceptance criteria and study for the ADVIA Chemistry β2-Microglobulin reagent:
Acceptance Criteria and Device Performance
The document does not explicitly state pre-defined acceptance criteria in a dedicated section. However, the "Performance" section (Section 5, 6, 7, 8) outlines the studies conducted and their results, implying that these results met the criteria for substantial equivalence to the predicate device.
Based on the studies described, the implied acceptance criteria and reported device performance are summarized below:
| Performance Characteristic | Implied Acceptance Criteria (relative to predicate) | Reported Device Performance (ADVIA 1650 Chemistry β2-Microglobulin assay) |
|---|---|---|
| Analytical Sensitivity (LoD) | Limit of Detection (LoD) should be adequate for intended use and comparable to predicate. | LoD = 0.25 mg/L |
| Analytical Sensitivity (LoB) | Limit of Blank (LoB) should be adequate for intended use and comparable to predicate. | LoB = 0.20 mg/L |
| Imprecision (Total CV%) | Within acceptable biological and analytical variability for the analyte, and comparable to predicate. | Levels: 0.74 mg/L (3.3%), 1.77 mg/L (2.6%), 3.68 mg/L (2.4%), 12.52 mg/L (2.1%) |
| Interfering Substances | No significant interference (NSI) for common interferents at specified concentrations, defined as a percentage effect ≤ 10%. | NSI for most tested substances at specified levels. Exceptions: Ascorbic Acid at 100 mg/dL (-15.3%) and 200 mg/dL (-13.4%). |
| Method Comparison (Correlation) | Strong correlation (high 'r' value) and good agreement (slope close to 1, y-intercept close to 0) with the predicate device. | n=88, r=0.99, Slope=1.03, Y-int=-0.38 (vs. Siemens N Latex β2-Microglobulin) |
| Serum/Plasma Equivalency | No significant differences between different sample tube types (serum vs. potassium EDTA, serum vs. lithium heparin). | Potassium EDTA: N=57, y = 1.00x - 0.04, Sy.x=0.19, r=0.99 |
| Lithium Heparin: N=57, y = 1.01x + 0.01, Sy.x=0.21, r=0.99 | ||
| (No significant differences observed) |
Study Details
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Sample sizes used for the test set and the data provenance:
- Analytical Sensitivity (LoD/LoB): 60 replicates of a blank sample, 60 replicates of a low serum sample.
- Imprecision: 4 serum-based samples, tested 2 times per run, 2 runs per day, for at least 20 days (resulting in n=80 per level).
- Interfering Substances: Multiple concentrations of β2-microglobulin (approx. 1, 3, and 11 mg/L) tested with various concentrations of interferents.
- Method Comparison: 88 serum samples.
- Serum/Plasma Equivalency: 57 matched specimens (serum, potassium EDTA plasma, lithium heparin plasma).
Data Provenance: The document does not explicitly state the country of origin for the data or whether it was retrospective or prospective. It implies the studies were conducted by Siemens Healthcare Diagnostics. Given the context of a 510(k) submission, these would typically be controlled prospective studies conducted in a laboratory setting to demonstrate analytical performance.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This is a laboratory assay for quantitative determination of β2-microglobulin. The "ground truth" for such assays is established through analytical methods and verification against reference materials or established predicate devices, not via expert consensus or clinical adjudication as would be for diagnostic imaging or clinical decision support systems. Therefore, the concept of "experts" to establish ground truth in the traditional sense doesn't apply here. The accuracy of the analytical measurements and the comparison to a legally marketed predicate device (Siemens N Latex β2-Microglobulin) serve as the basis for performance evaluation. -
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
Not applicable to a laboratory diagnostic assay of this type. Adjudication is typically used in clinical studies or for subjective interpretations (e.g., radiology reads) where multiple human readers are involved. This study evaluates the quantitative performance of an automated assay. -
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 is a study for an in vitro diagnostic assay, not an AI-assisted diagnostic tool involving human readers. -
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the studies described are for the standalone analytical performance of the ADVIA 1650 Chemistry β2-Microglobulin assay. It's an automated process performed on an instrument, and the results presented represent the algorithm's (assay's) performance. There is no human-in-the-loop described in these performance evaluations. -
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The "ground truth" for this in vitro diagnostic assay is primarily:- Reference materials/standards: For analytical sensitivity (LoD/LoB) and potentially for calibrator values (traceability to WHO 1st International Standard is mentioned for the calibrator).
- Measurements from a legally marketed predicate device: For method comparison (correlation study).
- Known concentrations in spiked samples: For interfering substances studies.
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The sample size for the training set:
Not applicable. This is an in vitro diagnostic assay, not a machine learning model that requires a separate training set. The assay's parameters would have been developed and validated internally by the manufacturer through R&D, but there isn't a "training set" in the context of typical AI/ML studies. -
How the ground truth for the training set was established:
Not applicable, as there is no training set mentioned or implied in the context of an AI/ML model for this type of IVD device. The assay development involves chemical and biological principles, calibration, and optimization based on known analytical standards and performance targets.
§ 866.5630
Beta -2-microglobulin immunological test system.(a)
Identification. Abeta -2-microglobulin immunological test system is a device that consists of the reagents used to measure by immunochemical techniquesbeta -2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement ofbeta -2-microglobulin aids in the diagnosis of active rheumatoid arthritis and kidney disease.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.