(234 days)
Immunological latex agglutination test for the in vitro quantitative determination of ß 2microglobulin in human serum and plasma.
Measurement of beta-2-microglobulin aids in the diagnosis of active rheumatoid arthritis and kidney disease.
The ß 2-microglobulin determination is based upon turbidimetric immunoinhibition (TINIA) using a serum or plasma blood sample. The sample containing B 2-microglobulin is transferred into a TRIS buffer solution (R1 reagent). In the second step, an aliquot of solution of polyclonal antirabbit ß 2-microglobulin antibodies (R2 reagent) is added to mixture of the first step. The antibody will bind to the ß 2-microglobulin in the sample to form "aggregates" such that the amount of aggregate formed is proportionate to the amount of B 2-microglobulin present in the sample. The resulting agglutination complex is measured turbidimetrically whereby increased turbidity is reflected through an increase in optical density. Therefore, the amount of ß 2-microglobulin in the sample is directly proportional to the amount of turbidity formed.
Here's an analysis of the provided text regarding the Tina-quant® ß 2-microglobulin Assay, structured to address your specific questions.
1. Table of Acceptance Criteria and Reported Device Performance
The submission doesn't explicitly state "acceptance criteria" in the format of a predefined pass/fail threshold for each performance characteristic. Instead, it presents performance data for the Tina-quant® ß 2-microglobulin assay and compares it to a predicate device (Abbott IMx® ß 2-microglobulin assay) to demonstrate substantial equivalence. Therefore, the "acceptance criteria" are implied to be the comparable performance to the legally marketed predicate device.
| Feature | Acceptance Criteria (Implied - Comparable to Predicate) | Tina-quant® ß 2-microglobulin Performance | Abbott IMx® ß 2-microglobulin Performance (Predicate) |
|---|---|---|---|
| Precision (Intra-Assay %CV) | Comparable to Predicate | Low: 4.4, Mid: 1.9, High: 1.0 | Low: 6.0, Mid: 4.4, High: 4.9 |
| Precision (Inter-Assay %CV) | Comparable to Predicate | Sample 1: 2.6, Sample 2: 2.7 | Low: 9.2, Mid: 6.8, High: 7.3 |
| Lower Detection Limit | Comparable to Predicate | 0.05 mg/L | 0.5 µg/L (0.0005 mg/L) |
| Linearity | Established, range defined | 0.20 - 8.0 mg/L | --- (Not explicitly stated in table) |
| Method Comparison (r-value) | High correlation with Predicate | r = 0.983 (Deming & Least Squares) | --- (Comparison done against this device) |
| Interfering Substances | No significant interference | No interference at defined conc. | --- (Not explicitly stated in table) |
| Specificity | Specific for target analyte | Specific for ß 2-microglobulin | Specific for ß 2-microglobulin |
Note on Lower Detection Limit: There appears to be a unit discrepancy (mg/L vs µg/L) between the Tina-quant® and Abbott IMx® in the table, but assuming the Tina-quant®'s 0.05 mg/L is a typo for 0.05 µg/L, this would suggest a comparable or better (lower) detection limit. If 0.05 mg/L is correct, then the predicate has a significantly lower detection limit. This is a point that would ideally need clarification for a full comparison. However, given the context of a 510(k) summary, the FDA found it substantially equivalent.
2. Sample Size Used for the Test Set and Data Provenance
- Precision Test Set (N values):
- Intra-Assay: 21 samples per level (Low, Mid, High) for Tina-quant®. 12 samples per level for Abbott IMx®.
- Inter-Assay: 21 samples per sample for Tina-quant® (Sample 1, Sample 2). 90 samples per level for Abbott IMx®.
- Method Comparison Test Set (N value): 36 samples.
- Data Provenance: Not explicitly stated (e.g., country of origin). The data presented is characteristic of laboratory studies performed with collected samples. It is not specified if the data is retrospective or prospective, but performance characteristic studies are typically prospective laboratory evaluations.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the given text. For an in-vitro diagnostic device like this, ground truth is typically established by:
- The concentration values of known controls or spiked samples in precision, linearity, and interference studies.
- The reference method (in this case, the Abbott IMx® device) for method comparison studies.
Therefore, "experts" in the traditional sense of clinical adjudication are not directly relevant here for establishing ground truth.
4. Adjudication Method for the Test Set
This information is not applicable/provided for this type of in-vitro diagnostic device. Clinical adjudication by experts is not a standard method for evaluating the performance characteristics (precision, linearity, method comparison) of an immunoassay. The comparison is done against a predicate device or defined reference values.
5. 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 device is an in-vitro diagnostic assay (a lab test), not an imaging or AI-assisted diagnostic tool that would involve human "readers" interpreting cases. Therefore, MRMC studies and AI assistance metrics are not relevant.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
The device is a laboratory assay. Its performance is inherently "standalone" in the sense that it provides a quantitative measurement based on chemical reactions, without direct human interpretation of complex images or data that an AI algorithm might produce. The "algorithm" is the immunoturbidimetric reaction principle itself. The performance data presented (precision, linearity, detection limit) directly represents the standalone performance of the assay.
7. The Type of Ground Truth Used
- Precision, Linearity, Interfering Substances: Ground truth would be based on known concentrations of beta-2-microglobulin in control materials, spiked samples, or serially diluted samples.
- Method Comparison: The ground truth for comparative purposes is derived from the results obtained from the predicate device (Abbott IMx® ß 2-microglobulin assay) on the same patient samples.
8. The Sample Size for the Training Set
Not applicable/provided. In-vitro diagnostic assays of this nature do not typically involve a "training set" in the machine learning sense. The assay's chemical reagents and methodology are developed and optimized through R&D, not by training on a dataset.
9. How the Ground Truth for the Training Set Was Established
Not applicable. As explained in #8, there is no "training set" or "ground truth for a training set" in the context of this immunoturbidimetric assay's development. The "ground truth" for developing such an assay would be the established chemical and biological principles of antibody-antigen reactions and turbidimetry, leading to the formulation and optimization of the reagents.
§ 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.