(178 days)
Immunological in vitro immunoturbidometric test for the quantitative determination of x -1antitrypsin in human serum and plasma.
The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition, alpha-1-antitrypsin deficiency has been associated with pulmonary emphysema.
The α -1-antitrypsin determination is based upon turbidimetric immunoinhibition (TINIA) using a serum or plasma blood sample. The sample containing α -1-antitrypsin is transferred into a TRIS buffer solution (R₁ reagent). In the second step, an aliquot of solution of polyclonal anti-human α -1-antitrypsin antibodies (R₂ reagent) is added to mixture of the first step. The antibody will bind to the α -1-antitrypsin in the sample to form “aggregates” such that the amount of aggregate formed is proportionate to the amount of α -1-antitrypsin 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 α-1-antitrypsin in the sample is directly proportional to the amount of turbidity formed.
The Boehringer Mannheim Tina-quant® α-1-Antitrypsin Assay is an immunoturbidometric assay for the quantitative in-vitro determination of α-1-antitrypsin. The device was deemed substantially equivalent to the currently marketed Behring BN® α-1-Antitrypsin assay.
1. Table of Acceptance Criteria and Reported Device Performance:
The document primarily focuses on comparative performance against a predicate device rather than pre-defined acceptance criteria. However, we can infer performance characteristics evaluated for equivalence.
| Feature | Acceptance Criteria (Implied by Predicate Performance) | Reported Device Performance (Tina-quant® α-1-Antitrypsin) |
|---|---|---|
| Precision | Comparable to Behring BN® α-1-Antitrypsin | Intra-Assay (%CV): Low: 3.1, Pool: 2.5, High: 2.5 |
| (Behring BN® provided only a combined %CV of 5.3 for Inter-Assay) | Inter-Assay (%CV): Sample 1: 2.1, Sample 2: 2.0 | |
| Lower Detection Limit | Comparable to Behring BN® α-1-Antitrypsin (30 mg/dL) | 10 mg/dL (Better than predicate) |
| Method Comparison | Good correlation with Behring BN® α-1-Antitrypsin | Vs Behring BN®: |
| (Behring BN®: y = 0.88x + 30.2, r = 0.967, N = 59) | Passing/Bablok: y = 0.993x + 9.9, r = 0.967, SEE = 9.7, N = 123 | |
| Least Squares: y = 0.971x + 12.2, r = 0.967, SEE = 11.4, N = 123 | ||
| Interfering Substances | No significant interference with common substances | No interference (≤ 10% error) at: Bilirubin 60 mg/dL, Hemoglobin 1000 mg/dL, Lipemia 1000 mg/dL, Rheumatoid Factor 100 IU/mL |
| Specificity | Specific for α-1-antitrypsin | Specific for α-1-antitrypsin |
2. Sample Size Used for the Test Set and Data Provenance:
- Precision Test Set (Intra-Assay): N = 21 for each of the three levels (Low, Pool, High).
- Precision Test Set (Inter-Assay): Not explicitly stated, but "Sample 1" and "Sample 2" are mentioned. The Behring BN® Inter-Assay tested 244 samples.
- Method Comparison Test Set: N = 123 for comparison against the Behring BN® α-1-Antitrypsin.
- Interfering Substances Test Set: Not explicitly stated, but specific concentrations of bilirubin, hemoglobin, lipemia, and rheumatoid factor were tested.
- Data Provenance: The document does not specify the country of origin for the data or whether it was retrospective or prospective. Given the context of a 510(k) summary for a diagnostic test, it's highly likely to be prospective clinical or analytical studies conducted in a controlled lab environment.
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 document. For an immunoturbidometric assay, the "ground truth" would typically be established by reference methods or validated quantitative measurements rather than expert human interpretation.
4. Adjudication Method for the Test Set:
This information is not applicable as the ground truth is established by quantitative laboratory measurements, not through expert review that would require adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for imaging or diagnostic tools that rely on human interpretation. This device is an in-vitro diagnostic assay for quantitative measurement.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, this is a standalone performance study. The device is an automated in-vitro diagnostic assay that provides a quantitative measurement of α-1-antitrypsin. Its performance is evaluated purely based on its analytical capabilities, not on human interpretation or interaction beyond sample handling.
7. The Type of Ground Truth Used:
The ground truth used for performance evaluation is based on quantitative analytical measurements from reference methods or established predicate devices. For instance, the method comparison directly compares the results of the Tina-quant® assay to those obtained with the Behring BN® α-1-Antitrypsin assay, which serves as a widely accepted reference for this analyte.
8. The Sample Size for the Training Set:
The document does not specify a separate training set size. For an in-vitro diagnostic assay, development and calibration would involve various samples, but a distinct "training set" in the context of machine learning (where this question typically applies) is not explicitly mentioned as relevant. The performance characteristics described are typically for validation/testing.
9. How the Ground Truth for the Training Set Was Established:
As no explicit "training set" is mentioned in the context of machine learning models, the method for establishing ground truth for such a set is not applicable or described. For the development and calibration of the assay, ground truth would be established through the use of characterized calibrators and controls with known α-1-antitrypsin concentrations, often traceable to international reference standards.
§ 866.5130
Alpha -1-antitrypsin immunological test system.(a)
Identification. Analpha -1-antitrypsin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques thealpha -1-antitrypsin (a plasma protein) in serum, other body fluids, and tissues. The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition,alpha -1-antitrypsin deficiency has been associated with pulmonary emphysema.(b)
Classification. Class II (performance standards).