(275 days)
Immunological.in. vitro immunoturbidometric.test for the quantitative determination of ferritin.in . .... human serum and plasma using clinical-chemistry analyzers.
The Ferritin determination is based upon turbidimetric immunoinhibition (TINIA) using a serum or plasma blood sample. The sample containing ferritin is transferred into a TRIS buffer solution (R₁ reagent). In the second step, an aliquot of solution containing fine latex particles coated with polyclonal anti-human ferritin antibodies (R₂ reagent) is added to mixture of the first step. The antibody-coated particles will bind to the ferritin in the sample to form "aggregates" such that the amount of aggregate formed is proportionate to the amount of ferritin 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 ferritin in the sample is directly proportional to the amount of turbidity formed.
The provided text describes the "Tina-quant® Ferritin Assay" and its substantial equivalence to a predicate device, the "Enzymun-Test® Ferritin assay." It includes performance characteristics and comparisons, which serve as the acceptance criteria and the results of the study.
Here's a breakdown of the requested information:
1. A table of acceptance criteria and the reported device performance
The document doesn't explicitly state "acceptance criteria" as a set of pass/fail thresholds. Instead, it presents the performance characteristics of the new device (Tina-quant® Ferritin) and compares them to the predicate device (Enzymun-Test® Ferritin). The implied acceptance criteria are that the performance of the Tina-quant® Ferritin assay should be comparable to or better than the predicate device.
| Feature | Acceptance Criteria (Implied - based on predicate device performance) | Tina-quant® Ferritin Performance (Reported Device Performance) |
|---|---|---|
| Precision (Intra-Assay %CV) | Low: ≤ 6.2% | |
| Mid: ≤ 2.7% | ||
| High: ≤ 2.5% | Low: 3.8% | |
| Mid: 1.4% | ||
| High: 1.1% | ||
| Precision (Inter-Assay %CV) | Low: ≤ 6.4% | |
| Mid: ≤ 4.3% | ||
| High: ≤ 4.9% | Low: 2.6% | |
| Mid: N/A (Sample 1 & 2 only) | ||
| High: N/A | ||
| Lower Detection Limit | Generally comparable to or better than 1.0 ng/mL | 3 ng/mL |
| Linearity | Generally comparable to or wider than 1.0 - 1000 ng/mL | 3 - 800 ng/mL |
| Method Comparison (Passing/Bablok) | r close to 1, SEE low | Vs Enzymun-Test® Ferritin: |
| y=1.04x + 4.8 | ||
| r=0.996 | ||
| SEE =13.68 | ||
| N=44 | ||
| Method Comparison (Least Squares) | r close to 1, SEE low | y = 1.00x + 13.1 |
| r = 0.997 | ||
| SEE = 13.52 | ||
| N = 44 | ||
| Interfering Substances (Bilirubin) | ≤ 10% error at 64.5 mg/dL | No interference at 68 mg/dL (≤ 10% error) |
| Interfering Substances (Hemoglobin) | ≤ 10% error at 1 g/dL | No interference at 500 mg/dL (≤ 10% error) |
| Interfering Substances (Lipemia) | ≤ 10% error at 1250 mg/dL | No interference at 1500 mg/dL (≤ 10% error) |
| Interfering Substances (Rheumatoid Factor) | N/A (predicate) | No interference at 100 IU/mL (≤ 10% error) |
| Specificity (Liver Ferritin) | 100% | 114.6% |
| Specificity (Spleen Ferritin) | 89% | 112.0% |
2. Sample size used for the test set and the data provenance
- Precision:
- Intra-Assay: 21 samples for each of the three levels (Low, Mid, High).
- Inter-Assay: 2 samples (Sample 1, Sample 2).
- Method Comparison: 44 samples (N=44) for comparison against the Enzymun-Test® Ferritin using Passing/Bablok and Least Squares methods.
- Interfering Substances: The document does not specify the exact sample size for interfering substances, but it indicates "No interference at" certain concentrations.
- Data Provenance: The document does not explicitly state the country of origin of the data or whether it was retrospective or prospective. It is a submission to the U.S. Food and Drug Administration (FDA), implying it was conducted for regulatory purposes in the US. The context suggests these were performance studies conducted with the device, likely prospective for the purpose of demonstrating performance.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This is an in-vitro diagnostic (IVD) device for quantitative determination of Ferritin. The "ground truth" for such devices is typically established through reference methods or highly accurate analytical techniques, not by human expert assessment in the same way an imaging device would be.
- The document mentions the use of NIBSC standard 80/602 and 80/578 (human liver and spleen) for calibration. These are recognized international standards for Ferritin, which serve as a form of "ground truth" for accuracy and calibration.
- No human experts are mentioned for establishing ground truth for the analytical performance of this type of quantitative assay.
4. Adjudication method for the test set
Not applicable for an in-vitro diagnostic analytical assay where ground truth is established chemically/biochemically using reference standards and methods, not through human interpretation requiring adjudication.
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 is an in-vitro diagnostic device, not an AI-powered image analysis or diagnostic support system for human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance characteristics provided (Precision, Detection Limit, Linearity, Method Comparison, Interfering Substances, Specificity) are measurements of the standalone performance of the Tina-quant® Ferritin assay. This device is designed to provide quantitative results directly from a clinical chemistry analyzer, without requiring human interpretation or "human-in-the-loop" decision-making for each result.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for this in-vitro diagnostic assay is established through:
- Reference standards: NIBSC standard 80/602 and 80/578 (human liver and spleen) are used for calibration and presumably for validating accuracy.
- Comparative methods: The device's performance is compared against another legally marketed device (Enzymun-Test® Ferritin assay), which implies using the results from the predicate as a reference for method comparison studies.
- Known concentrations: For studies like linearity and interfering substances, samples with known concentrations of ferritin or interfering substances would be used.
8. The sample size for the training set
Not explicitly stated. For IVDDs, particularly those based on established immunoturbidimetric principles, "training sets" in the AI sense are not typically used. The development process involves optimizing reagents and reaction conditions, followed by validation studies. However, the data for optimization or early development are generally not referred to as a "training set" in the context of this type of device.
9. How the ground truth for the training set was established
Not applicable in the AI sense of a "training set." For method development and optimization, ground truth would be established similarly to the test set: using reference materials, spiked samples with known concentrations, and comparisons to established analytical methods.
§ 866.5340 Ferritin immunological test system.
(a)
Identification. A ferritin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia.(b)
Classification. Class II (performance standards).