(624 days)
The DiaSorin LIAISON® Ferritin assay is a quantitative automated chemiluminescent immunoassay (CLIA) for the in vitro detection of ferritin in human serum, serum separator tubes (SST), or lithium (Li) heparin plasma to aid in the diagnosis of iron deficiency anemia and iron overload.
This assay must be performed on the LIAISON® XL Analyzer.
The chemiluminescence immunoassay method for the quantitative determination of ferritin is a sandwich immunoassay.
A specific mouse monoclonal antibody is coated on the magnetic particles (solid phase); another monoclonal antibody (mouse) is linked to an isoluminol derivative (isoluminolantibody conjugate).
During the incubation, ferritin present in calibrators, samples or controls binds to the solid phase monoclonal antibody, and subsequently the antibody conjugate reacts with ferritin already bound to the solid phase.
After incubation, the unbound material is removed with a wash cycle.
Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and hence the amount of isoluminol-antibody coniugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of ferritin concentration present in calibrators, samples or controls.
The provided document is a 510(k) Summary for the DiaSorin LIAISON® Ferritin assay, a chemiluminescent immunoassay for the quantitative determination of ferritin in human serum, serum separator tubes (SST), or lithium (Li) heparin plasma. Its intended use is to aid in the diagnosis of iron deficiency anemia and iron overload.
This document details the performance characteristics required to demonstrate substantial equivalence to a legally marketed predicate device (Roche Elecsys® Ferritin assay), rather than defining and proving against acceptance criteria in the context of an AI/ML device or a complex diagnostic with multiple discrete outcomes. The data presented are for an in vitro diagnostic immunoassay, which relies on analytical performance metrics rather than clinical outcome studies of the type implied by the original request's questions about expert consensus, MRMC studies, human-in-the-loop performance, etc.
Therefore, many of the requested elements are not applicable to the type of device and study described in this document.
Below, I've addressed the applicable points from your request based on the provided text.
Device: DiaSorin LIAISON® Ferritin assay (K193650)
Type of Device: Quantitative automated chemiluminescent immunoassay (CLIA) for the in vitro detection of ferritin.
Purpose of the Study (as presented in the 510(k) Summary): To demonstrate substantial equivalence of the DiaSorin LIAISON® Ferritin assay to the predicate device, Roche Elecsys® Ferritin assay, based on analytical performance characteristics.
Acceptance Criteria and Reported Device Performance
For an in vitro diagnostic assay, acceptance criteria typically relate to analytical performance metrics to ensure accuracy, precision, linearity, and other factors. While the document does not explicitly list "acceptance criteria" against each performance metric in a table format, it reports the results of various studies (e.g., method comparison, precision) which would have been previously agreed upon with the FDA as sufficient to demonstrate substantial equivalence.
Here's a summary of the reported performance. The implied "acceptance criteria" are that these results fall within acceptable ranges for diagnostic assays of this type, often relative to a predicate device or industry standards (e.g., CLSI guidelines).
| Performance Metric | Reported Device Performance (LIAISON® Ferritin) | Implied Acceptance Criteria (based on context of 510(k)) |
|---|---|---|
| Method Comparison (vs. Reference Method) | Regression Analysis (Passing & Bablok): |
- Slope: 0.965 (95% CI: 0.95 - 0.98)
- Intercept: -1.12 (95% CI: -2.13 to -0.32)
- R²: 0.995 | Slope close to 1, Intercept close to 0, and R² close to 1, indicating strong agreement with the reference method (likely the predicate or another validated method), within pre-defined acceptable limits for analytical measurements. |
| Sample Matrix Comparison | Serum vs. SST: - Slope: 1.002 (0.9727 to 1.038)
- Intercept: 0.0179 (-0.7744 to 0.6374)
Serum vs. Li Heparin: - Slope: 0.984 (0.9413 to 0.9905)
- Intercept: -1.732 (-2.137 to -0.5159) | Slopes near 1 and intercepts near 0 for different matrix types compared to serum, demonstrating equivalence across specified sample types. |
| Precision (Total %CV) | Kit Control 1 (32.81 ng/mL): 4.3%
Kit Control 2 (300 ng/mL): 5.4%
Panel 1 (5.84 ng/mL): 5.6%
Panel 2 (18.26 ng/mL): 4.6%
Panel 3 (178 ng/mL): 4.1%
Panel 4 (1093 ng/mL): 5.6%
Panel 5 (404.9 ng/mL): 4.6%
Panel 6 (1883 ng/mL): 6.4% | Total CV (Coefficient of Variation) within acceptable limits for a quantitative immunoassay across its measuring range, demonstrating reproducibility and reliability of results. These limits are typically defined by regulatory bodies or industry standards (e.g., CLSI EP5-A3). |
| Linearity | Equation for 2000 ng/mL sample:
Observed Ferritin = -1.402 + 1.006 * Expected Ferritin
R²=1.000 | R² close to 1, and slope near 1 with intercept near 0, demonstrating accurate measurement across the assay’s claimed analytical measuring range (0.46 – 2,200 ng/mL). |
| Recovery | Average Recovery: 101% (Individual recoveries ranging from 98% to 104% for spiked samples) | Recovery values typically between 90-110% (or tighter, depending on the analyte and assay sensitivity) for spiked samples, indicating the assay accurately measures the target analyte when added to a sample. |
| Limit of Blank (LoB) | 0.004 ng/mL | LoB consistent with the lower end of the claimed analytical measuring range and adequate for the intended clinical application. |
| Limit of Detection (LoD) | 100.0%
Human spleen ferritin: 78.8% | Specificity for the intended analyte (ferritin) without significant cross-reactivity with closely related substances or other components that could lead to false results. |
Applicable Information from the Request (Based on provided document):
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A table of acceptance criteria and the reported device performance: See table above.
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Sample sizes used for the test set and the data provenance:
- Method Comparison: 173 samples. Provenance not specified (e.g., country of origin, retrospective/prospective), but it usually implies clinical samples collected for analytical validation purposes.
- Sample Matrix Comparison: 37 matched patient sets (serum, Li Heparin plasma) and 6 contrived matched patient samples. Provenance not specified.
- Expected Values/Reference Range: 78 human serum samples; 39 healthy female, 39 healthy male subjects (age 18+). Provenance not specified.
- Precision: 2 kit controls and 6 samples assayed 320 times each (twice per day in duplicate, over 20 operating days on two LIAISON® XL Analyzers using two reagent lots). Provenance: DiaSorin GmbH, implying internal lab testing.
- Linearity: Dilution series of 4 samples.
- Recovery: 4 representative human serum samples. Provenance not specified.
- Interference, Cross-Reactivity, LoB/LoD/LoQ studies also involved specific numbers of samples/replicates, but detailed sample sizes for each are not individually listed beyond the overall study design (e.g., "controlled studies... at Ferritin level of approximately 20 ng/mL and 2000 ng/mL").
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. This document describes an in vitro diagnostic device measuring a quantitative biomarker (Ferritin). Ground truth is established through reference methods, calibration materials traceable to international standards (e.g., NIBSC 94/572 for Ferritin), and gravimetric/dilution/spiking studies, not by expert interpretation of images or clinical outcomes that require human experts for ground truth.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set: Not applicable. Adjudication methods are relevant for studies involving human interpretation (e.g., radiology reads) where discrepancies need to be resolved. This is an automated analytical test.
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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 assay, not an AI/ML device that assists human readers.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Not applicable in the context of an "algorithm" as typically referred to in AI/ML. The device itself is an automated analyzer that performs the "standalone" measurement of ferritin. No human interpretation is involved in the measurement process after sample loading.
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The type of ground truth used:
- For Method Comparison, the "Reference Method" was used as ground truth. This would typically be a highly accurate and precise method, often the predicate device itself or a laboratory developed test that is well-validated.
- For Linearity and Recovery, ground truth was established by preparing samples with known concentrations through spiking and dilution from a characterized stock solution or pool.
- For Precision, samples with known (or previously characterized) ferritin concentrations were used.
- For Traceability, the calibrators are traceable to an internal reference standard "oriented at the 2nd reference standard NIBSC 94/572." This international standard serves as a form of ground truth for absolute concentration.
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The sample size for the training set: Not applicable. This is a traditional immunoassay, not an AI/ML device that requires a "training set" in the computational sense. The "training" of such a system involves calibrating it with known standards, which were traceable to an international reference standard (NIBSC 94/572).
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How the ground truth for the training set was established: Not applicable, as there is no "training set" in the AI/ML sense. Calibration is performed using materials traceable to an international reference standard.
§ 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).