(67 days)
Medicon Ferritin - LATEX reagent is for the determination of Ferritin in human serum and plasma using automated clinical chemistry analyzers.
The measurement of ferritin may aid in the diagnosis of diseases affecting iron metabolism.
For in vitro diagnostic use.
The Ferritin – LATEX is an immunoturbidimetric assay. When serum or plasma specimen is mixed with the appropriate buffer (R1) and latex particles coated with anti-ferritin antibodies (R2), ferritin reacts with the antibodies leading to agglutination of latex particles. This agglutination is detected as turbidity change (600 nm) and it is proportional to ferritin concentration in the sample.
The Medicon Ferritin-LATEX device is an immunoturbidimetric assay for the quantitative determination of Ferritin in human serum and plasma using Olympus AU 400/600/640 automated clinical chemistry analyzers. The device's performance was compared to a predicate device, the Olympus Ferritin Reagent (K030124), to establish substantial equivalence.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Medicon Ferritin-LATEX device are implicitly established by demonstrating substantial equivalence to the predicate device, the Olympus Ferritin Reagent (K030124). The performance characteristics are compared as follows:
| Feature | Acceptance Criteria (Predicate Device K030124) | Reported Device Performance (Medicon Ferritin-LATEX) |
|---|---|---|
| Measuring Range | 8-450 µg/L | 4-450 ng/ml |
| Sample type | Serum | Serum and plasma |
| Precision | ||
| Within run CV | 2.25% @ 40.0 ng/ml | |
| 2.00% @ 101 ng/ml | ||
| 1.25% @ 383 ng/ml | 3.20% @ 38.0 ng/ml | |
| 1.31% @ 108.1 ng/ml | ||
| 0.99% @ 224.1 ng/ml | ||
| Precision | ||
| Total CV | 3.43% @ 40.0 ng/ml | |
| 2.81% @ 101 ng/ml | ||
| 2.12% @ 383 ng/ml | 3.94% @ 38.0 ng/ml | |
| 1.62% @ 108.1 ng/ml | ||
| 1.43% @ 224.1 ng/ml | ||
| Analytical Sensitivity (LDL) | 6.4 µg/L | 4 ng/ml |
| Linearity | 8.0 - 450 µg/L | 4 - 450 ng/ml |
| Method Comparison (Correlation to commercially available ferritin assay) | y = 0.964x - 2.549 | |
| R = 0.995 | y = 1.0016x + 4.3849 | |
| R = 0.9958 | ||
| Interferences | ||
| Haemolysis | ||
| Lipemic | ||
| Icterus | ||
| Rheumatoid Factor | Less than 10% up to 5 g/L hemoglobin | |
| Less than 10% up to 400mg/dL Intralipid® | ||
| Less than 5% up to 40mg/dL or 684 µmol/l bilirubin | ||
| Less than 5% up to 500 IU/ml RF | Less than 5% up to 500 mg/dl hemoglobin | |
| Less than 10% up to 400mg/L Intralipid® | ||
| Less than 5% up to 20mg/dl bilirubin | ||
| Less than 5% up to 900 IU/ml RF | ||
| Ascorbic acid: Less than 5% up to 3 mg/dl ascorbic acid | ||
| Prozone Effect | No hook effect observed up to 5000 ng/ml | No hook effect observed up to 10000 ng/ml |
| Reagent Stability (On board) | 30 days | 30 days |
| Calibration Interval | After each lot and 14 days | After each lot and 14 days |
| Traceability/Standardization | Standardized against the 3rd International Standard for ferritin, Recombinant NBSC code:94/572 | Standardized against the 3rd International Standard for ferritin, Recombinant NBSC code:94/572 |
Note on Units: The predicate device uses µg/L, and the new device uses ng/ml. While numerically equivalent (1 µg/L = 1 ng/ml), this is a difference in units presentation in the provided summary. For clarity in the table, the units as presented in the original text are retained.
Study Proving Device Meets Acceptance Criteria:
The study submitted for premarket notification K062746 comprised a series of analytical performance tests designed to demonstrate substantial equivalence to the predicate Olympus Ferritin Reagent (K030124). These tests included:
- Measuring Range/Linearity: Evaluation of the device's ability to accurately measure ferritin concentrations across its claimed range.
- Precision: Assessment of the reproducibility and repeatability of measurements (within-run and total CV).
- Analytical Sensitivity (Lower Detection Limit - LDL): Determination of the lowest concentration of ferritin that can be reliably detected.
- Method Comparison: Correlation of results from the Medicon Ferritin-LATEX with a "commercially available ferritin assay" using patient samples. Additionally, comparisons were made between serum and plasma samples using the Medicon Ferritin-LATEX.
- Interference Testing: Evaluation of the effect of potential interferents (hemolysis, lipemia, icterus, rheumatoid factor, ascorbic acid) on assay accuracy.
- Prozone Effect: Assessment of high-dose hook effect.
- Reagent Stability and Calibration Interval: Verification of the claimed stability and calibration requirements.
- Traceability/Standardization: Confirmation of standardization against recognized international standards.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size:
- Method Comparison (Ferritin-LATEX vs. commercially available ferritin assay): The summary states "patient serum samples," but the exact number of samples is not specified.
- Method Comparison (Ferritin-LATEX: serum vs. EDTA plasma): The summary states "patient serum and EDTA plasma," but the exact number of samples is not specified.
- Method Comparison (Ferritin-LATEX: serum vs. Li-Heparine plasma): The summary states "patient serum and Li-Heparine plasma," but the exact number of samples is not specified.
- Precision: Data is reported for 3 levels (38.0 ng/ml, 108.1 ng/ml, 224.1 ng/ml), implying multiple replicates were tested at each level to calculate CVs, but the total number of samples or runs is not explicitly stated.
- Interference: Concentrations for various interferents are provided, suggesting samples spiked with these substances were tested, but the number of samples is not specified.
- Prozone Effect: Samples up to 10000 ng/ml were tested, but the number of samples is not specified.
- Data Provenance: The document does not explicitly state the country of origin of the data. Given the "Medicon Hellas S.A." submitter information (Greece), it is plausible the studies were conducted in Greece or Europe, but this is not confirmed. The data appears to be from retrospective clinical samples (patient serum/plasma samples) and controlled laboratory studies (spiking experiments for interference, known concentrations for precision and linearity).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
For an in vitro diagnostic device like a Ferritin assay, ground truth is typically established through reference methods or established laboratory practices rather than expert consensus on interpretation.
- No "experts" in the sense of clinicians or radiologists interpreting images were involved in establishing ground truth for individual test samples.
- The ground truth for the method comparison study was established by another "commercially available ferritin assay." This assay itself would have been validated against a reference method or known standards.
- The predicate device and the new device are both stated to be "Standardized against the 3rd International Standard for ferritin, Recombinant NBSC code: 94/572." This international standard serves as the ultimate ground truth for ferritin concentration measurements.
4. Adjudication Method for the Test Set
Not applicable. As described above, the ground truth for this in vitro diagnostic device is based on quantitative measurements against an international standard and comparison to a legally marketed predicate device, not on expert consensus or adjudication of subjective interpretations.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This is an in vitro diagnostic device (a reagent for an automated clinical chemistry analyzer) and not an imaging or interpretive device that would typically involve human readers. Therefore, an MRMC study is not relevant or performed for this type of device.
6. Standalone Performance
Yes, the studies described (Precision, Analytical Sensitivity, Linearity, Interference, Prozone Effect) are all assessments of the standalone performance of the Medicon Ferritin-LATEX algorithm/reagent system on an automated analyzer. The method comparison studies also demonstrate the standalone performance against an existing method. The entire submission focuses on the performance of the device without human interpretation of the assay results, relying instead on the quantitative output of the automated analyzer.
7. Type of Ground Truth Used
The ground truth used is primarily:
- Reference Standards: The device is standardized against the "3rd International Standard for ferritin, Recombinant NBSC code:94/572." This is the fundamental ground truth for ferritin concentration.
- Comparative Reference Method: For method comparison, another "commercially available ferritin assay" served as the reference method, which itself would have been validated against standards.
- Known Concentrations: For studies like precision and linearity, samples with known or spiked concentrations were used against which the device's measurements were assessed.
8. Sample Size for the Training Set
The provided 510(k) summary does not contain information on a "training set" in the context of machine learning. This device is a biochemical reagent system, not an AI or machine-learning algorithm that typically requires a large training dataset. The development and optimization of such a reagent assay would involve internal development testing, but this is distinct from a "training set" as understood in AI/ML contexts.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no mention of a "training set" or AI/ML components in this 510(k) submission for a biochemical reagent. The ground truth for the device's development and validation would have been established using the accepted methods for in vitro diagnostics, as outlined in point 7.
§ 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).