(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 |
| PrecisionWithin run CV | 2.25% @ 40.0 ng/ml2.00% @ 101 ng/ml1.25% @ 383 ng/ml | 3.20% @ 38.0 ng/ml1.31% @ 108.1 ng/ml0.99% @ 224.1 ng/ml |
| PrecisionTotal CV | 3.43% @ 40.0 ng/ml2.81% @ 101 ng/ml2.12% @ 383 ng/ml | 3.94% @ 38.0 ng/ml1.62% @ 108.1 ng/ml1.43% @ 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 - 2.549R = 0.995 | y = 1.0016x + 4.3849R = 0.9958 |
| InterferencesHaemolysisLipemicIcterusRheumatoid Factor | Less than 10% up to 5 g/L hemoglobinLess than 10% up to 400mg/dL Intralipid®Less than 5% up to 40mg/dL or 684 µmol/l bilirubinLess than 5% up to 500 IU/ml RF | Less than 5% up to 500 mg/dl hemoglobinLess than 10% up to 400mg/L Intralipid®Less than 5% up to 20mg/dl bilirubinLess than 5% up to 900 IU/ml RFAscorbic 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.
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NOV 2 0 2006
510(k) Executive Summary
| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. | |
|---|---|---|
| SubmitterName, address,Contact | Medicon Hellas S.A.5-7 Melitona St.Gerakas, Attiki153 44 GREECEContact Person: George Psichas+30210-6606140Date Prepared: July 12, 2006 | |
| Device Name | Proprietary name: Medicon Ferritin – LATEX | |
| Common name: Ferritin Reagent | ||
| Classification name: Ferritin Immunological Test | ||
| DeviceDescription | 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. | |
| Reagent Composition: | ||
| Reagent | Components | |
| R1 | 120 mM Tris buffer pH=8.2AcceleratorSurfactantStabilizers |
Preservatives
pH=8.4 Stabilizers Preservatives
Latex particles coated with rabbit antihuman ferritin in 20 mM Tris buffer
R2
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510(k) Summary, Continued _ + = ( + ) = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =
.
| Kit Format: | ||
|---|---|---|
| Cat No. | Quantity | Storage |
| 1418-0270 | 4x6 ml R1+4x1.25ml R2 | |
| 2-8°C | ||
| 1418-0279 | 4x24ml R1+4 x 5ml R2 | |
| Intended use | In vitro diagnostic reagent intended for the determination ofFerritin in human serum and plasma using Olympus AU400/600/640 automated clinical chemistry analyzers. | |
| IndicationsFor Use | Medicon Ferritin -LATEX reagent is for the determination ofFerritin in human serum and plasma using automated clinicalchemistry analyzers. | |
| The measurement of ferritin may aid in the diagnosis of diseasesaffecting iron metabolism. | ||
| SubstantialEquivalance | The Ferritin - LATEX is substantially equivalent to other deviceslegally marketed in the United States. We claim equivalence tothe Olympus Ferritin Reagent (K030124). Both products areintended for use in the quantitative determination of Ferritinon Olympus AU 400/600/640 automated clinical chemistryanalyzers. |
| Substantialequivalence-Similarities | The following table compares the Medicon Ferritin - LATEX withthe predicate device. |
|---|---|
| --------------------------------------------- | ----------------------------------------------------------------------------------------- |
| Feature | Ferritin - LATEX | Ferritin(predicate) |
|---|---|---|
| Intended Use | In vitro diagnostic reagentintended for the determination ofFerritin in human serum andplasma using Olympus AU400/600/640 automated clinicalchemistry analyzers. | In vitro diagnostic reagentintended for thedetermination of Ferritin inhuman serum usingautomated Olympus clinicalchemistry analyzers. |
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| Indication for Use | Medicon Ferritin -LATEX reagentis for the determination oFerritin in human serum andplasma using automated clinicalchemistry analyzers.The measurement of ferritin mayaid in the diagnosis of diseasesaffecting iron metabolism. | Reagent for the determinationof ferritin concentrations inhuman serum using Olympusfamily of clinical chemistryanalyzers.Serum ferritin is an indicatorof body iron stores: it hasbeen shown to correlate withstainable bone marrow iron.Measurements of ferritin aidin the diagnosis of diseasesaffecting iron metabolism,such as hemochromatosis(iron overload) and irondeficiency anemia. |
|---|---|---|
| Assay Protocol | Particle enhancedImmunoturbidometric | Particle enhancedImmunoturbidometric |
| Instrument | Olympus Clinical ChemistryAnalyzers | Olympus Clinical ChemistryAnalyzers |
| Formulation | Final reactive ingredients:Tris Buffer pH: 8.2Latex particles coated with rabbitanti-human ferritinPreservative | Final reactive ingredients:Tris Buffer pH: 8.2Latex particles coated withrabbit anti-human ferritinPreservative |
| Calibrator | Olympus Serum Protein MultiCalibrator ODR3021 | Olympus Serum ProteinMulti-Calibrator ODR3021 |
| Controls | Olympus ITA Control Sera,ODC0014, ODC 0015, ODC 0016 | Olympus ITA Control Sera,ODC0014, ODC 0015, ODC0016 |
Substantial The following table compares the Ferritin – LATEX with the equivalenceSimilarities predicate device.
| Feature | Ferritin - LATEX | Ferritin(predicate) |
|---|---|---|
| Reagent Stability | On board: 30 days | On board: 30 days |
| Calibration Interval | After each lot and 14 days | After each lot and 14 days |
| Traceability/Standardization | Standardized against the 3rdInternational Standard for ferritin,Recombinant NBSC code:94/572. | Standardized against the 3rdInternational Standard forferritin, Recombinant NBSCcode:94/572 |
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The following table compares the Ferritin – LATEX with the Substantial equivalencepredicate device. differences
| Feature | Ferritin - LATEX | Ferritin(predicate) |
|---|---|---|
| Measuring Range | 4-450 ng/ml | 8-450 µg/l |
| Sample type | Serum and plasma | Serum |
| Reference Intervals | Serum / Plasma:Infants - 1 month: 6-400 ng/ml1 month - 6 months: 6-410 ng/ml6 months - 12 months: 6-80ng/ml1 year - 5 years: 6-60 ng/ml6 years - 19 years: 6-320 ng/mladult men: 20-250 ng/mladult women: 20-200 ng/ml | Serum:New born infants - 6 months:25- 200µg/l6 months - 15 years:7-142 µg/lAdult male: 20-300µg/lAdult female: 10-120µg/l |
The performance characteristics of the Ferritin-LATEX and the Substantial predicate device are compared in the table below: equivalence-Performance Characteristics
| Feature | Ferritin - LATEX | Ferritin(predicate) |
|---|---|---|
| Precision | Within run CV3.20% @ 38.0 ng/ml1.31% @ 108.1 ng/ml0.99% @ 224.1 ng/mlTotal CV3.94% @ 38.0 ng/ml1.62% @ 108.1 ng/ml1.43% @ 224.1 ng/ml | Within run CV2.25% @ 40.0 ng/ml2.00% @ 101 ng/ml1.25% @ 383 ng/mlTotal CV3.43% @ 40.0 ng/ml2.81% @ 101 ng/ml2.12% @ 383 ng/ml |
| Analytical sensitivity(LDL) | 4ng/ml | 6.4 µg/L |
| Linearity | 4 - 450 ng/ml | 8.0 - 450 µg/L |
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| Method Comparison | Linear regression analysis:Ferritin-LATEX v.s. commerciallyavailable ferritin assay on patientserum samples$y= 1,0016x+4,3849$$R= 0.9958$Ferritin-LATEX between patientserum and EDTA plasma$y= 0,9847x-1.1275$$R= 0.9987$Ferritin-LATEX between patientserum and Li-Heparine plasma$y= 0,9778x + 1.2886$$R= 0.9988$ | Linear regression analysis:Predicate device v.s.commercially available ferritinassay on patient serumsamples$y= 0,964x-2,549$$R= 0.995$ |
|---|---|---|
| Interferences | Haemolysis: Less than5% up to 500 mg/dlhemoglobin. Lipemic: Less than 10%up to 400mg/LIntralipid®. Icterus: Less than 5% upto 20mg/dl bilirubin. Rheumatoid Factor: Lessthan 5% up to 900 IU/mlRF. Ascorbic acid: Less than5% up to 3 mg/dl ascorbicacid. | Haemolysis: Lessthan 10% up to 5 g/Lhemoglobin. Lipemic: Less than10% up to 400mg/dLIntralipid®. Icterus: Less than 5%up to 40mg/dL or 684µmol/l bilirubin. Rheumatoid Factor:Less than 5% up to500 IU/ml RF. |
| Prozone Effect | No hook effect observed up to10000 ng/ml. | No hook effect observed upto 5000 ng/ml. |
:
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Image /page/5/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a stylized eagle with three tail feathers, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circle around the eagle. The eagle is black, and the text is also black.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mecicon Hellas S.A. c/o Mr. Daniel W. Lehtonen 2307 East Aurora Road Twinsburg, OH 44087
NOV 2 0 2006
Rc: K062746
Trade/Device Name: Medicon Ferritin-LATEX Regulation Number: 21 CFR 866.5340 Regulation Name: Ferritin Immunological Test System Regulatory Class: Class II Product Code: DBF Dated: September 13, 2006 Received: September 14, 2006
Dear Mr. Lchtonen:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration,
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally
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marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
ia m Chan for
Sr. Robert Becker
Robert L. Becker, Jr., M.D., Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if Known): K062746
Device Name: Medicon Ferritin - LATEX
Indications for Use:
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.
Prescription Use ------(Part 21 CFR 801 Subpart D)
AND/OR
Over- The Counter -- Use -------(21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Mana M Chan
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K062746
§ 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).