K Number
K031650
Date Cleared
2003-07-17

(50 days)

Product Code
Regulation Number
866.5340
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

In vitro diagnostic reagent system intended for use on COBAS INTEGRA system for the quantitative immunological determination of human ferritin in serum and plasma.

Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism such as hemochromatosis (iron overload) and iron deficiency anemia.

Device Description

A particle enhanced immunoturbidimetric assay in which human ferritin agglutinates with latex particles coated with anti-ferritin antibodies. The precipitate is determined turbidimetrically at 552 nm.

AI/ML Overview

Here's a summary of the acceptance criteria and study information for the Ferritin Generation 2 device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as numerical targets in the document. Instead, the performance of the Ferritin Generation 2 is demonstrated by direct comparison to a predicate device (COBAS Integra Ferritin assay, K963292). The assumption is that matching or improving upon the predicate's performance indicates substantial equivalence and meets acceptance.

FeatureImplicit Acceptance Criteria (Relative to Predicate)Ferritin Generation 2 PerformancePredicate Device Performance (COBAS Integra Ferritin)
PrecisionSimilar or improved CVsWithin run CV: 9.0% @ 19.8 ng/ml 2.5% @ 107.5 ng/ml Between Day CV: 7.8% @ 20.3 ng/ml 3.4% @ 157.0 ng/mlWithin run CV: 9.9% @ 19 ng/ml 1.2% @ 260 ng/ml Between Day CV: 10.2% @ 19 ng/ml 3.8% @ 260 ng/ml
Method ComparisonStrong correlation (r-value close to 1) and linear agreement with predicateBablok/Passing: $y = 1.30x + 12.98$ ng/ml $r = 0.922$Bablok/Passing: $y = 0.84x + 0.8$ ng/ml $r = 0.992$ (vs. commercially available system)
LimitationsNo significant interference / similar limitationsIcterus: No significant interference Hemolysis: No significant interference up to 596 µmol/l Lipemia: No significant interference up to 160 mg/dL Rheumatoid factors: No significant interferenceIcterus: No significant interference Hemolysis: No significant interference Lipemia: No significant interference Rheumatoid factors: No significant interference
Prozone EffectSimilar or improved high-end detectionNo effect up to 10,000 ng/mlIntegra 400/400 plus: No effect up to 4300 ng/ml Integra 700/800: No effect up to 45,000 ng/ml
Analytical Sensitivity (LDL)Similar or improved lower detection limit7.5 ng/ml5 ng/ml

2. Sample Size Used for the Test Set and Data Provenance

The document does not specify the exact sample size used for the test set or the data provenance (e.g., country of origin, retrospective or prospective nature) for any of the performance studies. It only presents the results of these studies.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This information is not available in the provided text. The studies relate to the performance of an in vitro diagnostic reagent system (a lab test), not an imaging-based or clinical diagnostic device requiring expert interpretation for ground truth.

4. Adjudication Method for the Test Set

This information is not available in the provided text. Adjudication methods are typically relevant for studies involving human interpretation of results, which is not the primary focus of this device's performance evaluation.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size

An MRMC comparative effectiveness study was not done. This type of study is not applicable to an in-vitro diagnostic reagent system like Ferritin Generation 2, which produces quantitative numerical results rather than interpretations requiring human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the studies presented are standalone performance evaluations of the diagnostic reagent system itself. The precision, method comparison, and interference studies assess the device's analytical performance independent of human interpretation beyond standard laboratory procedures (e.g., pipetting, running the instrument).

7. The Type of Ground Truth Used

For the Method Comparison study, the "ground truth" for the Ferritin Generation 2 device was a predicate device, specifically the COBAS Integra Ferritin assay. The comparison assessed how closely the new device's measurements correlated with the established predicate.

For other analytical performance characteristics (Precision, Limitations, Prozone Effect, Analytical Sensitivity), the "ground truth" implicitly refers to the true analytical values of the samples being tested, typically derived from reference materials or highly accurate reference methods, although these are not explicitly detailed. The device is designed to quantitatively determine human ferritin, and the ground truth would be the actual ferritin concentration in the samples.

8. The Sample Size for the Training Set

This information is not available in the provided text. This device is a reagent system, not an AI/ML-based algorithm that typically has a "training set" in the conventional sense. Its development would involve analytical testing and validation rather than a data training process.

9. How the Ground Truth for the Training Set was Established

This information is not applicable as the device is not an AI/ML system with a "training set." The performance characteristics are established through various analytical validation studies using reference materials and patient samples.

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K03/650

510(k) Summary

IntroductionAccording to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence.
Submittername, address,contactRoche Diagnostics Corporation9115 Hague RoadIndianapolis, IN 46250(317) 521 - 3544
Contact Person: Kay A. Taylor
Date Prepared: May 27, 2003
Device NameProprietary name: Ferritin Generation 2
Common name: Ferritin
Classification name: Ferritin, Antigen, Antiserum, Control
DeviceDescriptionA particle enhanced immunoturbidimetric assay in which human ferritinagglutinates with latex particles coated with anti-ferritin antibodies. Theprecipitate is determined turbidimetrically at 552 nm.
Intended useIn vitro diagnostic reagent system intended for use on COBAS Integra systemfor the quantitative immunological determination of human ferritin in serumand plasma.
Indications forUseMeasurements of ferritin aid in the diagnosis of diseases affecting ironmetabolism such as hemochromatosis (iron overload) and iron deficiencyanemia.
SubstantialEquivalenceThe Ferritin Generation 2 is substantially equivalent to other devices legallymarketed in the United States. We claim equivalence to the COBAS IntegraFerritin assay (K963292). Both products are intended for use in thequantitative determination of Ferritin on automated clinical chemistryanalyzers.

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510(k) Summary, Continued

Substantial equivalence similarities

The following table compares the Ferritin Generation 2 Assay with the predicate device.

FeatureFerritin Generation 2Ferritin(predicate)
Intended UseIn vitro diagnostic reagentsystem intended for use onCOBAS INTEGRA systemfor the quantitativeimmunologicaldetermination of humanferritin in serum and plasma.In vitro diagnostic reagentsystem intended for use onCOBAS INTEGRA systemfor the quantitativeimmunological determinationof human ferritin in serumand plasma.
Indication for UseFor the quantitativedetermination of ferritin inhuman serum and plasma.Measurements of ferritin aidin the diagnosis of diseasesaffecting iron metabolismsuch as hemochromatosis(iron overload) and irondeficiency anemia.For the quantitativedetermination of ferritin inhuman serum and plasma.Measurements of ferritin aidin the diagnosis of diseasesaffecting iron metabolismsuch as hemochromatosis(iron overload) and irondeficiency anemia.
Assay ProtocolParticle enhancedImmunoturbidometricParticle enhancedImmunoturbidometric
InstrumentCOBAS Integra ClinicalChemistry AnalyzersCOBAS Integra ClinicalChemistry Analyzers
Sample TypeSerum and plasmaSerum and plasma
FormulationR: Glycine buffer stabilizedwith 0.09% sodium azide,5mg/ml rabbit globulin invial B (liquid).R2: Latex particles coatedwith anti-human ferritin(rabbit) in glycine buffer,stabilized with 0.09%sodium azide in vial C(liquid).R: Glycine buffer stabilizedwith 0.09% sodium azide invial B (liquid).R2: Latex particles coatedwith anti-human ferritin(rabbit) in glycine buffer,stabilized with 0.09% sodiumazide in vial C (liquid).
CalibratorFERR T StandardFERR T Standard
ControlsFERR /MYO T ControlFERR /MYO T Control
Reagent StabilityOn board: 12 weeksOn-board: 12 weeks
FeatureFerritin Generation 2Ferritin(predicate)
Expected ValuesFemales: 15-150 ng/mlMales: 30-400 ng/ml(3 mos-16 yrs):20-200 ng/ml(2nd-3rd month):80-500 ng/ml(1st month):150-400 ng/ml(umbilical cord blood):50-250 ng/mlFemales: 10-120 ng/mlMales: 20-300 ng/ml
Measuring Range0-382 ng/mlIntegra 400: 0-280 ng/mlIntegra 700: 0-300 ng/ml
Traceability /StandardizationStandardized against theNIBSC Reagents for Ferritin(human spleen 80/578).Traceable to WHOReference Preparation forHuman Liver Ferritin (1stInternational Standard 1984)
Calibration IntervalAfter each lot and 84 daysAfter each lot

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510(k) Summary, Continued

Substantial equivalence differences

The following table compares the Ferritin Generation 2 Assay with the predicate device.

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510(k) Summary, Continued

Substantial equivalence performance characteristics The performance characteristics of the Ferritin Generation 2 Assay and the predicate device are compared in the table below.

FeatureFerritin Generation 2Apolipoprotein B(predicate)
PrecisionWithin run CV9.0% @ 19.8 ng/ml2.5% @ 107.5 ng/mlBetween Day CV7.8% @ 20.3 ng/ml3.4% @ 157.0 ng/mlWithin run CV9.9% @ 19 ng/ml1.2% @ 260 ng/mlBetween Day CV10.2% @ 19 ng/ml3.8% @ 260 ng/ml
Method ComparisonBablok/Passing:Ferritin Generation 2 (Y) /COBAS Integra Ferritin (X).$y = 1.30x + 12.98$ ng/ml$r = 0.922$Bablok/Passing:Ferritin (Y)/commercially availablesystem (X).$y = 0.84x + 0.8$ ng/ml$r = 0.992$
Limitations• Icterus: No significantinterference• Hemolysis: Nosignificant interferenceup to a level 596 µmol/l.• Lipemia: No significantinterference up to anIntralipid level of 160mg/dL• Rheumatoid factors: Nosignificant interference• Icterus: No significantinterference• Hemolysis: Nosignificantinterference• Lipemia: Nosignificantinterference• Rheumatoid factors:No significantinterference
Prozone EffectNo effect up to 10,000 ng/mlIntegra 400/400 plus:No effect up to 4300 ng/mlIntegra 700 /800:No effect up to 45,000ng/ml
Analytical sensitivity(LDL)7.5 ng/ml5 ng/ml

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure, composed of three curved lines that suggest movement or flight. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the bird-like figure.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Kay A. Taylor, MT (ASCP), RAC Regulatory Program Principal Centralized Diagnostic Submissions Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis. Indiana 46250-0457

JUL 17 2003

Re: K031650

Trade/Device Name: Roche COBAS Integra Ferritin Generation 2 Regulation Number: 21 CFR § 866.5340 Regulation Name: Ferritin Immunological Test System Regulatory Class: II Product Code: DBF Dated: July 7, 2003 Received: July 9, 2003

Dear Ms. Taylor:

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. Drue, 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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). 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 marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

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If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. 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 (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

510(k) Number (if known): N/A

Device Name: Ferritin Generation 2 Test System

Indications For Use:

In vitro diagnostic reagent system intended for use on COBAS INTEGRA system for the quantitative immunological determination of human ferritin in serum and plasma.

Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism such as hemochromatosis (iron overload) and iron deficiency anemia.

Prescription Use (Per 21 CFR 801.109)

OR

Over-The-Counter Use

(Optional Format 1-2-96)

J. Reeve for J. Bautista
Division Sign-Off

Division Sign-Off

ice of In Vitro Diagnostic Evaluation and

510(k) K031650

20

§ 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).