(191 days)
COBAS INTEGRA Ceruloplasmin: Ceruloplasmin
Indications For Use:
COBAS INTEGRA:
In vitro test for the quantitative immunological determination of ceruloplasmin in human serum and plasma on COBAS INTEGRA systems.
Measurements of Ceruloplasmin aid in the diagnosis of copper metabolism disorders.
Roche/Hitachi cobas c systems:
In vitro test for the quantitative determination of ceruloplasmin in human serum and plasma on Roche/Hitachi cobas c systems.
Measurements of Ceruloplasmin aid in the diagnosis of copper metabolism disorders.
The COBAS INTEGRA Ceruloplasmin cassette (CERU) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA SYSTEMS for the quantitative immunological determination of human ceruloplasmin in serum and plasma. The calibrator and control were cleared via K954992.
Measurements of ceruloplasmin aid in the diagnosis of copper metabolism disorders.
The test principle is an immunoturbidimetric assay. The calibrator is Serumproteins T Standard and the recommended control material is the Serumproteins T Control.
Here's a breakdown of the acceptance criteria and study information for the COBAS INTEGRA Ceruloplasmin device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Predicate Device (0.06-1.3 g/L) | COBAS INTEGRA Ceruloplasmin (Acceptance Criteria/Performance) |
|---|---|---|
| Measuring Range | 0.06-1.3 g/L | 0.06-1.26 g/L (Reported performance, implying this is the accepted range for the device) |
| Lower Detection Limit | 0.02 g/L | 0.017 g/L (Reported performance, implying this is the accepted limit for the device). This is an improvement compared to the predicate device. |
| Expected Values | 0.2-0.6 g/L | 0.2-0.6 g/L (Same as predicate, implying this is the accepted range for normal values) |
| Precision (Within run total CV%) | ||
| At ~0.2-0.27 g/L | 1.0% @ 0.27 g/L | 3.88% @ 0.2 g/L (Reported performance) |
| At ~0.34-0.35 g/L | 1.4% @ 0.34 g/L | 2.66% @ 0.35 g/L (Reported performance) |
| At ~0.62 g/L | 1.6% @ 0.62 g/L | (No corresponding data point provided for COBAS INTEGRA Ceruloplasmin) |
| Linearity | 0.06-0.69 g/L | 0.06-1.26 g/L (Reported performance, implying this is the accepted linear range for the device. This is an improvement compared to the predicate device.) |
| Endogenous Interferences | ||
| Hemolysis | no interferences up to 10 g/L | no significant interferences (Reported performance, implying this is the accepted level of interference) |
| Icterus | no interferences up to 600 mg/L | no significant interferences (Reported performance, implying this is the accepted level of interference) |
| Triglycerides/Lipemia | no interferences up to 25 g/L | no significant interferences (Reported performance, implying this is the accepted level of interference) |
| Rheumatoid factors | (Not mentioned) | no significant interferences up to 400 IU/mL (Reported performance) |
| Exogenous Interferences | (Not mentioned) | Gammopathy, in particular IgM, may cause unreliable results in rare cases (Reported, implying this is an accepted limitation) |
| Method Comparison (vs. DakoCytomation Anti Human Ceruloplasmin) | y = 1.0x - 0.0 g/L; r = 0.987 | y = 1.0x - 0.0 g/L; r =0.987 (Reported, implying agreement with the predicate is the accepted criterion) |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample sizes used for validating each performance characteristic (e.g., precision, linearity, interference studies, or method comparison). The data provenance is not specified regarding country of origin or an explicit retrospective/prospective design. However, the context of a 510(k) submission for a new in vitro diagnostic (IVD) device typically implies prospective testing conducted by the manufacturer, likely at their facilities.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable. This device is an in vitro diagnostic (IVD) assay for a quantitative biomarker (ceruloplasmin). The "ground truth" for such devices is established by analytical methods and comparison to a predicate device or reference material, not by expert interpretation of images or clinical cases.
4. Adjudication Method for the Test Set
Not applicable, as this is an IVD assay, not a device requiring human interpretation and adjudication of results. The method comparison refers to the statistical comparison of results from the new device against the predicate device.
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-assisted diagnostic tool that involves human readers interpreting cases.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this is an algorithm-only (standalone) performance. The device is a fully automated immunoturbidimetric assay system that quantitatively determines ceruloplasmin levels. There is no human intervention in the result generation process; the result is directly reported by the instrument.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth for this device's performance is established through:
- Reference materials: The device "Standardized against IFCC/BCR/CAP reference preparation CRM 470 (RPPHS 91/0619) for 14 serum proteins." This reference material serves as a "ground truth" for calibrating the assay.
- Comparison to a legally marketed predicate device: The method comparison data shows results against the DakoCytomation Polyclonal Rabbit Anti-Human Ceruloplasmin (K812486), which serves as a clinical benchmark (or "ground truth" in terms of clinical performance equivalence).
8. The Sample Size for the Training Set
Not explicitly stated. For IVD devices, a "training set" in the context of machine learning is not directly applicable. The "training" here refers to the development and optimization of the reagent formulation and assay parameters. The document doesn't provide specific sample sizes for these development phases.
9. How the Ground Truth for the Training Set Was Established
Not explicitly stated in the document. For IVD assays, the "ground truth" for development and optimization (analogous to training) would typically involve:
- Using known concentrations of ceruloplasmin (e.g., from purified human ceruloplasmin or spiked samples).
- Testing against established reference methods or highly characterized samples.
- Performing extensive analytical verification during the development phase to ensure the assay performs as intended across its measuring range and with various interference challenges.
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510(k) Summary – COBAS INTEGRA Ceruloplasmin KO 62114
According to the requirements of 21 CFR 807.92, the following information Introduction provides sufficient detail to understand the basis for a determination of substantial equivalence
Due to a misinterpretation caused in part by an error on the FDA Purpose classification database available on line, which had erroneously listed Ceruloplasmin as exempt until June 2005, this test system was erroneously considered by us to be exempt during its original application to the COBAS INTEGRA and Roche Hitachi families of analyzers. It was erroneously listed by us as exempt in the reagent lists accompanying the FDA-cleared premarket notification submissions for the COBAS INTEGRA 800 and Roche Hitachi 917 analyzers. The COBAS INTEGRA family of analyzers was cleared under K951595 and the Roche/Hitachi family of analyzers under K953239/A005.
In order to correct this error, Roche now submits a traditional 510(k) featuring performance data on the Integra 700 analyzer. The assay has already been applied to all Integra family members and to the Roche/Hitachi family of analyzers using the Application Validation Protocol submitted as part of this 510(k).
Roche Diagnostics Submitter name, address, 9115 Hague Rd contact Indianapolis IN 46250 (317) 521-3723
Contact person: Corina Harper
Date prepared: Jul 17, 2006
Device Name Proprietary name: COBAS INTEGRA Ceruloplasmin
Common name: Ceruloplasmin
Classification name: Ceruloplasmin immunological test system
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| DeviceDescription | The COBAS INTEGRA Ceruloplasmin cassette (CERU) contains an in vitrodiagnostic reagent system intended for use on COBAS INTEGRA SYSTEMSfor the quantitative immunological determination of human ceruloplasmin inserum and plasma. The calibrator and control were cleared via K954992. |
|---|---|
| Measurements of ceruloplasmin aid in the diagnosis of copper metabolismdisorders. | |
| The test principle is an immunoturbidimetric assay. The calibrator isSerumproteins T Standard and the recommended control material is theSerumproteins T Control. | |
| Intended use | The COBAS INTEGRA Ceruloplasmin cassette (CERU) contains an in vitrodiagnostic reagent system intended for use on COBAS INTEGRA SYSTEMSfor the quantitative immunological determination of human ceruloplasmin inserum and plasma (test CERU3, 0-666). |
| PredicateDevice | We claim substantial equivalence to the DakoCytomation assay forPolyclonal Rabbit Anti-Human Ceruloplasmin cleared as K812486. |
| Substantialequivalency -Similarities | The table below indicates the similarities between the COBAS INTEGRACeruloplasmin test and its predicate device (Polyclonal Rabbit Anti-HumanCeruloplasmin cleared as K812486). |
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| Feature | Predicate device: PolyclonalRabbit Anti-HumanCeruloplasmin (K812486) | COBAS INTEGRACeruloplasmin |
|---|---|---|
| General | ||
| Intended Use/Indications forUse | Polyclonal Rabbit Anti-HumanCeruloplasmin is intended for thequantitative determination ofCeruloplasmin in human samplematerial by turbidimetry andnephelometry. | The COBAS INTEGRACeruloplasmin cassette (CERU)contains an in vitro diagnosticreagent system intended for useCOBAS INTEGRA SYSTEMS forthe quantitative immunologicaldetermination of humanceruloplasmin in serum and plasma(test CERU3, 0-666). |
| Specimen type | Serum, plasma | Same |
| Test principle | ||
| Referencemethod | turbidimetry and nephelometry | turbidimetry |
| Reagent information |
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| Stability - shelflife and on-board | 2-8 °C until expiration dateStability of prediluted antibody: 28days at 2-8 °COn board stability: 28 days 2-8 °Cuntil expiration date | 2-8 °C until expiration dateCOBAS INTEGRA 400/400+On board in use 8 weeks at 10 to15° CCOBAS INTEGRA 700/800On board in use 8 weeks at 8°C |
|---|---|---|
| Calibrator | Human Serum Protein CalibratorInterval: each lot or 28 days | Serum Proteins T StandardInterval: each lot |
| Quality control | Human Serum Protein Low andHigh | Serum Proteins T ControlInterval: 24 hrs recommended |
| Traceability | Information not available. | Standardized againstIFCC/BCR/CAP referencepreparation CRM 470 (RPPHS91/0619) for 14 serum proteins. |
| Performance characteristics | ||
| Measuring range | 0.06-1.3 g/L | 0.06-1.26 g/L |
| Lower DetectionLimit | 0.02 g/L | 0.017 g/L |
| Expected values | 0.2-0.6 g/L | Same |
The table below indicates the similarities between the COBAS INTEGRA Substantial equivalency – Ceruloplasmin test and its predicate device (DakoCytomation assay for Differences Polyclonal Rabbit Anti-Human Ceruloplasmin cleared as K812486). 1
·
| Feature | Predicate device: PolyclonalRabbit Anti-HumanCeruloplasmin (K812486) | COBAS INTEGRACeruloplasmin |
|---|---|---|
| Reagent information | ||
| R1 | Purified immunoglobulin fraction ofrabbit antiserum provided in liquid.In 0.1 mol/L NaCl, 15 mmol/LNaN3 | R1: AcceleratorPolyethylene glycol (PEG) 50 g/L,in phosphate buffer stabilized with0.09% sodium azide in vial A(liquid) |
| R2 | ||
| R2=SR: | ||
| Anti-ceruloplasmin T antiserum(rabbit) specific for humanceruloplasmin >0.42 g/L inphosphate buffer stabilized with0.09% sodium azide in vial C(liquid) | ||
| Instrument | COBAS MIRA, Hitachi and otherinstruments | COBAS Integra family ofanalyzers, Roche/Hitachi family(including cobas c6000 series) |
| Performance characteristics | ||
| Precision | Within run total CV% | Within run total CV%: |
| 1.0% @ 0.27 g/L | 3.88% @ 0.2 g/L | |
| 1.4% @ 0.34 g/L | 2.66% @ 0.35 g/L | |
| 1.6% @ 0.62 g/L | ||
| Linearity | 0.06-0.69 g/L | 0.06-1.26 g/L |
| Endogenousinterferences | Hemolysis no interferences up to 10g/L | Hemolysis: no significantinterferences |
| Icterus no interferences up to 600mg/L | Icterus: no significant interferences | |
| Triglycerides no interferences up to25 g/L | Lipemia: no significantinterferences | |
| Intralipid at 10 g/L | Rheumatoid factors: no significantinterferences up to 400 IU/mL | |
| ExogenousInterferences | Gammopathy, in particular IgM,may cause unreliable results in rarecases | |
| Methodcomparison | y = COBAS INTEGRA Ceruloplasminx = DAKOCytomation Anti Human Ceruloplasmin | |
| Passing-Bablok results: y = $1.0x - 0.0$ g/L; r =0.987 |
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Proposed Labeling
Proposed labeling sufficient to describe the device, its intended use and the directions for use can be found in Section V. We believe the proposed version of the device labeling presented contains all of the technical information required per 21 CFR 809.10.
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| Validation andDesign Control | Development activities were conducted under appropriate design controlprocedures and the overall product specifications were met. The Declarationof Conformity with Design Controls and Results of Risk Analysis areprovided in Section 5.1. Analytical Performance. |
|---|---|
| Confidentiality | Roche Diagnostics Corporation requests that the FDA not disclose the natureor existence of this submission until the substantial equivalence decision hasbeen reached. |
| Closing | Therefore, we trust the information provided in this Traditional 510(k) willsupport a decision of substantial equivalence of the COBAS INTEGRACeruloplasmin test system to the predicate. |
| If you have any questions or require further information, please do nothesitate to contact this office. | |
| • Phone: (317) 521-3831• FAX: (317) 521-2324• email: corina.harper@roche.com |
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus, which is a symbol of medicine, with three lines representing the three branches of government. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the caduceus.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Roche Diagnostics Corporation. c/o Ms. Corina Harper Regulatory Affairs Consultant 9115 Hague Road Indianapolis, IN 46250
JAN 3 1 2007
Re: K062114
Trade/Device Name: COBAS INTEGRA Ceruloplasmin Model 2055953 Regulation Number: 21 CFR 866.5210 Regulation Name: Ceruloplasmin Immunological Test System Regulatory Class: Class II Product Code: CHN Dated: January 10, 2007 Received: January 11, 2007
Dear Ms. Harper:
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). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The
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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.
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 (240) 276-0450. 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,
Touh R. Beckerf
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
KO 62114 510(k) Number (if known):
COBAS INTEGRA Ceruloplasmin: Ceruloplasmin
Indications For Use:
COBAS INTEGRA:
In vitro test for the quantitative immunological determination of ceruloplasmin in human serum and plasma on COBAS INTEGRA systems.
Measurements of Ceruloplasmin aid in the diagnosis of copper metabolism disorders.
Roche/Hitachi cobas c systems:
In vitro test for the quantitative determination of ceruloplasmin in human serum and plasma on Roche/Hitachi cobas c systems.
Measurements of Ceruloplasmin aid in the diagnosis of copper metabolism disorders.
Prescription Use XXX (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 In Vitro Diagnostic Devices (OIVD)
Page 1 of 1
Mana M Chan
Division Sign-Off
Office of In Vitro Diagnostic
Device Evaluation and Safety
Ko62114
§ 866.5210 Ceruloplasmin immunological test system.
(a)
Identification. A ceruloplasmin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the ceruloplasmin (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin aid in the diagnosis of copper metabolism disorders.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.