CERULOPLASMIN, MODEL 2055953

K062114 · Roche Diagnostics Corp. · CHN · Jan 31, 2007 · Immunology

Device Facts

• Record ID: K062114
• Device Name: CERULOPLASMIN, MODEL 2055953
• Applicant: Roche Diagnostics Corp.
• Product Code: CHN · Immunology
• Decision Date: Jan 31, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5210
• Device Class: Class 2

Intended Use

The COBAS 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.

Device Story

The COBAS Ceruloplasmin cassette is an in vitro diagnostic reagent system for use on COBAS INTEGRA and Roche/Hitachi COBAS c501 analyzers. It utilizes an immunoturbidimetric assay to measure human ceruloplasmin in serum and plasma samples. The device consists of an accelerator (polyethylene glycol) and an anti-ceruloplasmin rabbit antiserum. When mixed with a patient sample, ceruloplasmin forms a precipitate with the antiserum, which is measured turbidimetrically at 340 nm. The resulting signal is proportional to the ceruloplasmin concentration, which is calculated via a standard curve. The device is intended for use by laboratory professionals in clinical settings. Results assist clinicians in diagnosing copper metabolism disorders. The system supports automated dilution for samples outside the reportable range.

Clinical Evidence

Bench testing only. Performance evaluated via precision studies (CLSI EP5-T2), linearity, interference testing (CLSI EP7-P), and method comparison. Method comparison with the predicate (n=97) showed a correlation coefficient (r) of 0.987. A secondary comparison with the Dade Behring assay (n=57) showed r=0.986. Platform comparison between COBAS c501 and INTEGRA 700 (n=91) showed high correlation. Matrix comparison (serum vs. lithium heparin plasma, n=46) showed acceptable recovery (89-105%). No clinical sensitivity or specificity data provided.

Technological Characteristics

Immunoturbidimetric assay. Reagents: polyethylene glycol (R1) and rabbit anti-human ceruloplasmin antiserum (R2). Analyzed at 340 nm. Measuring range: 0.03-1.40 g/L (extended: 0.03-4.20 g/L). Traceable to IFCC/BCR/CAP CRM 470. Compatible with COBAS INTEGRA 400, 400 plus, 700, 800, and Roche/Hitachi COBAS c501 analyzers.

Indications for Use

Indicated for the quantitative measurement of ceruloplasmin in serum and plasma to aid in the diagnosis of copper metabolism disorders.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• Polyclonal Rabbit Anti-Human Ceruloplasmin (K812486)

Submission Summary (Full Text)

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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 [phone]

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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| Device<br>Description | The COBAS INTEGRA Ceruloplasmin cassette (CERU) contains an in vitro<br>diagnostic reagent system intended for use on COBAS INTEGRA SYSTEMS<br>for the quantitative immunological determination of human ceruloplasmin in<br>serum and plasma. The calibrator and control were cleared via K954992. |
|----------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Measurements of ceruloplasmin aid in the diagnosis of copper metabolism<br>disorders. |
| | The test principle is an immunoturbidimetric assay. The calibrator is<br>Serumproteins T Standard and the recommended control material is the<br>Serumproteins T Control. |
| Intended use | The COBAS INTEGRA Ceruloplasmin cassette (CERU) contains an in vitro<br>diagnostic reagent system intended for use on COBAS INTEGRA SYSTEMS<br>for the quantitative immunological determination of human ceruloplasmin in<br>serum and plasma (test CERU3, 0-666). |
| Predicate<br>Device | We claim substantial equivalence to the DakoCytomation assay for<br>Polyclonal Rabbit Anti-Human Ceruloplasmin cleared as K812486. |
| Substantial<br>equivalency -<br>Similarities | The table below indicates the similarities between the COBAS INTEGRA<br>Ceruloplasmin test and its predicate device (Polyclonal Rabbit Anti-Human<br>Ceruloplasmin cleared as K812486). |

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| Feature | Predicate device: Polyclonal<br>Rabbit Anti-Human<br>Ceruloplasmin (K812486) | COBAS INTEGRA<br>Ceruloplasmin |
|-----------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| General | | |
| Intended Use/<br>Indications for<br>Use | Polyclonal Rabbit Anti-Human<br>Ceruloplasmin is intended for the<br>quantitative determination of<br>Ceruloplasmin in human sample<br>material by turbidimetry and<br>nephelometry. | The COBAS INTEGRA<br>Ceruloplasmin cassette (CERU)<br>contains an in vitro diagnostic<br>reagent system intended for use<br>COBAS INTEGRA SYSTEMS for<br>the quantitative immunological<br>determination of human<br>ceruloplasmin in serum and plasma<br>(test CERU3, 0-666). |
| Specimen type | Serum, plasma | Same |
| Test principle | | |
| Reference<br>method | turbidimetry and nephelometry | turbidimetry |
| Reagent information | | |

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| Stability - shelf<br>life and on-board | 2-8 °C until expiration date<br><br>Stability of prediluted antibody: 28<br>days at 2-8 °C<br><br>On board stability: 28 days 2-8 °C<br>until expiration date | 2-8 °C until expiration date<br><br>COBAS INTEGRA 400/400+<br>On board in use 8 weeks at 10 to<br>15° C<br><br>COBAS INTEGRA 700/800<br>On board in use 8 weeks at 8°C |
|----------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Calibrator | Human Serum Protein Calibrator<br><br>Interval: each lot or 28 days | Serum Proteins T Standard<br><br>Interval: each lot |
| Quality control | Human Serum Protein Low and<br>High | Serum Proteins T Control<br><br>Interval: 24 hrs recommended |
| Traceability | Information not available. | Standardized against<br>IFCC/BCR/CAP reference<br>preparation CRM 470 (RPPHS<br>91/0619) for 14 serum proteins. |
| Performance characteristics | | |
| Measuring range | 0.06-1.3 g/L | 0.06-1.26 g/L |
| Lower Detection<br>Limit | 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

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| Feature | Predicate device: Polyclonal<br>Rabbit Anti-Human<br>Ceruloplasmin (K812486) | COBAS INTEGRA<br>Ceruloplasmin |
|-----------------------------|---------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Reagent information | | |
| R1 | Purified immunoglobulin fraction of<br>rabbit antiserum provided in liquid.<br>In 0.1 mol/L NaCl, 15 mmol/L<br>NaN3 | R1: Accelerator<br>Polyethylene glycol (PEG) 50 g/L,<br>in phosphate buffer stabilized with<br>0.09% sodium azide in vial A<br>(liquid) |
| R2 | | |
| | | R2=SR: |
| | | Anti-ceruloplasmin T antiserum<br>(rabbit) specific for human<br>ceruloplasmin >0.42 g/L in<br>phosphate buffer stabilized with<br>0.09% sodium azide in vial C<br>(liquid) |
| Instrument | COBAS MIRA, Hitachi and other<br>instruments | COBAS Integra family of<br>analyzers, Roche/Hitachi family<br>(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 |
| Endogenous<br>interferences | Hemolysis no interferences up to 10<br>g/L | Hemolysis: no significant<br>interferences |
| | Icterus no interferences up to 600<br>mg/L | Icterus: no significant interferences |
| | Triglycerides no interferences up to<br>25 g/L | Lipemia: no significant<br>interferences |
| | Intralipid at 10 g/L | Rheumatoid factors: no significant<br>interferences up to 400 IU/mL |
| Exogenous<br>Interferences | | Gammopathy, in particular IgM,<br>may cause unreliable results in rare<br>cases |
| Method<br>comparison | y = COBAS INTEGRA Ceruloplasmin<br>x = 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 and<br>Design Control | Development activities were conducted under appropriate design control<br>procedures and the overall product specifications were met. The Declaration<br>of Conformity with Design Controls and Results of Risk Analysis are<br>provided in Section 5.1. Analytical Performance. |
|----------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Confidentiality | Roche Diagnostics Corporation requests that the FDA not disclose the nature<br>or existence of this submission until the substantial equivalence decision has<br>been reached. |
| Closing | Therefore, we trust the information provided in this Traditional 510(k) will<br>support a decision of substantial equivalence of the COBAS INTEGRA<br>Ceruloplasmin test system to the predicate. |
| | If you have any questions or require further information, please do not<br>hesitate to contact this office. |
| | • Phone: [phone]<br>• FAX: [phone]<br>• email: [e-mail] |

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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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Page 2 –

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 [phone]. 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 [phone] or [phone] 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)

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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