TINA-QUANT CYSTATIN C, CALIBRATOR F.A.S. CYSTATIN C AND CYSTATIN C ANDCYSTATIN C CONTROL SET

K080811 · Roche Diagnostics Corp. · NDY · Jun 20, 2008 · Clinical Chemistry

Device Facts

• Record ID: K080811
• Device Name: TINA-QUANT CYSTATIN C, CALIBRATOR F.A.S. CYSTATIN C AND CYSTATIN C ANDCYSTATIN C CONTROL SET
• Applicant: Roche Diagnostics Corp.
• Product Code: NDY · Clinical Chemistry
• Decision Date: Jun 20, 2008
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1225
• Device Class: Class 2

Intended Use

Reagent: Immunoturbidimetric assay for the quantitative in vitro determination of cystatin C in human serum and lithium-heparin plasma on Roche automated clinical chemistry analyzers. Cystatin C measurements are used as an aid in the diagnosis and treatment of renal diseases. Calibrator: Cfas (Calibrator for automated systems) Cystatin C is for use in the calibration of quantitative Roche methods on Roche clinical chemistry analyzers as specified in the value sheets. Control: Cystatin C Control Set is for use in quality control by monitoring accuracy and precision for the quantitative methods as specified in the value sheets.

Device Story

Tina-quant Cystatin C is a ready-to-use dual reagent assay; utilizes particle-enhanced immunoturbidimetric principle. Input: human serum or lithium-heparin plasma samples. Operation: latex particles coated with rabbit anti-cystatin C antibodies agglutinate with cystatin C in sample; precipitate measured turbidimetrically on Roche Hitachi 917 analyzer. Output: quantitative cystatin C concentration calculated via interpolation on standard curve. Used in clinical chemistry laboratories by trained personnel. Results aid clinicians in diagnosing and monitoring renal disease. System includes C.f.a.s. Cystatin C calibrator and bi-level control set for quality monitoring.

Clinical Evidence

Bench testing only. Precision studies (N=63 per material) showed total CVs 2.36-3.76%. Linearity confirmed 0.4-8.0 mg/L. Method comparison (N=94) against predicate yielded r²=0.9991. Interference testing showed no significant impact from common compounds or high-dose hook effect up to 20 mg/L. Reference range study conducted on 500 healthy donors.

Technological Characteristics

Particle-enhanced immunoturbidimetric assay. Reagents: latex particles coated with anti-cystatin C antibodies. Calibrator/Control: recombinant human cystatin C produced in E. coli in delipidated human serum matrix. Storage: 2-8°C. Analyzers: Hitachi 917, MODULAR P, cobas c 501. Connectivity: Automated clinical chemistry analyzer integration.

Indications for Use

Indicated for the quantitative determination of cystatin C in human serum and lithium-heparin plasma to aid in the diagnosis and treatment of renal diseases. No specific age or gender restrictions provided.

Regulatory Classification

Identification

A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

Predicate Devices

• DakoCytomation Cystatin C Immunoparticles, Cystatin C Calibrator Kit and Cystatin C Control Set (K041627)

Submission Summary (Full Text)

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Koso8//

JUN 2 0 2008

## 510(k) Summary - Roche Tina-quant Cystatin C, Calibrator and Control Set

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 Submitter Roche Diagnostics name, address. 9115 Hague Rd contact Indianapolis IN 46250 [phone] Contact person: Kerwin Kaufman Date prepared: May 30, 2008 Assay: Device Name Proprietary name: Tina-quant Cystatin C Common name: Cystatin C Classification name: Test, Cystatin C Calibrator: Proprietary name: Cfas (Calibrator for automated systems) Cystatin C Common name: Cystatin C calibrator Classification name: Calibrator, secondary Control: Proprietary name: Cystatin C Control Set Common name: Cystatin C Ouality control material (assayed) Classification name: Single (specified) analyte controls (assayed and unassayed) Device Assay: Description The Roche Tina-quant Cystatin C is an immunoturbidimetric assay for the quantitative in vitro determination of cystatin C in human serum and plasma on Roche automated clinical chemistry analyzers. The test principle is a particle enhanced immunoturbidimetric assay. Human cystatin C agglutinates with latex particles coated with anti-cystatin C antibodies. The precipitate is determined turbidimetrically.

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## 510(k) Summary – Roche Tina-quant Cystatin C, Calibrator and Control Set, Continued ______________________________________________________________________________________________________________________________________________________________________________

| Device<br>Description<br>(continued) | Calibrator:<br>Cfas Cystatin C is a liquid, ready-for-use calibrator based on pooled<br>delipidated human serum enriched with recombinant human cystatin C<br>produced in E. Coli. Single level calibrators with lot specific values are<br>diluted on board the analyzer to create a 6-point calibration curve. |
|-----------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Control:<br>Cystatin C Control Set contains 2 controls based on pooled delipidated human<br>serum enriched with human recombinant cystatin C produced in E. Coli.<br>The adjusted concentrations of the control component are in the low<br>concentration range for Control Low and the elevated concentration<br>range for Control High. |
| Intended use | Assay:<br>Immunoturbidimetric assay for the quantitative in vitro determination of<br>cystatin C in human serum and plasma on Roche automated clinical<br>chemistry analyzers. |
| | Calibrator:<br>Cfas (Calibrator for automated systems) Cystatin C is for use in the<br>calibration of quantitative Roche methods on Roche clinical chemistry<br>analyzers as specified in the value sheets. |
| | Control:<br>Cystatin C Control Set is for use in quality control by monitoring accuracy<br>and precision for the quantitative methods as specified in the value sheets. |
| Predicate<br>Device | We claim substantial equivalence to the DakoCytomation Cystatin C<br>Immunoparticles, Cystatin C Calibrator Kit and Cystatin C Control Set<br>cleared in 510(k) K041627. |
| Substantial<br>equivalency -<br>Reagent | The table below provides a comparison of the predicate device,<br>DakoCytomation Cystatin C Immunoparticles (K041627) and the new device<br>Roche Tina-quant Cystatin C. |

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| Feature | Predicate device:<br>DakoCytomation Cystatin C<br>Immunoparticles (K041627) | New Device:<br>Roche Tina-quant Cystatin C |
|------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use/<br>Indications for<br>Use | For in vitro diagnostic use. For<br>professional use only. Cystatin C<br>Immunoparticles are intended for<br>the quantitative determination of<br>cystatin C in human serum,<br>heparinized plasma and EDTA<br>plasma by turbidimetry and<br>nephelometry. Cystatin C<br>measurements are used as an aid in<br>the diagnosis and treatment of renal<br>diseases. | Immunoturbidimetric assay for the<br>quantitative in vitro determination<br>of cystatin C in human serum and<br>plasma on Roche automated<br>clinical chemistry analyzers.<br><br>Cystatin C measurements are used<br>as an aid in the diagnosis and<br>treatment of renal diseases. |
| Specimen type | Serum, heparinized plasma, EDTA<br>plasma | Serum and Lithium-heparinized<br>plasma |
| Method | Particle enhanced<br>immunoturbidimetric assay | Same |
| Traceability /<br>Standardization | The cystatin C value assignment has<br>been carried out by turbidimetry<br>using a precise transfer protocol<br>ensuring traceability to a pure<br>recombinant cystatin C reference<br>preparation, where the cystatin C<br>concentration was established by<br>dry mass determination. | This method has been standardized<br>against an in-house reference<br>preparation of pure recombinant<br>human cystatin C. The cystatin C<br>concentration of this reference<br>preparation was established by dry<br>mass determination as described in<br>reference. |
| Reagent Storage | 2 - 8°C | 2 - 8°C |
| Calibrator | DakoCytomation Cystatin C<br>Calibrator, single level<br>Diluted to form a 6-point calibration<br>curve | C.f.a.s. Cystatin C Calibrator,<br>single level<br>Diluted to form a 6-point<br>calibration curve |
| Quality control | DakoCytomation Cystatin C Control<br>Set, 2-level | Cystatin C Control Set, 2-level |
| Expected values | Individuals 1-50 years:<br>0.55-1.15 mg/L<br>Individuals > 50 years:<br>0.63-1.44 mg/L | Same |
| Analyzers | Hitachi 911, Hitachi 917,<br>MODULAR P, Cobas Mira Plus and<br>IMMAGE | Hitachi 917, MODULAR P, and<br>cobas c 501 |
| Measuring<br>Range | ~0.4 - 7.5 mg/L | 0.4 - 8.0 mg/L |
| Method<br>comparison<br>with Dako<br>predicate | Passing Bablok: y = $1.009x + 0.019$<br>$\tau = 0.96$<br>Linear regression: y = $1.014x + 0.011$<br>$r = 0.999$ | |
| Precision | | Within run CV:<br>0.91% @ 4.48 mg/L<br>0.97% @ 0.95 mg/L<br>1.71% @ 0.75 mg/L<br>0.67% @ 5.14 mg/L |
| | Total CV:<br>2.1% @ 3.95 mg/L<br>2.6% @ 0.96 mg/L<br>5.9% @ 0.45 mg/L<br>2.0% @ 1.71 mg/L<br>2.3% @ 5.37 mg/L | Total CV:<br>2.50% @ 4.35 mg/L<br>3.13% @ 0.94 mg/L<br>3.76% @ 0.73 mg/L<br>2.36% @ 4.98 mg/L |
| Limitations | Bilirubin, conjugated:<br>No interference was found for<br>conjugated bilirubin up to 600 mg/L<br>(60 mg/dL).<br><br>Bilirubin, unconjugated:<br>No interference was found for<br>unconjugated bilirubin up to 600<br>mg/L (60 mg/dL).<br><br>Hemoglobin:<br>No interference was found for<br>hemoglobin up to 10 g/L (1000<br>mg/dL).<br><br>Triglyceride:<br>No interference was found for<br>triglyceride up to 15 g/L (1500<br>mg/dL).<br><br>Rheumatoid Factor:<br>No interference was found for<br>rheumatoid factor up to 1200<br>IU/mL.<br><br>No antigen excess is found for<br>cystatin C concentrations below 28<br>mg/L (the highest concentration<br>tested).<br><br>All drugs described in reference 7<br>were investigated according to the<br>recommendations in reference 7.<br>No interference was observed. | Icterus: No significant interference<br>up to an I index of 60 (approximate<br>conjugated and unconjugated<br>bilirubin concentration: 60 mg/dL<br>or 1026 μmol/L).<br><br>Hemolysis: No significant<br>interference up to an H index of<br>700 (approximate hemoglobin<br>concentration: 700 mg/dL or 435<br>μmol/L).<br><br>Lipemia (Intralipid): No significant<br>interference up to an L index of<br>1000.<br>There is poor correlation between<br>the L index (corresponds to<br>turbidity) and triglycerides<br>concentration.<br><br>Rheumatoid factors < 1200 IU/mL<br>do not interfere.<br><br>A high-dose hook effect may occur<br>at cystatin C concentrations >20.0<br>mg/L.<br><br>Drugs: No interference was found<br>at therapeutic concentrations<br>using common drug panels (see<br>references 18 and 19 in labeling).<br><br>In very rare cases gammopathy, in<br>particular type IgM Waldenström's<br>macroglobulinemia), may cause<br>unreliable results. |

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| Substantial | The table below provides a comparison of the predicate device, |
|---------------|-------------------------------------------------------------------------|
| equivalency - | DakoCytomation Cystatin C Calibrator (K041627) and the new device, Cfas |
| Calibrator | (Calibrator for automated systems) Cystatin C. |

| Feature | Predicate device:<br>DakoCytomation Cystatin C<br>Calibrator (K041627) | New Device:<br>Roche Cfas (Calibrator for<br>automated systems) Cystatin C |
|--------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Cystatin C Calibrator is intended for<br>establishing calibration curves for<br>the quantitative immunological<br>determination of human cystat C by<br>turbidimetry or nephelometry. | Cfas (Calibrator for automated<br>systems) Cystatin C is for use in the<br>calibration of quantitative Roche<br>methods on Roche clinical<br>chemistry analyzers as specified in<br>the value sheets. |
| Analyte | Cystatin C | Same |
| Matrix | A liquid pool of delipidated human<br>serum enriched with recombinant<br>human cystatin C produced in E.<br>coli and preservative. | Same |
| Storage | 2 – 8 °C | Same |

| Substantial | The table below provides a comparison of the predicate device, |
|---------------|--------------------------------------------------------------------|
| equivalency - | DakoCytomation Cystatin C Control Set (K041627) and the new device |

- Control Set
DakoCytomation Cystatin C Control Set (K041627) and the new device,
Roche Cystatin C Control Set.

| Feature | Predicate device:<br>DakoCytomation Cystatin C<br>Control Set (K041627) | New Device:<br>Roche Cystatin C Control Set |
|--------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Cystatin C Control Set is an assayed<br>bi-level control intended to monitor<br>and evaluate the precision and<br>accuracy of the quantitative<br>immunological determination of<br>human cystatin C by turbidimetry or<br>nephelometry. | Cystatin C Control Set is for use in<br>quality control by monitoring<br>accuracy and precision for the<br>quantitative methods as specified in<br>the value sheets. |
| Analyte | Cystatin C | Same |
| Matrix | 2-level set with low and high<br>cystatin C levels, based on liquid<br>pools of delipidated human serum<br>enriched with recombinant human<br>cystatin C produced in E. coli and<br>preservative. | Same |
| Storage | 2 – 8 °C | Same |

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| Performance | evaluation | The Hitachi 917 Cystatin C test system was evaluated for several<br>performance characteristics described within the submission. |
|-------------|------------|------------------------------------------------------------------------------------------------------------------------------------------------------|
| | | In addition, the traceability, value assignment process, and stability of<br>the Cfas Cystatin C calibrator and Cytatin C Control set are described. |

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Image /page/6/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features an eagle with outstretched wings, symbolizing protection and care. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES. USA" are arranged in a circular pattern around the eagle. The seal is simple and monochromatic.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Roche Diagnostics Corp. c/o Kerwin Kaufman 9115 Hague Road Indianapolis, In 46250

JUN 2 0 2008

Re: k080811 Trade Name: Tina-Quant Cystatin C Regulation Number: 21 CFR 862.1225 Regulation Name: Test, Cystatin C Regulatory Class: Class II Product Codes: NDY, JIT, JJX Dated: March 21, 2008 Received: March 24, 2008

Dear Kerwin Kaufman:

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 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).

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Page 2 -

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 1 logal/y 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 tolloffee number [phone] or [phone] or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Jean M. Cooper, M.S., D.V.M.

Téan M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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## Indications for Use

KOSORII 510(k) Number (if known):

Device Name: Roche Tina-quant Cystatin C, Calibrator and Controls

Indications For Use:

Reagent:

Immunoturbidimetric assay for the quantitative in vitro determination of cystatin C in human serum and lithium-heparin plasma on Roche automated clinical chemistry analyzers. Cystatin C measurements are used as an aid in the diagnosis and treatment of renal diseases.

Calibrator:

Cfas (Calibrator for automated systems) Cystatin C is for use in the calibration of quantitative Roche methods on Roche clinical chemistry analyzers as specified in the value sheets.

Control:

Cystatin C Control Set is for use in quality control by monitoring accuracy and precision for the quantitative methods as specified in the value sheets.

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)

Carol C. Benson
Division Sign-Off

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Office of In Vitro Diagnostic Device Rvaluation and Safety

K080811