(88 days)
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.
Assay: 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.
Calibrator: Cfas Cystatin C is a liquid, ready-for-use calibrator based on pooled delipidated human serum enriched with recombinant human cystatin C produced in E. Coli. Single level calibrators with lot specific values are diluted on board the analyzer to create a 6-point calibration curve.
Control: Cystatin C Control Set contains 2 controls based on pooled delipidated human serum enriched with human recombinant cystatin C produced in E. Coli. The adjusted concentrations of the control component are in the low concentration range for Control Low and the elevated concentration range for Control High.
Here's an analysis of the acceptance criteria and study details for the Roche Tina-quant Cystatin C device based on the provided text, structured according to your requirements.
Note: The provided document is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device. Therefore, it does not explicitly state "acceptance criteria" in the way a performance specification document might. Instead, it presents performance data for the new device as part of the evidence for substantial equivalence, implying these results met the company's internal acceptance for market clearance. I will extract the relevant performance metrics and compare them to the predicate device where applicable, as the direct acceptance criteria for each measurement are not explicitly listed in threshold format.
Acceptance Criteria and Device Performance
The core acceptance criterion for this 510(k) submission is substantial equivalence to the predicate device, DakoCytomation Cystatin C Immunoparticles (K041627). This means the new device must perform comparably to the predicate across various analytical characteristics.
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Implied Acceptance Criteria (via predicate comparison or internal validation) | Reported Device Performance (Roche Tina-quant Cystatin C) |
|---|---|---|
| Intended Use | Substantially equivalent to predicate device's intended use. | Aid in diagnosis and treatment of renal diseases. |
| Specimen Type | Serum, heparinized plasma (predicate) | Serum and Lithium-heparinized plasma |
| Method | Particle enhanced immunoturbidimetric assay (same as predicate) | Same |
| Traceability / Standardization | Traceable to recombinant cystatin C reference (same as predicate). | Standardized against in-house reference preparation of pure recombinant human cystatin C by dry mass determination. |
| Reagent Storage | 2 - 8°C (same as predicate) | 2 - 8°C |
| Calibrator | Single-level, 6-point calibration curve (same as predicate). | C.f.a.s. Cystatin C Calibrator, single level, diluted to form a 6-point calibration curve. |
| Quality Control | 2-level control set (same as predicate). | Cystatin C Control Set, 2-level. |
| Expected Values | 1-50 years: 0.55-1.15 mg/L; >50 years: 0.63-1.44 mg/L (same as predicate). | Same |
| Analyzers | Compatibility with automated clinical chemistry analyzers. | Hitachi 917, MODULAR P, and cobas c 501 |
| Measuring Range | ~0.4 - 7.5 mg/L (predicate) | 0.4 - 8.0 mg/L |
| Method Comparison (vs. Dako predicate) | Passing Bablok: y = 1.009x + 0.019, $\tau$ = 0.96; Linear regression: y = 1.014x + 0.011, r = 0.999 | (These are the results themselves, demonstrating equivalence) |
| Precision | Demonstrated acceptable within-run and total CVs. | Within run CV: 0.91% @ 4.48 mg/L, 0.97% @ 0.95 mg/L, 1.71% @ 0.75 mg/L, 0.67% @ 5.14 mg/L. Total CV: 2.50% @ 4.35 mg/L, 3.13% @ 0.94 mg/L, 3.76% @ 0.73 mg/L, 2.36% @ 4.98 mg/L. |
| Limitations/Interferences | No significant interference from common interferents up to specified levels (predicate demonstrated this). | Icterus: No significant interference up to I index of 60. Hemolysis: No significant interference up to H index of 700. Lipemia: No significant interference up to L index of 1000. Rheumatoid factors < 1200 IU/mL do not interfere. High-dose hook effect may occur at >20.0 mg/L. No interference from common drugs. |
2. Sample Size Used for the Test Set and Data Provenance:
- Method Comparison Study: The document states "Method comparison with Dako predicate" and provides Passing Bablok and Linear Regression results. It does not explicitly state the sample size (number of patient samples) used for this comparison.
- Precision Study: Again, specific sample sizes (number of replicates, days of testing, or number of distinct samples) for the precision studies (Within run CV and Total CV) are not explicitly detailed.
- Interference Study: The number of samples or conditions tested for interference studies (Icterus, Hemolysis, Lipemia, Rheumatoid Factor, Drugs) is not detailed.
- Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. Given it's a submission to the FDA, it's highly likely the studies were conducted under Good Laboratory Practice (GLP) or similar quality systems, but the specific details are not provided.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:
Not applicable. This device is an in vitro diagnostic (IVD) assay measuring a quantitative biomarker (Cystatin C). "Ground truth" for such devices is established through analytical methods and reference materials, not typically by expert consensus of clinicians reviewing cases. The value assignment for the calibrators is tied to an in-house reference preparation of pure recombinant human cystatin C whose concentration was established by dry mass determination.
4. Adjudication Method for the Test Set:
Not applicable for this type of IVD device. Adjudication by multiple clinical experts is not commonly used for establishing the analytical accuracy (ground truth) of a quantitative biochemical assay.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study:
Not applicable. MRMC studies are typically used for medical imaging devices where human readers interpret images, sometimes with AI assistance. This device is a fully automated quantitative assay, not requiring human interpretation of clinical "cases" in the same way. The performance is assessed analytically.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:
Yes, the performance data presented (Method Comparison, Precision, Limitations) represents the standalone performance of the automated assay system (Roche Tina-quant Cystatin C on Roche automated clinical chemistry analyzers). There is no "human-in-the-loop" aspect to the basic measurement process, beyond proper sample handling and instrument operation.
7. Type of Ground Truth Used:
The ground truth for the assay's measurements is established by traceability to a high-purity reference material.
- The "cystatin C concentration of this reference preparation was established by dry mass determination." This is a fundamental analytical method.
- Calibrator value assignment ensuring traceability to this pure recombinant cystatin C reference preparation.
- Method comparison was done against a legally marketed predicate device (DakoCytomation Cystatin C Immunoparticles, K041627), implying the predicate's measurements serve as a comparative standard, which itself would have been traceable to a suitable reference.
8. Sample Size for the Training Set:
Not applicable. This is a biochemical assay, not an AI/machine learning device that requires a "training set" in the conventional sense. The "training" of the assay involves the development and optimization of the reagents and methodology, which is a laboratory R&D process rather than data-driven machine learning.
9. How the Ground Truth for the Training Set Was Established:
Not applicable, as there is no "training set" for concept described in machine learning. However, during the assay development process, the accuracy of the assay would be established through:
- Use of precisely characterized reference materials (like the recombinant human cystatin C standards).
- Validation against established analytical methods.
- Cross-validation with existing, validated assays.
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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 (317) 521-7637 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.
Continued on next page
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510(k) Summary – Roche Tina-quant Cystatin C, Calibrator and Control Set, Continued ______________________________________________________________________________________________________________________________________________________________________________
| DeviceDescription(continued) | Calibrator:Cfas Cystatin C is a liquid, ready-for-use calibrator based on pooleddelipidated human serum enriched with recombinant human cystatin Cproduced in E. Coli. Single level calibrators with lot specific values arediluted on board the analyzer to create a 6-point calibration curve. |
|---|---|
| Control:Cystatin C Control Set contains 2 controls based on pooled delipidated humanserum enriched with human recombinant cystatin C produced in E. Coli.The adjusted concentrations of the control component are in the lowconcentration range for Control Low and the elevated concentrationrange for Control High. | |
| Intended use | Assay:Immunoturbidimetric assay for the quantitative in vitro determination ofcystatin C in human serum and plasma on Roche automated clinicalchemistry analyzers. |
| Calibrator:Cfas (Calibrator for automated systems) Cystatin C is for use in thecalibration of quantitative Roche methods on Roche clinical chemistryanalyzers as specified in the value sheets. | |
| Control:Cystatin C Control Set is for use in quality control by monitoring accuracyand precision for the quantitative methods as specified in the value sheets. | |
| PredicateDevice | We claim substantial equivalence to the DakoCytomation Cystatin CImmunoparticles, Cystatin C Calibrator Kit and Cystatin C Control Setcleared in 510(k) K041627. |
| Substantialequivalency -Reagent | The table below provides a comparison of the predicate device,DakoCytomation Cystatin C Immunoparticles (K041627) and the new deviceRoche Tina-quant Cystatin C. |
.
:
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| Feature | Predicate device:DakoCytomation Cystatin CImmunoparticles (K041627) | New Device:Roche Tina-quant Cystatin C |
|---|---|---|
| Intended Use/Indications forUse | For in vitro diagnostic use. Forprofessional use only. Cystatin CImmunoparticles are intended forthe quantitative determination ofcystatin C in human serum,heparinized plasma and EDTAplasma by turbidimetry andnephelometry. Cystatin Cmeasurements are used as an aid inthe diagnosis and treatment of renaldiseases. | Immunoturbidimetric assay for thequantitative in vitro determinationof cystatin C in human serum andplasma on Roche automatedclinical chemistry analyzers.Cystatin C measurements are usedas an aid in the diagnosis andtreatment of renal diseases. |
| Specimen type | Serum, heparinized plasma, EDTAplasma | Serum and Lithium-heparinizedplasma |
| Method | Particle enhancedimmunoturbidimetric assay | Same |
| Traceability /Standardization | The cystatin C value assignment hasbeen carried out by turbidimetryusing a precise transfer protocolensuring traceability to a purerecombinant cystatin C referencepreparation, where the cystatin Cconcentration was established bydry mass determination. | This method has been standardizedagainst an in-house referencepreparation of pure recombinanthuman cystatin C. The cystatin Cconcentration of this referencepreparation was established by drymass determination as described inreference. |
| Reagent Storage | 2 - 8°C | 2 - 8°C |
| Calibrator | DakoCytomation Cystatin CCalibrator, single levelDiluted to form a 6-point calibrationcurve | C.f.a.s. Cystatin C Calibrator,single levelDiluted to form a 6-pointcalibration curve |
| Quality control | DakoCytomation Cystatin C ControlSet, 2-level | Cystatin C Control Set, 2-level |
| Expected values | Individuals 1-50 years:0.55-1.15 mg/LIndividuals > 50 years:0.63-1.44 mg/L | Same |
| Analyzers | Hitachi 911, Hitachi 917,MODULAR P, Cobas Mira Plus andIMMAGE | Hitachi 917, MODULAR P, andcobas c 501 |
| MeasuringRange | ~0.4 - 7.5 mg/L | 0.4 - 8.0 mg/L |
| Methodcomparisonwith Dakopredicate | Passing Bablok: y = $1.009x + 0.019$$\tau = 0.96$Linear regression: y = $1.014x + 0.011$$r = 0.999$ | |
| Precision | Within run CV:0.91% @ 4.48 mg/L0.97% @ 0.95 mg/L1.71% @ 0.75 mg/L0.67% @ 5.14 mg/L | |
| Total CV:2.1% @ 3.95 mg/L2.6% @ 0.96 mg/L5.9% @ 0.45 mg/L2.0% @ 1.71 mg/L2.3% @ 5.37 mg/L | Total CV:2.50% @ 4.35 mg/L3.13% @ 0.94 mg/L3.76% @ 0.73 mg/L2.36% @ 4.98 mg/L | |
| Limitations | Bilirubin, conjugated:No interference was found forconjugated bilirubin up to 600 mg/L(60 mg/dL).Bilirubin, unconjugated:No interference was found forunconjugated bilirubin up to 600mg/L (60 mg/dL).Hemoglobin:No interference was found forhemoglobin up to 10 g/L (1000mg/dL).Triglyceride:No interference was found fortriglyceride up to 15 g/L (1500mg/dL).Rheumatoid Factor:No interference was found forrheumatoid factor up to 1200IU/mL.No antigen excess is found forcystatin C concentrations below 28mg/L (the highest concentrationtested).All drugs described in reference 7were investigated according to therecommendations in reference 7.No interference was observed. | Icterus: No significant interferenceup to an I index of 60 (approximateconjugated and unconjugatedbilirubin concentration: 60 mg/dLor 1026 μmol/L).Hemolysis: No significantinterference up to an H index of700 (approximate hemoglobinconcentration: 700 mg/dL or 435μmol/L).Lipemia (Intralipid): No significantinterference up to an L index of1000.There is poor correlation betweenthe L index (corresponds toturbidity) and triglyceridesconcentration.Rheumatoid factors < 1200 IU/mLdo not interfere.A high-dose hook effect may occurat cystatin C concentrations >20.0mg/L.Drugs: No interference was foundat therapeutic concentrationsusing common drug panels (seereferences 18 and 19 in labeling).In very rare cases gammopathy, inparticular type IgM Waldenström'smacroglobulinemia), may causeunreliable 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:DakoCytomation Cystatin CCalibrator (K041627) | New Device:Roche Cfas (Calibrator forautomated systems) Cystatin C |
|---|---|---|
| Intended Use | Cystatin C Calibrator is intended forestablishing calibration curves forthe quantitative immunologicaldetermination of human cystat C byturbidimetry or nephelometry. | Cfas (Calibrator for automatedsystems) Cystatin C is for use in thecalibration of quantitative Rochemethods on Roche clinicalchemistry analyzers as specified inthe value sheets. |
| Analyte | Cystatin C | Same |
| Matrix | A liquid pool of delipidated humanserum enriched with recombinanthuman cystatin C produced in E.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:DakoCytomation Cystatin CControl Set (K041627) | New Device:Roche Cystatin C Control Set |
|---|---|---|
| Intended Use | Cystatin C Control Set is an assayedbi-level control intended to monitorand evaluate the precision andaccuracy of the quantitativeimmunological determination ofhuman cystatin C by turbidimetry ornephelometry. | Cystatin C Control Set is for use inquality control by monitoringaccuracy and precision for thequantitative methods as specified inthe value sheets. |
| Analyte | Cystatin C | Same |
| Matrix | 2-level set with low and highcystatin C levels, based on liquidpools of delipidated human serumenriched with recombinant humancystatin C produced in E. coli andpreservative. | Same |
| Storage | 2 – 8 °C | Same |
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| Performance | evaluation | The Hitachi 917 Cystatin C test system was evaluated for severalperformance characteristics described within the submission. |
|---|---|---|
| In addition, the traceability, value assignment process, and stability ofthe 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 (240) 276-0490. 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 (800) 638-2041 or (240) 276-3150 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
-Page 1 of
Office of In Vitro Diagnostic Device Rvaluation and Safety
§ 862.1225 Creatinine test system.
(a)
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.(b)
Classification. Class II.