(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 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.
§ 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.