(71 days)
Reagent: For in vitro diagnostic use in the quantitative determination of Cystatin-C (CYSC) in human serum or plasma (lithium heparin, potassium EDTA) on the ADVIA Chemistry systems. Measurement of Cystatin C aids in the diagnosis and treatment of renal disease.
Calibrator: For in vitro diagnostic use in the calibration of Cystatin C method on ADVIA Chemistry systems.
The CYSC latex reagent is a suspension of uniform latex particles coated with anticystatin-C antibody. When serum or plasma containing cystatin C is mixed with the latex reagent, agglutination takes place resulting in an increase in turbidity. This turbidity is measured at 571 and 805 nm. The cystatin C concentration in serum or plasma is determined from a calibration curve that is generated with the calibrators.
Here's an analysis of the provided text regarding the acceptance criteria and supporting study for the ADVIA® Chemistry Cystatin C Method:
1. Table of Acceptance Criteria and Reported Device Performance
The provided text does not contain explicit, quantitative acceptance criteria for device performance. Instead, it relies on demonstrating substantial equivalence to an existing predicate device (Dade Behring N Latex Cystatin C and Dade Behring N Protein Standard UY). The "performance" is implicitly deemed acceptable if it closely matches or is considered equivalent to the predicate device in various aspects.
Therefore, the table below reflects the comparative information provided rather than explicit acceptance criteria.
| Feature / Performance Aspect | Predicate Device Performance / Characteristic | Device Performance / Characteristic (ADVIA® Chemistry Cystatin C) |
|---|---|---|
| Intended Use (Reagent) | For quantitative determination of cystatin C in human serum and heparinized plasma; aids in diagnosis/treatment of renal disease. | For quantitative determination of Cystatin C in human serum or plasma (lithium heparin, potassium EDTA); aids in diagnosis/treatment of renal disease. |
| Intended Use (Calibrator) | For preparing reference curves for immunonephelometric determinations of a-1-micorglobulin and Cystatin C using BN systems. | For calibration of Cystatin C method on ADVIA Chemistry systems. |
| Antibody | Rabbit Polyclonal antibodies to human Cystatin C | Rabbit Polyclonal antibodies to human Cystatin C |
| Format | Liquid | Liquid |
| Use of Calibrators | Yes | Yes |
| Traceability | Internal standard of highly purified human cystatin C | Internal standard of highly purified human cystatin C |
| Reference Range | 0.53 - 0.95 mg/L | 0.56 - 0.95 mg/L |
| Sample Matrix | Serum or Heparinized Plasma | Serum, Heparinized Plasma, EDTA plasma |
| Reagents | Three: (1) latex coated with anti-cystatin C antibody, (2) Supplementary A (rabbit antibody), (3) Supplementary B (polyethylene glycol). | Two: R1 (buffer), R2 (latex coated with anti-cystatin C antibody from rabbit). |
| Technology / Methodology | Particle enhanced immunonephelometric assay | Latex enhanced turbidimetric assay |
| Number of Calibrators | 1 (diluted on system to 6 levels) | 6 (5 provided in package and zero-calibrator - DI water) |
| Calibrators | Urinary proteins of human origin, polygeline and preservatives (lyophilized). | Recombinant Cystatin C in human serum base (liquid). |
| Reportable Range | 0.05 - 8.0 mg/L | 0.1 - 8.0 mg/L |
2. Sample Size Used for the Test Set and Data Provenance
The document states: "Comparative testing described in the protocol included in this submission demonstrates substantial equivalent performance."
- Sample Size for Test Set: The specific sample size for the comparative testing (test set) is not explicitly mentioned in the provided text.
- Data Provenance: The country of origin and whether the data was retrospective or prospective is not explicitly mentioned. Given it's a submission to the FDA in the US, it's highly probable that some or all of the data generation occurred in the US or under US regulatory guidelines.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information (experts, qualifications) is typically related to diagnostic imaging or clinical interpretation where human judgment is a critical component of ground truth. For an in vitro diagnostic (IVD) like a Cystatin C blood test, the "ground truth" for the test set would be established by reference methods or validated laboratory results, not by human experts interpreting clinical data in the same way a radiologist would interpret an image.
Therefore, this information is not applicable in the context of this device and is not mentioned in the document.
4. Adjudication Method for the Test Set
Similar to point 3, adjudication methods (like 2+1, 3+1) are for resolving discrepancies in human expert interpretations. For an IVD, the "adjudication" would involve technical verification of reference methods and statistical comparison of analytical results.
Therefore, an adjudication method in this sense is not applicable and is not mentioned.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
An MRMC study is relevant for devices where multiple human readers interpret results, and the device's main benefit is to improve human reader performance (e.g., CAD for radiology). For an in vitro diagnostic like a Cystatin C assay, the device directly measures a biomarker; there is no "human reader" in the sense of interpreting complex diagnostic images or clinical scenarios.
Therefore, an MRMC study was not performed and is not applicable to this device type.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, a standalone performance assessment was effectively done. The entire premise of this 510(k) submission is to demonstrate the analytical performance of the ADVIA Chemistry Cystatin C Method as a standalone assay, comparing its analytical characteristics (e.g., intended use, antibody, format, traceability, reference range, reportable range) directly against the predicate device. The performance data would primarily be objective analytical measurements from the device itself.
7. Type of Ground Truth Used
For this in vitro diagnostic device, the "ground truth" would be established by:
- Reference methods: Highly accurate and precise laboratory methods for measuring Cystatin C.
- Established analytical performance characteristics: The predicate device itself serves as a benchmark for "ground truth" in terms of expected analytical performance and clinical utility. The new device demonstrates substantial equivalence to these established characteristics.
- Internal standards of highly purified human cystatin C: Used for traceability and calibration, indicating a defined chemical standard as part of establishing the truth for concentration measurements.
8. Sample Size for the Training Set
- The document does not specify the sample size used for the training set. For an IVD, "training" typically refers to the development of calibration curves and optimization of the assay parameters rather than a classical machine learning training set with labeled data in the same way an AI model is trained.
9. How the Ground Truth for the Training Set Was Established
For an IVD like this, the "ground truth" for developing or "training" the assay (e.g., establishing calibration curves, optimizing reagents) would likely be established through:
- Known concentrations of purified Cystatin C: Used to create calibration standards (as hinted by "internal standard of highly purified human cystatin C").
- Standard laboratory methods: Validated methods to assign target values to control materials and calibrators.
- Clinical panels: Samples from individuals with known physiological states (e.g., healthy controls, patients with renal disease at various stages) might be used during development to assess clinical correlation, though the analytical ground truth comes from quantitative measures.
The document directly mentions the use of "internal standard of highly purified human cystatin C" for traceability of calibrators, which is a key aspect of establishing ground truth for the quantitative measurement.
§ 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.