(79 days)
For In Vitro Diagnostic Use. For Professional Use Only.
Cystatin C Immunoparticles are intended for the quantitative determination of cystatin C in human serum, heparinized plasma and EDTA plasma by turbidimetry and nephelometry. Cystatin C measurements are used as an aid in the diagnosis and treatment of renal diseases.
Cystatin C Control Set is an assayed bi-level control intended to monitor and evaluate the precision and accuracy of the quantitative immunological determination of human cystatin C by turbidimetry or nephelometry.
The Cystatin C Calibrator is intended for establishing calibration curves for the quantitative immunological determination of human cystatin C by turbidimetry or nephelometry.
Cystatin C Immunoparticles are purified immunoglobulin fraction of rabbit antiserum directed against cystatin C covalently coupled to uniform polystyrene particles. The Cystatin C Immunoparticles are provided as a suspension preserved with 15 mmol/L sodium azide and are supplied ready for use. Recombinant human cystatin C produced in E. coli was used as an immunogen for raising the antibody coupled to the polystyrene particles.
In the DakoCytomation Cystatin C Assay, human serum or plasma is mixed with the Cystatin C Immunoparticles. The resulting immune complexes are measured by turbidimetry or nephelometry. The generated signal is correlated with the concentration of cystatin C in the sample. By interpolation on a standard curve, the concentration of cystatin C in the sample is calculated.
Cystatin C Control Set is a bi-level control. The controls are liquid pools of delipidated human serum enriched with recombinant human cystatin C produced in E. coli and preserved with 15 mmol/L sodium azide. Each donor has been tested and found negative for hepatitis B virus surface antigen, antibodies to hepatitis C virus and human immunodeficiency virus 1 and 2. The Cystatin C Control Set is supplied ready for use.
The cystatin C value assignment has been carried out by turbidimetry using the DakoCytomation Cystatin C Calibrator, code No. X 0974, as reference.
Cystatin C Calibrator is a liquid pool of delipidated human serum enriched with recombinant human cystatin C produced in E. coli and preserved with 15 mmol/L sodium azide. Each donor has been tested and found negative for hepatitis B virus surface antigen, antibodies to hepatitis C virus and human immunodeficiency virus 1 and 2. The Cystatin C Calibrator is supplied ready for use.
The cystatin C value assignment has been carried out by turbidimetry using a precise transfer protocol ensuring traceability to a pure recombinant human cystatin C reference preparation, where the cystatin C concentration was established by dry mass determination.
The provided text describes a 510(k) premarket notification for three in vitro diagnostic devices: Cystatin C Immunoparticles, Cystatin C Control Set, and Cystatin C Calibrator. The focus of the submission is to demonstrate substantial equivalence to previously marketed predicate devices rather than proving a new performance characteristic against a fixed set of acceptance criteria. Therefore, the information regarding acceptance criteria and performance studies is presented differently than would be expected for a device with novel performance claims.
Here's an analysis of the provided information:
1. A table of acceptance criteria and the reported device performance
The document does not present a formal table of distinct acceptance criteria with corresponding performance results similar to what might be found for a device with a specific diagnostic accuracy claim (e.g., sensitivity, specificity, AUC). Instead, the performance evaluations were conducted to demonstrate "substantial equivalence" to predicate devices. The performance characteristics studied include:
| Performance Characteristic | Description / Reported Performance |
|---|---|
| Precision | Studied and found to contribute to substantial equivalence. Specific quantitative results (e.g., CV%) are not provided in this summary. |
| Accuracy | Studied and found to contribute to substantial equivalence. Specific quantitative results are not provided in this summary. |
| Linearity | Studied and found to contribute to substantial equivalence. Specific quantitative results are not provided in this summary. |
| Sensitivity | Studied and found to contribute to substantial equivalence. Specific quantitative results are not provided in this summary. |
| Specificity | Studied and found to contribute to substantial equivalence. Specific quantitative results are not provided in this summary. |
| Security Ranges | Studied and found to contribute to substantial equivalence. Specific quantitative results are not provided in this summary. |
| Interferences | Studied and found to contribute to substantial equivalence. Details on specific interferents and their effects are not provided. |
| Stability Testing | Studied and found to contribute to substantial equivalence. Details on study methods and results are not provided. |
| Comparability (Turbidimetry/Nephelometry) | Assay results obtained with various commercially available turbidimeters and the IMMAGE® Immunochemistry System (nephelometer) were analyzed and found to be comparable. |
| Comparability to Predicate (Dade Behring) | A comparison of performance demonstrated substantial equivalence to the Dade Behring, Inc. N Latex Cystatin C Test Kit (K003503) and N Protein Standard UY (K003501). |
| Comparability to Predicate (Roche Diagnostics) | A comparison of performance demonstrated substantial equivalence to the Roche Diagnostics Corp. Creatinine Plus assay (K953239). |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
The document does not explicitly state the sample sizes used for the test sets for precision, accuracy, linearity, etc. It mentions human serum or plasma samples being used. There is no information regarding the country of origin of the data or whether the studies were retrospective or prospective.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This type of information (expert review, ground truth establishment) is typically relevant for diagnostic imaging AI devices, rather than for an in vitro diagnostic (IVD) immunoassay like Cystatin C measurement. For IVD devices, the "ground truth" often refers to a reference method or validated standard, not expert human interpretation of an image. The document mentions value assignment for controls and calibrators by turbidimetry and traceability to a pure recombinant human cystatin C reference preparation where the concentration was established by dry mass determination. This constitutes the "ground truth" for the calibrators and controls.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Adjudication methods are typically associated with human reader studies for subjective interpretations (e.g., radiology). This concept does not apply to the performance testing of an automated IVD assay where results are quantitative measurements. The "adjudication" in this context would be the validation of the reference methods and calibrator value assignments.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No, an MRMC comparative effectiveness study was not done. These are typically for AI-assisted diagnostic imaging where human readers interpret cases. This device is an in vitro diagnostic reagent and not an AI-assisted imaging device. The device itself is intended to quantitatively determine Cystatin C, and its performance is evaluated against predicate devices and analytical criteria, not human reader performance.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This refers to the inherent performance of the assay itself. The performance characteristics listed (precision, accuracy, linearity, sensitivity, specificity, interferences, stability) are all "standalone" performance evaluations of the assay components (Immunoparticles, Control Set, Calibrator) as they would be run on an automated analyzer. The device's primary function is quantitative measurement, not providing AI assistance to a human interpreter.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
For the DakoCytomation Cystatin C Assay, the "ground truth" for the calibrators and controls was established by:
- Turbidimetry using the DakoCytomation Cystatin C Calibrator (X 0974) as reference for the control set.
- Traceability to a pure recombinant human cystatin C reference preparation, where the cystatin C concentration was established by dry mass determination for the calibrator.
- For the overall performance, comparison to legally marketed predicate devices (Dade Behring N Latex Cystatin C Test Kit, Roche Diagnostics Corp. Creatinine Plus assay) served as a comparative "ground truth" in demonstrating substantial equivalence.
8. The sample size for the training set
The document does not describe a "training set" in the context of machine learning or AI. This device is an immunoassay, not an AI/ML product. The term "training set" is not applicable here. The development of the immunoparticles would involve reagent optimization and validation, but this is not typically referred to as a "training set" in this context.
9. How the ground truth for the training set was established
As there is no "training set" in the AI/ML sense, this question is not applicable. The development of the assay components would involve internal validation and standardization processes. For the purpose of regulatory substantial equivalence, the "ground truth" for comparison for the overall device performance was established by demonstrating comparable performance to the established predicate devices, which are legally marketed and are considered "safe and effective."
§ 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.