(129 days)
CRP Vario is an in vitro diagnostic test for the quantitative determination of C-reactive protein in human serum and lithium heparin or EDTA plasma samples by immunoturbidimetry. Measurement of C-reactive protein is useful in the detection and evaluation of infection, tissue injury and inflammatory disorders.
CRP Calibrators (CRP Calibrator Set, CRP Calibrator US and CRP Calibrator WR) are intended to be used for the calibration of the CRP Vario for the quantitative determination of C-reactive protein in human serum and EDTA or lithium heparinized plasma samples.
CRP Control US is intended for use as an assayed quality control material for serum C-reactive protein analysis.
The Sentinel CRP Vario kit is a latex in vitro diagnostic immunoassay for the quantitative determination of C-reactive protein (CRP) in human serum and in heparinized and EDTAplasma. Human CRP antigens in the sample bind to the specific anti-CRP antibody absorbed to latex particles, and agglutination occurs. This agglutination is detected as an absorbance change when read on an automated chemistry analyzer at wavelengths between 550 - 580 nm. The magnitude of the change in absorbance is proportional to the quantity of CRP in the sample. The actual concentration is then determined by interpolation from a calibration curve prepared from calibrators of known concentration using the CRP Calibrator Set, CRP Calibrator US, or CRP Calibrator WR.
The Sentinel CRP Calibrator Set, CRP Calibrator US and CRP Calibrator WR are prepared by diluting purified CRP with normal human serum to reach CRP concentrations of 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 16.0, 32.0 and 48.0 mg/dL.
By using the CRP Vario with the Sentinel calibrator kits, each used with specific analyzer settings called Methods, three measuring ranges can be achieved. The combinations of calibrators, method used and analytical ranges are listed in Table 5.1.
The Standard and the Wide Range Methods can be used with any available commercial quality control materials. The CRP Vario with the Ultrasensitive Method requires a Sentinel control, CRP Control US, for the approximate CRP concentration of 0.05 mg/dL to ensure the effectiveness of CRP measurements at very low CRP concentrations.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based solely on the provided K050836 510(k) summary for the Sentinel CRP Diagnostic Assay:
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary provided does not explicitly state pre-defined acceptance criteria (e.g., a specific target for sensitivity, precision, or correlation coefficient). Instead, it relies on demonstrating substantial equivalence to predicate devices. The performance data presented is comparative, showing "equivalence" rather than meeting pre-set numerical thresholds.
However, based on the information provided, we can infer the performance aspects evaluated and summarize the reported findings:
| Performance Aspect | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Sensitivity | Comparable to predicate device. | Performance evaluation included sensitivity testing. (Specific numerical details not provided in summary). |
| Precision | Comparable to predicate device (intra-assay and inter-assay). | Performance evaluation included intra- and inter-assay precision testing. (Specific numerical details not provided in summary). |
| Prozone | Acceptable levels comparable to predicate device. | Performance evaluation included prozone testing. (Specific numerical details not provided in summary). |
| Interference | Acceptable levels comparable to predicate device. | Performance evaluation included interference testing. (Specific numerical details not provided in summary). |
| Method Comparison | Equivalence to predicate device across the measurement range. | "Equivalence was demonstrated across the total measurement range of 0.01 to 48.0 mg/dL" when compared to the Beckman Coulter IMMAGE Immunochemistry System CRP reagent. (Specific statistical measures like correlation coefficients or bias not provided in summary, but "equivalence" is claimed). |
| Analytical Range | Achieves expected analytical ranges as claimed. | Three measuring ranges achieved: Standard (0.02 – 32.0 mg/dL), Ultrasensitive (0.01 – 16.0 mg/dL), and Wide Range (0.02 – 48.0 mg/dL). |
2. Sample Size Used for the Test Set and Data Provenance
The 510(k) summary does not explicitly state the sample size used for the performance evaluations (sensitivity, precision, prozone, interference, and method comparison).
It also does not specify the data provenance (e.g., country of origin of the data, retrospective or prospective). Given that the submitter is from Italy (Sentinel CH Srl) and the contact person is also based in Rome, Italy, the studies might have been conducted in Italy or Europe, but this is not explicitly stated. The summary does not indicate whether the data was retrospective or prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
This information is not applicable in the context of this diagnostic assay submission. The "ground truth" for quantitative laboratory tests like CRP is typically established by reference methods or accepted clinical laboratory practices, not by expert consensus interpreting images or clinical cases. The comparison is done against existing, cleared diagnostic devices or reference standards.
4. Adjudication Method for the Test Set
This information is not applicable as the ground truth is not established through expert review requiring adjudication in this type of diagnostic assay. The comparison is a quantitative measurement against known values or an established predicate device.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed, nor would it typically be relevant for this type of in-vitro diagnostic device (IVD). MRMC studies are usually associated with diagnostic imaging devices or other tests that rely on human interpretation of complex data, where reader variability is a significant factor. The Sentinel CRP Diagnostic Assay is an automated immunoassay.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the device performance described (sensitivity, precision, prozone, interference, method comparison) represents standalone performance. The Sentinel CRP Vario is an automated immunoassay where human interaction is primarily for sample loading, initiating the test, and interpreting the numerical result from the automated analyzer. The "performance data" section explicitly discusses evaluations of the assay itself.
7. The Type of Ground Truth Used
The ground truth for evaluating the Sentinel CRP Diagnostic Assay consisted of:
- Reference materials/standards: For evaluating sensitivity, precision, prozone, and interference, these would typically involve samples with known CRP concentrations (e.g., spiked samples, control materials).
- Results from a predicate device: For the method comparison study ("comparison between the Sentinel CRP assay and the Beckman Coulter IMMAGE Immunochemistry System CRP reagent"), the results obtained from the predicate device (Beckman Coulter IMMAGE) served as a form of "ground truth" or reference for demonstrating equivalence.
8. The Sample Size for the Training Set
The 510(k) summary does not provide information regarding a "training set" sample size. This concept of a distinct training set is more common for machine learning or AI-based devices rather than traditional in-vitro diagnostic assays, which are typically developed and validated using a series of experiments with various samples.
9. How the Ground Truth for the Training Set was Established
As no training set is explicitly mentioned or relevant for this type of IVD in the provided summary, information on how its ground truth was established is not provided. The development of such assays involves established chemical and immunological principles, and calibration is performed using materials of known concentration (as described for the calibrator sets), rather than learning from a "training set" with established ground truth in the AI sense.
§ 866.5270 C-reactive protein immunological test system.
(a)
Identification. A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.(b)
Classification. Class II (performance standards).