(333 days)
The C-Reactive Protein Extended Range (RCRP) method used on the Dimension® clinical chemistry system is an in vitro diagnostic test intended for the quantitative determination of CRP in human serum and plasma (lithium heparin). Measurement of C-Reactive Protein is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases.
The RCRP method is based on a particle enhanced turbidimetric immunoassay (PETIA) technique. Synthetic particles coated with antibody to C-Reactive Protein (AbPR) aggregate in the presence of C-Reactive Protein in the sample. The increase in turbidity which accompanies aggregation is proportional to the C-Reactive Protein concentration.
This document describes the RCRP Flex® reagent cartridge, an in vitro diagnostic test for the quantitative determination of C-Reactive Protein (CRP) in human serum and plasma. The submission is a special 510(k) for a modified device, primarily due to an update in traceability from IFCC CRM 470 to ERM-DA474/IFCC reference material and a change in the analytical measurement range (AMR).
Here's an analysis of the acceptance criteria and study data based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria and observed performance are provided for the method comparison studies.
| Attribute | Acceptance Criteria | Reported Device Performance (Modified RCRP vs. Predicate RCRP) | Pass/Fail | Reported Device Performance (RCRP Dimension RXL vs. N High Sensitivity CRP) | Pass/Fail |
|---|---|---|---|---|---|
| Slope | $1.00 \pm 0.1$ | 0.99 | Pass | 0.95 | Pass |
| y-intercept | $0.0 \pm 2.0$ mg/L | -0.5 mg/L | Pass | -1.6 mg/L | Pass |
| Correlation Coefficient (r) | $\geq 0.9600$ | 1.000 | Pass | 0.997 | Pass |
Detection Capability (LoB, LoD, LoQ)
| Specimen Type | Detection Capability | Acceptance Criteria | Result (mg/L / mg/dL) |
|---|---|---|---|
| Serum and Lithium Heparin Plasma | LoB | ≤ LoD | 0.6 mg/L (0.06 mg/dL) |
| LoD | ≤ LoQ | 1.0 mg/L (0.10 mg/dL) | |
| LoQ | ≤ 5.0 mg/L | 5.0 mg/L (0.50 mg/dL) |
Interference
| Endogenous Substance Tested | Endogenous Substance Concentration | Analyte Concentration | Acceptance Criteria (Bias) | Bias (%) |
|---|---|---|---|---|
| Hemoglobin (hemolysate) | [500 mg/dL] 5.0 g/L | [11.6 mg/L] 1.16 mg/dL | Bias exceeding 10% is interference | 0% |
| Bilirubin (Unconjugated) | [40 mg/dL] 684 µmol/L | [11.7 mg/L] 1.17 mg/dL | Bias exceeding 10% is interference | 2% |
| Lipemia (Intralipid) | [250 mg/dL] 2.5 g/L | [11.8 mg/L] 1.18 mg/dL | Bias exceeding 10% is interference | -9% |
| Lipemia (Triglyceride Fraction) | [750 mg/dL] 7.5 g/L | [11.1 mg/L] 1.11 mg/dL | Bias exceeding 10% is interference | -7% |
2. Sample Sample Size Used for the Test Set and Data Provenance
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Method Comparison – Modified RCRP assay vs Predicate RCRP assay:
- Sample Size: 132 individual human native serum samples.
- Data Provenance: Samples were obtained from "specimen vendors". The country of origin is not specified, nor is whether the data is retrospective or prospective.
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Method Comparison - RCRP assay on Dimension RXL system vs N High Sensitivity CRP on the BN™ System:
- Sample Size: 171 for the overall comparison (5.3 to 241.3 mg/L) and 39 for the narrower range (5.3 to 20.2 mg/L).
- Data Provenance: This study involved "re-analyzed historical IFU data." The original provenance (country, retrospective/prospective) of this historical data is not specified.
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Linearity Testing: Not specified, but generally involves a set of diluted samples or spiked matrix covering the analytical measurement range.
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Detection Capability (LoB, LoD, LoQ): Not specified.
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Precision:
- Sample Size: 6 serum samples, analyzed with N=10 replicates each day for 5 days (total of 50 replicates per sample level).
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Specimen Equivalency:
- Sample Size: 73 samples.
- Data Provenance: Not specified, but likely from specimen vendors similar to the method comparison.
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Interference:
- Sample Size: Not explicitly stated, but typically involves a control sample and test samples (with interferent) for assessment of bias.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This document describes an in vitro diagnostic (IVD) test, specifically an immunoassay for C-Reactive Protein. The "ground truth" for such devices is typically established through a reference method or known concentrations of certified reference materials, not through expert consensus or interpretation in the same way an imaging AI might.
- No human experts (e.g., radiologists) were used to establish ground truth for this type of device. The assessment is based on measured concentrations against established reference standards.
4. Adjudication Method for the Test Set
Not applicable. As described above, the ground truth for an IVD device like this is based on quantitative measurements and reference materials, not subjective interpretations requiring adjudication.
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
Not applicable. This is an in vitro diagnostic assay, not an AI-powered image analysis or diagnostic assist device that would involve human readers.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
This device is a standalone algorithm/reagent system designed for automated quantitative measurement on a clinical chemistry system. Its performance is evaluated intrinsically through various analytical studies (method comparison, linearity, precision, detection capability, interference) without human-in-the-loop performance influencing the measurement itself. The results are then interpreted by clinicians.
7. The Type of Ground Truth Used
The ground truth for this device is based on:
- Reference Materials: For standardization, the device is traceable to ERM-DA474/IFCC reference material (and previously IFCC CRM 470). These are internationally recognized certified reference materials for CRP.
- Comparative Methods: The performance is benchmarked against a predicate RCRP assay and the N High Sensitivity CRP on the BN™ System. These are established laboratory methods.
- Clinical Laboratory Standards (CLSI): The studies follow guidelines from CLSI, which define how to robustly evaluate analytical performance parameters like precision, linearity, and detection limits.
8. The Sample Size for the Training Set
This document does not describe a machine learning or AI model that requires a distinct "training set" in the conventional sense. The device is a chemical reagent and assay system. Its "training" or development would involve extensive experimentation and optimization during the R&D phase to ensure reagent stability, reaction kinetics, and signal transduction are robust and accurate. This is not typically quantified as a "training set size" like in AI/ML contexts.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as this is not an AI/ML device with a defined training set and ground truth in that context. The "ground truth" for the development of such an assay would be through rigorous chemical and biological characterization, using known concentrations of analytes, reference materials, and established analytical chemistry principles.
§ 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).