(198 days)
FastPack® High Sensitivity C-Reactive Protein Immunoassay is to be used for evaluation of conditions thought to be associated with inflammation, in otherwise healthy individuals. The FastPack® High Sensitivity C-Reactive Protein Immunoassay is intended for use with the FastPack® Analyzer. Not intended for Point-of-Care use.
FastPack® High Sensitivity C-Reactive Protein Calibrators are used for calibrating the quantitative FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.
FastPack® High Sensitivity C-Reactive Protein Controls are used for quality control of the FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.
FastPack® High Sensitivity C-Reactive Protein Verifiers are used in the quantitative verification of calibration and assay range of the quantitative FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.
The FastPack® High Sensitivity C-Reactive Protein Immunoassay employs a Sandwich immunoassay principle. Endogenous CRP in a patient sample, calibrator, control, or verifier is dispensed into a FastPack® reagent pack. In the reagent pack, the sample binds with a monoclonal anti-CRP antibody covalently linked to alkaline phosphatase (ALP) and a different monoclonal anti-CRP antibody linked to biotin. After incubation, immunoreacted complex (Monoclonal anti-CRP antibody-ALP conjugate and anti-CRP antibody linked to biotin reacted with CRP in the sample) is mixed with streptavidin coated paramagnetic particles. After washing steps (using a Tris buffer containing detergents) to separate bound from unbound anti-CRP monoclonal antibody-ALP, a chemiluminogenic substrate mixture is added to the system. This mixture contains indoxyl-3-phosphate, a substrate for ALP, and lucigenin (N,N'-dimethyl-9,9'-biacridinium dinitrate). ALP dephosphorylates indoxyl-3-phosphate to indol-3-ol, which subsequently undergoes oxidation. As a result, lucigenin is reduced to form a dioxetane structure that is cleaved to yield Nmethylacridone. This compound produces a sustained luminescent glow following excitation. The raw relative luminescence units (RLUs) generated are measured by a photomultiplier tube in the FastPack® Analyzer and are directly proportional to the concentration of CRP in the sample. The entire reaction sequence takes place at 37 ± 0.5 ℃ and is protected from external light.
The provided document describes the FastPack® High Sensitivity C-Reactive Protein Immunoassay (device) and its performance to demonstrate substantial equivalence to a predicate device.
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly list "acceptance criteria" as a separate section with pass/fail values. Instead, it presents performance characteristics and compares them to the predicate device or established guidelines (e.g., CLSI). Based on the provided sections, a table can be constructed as follows:
| Acceptance Criteria (Implied) | FastPack® High Sensitivity C-Reactive Protein Immunoassay Performance | Predicate Device Performance (Olympus CRP Latex reagent K051564) |
|---|---|---|
| Precision | ||
| Within-run %CV | ≤ 1.0% (across various CRP levels) | ≤ 3.2% |
| Between-run %CV | ≤ 5.2% (across various CRP levels) | N/A (Total: ≤ 3.8%) |
| Total %CV | ≤ 9.0% (across various CRP levels) | ≤ 3.8% |
| Limits (LOB, LOD, LOQ) | ||
| LOB | 0.005 mg/L | Not explicitly stated, implied to be comparable as predicates are established assays. |
| LOD | 0.032 mg/L | |
| LOQ | 0.063 mg/L | |
| Linearity Range | 0.063 mg/L to 15.0 mg/L | 0.2 - 160 mg/L (High Sensitivity Application: 0.2 - 15.0 mg/L is comparable to FastPack's application range) |
| Interferences | No interference from specified endogenous and exogenous substances at noted concentrations. | No interference from high levels of bilirubin, hemoglobin, and triglycerides. |
| Cross-reactivity | No cross-reactivity from Rheumatoid factor (up to 1000 U/mL), human anti-mouse IgG (up to 4 ug/mL), and heterophile samples (up to 3641 ng/mL). | Not explicitly detailed for all substances, but implied to have established specificity. |
| Serum and Plasma Equivalence (vs. Serum) | N/A (Device-specific validation) | |
| EDTA Plasma Slope | 0.94 | |
| EDTA Plasma R | 0.984 | |
| Lithium-Heparin Plasma Slope | 1.00 | |
| Lithium-Heparin Plasma R | 0.993 | |
| Method Comparison (vs. Predicate) | ||
| Correlation Coefficient (R) | 0.99 | 0.999 (AU400 vs. AU640, a different comparison for predicate) |
| Slope | 0.98 (95% CI: 0.95-1.02) | 1.025 (Predicate's own method comparison) |
| y-intercept | -0.12 (95% CI: -0.23 to 0.00) | -0.022 (Predicate's own method comparison) |
2. Sample Size Used for the Test Set and the Data Provenance:
- Precision Study: 6 serum patient samples were used, each with 320 replicate determinations.
- Limits of blank, detection, and quantitation: Information not provided about the specific "samples" used for these determinations.
- Linearity Study: A high patient sample was intermixed with a low sample to generate 8 concentration levels, each tested in triplicate.
- Interferences: Specific concentrations of various substances were tested. The number of samples/replicates isn't explicitly stated, but implies a controlled study.
- Cross-reactivity: Specific concentrations of substances like Rheumatoid factor, human anti-mouse IgG, and heterophile samples were tested.
- Serum and Plasma Equivalence: Blood collections from 41 volunteers.
- Expected Values/Reference Intervals: Serum samples from 211 subjects.
- Method Comparison: 131 samples.
Data Provenance:
The document states that the reference interval study employed serum samples from "211 subjects representing 4 different geographic regions of the United States." This indicates a prospective or retrospective collection of patient samples within the US for this specific study. For other studies (precision, linearity, interferences, serum/plasma equivalence, method comparison), specific provenance details like country of origin or retrospective/prospective nature are not explicitly stated, but are generally assumed to be carried out under controlled laboratory conditions often using commercially available or anonymized clinical samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts:
This information is not applicable to this type of device (in-vitro diagnostic immunoassay). The "ground truth" for a C-reactive protein immunoassay is typically the actual concentration of CRP in the sample, which is determined by established reference methods or by the device's own calibrated measurement. There are no human "experts" establishing ground truth in the sense of image interpretation or clinical diagnosis for this kind of analytical device. The "ground truth" for method comparison is the result obtained from the predicate device or a reference method.
4. Adjudication Method for the Test Set:
This information is not applicable for this type of device. Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies where multiple human readers interpret data (e.g., medical images) and their interpretations need to be resolved for ground truth. For an immunoassay, the results are quantitative measurements, 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:
This information is not applicable to this device. An MRMC study is relevant for AI-assisted diagnostic tools where human readers are part of the diagnostic workflow. The FastPack® Immunoassay is an automated analytical device that directly measures CRP concentration, not an AI system assisting human interpretation.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done:
The device described, the FastPack® High Sensitivity C-Reactive Protein Immunoassay, is an automated immunoassay system. Its performance is inherently "standalone" in the sense that the analyzer performs the measurement without human intervention influencing the quantitative result. The performance data presented (precision, linearity, limits, interference, method comparison) is the standalone performance of the algorithm/system. There is no "human-in-the-loop" component in terms of result generation for this type of device.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):
The "ground truth" for the performance studies of this immunoassay primarily relies on:
- Reference Methods/Predicate Device Results: For method comparison, the results obtained from a legally marketed predicate device (Olympus AU2700 for the method comparison) served as the reference for comparison.
- Known Concentrations: For studies like linearity, limits of detection/quantitation, and precision, samples with known, spiked, or characterized CRP concentrations are used.
- Clinical Samples: For serum and plasma equivalence and reference interval studies, collected human serum and plasma samples are used. The CRP concentrations in these samples, as measured by the device itself or a reference method, serve as the "true" or observed values for evaluating performance parameters.
8. The Sample Size for the Training Set:
This information is not applicable in the context of this document. This device is an immunoassay, not an AI/machine learning system that requires a "training set" in the computational sense. The device's operational parameters, calibration curves, and analytical procedures are established through manufacturing and analytical validation processes, not through machine learning training on a dataset.
9. How the Ground Truth for the Training Set was Established:
This information is not applicable as there is no "training set" for this type of immunoassay device in the context of an AI/machine learning system. The "ground truth" for calibrating immunoassays is established using reference materials with assigned values traceable to international standards (e.g., ERM-DA474/IFCC for CRP, as mentioned in the device's traceability). These reference materials are meticulously characterized using highly accurate and precise analytical methods.
§ 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).