(141 days)
The Nanopia Wide Range CRP Reagent is intended for the quantitative measurement of C-Reactive Protein (CRP) concentration in serum or plasma.
Measurement of CRP is useful for determining the existence of inflammatory lesions and to monitor treatment.
The Nanopia Wide Range CRP Calibrator is intended for the calibration of the Nanopia Wide Range CRP assay.
The Nanopia Wide Range CRP Reagent is intended for the quantitative measurement of C-Reactive Protein (CRP) in serum or plasma. The assay is intended for use in the evaluation of infection, tissue injury, and inflammatory disorders in combination with a complete clinical evaluation.
The Nanopia Wide Range CRP assay consists of two liquid reagents. Reagent 1 is a buffering solution and Reagent 2 contains latex beads coated with mouse monoclonal anti-human CRP antibodies. The assay is for use on general clinical chemistry analyzers.
Here's an analysis of the provided text regarding the Nanopia Wide Range CRP device, structured to answer your questions:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" for each performance characteristic in a separate, dedicated section. However, the study results implicitly define what was considered acceptable by stating the findings and, in one instance (linearity), explicitly stating the criteria.
| Performance Characteristic | Acceptance Criteria (Implicit/Explicit) | Reported Device Performance |
|---|---|---|
| Precision | Not explicitly stated as a numerical threshold, but presumably low % CVs desired. | Within-Run % CV: |
- Control 1 (0.886 mg/L): 1.83%
- Control 2 (6.71 mg/L): 0.76%
- Control 3 (38.88 mg/L): 0.61%
Total % CV: - Control 1 (0.886 mg/L): 2.46%
- Control 2 (6.71 mg/L): 1.31%
- Control 3 (38.88 mg/L): 1.11% |
| Linearity | 100% ± 5% recovery | % Recovery from 0 to 400 mg/L: Ranged from 97.5% to 102.7% (e.g., at 40 mg/L: 99.4%, at 160 mg/L: 97.5%, at 360 mg/L: 102.7%). The document states, "The results above indicate that the assay is linear across the measuring range of the assay." |
| Assay Reportable Range | Defined as the linear range | 0.10 - 400 mg/L (Limit of Quantification to the upper end of the linear range). |
| Detection Limit | Lowest concentration at which the assay performs with +/- 2 SD | Functional sensitivity: 0.10 mg/L (derived by extrapolation). |
| Analytical Specificity | No interference, defined as a result +/- 5% of the control | No interference was noted for hemoglobin (up to 500 mg/dL), ascorbic acid (up to 100 mg/dL), free bilirubin (up to 50 mg/dL), conjugated bilirubin (up to 50 mg/dl), lipid emulsion (up to 5000 turbidity), Rheumatoid factor (up to 500 IU/mL) on serum samples containing 3.7 mg/L nominal CRP. |
| Method Comparison (vs. Predicate) | Presumably, a strong correlation (high R2 and slope close to 1, intercept close to 0) indicating substantial equivalence. | Serum Samples (n=98): Nanopia = 1.015(Predicate) - 0.0349; R² = 0.9992. This indicates a very high correlation and closeness to the predicate device. |
| Matrix Comparison | No significant differences between sample types (serum/plasma, or spiked serum). | Paired samples of serum and EDTA plasma (n=50): Plasma = 0.994(Serum) + 0.03; r = 0.999.
No significant differences observed with sodium citrate, sodium oxalate, EDTA, and sodium heparin spiked serum pools. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Test Set: Triplicate measurements daily for 20 days on 3 spiked serum samples (Control 1, 2, and 3). So, 3 samples * 3 replicates * 20 days = 180 total measurements.
- Linearity Test Set: One sample with high CRP (400 mg/L) serially diluted into 10 concentrations, plus a zero concentration sample. Each run in duplicate. So, 11 concentrations * 2 replicates = 22 measurements.
- Detection Limit Test Set: A serum sample with 0.5 mg/L diluted to 0.0 mg/L, measured in 10 replicates.
- Analytical Specificity (Interference) Test Set: Serum samples containing a nominal CRP of 3.7 mg/L, tested with various interfering substances. The number of samples per substance or replicates is not specified.
- Method Comparison Test Set: 98 serum samples ranging from 0.0 to 293 mg/L.
- Matrix Comparison Test Set: 50 paired samples of serum and EDTA plasma from individuals, plus additional serum pools spiked with anticoagulants.
Data Provenance: The document does not explicitly state the country of origin for the patient samples or if they were retrospective or prospective. Given it's a 510(k) summary for a US submission, the studies were likely conducted to meet US regulatory requirements, but the origin of the samples themselves is not detailed. The samples used for precision, linearity, and detection limit were "spiked serum samples" or "serum pools," suggesting laboratory-prepared samples rather than directly from patients in some instances. The "98 serum samples" and "50 paired samples" used for comparison studies were likely patient samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
Not applicable. This device is an in vitro diagnostic (IVD) for quantitative measurement of C-Reactive Protein (CRP). The "ground truth" for such devices is typically established by reference methods, traceable calibrators, or known concentrations, not by expert consensus on visual interpretation as might be the case for imaging devices.
For example:
- The calibrator is traceable to CRM470, which serves as a ground truth reference.
- For linearity, theoretical concentrations are the ground truth comparing to measured values.
- For method comparison, the predicate device's measurements serve as the reference for comparison, effectively a proxy for ground truth for demonstrating equivalence.
4. Adjudication Method for the Test Set
Not applicable. Adjudication methods (like 2+1, 3+1) are common in studies involving human interpretation (e.g., radiology reads). For quantitative IVD assays, the "truth" is determined by direct measurement against a standard or reference method, not by human interpretation that requires adjudication.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
No, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not done. This type of study typically involves multiple human readers evaluating cases, often with and without AI assistance, to assess the impact of AI on reader performance. For a quantitative IVD device like the Nanopia Wide Range CRP, which performs an automated measurement, MRMC studies are not relevant.
6. Standalone Performance Study
Yes, a standalone performance study was done. The entire "Performance Characteristics" section (K.1. Analytical performance) details the algorithm's performance independent of human input. This includes:
- Precision/Reproducibility
- Linearity/Assay Reportable Range
- Traceability
- Detection Limit
- Analytical Specificity
- Method Comparison with predicate device
- Matrix Comparison
All these evaluate the device's inherent analytical capability to accurately measure CRP concentration.
7. Type of Ground Truth Used
The ground truth for the analytical performance studies primarily relied on:
- Reference Materials/Standards: The calibrator is stated to be traceable to CRM470.
- Known Concentrations: For linearity, samples were prepared with theoretical (known) CRP concentrations. For detection limit, dilutions were made to specific concentrations. For analytical specificity, samples contained a "nominal concentration."
- Predicate Device Measurements: For method comparison, the measurements from the legally marketed predicate device (N-Geneous Wide Range CRP Reagent) served as the comparative "truth" to establish substantial equivalence.
8. Sample Size for the Training Set
The document does not provide information about a "training set" in the context of machine learning. The Nanopia Wide Range CRP is a turbidimetric immunoassay, which is a traditional chemical measurement system, not an AI/ML-based device that would require a training set in the typical sense. Its "training" involves calibration using standard calibrators (a set of 5 with targeted CRP concentrations).
9. How the Ground Truth for the Training Set Was Established
As mentioned above, the device is not an AI/ML-based system with a "training set" in that context. The "training" for such an assay is the calibration process. The ground truth for the calibrators is established as:
- The calibrator is traceable to CRM470 (Certified Reference Material 470).
- A master calibrator is prepared, and its value is assigned by multiple measurements of multiple lots using the device.
- The sold calibrators are then traceable to this master calibrator and are value-assigned using the device.
§ 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).