(70 days)
Yumizen C1200 CRP reagent is intended for use as a high sensitive assay for the quantitative in vitro diagnostic determination of the C-reactive protein in human serum and plasma based on an immunoturbidimetric assay. CRP is used to evaluate conditions thought to be associated with inflammation in otherwise healthy individuals.
Yumizen C1200 CRP reagent is intended for use as a high sensitive assay for the quantitative in vitro diagnostic determination of the C-reactive protein in human serum and plasma based on an immunoturbidimetric assay.
The provided text describes the analytical performance characteristics of the Yumizen C1200 CRP device, supporting its substantial equivalence claim for FDA 510(k) clearance.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance:
The document outlines various analytical performance characteristics (measuring range, accuracy, precision, interferences, matrix comparison, method comparison, and reagent stability) but does not explicitly state acceptance criteria in a single, dedicated table with pass/fail results. Instead, it presents the study methods and the results obtained, often followed by a statement indicating whether the results are "within specifications" or "appropriate." The acceptance criteria are implicitly defined by the chosen CLSI guidelines and the internal specifications of HORIBA Medical.
Based on the information provided, here's a table summarizing the reported device performance and the implicit acceptance as demonstrated by the study results:
| Performance Characteristic | Implicit Acceptance Criteria (based on CLSI guidelines & stated outcomes) | Reported Device Performance (Results) | Device Meets Criteria? |
|---|---|---|---|
| Measuring Range | Limit of detection, quantitation, and linearity appropriate for intended use. | Serum: | Yes (Stated "appropriate") |
| LOD (Detection Capability) | 0.13 mg/L | Yes | |
| LOQ (Quantitation Capability) | 0.16 mg/L | Yes | |
| Linearity Range | 0.03 to 11.53 mg/L | Yes | |
| Measuring Range | 0.2 to 10 mg/L (For hsCRP with 1:5 dilution, EMI is 10-50 mg/L) | Yes | |
| Accuracy and Precision | Within-run and total precision (CV limits) within defined specifications. | Serum (Calibration every week): | Yes (Stated "within specifications") |
| Within-run (%CV) | Low: 1.5-4.7%, Mid: 1.6-2.8%, High: 0.6-0.8% (for samples 1-4); Stated CV limits (general): Low 9.0%, Mid 4.5%, High 3.8% | Yes | |
| Total Precision (%CV) | Low: 3.0-5.9%, Mid: 2.1-3.8%, High: 2.4-3.1% (for samples 1-4); Stated CV limits (general): Low 12.0%, Mid 6.0%, High 5.0% | Yes | |
| Heparin-Lithium (Within-run precision): | Sample 1 (0.35 mg/L): 2.17% CV; Sample 2 (0.51 mg/L): 2.11% CV; Sample 3 (1.25 mg/L): 1.00% CV; Sample 4 (4.75 mg/L): 2.27% CV; Sample 5 (7.77 mg/L): 1.31% CV; Sample 6 (9.31 mg/L): 0.69% CV. Stated CV limits: Low 9.0%, Mid 4.5%, High 3.8%. | Yes (Stated "within specifications") | |
| Interferences | Acceptable bias +/-10% of value without interfering substances. | Highest values with no >10% interference: Hemoglobin 290 µmol/L, Triglycerides 279 mg/dL (Note: specific observation of -11.2% at 395 mg/dL triglycerides for 4.15 mg/L CRP, and -10.5% at 517 mg/dL for 0.83 mg/L CRP), Total Bilirubin 27.61 mg/dL, Direct Bilirubin 30.41 mg/dL, Ascorbic Acid 5.98 mg/dL, Acetylsalicylic Acid 65.16 mg/dL, Ibuprofen 50.10 mg/dL, Acetaminophen 20 mg/dL, Rheumatoid Factor up to 400 IU/mL. | Yes (Interference data stated to be included in labeling) |
| Matrix Comparison | No significant difference between Serum and Heparin-Lithium specimens. | Passing Bablok: N=54, Intercept -0.003012, Slope 0.9787, Correlation 0.998. | Yes (Stated "no significant difference") |
| Method Comparison | Good correlation/agreement with comparator device. | Passing Bablok (with predicate): N=138, Intercept -0.06852, Slope 0.9987, Correlation r² 0.995. | Yes |
| Reagent Stability | Meeting specified shelf life and on-board stability. | Closed Stability: 24 months (stable until expiry date at 2-10°C). | Yes |
| Open Stability (On-board): 8 weeks. | Yes (Stated "correct") |
2. Sample Size Used for the Test Set and Data Provenance:
-
Measuring Range (Linearity): Not explicitly stated how many samples were used, but the method refers to CLSI EP06-A.
-
Accuracy and Precision:
- Serum: 240 measurements for each of 5 samples/controls (internal control, Sample 1-4) in both "calibration every week" and "calibration only at beginning" studies.
- Heparin-Lithium: 20 measurements for each of 6 specimens.
-
Interferences: Not explicitly stated how many samples were tested for each interfering substance, but the study method refers to CLSI EP07-A2.
-
Matrix Comparison (Serum vs. Heparin-Lithium): 54 samples.
-
Method Comparison (with comparator device): 138 native samples.
-
Data Provenance:
- The document states "Anonymous remnants of human serum specimens collected from routine clinical laboratory" for some studies (precision for lithium-heparin, method comparison). For the matrix comparison, it mentions "individual donors from blood bank (in serum and plasma for each donor)".
- The studies appear to be retrospective as they use "remnants" and "collected" samples.
- The country of origin is not explicitly stated, but the manufacturer (HORIBA ABX SAS) is based in Montpellier, France, suggesting the studies were likely conducted in France or a European context.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
This device (Yumizen C1200 CRP) is an in vitro diagnostic device for quantitative measurement of C-reactive protein (CRP) in human serum and plasma. For such devices, ground truth is typically established by:
- Reference Methods: Highly accurate and precise laboratory methods (e.g., mass spectrometry, or comparison to a cleared predicate device).
- Certified Reference Materials: Samples with a known and certified concentration of the analyte.
The document does not mention the use of human experts (like radiologists for image analysis) to establish ground truth for the test set of this type of device. The accuracy and precision are determined by comparing results to expected values or reference materials, and the method comparison is done against a predicate device.
4. Adjudication Method for the Test Set:
Not applicable. As described above, for IVD devices like this, ground truth is established through analytical precision and accuracy, reference methods, and comparison against a predicate device, not through human reader adjudication like in imaging studies.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done:
No. An MRMC study is relevant for diagnostic imaging AI systems where human readers interpret images. This device is a laboratory assay; therefore, MRMC studies are not applicable.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the entire analytical performance evaluation (measuring range, precision, interference, matrix comparison, method comparison, stability) describes the standalone performance of the Yumizen C1200 CRP device. This is typical for IVD devices where the result is generated solely by the analyzer and reagent system, without human interpretive input altering the result itself.
7. The Type of Ground Truth Used:
- Certified Reference Materials/Control Materials: Used for precision and accuracy studies (e.g., "Low CRP Control (internal control)").
- Native Patient Samples: Used for matrix comparison and method comparison studies (comparison against a predicate device).
- Spiked Samples: Used for interference studies (adding known interferents to samples).
- Reference Methods/Predicate Device: The predicate device (VITROS Chemistry Products hsCRP Reagent K160712) served as the comparative "ground truth" for method comparison and demonstrating substantial equivalence. The document explicitly states the method comparison was carried out using recommendations from CLSI EP-9A3 ("Measurement Procedure Comparison and Bias Estimation Using Patient Samples").
8. The Sample Size for the Training Set:
The document describes pre-market validation studies for a medical device submitted for 510(k) clearance. For traditional IVD devices (non-AI/ML based), there isn't typically a "training set" in the machine learning sense. The "training" of the device is inherent in its design, calibration, and manufacturing process. The studies described are validation and verification studies to demonstrate performance.
9. How the Ground Truth for the Training Set Was Established:
Not applicable, as there is no "training set" in the context of an AI/ML device for this traditional IVD product. The calibration curves for the device are established during the development phase using calibrator materials, which would have their values traceable to a higher-order reference method or standard. The document mentions "Yumizen C1200 CRPhs Cal" as the calibrator used, and its properties would be traceable to ensure accurate measurements.
§ 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).