(190 days)
Yumizen C1200 Immunoglobulin A reagent is intended for the quantitative in vitro diagnostic determination of Immunoglobulin A (IgA) in serum and lithium heparin plasma by immunoturbidimetry on Yumizen analyzers.Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. This test should be used in conjunction with other findings,
Yumizen C1200 Immunoglobulin G reagent is intended for the quantitative in vitro diagnostic determination of Immunoglobulin G (IgG) in serum and lithium heparin plasma by immunoturbidimetry on Yumizen analyzers.Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. This test should be used in conjunction with other findings.
Yumizen C1200 Immunoglobulin M reagent is intended for the quantitative in vitro diagnostic determination of Immunoglobulin M (IgM) in serum and lithium heparin plasma by immunoturbidimetry on Yumizen analyzers. Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.
This test should be used in conjunction with other laboratory and clinical findings.
This submission consists in the Yumizen C1200 Immunoglobulin A (1300023881), Yumizen C1200 Immunoglobulin G (1300023883) and Yumizen C1200 Immunoglobulin M (1300023884) reagent for serum and plasma testing for Yumizen C1200 reagent.
The Yumizen C1200 Level 1 Protein Control (1300023944) and Yumizen C1200 Level 2 Protein Control (1300023945) for use on Yumizen C1200 Analyzer and the Yumizen C1200 Protein Cal (1300023893) for use on Yumizen C1200 Analyzer are sold separately.
This document describes the analytical performance characteristics of the Yumizen C1200 Immunoglobulin A, G, and M reagents, intended for quantitative in vitro diagnostic determination of immunoglobulins in serum and lithium heparin plasma. The study aims to demonstrate that the device meets acceptance criteria for various analytical parameters, ensuring its safety and effectiveness.
1. Table of Acceptance Criteria and Reported Device Performance
| Feature/Metric | Acceptance Criteria | Yumizen C1200 Immunoglobulin A Performance | Yumizen C1200 Immunoglobulin G Performance | Yumizen C1200 Immunoglobulin M Performance |
|---|---|---|---|---|
| Measuring Range | Appropriateness supported by LOD, LOQ, and linearity studies. | Serum: 0.10 to 7.00 g/L | ||
| (Post-dilution): 7.00 to 21.00 g/L | ||||
| (Linearity Range): 0.21 - 6.60 g/L (Slope 1.027, R^2 0.9975) | Serum: 0.75 to 30.00 g/L | |||
| (Post-dilution): 30.00 to 90.00 g/L | ||||
| (Linearity Range): 0.82 – 29.42 g/L (Slope 0.9965, R^2 0.9986) | Serum: 0.20 to 5.00 g/L | |||
| (Post-dilution): 5.00 to 15.00 g/L | ||||
| (Linearity Range): 0.26 - 4.16 g/L (Slope 1.013, R^2 0.9994) | ||||
| Precision | Within-Run CV: Low (≤4.5%), Middle (≤3.8%), High (≤3%) | |||
| Total Precision CV: Low (≤6.0%), Middle (≤5.0%), High (≤4.0%) | Total Precision (Analyzer Variability): | |||
| Control Level 1: 3.7% | ||||
| Control Level 2: 3.1% | ||||
| Samples: 1.7%-3.8% | ||||
| Lot-to-Lot Variability: | ||||
| Control Level 1: 1.2% | ||||
| Control Level 2: 1.1% | ||||
| Samples: 1.2%-4.1% | Total Precision (Analyzer Variability): | |||
| Control Level 1: 2.9% | ||||
| Control Level 2: 3.3% | ||||
| Samples: 1.8%-3.0% | ||||
| Lot-to-Lot Variability: | ||||
| Control Level 1: 1.7% | ||||
| Control Level 2: 1.9% | ||||
| Samples: 1.4%-2.3% | Total Precision (Analyzer Variability): | |||
| Control Level 1: 2.1% | ||||
| Control Level 2: 1.8% | ||||
| Samples: 1.3%-2.4% | ||||
| Lot-to-Lot Variability: | ||||
| Control Level 1: 1.6% | ||||
| Control Level 2: 1.7% | ||||
| Samples: 1.0%-2.7% | ||||
| Interferences | Acceptable bias: +/-10% of value without interfering substances | Reported highest values for which no interferences >10% were observed for various substances (Hemoglobin, Triglycerides, Bilirubin, Ascorbic Acid, Acetylsalicylic Acid, Ibuprofen, Acetaminophen). | Reported highest values for which no interferences >10% were observed for various substances (Hemoglobin, Triglycerides, Bilirubin, Ascorbic Acid, Acetylsalicylic Acid, Ibuprofen, Acetaminophen). | Reported highest values for which no interferences >10% were observed for various substances (Hemoglobin, Triglycerides, Bilirubin, Ascorbic Acid, Acetylsalicylic Acid, Ibuprofen, Acetaminophen). |
| Matrix Comparison | No significant difference between serum and heparinized plasma specimens (implied by correlation and slope close to 1). | IgA: | ||
| N=62 (paired serum/heparin plasma) | ||||
| Slope: 1.000 | ||||
| Correlation: 0.999 | IgG: | |||
| N=43 (paired serum/heparin plasma) | ||||
| Slope: 0.9929 | ||||
| Correlation: 0.988 | IgM: | |||
| N=43 (paired serum/heparin plasma) | ||||
| Slope: 1.000 | ||||
| Correlation: 0.999 | ||||
| Method Comparison | Demonstrated substantial equivalence through correlation with predicate device. | IgA: | ||
| N=190 (native serum samples) | ||||
| Slope: 0.9941 | ||||
| Correlation: 0.993 | IgG: | |||
| N=214 (native serum samples) | ||||
| Slope: 1.016 | ||||
| Correlation: 0.993 | IgM: | |||
| N=153 (native serum samples) | ||||
| Slope: 1.005 | ||||
| Correlation: 0.993 | ||||
| Reagent Stability | Shelf life and on-board stability for opened reagents. | Closed: 24 months at 2-8°C | ||
| On-Board (Opened): 6 weeks | Closed: 24 months at 2-8°C | |||
| On-Board (Opened): 6 weeks | Closed: 24 months at 2-8°C | |||
| On-Board (Opened): 6 weeks | ||||
| Reference Range | Verification studies support established ranges through literature. | 0.70 - 4.00 g/L (70 - 400 mg/dL) | 7 – 16 g/L (700 - 1600 mg/dL) | 0.40 - 2.30 g/L (40 - 230 mg/dL) |
2. Sample Sizes Used for the Test Set and Data Provenance
- Measuring Range (Linearity):
- IgA, IgG, IgM: Samples were "spiked" to create different concentrations, then serially diluted. The exact number of initial samples for spiking is not specified, but dilutions were "assayed in quadruplicate within a single run."
- Precision (Total Precision: analyzer variability - 20x2x2 study):
- IgA, IgG, IgM: 5 human sera samples and 2 levels of Yumizen C1200 Protein Control. Tested with "two replicates per run, two runs per day for 20 days on each of three analyzers" (n=240 per sample).
- Precision (Lot to Lot variability study: 3x5x2x3):
- IgA, IgG, IgM: 5 human sera samples and 2 levels of Yumizen C1200 Protein Control. Tested in "triplicates per run, two runs per day for five days on each of three lots" (n=90 per sample).
- Interferences: The exact sample size is not stated, but the study implies testing samples with varying concentrations of interfering substances to determine acceptable bias.
- Matrix Comparison:
- IgA: 62 paired samples (serum and heparinized plasma) from single donors.
- IgG: 45 paired samples (serum and heparinized plasma) from single donors. Of these, 43 were used for correlation analysis.
- IgM: 43 paired samples (serum and heparinized plasma) from single donors.
- Method Comparison:
- IgA: 190 "native samples" from human serum.
- IgG: 214 "native samples" from human serum.
- IgM: 153 "native samples" from human serum.
Data Provenance: The human serum samples used for precision, matrix comparison, and method comparison studies were "anonymous remnants of human serum specimens collected from blood bank." "Spiked" samples were used for linearity studies, and "normal samples" from a blood bank were used for reference range verification. The document does not explicitly state the country of origin, but the manufacturer is based in France. The studies appear to be prospective analytical performance evaluations.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
No external experts are mentioned for establishing ground truth in these analytical performance studies. The studies rely on established CLSI guidelines for evaluation and comparison with a legally marketed predicate device. The ground truth for quantitative measurements is the direct measurement by the devices themselves and comparison against predicate devices or known spiked concentrations.
4. Adjudication Method for the Test Set
Not applicable. These are analytical performance studies for an in vitro diagnostic device, not studies involving human interpretation or adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This document describes the analytical performance of an in vitro diagnostic reagent and analyzer system, not a device requiring human interpretation for diagnostic purposes where MRMC studies would typically be conducted.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, this can be considered a standalone performance study. The Yumizen C1200 system (reagents and analyzer) performs the quantitative determination of immunoglobulins. The studies evaluate the analytical capabilities of the system itself, such as accuracy (via method comparison, linearity), precision, interference, and stability, without direct human intervention in the result generation or diagnostic interpretation loop. The intent is to demonstrate the device's ability to accurately measure predefined analytes.
7. Type of Ground Truth Used
The ground truth for these analytical performance studies is established through:
- Known concentrations: For linearity studies, spiked samples with known concentrations were used.
- Predicate device measurements: For method comparison, results from the candidate device were compared against measurements obtained from legally marketed predicate devices (Beckman Coulter's Olympus IgA, IgG, IgM reagents on AU analyzers).
- CLSI guidelines and established methodologies: The studies adhere to CLSI guidelines (e.g., EP05-A3 for precision, EP17-A2 for detection capability, EP06-A for linearity, EP25-A for stability, C28-A3 for reference intervals, EP-9A3 for method comparison) which define accepted methods for evaluating analytical performance and establishing performance characteristics.
- Literature-established reference ranges: For reference range verification, the device's measurements on "normal" samples were compared against ranges cited in scientific literature (e.g., Dati et al., 1996).
8. Sample Size for the Training Set
The document does not explicitly delineate a "training set" in the context of machine learning or AI models. This device is an in vitro diagnostic reagent and analyzer system, not an AI/ML-based diagnostic algorithm that typically undergoes a distinct training phase with a dedicated dataset. The performance studies described here are for analytical validation rather than algorithm training.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no mention of a "training set" in the context of an AI/ML model for this in vitro diagnostic device. The analytical evaluations described involve testing the reagent and instrument system, not training a learning algorithm.
§ 866.5510 Immunoglobulins A, G, M, D, and E immunological test system.
(a)
Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.(b)
Classification. Class II (performance standards).