(88 days)
The Access Myoglobin assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of myoglobin levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis of heart or renal disease.
The Access Myoglobin assay is a sandwich immunoenzymatic assay. The Access Myoglobin assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access Myoglobin assay reagent pack, Access Myoglobin assay calibrators, along with the UniCel Dxl Wash Buffer II are designed for use with the Dxl 9000 Access Immunoassay Analyzer in a clinical laboratory setting.
The provided text describes the Beckman Coulter Access Myoglobin assay, which is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of myoglobin levels in human serum and plasma. The K231832 submission seeks to demonstrate substantial equivalence to the predicate device (Access Myoglobin assay, K021229) when run on the Dxl 9000 Access Immunoassay Analyzer.
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a separate section with pass/fail thresholds for all performance metrics. However, it presents the results of various performance studies against industry guidelines (CLSI standards), which implicitly serve as the acceptance criteria for demonstrating appropriate performance.
| Performance Characteristic | Acceptance Criteria (Implicit from CLSI guidelines and typical assay requirements) | Reported Device Performance (Access Myoglobin on Dxl 9000) |
|---|---|---|
| Method Comparison (vs. Predicate) | Slope near 1.0, Intercept near 0, High correlation (R) | Slope: 0.99, Intercept: 0.47, R: 1.00 |
| Imprecision | ≤ 1.10 ng/mL SD at concentrations ≤ 11.0 ng/mL; ≤ 10.0% CV at concentrations > 11.0 ng/mL | Repeatability (Within-Run): 2.0-2.3% CV, 0.18 SD (low) |
| Between-Run: 2.2-4.0% CV, 0.18-85.9 SD | ||
| Between-Day: 0.0-3.0% CV, 0.0-3.0 SD | ||
| Within-Laboratory: 3.7-5.4% CV, 0.31-101.9 SD | ||
| Linearity | Demonstrate linearity across the measuring interval (e.g., polynomial fit not significantly better than linear) | Demonstrated linearity across the measuring interval |
| Limit of Blank (LoB) | Establish a LoB that is analytically sound | 3.0 ng/mL (μg/L) |
| Limit of Detection (LoD) | Establish a LoD that is analytically sound | 3.0 ng/mL (μg/L) |
| Limit of Quantitation (LoQ) | Establish a LoQ with acceptable imprecision (e.g., ≤ 20% within-lab CV) | 3.0 ng/mL (μg/L) at ≤ 20% within-lab CV |
2. Sample Sizes Used for the Test Set and Data Provenance
- Method Comparison: N = 155 (This refers to 155 patient samples). The data provenance (country of origin, retrospective/prospective) is not specified in the provided text.
- Imprecision: N = 80 per sample assessed (e.g., Sample 1, Sample 2, etc.), which involved multiple samples tested in duplicate in 2 runs per day for a minimum of 20 days.
- Linearity: Sample size not explicitly stated, but typically involves a series of diluted/spiked samples.
- LoB, LoD, LoQ: Not explicitly stated as a single "sample size" but involved multiple reagent lots and 3 instruments over a minimum of 3-5 days.
The data provenance for all studies (country of origin, retrospective or prospective) is not specified in the provided document.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The Access Myoglobin assay is an in vitro diagnostic device for quantitative measurement of a biomarker. Its "ground truth" is established through analytical performance studies, not typically by expert review of individual cases as would be done for imaging or clinical decision support AI. Therefore, this section is not applicable in the traditional sense for this type of device. The "truth" is based on the accurate measurement of myoglobin concentration.
4. Adjudication Method for the Test Set
As this is an in vitro diagnostic quantitative assay, there is no adjudication method described or necessary in the context of expert consensus, as might be found for imaging AI. The performance is assessed against reference methods or calibrated controls.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the Effect Size
No MRMC comparative effectiveness study was done. This type of study is relevant for imaging or clinical decision support AI where human readers interpret results, and the AI might augment their performance. For a quantitative immunoassay, the "reader" is effectively the instrument, and the performance is evaluated on its analytical accuracy and precision.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented (Method Comparison, Imprecision, Linearity, LoB/LoD/LoQ) demonstrate the standalone performance of the Access Myoglobin assay on the Dxl 9000 Access Immunoassay Analyzer. These are analytical performance studies of the device itself, without human interpretation as a primary variable.
7. The Type of Ground Truth Used
The ground truth for these analytical performance studies is based on:
- Reference measurements: For method comparison, the predicate device (Access 2 Immunoassay System) served as the reference standard.
- Established concentrations/materials: For imprecision, linearity, LoB/LoD/LoQ, the ground truth is based on known concentrations of myoglobin in controls, calibrators, and spiked samples, prepared according to industry standards.
- Analytical principles: The assay measures myoglobin concentration, and the "ground truth" is the actual quantity of myoglobin present in a sample, determined through scientifically validated methods.
8. The Sample Size for the Training Set
This information is not provided in the document. For an immunoassay like this, there isn't a "training set" in the machine learning sense. The device's operational parameters and assay design are developed through extensive research and development, but this is distinct from an AI training dataset.
9. How the Ground Truth for the Training Set Was Established
As there is no explicit "training set" in the AI sense for this immunoassay submission, this question is not directly applicable. The "ground truth" during the development and optimization of such an assay would involve internal analytical studies using characterized materials and reference methods to ensure the assay accurately measures myoglobin concentrations.
§ 866.5680 Myoglobin immunological test system.
(a)
Identification. A myoglobin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the myoglobin (an oxygen storage protein found in muscle) in serum and other body fluids. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.(b)
Classification. Class II (performance standards).