(59 days)
The Access CK-MB assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CK-MB levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.
The Access CK-MB assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CK-MB levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. The Access CK-MB assay is a two-site immunoenzymatic ("sandwich") assay. Patient sample is added to a reaction vessel with mouse monoclonal anti-human CK-MB antibody-alkaline phosphatase conjugate and paramagnetic particles coated with mouse monoclonal anti-human CK-BB. Human serum CK-MB binds to the anti-CK-MB conjugate and is immobilized on the paramagnetic particle coated with anti-CK-BB. The CK-MB in the human serum or plasma binds to the immobilized anti-CK-BB on the solid phase by the sub-unit B epitope (common to CK-BB and CK-MB isoforms), while the mouse anti-CK-MB conjugate reacts specifically with the serum or the plasma CK-MB (no reaction with CK-MM or CK-BB isoforms). After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of analyte in the sample. Analyte concentration is automatically determined from a stored calibration.
The provided text describes the 510(k) premarket notification for the Beckman Coulter Access CK-MB assay on the Dxl 9000 Access Immunoassay Analyzer. This document focuses on demonstrating substantial equivalence to a previously cleared predicate device (Access CK-MB assay on the Access 2 Immunoassay System, K030012), rather than proving that an AI-driven device meets specific acceptance criteria.
Therefore, many of the requested details regarding AI/ML device validation (e.g., sample size for test set, data provenance, number of experts for ground truth, adjudication methods, MRMC studies, standalone AI performance, training set details) are not applicable to this submission content.
This submission is for an in vitro diagnostic (IVD) immunoassay, which is a chemical/biological test, not an AI or imaging device. The "device" here refers to the measurement system (the assay and the immunoassay analyzer), not an AI algorithm.
However, I can extract the acceptance criteria and performance data for the analytical performance of this IVD device as presented in the document.
Acceptance Criteria and Reported Device Performance (Access CK-MB Assay on Dxl 9000 Access Immunoassay Analyzer)
The studies presented here are analytical validation studies for an in vitro diagnostic immunoassay, not clinical validation studies for an AI/ML or imaging device. The "acceptance criteria" are based on performance claims typically established for IVD assays to demonstrate substantial equivalence to a predicate device and suitability for their intended use.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria / Design Goal | Reported Device Performance (Dxl 9000 Access Immunoassay Analyzer) |
|---|---|---|
| Method Comparison | Demonstrated substantial agreement with predicate device (Access 2). | Correlation Coefficient: 1.00 (between Access 2 and Dxl 9000). |
| Slope: 1.04 (95% CI: 1.03 - 1.05) | ||
| Intercept: 0.0066 (95% CI: -0.019 - 0.032) | ||
| (Range: 0.29 - 271 ng/mL) | ||
| Imprecision | Within-laboratory: |
- SD ≤ 0.04 ng/mL for values ≤ 0.5 ng/mL
- CV ≤ 8.0% for values > 0.5 ng/mL | Sample 1 (Mean 0.2 ng/mL):
- Repeatability SD: 0.01, %CV: 5.2
- Between-run SD: 0.01, %CV: 3.4
- Between-day SD: 0.003, %CV: 1.9
- Within-Laboratory (Total) SD: 0.01, %CV: 6.5
Sample 2 (Mean 9.2 ng/mL):
- Within-Laboratory (Total) %CV: 3.4
Sample 3 (Mean 54 ng/mL): - Within-Laboratory (Total) %CV: 3.0
Sample 4 (Mean 120 ng/mL): - Within-Laboratory (Total) %CV: 3.0
Sample 5 (Mean 220 ng/mL): - Within-Laboratory (Total) %CV: 2.5 |
| Linearity | Demonstrated linearity across the measuring interval. | Result: Assay demonstrated linearity across the measuring interval (0.2 - 300 ng/mL). |
| Limit of Blank (LoB) | Not explicitly stated as acceptance criterion, but determined. | Result: 0.1 ng/mL |
| Limit of Detection (LoD)| Not explicitly stated as acceptance criterion, but determined. | Result: 0.1 ng/mL |
| Limit of Quantitation (LoQ)| LoQ ≤ 20% within-lab CV. | Result: 0.2 ng/mL (at ≤ 20% within-lab CV) |
| Measuring Range | Comparability to predicate. | 0.2 - 300 ng/mL (Predicate: 0.1 - 300 ng/mL) |
| Reference Interval | Updated/verified for all sample types. | Serum, Lithium heparin and EDTA plasma: 0.6 ng/ml - 6.3 ng/ml (Predicate: EDTA plasma: 0.5-5.0 ng/ml; Serum/Lithium heparin plasma: 0.6-6.3 ng/ml) |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison: N=146 samples (Concentration Range: 0.29 - 271 ng/mL).
- Imprecision: 80 replicates per sample level. Assays were run for a minimum of 20 days (2 runs per day, in duplicate).
- LoB, LoD, LoQ: "multiple reagent lots and 3 instruments over a minimum of 3 days" (LoB) or "minimum of 5 days" (LoD/LoQ).
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective), but these are typically controlled laboratory studies conducted under GLP (Good Laboratory Practice) guidelines. Given the manufacturer's location (Chaska, MN, USA), it's highly probable the studies were conducted in the US. The studies are prospective analytical validation studies specific to the device, not retrospective analysis of clinical patient data.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Experts
- Not applicable. This is an IVD assay measuring an analyte (CK-MB concentration). The "ground truth" for these analytical studies is the quantitative measurement of the CK-MB concentration by a reference method or the predicate device, not expert consensus interpretation of images or clinical outcomes.
4. Adjudication Method for the Test Set
- Not applicable. See point 3.
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
- Not applicable. This is an IVD assay, not an AI/ML or imaging device. There are no "human readers" interpreting results in the way an MRMC study would apply.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Not applicable. This is an IVD assay, not an AI algorithm. The performance described is the standalone analytical performance of the instrument/assay system.
7. The Type of Ground Truth Used
- For Method Comparison, the "ground truth" or reference was the predicate device (Access 2 Immunoassay System) which measured CK-MB concentrations in patient samples.
- For Imprecision, Linearity, LoB/LoD/LoQ, the "ground truth" is the true analytical concentration of the analyte in control materials or spiked samples, assessed through various statistical methods (e.g., CLSI guidelines). It's essentially the actual concentration values.
8. The Sample Size for the Training Set
- Not applicable. This device is an immunoassay, not an AI/ML algorithm that requires a "training set" in the computational learning sense. The "training" in manufacturing would relate to calibrating the instrument and assay reagents.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. See point 8. The "ground truth" for assay calibration (analogous to training) would be established by reference materials traceable to international standards, if available, or highly characterized in-house control materials with assigned values. The document mentions "Liquid calibrators prepared from buffered bovine serum albumin matrix with recombinant CK-MB at specified levels." These calibrators define the "ground truth" for the device's internal calibration.
§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.
(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.