(266 days)
Access hsTnI is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnI) levels in human serum and plasma using the Unicel DxI Immunoassay Systems to aid in the diagnosis of myocardial infarction (MI).
The Access hsTnI is a two–site immunoenzymatic ("sandwich") assay. Monoclonal anti–cTnI antibody conjugated to alkaline phosphatase is added to a reaction vessel along with a surfactant–containing buffer and sample. After a short incubation, paramagnetic particles coated with monoclonal anti–cTnI antibody are added. The human cTnI binds to the anti–cTnI antibody on the solid phase, while the anti–cTnI antibody–alkaline phosphatase conjugate reacts with different antigenic sites on the cTnI molecules. 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.
Here's a breakdown of the acceptance criteria and study information for the Access hsTnI device, based on the provided FDA 510(k) clearance letter:
Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Acceptance Criteria | Reported Device Performance (Access hsTnI Candidate on UniCel DxI 800) |
|---|---|---|
| Method Comparison | Slope of Passing-Bablok linear regression model: 1.00 ± 0.10 | Met acceptance criteria (exact slope not provided, but stated that the study "met the acceptance criteria of slope 1.00 ± 0.10"). Bias data supported that reference intervals have not changed appreciably from the commercialized product. |
| Imprecision | Within-laboratory (total) CV: ≤ 10% for concentrations ≥ 11.5 pg/mL | |
| Within-laboratory (total) SD: ≤ 1.15 pg/mL for concentrations 0.05). If significant, the fit of the polynomial regression demonstrating significance should have ≤ 10% bias across the analytical measuring range. | The analysis of the data found that across the UniCel DxI 800 instruments, and for each sample concentration range, the higher order (2nd or 3rd) term of the polynomial fit is non-significant (p > 0.05), and if significant, the fit of the polynomial regression demonstrating significance had ≤ 10% bias across the analytical measuring range. | |
| LoB/LoD | Not explicitly stated as an "acceptance criteria" but limits are reported for the predicate. | LoB estimate of the Access hsTnI is 1.5 (serum and plasma). |
| LoD estimate of the Access hsTnI is 1.8 (serum and plasma). | ||
| LoQ | Not explicitly stated as an "acceptance criteria" but limits are reported for the predicate. | The LoQ for Access hsTnI at ≤20% within-lab CV was determined to be 1.3 pg/mL (serum) and 1.2 pg/mL (plasma). |
| Carryover | Not explicitly stated as an "acceptance criteria" for numeric limits, but the sponsor performed studies and included a limitation in labeling acknowledging observed carryover. | When a sample with cTnI > 150,000 pg/mL (ng/L) was tested, intra-assay carryover was observed if an Access hsTnI was tested after a high cTnI sample. Estimated carryover was 3-5 pg/mL (ng/L) from a high sample at 270,000 pg/mL (ng/L) and 5-8 pg/mL (ng/L) from a high sample at 500,000 pg/mL (ng/L). Limitation statements related to carryover are to be added. |
| Analytical Measuring Range | 2.3 pg/mL to 27,027 pg/mL (Predicate) | Similar (Candidate) |
Study Details
The provided document describes a study primarily focused on demonstrating the substantial equivalence of the Access hsTnI assay when run on the UniCel DxI 800 Immunoassay System compared to its predicate device (Access hsTnI on the Access 2 Immunoassay System). This is achieved through performance testing of various analytical aspects.
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Sample Size Used for the Test Set and Data Provenance:
- Method Comparison: 239 samples (119 Lithium Heparin Plasma and 120 Serum).
- Data Provenance: Not specified (e.g., country of origin). The document indicates it's a retrospective comparison between the "IVD Access hsTnI (Current Assay Protocol File (APF))" and the "proposed Access hsTnI (Proposed APF)" on the UniCel DxI 800 instruments, implying existing samples or previously collected data.
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Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- Not Applicable. This device is an in-vitro diagnostic (IVD) immunoassay for quantitative determination of cTnI levels. The "ground truth" for the test set in this context refers to the measured cTnI values, which are inherently quantitative and determined by the predicate device's method and the proposed device's method, not by expert consensus or interpretation of images/clinical findings.
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Adjudication Method for the Test Set:
- Not Applicable. As noted above, this is a quantitative analytical method comparison, not a diagnostic interpretation or clinical outcome study that would require adjudication.
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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 in-vitro diagnostic device, not an AI-based image interpretation or diagnostic aid system involving human readers.
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If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
- Yes, implicitly. The studies described (Method Comparison, Imprecision, Linearity, LoB/LoD, LoQ, Carryover) evaluate the performance of the analytical instrument and assay without human intervention in the measurement process. The device itself is an automated immunoassay system that produces quantitative results.
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The Type of Ground Truth Used:
- The "ground truth" in this context refers to the quantitative measurements of cTnI levels themselves. For the method comparison, the predicate device (Access hsTnI on the Access 2 Immunoassay System, or the "Current Assay Protocol File (APF)" on the DxI 800) essentially serves as the reference for comparison against the "Proposed APF" on the UniCel DxI 800. Therefore, it's a comparison against an established, legally marketed reference measurement method.
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The Sample Size for the Training Set:
- Not specified. This documentation primarily focuses on the validation of the device's analytical performance. While there would have been internal development and optimization (which could be considered "training"), the document does not distinguish a formal "training set" (as might be seen with AI/ML models) from "internal validation" data. The tested datasets described are for analytical validation.
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How the Ground Truth for the Training Set Was Established:
- Not specified / Not applicable in the traditional sense. As an IVD assay, the "ground truth" for developing such a test is the accurate quantitative measurement of the analyte (cTnI) in biological samples, requiring highly controlled reference methods and materials. The document indicates the device's principle is a "two-site immunoenzymatic ('sandwich') assay," which is a well-established biochemical technique. The development process would involve extensive characterization against reference standards and known concentrations, rather than establishing ground truth through, for example, expert labeling of clinical data.
§ 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.