(224 days)
The 3-Reagent Homocysteine Assay for Beckman Coulter SYNCHRON® and UniCel® systems is intended for in vitro quantitative determination of total homocysteine in human serum and plasma. The device can assist in the diagnosis and treatment of patients suspected of having hyperhomocysteinemia and homocystinuria.
Bound or dimerised homocysteine (oxidised form) is reduced to free homocysteine, which then reacts with serine catalysed by cystathionine beta-synthase (CBS) to form cystathionine. Cystathionine in turn is broken down by cystathionine beta-lyase (CBL) to form homocysteine, pyruvate and ammonia. Pyruvate is then converted by lactate dehydrogenase (LDH) to lactate with nicotinamide adenine dinucleotide (NADH) as coenzyme. The rate of NADH conversion to NAD+ is directly proportional to the concentration of homocysteine (delta A340 nm).
Here's a breakdown of the acceptance criteria and study details for the 3-Reagent Homocysteine Assay, based on the provided text:
1. Acceptance Criteria and Reported Device Performance
The submission focuses on establishing substantial equivalence to a predicate device. The acceptance criteria are implicitly defined by the performance of the predicate device (Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent) and demonstrated through method comparison metrics.
| Acceptance Criteria (Implicit, based on predicate performance) | Reported Device Performance (SYNCHRON®/UniCel® vs. Olympus AU400) |
|---|---|
| Method Comparison (SYNCHRON® LX Pro Analyzer): | |
| Close to 1.0 (95% CI) for slope | Slope: 1.01 (95% CI: 0.99 to 1.04) |
| Close to 0.0 (95% CI) for intercept | Intercept: 0.07 (95% CI: -0.30 to 0.44) |
| Close to 1.0 (95% CI) for correlation coefficient (r) | Correlation coefficient (r): 0.997 (95% CI: 0.99 to 1.00) |
| Method Comparison (UniCel DxC Analyzer): | |
| Close to 1.0 (95% CI) for slope | Slope: 0.99 (95% CI: 0.97 to 1.02) |
| Close to 0.0 (95% CI) for intercept | Intercept: 0.74 (95% CI: 0.30 to 1.11) |
| Close to 1.0 (95% CI) for correlation coefficient (r) | Correlation coefficient (r): 0.994 (95% CI: 0.99 to 1.00) |
| Other Non-Clinical Performance: | Substantially equivalent performance |
| Precision (comparable to predicate) | Demonstrated to be substantially equivalent |
| Calibration (comparable to predicate) | Demonstrated to be substantially equivalent |
| Limit of Detection (comparable to predicate) | Demonstrated to be substantially equivalent |
| Linearity on Dilution (comparable to predicate) | Demonstrated to be substantially equivalent |
2. Sample Size and Data Provenance (Test Set)
- Sample Size: 100 samples
- Data Provenance: The text does not explicitly state the country of origin or whether the data was retrospective or prospective. It only mentions "human serum and plasma" samples.
3. Number and Qualifications of Experts for Ground Truth (Test Set)
The concept of "experts" and "ground truth" as typically applied in AI/imaging device studies (e.g., radiologists) is not applicable to this type of chemical assay. For this device, the comparison is against a legally marketed predicate device, where the "ground truth" is essentially the established performance of that predicate using accepted laboratory methods (e.g., a "reference" assay or the predicate itself).
4. Adjudication Method (Test Set)
Not applicable. This is a quantitative chemical assay, not an interpretative task requiring human adjudication of results in the way an imaging study would. The comparison is statistical (Passing & Bablock method comparison and Pearson correlation analysis) between the new device and the predicate.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This type of study is not relevant for a quantitative chemical assay like a homocysteine test. MRMC studies are used to assess the impact of a device on decision-making or diagnostic accuracy when human interpretation is involved.
6. Standalone (Algorithm Only) Performance Study
Yes, in a sense. The described "method comparison study" implicitly evaluates the standalone performance of the 3-Reagent Homocysteine Assay against the already established performance of the legally marketed predicate device (Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent) when run on different analyzer platforms. There is no human-in-the-loop component for these quantitative results.
7. Type of Ground Truth Used (Test Set)
The "ground truth" for the test set is the results obtained from the legally marketed predicate device (Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent) when tested on the Olympus AU400 analyzer. The study design is a method comparison, where the new device's results are compared to the predicate's results for the same samples.
8. Sample Size for the Training Set
Not applicable. This is a reagent-based assay, not a machine learning or AI algorithm that requires a "training set" in the traditional sense. The device's performance is inherent to its chemical reactions and physical characteristics.
9. How the Ground Truth for the Training Set was Established
Not applicable. As stated above, there is no "training set" for this type of device. The development and optimization of the reagent formulations would involve various internal validation steps (e.g., verifying chemical reactions, stability, sensitivity) rather than establishing "ground truth" through a dataset that directly trains an algorithm.
§ 862.1377 Urinary homocystine (nonquantitative) test system.
(a)
Identification. A urinary homocystine (nonquantitative) test system is a device intended to identify homocystine (an analogue of the amino acid cystine) in urine. The identification of urinary homocystine is used in the diagnosis and treatment of homocystinuria (homosystine in urine), a heritable metabolic disorder which may cause mental retardation.(b)
Classification. Class II.