(83 days)
CO2E reagent, when used in conjunction with UniCel® DxC 600/800 System(s) and SYNCHRON® Systems AQUA CAL 1 and 3, is intended for the quantitative determination of Carbon Dioxide in human serum or plasma.
The SYNCHRON Enzymatic CO2 (CO2E) Reagent is intended for use in the quantitative determination of Carbon Dioxide concentration in human serum or plasma. The SYNCHRON Systems CO2E assay is an enzymatic method utilizing phosphoenolpyruvate carboxylase (PEPC) and a stabilized NADH analog in two coupled enzymatic reactions. In the first reaction. PEPC catalyzes the reaction between phosphoenolpyruvate and HCO3 to yield oxaloacetate and inorganic phosphate. In the second step, oxaloacetate is reduced by a stable NADH analog to malate in the presence of malate dehydrogenase (MDH). The resulting decrease in absorbance at 410 nm is spectrophotometrically measured and directly proportional to the CO2 concentration in the test sample via measurement of bicarbonate ions (HCO3). The SYNCHRON DxC Systems utilize a twolevel calibrator for the Carbon Dioxide assay.
The SYNCHRON Enzymatic CO2 (CO2E) Reagent is designed for optimal performance on the UniCel DxC SYNCHRON Clinical Systems (UniCel DxC 600/800 SYNCHRON and UniCel DxC 600i/660i/860i/860i/880i SYNCHRON Access Clinical Systems). The reagent kit contains two 300-test cartridges that are packaged separately from the associated calibrator.
Here's an analysis of the provided text regarding the acceptance criteria and study for the SYNCHRON® Systems Enzymatic CO2 (CO2E) Reagent:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a separate section with pass/fail thresholds. However, it presents performance data for method comparison and precision that are implicitly the metrics used to demonstrate substantial equivalence to the predicate device.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (SYNCHRON CO2E Reagent) |
|---|---|---|
| Method Comparison | To be substantially equivalent to the predicate (UniCel DxC 800 SYNCHRON Clinical System CO2 rate pH) | |
| Slope | Close to 1.0 | 0.974 |
| Intercept | Close to 0.0 | 0.514 |
| R (Correlation) | Close to 1.0 | 0.996 |
| Precision (Imprecision Study Results) | To demonstrate acceptable reproducibility for clinical use. | |
| Within-Run Imprecision | ||
| Level 1 (%CV) | Implicitly acceptable for clinical lab assays | 3.4% |
| Level 2 (%CV) | Implicitly acceptable for clinical lab assays | 1.9% |
| Total Imprecision | ||
| Level 1 (%CV) | Implicitly acceptable for clinical lab assays | 4.6% |
| Level 2 (%CV) | Implicitly acceptable for clinical lab assays | 2.5% |
2. Sample Size Used for the Test Set and Data Provenance:
- Method Comparison Test Set Sample Size: N = 143
- Precision Test Set Sample Size: 80 for each level (Level 1 and Level 2) for both Within-Run and Total Imprecision. This seems to be the number of data points, not necessarily unique patient samples, as precision studies often involve repeated measurements on the same samples.
- Data Provenance: The document does not specify the country of origin. It is a premarket notification for an in vitro diagnostic device, typically based on internal laboratory studies. The studies are prospective in the sense that they were conducted for the purpose of this FDA submission to evaluate the device's performance against the predicate.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
This information is not provided in the document. For in vitro diagnostic reagents like this, the "ground truth" for method comparison and precision studies is typically the measurement obtained by the predicate device (the UniCel DxC 800 SYNCHRON Clinical System CO2 rate pH in this case) and the inherent chemical/physical properties of the control materials. There are no human experts involved in establishing ground truth in the same way there would be for image interpretation.
4. Adjudication Method for the Test Set:
This information is not applicable for this type of in vitro diagnostic device study. Adjudication methods (like 2+1, 3+1) are typically used in studies involving human interpretation or subjective assessments, where discrepancies between multiple readers need to be resolved to establish ground truth. Here, the comparison is against an objective measurement from a predicate device.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done:
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for devices where human readers (e.g., radiologists) interact with the device's output, and the goal is to evaluate the improvement in human performance with AI assistance. The SYNCHRON CO2E Reagent is an automated in vitro diagnostic assay where results are generated directly by the instrument, not interpreted by human readers in a diagnostic capacity that would warrant an MRMC study.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the data presented effectively represents the standalone performance of the SYNCHRON CO2E Reagent. The method comparison and precision studies evaluate the algorithm's (reagent's) ability to quantitatively determine Carbon Dioxide concentration independently, without direct human intervention in the result generation or interpretation to correct for algorithm errors. The results are compared directly to a "gold standard" (the predicate device) or evaluated for inherent reproducibility.
7. The Type of Ground Truth Used:
The ground truth used for the method comparison study is the measurements obtained from the predicate device, the UniCel DxC 800 SYNCHRON Clinical System CO2 rate pH. For precision studies, the ground truth is the expected value of the control materials and the ability of the device to consistently produce measurements close to that expected value. It is not expert consensus, pathology, or outcomes data in the usual sense.
8. The Sample Size for the Training Set:
The document does not specify a training set size. This is because the SYNCHRON CO2E Reagent is a chemical reagent and an enzymatic assay, not an AI/machine learning algorithm that typically requires a distinct training phase with a large dataset. The "development" of such a reagent involves chemical formulation, optimization, and characterization, not machine learning training.
9. How the Ground Truth for the Training Set was Established:
This question is not applicable as there is no mention of a "training set" in the context of an enzymatic reagent. The development process for such a reagent involves optimizing chemical compositions and reaction conditions rather than training an algorithm on a dataset with established ground truth.
§ 862.1160 Bicarbonate/carbon dioxide test system.
(a)
Identification. A bicarbonate/carbon dioxide test system is a device intended to measure bicarbonate/carbon dioxide in plasma, serum, and whole blood. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.(b)
Classification. Class II.