B-304 Open-Channel Validation of Urea and Phosphorus: Analytical Performance and Reagent Equivalence under Routine Laboratory Conditions

Abstract

Background Validation is a complex process performed to confirm analytical performance under routine laboratory conditions. Under regulatory requirements, commercial reagents are validated by manufacturers within a specific analytical system (instrument, reagent, and sample matrix). However, when modifications to an analytical system are necessary, laboratory validation becomes required, especially during supply disruptions, even when product equivalence is recommended and documented by the manufacturer. This process ensures proper system operation, compliance with internal quality requirements, and reliable patient results. This study aimed to evaluate the analytical performance of urea and phosphorus (serum and urine) using Advia reagents on the Atellica CH analyzer in an open-channel configuration. Methods Three studies were performed to determine analytical performance: precision, method comparison, and linearity. For precision, two levels of routine commercial quality controls were analyzed in quintuplicate over five days. Acceptance criteria included compliance with the manufacturer’s instructions for use and/or a variation below one-quarter of the total allowable error (TEa). For method comparison, at least 40 samples were analyzed using the ADVIA® Chemistry Inorganic Phosphorus (IP) reagent (test) and Atellica CH Inorganic Phosphorus (IP) reagent (reference), on the Atellica CH analyzer (all from Siemens healthineers®), with acceptance criteria including a correlation coefficient r²>0.95, agreement within the TEa, and/or semiquantitative analysis (when applicable). For linearity, two samples (high and low concentrations) were selected and mixed to obtain four dilutions (20%, 40%, 60%, and 80%). All six levels were analyzed in duplicate. Acceptance criteria were r² > 0.99 and a difference below ½ TEa. The TEa used in the analysis was derived from the laboratory’s internal quality control program. All analyses were performed using EP Evaluator software, version 12.4. Results The analytical system evaluated in this study was implemented according to the manufacturer’s recommendations, with stated equivalence between the Advia and Atellica reagents. Minor protocol adjustments were implemented to optimize performance on the Atellica CH analyzer in an open-channel configuration, as defined by Siemens technical support. Imprecision ranged from 1.2% to 4.9%, in accordance with one or more of the established criteria. The method comparison analysis showed r²>0.95 and variation within the TEa. Furthermore, in the comparison study, serum urea demonstrated a positive bias of the test method relative to the reference; therefore, a semiquantitative analysis was performed and the generated data demonstrated the absence of clinically significant impact. In the linearity studies, excellent correlation was observed (r²>0.99), with the only limitation related to the difficulty of obtaining high-concentration samples to fully assess the linearity range reported by the manufacturer. Conclusion The open-channel validation demonstrated results consistent with the established acceptance criteria, confirming the accuracy and precision of the changed analytical system. The findings support the manufacturer’s recommendation regarding product equivalence while reinforcing the importance of laboratory-level validation to identify and understand minor analytical differences between reagents, such as small systematic biases. These investigations allow laboratories to confirm the expected performance of open systems under routine conditions, understand operational differences, and appropriately monitor internal quality control indicators, even in the absence of clinical or statistical impact.