earticle

영어

This study aimed to re-evaluate the robustness of the current testing method for determining the potency of aprotinin, one of the quality control for fibrin sealant kits, by applying Analytical Quality by Design (AQbD). A processing map and an Ishikawa diagram were used to identify potential test variables. The critical method attributes (CMAs) were defined as the coefficient of determination of the calibration curve, the relative standard deviation of system suitability solution measurements, and the relative range of test sample measurements. Through preliminary experiments and risk assessment, column oven temperature, flow rate, and mobile phase buffer composition were identified as critical method parameters. A design of experiment established the design space satisfying CMA requirements: 10–20oC for column oven temperature, 0.5–1.5 mL/min for flow rate, and 80–100% for mobile phase buffer composition. Robustness within this space was verified through an inter-laboratory collaborative study at low, medium, and high conditions, with all conditions satisfying CMA requirements. These results confirm that the current testing method falls within the validated design space and possesses adequate robustness. This study demonstrates that AQbD can be applied to ensure consistency and re-validation of plasmaderived medicinal product testing, contributing to enhanced reliability in national lot release outcomes.