A Protocol for Conformity and Risk Assessment of Pharmaceutical Product by High Performance Liquid Chromatography Based on Measurement Uncertainty

Abstract

Conformity assessment plays a critical role in the process of drug manufacturing, significantly influencing product outcomes of acceptance or rejection. Measurement uncertainty is an important parameter inherent to the analysis method itself. The introduction of uncertainty can effectively control and assess the risk of making wrong decisions in the conformity assessment process. This protocol provides guidelines for conformity and risk assessment of pharmaceutical products based on measurement uncertainty. The procedure is successfully applied to the HPLC analytical method of determination of berberine hydrochloride in Daochi pills. The correlation coefficient (r) of berberine hydrochloride was 0.9999, which indicated a good linear relationship within the range of 0.02317∼2.317 ug·mL⁻¹. The validation experiment adopted an experimental design of 3 replicates × 3 days × 3 concentrations. The results showed the accuracy as mean recovery was 100.29% with repeatability of 1.72% and intermediate precision of 1.76% (n = 27). And the relative expanded uncertainty of the HPLC method was 4.04%. Furthermore, the acceptable limit of the content of berberine hydrochloride in Daochi pills was calculated for the conformity assessment. The risk assessment was accomplished by the Monte Carlo simulation, with the customer risk and producer risk as 3.64% and 5.89%, respectively.