Total combined risk of false conformity decisions in pharmaceutical equivalence of acetaminophen oral solution

Abstract

Pharmaceutical equivalence studies are fundamental to ensure the interchangeability, quality, efficacy, and safety of generic and similar medications. This work addresses the crucial aspect of estimating the total combined risk of false conformity decisions in such studies, focusing on acetaminophen oral solutions. Traditionally, these studies rely on pairwise comparisons, but this work introduces a multiple comparison evaluation (for 3 or more medicines). Based on measurement uncertainty evaluations and Monte Carlo simulations, the study reveals varying risk levels among different acetaminophen products. Products (A and E), with pH test results near or exceeding specification limits, exhibit higher risks. Furthermore, the impact of correlations between measured parameters within a single product on total combined risk values was considered. The assessment of risk considering multiple comparisons was affected by the number of medications considered (simultaneous comparisons between 3, 4, or 5 medicines). This study highlights the critical role of rigorous analytical assessment and underscores the need to consider the measurement uncertainty data and correlations between measured parameters in decision-making in pharmaceutical quality assurance.