The research article delves into the intricate details of designing in vitro bioequivalence trials. The paper emphasizes the importance of tailoring the design of these trials to the predicted product properties rather than adhering to a prescribed method. The article investigates the performance of the Population Bioequivalence (PBE) test under different circumstances and explores the impact of possible changes from the minimum trial design recommended in many FDA Product-Specific Guidances (PSGs).
The article discusses how the PBE test is recommended for bioavailability and bioequivalence studies for nasal aerosols and nasal sprays for local action, and multiple PSGs for metered dose inhalers and dry powder inhalers. It also highlights the key properties of Orally Inhaled and Nasal Drug Products (OINDPs), such as the normal distribution of performance metrics like impactor stage mass and delivered dose, which breaks the assumption of log-normality in the PBE test.
The article further explores the design of in vitro bioequivalence trials using statistical power and assurance. It explains how power and assurance calculations can be used to explore the impacts of possible changes from the minimum trial design recommended in many FDA PSGs. The article concludes by emphasizing the need for careful design of bioequivalence trials using novel performance metrics to ensure an adequate chance of determining bioequivalence when it is true and avoiding costly underpowered trials.
