In regulatory bioequivalence studies, which PK parameters are primarily compared between products, and what is the typical acceptance range?

• A. Cmax and AUC; 90% confidence intervals for the test/reference ratio are within 80–125%.
• B. Tmax and half-life; 90% confidence intervals within 70–130%.
• C. Cmin and AUC; 90% CIs within 60–140%.
• D. Cmax and Tmax; 90% CIs within 50–150%.

Answer: (A)

In regulatory bioequivalence, the focus is on comparing how much and how quickly the drug reaches systemic circulation. The two PK parameters that capture this are Cmax, the peak plasma concentration reflecting the rate of absorption, and AUC, the area under the concentration–time curve representing overall extent of exposure. The analysis uses the ratio of the test product to the reference product for these parameters, based on log-transformed data, and the 90% confidence interval for that ratio must fall between 80% and 125%. This range is chosen to accommodate typical intersubject variability while ensuring the test product delivers exposure similar to the reference. Tmax and half-life are not primary criteria in regulatory BE because they are more variable and do not directly convey comparable overall exposure; Cmin is also not a primary endpoint for establishing BE.