Which statement about regulatory bioequivalence criteria is accurate?

• A. BE criteria require 95% confidence interval to fall within 90-125%
• B. The criterion uses geometric mean of T/R
• C. BE is based solely on Cmax
• D. BE acceptance is defined by 90% CI for T/R ratios within 80–125%

Answer: (D)

In regulatory bioequivalence, the key idea is to show that the test product behaves like the reference in how quickly and how much of the drug gets into the body. This is assessed by comparing PK metrics such as Cmax (peak concentration) and AUC (extent of exposure) between the two products. The proper way to summarize this comparison is to analyze the data on a log scale, which stabilizes variance and makes the distribution of ratios more normal. From that analysis, you obtain a 90% confidence interval for the ratio of test to reference means. When you exponentiate this interval, you get a confidence interval for the ratio of geometric means (the T/R ratio) on the original scale. The critical regulatory rule is that this 90% CI for the T/R ratio must lie entirely within 80% to 125% for each primary PK parameter considered (typically Cmax and AUC). If both parameters meet this criterion, the products are considered bioequivalent; if one fails, they are not. It’s not based on a 95% confidence interval, and it isn’t based solely on Cmax—the 80–125% window applies to the T/R ratio for the primary endpoints, usually including AUC as well.