Bioequivalence and Bioavailability Forum

Helllo Yura,

❝ Is it possible that the confidence interval is expanded to Cmax for non highly variable drugs?

I can't see this happening in any of the regulatory territories I work with. There could in theory be product-specific guidances allowing it but I can't think of any from the top of my head.

Dear Yura
the width of the confidence interval depends on the variability of the drug and the number of subjects. I guess what you mean is widening of the acceptance range. As explained by ElMaestro this is not possible in case of non highly variable drugs. If you have a non highly variable drug you need to increase the number of subjects in order to tighten the confidence interval in such a way that it fits in the general acceptance range of 80 - 125%.

Assuming that you're asking about widening the acceptance criteria, at least for EMA and FDA that would be impossible. The definition of highly variable drugs is clear in both EMA and FDA guidances. No drug is considered highly variable by itself. In fact, the same drug could be highly variable in one study and fail to met the criteria in another different study. As far as I know, fed studies likely produce results with higher variability so the same drug may be considered "highly variable" in the fed study but fail to met the criteria for the fasting study.