Bioequivalence and Bioavailability Forum

Dear Helmut et al

In an upcoming BE study, we are planning to use the two-stage design as recommended in the draft guideline. Our rationale is as follows: (a) variability of the drug substance is unknown & not published; (b) for formulation reasons there is a significant risk of bio-inequivalence (making the option to stop after the first group an attractive one).

To our surprise, in assessing the protocol the local regulators (Irish) have questioned our approach on the grounds that they are not sure whether the two-stage approach will ultimately prove acceptable in the future. Informal advice from the MHRA is similar. [Effectively they are saying we use this approach at our own risk. So, nothing new there!]
It is clear that the two-stage design is acceptable to some regulators and not to others; I presume that those who accept this approach got their way when the new guideline was drafted. That said, it looks as though this will remain in the final guideline.

My questions are:
Has anyone heard otherwise (will two-stage stay or go)?
Is anyone else using this approach yet?

Kind regards

Andrew

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Edit: Category changed. [Helmut]