Bioequivalence and Bioavailability Forum

There have been rumors during last week's IIR's 'Dissolution, Biovailability & Bioequivalence 2005' conference in Amsterdam about a planned Update of the European NfG (Note for Guidance) on the Investigation of Bioavailability and Bioequivalence (CPMP/EWP/QWP/1401/98).

Potential candidates for a change are:
3.1 Design
where for HVDs a steady-state study in order to reduce variability may not be acceptable any more. A replicate design should be considered instead.
A maximum number of subjects (e.g., n=40 as in New Zealand’s Guideline) is also under discussion.
3.6.2 Acceptance range for pharmacokinetic parameters
which according to the current NfG may be widened from 0.8–1.25 if prospectively defined and justified based on clinical grounds (i.e., safety or efficacy concerns for patients switched between formulations). This procedure provoced a good deal of discussions between applicants and regulators; dropping the widened acceptance range would lead to harmonization with the FDA, where not exceptions are allowed.

Hopefully, the picture will be sharpened next month at the Bio-International 2005 in London.