Bioequivalence and Bioavailability Forum

Hi Erkin and Helmut,

❝ ❝ But I don't understand is: we made a bioequivalence study and we found the products as bioequivalent.

❝

❝ Fine. End of story.

From BE standpoint, I couldn't agree more. But if you are the one developing the product then ...

❝ ❝ After that why we bother about ƒ₂ unless sponsor wants to improve their product (and they need to do a new BE study afterall.)

Not all change of formulation require additional BE. For major changes, obviously yes; but for some small modification post approval some times you only need to demonstrate similarity by in vitro dissolution profiles. However, if the profiles are not similar for bio-batch, you might end up with doing BE for those changes that normally do not require in vivo study.

This is the request from one EU regulatory agency:

Bioequivalence between the formulation applied for and the brand leader product has been demonstrated in-vivo; however, similarity of dissolution profiles could not be demonstrated in vitro. Therefore, the dissolution method is considered to be over-discriminating; as a consequence if any future changes in the formulation are proposed the comparison of dissolution profiles cannot be used as similarity of formulations and new bioequivalence studies have to be carried out.

Since I'm working directly with formulation / manufacturing team, my experience is that the possibility of the change of formulation is quite high; actually much higher than you would expect. So it might pay later if you can develop a better in vitro method.

Of course, if you are working in a BE CRO then you shouldn't worry it at all. BE passed, in vivo result prevail. sponsor has a dossier to present. End of story. If they change anything later, more BE business for you.