Bioequivalence and Bioavailability Forum

Dear All,

❝ As far as I know regulators do ask for such study for mentioned products, referring to Q&A which should be read in conjuction with product specific guidelines. Draft of Apixaban product specific guideline already requires such study, unless justified. It's unknown if EMA will update Riva and Tica guidelines. Anyway, for me this whole concept of product specific guielines makes not much sense, if you still need to verify if finalized gudieline is consistent with current EMA thinking published in other documents. Especially that date of coming of these gudeiline into effect was same as publishing Q&A (NOV 2016). So they were already outdated when coming into effect (!).

The EMA has revised its position on this topic on March 2019, Now, It is no need to conduct any further studies with this additional mode of administration.


https://www.ema.europa.eu/en/human-regulatory/research-development/scientific-guidelines/clinical-pharmacology-pharmacokinetics/clinical-pharmacology-pharmacokinetics-questions-answers


the PKWP has revised its position on this topic and presently considers that it is highly unlikely that the change in bioavailability will be different between test and reference, once bioequivalence has been shown between test and reference with the intact or non-dispersed tablet.

Consequently, if the SmPC of the reference product allows for the possibility to administer the tablet crushed/disintegrated (and dispersed in food), bioequivalence does not need to be also demonstrated with this additional mode of administration.

Best regards,
Osama