Bioequivalence and Bioavailability Forum

Dear Ahmed!

❝ [...] When one of my colleague submitted dossier for fluoxetine 20 mg capusule in sweden it has been queried by swedish authorities why we had submitted a single dose study on fluoxetine for estabilishing BE. Reason for this is (given by swedish authorities) both fluoxetine and its metabolite nor fluoxetine follows nonlinear kinetics. As per their view, "for substances with nonlinear kinetics normally BE should be estabilshed during the most saturated condtion achieved therapeutically"

OK, the Swedish statement possibly is a misinterpretation (Dose proportionality of several strengths) of the EU Guidance on BA/BE (#5.4, page 15).
For a clarification have a look at the recent Q&A-Document (#9, page 4).

❝ (Whether it means Steady State conditions ??!!)

IMHO, no; but in the worst case they want BE demonstrated at the highest recommended dose (according to the SmPC of the reference product), which for fluoxetine means 60 mg (in some countries and for some indications even 80 mg).
In such a case a study in healthy volunteers is infeasible (AEs!).

Your colleague should consider applying for a Scientic Advice at the Swedish MPA to clarify the question.