Bioequivalence and Bioavailability Forum

Hi John & A-M-R!

❝ I don't see how A-M-R can bypass BE studies other than going with BCS classifiation (FDA?).

Exactly. Same with EMA’s rules. A-M-R hasn’t stated the regulation he/she is aiming at. Maybe there are still countries with a “positive list” (i.e., drugs where no studies were required at all…). Such lists existed in Germany and Poland, and – until last year for national authorizations only – in The Netherlands. Must have been fun to be an assessor in Holland:

• First dossier: National application. Drug on the positive list. No BE study, no biowaiver requested, only quality data submitted.
  Approved.
    Go for lunch.
  
• Second dossier: Same drug, same test and reference formulations as above. Well, there was no reference above… Concerned member state in a mutual recognition procedure. Two large BE studies, fasting/fed. Fasting study passed, fed study’s C_max ratio 90% CI 85.00–125.01%.
  Rejected.
    Have a coffee-break.

❝ […] if he goes with BCS it will probably be cheaper and less time consuming in the long run? He also needs to make sure that the reference product is rapidly dissolving (as per FDA guidance).

Absolutely. Look at my last sentence above. With nothing published this will be a tough job (I wouldn’t even think about it). Even if one overcomes all these obstacles, the risk assessment will be the show-stopper. A-M-R, to get an idea have a look at FIP’s biowaiver monographs.
Unfortunately many colleagues still think that a biowaiver means only a bunch of nice f₂ values and mass balance from the literature. It’s not that easy.