Bioequivalence and Bioavailability Forum

Dear Members,

We have developed Mesalamine Enteric coated tablets 1000 mg. We could not achieve BE in pivotal BE studies due to intrinsic high variability. In addition to that as per EMA guideline AUC must be within 80 to 125% which makes even more difficult to achieve BE.

Can we use PBPK model instead of conducting BE studies and get biowaiver? Our main target market is Turkish MoH. We do have in vitro dissolution data and in vivo data from fasting and fed BE studies.

Please provide your opinion.

Note:
Challenges and some additional information:
Although mesalamine product is administered orally, its bioavailability is limited (15-20%). It has been shown in the literature that there is no clear correlation between plasma concentration levels obtained in the mesalamine pharmacokinetic study and clinical efficacy, and therapeutic efficacy is related to local concentrations in the intestinal mucosa. Mesalamine is highly variable drug but variability is likely due to GI physiological conditions, not formulation.


Regards,
QA