Bioequivalence and Bioavailability Forum

Dear mittyri
Yes, you are right, you need to perform dissolution tests at three different buffers for the BEQ batches of test and reference and to perform dissolution tests at three different buffers for BEQ batch (test) and all additional strengths of test product if linearity of PK is proven and if the different strengths are qualitative and quantitative proportional (otherwise you would need additional BE studies). 12 units of the Test and the Reference product respectively are needed for each experiment to enable statistical evaluation. According to the EMA guideline similarity of in vitro dissolution should be demonstrated at all conditions within the applied product series, i.e. between additional strengths and the strength(s) (i.e. batch(es)) used for bioequivalence. You do not need to compare your strengths with the respective originator strengths. Instability of the active substance in one of ph media is a substance specific property and will occur for the Test formulation in the same way as for the Reference formulation (there should be no formulation effect). In consequence the dissolution profiles should not differ and you have to demonstrate this.
I hope this helps.
Kind regards
Dan