Bioequivalence and Bioavailability Forum

Hello Skar,

❝ Normally we use Expected deviation of 5% or 7.5% in sample size calculation for bioequivalence study. please suggest me the maximum Expected deviation that can be used for sample size calculation?

EU regulators put in the sentence "Unless otherwise justified, the assayed content of the batch used as test product should not differ more than 5% from that of the batch used as reference product determined with the test procedure proposed for routine quality testing of the test product." in the 2010 guideline for BE. and from that perspective you might say that this should be reflected in the powering; at least I know of a few companies doing it this way.
But I think that answering your question is not as simple as just that, mainly because real life can be rather cruel. For this reason Potvin's method for two-stage design was recently extended to T/R's of 0.9, which I see as a recognition of the fact that T/R deviating e.g. 5% from unity is not always realistic. In addition, some dosage forms do not have a well-defined release method that fit neatly into this way of thinking and for which PK may still be used to qualify BE or TE. Examples include nasal sprays and inhalation products. You have all sorts of weird parameters you could try, like delivered dose (which will vary between start and end of canister or spray-bottle) and various size partitions corresponding to what may be expected to reach the relevant sites of absorption or action.
Finally, when something is BE then it is because we are 90% sure that the real T/R is within some acceptance range. A product can be shown BE even if the true T/R is terrible like 0.85. It may just cost a lot of money to prove it.
I am not aware of any other strict rule regarding the maximum expected deviation, but of course some..... erm hehe.... common sense (sorry HS, I couldn't think of any other term) is needed here. If you have a good method in vitro for your expected T/R and it turns out the expected T/R is 0.85 then it might be a good idea to reformulate rather than initiate a study. From an ethics perspective I do see a bit of reason in doing so.