Bioequivalence and Bioavailability Forum

Dear Vernon,

first welcome to the Forum!

❝ We are comparing 2 formulations used in pivotal studies and the drug is given with food in clinical trials. Based on the FDA guidance, a fasted study should be conducted and a fed BE may also be required (not sure?). FDA recommends high-fat meal for fed BE but EMEA (Sept 2006) recommends a light meal to mimic clinical conditions. Should we go for a medium-fat as a compromise?

OK, I think we will need a little more information. Are you going for approval in the US or in the EU?

Since it's an NDA, do you have any information on the food effect yet?
For the FDA you should have this information according to the http://www.fda.gov/cder/guidance/5194fnl.pdf December 2002 Guideline.
Since you have done your clincial studies in the fed state, I think you had good reasons (AEs?). If this is the case, I think it's reasonable to do fed-BE only - being aware that this will go straight into the labeling.

Concerning the European perspective: I guess you are referring to EMEA's Q&A Document. European practice was BE testing in the fasting state, if no reference to food intake was stated in the SmPC, and in the fed state if such was recommended for the reference.
If you have done your clinical studies in fed state only, I would suggest to use the same type of meal in your BE study of the new formulations (since you have set - although implicit - a standard for intake with food).

You are raising a tricky question; at least for the EU I would suggest a scientic advisory meeting.

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Edit: Link corrected for FDA’s new site. [Helmut]