Bioequivalence and Bioavailability Forum

Hi all,

I'm hoping that in spite of the lack of any discussions on irritation/sensitization studies, this is an appropriate place for this discussion.

From a product specific FDA guidance on a patch product:

"If a patch completely detaches, it should be replaced within 24 hours and the subject should continue in the study. During the 21-day Induction Phase, if a patch is completely detached for more than 24 hours (unless the patch was removed for an unacceptable degree of irritation), the subject should be excluded from both the irritation and sensitization analyses for that product."

This suggests that in case of detachment, as long as the patch is reattached within 24 hrs, the subject may continue and be included in the I/S analyses. For most products, a new patch is attached every 24 hrs. However, if we take the extreme example of a subject having his/her patch detach after a couple of hours each day (therefore, always having a new patch applied before the 24 hrs elapse), the subject would be included in the analysis because he/she never had a patch off for more than 24 hrs. Yet the subject's exposure to the patch would be severely affected with only a partial exposure to the product. Wouldn't it make more sense to exclude subjects who had a total cumulative time of detachment greater than 24 hrs over the whole study (21 days)? In this latter case, the subject I had mentioned would be excluded from analysis since he/she had the patch off for more than 24 hrs. If I were to put this cumulative criteria in the protocol, would that be acceptable for the FDA?

Looking forward to your input.
Thank you.