Bioequivalence and Bioavailability Forum

Hi R101,

❝ What is the time limit deviations that are accepted (before and after) in the 24, 36, 48 and 72 h interval

I do not know of any specific rules in any guideline.
As I see it, one can make a case for saying that the way to deal with time point deviations should be API-specific as well as time-specific.

Some CROs define a window in terms of time (for each time point); if the sample is taken with the window then the nominal time is used for PK (for AUC calculation), otherwise the actual time. Some CROs will always use the actual time. Both approaches seem to work well across jurisdictions. The option that does not work is to use nominal time regardless of sampling time.
All this requires a rock solid way of having the actual time points conveyed to the people doing PK. Some CROs will have the clinical people calculate the actual time used for PK and then let PK staff do their work on the data; other CROs will let PK-people scan over the sampling time to derive their actual time for AUC-calculation.

Another issue is if or when a deviation of sampling time is a protocol deviation. From the top of my head I am thinking most CROs specifically do not call a time point deviation a PD, but has another category for it. They for instance put those situations in an odd sock drawer called "Other types of deviations".