Bioequivalence and Bioavailability Forum

Dear All,

Recently I was in terrible situation, where one of my FDA submission study got failed in AUC 0to72, the drug under investigation was long half life drug and therefore blood samples were only collected upto 72 hrs post dose. During PK analysis actual time of blood sample collection was used, and CI limits were for AUC 0to72 were (79.34 -114.22). Sponsor subsequently done PK analysis at his end and came up with CI limits of (89.12 -108.11), after investigation it was realized that sponsor has considered the scheduled time for last ambulatory visit with the explanation that our parameter was AUC 0to72 and if we consider actual time (for some of the subjects 72 hr ambulatory sample was collected up to 74 hrs) the PK parameter becomes AUC 0to74, therefore for truncated study only schedule time should be considered.

Further sponsor provided explanation that since there is a window period of 2 hrs for ambulatory visit, we should consider only schedule time for ambulatory sample (i.e. 72 hr; even if the sample is collected by 74 hrs) and for all the samples which are collected after window period of 2 hrs actual time should be considered.

Expert views are highly appreciated, on the consideration of actual time for PK analysis.

Regards,

Ratnakar

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Edit: Category changed. [Helmut]