Bioequivalence and Bioavailability Forum

Hi javier,

❝ the big question is how to calculate the amount of time to reach this conclussion about AUCt is at least 80% if you only have the information of the SmPC? (with so many important PK information omited )

❝

❝ on another way: how to forecast the number of days that you will need to takes blood samples to cover the magic number of 80%?

This is not what you want to do. This what your boss wants you to do.
Biologics are much less defined that synthetic drugs, especially if they are produced by eukaryotic cells (S. cerevisiae etc). There are all sorts of little games going on with them which is not well understood and well controlled even in the most strictly regulated GMP facility. Check for example your batch release chromatograms (if you have them, if chromatolophystique is used where you work): You will see chromatograms that look like porcupines or someone having a really bad hair-day and where the individual spikes correspond to variants of post-translational modfication and where you don't really know
-exactly which ones are active
-their exact structure
-how potent they are
-and which ones aren't potent/active.

All these species may have different properties in terms of ADME. You will likely see differences in apparent t½ for Test and Ref.

I recommend that you do a pilot trial and forget all about the info on the SPC. You are facing a source of error that is potentially much much higher than what you are used to from synthetics.

I think a pilot trial in a dedicated phase I facility is also the ethically correct thing to do.