Log in
RegisterBeware of flip-flop PK [Design Issues]
Dear Chirag!
I don't recall running ANDA BE studies. However when I conducted BA (relative bio) studies comparing two ER products (its was for a 505(b)2 submission, to demonstrate bioequivalence between 2 product of same active but in different salt form), the pk profile timepoints were set based on the half-life of the drug (t1/2 was something like 16-20 hrs)...
John
❝ ❝ Is anyone aware of the guidelines for truncation of AUC at 72 hrs for modified release products having longer half life.
❝
❝ I don’t know any. If IR is concerned long half life is irrelevant for truncation (see EMA’s GL); it’s high time for the FDA to revise their guidance. 
The 72 hours are based on the longest passage time of a formulation in the GIT.
❝ If the MR formulation is DR IMHO truncation should be applicable as well.
❝ For CR you might observed flip-flop PK – terminal phase represents absorption or is at least influenced by it. Personally I would be very wary to even use AUCt as the main metric. I would rather use AUC∞ and aim for an extrapolated area of well below 20%.
I don't recall running ANDA BE studies. However when I conducted BA (relative bio) studies comparing two ER products (its was for a 505(b)2 submission, to demonstrate bioequivalence between 2 product of same active but in different salt form), the pk profile timepoints were set based on the half-life of the drug (t1/2 was something like 16-20 hrs)...
John
Complete thread:
- Truncated AUC for modified release products cakhatri 2013-03-12 16:44
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Beware of flip-flop PK Helmut 2013-03-12 16:57
- Beware of flip-flop PKjag009 2013-03-12 20:24
- Beware of flip-flop PK Helmut 2013-03-12 16:57
Ing. Helmut Schütz