Bioequivalence and Bioavailability Forum

Hi dshah,

❝ I am having few doubts for harmonization.

Welcome to the club!

❝ Why regulatory bodies does have different requirement for scaling acceptance …

IMHO, not related to science at all but to politics.
I attended all conferences of the ‘Global Bioequivalence Harmonization Initiative’ and was a member of the panel of the session ‘Scaling Procedure and Adaptive Design(s) in BE Assessment of Highly Variable Drugs’ (2^nd GBHI, Rockville, September 2016). Justifications? Not really. I guess (‼):

• The FDA essentially walked in the footsteps of IBE (where reference-scaling was part of the method). Being aware that problems may exist with any PK-metric, RSABE not limited to C_max.
  
• In Europe many products were approved in the 1990s based on wider limits for C_max (Δ of 0.30 → 70.00–142.86%). Do these numbers look familiar?
  
• Health Canada faced no problems with C_max in the past because the confidence interval was never required.

❝ Or for NTI- limit of 90.00-111.11 is more relevant than RSABE approach and does justify the safety and efficacy?

Good question, next question.