Bioequivalence and Bioavailability Forum

Dear Swapnil!

❝ Dear HS,

    ▲ Not interested in opinions of other members of the forum?

❝ Which parameters of bioequivalence needs to be evaluated to ensure that clinical trials are focused in right areas?

I’m confused as well – can you reword your question?
What do you mean by ‘… to ensure that clinical trials are focused in right areas’? The basic assumption (!!) of bioequivalence is that similar concentrations in biological matrix (whatever ‘similar’ means – based on PK and some statistical magic) lead to similar concentrations at the receptor. Therefore safety/efficacy should be similar as well.
Which PK metrics (I prefer this term in NCA; parameters refer to a model) are best suitable depend on the formulation and design.

• single dose
  Extent of absorption: AUC_t (EU and many other countries) + (!) AUC_∞ (USA)
  – or: AUC₇₂ (no extrapolation)
  Rate of absorption: C_max (everywhere)
  If clinical relevant, early exposure: Partial AUC truncated at the median t_max of the reference (USA, Canada); t_max (EU and many other countries)
  
• multiple dose
  Extent of absorption: AUC_τ (everywhere)
  Rate of absorption: C_max (everywhere)
  Optional – depending on the formulation (mostly MR): C_min, PTF, MRT, HVD, t_75%,…

If you show bioequivalence you may claim exactly the same indications as the innovator. Well, theoretically you could claim fewer – but not more!