Bioequivalence and Bioavailability Forum

Dear satya!

❝ How do one consider the biological variation in determining the

❝ bioequivalncy of two formulations?

By performing an in vivo bioequivalence study.

❝ Isnt it possible for two products to fail equivalency test in vivo (due

❝ to interindividaul differences) even though their all in vitro paratmeters

❝ are identical?

Yes, this is not even possible, but very likely if:
1. the drug belongs to BCS classes II and IV (permeability controls absorption),
2. your drug belongs to BCS I (or maybe III) and your dissolution method is not discriminative,
3. no IVIVC (in vivo - in vitro correlation) exists.

-> 1. For such a drug you will never be able to predict BE, because you are simply missing the important barrier (the gut wall) in the dissolution apparatus. Therefore similarity of in vitro dissolution profiles is meaningless in predicting the in vivo situation.
-> 2. In such a case you will fail to show in vivo BE, because your predictions are wrong.
-> 3. This is just a special case of #2 - you tried hard, but failed.

Since in vivo bioequivalence is a surrogate of clinical efficacy/safety this study is the 'gold standard'.
Some people call volunteers participating in a BE study 'human test tubes' because we are comparing the performance of formulations in a kind of 'biological dissolution model'. Only this model incorporates biological variability. Just remember that we will treat patients with the new formulation - not a dissolution beaker...