Bioequivalence and Bioavailability Forum

Dear yvk!

❝ If a drug is not bioequivalent then we can submit to regulatory by

❝ considering pharmacokinetic equivalence?

The term 'pharmacokinetic equivalence' doesn't exist - I would be glad if anybody would be able to come up with a reference.
Bioequivalence itself is of course based on a pharmacokinetic concept, namley '...the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.'

If a product is not bioequivalent, IMHO we have two realistic (out of four theoretical) options:

1. If the point estimate was within the acceptance range, the study was only underpowered to demonstrate BE → new study (e.g. better standardization, more subjects, scaled-ABE, replicate design, etc.)
   
2. If the confidence interval of the PE was outside the acceptance range, the study demonstrated bioinequivalence at alpha <0.05. Repetition of the study is futile → reformulate
   
   
3. Demonstrate equivalence of PD (see this post about your chances). Sample size: dozens to the hundreds (healthy subjects or patients)...
   
4. A clinical equivalence study (placebo-controlled parallel groups). Sample size: hundreds to thousands of patients...; again, any reference is appreciated...