Bioequivalence and Bioavailability Forum

Hi LB,

❝ If one wants to develop a generic formulation fr the same, what route he/she should take

❝ 1. Invitro tests/Tests for DPI formulation and a BE study on healthy volunteers

❝ or

❝ 2. Invitro tests/Tests for DPI formulation and a PK and/or PD end point study on patients?

There is at the moment no single and clear answer to your question.
See here: paper 1 and paper 2.
FDA still hasn't published guidance. In paper 2 there is a nice figure discussing four aspects that the FDA expect (-ed at the time of publication): Device + in vitro + PK + PD as long as we talk a plain ANDA.

There's a draft in vitro guideline from 2003 which discusses in vitro characterisation in detail. Very difficult to actually carry out the experiments (bootstrap stats) and no way to dimension according to variability.

❝ So, what should be the way for a generic developer??

1. Team up with a good consultant from the field of equivalence and inhalation
   
2. Think hard and consider 505(b)(2) as a potential alternative to 505(j). I am not saying 505(b)(2) has an advantage over 505(j) just that it is an alternative you could consider.
   
3. Enter a dialogue with regulators.

Another paper (like paper 1 but more broad in scope) is coming up where regulators are involved as authors. I don't know the publication date yet.

Be prepared for a really tough ride - there's going to me a million surprises for you with the DPIs.