Bioequivalence and Bioavailability Forum

Hi Aan,

For a long answer, I think there are 2 aspects here: scientific and regulatory point of views, which, unfortunately, are not always the same.

From what you said I would summarise/infer the following based on my experience:

--- in fasting, reference has mean AUC of 3377.07 ng.h/ml and in fed, reference has mean AUC 1382.98 ng.h/ml, which is expected; after all, food effect of PPI is well known.
--- In fasting, test is BE to reference but in fed, test has much higher AUC values but those values are lower than the AUC values of reference in fasting; in another word, AUC of test in fed is much less than 3377.07 ng.h/ml.

If so, from a pure scientific point of view, I’d say that you have a “better” formulation since your formulation has less food effect, as pointed out by Helmut, which is not a surprise really since most of PPI products are old formulations and the technology improved so much recently the new formulation would have less food effect (at least this is my experience of 4 PPIs). In addition, there shouldn't be any safety concern if the above assumption is true.

Of course, to actually claim that you have a "better" formulation you would need clinical study to prove it but that’s beyond the point we are talking about.

From regulatory point of view, for a product to be fulfil the definition of generic, at least according to EMA’s guideline, your formulation should be “as good as” or “as bad as” the reference product, so to speak. Your product seems as good as the reference in fasting but not as bad as the reference in fed. This was the “end of story” Helmut and Ohlbe referred to. And I agree of course.

However, I do have a different opinion with regard to “additional clinical study” for “hybrid application” as mentioned by Helmut.

I had similar product with the same situation and we registered the product in several EU countries based on "hybrid" application without any additional study. We also managed to register it as generic product in one EU country based on scientific argument (don't ask me where and how ). So I guess it may also depend on who’s actually evaluating your dossier.

So to answer your question,

❝ So in this case a additional clinical study is required ? or the same BE study is enough for the submission to the regulatory as Generic.?

I would say that it would be really difficult to submit the dossier nowadays as generic but the probability of register it via hybrid application without any additional study is high.

I hope this helps.