Directive 2001/83/EC, Article 10(3) = hybrid [Design Issues]

posted by Helmut Homepage – Vienna, Austria, 2021-01-25 17:39 (141 d 15:15 ago) – Posting: # 22189
Views: 522

Hi Brus,

» » So far so good. Since you are mentioning RLD you are targeting the FDA, right?
» I called reference product as RLD, but it is not for FDA, it is for EMA. Sorry for the misunderstanding

OK, then it’s a hybrid (see Dr_Dan’s post).

In cases where the medicinal product does not fall within the definition of a generic medicinal product as provided in paragraph 2(b) or where the bioequivalence cannot be demonstrated through bioavailability studies or in case of changes in the active substance(s), therapeutic indications, strength, pharmaceutical form or route of administration, vis-à-vis the reference medicinal product, the results of the appropriate pre-clinical tests or clinical trials shall be provided.

» » Is a single (not daily) 150 mg dose approved?
» Yes. According SmPC of reference product, it is possible to administer one single dose of 150 mg.


» » In Europe that’s the hybrid pathway. Additionally to this study generally clinical studies are required as well.
» Why? If efficacy has indeed been demonstrated with 150 mg and SmPC establishes a 150 mg dose regimen. What more can you ask for? To my understanding, you just have to show that your 150 mg provided in your tablet will behave in the same way as the 150 mg of the reference product provided by a 100 mg tablet and a 50 mg tablet. What am I missing?

Since no 150 mg reference exists, you can’t go the generic pathway acc. to Article 10(2)(b).
I strongly suggest a scientific advice (at a “difficult” agency). That’s what I did in all of my hybrid applications. What you need additionally to the comparative BA study needs to be settled. If it’s a simple IR product (no excipients influencing gastric motility, no solubility problems) maybe clinical trials can be waived.

Dif-tor heh smusma 🖖
Helmut Schütz

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