SR formulations - no MD study? [General Sta­tis­tics]

posted by Helmut Homepage – Vienna, Austria, 2007-01-22 20:09 (6498 d 04:33 ago) – Posting: # 479
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Dear hirenpharm!

❝ If a single dose BE study of a SR product Vs SR product...we find AUC0-last failing but AUC 0-T(Tau)(say 0-24 hrs) passing and Cmax and AUC0-inf is also passing.(fast and fed)…


First of all have a look at Imran's post about metrics in steady state.
Single dose parameters are AUClast, AUCinf, and Cmax (although depending on the drug and the type of formulation other parameters like Cmax/AUC, HVD, and MRT may be of interest).

Do I get you right:
AUClast and AUCinf passed, whereas AUC truncated at 24 h did not? This is an interesting phenomenon I never came across before!

❝ …and no need for steady state.


Based on what?
Do you mean that if you do not expect any accumulation, there is no need for such a study?

❝ Can be seek TGA approval for the study?


Yes, but I strongly would suggest a scientific advisory meeting beforehand.

Just to give you an example, we tried to get around a multiple dose study for a formulation with following properties:We had 5 years of development time, a lot of single dose data (vs. solution, IR, fasting, fed, different types of food...), two scientific advisory meetings, a couple of deficiency letters, and finally an approval in 15 European members states. Retrospectively I'm not sure whether it was worth the trouble.

❝ Which objections are anticipated?


OK, the simple one: it's against the guidelines - at least in many countries.
The rationale for a multiple dose study is not only to show BE in steady state, but to get information about potential problems (i.e., even if you have demonstrated no food effect in single dose, and dose dumping is a rare event, you have a higher chance to 'see something' in steady state).

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