Dissolution and bracketing - EMA [Regulatives / Guidelines]

posted by Susanh – Iceland, 2020-03-19 19:39 (1350 d 00:11 ago) – Posting: # 21287
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The dissolution at all pHs required for the biowaiver of strengths for submission of generic drugs in EU can be very difficult for drugs with low solubility. I know that the EU guideline allows for some variations were sink conditions are not achieved, e.g. the use same dose comparison (2 x 5 mg vs 10 mg) but this should be confirmed by comparison to the behaviour of the reference product.

I am repeatable running into problems showing similarity between strengths - also when comparing the same dose. And often the reference product does not behave as the test product.

The EU immediate release guideline (CPMP/EWP/QWP/1401/98 Rev. 1/ Corr **) allows for bracketing approach - see below.

Can bracketing be used for additional strengths were the dissolution is not similar? Could BE-studies been done on the highest and lowest strength and not on middle strengths in this case?

Bracketing approach
Where bioequivalence assessment at more than two strengths is needed, e.g. because of deviation fromproportional composition, a bracketing approach may be used. In this situation it can be acceptable toconduct two bioequivalence studies, if the strengths selected represent the extremes, e.g. the highestand the lowest strength or the two strengths differing most in composition, so that any differences incomposition in the remaining strengths is covered by the two conducted studies.

looking forward to your comments.

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