Dabigatran EMA - product-specific guide [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2019-02-14 11:12  – Posting: # 19916
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Hi nobody,

» Have a look at the comments by the originator and the final guidance.
» OK, pH and dabigatran is an issue, …

Highly variable in fasted but not in fed state.

» … but is it really sufficient that the originator writes some 15-20 lines of text (without any citation?) to introduce a rather complex study to the development of a generic? No data at all supporting this claim? And EMA just buys it? Are we back to the 1950's?

Aren’t you notoriously shouting “It’s the originator, stupid…”?
I’m more concerned about the first footnote in the guidance

* As intra-subject variability of the reference product has not been reviewed to elaborate this product-specific bioequivalence guideline, it is not possible to recommend at this stage the use of a replicate design to demonstrate high intra-subject variability and widen the acceptance range of Cmax. If high intra-individual variability (CVintra > 30 %) is expected, the applicants might follow respective guideline recommendations.

meaning that one can plan for the EMA’s method of reference-scaling. Was the EMA’s PKWP not aware of the the FDA’s guidance?

Helmut Schütz

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