Biowaiver criterion <5% (not ≤5%) [Regulatives / Guidelines]

posted by wienui  – Germany/Oman, 2022-08-16 20:22 (109 d 18:39 ago) – Posting: # 23223
Views: 553

(edited by wienui on 2022-08-17 12:23)

Dear Laura, Helmut & all,

It is true that the EMA GL states that for an additional strength biowaiver, the Amount of API(s) must be < 5% of the tablet (capsule) core weight for both strengths, the BE strength and the biowaiver one.

Moreover, the Amounts of excipients are the same per strength, or Only the amount of a filler is changed to account for changes in API weight.

From assessor's point of view, who considers that Guidelines ( Guidances) are not "carved in stone" as Helmut always says, we have to take the physicochemical characteristics of the API itself into consideration, we have to differentiate also if the API is a Narrow therapeutic drug index (NTI) or wide range one with well established therapeutic equivalence, for such later one I think a variation of about 10% from the 5% rule could be acceptable.

"Quantitative sameness (Q2) generally is interpreted by FDA (OGD) to mean a concentration that is within 95-105% of the RLD concentration."

Please note that The US FDA doesn't consider this 5% rule and the requirements for an additional strength biowaiver are as follows:
The total weight of the dosage form is nearly the same for all strengths
Same inactive ingredients in each strength
Change in strength obtained by varying active and one or more inactive ingredients.


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