Laura Carreiras
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Portugal,
2022-08-12 14:03
(172 d 18:17 ago)

Posting: # 23218
Views: 1,033
 

 Biowaiver criteria - 5% [Regulatives / Guidelines]

Hello everyone!


As described in the bioequivalence guideline:

[image]

I would like to know if anyone has experience with a similar situation. If the active substance is equal to 5.00% of the tablet core weight, can it be considered proportional?

Thank you in advance for the help.
Helmut
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Vienna, Austria,
2022-08-12 14:17
(172 d 18:03 ago)

@ Laura Carreiras
Posting: # 23219
Views: 833
 

 Biowaiver criterion <5% (not ≤5%)

Hi Laura,

[image]


❝ I would like to know if anyone has experience with a similar situation. If the active substance is equal to 5.00% of the tablet core weight, can it be considered proportional?


Do you have rounding here, say, 5.0049% → 5.00%?
Even if not, ‘less than’ ‘less or equal than’…

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Laura Carreiras
☆    

Portugal,
2022-08-12 14:37
(172 d 17:42 ago)

@ Helmut
Posting: # 23220
Views: 824
 

 Biowaiver criterion <5% (not ≤5%)

Dear Helmut,

Thank you for your quick answer.

Well, I agree with your answer, in fact the guideline is clear. In our case, the value is 5.00%, without rounding. We wanted to know if anyone had already been through this situation and if the competent authorities accepted proportionality.

Thanks again.


Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5[Helmut]
wienui
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Germany/Oman,
2022-08-16 20:22
(168 d 11:58 ago)

(edited by wienui on 2022-08-17 12:23)
@ Laura Carreiras
Posting: # 23223
Views: 766
 

 Biowaiver criterion <5% (not ≤5%)

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.

Cheers,
Osama
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