Bioequivalence and Bioavailability Forum • Waiver of lower strength

Averroes
☆

Spain,
2011-10-20 16:45
(4973 d 04:56 ago)

Posting: # 7526
Views: 3,651

Waiver of lower strength [Regulatives / Guidelines]

Dear All,

Thanks for this great forum. I learn a lot from it!!

As per EMA guideline (Section 4.1.6), proportionality in composition is still fulfilled if the amount of the active substance is less than 5% of the tablet core weight in both the strength used in the BE study and the strength for which a waiver is considered.

My question is simple: the weight of the active substance (salt) is more than 5% in the higher strength, but if we consider the base, it is less than 5% in both formulations.

Which is considered by EU Regulators the active substance for calculations, salt or base?
Can we expect a waiver for lower strength taking into account we meet the criteria for the base?

Thanks in advance!!!

JMCardot
☆

France,
2011-10-24 14:02
(4969 d 07:40 ago)

(edited on 2011-10-24 17:07)
@ Averroes
Posting: # 7534
Views: 3,091

Waiver of lower strength

Post reply

Dear Averroes

I will give a common sense answer to your question (and I apologize as I am not a specialist).

For me you have to take into account the quantitative formula that is in your dossier in percent of ingredient use in the process/formula as it is the reality. I.e. you have 30 mg of salt (correspond to 25 mg of base) for a total mass of 500 mg tablet which lead for me a proportion of 6% of active ingredient as it is the reality of your formulation and production process. The reason is that the amount of API and its limits are based on possible influence of the final behavior of the tablet.

If you take a non-sense example: 250 mg of salt corresponding to 25 mg of base in a 500 mg final mass tablet, the API in form of salt could deeply influence the behavior of the tablet.

Of course if you are just border line you could try to discuss with agencies...

Best regards,

JM

Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]

Averroes ☆ Spain, 2011-10-24 19:18 (4969 d 02:24 ago) @ JMCardot Posting: # 7538 Views: 2,975	Waiver of lower strength Post reply
	Dear JM, Thanks for your reply, it's really clarifying, specially the non-sense example you mentioned. I totally agree and it's in line with my thoughts, but I wanted to get a second oppinion. In any case, as you said, we are borderline here (below 7% in the BE dose), so we will probably ask authorities. Thank you very much!!!