We all know that anti oxidants helps to decrease the generation of NDSRI impurities in many products and FDA already gave clarity on the requirement of bioequivalence after reformulating the drug product using antioxidant and alkalizer. But What is EMA’s thinking on the same change is still not clear. Does anyone is having experience on addition of antioxidant/alkalizer by changing granulating solvent fall under which type of variation? Is this call for new BE study?
Dear @nirav0904
Have you checked Doc. Ref.: CPMP/EWP/QWP/1401/98 Rev. 1/ Corr ** section 4.4. ?
You may also refer to Antioxidant as a risk mitigation strategy - a couple of interesting papers are already posted there.
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Dear Nirav,
could you please elaborate on your comment that FDA gave clarity on the requirement of bio equivalence after reformulating the drug product using antioxidant and alkalizer? Is there any defined quantity of antioxidant or alkalizer from which over this a bioequivalence should be performed?
christos
thanks in advance
Couple of things to keep on the radar:
- pH is a mitigation pathway that is commonly overseeing. Keep this as part of your mitigation tools.
- Do not miss the upcoming FDA-CRCG workshop, where FDA will present research about the use of scavengers and pH as mitigation tool. (I saw some of the preliminary data, and the outcome will be unexpected!)
Dear Chrischar,
In latest guidance, USFDA gave clarity that if reformulation done by adding antioxidant/alkalizer, the bioequivalence is not required in below conditions.
- If Drug is BCS Class I, II or III
- Antioxidant/alkalizer used from FDA evaluated list i.e. Ascorbic acid, sodium ascorbate, propyl gallate, cysteine hydrochloride or sodium carbonate.
- Quantity of antioxidant/alkalizer used is less than 10 mg/day.
So, my question was no such clarity till date from EMA and if anyone from the community is having experience with EMA, can share their experience.
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Dear nirav,
thank you very much for your quick response!!
with regards
Christos