The European Medicines Agency (EMA) has published the sixth revision of the Appendix 1 (“Acceptable intakes (AIs) established for N-nitrosamines”) of the EMA Questions and answers for marketing authorization holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products (EMA/409815/2020 Rev.21).
Nitrosamines are formed by a reaction between nitrates or nitrites and certain amines. Medical reviews have reported a positive association between nitrite and nitrosamine intake and gastric cancer.
The update provides new guidance on acceptable intakes (AIs) were proposed for N-nitrosamines in APIs such as acebutol, buspirenone, ciprofloxacin, dimetindene, diclofenac, maprotiline, melipramin, propafenone, rivastigmine, valsartan, vanzacaftor and vildagliptin.
In addition, the US FDA has published the second revision to the industry guidance on “Control of Nitrosamine Impurities in Human Drugs”.