The revision includes an update of the following questions:
- Q&A 4 was updated to reflect the update of the Guidance on root causes and risk factors for contamination with nitrosamines.
- Q&A 8 was updated on the requirements and conduct of confirmatory testing.
- Q&A 15 includes new dossier requirements to allow testing of intermediates, raw materials or active substances under certain circumstances.
- The new Q&A 20 includes clarifications on the regulatory steps to be taken in dealing with scenario A cases, i.e., after the identification of nitrosamine with exceeded tolerable intake.
- Q&A 10 now includes these Nitrosamines with their acceptable intake:
- N-nitrosomethylphenidate, (1300 ng/day)
- N-nitrosopiperidine, (1300 ng/day)
- N-nitrosorasagilene, (18 ng/day)
- 7-Nitroso-3-(trifluoromethyl)-5,6,7,8 tetrahydro[1,2,4]triazolo-[4,3-a]pyrazine, (37 ng/day)
- N-nitroso-1,2,3,6-tetrahydropyridine, (37 ng/day)
- N-nitrosonortriptyline, (8 ng/day)
- N-methyl-N-nitrosophenethylamine, (8 ng/day)
along with guidance on use of Ames test.
The new Step 2-template can be found here.
EMA: Website on Nitrosamine impurities
EMA: Q&A 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