Sixth Nitrosamine Implementation Oversight Group (NIOG) - meeting with pharmaceutical industry

EMA published the documents used in the NIOG meeting with pharmaceutical industries.

Agenda - 6th meeting of the Nitrosamine Implementation Oversight Group - Industry Association

Highlights from the 6th meeting of the Nitrosamine Implementation Oversight Group (NIOG) industry partners (IP)

Presentation - Nitrosamines survey results implementation of nitrosamines guidance throughout EU MSs

Presentation - Update on new developments for nitrosamines

The excerpts of presentation slides from industries are as follows;

Harmonization of actions is expected.


I want to add information.

From indutry presentation:

From highlight:
NIOG reiterated that the LTL approach is for use by NCA for authorised products when necessary to avoid shortages.

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Thanks for sharing @Yosukemino. I recently did a comparison survey of APIs with FDA vs EMA limits. The differences in the list were astounding. I can see why multi market products would face real issues.


The EMA indeed confirmed that the Q&A 22 is really seen as a national measure for already authorized products, to avoid shortages in the market, and not speed up the time to market for new products. The EMA is pragmatic here however, and has evaluated the exclusion of new products again during the summer of 2023 when new Q&A 10 AI setting options became available and the Q&A 22 was extended to chronic use products. At the moment there is no Q&A 22 extension to ongoing applications planned, but the discussions do continue. In preparation of the next meeting Industry and EMA are evaluating if there are examples where the LTL would be useful for ongoing applications (including mapping of patient impact where the approach would lead to swifter launches). This would be applications where CPCA/EAT/in vivo mutagenicity studies are not helpful enough.

That deciding on market actions for medicines exceeding the guided AI is and will remain a national prerogative for nationally authorized products, as it would be for any other contaminant was also an important point of the discussions indeed. The scientific assessment part (the review of the science behind the testing data and the AI) happens in a harmonized way via a LMS system for scientific intergovernmental collaboration and publication of guided AIs centrally, the second part, the market actions possibly following the scientific assessment are market specific as this is how the European regulatory network deals with nationally authorized products. A proposal to also fully centralize regulatory decision making for the second part (temporary higher limit or market actions?) goes against the DNA of NAPs and cannot be accepted at the moment.


Yes I agree. for N- nitroso nortriptyline for example the FDA AL is 26ng/day whereas the EMA has an AL of 8ng/day. How can we challenge this lack of harmonization?

It is noteworthy that several regulatory agencies, including Health Canada [(55)](javascript:void(0):wink: and the EMA, [(54)](javascript:void(0):wink: have established an extremely low AI limit of 8 ng/day for N-nitroso nortriptyline based on the TD50 of 0.008 mg/kg/day for N-nitroso methylphenethyl amine. However, recent findings raise a question about the appropriateness of such a low AI limit for this particular NDSRI, given its relatively low α-hydroxylation value of only 0.07, in comparison to the higher values observed for the three analogues, including N-nitroso methylphenethyl amine.