Interesting times for nitrosamine science.
When you let the science lead, science will prevail:
24 September 2026: FDA published guidance on applying the ICH M7 less-than-lifetime (LTL) adjustment to nitrosamine impurities. (Supported by Felter 2025 & Felter 2027.)
3 November 2026: EMA followed with Rev. 24 of the nitrosamine Q&A. New Q&A 24 concludes that the ICH M7 LTL framework can be applied to nitrosamines.
EMA also extends the CAPA implementation timeline under interim limits from 3 to up to 7 years from publication of the initial AI. For AIs published since 1 July 2023 (when the EMA introduced the CPCA and EAT, and AI publication ramped up) that window reaches to (at least) around 30 June 2030 (with LTL approach application during CAPA period under Q&A 22), the same horizon as Step 4 (finalize guidance) of the ICH M7 addendum on nitrosamines, anticipated to be available by 31 March 2030.
The gap between EMA timelines and the ICH M7 EWG timelines is now largely closed, giving applicants an opportunity to maximize the valorization of the science of the ICH M7 Nitrosamines Addendum for which consensus on the draft is anticipated by 30 June 2028, about 2 years before the end of the EMA CAPA window (for AIs published upon CPCA introduction). For products intended for lifetime use, which cannot rely on a permanent LTL adjustment of the AI, this gives time for progress on science and consensus for alternative AI setting methods or remediation.
Q&A 10 now also sets out how to derive limits for nitrosamines originating from excipients.
An emerging topic now also lands in the EU: nitrosamines in parenteral products packaged in polymer (IV) bags. First flagged by FDA on 18 August 2025 for leachable NDBA and other small molecule nitrosamines, it is now a root cause in Q&A 4. EMA cites the research of Dr. Jost and team on trace nitrosamines in plastic pharmaceutical packaging materials (https://doi.org/10.5731/pdajpst.2025-000072.1). A clear call to look closely at extractables and leachables studies.
New Q&A 23 clarifies the principles for other N-nitroso compounds, including AIs assessed case by case (EAT, read-across), without the CPCA and without LTL correction.
What I see: regulators converging on science based, harmonized principles, and real momentum for the ICH M7 addendum. I am encouraged by the direction this is taking.
For marketing authorisation holders, now is the time to revisit risk assessments, interim limits, final AI setting approaches and CAPA plans, an ideal moment to refocus. Products used for less than a lifetime may now have a clear path forward, while chronically used products gain a new timeline and new opportunities to advance alternative AI setting or remediation.
Wondering what this means for your portfolio? At Clarbonyx, I help companies translate these regulatory signals and scientific evolutions into practical, defensible strategies.