Yosuke: Could you please give us some examples of the types of discussions taking place in each category within Nitrosamines Exchange?
GPT5: Below are real examples of discussion threads or topics from Nitrosamines Exchange, grouped by the major categories. These illustrate the kind of issues, questions, and knowledge that participants exchange. (All examples are drawn from the publicly visible forum) (Nitrosamines Exchange)
1. Confirmatory Testing & Analytical Challenges
- “What if the answer you’re looking for is already here …” — A user discusses challenges in developing ultra-sensitive methods, matrix effects, isotope-labeled internal standards, and invites others to share their lab difficulties and adaptations. (Nitrosamines Exchange)
- “Synthesis Attempts and Failure Report” — A thread about APIs for which nitrosamines could not be generated experimentally, including sharing of negative synthetic trials and discussion on how such failure reports might help in regulatory justification. (Nitrosamines Exchange)
- “Method of Analysis for N nitroso Diclofenac and Quetiapine” — A thread where people share method details or challenges in quantifying nitrosamines in complex drug formulations. (Nitrosamines Exchange)
2. Risk Assessment Strategy / Tools & Technology
- “
Risk assessment not strong enough …” — A thread questioning adequacy of risk assessments especially for related impurities containing secondary amines, and seeking community input on improving rigor. (Nitrosamines Exchange) - “Potential Topic … obtaining the right level of Nitrosamine Risk Assessment information from your CMOs” — A discussion on how to get meaningful nitrosamine risk data (including solvents, starting materials) from contract manufacturers and suppliers, and how to deal with insufficient supplier input. (Nitrosamines Exchange)
3. Limits / Acceptable Intake (AI) & Regulatory / Guidance
- “EMA has updated its AI limits on 01 Aug 2025” — Participants share news about EMA’s updated AI values in Appendix 1 and discuss potential impacts. (Nitrosamines Exchange)
- “N-Nitrosamines without published AI, and possibly negative for carcinogenicity” — A thread discussing nitrosamines not yet covered by regulatory AI tables and evaluating whether negative mutagenicity or carcinogenicity data might safely exclude them. (Nitrosamines Exchange)
4. Manufacturing / Process / Mitigation
- “Monitoring the Concentration of Nitrogen Oxides in the Fluidized Bed Drying/Granulation Process and Evaluation of Reduction Methods” — Discussion about NOₓ monitoring in manufacturing, filter strategies, and how to reduce nitrosamine risk in equipment. (Nitrosamines Exchange)
- “The effect of nitrite and nitrate presence in raw materials on nitrosamine risk” — Debate on how nitrite/nitrate levels in excipients or raw materials contribute to nitrosamine formation, how to interpret supplier data, and how to set acceptable nitrite levels. (Nitrosamines Exchange)
5. New Scientific Knowledge / Development
- “A Simple and Scalable Synthesis of N-Nitroso Salbutamol Impurities A, D, and F — Pub” — A thread sharing a new synthetic route and discussing how that impacts understanding of impurity formation. (Nitrosamines Exchange)
- “NDMA production in the presence of formaldehyde: Competition between acid-catalyzed and formaldehyde-catalyzed reactions” — A mechanistic chemistry discussion around how nitrosation reactions might proceed under different reaction pathways. (Nitrosamines Exchange)
6. Guidance / Documents / Resources / Events
- “FDA Control of Nitrosamine Impurities in Human Drugs revision2” — Announcement and discussion about the revised FDA guidance. (Nitrosamines Exchange)
- “Potential Topic …” (see above) — participants solicit new topics, especially regarding interactions with CMOs and supplier data gaps. (Nitrosamines Exchange)
- “Nitrosamines Exchange – Analytical Hub” — The hub is introduced and explained—its purpose is to host non-compendial method “Application Notes” shared by community members. (Nitrosamines Exchange)