An updated version of the Guidance on nitrosamine impurities in medications has been posted online.
The guidance document has been updated to indicate that the timeline for completing Changes to the Market Authorization (Step 3 of Health Canada’s call for review) has been extended to August 1, 2025 for drug products containing chemically synthesized and semi-synthetic active pharmaceutical ingredients and for biological and radiopharmaceutical drug products.
Updates to some General, Safety (Appendix 2) and Quality-related topics (including Appendix 1) are also included. For example, the updated guidance document includes additional recommendations for managing and submitting Step 3 changes to the market authorization relating to risk mitigation measures (section 13), updates to the thresholds for reporting to Health Canada on the presence of nitrosamine impurities in drug products (numbers 3 and 15), established Acceptable Intakes (AI) for 3 additional nitrosamine impurities and revisions to the AI limits for 2 nitrosamine impurities.
Those sections that have updated from the previous version are identified with the descriptor “updated”.
Thank you for the update @Naiffer_Host
Newly added AIs for:
- 3-Amino-N-nitrosopiperidine → AI 400 ng/day, CPCA Category- 3
- 5-chloro-N-[[(5S)-2-oxo-3-[4-(N-nitroso-2-(carboxymethoxy)ethylamino)phenyl]-5-oxazolidinyl]methyl]-2-thiophenecarboxamide → AI 1500 ng/day, CPCA Category- 4
- N-nitroso-cinacalcet → AI 400 ng/day, CPCA Category- 3
Revised AIs for:
- N-Nitroso-sertraline → AI 1500 ng/day
- N-Nitroso-varenicline → AI 400 ng/day, CPCA Category- 3
Thanks @Naiffer_Host for this valuable update, wondering if any of the other regulatory bodies would do same like Health Canada? I mean for extending step 3 " Step 3: Update marketing authorisations". The latest update I found in European Medicine Agency was still referring to Oct 2023 for chemical medicines.
That’s accurate; there are no changes in the timelines for EMA. FDA provided an extension but only for NDSRI assessments.
Thanks @Naiffer_Host, I explored the TGA website to check situation in Australia, and found that the TGA are not requesting sponsors to provide risk assessments for the potential of nitrosamine impurities as per below:
“We are not requesting that sponsors provide risk assessments for the potential for nitrosamine impurities to the TGA where they do not identify a concern in existing medicine products. However, this information should be available if requested by us.”
This is as per my today visit to the link below:
Hello team, your input is highly appreciated. I’m looking for any updates regarding the FDA’s guidance on NDSRIs. The guidance suggests that if NDSRIs weren’t considered in previous risk assessments, manufacturers and applicants should review the risks within three months of the guidance’s publication. The recommended deadline for completion is November 1, 2023, as part of an overall risk management strategy.
I’m wondering if the FDA is requesting a theoretical NDSRI assessment and if it’s feasible for all drug products to meet this strict deadline.
Do we have any information on whether this deadline might be extended? Because to evaluate the NDSRI in a drug product we need a thorough assessment of drug product components, manufacturing method etc. @Naiffer_Host