On August 1, 2025, Health Canada updated its Guidance on nitrosamine impurities in medications. The revised guidance includes several key changes:
- Timelines for Corrective Actions: Manufacturers have up to three years to implement corrective and preventative actions (CAPAs) for nitrosamine impurities. The deadline is three years from the date an Acceptable Intake (AI) limit is established and published in the guidance document.
- New Impurities and Limits: Seventeen new nitrosamine impurities and their corresponding AI limits were added. The AI limit for N-nitroso-N-desmethyl-doxylamine was also revised from 18 ng/day to 100 ng/day.
- Updated Guidance: The document provides new information on confirmatory testing, control strategies, and analytical procedures. It also includes new guidance for regulatory submissions (Supplements, Notifiable Changes, and Post-DIN changes) where there is no increased risk of nitrosamine impurities.
- Bioequivalence Studies: A new appendix was added to address bioequivalence studies for reformulated drugs that use agents like antioxidants or pH modifiers to suppress nitrosamine formation.
