Nitrosamine Impurities in Medications: Overview

This document provides information on nitrosamine impurities in medications, including recent updates on guidance, recalls, testing methods, and results. It highlights the presence of nitrosamine impurities, such as N-Nitroso Dimethylamine (NDMA), in certain medications containing the Active Pharmaceutical Ingredient (API) Valsartan. Health Canada has updated its list of Acceptable Intake (AI) limits, incorporating nine additional nitrosamine impurities with limits derived from the Carcinogenic Potency Categorization Approach (CPCA). Appendix 1 of the document has been expanded to include AI limits for thirteen new nitrosamines, reflecting the CPCA-derived limits.

An updated version of the list of established acceptable intake limits has been posted online, now including eight additional nitrosamines. All Market Authorization Holders (MAHs) have been informed of the confirmed nitrosamine impurities in related drug products through an informational update. Health Canada has also provided AI limits for several nitrosamines deemed acceptable.

Updates to general and quality-related topics cover notifying Health Canada of nitrosamine impurities, conducting risk assessments for these impurities in drug submissions, establishing thresholds for routine testing specifications, and testing approaches for multiple strengths of a dosage form. It also outlines expectations for nitrosamine impurities that are not synthesizable or purifiable. The document includes comprehensive information on nitrosamine impurities, such as news updates, background details, Health Canada’s actions, webinars, and Q&A documents.

Source: https://www.hsa.gov.sg/docs/default-source/hprg-tpb/guidances/tpb-sub-002-006-appendix-1_patent-declaration-forms.pdf?sfvrsn=d29bd9d4_2##~https://www.hsa.gov.sg/therapeutic-products/guidance-documents

Region: Singapore