European Pharmacopoeia Activities (Policy) on Mutagenic Impurities with Focus on Nitrosamines
- Ph. Eur. General policy on DNA reactive impurities
- Control of Nitrosamines in Ph. Eur.
- Changes in individual and general monographs following the Sartan case
- New general chapter on control of nitrosamines
Root Causes for Nitrosamine Impurities and other Mutagenic Impurities – Practical Approaches to Assess the Risks
- Development of a systematic risk based approach
- Key factors and the development of a decision tree
- API
- Drug Product
- Packaging
Analytical Solutions for Monitoring Presence/Formation of N-Nitrosamines within APIs and Drug Products
- Detection limits requested by in Article 5(3) of Regulation EC (No) 726/2004
- Techniques used for analysis of non-API related N-Nitrosamines
- Formation of N-nitrosylated APIs in drug products
- Analytical methods used for quantification of N-nitrosylated APIs in drug products
Workshop: Conducting a Risk Assessment
In this Workshop the participants will work on several case studies and perform a risk assessment for different scenarios taking into account e.g. manufacturing equipment, dosage form of the drug product etc.
Nitrosamines and Other Genotoxic Impurities – Authorities' Expectations and Dossier Requirements
- The assessor’s approach: principles of toxicological assessment
- Structural alerts
- Limits and Permitted Daily Exposure
- The ALARP principle
- Examples of low daily dose drug substances
- Impurities derived from alkylating agents (mesilate, besilate, tosilate, diisothionate); examples
- Nitrosamines – the Valsartan case
- Potential mutagenicc residual solvents
- Impurities derived from metal catalysts