The European Medicines Agency (EMA) has updated its Guideline on the Chemistry of Active Substances (EMA/CHMP/QWP/49484/2026), bringing important changes for manufacturers, regulatory professionals, and quality teams.
The revision reflects lessons learned from impurity-related incidents, in particular nitrosamine contamination, and strengthens expectations for the manufacture, control, and documentation of active pharmaceutical ingredients (APIs).
Key highlights from the updated guideline:
- Expanded guidance on identifying risk factors for N-nitrosamine formation and other “cohort of concern” impurities
- Clearer expectations on control strategies to prevent impurity formation
- Additional requirements for documentation in regulatory submissions
- More detailed considerations for maximum daily dose, route of administration, and treatment duration when defining specifications
- Consolidation of requirements for new and existing active substances into a single guideline structure aligned with the ICH CTD format
The guideline sets out the information required for manufacture and control of active substances used in medicinal products, clarifying differences between new and existing APIs and strengthening expectations across the lifecycle.
Why this matters:
- Greater scrutiny on impurity risk management
- Stronger emphasis on science-based control strategies
- Increased alignment between development, quality, and regulatory teams
- Potential impact on existing dossiers and lifecycle management
A timely reminder that API chemistry expectations continue to evolve, with risk-based thinking and proactive quality management at the center.
With the guideline becoming applicable before 01 September 2026, now is the time to:
- Review impurity risk assessments
- Evaluate current API control strategies
- Identify gaps in CMC documentation
- Plan variation strategies where needed
- Align internal stakeholders early
Get in touch to ensure your organization is compliant well ahead of the deadline at [email protected] or visit our website at Starodub.nl.
