The European Medicines Agency (EMA) has published Revision 3 of the Guideline on Stability Testing for Applications for Variations to a Marketing Authorisation (EMA/CHMP/QWP/441071/2011-Rev.3), which will come into legal effect on 15 January 2026. This update replaces Revision 2 and reflects the evolving expectations for stability testing in the context of post-approval changes to human medicinal products.
The updated guideline introduces clearer, risk-based, science-driven stability expectations for variation submissions:
Enhanced Scope and Clarity
The guideline outlines the stability data required for Type IA, IB and Type II variations with a stronger focus on scientific justification. Its application is limited to human medicines (chemical active substances, finished products, herbal substances) and excludes biologicals, radiopharmaceuticals, and biotechnology-derived products. Veterinary products have a separate, newer guideline (EMA/CVMP/QWP/515653/2023)
Risk-Based Stability Strategies
Applicants must evaluate whether a proposed change might impact the product’s stability profile. When risk exists, data should demonstrate that quality is maintained throughout the approved shelf-life. This emphasis on risk and science aligns more closely with ICH principles and modern regulatory expectations.
Comparative and Commitment Studies
For Type II variations (major changes), comparative stability data (long-term and accelerated) are expected to show that the post-change product performs consistently with pre-change data. Commitment batches, especially the first production batch post-change, must be placed on documented long-term stability studies spanning the full shelf-life.
Ongoing Obligations and Reporting
Stability testing supporting a variation application must continue through the entire approved shelf-life or retest period. Any out-of-specification results or concerning trends should be reported promptly to regulators.
This revision encourages consistency and scientific justification in how companies demonstrate product stability after post-approval changes. Key practical impacts include: Stronger comparability requirements for stability data in variation dossiers. Clearer expectations on what data regulators expect across different types of changes. Continued lifecycle management focus, stability evidence now plays an even greater role in post-approval quality assurance.
Marketing Authorisation Holders and Regulatory Affairs teams should review their variation strategies and stability programs to ensure alignment ahead of the implementation date.
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