EMA Guideline on Stability Testing for Applications for Variations to a Marketing Authorisation

Post-authorisation changes are an inevitable part of medicinal product lifecycle management, and stability data play a critical role in demonstrating that such changes do not compromise product quality, safety, or efficacy. To harmonise expectations across the EU, the European Medicines Agency has issued Revision 3 of the Guideline on stability testing for applications for variations to a marketing authorisation.

Adopted in December 2025 and effective from January 2026, this revision replaces earlier versions and reflects EMA’s current scientific and regulatory thinking.

The guideline defines how stability data should be generated and submitted to support variations to an existing marketing authorisation.

EMA positions this document as a practical framework to ensure consistency in regulatory decisions while allowing flexibility where scientifically justified. The guideline is relevant to Type IA, IB, and Type II variations, with particular emphasis on common major variations.

General Stability Principles for Variations

EMA reinforces that stability testing for variations should be risk-based and knowledge-driven. Applicants must assess whether the proposed change could affect the stability profile of the active substance or finished product. Where stability data are required, studies should build on existing stability knowledge, including historical data, stress testing results, and prior shelf-life experience.

Stability studies supporting a variation must continue until the full approved retest period or shelf life is reached, even after submission. Any out-of-specification or concerning trends must be promptly reported to competent authorities. EMA also supports the use of bracketing and matrixing approaches when scientifically justified.

Commitment Batches and Ongoing Stability Obligations

EMA emphasises that stability assurance does not end at approval of the variation. For Type IA and IB variations, follow-up stability studies may be required where stability data are relevant. For Type II variations, at least the first production-scale batch manufactured under the approved change must be placed on long-term stability studies. These studies must continue for the full shelf life and be available for regulatory inspection. Extrapolation and Shelf-Life Considerations

Revision 3 clarifies that extrapolation of retest periods or shelf life may be acceptable when supported by low variability and favourable stability trends. However, extrapolation is always assessed on a case-by-case basis. Where adverse trends emerge following a variation, retention of the original shelf life is not acceptable, and a revised shelf life must be proposed. By aligning stability requirements with the nature and risk of each variation, the guideline helps marketing authorisation holders plan efficient regulatory strategies while maintaining robust quality assurance. Stability testing remains a cornerstone of lifecycle management, and this updated guidance clarifies how it should be applied consistently across the EU.

For more information, see the official guidance:

Guideline on stability testing for applications for variations to a marketing authorisation (Revision 3)