On 22 September 2025, the European Commission approved new Guidelines concerning the examination of variations to the terms of marketing authorisations (MAs) for human medicinal products and the related documentation required under such procedures.

The document, drafted in collaboration with the European Medicines Agency (EMA), aims to support the interpretation and application of Regulation (EU) No 1234/2008 (commonly known as the “Variations Regulation”) by providing detailed information on the implementation of relevant procedures — from the submission of a notification or variation application to the final outcome of the process.

The new guidelines highlight the use of tools such as Product Lifecycle Management (PLCM) — a lifecycle management document relating to the active substance — and the Post-Approval Change Management Protocol (PACMP), a protocol for managing post-approval changes concerning the active substance. These are now officially recognised as strategic tools for the long-term planning and management of complex changes.

To support the implementation of the new provisions, updated technical and procedural documentation will be made available by the end of 2025, aimed at facilitating the adjustment process for MA holders and national competent authorities.

The document replaces the previous 2013 guidance, reflecting the 2024 amendment to the Variations Regulation, and will apply from 15 January 2026. Applications submitted before that date should follow the 2013 guidance.