--- title: "Regulation (EU) 2025/1466: What Has Changed in Signal Management and Where We Are" description: "Regulation (EU) 2025/1466 changes EU signal management and EudraVigilance monitoring. Learn what MAHs need to implement and document." url: https://qbdgroup.com/en/blog/eu-2025-1466-signal-management-eudravigilance type: "Blog post" language: en published: 2026-10-07 author: "Almudena del Castillo" category: "Vigilance" publisher: "QbD Group" citation: "QbD Group, \"Regulation (EU) 2025/1466: What Has Changed in Signal Management and Where We Are\", https://qbdgroup.com/en/blog/eu-2025-1466-signal-management-eudravigilance" --- # Regulation (EU) 2025/1466: What Has Changed in Signal Management and Where We Are > Regulation (EU) 2025/1466 changes EU signal management and EudraVigilance monitoring. Learn what MAHs need to implement and document. Since August 2025, signal management in the EU has been operating under a revised legal framework. For many Marketing Authorisation Holders (MAHs), the practical consequences are only now reaching procedures, resourcing plans and inspection preparation. Commission Implementing Regulation (EU) 2025/1466, adopted on 22 July 2025, amends Implementing Regulation (EU) No 520/2012, which sets out how pharmacovigilance activities are performed in the EU. Its signal management provisions were the first to apply, in August 2025, while the remaining updates have applied since 12 February 2026. The legal changes are therefore already in force. **The challenge for MAHs now is turning them into a signal management process that is proportionate, documented and defensible.** ## In This Blog Post - What Regulation (EU) 2025/1466 changes for signal management - What the end of the EudraVigilance signal detection pilot means for MAHs - Why the standalone signal notification form is no longer used - How EMA expects EudraVigilance data to be incorporated into signal management - Which decisions companies now need to make and document - Where things stand while the industry awaits the updated GVP Module IX ## What Has Changed Under Regulation (EU) 2025/1466? Two changes are particularly important for signal management. ### 1. The EudraVigilance Signal Detection Pilot Has Ended The most visible change is the end of the EudraVigilance signal detection pilot. Launched on 22 February 2018, the pilot required signal detection in EudraVigilance only from MAHs holding an active substance included on a limited pilot list. Under the amended regulation, that phase has ended. **All MAHs with medicinal products authorised in the European Economic Area (EEA) must now monitor the data available in EudraVigilance and use it as an additional source of safety information.** That information should support the MAH's own signal management processes and strengthen signals detected through other sources. EMA also clarifies that MAHs with EU products authorised in Northern Ireland are included, even where they hold no authorisation in an EU or EEA Member State. This represents a significant expansion of responsibility. EudraVigilance monitoring is no longer an activity limited to MAHs covered by the pilot. It now needs to be considered within the signal management approach of every MAH in scope. ### 2. The Standalone Signal Notification Form Has Been Removed The second important change is the deletion of Article 21(2). As a result, validated signals are no longer submitted to EMA and national competent authorities through the standalone signal notification form. Instead, signals from every source, including EudraVigilance, are handled within the MAH's own signal management process, taking GVP Module IX into account. Where the assessment of a signal results in regulatory action, that action follows the existing legal framework. This can include: - variations to keep product information up to date - inclusion in the Periodic Safety Update Report (PSUR), where the MAH is required to submit one The change therefore does not reduce the importance of signal management. Rather, it places the emphasis on having an internal process capable of appropriately identifying, validating, evaluating and acting on signals from all relevant sources. ## What Does EMA Expect From MAHs Today? EMA's Questions and Answers document on Regulation (EU) 2025/1466 provides the main practical guidance for companies implementing the revised framework. MAHs should explain in their signal management and pharmacovigilance procedures: - how EudraVigilance data will be monitored - how that data will be used alongside other sources - at which stage of the signal management process it will be considered - how frequently monitoring will take place That frequency should be proportionate to the: - risk associated with the product - known safety profile - characteristics of the individual product There is therefore no single monitoring frequency that automatically applies to every medicinal product. Companies need to determine an approach appropriate to their own portfolio and justify it accordingly. ## Where Should EudraVigilance Data Enter the Signal Management Process? This is one of the practical decisions MAHs now need to make. EudraVigilance can be screened as a **primary source for signal detection**, using an established monitoring frequency. EMA also expects EudraVigilance data to be used during the **validation and evaluation stages** of signal management. For signals assessed by the Pharmacovigilance Risk Assessment Committee (PRAC), and where PRAC requests cumulative reviews, MAHs are also expected to include relevant EudraVigilance data. That assessment should consider the wider context of the substance on the market, including potential differences in: - indications - formulations - routes of administration The key point is that simply having access to EudraVigilance is not enough. **The organisation needs to define where and how those data contribute to its signal management process.** ## There Is No Single Signal Management Model for Every MAH The revised framework establishes a clear expectation. What it does not do is prescribe one operating model that every company must follow. Each MAH therefore needs to analyse its own situation before deciding: - where EudraVigilance data enter the process - how frequently the data are reviewed - which products require which approach - how EudraVigilance fits alongside other safety data sources - what resources are required to sustain the chosen model Relevant considerations include the risk profile of individual products, the sources already being monitored and the resources available within the organisation. That flexibility is useful, but it also places responsibility back on the MAH. **If the regulation does not prescribe the exact process, the company needs to be able to explain why the process it selected is appropriate.** That reasoning should be reflected in procedures and should be clear enough to explain to an auditor or inspector. ## What About GVP Module IX? One important piece of the framework is still evolving. EMA has stated that **GVP Module IX will be updated** to align with the revised legal framework. Companies should therefore continue to monitor that development. In the meantime, EMA's Questions and Answers document remains the main practical reference for implementing the changes introduced by Regulation (EU) 2025/1466. That should not, however, be interpreted as a reason to postpone implementation. The legal changes are already applicable. The task for MAHs today is to implement a proportionate approach based on the regulatory framework and currently available guidance, while remaining ready to adapt procedures when the revised GVP Module IX becomes available. ## What Should MAHs Be Doing Now? At this stage, the challenge is less about interpreting whether the changes apply and more about making sure they have been translated into routine pharmacovigilance practice. MAHs should consider: 1. **Reviewing their current signal management procedures** to determine whether EudraVigilance monitoring is appropriately incorporated. 2. **Defining where EudraVigilance data enter the process**, including detection, validation and evaluation. 3. **Establishing an appropriate monitoring frequency** based on product risk, safety profile and other relevant characteristics. 4. **Assessing the impact on resources**, particularly where EudraVigilance monitoring represents a new or expanded activity. 5. **Updating procedures and responsibilities** so that the chosen approach is clearly documented. 6. **Ensuring the rationale is inspection-ready**, with enough documentation to explain why the selected approach is proportionate. 7. **Monitoring the forthcoming GVP Module IX update** and assessing whether further procedural changes are needed once it is published. ## From Regulatory Change to a Defensible Signal Management Process Regulation (EU) 2025/1466 has already changed the legal framework for signal management. The end of the EudraVigilance pilot expands monitoring expectations across MAHs, while the removal of the standalone signal notification route places signals firmly within companies' established signal management processes. The main open point is now the announced update to GVP Module IX. But for MAHs, the immediate work is already clear. Analyse your products, safety sources and available resources. Decide where EudraVigilance data fit into your signal management process and how frequently they should be reviewed. Then document the reasoning behind those decisions. **A decision that is clear, proportionate and documented is the most solid starting point while the guidance continues to consolidate.** ## Prepare Your Signal Management Process for the New Framework Implementing Regulation (EU) 2025/1466 requires more than adding EudraVigilance to a procedure. Organisations need to determine how the data fit into their existing signal management processes, establish a risk-based monitoring approach and ensure that the resulting decisions and rationale can withstand regulatory scrutiny. QbD Group supports pharmaceutical and biotech companies across pharmacovigilance, signal management, regulatory intelligence, quality systems and inspection readiness. **Need to assess how Regulation (EU) 2025/1466 affects your signal management process? [Get in touch with our Pharmacovigilance experts](/en/contact) to translate the new requirements into a practical, proportionate and inspection-ready approach.** --- Source: https://qbdgroup.com/en/blog/eu-2025-1466-signal-management-eudravigilance — © QbD Group. Quote freely with attribution and a link back.