The European Medicines Agency (EMA) has clarified regulatory expectations for signal management with updated guidance following the revised Implementing Regulation (EU) 2025/1466 and an EMA Q&A document published in January 2026. These changes mark the end of the EudraVigilance signal detection pilot and establish a mandatory requirement for Marketing Authorisation Holders (MAHs) to systematically integrate EudraVigilance data throughout their signal management processes starting in 2026. This includes defining how EudraVigilance is used for signal detection, validation, and evaluation, documenting all related procedures, and justifying the frequency and methodology of EudraVigilance screening based on risk profiles and regulatory expectations. Organisations that delay implementation risk non-compliance findings and gaps in their pharmacovigilance systems.

How Billev Pharma East supports your signal management implementation

At Billev Pharma East, we help MAHs translate EMA’s updated signal management expectations into practical, compliant internal processes. Our specialized services include:

• Signal management readiness assessment: we evaluate your current signal management framework to identify gaps and recommend prioritized actions to align with EMA’s clarified requirements.
• Procedure development and SOP updates: we draft and refine signal management Standard Operating Procedures (SOPs) that explicitly incorporate systematic use of EudraVigilance data across detection, validation, evaluation, and documentation steps.
• Risk-based monitoring strategies: we assist in establishing justified screening frequencies and methodologies tailored to your product portfolio, risk profiles, and lifecycle stages to strengthen your signal management practices.
• Inspection readiness and documentation support: we ensure your governance structures, quality system documents, and signal management records clearly demonstrate compliance and readiness for regulatory inspection.
• Ongoing pharmacovigilance support: from managing detected signals to supporting regulatory submissions and updates to safety reporting, we provide hands-on assistance throughout your signal management lifecycle.

Signal management in practice: EMA’s clarified expectations

Many Marketing Authorisation Holders (MAHs) struggle to keep up with evolving regulatory expectations for signal management, especially in light of recent changes to EU pharmacovigilance rules that expand the role of EudraVigilance data. With ambiguity around how to systematically integrate these requirements, companies risk non-compliance and inspection findings that could disrupt product safety monitoring. The EMA’s updated guidance clarifies these expectations and offers a clear path to embed EudraVigilance into signal management processes with justified frequency and documented procedures, helping MAHs strengthen compliance and readiness for inspection.

EMA clarifies EudraVigilance use in signal management for 2026

The European Medicines Agency (EMA) has issued updated guidance that clarifies regulatory expectations for Marketing Authorisation Holders (MAHs) regarding the use of EudraVigilance data in signal management. This update is based on the revised Implementing Regulation (EU) 2025/1466 and an updated Q&A document published by EMA in January 2026. These changes mark a significant shift in how EudraVigilance should be systematically integrated into pharmacovigilance processes across the European Economic Area (EEA).

What signal management means in pharmacovigilance

Signal management refers to the set of activities involved in detecting, validating, analysing, prioritising, evaluating, and acting on safety signals related to medicinal products. In the EU, signal management processes are a cornerstone of pharmacovigilance and are defined in Good Pharmacovigilance Practices (GVP) Module IX. Safety signals can originate from multiple sources, including spontaneous adverse reaction reports, clinical studies, literature, and databases such as EudraVigilance, which holds suspected adverse reaction reports from across the EEA.

EMA’s updated expectations for signal management

With the termination of the signal detection pilot in EudraVigilance, the revised Implementing Regulation (EU) 2025/1466 now requires all MAHs with medicines authorised in the EEA to monitor EudraVigilance data and use it as an additional source of safety information to support their internal signal management processes. The pilot, which ran from 2018 to 2025, was previously limited to a defined list of active substances and MAHs but has now been replaced by a universal obligation.

EMA’s Q&A clarifies that MAHs must determine at which steps of the signal management process EudraVigilance data will be applied, including detection, validation, and evaluation. This integration should be documented within internal procedures, with the frequency and methodology of EudraVigilance screening justified based on risk profiles, product characteristics, and lifecycle considerations.

Integrating EudraVigilance into signal management processes

Under the updated framework, MAHs are no longer required to submit validated safety signals via a standalone notification form to EMA and national authorities; such signals should instead be managed via the MAH’s own signal management procedures. Actions resulting from signal assessments—such as updates to product information, variation submissions, and inclusion in periodic safety update reports—should be performed according to the existing EU legal framework.

It is also specifically acknowledged that EudraVigilance data should be used beyond the detection phase and actively considered in signal validation and evaluation activities. The practical implication is that MAHs must formalise how EudraVigilance contributes to each activity within the signal management workflow.

Practical steps to strengthen your signal management

MAHs should start by reviewing and updating standard operating procedures (SOPs) to explicitly describe the role of EudraVigilance across all relevant stages of signal management. Procedures should clearly document how data are monitored, how often screening occurs, and how outputs inform downstream evaluation and decision-making. These procedural updates are essential to demonstrate compliance and prepare for regulatory inspections.

The updated EMA guidance also notes that an amendment to GVP Module IX is expected to be implemented in 2026 to further align practical guidance with the revised legal requirements. Until then, MAHs should align their internal processes with the clarified expectations, ensuring proportionality and transparency in how EudraVigilance data are used.

Signal management and inspection readiness

The emphasis on structured use of EudraVigilance data and systematic signal management reflects a broader regulatory trend toward audit-ready pharmacovigilance systems. As EMA and national competent authorities increasingly inspect pharmacovigilance quality systems, documentation that clearly shows how EudraVigilance contributes to signal detection, validation, and evaluation will be crucial.

MAHs are encouraged to ensure that their internal governance, roles, and quality systems support the effective use of EudraVigilance within signal management. Inspection readiness also requires ensuring that any methodological choices—such as screening frequency and data integration strategies—are justified and evidenced within documented processes.

Looking ahead: evolving regulatory expectations

The clarification provided by EMA underscores the importance of robust signal management as a continuous, risk-based process that sits at the heart of effective pharmacovigilance and regulatory affairs. As regulatory expectations evolve and new guidance is published, MAHs will need to adapt their pharmacovigilance frameworks to maintain not only compliance but also quality and transparency in safety monitoring. Embedding EudraVigilance data systematically within signal management supports both efficient regulatory affairs operations and stronger preparedness for inspections, helping organisations demonstrate that their safety monitoring systems are fit for purpose in a rapidly changing regulatory environment.

Sources: 1 – European Medicines Agency. (2026). Questions and answers on Implementing Regulation (EU) 2025/1466: Amendment of Regulation (EU) No 520/2012 and conclusion of the signal detection in EudraVigilance pilot by marketing authorisation holders (EMA/243145/2025 Rev. 2), 2 – European Medicines Agency. (n.d.). Signal management (guidance on pharmacovigilance activities), 3 – European Union. (2025). Commission Implementing Regulation (EU) 2025/1466 of 22 July 2025 amending Implementing Regulation (EU) No 520/2012 on the performance of pharmacovigilance activities (Official Journal L), 4 – EMA Q&A context (secondary source). (2025). Questions and answers on Implementing Regulation (EU) 2025/1466 and conclusion of the EudraVigilance signal detection pilot by marketing authorisation holders, 5 – Industry overview (secondary source). (2025). EMA ends signal detection pilot, directs all MAHs to monitor EudraVigilance, 6 – Regulatory summary (secondary source). (2025). New requirements for EudraVigilance signal monitoring under Implementing Regulation (EU) 2025/1466.

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