October 30, 2024

In the EU, transitioning a medicinal product from clinical trials to full market release brings a new level of responsibility for the Marketing Authorization (MA) Holder, who must ensure an extensive Pharmacovigilance (PV) system is in place to protect patient safety. While clinical trials provide initial insights into drug safety, only once a product is widely available are more extensive real-world safety profiles established. Ensuring regulatory compliance through a dedicated PV system, which includes safety monitoring and risk management, is essential for long-term patient safety and regulatory adherence.

Here, we outline the key requirements for establishing and maintaining an EU-compliant PV system and share some insights on outsourcing strategies that can support these critical functions.

Key Pharmacovigilance Requirements in the EU

1. Core PV System Requirements

A robust PV system must cover all aspects of adverse event monitoring and include tools, processes, and personnel to handle data from diverse sources, including patients, healthcare professionals (HCPs), global literature, and social media. All adverse events (AEs), including non-serious cases and “special situations” such as off-label use or medication errors, must be documented and managed systematically.

2. Qualified Person for Pharmacovigilance (QPPV)

The EU requires each MA Holder to appoint a Qualified Person for Pharmacovigilance (QPPV) to oversee and ensure the reliability of the PV system and patient safety data. The QPPV must reside in the European Economic Area (EEA), ideally in proximity to the primary PV operations. Some EU countries also mandate local safety representatives fluent in the national language, depending on local legislation.

3. Pharmacovigilance System Master File (PSMF)

A PSMF is mandatory and provides a detailed description of the PV system. This “living” document must be updated regularly and be readily accessible to European Medicines Agency (EMA) inspectors and national regulatory authorities. It includes critical information about system oversight, personnel, processes, and reporting methods.

4. Risk Management and Minimization

A Risk Management Plan (RMP) is a fundamental part of any MA application within the EU, detailing known and potential risks and specific minimization strategies. It must be maintained throughout the product’s lifecycle, especially in response to new information affecting benefit-risk. Advanced Therapy Medicinal Products (ATMPs) require even more stringent risk management due to their complex biological nature.

5. Signal Management

Signal management is crucial for identifying and assessing new safety signals. Signals, which indicate potential adverse reactions, can arise from any data source and require assessment by the MA Holder’s PV team in alignment with EU regulations. Should a validated signal reveal new safety risks, it may lead to regulatory actions such as updates to the product’s prescribing information or even withdrawal from the market.

6. Global Literature Monitoring

The MA Holder must monitor scientific and medical literature weekly to identify emerging safety data relevant to their products. These searches should include both individual case safety reports (ICSRs) and broader safety information. The EMA provides Medical Literature Monitoring (MLM) services for certain products, but the MA Holder retains responsibility for vigilance on unlisted products.

7. EudraVigilance Database Maintenance

Registration with EudraVigilance (EV) is required for submitting and receiving ICSRs in the EU. The MA Holder must keep the EV database up to date, including the QPPV details, product information, and the location of the PSMF. EV access enables the MA Holder to monitor EudraVigilance for potential safety concerns.

Addressing Common Inspection Findings

Inspectors frequently identify gaps in systems used to collect safety data from internal and external sources, including commercial teams, vendors, and market research channels. Ensuring comprehensive safety data exchange and strong Quality Management Systems (QMS), along with qualified personnel and IT systems, is vital for effective PV.

Outsourcing PV Activities: Key Considerations

Setting up and maintaining a PV system can be resource intensive. As such, many MA Holders outsource part or all PV activities to third-party providers. While this can reduce costs and accelerate set-up, the MA Holder remains ultimately responsible for all safety obligations and must conduct due diligence with the chosen provider to verify regulatory compliance.

Conclusion

The EU’s pharmacovigilance requirements, as outlined in the Good Pharmacovigilance Practice (GVP) modules, emphasize a proactive approach to patient safety through the lifecycle of a medicinal product. Whether establishing an in-house team or outsourcing to a third-party PV provider, compliance with these requirements is essential. A solid PV framework not only supports market access but also protects patient welfare, product reputation, and long-term market success.

For more information on EU PV compliance and how Maven can support your pharmacovigilance needs, please reach out to us at info@mavenrs.com or visit our website at www.mavenrs.com.