Post-marketing pharmacovigilance obligations in Europe
Marketing Authorization (MA) granted by health authorities, particularly following a positive benefit/risk assessment for the drug, does not mark the end of the monitoring process, but rather its reinforcement. Once the drug is marketed, it is used in much broader conditions than during clinical trials: by a larger number of patients with varied profiles and in prescription or use situations that are sometimes far removed from the conditions of the trials. This real-world use may reveal new risks. Post-marketing pharmacovigilance is therefore essential for detecting, analyzing, and preventing these risks, and for adapting the conditions of use if necessary. This is why it is essential for Marketing Authorization holders to be familiar with the regulations in order to ensure rigorous and compliant monitoring, which guarantees patient safety.
What is pharmacovigilance?
Pharmacovigilance is the science and set of activities aimed at monitoring, evaluating, preventing, and managing the risks of adverse effects related to the use of medicines. It is applied continuously, before and after medicines are marketed, and is a central part of monitoring the safety of treatments.
Its main objective is to detect and evaluate any adverse effects, whether they occur:
- in the context of use in accordance with the Marketing Authorization,
- or in other situations: overdose, misuse, abuse, medication errors, etc.
The pharmacovigilance system is based on:
- The reporting of adverse effects by healthcare professionals, manufacturers, and also patients and their associations;
- The collection, analysis, and evaluation of safety information;
- The conduct of additional studies or specific work on the safety of medicines when necessary;
- The implementation of corrective or preventive actions to reduce risks.
In Europe, these activities are governed by a set of regulations and directives, supplemented by Good Pharmacovigilance Practices (GVP) defined by the European Medicines Agency (EMA). In France, these activities are also defined in the Public Health Code and supplemented by local Good Pharmacovigilance Practices. They involve various stakeholders: health authorities, regional pharmacovigilance centers, exploitant laboratories, healthcare professionals, and patients.
Why is pharmacovigilance important after obtaining Marketing Authorization?
Marketing Authorization does not mean that monitoring of a drug stops. Marketing Authorization holders must ensure continuous monitoring of safety data, in particular by reporting adverse effects to their drugs to the EMA via the European EudraVigilance system, which is mandatory under EU regulations.
This ongoing vigilance makes it possible to detect unknown or rare signals in real-world conditions and to continuously reassess the benefit/risk balance.
In the event of a proven risk, public health measures may be implemented, such as changes to indications, restrictions on use, or withdrawal of the drug from the market. Post-authorization studies (PASS/PAES) are often required to confirm a safety profile or measure the effectiveness of risk management measures.
Regulatory framework for pharmacovigilance in Europe
The European Union’s pharmacovigilance system monitors the safety of medicines marketed in Europe. This system, which has been in place for several years, has evolved over time to adapt to current practices and needs.
The European Commission revised this system with new regulations adopted by the European Parliament and the Council in December 2010, which came into force in July 2012. The European Medicines Agency (EMA) and EU Member States are responsible for its implementation.
This European regulation strengthens the existing system, making it more robust and transparent, to improve patient safety through better detection, assessment, understanding, and prevention of adverse effects or other problems related to medicines.
Major changes include:
- The obligation for local authorities to set up a national web portal enabling patients to report adverse effects directly.
- The broadening of the definition of adverse effect to include reactions related to misuse, medication errors, abuse, or occupational exposure.
- The harmonization at European level of the concept of “additional monitoring” for medicinal products, particularly for new active substances and biological medicinal products.
- The publication of certain data from the European EudraVigilance database, accessible to the public and healthcare professionals via www.adrreports.eu.
Challenges and good practices for staying compliant
Non-compliance in pharmacovigilance can compromise patient safety, which is the primary goal of post-marketing surveillance. It can also result in financial penalties and severe regulatory measures ranging from restrictions on use to changes to the summary of product characteristics (SmPC), or even suspension or withdrawal of the Marketing Authorization. Finally, these breaches can also have repercussions on scientific credibility and the trust placed in the laboratory by authorities and healthcare professionals. To remain compliant, Marketing Authorization holders must:
- Establish and maintain precise procedures covering, in particular, the collection, analysis, and transmission of safety data.
- Regularly train their teams to ensure that processes are mastered and procedures are properly applied.
- Plan regular internal audits to assess the effectiveness of the pharmacovigilance system and detect weaknesses before an inspection;
- Continuously monitor regulatory developments at European and national level to anticipate new obligations;
- Integrate pharmacovigilance into the overall governance of the company, considering it as a strategic lever and not a regulatory requirement.
Post-marketing pharmacovigilance is an essential requirement for ensuring patient safety. It requires continuous monitoring, rigorous processes, and constant adaptation to European regulatory requirements.
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