New European pharmacovigilance legislation

messages in brief | 09/07/2012

The following innovations are planned throughout Europe:

Risk and risk managementAllmedicinal products carry known and unknown risks at the time of their authorization. The previous version of Regulation 726/2004 already takes this knowledge into account by stipulating the mandatory submission of risk management plans (RMPs). The new legislation no longer views risk as an isolated concept, but rather sees it as inextricably linked to benefit.


The goal of effective risk management is thus to achieve the greatest possible benefit with the lowest possible risk. To this end, the previous activities (characterization of the safety profile of the active ingredient, planning of pharmacovigilance activities for unknown risks, definition of risk-minimizing measures) are expanded to include the obligation to measure and evaluate the effectiveness of measures taken.


In addition to the requirement to conduct post-authorization safety studies (PASS), there will also be the possibility in future to order further efficacy studies (post-authorization efficacy studies, PAES) as part of the RMP. This extended proof of efficacy will be particularly important for drugs for which the long-term benefit is decisive. This is especially true for pediatric drugs, Advanced Therapy Medicinal Products, and vaccines.

Post-approval monitoringSignal detection, RMP and Periodic Safety Update Reports (PSUR) are used to evaluate drug safety. Signals are generated from a variety of sources, including clinical and non-clinical information, but spontaneous reporting systems and structured data collections, such as patient registries, remain a key reference point.


The new legislation also changes the nature of reporting and the process. Whereas healthcare professionals were previously only required to report serious reactions, the obligation now expands to include non-serious reactions. Electronic reporting portals at the national drug agencies are expected to facilitate and accelerate the reporting process. In Austria, the reporting portal at will soon be activated. Also new is the future possibility for patients or relatives to report side effects. This "consumer reporting" will be introduced in every member state with the new legislation.


The Periodic Safety Update Report (PSUR) will be used to periodically review the safety of the drug. Whereas the preparation and evaluation of these reports previously focused on the risks of the respective period, a detailed and critical analysis of the risk-benefit ratio based on cumulative data is now prepared for each report submission, and an evaluation of the effectiveness of risk-minimizing measures is prepared. This new form of post-marketing evaluation covers the entire life cycle of the drug.


The risk management process ends with the decision on regulatory measures, such as changes to the technical information and directions for use or the marketing authorization status. For this purpose, the new legislation provides for a clear division of roles between the European Medicines Agency (EMA) and the national medicines agencies: Safety signals are assessed at the pan-European level and measures are harmonized and implemented simultaneously across Europe. A new working committee (Pharmacovigilance Risk Assessment Committee, PRAC) is starting its work in this sense. In addition to representatives of the member states, this committee will also include patients and healthcare professionals.

TransparencyTheEudraVigilance Access Policy implements the principle of transparency. In the future, healthcare professionals and private individuals will also have access to the system under the link, in addition to authorities, marketing authorization holders and sponsors of clinical trials.


Via web portals to be set up specifically for this purpose, EMA and national drug regulatory authorities will in future not only ensure access to current technical and usage information, but also provide information on currently ongoing proceedings on possible safety signals and their outcome. Under certain conditions, some of the PRAC meetings will also be held with the public present.


Also new is that it is now mandatory for national drug agencies and EU member states to publish RMP summaries in layman's terms. Where appropriate, associated information material, such as special follow-up questionnaires, may also be published by the authorities. To increase patients' willingness to participate, the authority may also provide information about the existence and access modalities of patient registries.


Further information:

European Medicines Agency Summary (07/06/2012).


Further inquiry note