Medicinal products for human use
All medicinal products in the EU are subject to a strict testing and assessment of their quality, efficacy and safety before being authorised. Once placed on the market they continue to be monitored so to assure that any aspect which could impact the safety profile of a medicine is detected and assessed and that necessary measures are taken. This monitoring is called pharmacovigilance.
Pharmacovigilance is the process and science of monitoring the safety of medicines and taking action to reduce the risks and increase the benefits of medicines. It is a key public health function.
Pharmacovigilance activities include:
- Collecting and managing data on the safety of medicines.
- Looking at the data to detect "signals" (any new or changing safety issue).
- Evaluating the data and making decisions with regard to safety issues.
- Pro-active risk management to minimise any potential risk associated with the use of the medicine.
- Acting to protect public health (including regulatory action).
- Communicating with and informing stakeholders and the public.
- Audit, both of the outcomes of action taken and of the key processes involved.
Those directly involved in pharmacovigilance include:
- Patients who are the users of medicines.
- Doctors, pharmacists, nurses and all other health care professionals working with medicines.
- Regulatory authorities, including the European Medicines Agency (EMA) and those in the Member States responsible for monitoring the safety of medicines.
- Pharmaceutical companies and companies importing or distributing medicines.
The legal framework
The legal framework of pharmacovigilance for medicines marketed within the EU is provided for in Regulation (EC) No 726/2004 with respect to centrally authorised medicinal products and in Directive 2001/83/EC with respect to nationally authorised medicinal products (including those authorised through the mutual recognition and decentralised systems).
In addition, Commission Implementing Regulation (EU) No 520/2012 on the performance of pharmacovigilance activities stipulates operational details in relation to certain aspects of pharmacovigilance to be respected by marketing authorisation holders, national competent authorities and EMA.
Finally, the EMA has released good pharmacovigilance practice guidelines (GVP) in order to facilitate the performance of pharmacovigilance activities. These GVP modules replace Volume 9A of, "The rules governing medicinal products in the European Union - Pharmacovigilance".
The EU pharmacovigilance system is now one of the most advanced and comprehensive systems in the world and represents a robust and transparent instrument to ensure a high level of public health protection throughout the Union.
The EU pharmacovigilance legislation has been subject to a major review that lead to the adoption of new legislation in 2010. The new legislation, a Regulation and a Directive, became applicable in July 2012.
For more information see Eudralex - Volume 1.
The 2010 legislation strengthens and rationalises the system for monitoring the safety of medicines on the European market. It improves patient safety and public health through better prevention, detection and assessment of adverse reactions to medicines. It also allows patients to report adverse drug reactions directly to the competent authorities. Additionally, reporting of adverse reactions is broadened to cover, for example, medication errors and overdose.
The main pillars of the new legislation are:
- Proactive and proportionate risk management.
- Higher quality of safety data.
- Stronger link between safety assessments and regulatory action.
- Strengthened transparency, communication and patient involvement.
- Clear tasks and responsibilities for all parties (marketing authorisation holders, competent authorities, EMA).
- Improved EU decision-making procedures (harmonised decisions and efficient use of resources).
- Establishment of a new scientific committee at the European Medicines Agency: the Pharmacovigilance Risk Assessment Committee.
While the new pharmacovigilance legislation became applicable in July 2012, some of its new features will be subject to a phased implementation over the coming years.
In this context, and in order to facilitate the move to the new system, the Commission has published a Question and Answer document on transitional arrangements. Additionally, the European Medicines Agency has made available a more comprehensive Q&A covering the different processes affected by the new legislation.
With the application of the 2010 legislation Commission Regulation (EEC) 540/95 on "suspected unexpected non-serious adverse reactions" ceases to apply to human medicinal products, as it is superseded by the new provisions.
Some pharmacovigilance incidents in the Union have shown the need for further improvements of the 2010 legislation. These issues have been addressed by Directive 2012/26/EU and Regulation (EU) No 2012/1027/EU, which start to apply from June and October 2013.
On 7 March 2013, the Commission adopted an Implementing Regulation introducing a Black Symbol to identify medicinal products that are subject to additional monitoring. The black symbol will allow patients and healthcare professionals to identify these products, and the accompanying text will encourage them to report unexpected adverse reactions through national reporting systems.
In spring 2014, the Commission adopted a Delegated Regulation on post-authorisation efficacy studies, which specifies the situations in which such studies may be required. Generally speaking, such additional studies may be required to address certain well-reasoned scientific concerns, which could have a direct impact on the maintenance of the marketing authorisation.