Review Article

Drug Safety

, Volume 34, Issue 3, pp 187-197

First online:

Strengthening and Rationalizing Pharmacovigilance in the EU: Where is Europe Heading to?

A Review of the New EU Legislation on Pharmacovigilance
  • John-Joseph BorgAffiliated withMedicines Authority Email author 
  • , George AislaitnerAffiliated withNational Organization for Medicines (EOF)
  • , Michal PirozynskiAffiliated withDepartment of Anaesthesiology and Critical Care Medicine, Postgraduate Medical School
  • , Stephen MifsudAffiliated withPermanent Representation of Malta to the European Union

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Amendments to the European pharmacovigilance legislative framework are expected to come into force in 2011, following the adoption of the proposed amendments to Directive 2001/83/EC on the community code relating to medicinal products for human use (hereinafter referred to as the Directive) and to Regulation (EC) No. 726/2004 laying down community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (EMA) [hereinafter referred to as the Regulation]}. The Regulation shall apply 18 months after publication in the Official Journal of the European Union. The amendments to the Directive and the Regulation will induce changes in the EU in terms of evaluation of risk associated with medicinal products as well as the framework on how the EU takes harmonized regulatory action on drug safety. In this review, the text agreed between the European Parliament and Council is examined and compared with the pharmacovigilance legislative framework currently in force. We argue that the new legislation has improved numerous uncertainties in current legislative framework and provides for the following: (i) clear roles, responsibilities and obligations for the key responsible parties; (ii) rationalization of EU decision making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products across the community with a view to preventing unnecessary patient exposure to risks; (iii) strengthening medicine safety transparency and communication so that the understanding and trust of patients and health professionals in the safety of medicines will improve, as well as the penetration of key warnings; (iv) strengthening companies’ pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; (v) ensuring the proactive and proportionate collection of high-quality data relevant to the safety of medicines through risk management and structured data collection in the form of Post-Authorization Safety Studies (PASS), together with rationalized single-case and periodic reporting of suspected adverse drug reactions (ADRs); (vi) involvement of stakeholders in pharmacovigilance through direct patient reporting of uspected ADRs and inclusion of patients and healthcare professionals in decision making; and (vii) simplification of the current community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators.

For the first time, companies can be made legally liable to carry out PASS and Post-Authorization Efficacy Studies. The amendments to the Regulation and to the Directive will strengthen the European network on pharmacovigilance. A Pharmacovigilance Risk Assessment Committee (PRAC) based at the EMA will be set up, which will be responsible for all matters related to pharmacovigilance at an EU level. Three European databases will be strengthened (EudraVigilance, EudraPharm and the European Pharmacovigilance issues Tracking Tool) as well as the setting up of an EU safety portal to better inform the public on all safety issues being discussed at an EU level. Public hearings at the PRAC will improve transparency in the decision-making process, whilst details and results of all PASS agreed to by the PRAC will also be made publically available.

Pharmacovigilance is the science of, and activities relating to, the detection, assessment, understanding and prevention of adverse effects of marketed medicines; specifically, taking action to increase the products’ benefits and reduce their risks. This is achieved by monitoring the use of medicines in normal conditions of use to identify previously unrecognized adverse effects or changes in the patterns of adverse effects; assessing the benefits and risks of medicinal products to take a decision on what action, if any, is necessary to improve the safe use of medicinal products; providing information to the public and healthcare professionals to optimize the safe and effective use of medicines; and assessing the impact of any action taken. It is imperative that pharmacovigilance is carried out by both industry and regulators since notification and reporting of suspected adverse drug reactions (ADRs) arising with the use of medicinal products, by healthcare professionals and consumers, is an essential source of new information for the achievement of these objectives.

Not all hazards can be identified under the limited and restricted environment of testing in clinical trials, before a medicinal product is marketed. Since patients, consumers and indeed some healthcare professionals have expectations that medicinal products available are ‘safe’, they are, from time to time, surprised when regulatory action is taken to restrict their use, introduce new warnings in the product information, or withdraw medicines as a result of the emergence of new data regarding safety issues affecting the positive benefit-risk assessment of the product.

Information collected during the premarketing phase of a medicinal product is inevitably insufficient in compiling a complete safety profile of a product, as animal testing is sometimes not necessarily predictive of human safety. Data from clinical trials are limited by various factors, including their (sample) size and duration. Furthermore, conditions of use differ during clinical trials from those encountered during normal clinical practice. Information about rare but serious ADRs, chronic toxicity, use in special groups (such as children, the elderly or pregnant women), or drug interactions could not be available for all of the medicinal products, thus emphasizing the need for ongoing surveillance.

In December 2008, the European Commission (EC) launched legislative proposals for a European Regulation and a Directive to strengthen and rationalize pharmacovigilance in the EU.[1,2] Following a public consultation procedure,[3] proposals for amending the Regulation and the Directive, in those aspects relating to pharmacovigilance, were drawn up based on a system of measures to decrease bureaucracy associated with the regulatory process of carrying out pharmacovigilance and to introduce legislative tools so that harmonized action on drug safety across the EU can be taken. The aim of this review is to present the structure and functions of the new proposed pharmacovigilance system in the EU, which is expected to have a major impact on the EU regulators (and competent authorities of accession countries [such as Croatia and Turkey]) and on the pharmaceutical industry.