Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Pharmacovigilance Referrals - Changes in line with the new Pharmacovigilance Legislation 2010 / 2012 ***

Beate Stadler (Abschlußjahr: 2013)

Summary
Language: English

Regulatory agencies and pharmaceutical companies both are obliged to ensure that emerging safety information is reported and appropriate action is taken to safeguard public health. The two keystones of legislation that underpin pharmacovigilance activities in the European Union (EU) are Regulation 726/2004/EC and Directive 2001/83/EC as amended.
Since 2004 a number of weaknesses of the pharmacovigilance legislation have been revealed. Examples for this are the withdrawal of rofecoxib in 2004 or the suspension of the marketing authorisation of rosiglitazone after a great deal of discussion about its cardiovascular safety. In the course of the changing EU market a need for an improvement of the pharmacovigilance system became obvious.
In December 2010 a new European Pharmacovigilance legislation (Directive 2010/84/EC and Regulation 1235/2010/EC) was passed and came into effect in July 2012.
In 2012 a further amendment of the pharmacovigilance legislation became necessary since the so-called “Mediator case” raised people´s awareness of emerging safety issues. In this connection the EC had taken a closer look into the new pharmacovigilance legislation (“stress test”) and identified further weak points. Therefore in December 2012, with regard to pharmacovigilance, the legislation was amended by the adoption of Directive 2012/26/EC and Regulation 1027/2012/EC.
The new pharmacovigilance legislation in 2010/2012 has made substantial changes with regard to existing pharmacovigilance requirements, e.g. more post-authorisation safety and efficacy studies, a new Pharmacovigilance Risk Assessment Committee (PRAC) at the European Medicines Agency (EMA) and a broader reporting of side-effects by patients.
A further part of these changes applies to the pharmacovigilance referrals (“safety referrals”). This master thesis is intended to identify the main changes of the pharmacovigilance referrals in line with the new legislation taking into account the historical development, the different impacts and the outlook for the future.
The pharmacovigilance referrals are an instrument for taking regulatory action needed to protect public health, e.g. by changing the Product Information or revoking  the marketing authorisation.
In the course of the new legislation the number of safety referrals was reduced from five to four: Art. 107i and Art. 31 of Directive 2001/83/EC as well as Art. 20 and Art. 5(3) of Regulation 726/2004/EC.
The latest amendment to Art. 107i (by Directive 2012/26/EC) provides an automatic assessment including an EU safety evaluation and possible EU-wide withdrawal of the medicinal product in certain circumstances
From the regulatory perspective the pharmacovigilance system has taken a great step forward. However, it has not yet been proven if these changes contribute to a better drug surveillance and thus to an increase in drug safety.
The pharmacovigilance legislation especially the further amendment in 2012, is still rather new. More practical experience and more time will show whether hospitalisations and the severe cases of adverse drug reactions decrease and whether the new legislation is really able to fill the gaps in European drug safety monitoring systems.

Pages: 50