Overview of medicines legislation and guidance: Pharmacovigilance

A nurse talking about safety advice with a patient

In this section...

Clinical trials
Clinical trials ar governed by Directive 2001/20/EC (implemented in 2004). The relevant UK legislation is The Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004 no. 1031) (external link).


Post marketing
For products authorised through the national procedures, including the mutual recognition and decentralised procedures, the following legislation applies:

Directive 2001/83/EC Title IX Articles 101 to 108 (external link): Pharmacovigilance requirements
Title XI Articles 111, 116 and 117. Supervision and sanctions

For products authorised through the centralised procedure:

  • Regulation (EC) No 726/2004 (external link) Title II Ch. 3 Articles 21 to 29: Pharmacovigilance requirements
    Title II Ch. 2 Articles 16 to 20: Supervision and Sanctions (these articles link back to the provisions of Title XI of Directive 2001/83/EC [external link])
  • Title IV Ch. 1 Article 57: Duties of the EMEA Commission Regulation 540/95 : Reporting of non-serious unexpected adverse reactions.
    Regulation (EC) No 1394/2007 (external link): Specific pharmacovigilance requirements for advanced therapy medicinal products

The legal provisions relating to pharmacovigilance were modified by Directive 2004/27/EC (amending Directive 2001/83/EC) (external link) and Regulation (EC) No 726/2004 (external link) which replaced Regulation 2309/93 from 20-Nov-2005.

The legislation is supported by a series of guidelines. Of particular importance are:

For clinical trials:

  • European Commission guideline on the collection, verification and presentation of adverse reaction reports arising from clinical trials on medicinal products for human use.
  • European Commission guideline on the European database of suspected unexpected serious adverse reactions (EudraVigilance-Clinical Trial Module).

Volume 10 of Notice to Applicants (external link)

For marketed products:

  • EUDRALEX Notice to Applicants Volume 9A (external link) - includes the major guidelines relating to post-marketing pharmacovigilance. This volume also contains some information relating to clinical trial data, in particular Part III deals with the electronic reporting requirements for both pre-and post-authorisation phases.

Company responsibilities:

For clinical trials:
The sponsor of the clinical trial is responsible for pharmacovigilance activities and needs to have systems in place to record and analyse reported adverse events/reactions.

Company derived pharmacovigilance data includes reports of suspected unexpected serious adverse reactions (SUSARs) and annual reports.

The sponsor must continually evaluate the safety data received on investigational medicinal products and ensure that any necessary regulatory action is taken. For details on the system for reporting suspected adverse reactions, see:

Safety reporting - SUSARS and ASRs

For marketed products:
The marketing authorisation holder must operate appropriate pharmacovigilance and risk management systems in order to assure responsibility and liability for its marketed products and to ensure appropriate action can be taken when necessary.

Since 2005, the legislation has required the applicant to include a detailed description of their pharmacovigilance system in marketing authorisation applications (CTD: Module 1 Section 1.8.1).

This is a general description (not product specific) and includes proof of the availability of the services of a qualified person for pharmacovigilance and proof that the marketing authorisation holder has the necessary means for the collection and notification of adverse reactions.

Part I Section 2 of Volume 9A (external link) 

Company-derived pharmacovigilance data includes adverse reaction case reports, periodic safety update reports and company sponsored post-authorisation studies. The marketing authorisation holder must continually evaluate the pharmacovigilance data received and ensure that marketing authorisations are maintained to reflect the latest information.

The marketing authorisation holder must have a qualified person responsible for pharmacovigilance, resident in the Community, permanently and continuously available . Details relating to the experience and qualifications for qualified persons are provided in Part I Section 1 of Volume 9A (external link).

Details on how companies report adverse drug reactions to the MHRA are available on the website.

Reporting suspected adverse drug reactions

Periodic Safety Update Reporting

Black Triangle Scheme


Page last modified: 11 February 2011