2010 pharmacovigilance legislation: strengthening the monitoring of medicines

New pharmacovigilance legislation (a directive and a regulation) amending existing legislation was adopted in the European Union (EU) in December 2010. The legislation aims to save lives by strengthening the European-wide system for monitoring the safety of medicines.

The new legislation forms part of a three-piece ‘pharmaceutical package’ and amends existing pharmacovigilance legislation contained in Directive 2001/83/EC and Regulation (EC) No. 726/2004. The remaining parts concerning falsified medicines and information to patients have not yet been adopted by the European Parliament and the European Council.

European Medicines Agency's role

The European Medicines Agency and the EU Member States are responsible for implementing much of the new legislation.

The Agency will work with a wide range of stakeholders including pharmaceutical companies, national medicines regulatory authorities, patients and healthcare professionals to ensure effective implementation. Most of the legislation must be implemented within 18 months of becoming law or by July 2012.

For more information, see planning for the implementation of the new legislation on pharmacovigilance.

Background to the new legislation

A strong factor in the development of the new Directive and Regulation is the incidence of so-called adverse drug reactions (ADRs) - responses to a medicine that are ‘noxious and unintended’. ADRs are estimated to cause 197 000 deaths per year in the EU. A strengthened European safety monitoring system aims to reduce the number of ADRs.

The European Commission began a review of the European system of safety monitoring in 2005 including an independent study sponsored by the European Commission and extensive public consultation in 2006 and 2007. The legislation was adopted by the European Parliament and Council of Ministers in December 2010.

Impact of the new legislation on EU citizens and patients

For patients and EU citizens, the new legislation aims to:

inform EU citizens and patients on the benefit-risk aspects of taking a medicine;
provide the opportunity for patients to be independent and proactive in feedback by:
- allowing citizens to report perceived problems with a medicine through online reporting forms;
- participation in the public hearing process;
raise awareness of safety issues through:
- the creation of new public-facing websites managed by the Agency and Member States with content uniquely focused on medicine safety issues, including;
  - safety announcements on medicines prescribed in the EU;
  - a list of medicines prescribed in the EU under special safety monitoring provisions. These medicines will also have a symbol and explanatory wording added in the online patient information leaflet and summary of product characteristics for medicines;
  - a list of the status of all medicines in the EU, i.e. authorised, suspended or withdrawn;
  - agendas and minutes of committee meetings where medicines with safety concerns have been discussed;
- holding public hearings on medicines or classes of medicine where particular safety issues are being discussed;
increase public confidence in the safety monitoring system and the positive-risk benefit of medicines generally by:
- creating a new European pharmacovigilance committee based at the Agency whose work will focus solely on the assessment and communication of safety issues with medicines;
- being more open and transparent on safety issues by publishing information proactively on the Internet and holding public hearings;
- ensuring that companies strengthen their pharmacovigilance systems
- ensuring proactive and proportionate monitoring of medicines.
- ensuring that roles and responsibilities are clear between the pharmaceutical industry, national regulators and the Agency.

For more information on the regulatory impact of the new legislation, see new 2010 pharmacovigilance legislation.

Patient and healthcare professional involvement in the implementation of the legislation

The EMA plans to hold up to six stakeholder workshops before July 2012. Patients and Healthcare professionals will be represented at these workshops by members of the established Patients' and Consumers' Working Party and Healthcare Professionals' Working Group, which already have strong working relationships with the Agency.

Stakeholder events

On 15 April 2011 the Agency held the first stakeholder forum on the implementation of the new 2010 pharmacovigilance legislation. The meeting involved a broad cross-section of participants including industry, patient and healthcare professional representatives and national medicines regulatory authorities.

This was the first in a series of stakeholder meetings taking place during 2011 and 2012 where the Agency aims to raise awareness of the requirements of the new legislation and promote the exchange of ideas, concerns and opinions. During the meeting, immediate feedback from stakeholders was received mainly in relation to the Agency's and Member States' technical contribution to draft European Commission implementing measures.

Impacts of the new legislation on marketing authorisation holders

Marketing authorisation applicants and holders will be impacted by the legislation in a number of key areas. The legislation aims to make roles and responsibilities clear, minimise duplication of effort, free up resources by rationalising and simplifying adverse drug reaction (ADR) reporting and periodic safety update report (PSUR) reporting and establish a clear legal framework for post-authorisation monitoring.

Examples of impacts on marketing authorisation holders and applicants specifically include:

Eudravigilance/ADR reporting

Following a successful audit, marketing authorisation holders will submit Adverse Drug Reaction reports only into Eudravigilance – currently reports go via the individual National Competent Authority. This will include reporting of medication errors that result in an adverse reaction.

Additional monitoring

PSURs will have a single assessment for the same active substance or a combination of active substances.
Routine PSUR reporting is no longer necessary for products with low risk or for old or established products unless concerns arise.
PSUR reporting will be electronic following the establishment of an EU repository. PSURs will be sent directly to the European Medicines Agency.
There will be a strengthened legal basis for requesting post-authorisation safety and efficacy studies (PASS/PAES) from the pharmaceutical industry.
Risk-management systems will be required for all newly authorised medicines.

Referrals

All pharmacovigilance referrals will be discussed by the new Pharmacovigilance Risk Assessment Committee (PRAC) and the Committee for Medicinal Products for Human Use (CHMP) or the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh). Opinions will be adopted as a result.

Inspections and pharmacovigilance systems

Marketing authorisation holders will be required to maintain a Pharmacovigilance System Master File (PSMF) permanently available for submission or inspection by the National Competent Authority. The PSMF replaces the current Detailed Description of the Pharmacovigilance System (DDPS).

Supply of medicinal product information to the European Medicines Agency

Article 57(b) of Regulation 1235/2010 states that by 2 July 2012 ,marketing-authorisation holders will need to submit information to the Agency on medicinal products for human use authorised or registered in the EU using an electronic format provided by the Agency. Marketing-authorisation holders will also be responsible for maintaining this information once submitted.

Implementation of the new legislation

The new legislation requires a set of legislative implementing rules adopted by the European Commission based on the requirements of the Regulation and Directive.

The Agency and Member States are drafting a concept paper describing the implementation of the legislation. In addition a joint implementation checklist has been published describing the planning and implementation of the new legislation until the end of 2012.

The Agency has also put in place a project implementation governance structure has been in put in place. This comprises of sub-project teams at the Agency and three oversight committees comprised of Agency staff and committee members, and representatives of Member States and the European Commission.

For more information, see planning for the implementation of the new legislation on pharmacovigilance.

Latest documents for public consultation

The Agency is publishing a series of documents for public consultation related to the implementation of the new pharmacovigilance legislation.

Working with the pharmaceutical industry on implementation of the new legislation

The Agency hopes to work closely with its key stakeholders over the coming months including the pharmaceutical industry. A number of workshops are planned during 2011 and 2012 to promote dialogue with key groups.