Risk-management plans

The pharmacovigilance legislation strengthened procedures concerning risk-management plans. This includes requiring a risk-management plan for all new medicines and the publication of summaries of risk-management plans, which the Agency began in March 2014. Risk-management plans ensure that proactive planning of data collection and of risk minimisation takes place. They are essential for the safe introduction of new products for patients.

Periodic safety update reports

The legislation sets out the format and content for periodic safety update reports (PSURs) and foresees the 'single assessment' of PSURs for multiple products that contain the same active substance or combination of active substances.

Single assessments of PSURs for centrally authorised medicines began in July 2012. Single assessment was expanded to nationally authorised medicines in April 2013.

Routine PSUR reporting is no longer necessary for generic products, although regulatory authorities can request PSURs if concerns arise.

PSUR repository

In accordance with the pharmacovigilance legislation, EMA launched an electronic central repository for PSURs and their assessment reports on 26 January 2015.

On 12 June 2015, the EMA Management Board gave its green light for the repository to be used as the single, central platform for all information related to PSURs in the EU. The use of the repository is mandatory since 13 June 2016.

The repository facilitates the pharmaceutical industry's submission of PSURs electronically, and gives secure access to authorised users from national competent authorities in EU Member States, EMA, EMA committees, and the European Commission. This ensures that all parties involved in benefit-risk assessments of medicines have timely access to all relevant documents in one location.

Post-authorisation safety and efficacy studies

The legislation strengthened the legal basis for requesting post-authorisation safety studies (PASSs) and post-authorisation efficacy studies (PAESs) from the pharmaceutical industry.

The Pharmacovigilance Risk Assessment Committee (PRAC) now has the task of approving PASS protocols. It can also require and enforce PASSs or PAESs, in order to improve the benefit-risk monitoring of medicines.

Data submission for authorised medicines

The legislation requires marketing-authorisation holders to submit structured electronic information to the Agency on medicines authorised in the European Union (EU) and European Economic Area (EEA).

This is to ensure that the pharmacovigilance systems of the Agency, national competent authorities and industry are driven by accurate, complete and reliable information on medicines, substances and organisations.

During 2014, the pharmaceutical industry was required to re-submit data to the Agency to ensure that it is up-to-date, complete and of high-quality.

Since the start of 2015, the focus is on maintaining the data. Marketing-authorisation holders must notify EMA on:

For more information, see Data submission for authorised medicines.

Adverse-drug-reaction reporting by patients and healthcare professionals

The legislation introduced the right of individual European citizens to report suspected side effects directly to national medicine regulatory authorities and marketing-authorisation holders.

Information on suspected side effects of medicines is available to view in the European database of suspected adverse drug reaction reports.

For more information, see 'Guideline on good pharmacovigilance practices: Module VI – Management and reporting of adverse reactions to medicinal products' on good pharmacovigilance practices.

Pharmacovigilance system master files

Marketing-authorisation holders are now required to maintain a pharmacovigilance system master file (PSMF) permanently available for submission or inspection by regulatory authorities.

Notification requirements for cessation of marketing and withdrawal

Since the 2012 amendments to the pharmacovigilance legislation, marketing-authorisation holders of human medicines have to notify EU regulators of any action to withdraw a product from the market, together with the reason for this action, when the decision is based on any of the following grounds:

• the medicine is harmful;
• the medicine lacks therapeutic efficacy;
• the risk-benefit balance of the medicine is not favourable;
• the qualitative and quantitative composition of the medicine are not as declared;
• manufacturing or inspection issues have been identified.

For more information, see Withdrawals and cessation of centrally and nationally authorised medicines: questions and answers.

Medical literature monitoring

The legislation requires the Agency to provide a service to monitor selected medical literature on suspected adverse reactions to medicinal products containing certain active substances. This ensures that individual cases are entered into EudraVigilance in the required electronic format for adverse reaction reporting. These reports are subsequently forwarded to the national competent authority of the respective European Economic Area (EEA) Member State.

This is in line with the reporting principles set out in module VI of the guideline on good pharmacovigilance practices.

The pharmaceutical industry are able to download Individual case safety reports (ICSRs) from the system. This allows marketing-authorisation holders to process these ICSRs in their safety databases and meet their reporting obligations outside the EEA as applicable.

EMA has published the list of active substances covered by the medical literature monitoring service. The list contains active substances, including herbals, with high numbers of marketing authorisations granted to various marketing-authorisation holders in the EEA.

The service became fully operational on 1 September 2015, covering 300 chemical active substance groups and 100 herbal active substance groups monitored by EMA.