Implementation of the pharmacovigilance legislation

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The new pharmacovigilance legislation, which came into effect in 2012, introduced a range of new tasks and streamlined existing responsibilities for regulators and the pharmaceutical industry in the European Union (EU).

The activities introduced with the pharmacovigilance legislation fall into four main areas:

Information on EU pharmacovigilance fees to be charged for human pharmacovigilance activities is available on Pharmacovigilance fees payable to the European Medicines Agency

One-year report on implementation

In May 2014, the European Commission published a report by the European Medicines Agency (EMA) on the tasks EMA undertook during the first year of application of the new legislation together with medicines regulatory authorities in Member States and the European Commission.

The report covers the period 2 July 2012 to 1 July 2013. During this period, the Agency coordinated delivery of the main objectives of the new legislation, including:

  • an increase of more than 9,000 in patient reports of suspected adverse drug reactions;
  • product information changes as a consequence of assessment of signals of new or changing safety issues with certain medicines;
  • initiation of major public-health reviews, including combined hormonal contraceptives and venous thromboembolism, medicines containing cyproterone acetate / ethinylestradiol and venous thromboembolism, and codeine-containing products used for pain relief and overdose in children;
  • training thousands of individuals in pharmacovigilance.

For more information, see One-year report on human medicines pharmacovigilance tasks of the European Medicines Agency.


Collection of key information on medicines

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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 will be mandatory from 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 new 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. 

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

  • new marketing authorisations within 15 calendar days from the date of notification of the granting of the marketing authorisation by the national competent authority;
  • any amendments to the terms of marketing authorisations following variation, transfer, renewal, suspension, revocation or withdrawal no later than 30 calendar days from the date on when the amendments were authorised.

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:

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 new 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 from 1 September 2015, covering 300 chemical active substance groups and 100 herbal active substance groups monitored by EMA. 

Analysis and understanding of data and information

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Strengthened signal detection

The legislation brought in a stronger process for detecting safety signals for centrally authorised medicines by the Agency and strengthened the coordination of Member State signal detection for nationally authorised medicines.

Improving EudraVigilance

The legislation foresees strengthening and increasing the functionality of EudraVigilance. The Agency is working on improving the quality of data in the database and improving access to this data for national medicine regulatory authorities by:

  • complying with international data standards, including backward and forward conversion tools for E2B(R2)/(R3) messages;
  • converting legacy data, including more than 7 million individual case safety reports;
  • improving system performance and scalability, to account for more users and more data;
  • reinforcing security in terms of user authentication, authorisation and data transaction.

This is expected to result in:

  • simplified reporting and enhanced access to data for marketing-authorisation holders;
  • enhanced data analysis, signal detection and tracking for authorities in EU Member States;
  • prompt availability of information on suspected adverse drug reaction reports for the World Health Organization;
  • greater access to information on suspected adverse drug reactions for the general public.

More information is available in:

Additional monitoring of medicines

The new legislation introduced the concept of additional monitoring for medicines that are being monitored particularly closely by regulatory authorities. These medicines have an inverted black triangle printed on the product information.


Regulatory action to safeguard public health

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Changes in scientific committees and decision-making

The legislation established the PRAC, which began meeting in July 2012.

It also changed the mandate of the existing Coordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh). This Group now leads on decision-making based on recommendations from the PRAC for nationally authorised medicines, ensuring harmonised implementation of safety recommendations across the EU.

Strengthened referral procedures

The legislation introduced the Article 107i procedure for safety-related issues to rapidly assess significant emerging safety issues linked with a medicine available in the EU. This procedure can be used regardless of the medicine's initial authorisation route, either central or national.

All pharmacovigilance referrals are assessed by the PRAC, whose recommendations are relied upon by the Committee for Medicinal Products for Human Use (CHMP) or the CMDh. 

The legislation also increased transparency for safety referrals procedures, with the publication of more information on each referral online and the opportunity for the public to engage with the Agency through public hearings.


Communicating with stakeholders

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Publishing of information on medicines

The Agency publishes the agendas and minutes of all of its committees, including the PRAC and CHMP in line with the legislation.

The Agency is also working towards the launch of the European medicines web portal, which will include information on all medicines authorised in the EU. Until the launch of the fully functional portal, this website (ema.europa.eu) publishes all relevant information in accordance with the legislation.

Coordination of safety messages

The new legislation gives the Agency a central role in coordinating announcements on the safety of medicines across the EU, including nationally authorised medicines. This aims to ensure consistent and coherent safety advice on medicines that are available in more than one Member State.

For more information, see:

Public hearings (updated)

The legislation gives the Agency the ability to organise public hearings for safety-related referral procedures. When considered necessary by the PRAC, members of the public can take part in public hearings on specific issues relating to the safety of medicines, either in person or online.

The PRAC adopted the rules of procedure for public hearings in April 2016, after they were endorsed by EMA's Management Board:

For more information, see Public hearings

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