Brussels, 10 December November 2008
Strengthening pharmacovigilance to reduce
adverse effects of medicines
Medicinal products contribute considerably to the
health of EU citizens. They can, however, also have adverse effects. It is
estimated that 5% of all hospital admissions are due to an adverse drug reaction
(ADR), and that ADR is the fifth most common cause of hospital death. In light
of experience and following an assessment made of the EU pharmacovigilance
system (supervision and monitoring of ADR) made by the Commission it has become
clear that new measures are necessary to improve how the EU rules operate on the
pharmacovigilance of medicinal products. Today’s proposals seek to change
the existing EU legislation on pharmacovigilance (provisions in Regulation (EC)
No 726/2004 and Directive 2001/83/EC). They aim at strengthening and
rationalizing the EU pharmacovigilance system, with the overall objectives of
better protecting public health, ensuring proper functioning of the internal
market and simplifying the current procedures.
Some adverse reactions can only be detected after a medicine has been
authorised. The full safety profile of medicines can only be known once they
have entered the market. The supervision and monitoring of adverse reactions of
authorised medicines are carried out through the EU’s pharmacovigilance
system. This system ensures that any product, which presents an unacceptable
level of risk, can be rapidly withdrawn from the market. Thus pharmacovigilance
comprises collecting and managing data on the safety of medicines, evaluating
this data and deciding to act to protect public health. It is estimated that
197,000 deaths per year in the EU are caused by ADRs and that the total cost to
society of ADRs in the EU is €79 billion. Today’s proposals are
aimed at further improving the current system. They will save many lives per
year across the EU. In addition, they will help to cut red tape by decreasing
the administrative burden by ca. € 145 billion p.a.
What are the key measures proposed?
The improvement in the protection of public health will be achieved
- Providing clear roles and responsibilities for the key responsible
parties and clear obligations (see point 1 below for more details);
- Strengthening transparency and communication on medicine’s safety
issues to increase the understanding and trust of patients and health
professionals and improve the penetration of key warnings (see point 2 below for
- Strengthening companies' pharmacovigilance systems, allowing
companies to improve their systems regularly whilst reducing administrative
burden (see point 3 below for more details);
- Introducing a risk management planning for each new medicinal product
(see point 4 for more details).
- Strengthening the reporting system for adverse reactions by
rationalising current system and involving all stakeholders in
pharmacovigilance (see point 5 below for more details);
- Ensuring the proactive and proportionate collection of high quality data
relevant to the safety of medicines through risk management and
structured data collection (see point 6. for more details).
addition to achieving better protection of public health the proposals will also
simplify the current EU procedures with consequent efficiency gains for
both the pharmaceutical industry and medicines’ regulators.
Some of the proposed new rules in more detail:
1. Clear roles and responsibilities
- Member States should remain central to the operation of
pharmacovigilance, with increased cooperation and work-sharing mechanisms
(Member States not the Commission).
- Companies’ responsibilities are clarified, in particular as
regards the scope of their obligation to continuously monitor the safety of
products thereby ensuring that all information available is brought to the
attention of the authorities.
- A new scientific committee, the Pharmacovigilance Risk
Assessment Advisory Committee, is created within the EMEA and it will play a
key role in the pharmacovigilance assessments in the EU.
- The mandate of the coordination group composed of Member States
representatives is enhanced for the sake of closer cooperation between the
Member States and in order to increase work-sharing.
- The EU procedure for the assessment of serious safety issues for
nationally authorised products is stream-lined through clear and binding
initiation criteria for the Member States.
2. Transparency and
Clear, EU coordinated messages about specific safety risk issues:
- The Eudravigilance database should become the single point of receipt
of pharmacovigilance information for medicinal products authorised in the
- EU coordination of communication about safety issues and
establishment of a European medicines safety web-portal.
- Introduction of a new ‘key information' section in the summary
of the product characteristics and the package leaflet.
Pharmacovigilance obligations by industry
Currently legislation requires a ‘detailed description of the
pharmacovigilance system’ to be submitted in marketing authorisation
applications. Today’s proposals simplify the existing requirement by
introducing the "Pharmacovigilance system master file". In the
applications only key elements of the pharmacovigilance system should be
submitted, but this is balanced with a requirement for companies to maintain a
detailed file on site.
4. Risk management planning and non-interventional safety studies
In the existing provisions, companies may provide a risk management system
for specific medicinal products if considered appropriate, and there is no
explicit legal basis for competent authorities to request it. Today’s
- A risk management system for each new medicinal product (or for
existing products on the basis of safety concerns), which should be
proportionate to the identified risks, potential risks, and the need for
additional information on the medicinal product.
- Harmonised guiding principles and a procedure for the supervision of
non-interventional post-authorisation safety studies (i.e. safety studies of
authorised products that are not clinical trials), in particular to ensure that
they are non promotional, and the follow-up of any safety date generated in such
5. Adverse drug reaction case reports
Current reports are submitted to several authorities if a product is
authorised in more than one Member State, and lead to duplicative
assessments as there is no provision to group assessments by products or
substances. The proposals are intended:
- To make reporting proportionate to risks;
- To empower patients to report their side effects;
- To ensure that overdoses and medication errors are reported;
- To simplify adverse reaction reporting. It is proposed to report all adverse
reaction data directly to the Eudravigilance database.
- For the Agency to take on a new task for the monitoring of selected
scientific literature and for entering case reports of adverse effects onto the
- For medication errors that result in an ADR to be reported to the competent
authorities for medicines. Member State authorities should ensure that data is
shared (including between the authorities for medicines and any authorities for
patient safety) and make clear the legal basis for patients to report suspected
adverse drug reactions.
6. Periodic safety update reports and
other safety related assessments
As there is currently no provision for group submissions and assessments on
products or substances, this leads to duplicative submissions and
assessments. The update of product information as a result of
these assessments is not governed in detail by the actual legislation. The
- Simplify periodic safety update report submission by industry
and make it proportional to the knowledge about the safety/risk of the product;
- Would introduce work-sharing mechanisms for the assessments, with a
prominent role in all cases by the Pharmacovigilance Risk Assessment Advisory
Committee (see 1. above), and faster updating of product information;
- Amend the scope of periodic safety update reports to become an
analysis of the risk-benefit balance of a medicinal product rather than a
detailed presentation of individual case reports as a result of the submission
of all ADR data directly to the Eudravigilance database,;
- Make the requirements for periodic safety update reports proportional to
the risks posed by medicinal products, and routine reporting is no longer
necessary for products considered low risk or where reporting would be
duplicative (with the possibility for ad-hoc requests for such products).
- Make explicit provision for the regulatory follow-up of assessments of
periodic safety update reports, to ensure a clear link between
pharmacovigilance evaluations and the review and updating of marketing
authorisations authorised in the EU.
- Create the framework for the shared use of resources between
competent authorities for the assessment and follow-up of periodic safety update
reports, with a strong involvement of the Agency's Pharmacovigilance Risk
Assessment Advisory Committee.
- Foresee a single assessment of periodic safety update reports for
medicinal products authorised in more than one Member State,(including all
products containing the same active substance),. This will also be the case for
products authorised by the Member States and/or by the Commission.
Finally, the proposals also contain two provisions to improve the
availability of medicine in Member States, in particular the smaller ones.
When will this become law?
The proposals will now be transmitted to the European Parliament and the
Council where it will be discussed and voted in the “co-decision
procedure”. The legal proposal could become law at the earliest in 18
months following adoption and publication by the European Parliament and the
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