Medicinal products for human use: pharmacovigilance of products

2008/0260(COD)

PURPOSE: to amend, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use.

PROPOSED ACT: Directive of the European Parliament and of the Council

CONTENT: 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. Some adverse reactions will only be detected after a medicine has been authorised and the full safety profile of medicinal products can only be known once they have entered the market. Pharmacovigilance rules are therefore necessary for the protection of public health in order to prevent, detect and assess adverse effects of medicinal products.

The proposals aim at the strengthening and rationalising the Community pharmacovigilance system of medicinal products for human use The specific objectives are:

  • providing clear roles and responsibilities for the key responsible parties and clear obligations;
  • 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;
  • strengthening companies' pharmacovigilance systems, allowing companies to improve their systems regularly whilst reducing administrative burden;
  • introducing a risk management planning for each new medicinal product
  • strengthening the reporting system for adverse reactions by rationalising current system and involving all stakeholders in pharmacovigilance
  • ensuring the proactive and proportionate collection of high quality data relevant to the safety of medicines through risk management and structured data collection.

In 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.

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.

Transparency and communication: 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.
  • 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. These 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.

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. These proposals require:

  • 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 studies.

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 Eudravigilance database.
  • 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.

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 proposals:

  • 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, 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.
  • introduce 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.

Lastly, the proposal also contains two provisions to improve the availability of medicine in Member States, in particular the smaller ones.