European Pharmacovigilance for Medicinal Products

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Chapter: Pharmacovigilance: Legal Basis – EU

European Pharmacovigilance for Medicinal Products Authorised by National or Mutual Recognition Licensing Procedures – Directive 2001/83/EC


Title IX of Directive 2001/83/EC deals with phar-macovigilance obligations imposed on the Agency, the Commission, marketing authorisation holders and the Member States for medicinal products authorised through national and mutual recognition procedures. Article 102 explains that:

• ‘In order to ensure the adoption of appropriate and harmonised regulatory decisions concerning the medicinal products authorised within the Commu-nity, having regard to information obtained about adverse reactions to medicinal products under normal conditions of use, the Member States shall operate a pharmacovigilance system. This system shall be used to collect information useful in the surveillance of medicinal products, with particular reference to adverse reactions in human beings, and to evaluate such information scientifically.

• Member States shall ensure that suitable information collected within this system is communicated to the other Member States and the Agency. The informa-tion shall be recorded in the database referred to in [Regulation (EC) No. 726/2004] and shall be perma-nently accessible to all Member States and without delay to the public.

• This system shall also take into account any avail-able information on misuse and abuse of medicinal products which may have an impact on the evaluation of their benefits and risks.’


Article 105 requires the Agency, in collaboration with the Member States and the Commission, to set up a data-processing network to facilitate the exchange of pharmacovigilance information to enable all the competent authorities to share pharmacovigi-lance information at the same time. The development of the EudraVigilance facility is discussed further below.


As discussed previously, the Commission has obliga-tions under Article 106 in relation to the publication of pharmacovigilance guidance.


Article 104 of Directive 2001/83/EC sets out the obli-gations of marketing authorisation holders. Marketing authorisation holders must maintain detailed records of all suspected adverse reactions occurring either in the Community or in a third country. Save in exceptional circumstances, these reactions must be communicated electronically in the form of a report in accordance with the guidance in Volume 9. All suspected serious adverse reactions brought to the attention of the marketing authorisation holder by health care professionals must be recorded and reported to the competent authority of the Member State where the incident occurred within 15 days of receipt of the information.

In addition, marketing authorisation holders are required to record and report all other suspected seri-ous adverse reactions of which they can reasonably be expected to have knowledge and which meet the noti-fication criteria set out in Volume 9. This addresses the fact that, in addition to adverse reactions reported by health care professionals, others will be identi-fied in worldwide scientific literature or during post-authorisation studies.

Marketing authorisation holders must ensure that all suspected serious unexpected adverse reactions and any suspected transmission through a medicinal product of any infectious agent occurring in the territory of a third country are reported to the Agency and the competent authorities of the Member States where the product is authorised, within 15 days of receipt of the information. The format for these reports is set out in Volume 9.

Where a medicinal product has been authorised through the mutual recognition procedure, the market-ing authorisation holder must ensure that all suspected serious adverse reactions occurring in the Community are reported in such a way as to be accessible to the Member State that first authorised the product (‘Reference Member State’) or to any competent authority acting as Reference Member State. The Refer-ence Member State shall assume the responsibility of analysing and monitoring such adverse reactions.

All suspected adverse reactions must be submitted to the competent authorities in the form of a periodic safety update report (‘PSUR’) (including a scientific evaluation of the risk/benefit balance):

• immediately upon request or at least every  6 months after authorisation and until the placing on the market;

• immediately upon request, or at least every 6 months during the first 2 years following the initial placing on the market and

• once a year for the following 2 years.

After this period, the PSURs must be submitted at 3-year intervals or immediately upon request. Follow-ing the grant of a marketing authorisation, the market-ing authorisation holder may request the amendment of these periods. There is also a specific provision that states that a marketing authorisation holder may not communicate information relating to pharmacovigil-ance concerns about its products to the general public without giving prior or simultaneous notification to the competent authority. In any case, the marketing authorisation holder must ensure that all such infor-mation is presented objectively and is not misleading. If a marketing authorisation holder fails in this duty, the Member States are under an obligation to apply effective, proportionate and dissuasive penalties.


Article 103 of Directive 2001/83/EC requires market-ing authorisation holders to have an appropriately qualified person, who must be resident in the Community and who is responsible for pharmacovigi-lance, permanently and continuously at their disposal. Volume 9 provides that this qualified person may be resident in the EEA, reflecting the fact that the pharmacovigilance legislation is not, in fact, limited to the EU. The qualified person is responsible for:

• establishing and maintaining a system which ensures that information about all suspected adverse reac-tions, reported to people within the company and medical representatives, is collected and collated at a single point within the Community;

• preparing the reports that the marketing authorisa-tion holder is obliged to prepare (see p. 15) for the competent authorities, in accordance with national guidelines and Volume 9;

• ensuring a full and prompt response to any request from a competent authority for additional informa-tion (including information about volume of sales or prescriptions) necessary for a risk/benefit eval-uation of a medicinal product; and

• providing the competent authorities with any other relevant information about the benefits and risks afforded by a medical product, including informa-tion on post-authorisation safety studies.


Article 101 of Directive 2001/83/EC requires Member States to take all appropriate measures to encourage all health care professionals to report suspected adverse reactions to the competent authorities. Member States can also impose specific reporting requirements on health care professionals, in respect of the reporting of suspected serious or unexpected adverse reactions.

Once notified of suspected serious adverse reac-tions, Article 105 requires Member States to ensure that they are brought to the attention of the Agency, the other Member States and the marketing autho-risation holder within 15 days using the Agency’s data-processing network. Where, following an eval-uation of adverse reaction reports, a Member State decides that a marketing authorisation should be varied, suspended or revoked, Article 107 imposes an obligation to notify the Agency, other Member States and the marketing authorisation holder forthwith. In urgent cases, a Member State may suspend the market-ing authorisation of a medicinal product on the condi-tion that the Agency, Commission and other Member States are informed no later than the following working day.


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