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Published by EMA News 31/10/2013

Amendments of the European Union (EU) pharmacovigilance legislation that were adopted in October 2012 came into force on Monday 28 October 2013. These changes, which cover various aspects of the legislation, aim to further strengthen the protection of patient health by increasing the ability of the European medicines network to take prompt and appropriate regulatory action.

The amendments include changes to notification requirements. Since 28 October 2013, marketing-authorisation holders of human medicines have had to notify EU regulators of any action to withdraw a product from the market, together with the reason for this action. These notifications need to be sent to the European Medicines Agency both for centrally and for nationally authorised medicines, and also to the concerned Member States for nationally authorised medicines, when the decision to withdraw the product is based on any of the following grounds:

the medicine is harmful;
the medicine lacks therapeutic efficacy;
the benefit-risk 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.
These requirements apply for the following actions:

a temporary or permanent marketing cessation or suspension of marketing of a medicine;
a withdrawal of a medicine from the market;
a request to withdraw a marketing authorisation;
the intention not to apply for the renewal of a marketing authorisation.
Specific notification requirements apply, depending on whether the medicine is centrally authorised or nationally authorised and whether the action is taken within the EU or outside of the EU. Further details on these requirements are described in Withdrawals and cessation of centrally and nationally authorised medicines: questions and answers. The notifications of the (intended) actions and related reasons should be sent to the Agency using a specific template and cover letter via the email address withdrawnproducts@ema.europa.eu, and to the competent authorities of the Member States concerned as applicable.

These new requirements are without prejudice to any other existing notification obligations related to medicinal products (e.g. quality defects, pharmacovigilance issues, etc.).

The Agency is actively investigating whether these notification requirements can be combined with updates to the Article-57(1)(l) database in the longer term.

The Agency will regularly publish a list of medicines for which a marketing authorisation has been refused, revoked or suspended in the EU, whose supply has been prohibited or which have been withdrawn from the market, including the reasons for such actions.

Other aspects of the amendments

The 2012 amendments of the pharmacovigilance legislation include other aspects that also apply from 28 October 2013:


The amendments have clarified the scope and strengthened safety-referral procedures in the EU, to improve coordination and facilitate swift action and assessment, for the benefit of public health.

With regard to the Article-107i referral procedure, the ‘urgent Union procedure’, the legislation now foresees that a referral procedure will be automatically triggered at the EU level if a Member State or the European Commission, takes any of the following actions as a result of the evaluation of data resulting from pharmacovigilance activities:

suspension or revocation of a marketing authorisation;
prohibition of the supply of a medicine;
refusal of the renewal of a marketing authorisation.
An Article-107i referral procedure will also be automatically triggered if a Member State or the Commission is informed by a marketing-authorisation holder that, on the basis of safety concerns, it has interrupted the placing on the market of a medicine or has taken action to have a marketing authorisation withdrawn, or that it intends to do so.

In cases where a Member State or the Commission considers a new contra-indication, a reduction in the recommended dose or a restriction of indication to be necessary for a medicine, but when this is not an urgent measure, the case will be brought to the attention of the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) for coordination of action at EU level.

With regard to Article-31 referral procedures, the amendments foresee that the Commission or a Member State can decide to suspend or prohibit the use of a medicine at any stage of the procedure when it considers this necessary to protect public health, as a temporary measure until a definitive decision on the referral is adopted. The amendments also stipulate that for procedures covering a range of medicines, centrally authorised medicines shall be included in the procedure whether the grounds for the procedure are based on safety, efficacy or quality issues.

The Agency’s guidance documents will be updated to describe these new requirements within the next few weeks.

Translation exemption

To facilitate the availability of medicines across the EU, the 2012 amendments of the pharmacovigilance legislation have extended the scope of translation exemptions to include cases of severe issues of availability, including shortages of medicines. In these cases, the marketing-authorisation holder can request an exemption to translate the package leaflet, and now also the labelling, of the medicine into the official languages of the Member State concerned. Prior to these amendments, translation exemptions already applied to medicines intended for the treatment of rare conditions and medicines that are administered by healthcare professionals only.

These requirements are described in the European Commission’s guideline on the packaging information of medicinal products for human use authorised by the Union.

Additional monitoring

The mandatory scope of the medicines subject to additional monitoring has been extended to include:

medicines given conditional approval or authorised under exceptional circumstances and medicines authorised with specific obligations on the recording or monitoring of suspected adverse drug reactions;
medicines for which the marketing-authorisation holder is required to carry out a post-authorisation safety study (PASS).