The EMA has a coordinating role in the decision-making process at the European level. Several committees have been appointed within the EMA to perform scientific evaluations and to provide advice about the safety of medicinal products.

The primary committee involved in this is the Pharmacovigilance Risk Assessment Committee (PRAC). There is also a role for the Committee for Medicinal Products for Human Use (CHMP) and the Committee for Advanced Therapies (CAT) where centrally authorised products are concerned. The Coordination Group for Mutual Recognition and Decentralised Procedures – human (CMDh), which forms part of the Heads of Medicines Agencies (HMA), plays a role in the products that are authorised nationally and via the mutual recognition procedure or decentralised procedure. The MEB is represented on the above-mentioned committees and in the coordination group.

The PRAC plays an important role in monitoring the safety of human medicinal products in Europe. The appointment of this scientific committee is a direct result of the pharmacovigilance legislation that came into effect in July 2012. The PRAC processes questions related to the risks of a medicinal product or group of medicinal products and drafts recommendations about this. These recommendations are then sent to the CHMP or the CMDh, depending on the admission procedure for the medicinal product.

Decision-making process at the European level

Referral procedures

A referral is a procedure that is implemented to discuss concerns about the benefit-risk assessment of a medicinal product or a group of medicinal products at a European level. In this procedure, one of the Member States (or the European Commission for centrally authorised products) will refer a specific medicinal product or a group of medicinal products to the Pharmacovigilance Risk Assessment Committee (PRAC). A referral procedure is started automatically if one of the Member States takes action (for example, suspension) relating to a nationally authorised product or has stated the intention to do so.

The transparency surrounding the procedures has also improved since the implementation of the new legislation and the risk-related referral procedures are listed extensively and in a timely manner in the reports surrounding the PRAC, including the timelines associated with the evaluation.

There are various types of referral procedures. Three procedures relate to the risks, quality or efficacy of medicinal products: the Article 107i Urgent Union procedure, the Article 31 procedure and the Article 20 procedure. The abovementioned articles refer to the amended European Directive 2001/83/EC.

Article 107i Urgent Union procedure

This referral procedure is implemented if a Member State or the European Commission deems urgent action necessary due to concerns about the safety of a medicinal product or group of medicinal products. This procedure must also be followed if a Member State announces the intention to take action, such as the suspension of a medicinal product.

This procedure is used to determine whether the marketing authorisation for a medicinal product must be suspended – or withdrawn – or whether the marketing authorisation/product information must be amended, such as an adjusted dose, indications or contra-indications. This procedure must be completed by the PRAC within a strict period of 60 days. In practice, this equates to the period of three consecutive PRAC meetings. The list of questions for the authorisation holders is drafted during the first meeting.

Article 31 procedure

This referral procedure comes into effect if the interests of the European Union are involved, if there are concerns related to the quality, safety or efficacy of a nationally authorised medicinal product or a group of nationally authorised medicinal products. The aim is the same as an Article 107i Urgent Union procedure, but the need to take action is deemed as less urgent. The timeframe maintained by the PRAC is less stringent than for an Article 107i Urgent Union procedure.

Article 20 procedure

This referral procedure is started by the director of the EMA and concerns medicinal products that are authorised via the central procedure and deals with matters such as the quality and safety or efficacy of medicinal products. Again, this procedure is used to determine whether the marketing authorisation for a medicinal product must be suspended – or withdrawn – or whether the marketing authorisation/product information must be amended, such as an adjusted dose, indications or contra-indications.

Handling of PRAC recommendations

In the event of a centrally authorised product, the PRAC recommendation is sent to the CHMP. The CHMP will then make a decision within 30 days based on a majority of votes (a so-called “Opinion”), which is sent to the European Commission. The authorisation holders have the option to appeal against the decision by the CHMP before it is sent to the European Commission.

For a product that is nationally authorised or authorised nationally via the Mutual recognition or Decentralised procedure, the recommendation by the PRAC is sent to the CMDh. Under the new pharmacovigilance legislation, all nationally authorised medicinal products that are referred for review by the PRAC due to a potentially severe risk to public health are discussed by the CMDh (these used to be dealt with via the CHMP). If the Member States in the CMDh reach a unanimous decision, their decision can be enforced immediately. If the decision is not unanimous, both the majority view and the minority view(s) of one or more Member States will be submitted to the European Commission.

A legally binding decision will only come into force once the European Commission has ruled on the matter (or possibly sooner in the event of nationally authorised products, provided that the CMDh was unanimous). If the European Commission or a Member State deems that further discussion of the majority view of the CHMP or CMDh with all Member States is necessary, a Standing Committee can be convened for the decision-making process. So-called “weighted votes” are then used to make a decision (the number of votes that a country has is determined by the number of residents of that country).

However, if the PRAC is of the opinion that urgent action is required, it has a mandate to advise interim measures, for example by informing the professional groups directly by means of a Direct Healthcare Professional Communication (DHPC) about changes in the use of a medicinal product or – in extreme cases – to recommend that countries withdraw a product from the market immediately if this is necessary.