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  • Under evaluation
  • CHMP opinion
  • European Commission final decision
Current status:
European Commission final decision


On 30 September 2002, the European Commission issued a Decision valid throughout the European Union for the medicinal product Actilyse, which contains alteplase. This decision was based on the arbitration assessment report and on the favourable opinion adopted by the Committee for Proprietary Medicinal Products (CPMP) on 27 June 2002. The Marketing Authorisation Holder responsible for this medicinal product is Boehringer Ingelheim Pharma KG.

The new approved indication subject of arbitration is “for fibrinolytic treatment of acute ischemic stroke”.

Between 12 September and 14 September 2000 Boehringer Ingelheim Pharma KG, submitted applications for Mutual Recognition of the Marketing Authorisation granted on 21 August 1999 by the German Competent Authorities, acting as Reference Member State, for Actilyse, powder and solvent for solution for injection and infusion. The Mutual Recognition procedure started on 23 September 2000. The Concerned Member States were Austria, Belgium, Denmark, Greece, Spain, Finland, Ireland, Italy, Luxemburg, France, the Netherlands, Portugal, Sweden and the United Kingdom. The Concerned Member States; the Netherlands, Spain, Greece and the United Kingdom, not being able to agree with the Mutual Recognition of the Marketing Authorisation granted by the Reference Member State referred the reasons for disagreement to the EMEA on 22 December 2000.

The main points to be considered by the CPMP were:

  • Whether there is sufficient clinical data with reference to efficacy as well as safety e.g. risk of intra-cranial bleeding, to grant a Marketing Authorisation for the new indication 'For fibrinolytic treatment of acute ischaemic stroke' without putting public health at risk. In particular, the major concern for most of the Concerned Member States was the lack of replication of the favourable results of the pivotal US trial (Study NINDS B) in the European studies (ECASS-I and ECASS-II) as well as in another US trial (Atlantis);
  • The need to introduce further requirements in the SPC to ensure a safe use of the product.

The Reference Member State sent its report to the EMEA on 10 January 2001. The matter was referred to the CPMP on 25 January 2001. The Marketing Authorisation Holder provided supplementary information on 9 August 2001. Written explanations were provided by the Marketing Authorisation Holder on 22 March 2002 and on 29 May 2002. Additional written explanations were provided on 20 June 2002. The Marketing Authorisation Holder provided oral explanations at a hearing before a CPMP Ad Hoc expert group on 22 April 2002 and at hearings before the CPMP plenary on 20 February 2002 and 23 April 2002.

An overall summary of the scientific evaluation is provided, together with the amended Summary of Product Characteristics (SPC) of the Reference Member State (see Annex I).

Key facts

Approved name
International non-proprietary name (INN) or common name


Reference number
Article 29(4) referrals

This type of referral is triggered when there is a disagreement between Member States regarding a marketing authorisation application being evaluated in a mutual-recognition or decentralised procedure, on the grounds of a potential serious risk to public health.

European Commission final decision
Opinion date
EC decision date

All documents

Document description

  • Questions and answers (Q&A) - easy-to-understand summary of key issues and Committee conclusions
  • Summary of Opinion - contains the CHMP opinion of the referred medicine(s)
  • List of the medicines affected by the referral (Annex I)
  • Scientific conclusions of the Committee (Annex II)

The following two documents are sometimes available:

  • Changes to the summary of product characteristics, labeling or package leaflet (also known as Annex III) - available when changes havebeen recommended by the Committee
  • Conditions of the marketing authorisation (also known as Annex IV) - available when the Committee recommends measures to be takenfor the marketing authorisation(s) such as safety measures or extra studies

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