Actilyse - referral

Current status

European Commission final decision

Overview

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).

Summary information on a referral opinion following an arbitration pursuant to Article 29 of Directive 2001/83/EC, for Actilyse International Non-Proprietary Name (INN): Alteplase: Background information and Annex I

Adopted Reference Number: CPMP/3346/02-EN

Key facts

About this medicine

• Approved name:
  Actilyse
• International non-proprietary name (INN) or common name:
  alteplase

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  CPMP/3346/02
• Type:
  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.

Key dates and outcomes

• CHMP opinion date:
  27/06/2002
• EC decision date:
  30/09/2002

All documents

Summary information on a referral opinion following an arbitration pursuant to Article 29 of Directive 2001/83/EC, for Actilyse International Non-Proprietary Name (INN): Alteplase: Background information and Annex I

Adopted Reference Number: CPMP/3346/02-EN

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

• Overview - lay-language summary of the stage of the procedure
• Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
• Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
• List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
• Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
• List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
• List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
• Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
• Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
• Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
• Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
• Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
• Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.