Botox - referral

Current status

European Commission final decision

Overview

Botox [Clostridium botulinum toxin type A neurotoxin complex] inhibits the release of acetylcholine at the presynaptic membrane on cholinergic neurons. Botox was first licensed in the European Union in 1994 for neuromuscular disorders via intramuscular route.

In June 2002, the Marketing Authorisation Holder, Allergan Pharmaceuticals (Ireland) Ltd applied for a new indication through Mutual Recognition Procedure (MRP), for Botox for the treatment of axillary hyperhidrosis. Primary hyperhydrosis is a chronic idiopathic disorder of excessive and uncontrolled sweating. The mechanism of action of Botox in hyperhidrosis is thought to be the inhibition of cholinergically-induced excessive sweating by blockage of autonomic sympathetic nerve fibres innervating sweat glands.

The Reference Member State for this MRP was Ireland with Austria, Belgium, Denmark, Germany, Greece, Finland, Iceland, Italy, Luxembourg, Norway, Portugal, Spain, and Sweden as Concerned Member States. On September 3rd 2002 a referral for arbitration according to article 29 of Directive 2001/83/EC was triggered by Germany and Italy regarding the major objections on the clinical safety and efficacy of this new indication for the medicinal product Botox.

The procedure started on 17 October 2002. Supplementary information was provided by the Marketing Authorisation Holder on 11 November 2002 and further written explanations on 5 February 2003.

The CPMP, having considered the points of disagreement and the responses provided by the Marketing Authorisation Holder, was of the opinion that the objections raised by Germany and Italy should not prevent the granting of a Marketing Authorisation for the new indication “persistent severe primary hyperhidrosis of the axillae, which interferes with the activities of daily living and is resistant to topical treatment” subject to certain essential conditions for the safe and effective use of the medicinal product. The CPMP adopted a positive opinion on 20 February 2003.

The scientific conclusions and the grounds for the amendment of the Summary of Product Characteristics are set out in Annex II.

The final opinion was converted into a decision by the European Commission on 25 June 2003.

Summary information on referral opinion following arbitration pursuant to Article 29 of Council Directive 2001/83/EC for Botox Active substance: Clostridium Botulinum type A neurotoxin complex: Background information

Adopted Reference Number: EMEA/CPMP/4260/03/en

Key facts

About this medicine

• Approved name:
  Botox
• International non-proprietary name (INN) or common name:
  Clostridium botulinum type A neurotoxin complex

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  CPMP/4260/03
• 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:
  21/02/2003
• EC decision date:
  25/06/2003

All documents

Botox - Article 29 referral - Annex I, II, III

Adopted

Summary information on referral opinion following arbitration pursuant to Article 29 of Council Directive 2001/83/EC for Botox Active substance: Clostridium Botulinum type A neurotoxin complex: Background information

Adopted Reference Number: EMEA/CPMP/4260/03/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.