Activelle - referral

Current status

European Commission final decision

Overview

Activelle and associated names, estradiol 0.5mg and norethisterone acetate 0.1 mg film-coated tablets is a continuous combined hormone replacement therapy (HRT) for oestrogen deficiency symptoms in women more than one year after menopause.

Novo Nordisk A/S submitted applications for mutual recognition of Activelle and associated names, estradiol 0.5mg and norethisterone acetate 0.1 mg film-coated tablets on the basis of the marketing authorisation granted by Sweden on 3 August 2007. The Mutual Recognition Procedure started on 20 September 2007. The Reference Member State was Sweden and the Concerned Member States were Austria, Belgium, Bulgaria, Czech Republic, Germany, Denmark, Estonia, Spain, Finland, France, Hungary, Ireland, Iceland, Italy, Lithuania, Luxembourg, Latvia, Netherlands, Norway, Portugal, Romania, Slovenia, Slovak Republic and United Kingdom. These Member States were not able to reach an agreement in respect of the Mutual Recognition of the Marketing Authorisation granted by the Reference Member State. Sweden referred the reasons for disagreement to the EMEA on 3 March 2008.

Significant difference has been identified with regard to clinical safety. This refers to endometrial safety of Activelle 0.5 mg/0.1 mg, which had been insufficiently demonstrated according to the CHMP guideline for HRT products (EMEA/CHMP/021/97 rev 1) and this was considered to be of serious public health concern.

The arbitration procedure started on 19 March 2008 with the adoption of a list of questions. The Rapporteur was Dr Pierre Demolis (FR) as Rapporteur and Co-Rapporteur(s) was Dr Ingemar Persson (SE). The Marketing Authorisation Holder provided written explanations on 5 May 2008.

During their June 2008 meeting, the CHMP, in the light of the overall data submitted and the scientific discussion within the Committee, was of the opinion that the benefit/risk ratio is favourable for Activelle and associated names, that the objections raised by France and Germany should not prevent the granting of a Marketing Authorisation and that the Summary of Product Characteristics, labelling and package leaflet of the Reference Member State should be amended. A positive opinion was adopted by majority on 26 June 2008.

The list of the product names concerned is given in Annex I. The scientific conclusions are provided in Annex II, together with the Summary of Product Characteristics in Annex III.

The final opinion was converted into a Decision by the European Commission on 11 September 2008.

Opinion following an Article 29(4) referral for Activelle and associated names International Non-Proprietary Name (INN): estradiol and norethisterone acetate: Background information

Adopted Reference Number: EMEA/CHMP/496102/2008

Key facts

About this medicine

• Approved name:
  Activelle
• International non-proprietary name (INN) or common name:
  • estradiol
  • norethisterone acetate

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  CHMP/336151/08
• 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:
  26/06/2008
• EC decision date:
  11/09/2008

All documents

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

Adopted

Opinion following an Article 29(4) referral for Activelle and associated names International Non-Proprietary Name (INN): estradiol and norethisterone acetate: Background information

Adopted Reference Number: EMEA/CHMP/496102/2008

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.