Ciclosporin IDL - referral

Current status

European Commission final decision

Overview

On 23 April 2009, the European Medicines Agency completed an arbitration procedure following a disagreement among Member States of the European Union (EU) regarding the authorisation of the medicine Ciclosporin IDL. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of Ciclosporin IDL do not outweigh its risks, and that the marketing authorisation granted in the Netherlands cannot be recognised in other Member States of the EU and that the marketing authorisation in the Netherlands should be suspended.

The company that markets Ciclosporin IDL, International Drug Licensing, requested a re-examination of the opinion. After having considered the grounds for this request, the CHMP re-examined the initial opinion, and confirmed the recommendation for the refusal and suspension of the marketing authorisation on 23 July 2009.

The review was carried out under an 'Article 29' referral¹.

A European Commission decision on this opinion will be issued in due course.

¹ Article 29 of Directive 2001/83/EC as amended, referral on the grounds of potential serious risk to public health

What is Ciclosporin IDL?

Ciclosporin IDL is an immunosuppressive medicine (a medicine that reduces the activity of the immune system, the body's natural defences). It is used in patients who have had a transplant, to prevent rejection (when the immune system attacks the transplanted organ). It is also used to treat or prevent graft-versus-host disease (when the immune system of the transplanted organ attacks the patient's tissues).

Ciclosporin IDL is also used to treat autoimmune diseases. An autoimmune disease is a disease which is caused by the body's own defence system attacking normal tissue, such as psoriasis (a disease causing red, scaly patches on the skin), atopic dermatitis (eczema, an itchy red rash), nephrotic syndrome (a kidney disease) and rheumatoid arthritis (inflammation of the joints).

The active substance in Ciclosporin IDL, ciclosporin, acts on some special cells in the immune system called T-cells that are responsible for attacking transplanted organs or, in auto-immune diseases, normal tissue.

Ciclosporin IDL is a generic medicine that is based on a reference medicine authorised in Germany (Sandimmun Optoral 25 mg capsules).

Why was Ciclosporin IDL reviewed?

The company International Drug Licensing (IDL) submitted Ciclosporin IDL for mutual recognition on the basis of the initial authorisation granted by the Netherlands on 10 August 2007. The company wanted the authorisation to be recognised in Belgium, Germany, Italy, Spain, Sweden and the United Kingdom (the 'concerned Member States'). However, because the concerned Member States were not able to reach an agreement, the Dutch medicines regulatory agency referred the matter to the CHMP for arbitration on 2 December 2008.

The grounds for the referral were that five of the concerned Member States did not agree that enough evidence had been presented to show that Ciclosporin IDL was 'bioequivalent' to the reference medicine. Two medicines are bioequivalent when they produce the same levels of the active substance in the body.

What are the conclusions of the CHMP?

Based on evaluation of the currently available data and the scientific discussion within the Committee, the CHMP was of the opinion that bioequivalence between Ciclosporin IDL and the reference medicine had not been sufficiently demonstrated. The CHMP therefore concluded that the benefits of Ciclosporin IDL do not outweigh its risks, and that the marketing authorisation should not be granted in the concerned Member States. In addition the Committee has also recommended that the marketing authorisation for Ciclosporin IDL in the Netherlands and other member states in the EU where the product has been authorised should be suspended until satisfactory bioequivalence data are obtained.

The CHMP opinion was confirmed after re-examination.

The European Commission issued a decision on 22 July 2010.

Questions and answers on the referral for Ciclosporin IDL and associated names capsules containing ciclosporin 25 mg, 50 mg and 100 mg - Re-examination

AdoptedReference Number: EMEA/CHMP/466894/2009 Rev.1

Key facts

About this medicine

• Approved name:
  Ciclosporin IDL
• International non-proprietary name (INN) or common name:
  ciclosporin

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-29/1105
• 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:
  18/03/2010
• EC decision date:
  22/07/2010

All documents

Questions and answers on the referral for Ciclosporin IDL and associated names capsules containing ciclosporin 25 mg, 50 mg and 100 mg - Initial

AdoptedReference Number: EMEA/CHMP/71684/2009

European Commission final decision

Ciclosporin IDL - Article-30 referral - Annex I, II, III

Questions and answers on the referral for Ciclosporin IDL and associated names capsules containing ciclosporin 25 mg, 50 mg and 100 mg - Re-examination

AdoptedReference Number: EMEA/CHMP/466894/2009 Rev.1

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.