Legal Updates - Marketing Authorisation Orphacol

Regulatory Law – Medicines – Marketing Authorisation Orphacol


In a recent decision, the General Court of the European Union overruled the European Commission’s decision not to grant Orphacol a marketing authorisation under Article 10a of Directive 2001/83/EC, after the European Commission went against the European Medicines Agency’s recommendation that a marketing authorisation be granted.


Article 10a of Directive 2001/83/EC


The usual position is that an application for a marketing authorisation in relation to a medicinal product must be accompanied by results of pre-clinical and clinical trials tests results.


Article 10a of Directive 2001/83/EC relating to medicinal products for human use (the “Directive”) allows for an applicant to obtain a marketing authorisation for a medicinal product if it can be shown that the active substance has a “well-established use”.


Article 10a of the Directive requires that the applicant:


"demonstrate that the active substances of the medicinal product have been in well-established medicinal use within the [EU] for at least 10 years, with recognised efficacy and an acceptable level of safety in terms of the conditions set out in Annex I".


Unlike a full application for marketing authorisation, under Article 10a the application does not need to submit pre-clinical or pre-trial data in relation to the safety and efficacy of the product. Article 10a of the Directive also allows the applicant to refer to a pre-existing marketing authorisation in relation to the same active substance, which is based on such data.




  • Laboratoires (Cell Therapies Research & Services) (“CTRS”) sought to obtain a centralised marketing authorisation under Article 10a (well-established use) for its medicinal product, Orphacol;
  • Orphacol is an orphan medicinal product that is used to treat rare but serious liver disorders;
  • The active ingredient in Orphacol is cholic acid;
  • The Committee for Medicinal Products for Human Use (“CMPHU”) of the European Medicines Agency (“EMA”) recommended that a marketing authorisation be granted to Orphacol;
  • The European Commission attempted to persuade the committee to change its opinion, without success;
  • The European Commission subsequently prepared a draft decision refusing to grant a marketing authorisation to Orphacol on the grounds that there was no legal basis for granting an authorisation;
  • Laboratoires CTRS appealed, seeking to annul the European Commission’s decision.




  • The European Commission argued that:
    • There was no proven well-established use of cholic acid;
    • It was inconsistent with the well-established medicinal use route for Laboratoires CTRS to have been able to rely on Article 22 of the Directive, which allows one to rely on “objective, verifiable reasons” for not providing comprehensive data on safety and efficacy.
    • The grant of such a marketing authorisation would undermine the objectives of the EU Paediatric Regulation (1901/2206) and the protection of innovation.


  • The General Court disagreed. In particular:
    • It noted the use of cholic acid as a hospital preparation in France between 1993 and 2007, provided on medical prescription. It held that ‘hospital preparations’ are covered by the Directive, specifically Article 5(1), which exempts certain medicinal products from the provisions of the Directive, including obtaining a marketing authorisation;
    • It held that there is nothing in the Directive that prevents one from applying the concepts of 'well-established medicinal use' as well as 'exceptional circumstances'. In this case, Laboratoires CTRS has justified why it is not possible to provide comprehensive information on the efficacy and safety of the orphan medicinal product and has justified the risk/benefit balance for that product by providing a list of bibliographical references to studies on cholic acid and demonstrating that it was unable to provide comprehensive data for objective, verifiable reasons: namely, the rareness of the disorders in question and ethical considerations.


  • The General Court upheld the appeal by Laboratoires CTRS and annulled the European Commission’s decision.


For any queries on marketing authorisations or other regulatory law issues, you may contact us by email Visit


© RT COOPERS, 2013. This Briefing Note does not provide a comprehensive or complete statement of the law relating to the issues discussed nor does it constitute legal advice. It is intended only to highlight general issues. Specialist legal advice should always be sought in relation to particular circumstances.


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