1. 7 Types of Marketing Authorisation Applications

1.5. Well-established use application

Results of non-clinical tests and/or clinical trials are not required if the applicant can demonstrate that the active substances of the medicine have been in well-established medicinal use for at least ten years in the EU, with accepted efficacy and an acceptable level of safety. Results of non-clinical tests and/or clinical trials have to be replaced by detailed reference to appropriate scientific literature (information available in the public domain).

For such applications, Modules 1, 2 and 3 should be submitted following the provisions in Annex I to Directive 2001/83/EC. For Modules 4 and 5, a detailed scientific bibliography shall address all required non-clinical and clinical characteristics, and should be summarised in Module 2. They are considered as full and independent applications. If parts of the dossier are incomplete, such absences in the non-clinical/clinical overviews must be justified, as with any other full application.

Criteria to consider for well-established use:

  • the time over which a substance has been used with regular application in patients;
  • quantitative aspects of the use of the substance;
  • the extent of use on a geographical basis;
  • the extent to which the use of the substance has been monitored by pharmacovigilance or other methods;
  • the degree of scientific interest in the use of the substance (reflected in the published scientific literature) and the coherence of scientific assessments;

Legal basis: Article 10a of Directive 2001/83 (EC)