Orphan drug designation in Europe-Procedural guidance and challenges
The European legislative framework on orphan medicinal products was implemented to stimulate the development of medicinal products against rare diseases and to ensure the patient’s adequate access to qualitative and specific treatment methods. Between 2000 and 2018 3210 orphan drug designation applications were submitted in Europe of which 2121 orphan designations have been issued by the European Commission. (1) Though the definitions for orphan medicinal products and the regulatory procedures are well defined, a high degree of regulatory knowledge is needed and strategic decisions on the development program must be considered at a very early stage of development: in fact, only 164 of the 2121 designated orphan development products have resulted in authorised orphan medicinal products since the orphan legislation was implemented.
In this article, the requirements and procedures for the orphan designation application and maintenance at the time of marketing authorisation application are discussed in the context of the European Regulation.
2. European Commission. Regulation (EC) No. 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products [Internet]. EC; 1999 [cited 2019 Jul 22]. Available from:
3. EUCERD Joint Action. 2014 Report on the state of the art of rare disease activities in Europe. Part I: Overview of rare disease activities in Europe [Internet]. EUCERD; 2014 [cited 2019 Jul 25]. Available from:
4. EURORDIS Rare diseases Europe. What is a rare disease? [Internet]. 2007 [cited 2019 Jul 27]. Available from:
5. Giannuzzi V, Landi A, Enrico B, Giannuzzi F, Nicotri S, Torrent-Farnell J, et al. Failures to further developing orphan medicinal products after designation granted in Europe: an analysis of marketing authorisation failures and abandoned drugs. BMJ Open. 2016; 7:e017358.
6. European Commission. Regulation (EC) No 847/2000 of 27 April 2000 laying down the provisions for implementation of the criteria for designation of a medicinal product as an orphan medicinal product and definitions of the concepts ‘similar medicinal product’ and ‘clinical superiority’ [Internet]. EC; 2000 [cited 2019 Jul 27]. Available from:
7. European Commission. Commission Regulation (EU) 2018/781 of 29 May 2018 amending Regulation (EC) No 847/2000 as regards the definition of the concept ‘similar medicinal product’ [Internet]. EC; 2018 [cited 2019 Jul 24]. Available from:
https://eur-lex.europa.eu/legal-content/EN/TXT/ PDF/ ?uri=CELEX:32018R0781&from=EN
8. European Medicines Agency. Applying for orphan designation [Internet]. 2019 [cited 2019 Jul 28]. Available from:
9. European Commission. Guideline on the format and content of applications for designation as orphan medicinal products and on the transfer of designations from one sponsor to another, 27.03.2014 [Internet]. EC; 2014 [cited 2019 Jul 26]. Available from:
10. Committee for orphan medicinal products (COMP). Points to consider on the estimation and reporting on the prevalence of a condition for the purpose of orphan designation. EMA/COMP/436/01 Rev. 1 [Internet]. EMA; 2019 [cited 2019 Jul 27]; Available from:
11. Richter T, Nestler-Parr S, Babela R, Khan Z M, Tesoro T, Molsen E, et al. Rare Disease Terminology and Definitions - A Systematic Global Review: Report of the ISPOR Rare Disease Special Interest Group. Value Heal. 2015;18(6):906-14.
12. European Commission. Regulation(EC) No 726/2004 of the European parliament and of the council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a Europ. Medicines Agency [Internet]. EC; 2004 [cited 2019 Jul 23]. Available from:
13. European Medicines Agency. Standard operating procedure SOP/H/3190. Review of orphan designation at the time of granting/varying a marketing authorisation [Internet]. EMA; 2017[cited 2019 Jul 21]. Available from:
14. European Commission. Community Register of orphan medicinal products [Internet]. 2019 [cited 2019 Jul 08]. Available from:
15. Medicines and Healthare products Regulatory Agency. Further guidance note on the regulation of medicines, medical devices and clinical trials if there’s no Brexit deal [Internet]. 2019 [cited 2019 Jul 28]. Available from:
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