Legal framework: orphan designation
This page summarises the legal background to the procedure for orphan designation in the European Union (EU). It includes the key milestones in EU legislation adopted since the Orphan Regulation was first adopted in 1999.
The European Commission has conducted a comprehensive review of the strengths and weaknesses of the EU regulatory framework governing orphan medicines.
The evaluation found that the Orphan Regulation has fostered the development and availability of medicines for patients with rare diseases. It has redirected private and public investment towards previously neglected areas through incentives, obligations and rewards.
Thanks to the treatment with medicines for rare diseases, patients benefited from an improvement in their quality of life. However, it also found that it has not sufficiently managed to support development in areas where the need for medicines is greatest, and has increased costs for healthcare systems.
The European Commission evaluated the Orphan Regulation together with the Paediatric Regulation, with similar findings for both.
Both regulations set out to address the lack of medicines available for the patient groups concerned, and they often address the same therapeutic areas, since many childhood diseases are rare.
The outcome of this review is intended to guide future legislative changes and shape the EU’s pharmaceutical strategy.
Commission notice 2016/C 424/03
On 18 November 2016, the European Commission adopted Commission notice on the application of Articles 3, 5 and 7 of Regulation (EC) No 141/2000 on orphan medicinal products (2016/C 424/03), which is intended to facilitate the application of Articles 3 (criteria for designation), 5 (procedure for designation and removal from the register) and 7 (Union marketing authorisation) of Regulation (EC) No 141/2000. The notice replaces the Communication 2003/C 178/02 of 29 June 2003.
On 16 December 1999, the European Parliament adopted Regulation (EC) No 141/2000 (the Orphan Regulation). This was published in the Official Journal of the European Communities on 22 January 2000.
On 27 April 2000, the European Commission adopted Regulation (EC) No 847/2000, which:
- lays down implementing rules;
- sets out definitions essential for the application of the Orphan Regulation.
This Regulation entered into force on 28 April 2000. On this date, sponsors could begin to submit applications for orphan designation to the European Medicines Agency.
On 31 March 2004, the European Parliament adopted Regulation (EC) No 726/2004, which provides the legal framework for the centralised authorisation and supervision of medicines for human and veterinary use and establishes the European Medicines Agency (EMA). It determines that:
On 29 March 2006, the European Parliament adopted Regulation (EC) No 507/2006, which provides the legal framework for the granting of a conditional marketing authorisation to medicines that fall within the scope of Regulation (EC) No 726/2004. It establishes that orphan medicines can be granted a conditional marketing authorisation within this legal framework.
On 12 December 2006, the European Parliament adopted Regulation (EC) No 1901/2006 on medicinal products for paediatric use. It establishes that the usual period of market exclusivity for orphan medicines may be extended to twelve years if study results are submitted in compliance with an agreed paediatric investigation plan at the time of marketing authorisation.
On 15 December 2005, the European Commission adopted Regulation (EC) No 2049/2005 regarding the payment of fees to, and receipt of assistance from, the EMA by micro, small and medium-sized enterprises (SMEs). It determines that scientific advice and scientific services for designated orphan medicines shall be provided by the EMA to SMEs free of charge.
The European Commission has also issued guidelines on aspects of the application of the Orphan Regulation:
- Commission Notice 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 2022/C 440/02
- Guideline on aspects of the application of Article 8(1) and (3) of Regulation (EC) No 141/2000: Assessing similarity of medicinal products versus authorised orphan medicinal products benefiting from market exclusivity and applying derogations from that market exclusivity;
- Guideline on aspects of the application of Article 8(2) of Regulation (EC) No 141/2000 of the European Parliament and of the Council: Review of the period of market exclusivity of orphan medicinal products.