Medicinal products for human use

Orphan medicinal products - Major developments

Orphan medicinal products

Major developments

24/03/2017
Responses to the public consultations on the concept of "similar medicinal product" in the context of the orphan legislation.

A public consultation took place from 29 July 2016 to 04 November 2016 on the concept of "similar medicinal product" in the context of the orphan legislation.

A summary of the comments as well as the replies are available here.

18/11/2016
Commission notice on the application of Articles 3, 5 and 7 of Regulation (EC) N° 141/2000 on orphan medicinal products.

The European Commission published a guidance document on the application of certain key provisions within the orphan regulation (Articles 3, 5 and 7). It covers especially topics related to the designation of a medicinal product as an orphan development and/or orphan medicinal product. The notice updates and replaces a previous Commission Communication from 2003 in view of the experience acquired over the last 13 years. The new notice is available here.

02/03/2016
Responses to the public consultation on notice from the Commission on aspects of the application of Article 3, 5 and 7 of Regulation (EC) N° 141/2000 on orphan medicinal products.

A public consultation took place from 16 November 2015 to 15 February 2016 on notice from the Commission on aspects of the application of Article 3, 5 and 7 of Regulation (EC) N° 141/2000 on orphan medicinal products.

The responses to the public consultations can be found here.

29/01/2016
Today, the Commission publishes an inventory of Union and Member State incentives to support research into, and the development and availability of, orphan medicinal products.Commission report on orphan medicinal products

To date, the Commission has authorised 117 orphan medicines for the benefit of patients suffering from rare diseases, 82 % of which consist of new active substances. Some 25 orphan marketing authorisations are from SMEs. The number of products authorised has grown over the years (which is encouraging for the future), but remains limited bearing in mind the existence of 5 000 to 8 000 distinct rare diseases. We can conclude that just 1 % of these are currently covered by authorised medicinal products in the EU. The incentives of the orphan drug legislation are therefore essential to facilitate pharmaceutical development. The most frequently authorised medicinal products are treatments for pulmonary arterial hypertension, acute myeloid leukaemia, cystic fibrosis, multiple myeloma and acute or chronic lymphoblastic leukaemia.

This paper also includes information about the European expert group on rare diseases, the EU funded research on rare diseases and examples of national measures to support R&D and the availability of orphan medicinal products (e.g. reduction of taxes, pilot project on joint procurement, direct reimbursement after marketing authorisation, ...).

Inventory of Union and Member State incentives to support research into, and the development and availability of, orphan medicinal products — state of play 2015:

02/10/2014
Commission Call for Expressions of Interest for the position of member of the Committee for Orphan Medicinal Products (COMP) as representing patient organisations.

This call for expressions of interest relates to the appointment by the Commission of members representing patient organisations at the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency.

More detailed information and application documents are here.

28/03/2014
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, March 2014.

  • Annex to 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: PDF format - Word format.

25/10/2013
Responses to the public consultation on the 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.

A public consultation took place from 5 July 2013 to 30 September 2013 on the 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.

The responses to the public consultations can be found here.

21/01/2009
Implementation of the Regulation of Orphan Medicinal Products: Public call for expressions of interest for Commission appointees to the Committee for Orphan Medicinal Products of the European Medicines Agency.

The Commission publishes today a public call for expressions of interest related to the appointment by the European Commission of members representing patients' organisations at the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMEA).

The public call is available here.

Expressions of interest should be notified to the European Commission by e-mail to: entr-pharmaceuticals@ec.europa.eu.
The deadline for receipt of the notifications is Friday 13 March 2009.

19/09/2008
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.

This guideline concerns the granting of market exclusivity for authorised orphan medicinal products according to Article 8(1) of Regulation (EC) No 141/2000, in particular the assessment of the "similarity" criterion - and the granting of derogations from that market exclusivity under Article 8(3) of that regulation.

17/09/2008
Guideline on aspects of the application of Article 8(2) of Regulation (EC) No 141/2000: Review of the period of market exclusivity of orphan medicinal products.

This guideline concerns the review of market exclusivity for authorised orphan medicinal product according to Article 8(2) of Regulation (EC) No 141/2000. It sets out the general principles and procedures by which the period of market exclusivity of orphan medicinal products is reviewed and may be reduced from ten to six years.

11/07/2007
Update of the "Guideline on format and content of applications for designation as orphan medicinal products and on the transfer of designations from one sponsor to another".

The "Guideline on format and content of applications for designation as orphan medicinal products and on the transfer of designations from one sponsor to another" has been updated: sponsors will from now on be required to provide only ONE paper version of their application (instead of three paper versions); instead, an additional electronic version (CD Rom) will be requested.

24/10/2006
Update of the annex to Guideline on format and content of applications for designation as orphan medicinal products and on the transfer of designations from one sponsor to another.

In preparation of the coming enlargement, the annex to Guideline on format and content of applications for designation as orphan medicinal products and on the transfer of designations from one sponsor to another has been updated: Word format, revision October 2006.

07/09/2006
Inventory of Community and Member States' incentive measures to aid the research, marketing, development and availability of orphan medicinal products. Revision 2005.

The Regulation on Orphan Medicinal Products adopted in 2000 requires Member States to communicate to the Commission detailed information concerning any measure that they have enacted to support research into, and the development and availability of, orphan medicinal products or medicinal products that may be designated as such. On the basis of this information, the Commission prepared and published on 1 January 2001 a first detailed inventory of all incentives made available by the Community and the Member States to support research into and availability of orphan medicinal products, thus meeting its obligations according to the regulation. This inventory has been updated in 2006 for the second time.

27/06/2006
Commission Staff working document on the experience acquired as a result of the application of Regulation (EC) No 141/2000 on orphan medicinal products and account of the public health benefits obtained (Document on the basis of Article 10 of Regulation (EC) No 141/2000).

03/04/2006
Orphan Medicinal Products: Outcome of consultation on a general report on the experience acquired as a result of the application of Regulation (EC) 141/2000 on orphan medicinal products and account of the public health benefits obtained.

As required by Article 10 of Regulation (EC) 141/2000 on orphan medicinal products, the European Commission has drafted a Commission Staff Working Document on the experience acquired as a result of the application of Regulation (EC) 141/2000 on orphan medicinal products and account of the public health benefits obtained.
All interested parties were invited to comment on the draft Commission Staff Working Document until 8 March.

The outcome of the consultation is now published here until publication of final document.

08/02/2006
Consultation on a general report on the experience acquired as a result of the application of Regulation (EC) No 141/2000 on orphan medicinal products and account of the public health benefits obtained.

As required by Article 10 of Regulation (EC) No 141/2000 on orphan medicinal products, the European Commission has drafted a Commission report on the experience acquired as a result of the application of Regulation (EC) No 141/2000 on orphan medicinal products and account of the public health benefits obtained. All interested parties are invited to comment on the attached draft Commission Staff Working Document.

Comments should be sent to Elena Prats, European Commission, BREY 10/130, 1049 Brussels, Belgium.

E-mail submissions are preferred and should be sent to elena.prats@ec.europa.eu. The consultation will be closed on 8 March 2006.

20/12/2004
Study on the price of orphan drugs (see 16/11/04).

16/12/2004
Draft guideline on similarity of medicinal products and "clinical superiority" related to the orphan regulation.

The Commission invites comments on a draft guideline on similarity of medicinal products and "clinical superiority" related to the orphan regulation (Regulation (EC) No 141/2000 of the European Parliament and of the Council on orphan medicinal products). Comments should be sent by 4 February 2005 to Dr Peter Arlett, DG Enterprise and Industry. Electronic submissions are preferred and should be sent before the deadline to entr-pharmaceuticals@ec.europa.eu.

Please note that the guideline does not cover the application of Article 8 paragraph 2 of the Regulation relating to the reduction of the period of market exclusivity.

The draft guideline can be found here.

16/11/2004
Study on the price of orphan drugsThe Commission has published an independent study on the price of orphan drugs.

The study, conducted by Alcimed, looks at the price of orphan drugs authorised in the EU and how these prices were arrived at. In addition, the study discusses how sufficient profitability might be assessed and judged. This latter aspect relates to the operation of Article 8 (market exclusivity) of the Orphan Regulation (Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products).The study will inform discussions on the development of both guidelines relating to the operation of Article 8 and the 2006 Commission report foreseen in Article 10 of the Orphan Regulation. Any opinions in this report are those of the authors and do not necessarily reflect those of the European Commission.

Please note that the French version is the original one. The English version is a translation.

26/08/2004
Revised Commission guideline on applications for orphan medicinal products.

The 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" has been updated. The revisions to the guideline include reference to Icelandic and Norwegian participation in the designation process, EU Enlargement, and cross-reference to the Commission Communication (2003/C 178/02).The Commission conducted a three-month public consultation on the revisions.

Two responses to the consultation were received from the Bioindustry Association and the Emerging Biopharmaceutical Enterprises group within the European Federation of Pharmaceutical Industry Associations. The responses were carefully considered by the Commission in consultation with the EMEA Committee for Orphan Medicinal products. Where possible, the changes suggested in the responses have been included. Some of the suggestions were considered outside the scope of the current revision and will be taken into consideration in the overall review of the orphan regulation foreseen for 2005.

01/08/2003
Commission Communication on Regulation (EC) No 141/2000 on orphan medicinal products.

Following the first three years of application of the Regulation on orphan medicinal products, the Commission has issued a Communication which sets out a position on certain matters relating to the implementation of the designation and market exclusivity provisions. This has been done in response to requests for interpretation and clarification.

The Communication is intended to provide guidance to the European Medicines Evaluation Agency, the Member States, the pharmaceutical industry and other interested parties.

The Communication considers points in relation to:

  • Article 3 (criteria for designation)
  • Article 5 (procedure for designation and removal from the Community register on orphan medicinal products)
  • Article 7 (Community marketing authorisation)

In addition, the Commission is obliged to draw up detailed guidelines on the application of Article 8 of Regulation (EC) No 141/2000. This obligation is met in part by section D on market exclusivity (Article 8) in the Communication.

The Communication is published in the Official Journal of the European Union C 178, 29.07.2003, p. 2.

14/10/2002
First revision and update of guideline on format and content of applications for designation as orphan medicinal products and on the transfer of designations from one sponsor to another.

Following the end of the comment period, and in accordance with Article 5. 3 of Regulation 141/2000 on orphan medicinal products a first revision and update of the format and contents guideline is now available: PDF format - Word format.

27/08/2002
DG Enterprise publishes an update of the inventory of national and community measures supporting research into and availability of orphan medicinal products.

The Regulation on Orphan Medicinal Products adopted in 2000 requires Member States to communicate to the Commission detailed information concerning any measure that have enacted to support research into, and the development and availability of, orphan medicinal products or medicinal products that may be designated as such. On the basis of this information, the Commission prepared and published on 1 January 2001 a first detailed inventory of all incentives made available by the Community and the Member States to support research into and availability of orphan medicinal products, thus meeting its obligations according to the regulation. This inventory has been updated for the first time.

12/04/2002
Final version of guideline on format and content of applications for designation as orphan medicinal products and on the transfer of designations from one sponsor to another.

Following the end of the comment period, and in accordance with Article 5. 3 of Regulation 141/2000 on orphan medicinal products a final version of the format and contents guideline is now available.

The annex to this guideline is available here: PDF format - Word format.

12/02/2002
The Committee for Orphan Medicinal Products (COMP) list of members.

Following changes to the Committee an updated list of members is provided.

01/06/2001
DG Enterprise publishes its first inventory of national and community measures supporting research into and availability of orphan medicinal products inventory.

The Regulation on Orphan Medicinal Products adopted last year requires Member States to communicate to the Commission detailed information concerning any measure that have enacted to support research into, and the development and availability of, orphan medicinal products or medicinal products that may be designated as such. On the basis of this information, the Commission has prepared a first detailed inventory of all incentives made available by the Community and the Member States to support research into and availability of orphan medicinal products, thus meeting its obligations according to the regulation. This inventory shall be updated regularly.

04/09/2000
8th August 2000 Commission designates first three Orphan Medicinal Products.

Following the entry into force of the regulation on Orphan Medicinal Products, the Commission, on 8th August 2000, adopted the first three Community decisions designating potential new compounds as Orphan medicinal products. These medicinal products have now been entered into the newly created Community Register for Orphan medicinal products. It should however be noted that the safety, efficacy and quality of these products have not yet been assessed through the Community marketing authorisation procedures and therefore they cannot at this time be marketed in the European Community.

28/04/2000
Rules on Orphan Medicinal Products become applicable.

On 27 April 2000, the Commission adopted a regulation laying down implementing rules and setting out definitions essential for the application of the regulation on Orphan Medicinal Products. This means that companies may, as from 28 April submit applications for designation as Orphan Medicinal Products to the EMEA for consideration by the newly created Committee of Orphan Medicinal Products.

Submitted applications must be in accordance with the criteria laid down in this regulation draft guidelines on format and content, application forms and will be validated by the EMEA to ensure that all required documentation has been submitted before being provided in summary form to the Committee.

14/04/2000
Commission nominates members of the Committee for Orphan Medicinal Products.

The recently adopted regulation on Orphan Medicinal Products creates a new Committee, the Committee for Orphan Medicinal Products, responsible for providing opinions on whether or not a new medicinal product should be designated as an Orphan Medicinal Product. Designation allows the medicinal product concerned access to a series of incentives including market exclusivity, fee waivers and assistance with the protocols for clinical trial investigations. This Committee marks an important step in the increasing co-operation between regulatory authorities and patients, being the first European Scientific Committee to have representatives from patient organisations as full members. Based on an internal selection procedure the Committee has nominated the following members to represent patient organisations, Yann Le Cam, Moises Abascal Alonso, representing the European Association for Orphan Diseases, Eurordis and Alastair Kent representing the European Alliance of Genetic Support Groups. The Commission also nominated Professor Jean-Michel Alexandre, Dr. Mary Teeling, current president and vice president of the CPMP and Dr. Gianmartino Benzi who is on the management board of the EMEA to facilitate close liaison and interaction with the work of the EMEA.

The list of members from the EU Member States is provided here.

31/03/2000
COMMISSION REGULATION 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".

Standing Committee gave a positive opinion on 23 March 2000. The agreed text is available here.

This text is now subject to linguistic verification by Member States before it will be finally adopted by the Commission.

24/01/2000
Regulation on Orphan Medicinal Products enters into force.

On 22/1/2000, Regulation (EC) No.141 /2000 of the European Parliament and of the Council of on Orphan Medicinal Products was published in Official Journal of the European Communities L18. According to Article 10 of this regulation, the regulation is now in force. Applications will be accepted from the date of adoption of its implementing regulations. The Commission is currently preparing the first draft of an implementing regulation as foreseen in Article 3(2) and Article 8(4).

15/12/1999
Regulation on Orphan Medicinal Products, European Parliament, Strasbourg, 15th December 1999.

The European parliament accepted the common position of the Council on the proposal for a regulation on Orphan medicinal products without amendment - an example of the increasing co-operation between the European institutions. This regulation, which was proposed by the Commission in July 1998, offers incentives to encourage the research, development and marketing of medicines to treat rare diseases, thus providing patients with these diseases with new possibilities for treatment. The regulation will enter into force on the date of its publication in the Official Journal, and will apply from the date of adoption by the Commission of two implementing regulations, which are currently being drafted by the Commission, foreseen for early March 2000.

20/10/1999
European Parliament adopts timetable for second reading of Regulation on Orphan Medicinal products.

Mme. Grosstête has been apppointed as rapporteur.

27/09/1999
Council reaches common position on amended Orphan Medicinal Products regulation.

Formal agreement on a common position on a draft regulation on Orphan Medicinal products was reached in Strasbourg. The text will now be forwarded to the European Parliament for its second reading.

23/06/1999
Council reaches political agreement on amended Orphan Medicinal Products regulation.

Luxembourg, 21 June 1998. The Internal market Council reached a unanimous political agreement on a common position on a draft regulation on Orphan Medicinal products (see news of 15 June). The common position will be formally adopted at the next Council meeting after linguistic and legal verifications.

15/06/1999
The Commission adopted its amended proposal for a European Parliament and Council Regulation on Orphan Medicinal Products on 15th June.

The amended proposal takes account of the amendments proposed by the European Parliament and preliminary discussions in Council. The proposal aims to establish a centralised procedure for the designation of orphan medicinal products and to put in place incentives for the research, marketing and development of orphan medicinal products, in particular by the granting of a 10 year market exclusivity period post authorisation for designated products.

27/07/1998
The European Commission has adopted a Proposal for a European Parliament and Council Regulation on Orphan medicinal products.

The aim of this proposal is to establish a Community procedure for designating orphan medicinal products and to introduce incentives for the research, development and marketing of orphan medicinal products, by providing : protocol assistance, direct access to the Community centralised procedure, fee waivers, and exclusive marketing rights for a ten year period.

Additional information: