COMMISSION STAFF WORKING DOCUMENT EXECUTIVE SUMMARY OF THE EVALUATION Joint evaluation of Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products
Date: 2020-08-11
Institutions: Directorate-General for Health and Food Safety, European Commission
Subjects: drug surveillance, drugs classification, generic drug, innovation, market approval, medical research, orphan disease, orphan drug, paediatrics, therapeutics

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  EN 

   EUROPEAN COMMISSION  Brussels, 11.8.2020  SWD(2020) 164 final  COMMISSION STAFF WORKING DOCUMENT  EXECUTIVE SUMMARY OF THE EVALUATION  Joint evaluation of Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products {SEC(2020) 291 final} - {SWD(2020) 163 final}  
 
 
1.  CONTEXT 

In the 1980s and 1990s, the level of awareness concerning the lack of satisfactory treatments 
for patients with rare diseases and for children in the EU started to increase. 

The pharmaceutical industry showed insufficient interest in investing in the development of 
medicines for rare diseases and for children. Doctors treating patients with rare diseases often 
had no medicines available, and a similar situation occurred for children. In 2000 and 2007 
the EU therefore introduced two regulations to foster the development of medicines for rare 
diseases1 and for children2. 

The  results  of  the  evaluation  will  guide  reflections  on  any  future  changes  to  the  legislative 
framework. It will also inform the EU’s pharmaceutical strategy, which seeks to improve and 
accelerate  patients’  access  to  safe,  effective  and  affordable  medicines  and  to  support 
innovation in the EU pharmaceutical sector.  

2.  EVALUATION 

The evaluation assesses the strengths and weaknesses of the two regulations over 2000-2017 
(medicines for rare diseases) and 2007-2017 (medicines for children). It follows an evidence-
based  analysis  of  the  functioning  of  the  two  instruments  from  a  public  health  and  socio-
economic  perspective.  The  two  regulations  are  evaluated  together  as  the  majority  of  rare 
diseases may appear already in children and many children’s diseases are also rare. 

Three independent studies3 were used, as well as reports by the European Commission4 and 
the European Medicines Agency.5 The evaluation also gathered information from all relevant 
interested  parties  through  workshops,  public  and  targeted  consultations.  Triangulation  of 
information has been sought through the use of different sources of information and inclusion 
of  a  large  number  of  stakeholders.  However,  some  areas  are  supported  by  less  robust 
evidence than others. That was in particular the case for the baseline scenario and the cost-
benefit assessment. 

1 Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan 
medicinal products. 
2 Regulation  (EC)  No  1901/2006  of  the  European  Parliament  and  of  the  Council  of  12  December  2006  on 
medicinal  products  for  paediatric  use  and  amending  Regulation  (EEC)  No  1768/92,  Directive  2001/20/EC, 
Directive 2001/83/EC and Regulation (EC) No 726/200. 
3 Study on the economic impact of the Paediatric Regulation, including its rewards and incentives; Orphan study 
report (2019); Study on the economic impact of supplementary protection certificates, pharmaceutical incentives 
and rewards in Europe (2018). 
4 Commission Report on the Paediatric Regulation, COM(2017) 626 
5 General report on the experience acquired as a result of the application of the Paediatric Regulation (10-year 
Report from EMA to the European Commission, 2017); General report on the experience acquired as a result of 
the application of the Paediatric Regulation (5-year Report from EMA to the European Commission,  2012) and 
annual reports from the Agency. 

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3.  KEY FINDINGS 

The evaluation found that both regulations have fostered the development and availability 
of medicines for patients with rare diseases and for children. They have redirected private and 
public  investment  towards  previously  neglected  areas  through  incentives,  obligations  and 
rewards. Member States alone could not have achieved this result due to the small number of 
patients concerned and the fragmentation of the market. 

A  number  of  both  EU  and  national  research  programmes  in  the  field  of  rare  diseases  have 
complemented the legislation. However, the information available does not allow a direct link 
to be drawn between the public funding and the medicines effectively developed. 

The  number  of  medicines  for  patients  with  rare  diseases  and  for  children  has  increased. 
Medicines for patients with rare diseases have also become available faster and have reached 
a higher number of patients in the Member States. Similarly, the Regulation on medicines for 
children  increased  the  number  of  clinical  trials  in  children  and,  consequently,  the 
development of new medicines for them. It reduced the ‘off-label’ use of medicines for adults 
in  children,  which  were  not  specifically  tested  or  adapted  for  use  in  children  (‘off-label’ 
use)and favoured the creation of a ‘paediatric research environment’ in Europe.  

Nevertheless,  both  regulations  have  not  adequately  managed  to  support  development  in 
areas  where  the  need  for  medicines  is  greatest.  Products tend to be developed in certain 
more profitable therapeutic areas for which the number of available treatments is increasing. 

The evaluation questions focus on whether the threshold of fewer than 5 in 10 000 patients is 
the  right  tool  for  identifying  rare  diseases  which  need  specific  support  in  medicines 
development. Advances in science, such as personalised medicine and the use of biomarkers 
could  add  another  layer  of  complexity  to  the  current  regulatory  framework.  While  such 
developments  may  hold  great  potential  for  optimal  tailoring  of  treatments  to  diseases,  they 
should  not  lead  to  unnecessary  multiplications  of  rare  diseases  out  of  common  diseases, 
neither proliferation of exclusivity periods. 

The Regulation for medicines for rare diseases can also support products (such as antibiotics) 
for which companies cannot expect sufficient return on investment. However, this possibility 
was difficult to implement and has never been used. 

The  Regulation  for  medicines  for  children  obliges  companies  to  test  new  medicines  in 
children but has no dedicated instrument to direct development in areas relevant for children. 
The development of new medicines for children therefore remains mainly driven by adults’ 
needs. As a result, it does not necessarily address the greatest therapeutic needs of children 
(such as treatments for children’s cancers and for newborns).  

The  evaluation  found  that  incentives  remain  relevant  to  encourage  the  development  of 
medicines for rare diseases. However, for some rare diseases the market has started to look 
more similar to ‘standard’ medicines. Hence, in such cases it could be questionable whether a 
10-year market exclusivity is justified. The Orphan Regulation allows for a shortening of the 
market  exclusivity  period  once  a  medicine  becomes  commercially  successful.  In  practice, 
Member  States  did  not  trigger  the  procedure  because  it  is  too  difficult  to  provide  the 
necessary evidence.  

2 

 
 
 
 
 
 
 
 
 
 
For  medicines  for  children,  the  cost  of  conducting  clinical  studies  in  children  can  be 
compensated  by  extending  the  patent  (Supplementary  Protection  Certificate,  ‘SPC’).  While 
this  reward  is  partly  fulfilling  its  role,  it  has  not  shown  to  be  effective  in  stimulating  the 
development  of  medicines  whose  development  for  adults  is  not  attractive.  Obtaining  this 
reward may be complex, as companies have to request it individually at the various national 
patent offices.  

The  incentives  and  rewards  provided  by  both  regulations  come  with  a  cost.  The  evaluation 
found that both regulations have increased costs for healthcare systems. However, thanks to 
the  treatment  with  medicines  for  rare  diseases,  patients  benefited  from  an  improvement  in 
their quality of life. The benefits the legislation brought for children appear to outweigh the 
costs imposed on both industry and society.   

The evaluation has also shown that the medicines developed thanks to the two regulations are 
not accessible by patients equally in all Member States. This is mainly due to factors outside 
the scope of the regulations, such as strategic launch decisions by pharmaceutical companies 
and national pricing policies and reimbursement systems.  

For both regulations, some inefficiencies and undesirable consequences were observed. Any 
future  solution  to  the  shortcomings  identified  should  strike  a  balance  between  the  needs  of 
fostering innovation and ensuring the availability of and access to medicines for patients with 
rare diseases  and  for  children. These  aspects  are  closely  linked to  the  key objectives of  the 
Pharmaceutical  strategy  for  Europe,  which  includes  these  regulations.  The  strategy  aims  to 
create  a  future-proof  regulatory  framework 
the 
pharmaceutical sector. 

through  a  holistic  reflection  on 

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