Proposal for a Regulation of the European Parliament and of the Council on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/83/EC and Regulation (EC) No 726/2004 {SEC(2004) 1144}
Date: 2004-09-29
Institutions: European Commission
Subjects: European Medicines Agency, child, child protection, drug surveillance, market approval, medical research, medicinal product, paediatrics, pharmaceutical legislation

COMMISSION OF THE EUROPEAN COMMUNITIES 

Brussels, 29.9.2004 
COM(2004) 599 final 

2004/0217 (COD) 

Proposal for a 

REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL 

on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, 
Directive 2001/83/EC and Regulation (EC) No 726/2004 

(presented by the Commission)  

{SEC(2004) 1144} 

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EXPLANATORY MEMORANDUM 

1. 

INTRODUCTION AND BACKGROUND 

The public health concern and its causes 

The  paediatric  population  is  a  vulnerable  group  with  developmental,  physiological  and 
psychological differences from adults, which makes age and development related research of 
medicines particularly important. In contrast to the situation in adults, more than 50% of the 
medicines used to treat the children of Europe have not been tested and are not authorised for 
use in children: the health and therefore quality of life of the children of Europe may suffer 
from a lack of testing and authorisation of medicines for their use. 

Although there may be concerns voiced about conducting trials in the paediatric population, 
this  has  to  be  balanced  by  the  ethical  issues  related  to  giving  medicines  to  a  population  in 
which they have not been tested and therefore their effects, positive or negative, are unknown. 
In order to address the concerns about trials in children, the EU Directive on clinical trials1 
lays down specific requirements to protect children who take part in clinical trials in the EU. 

Related initiatives: EU Orphan Regulation and US legislation on medicines for children 

The absence of research into treatments for rare diseases led the Commission to propose the 
Regulation  on  orphan  medicinal  products,  subsequently  adopted  in  December  1999.  This 
Regulation  has  proved  successful  in  stimulating  research  leading  to  the  authorisation  of 
medicines to treat rare diseases. 

In the US, specific legislation to encourage the performance of clinical trials in children has 
been  introduced,  containing  combined  measures  of  incentives  and  obligations  which  have 
proven successful in stimulating the development of medicinal products for paediatric use. 

Council Resolution 

The Council Resolution of 14 December 2000 called on the Commission to make proposals in 
the form of incentives, regulatory measures or other supporting measures in respect of clinical 
research and development to ensure that new medicinal products for children and medicinal 
products already on the market are fully adapted to the specific needs of children. 

2. 

JUSTIFICATION 

Objective 

The overall policy objective is to improve the health of the children of Europe by increasing 
the research, development and authorisation of medicines for use in children. 

General objectives are: to increase the development of medicines for use in children; to ensure 
that  medicines  used  to  treat  children  are  subject  to  high  quality  research;  to  ensure  that 
medicines used to treat children are appropriately authorised for use in children; to improve 

1 

OJ L 121, 1.5.2001, p. 34. 

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the information available on the use of medicines in children, and; to achieve these objectives 
without  subjecting  children  to  unnecessary  clinical  trials  and  in  full  compliance  with  the 
EU Clinical Trials Directive. 

Scope, legal basis and procedure 

The  proposed  system  covers  medicinal  products  for  human  use  within  the  meaning  of 
Directive 2001/83/EC. 

The  proposal  is  based  on  Article  95  of  the  EC  Treaty.  Article  95,  which  prescribes  the 
codecision procedure described in Article 251, is the legal basis for achieving the aims set out 
in Article 14 of the Treaty, which includes the free movement of goods (Article 14(2)), in this 
case human medicinal products. While taking account of the fact that any regulations on the 
manufacture  and  distribution  of  medicinal  products  must  be  fundamentally  aimed  at 
safeguarding public health, this aim must be achieved by means that do not impede the free 
movement of medicinal products within the Community. Since the Amsterdam Treaty came 
into force, all legislative provisions adopted by the European Parliament and the Council in 
this  field  have  been  adopted  on  the  basis  of  that  Article,  since  the  differences  between  the 
national  legislative,  regulatory  and  administrative  provisions  on  medicinal  products  tend  to 
hinder  intra-Community  trade  and  therefore  directly  affect  the  operation  of  the  internal 
market. Any action to promote the development and authorisation of medicinal products for 
paediatric use is justified at a European level with a view to preventing or eliminating these 
obstacles. 

Subsidiarity and proportionality 

The  proposal  builds  on  the  experience  gained  with  the  existing  regulatory  framework  for 
medicines in Europe and learns from the requirements and incentives for paediatric medicines 
in the US and the EU orphan regulation. On the basis of the available evidence it is concluded 
that it is unlikely that the current public health issue regarding medicines for children will be 
resolved in the EU until a specific legislative system is put in place. 

Community action allows the best possible use of the instruments set up in the pharmaceutical 
sector to complete the internal market. In addition, authorisation of medicines for children is a 
Europe-wide issue. However, Member States will have an important role in the fulfilment of 
the objectives of the proposal. 

Legislative and administrative simplification 

All  the  key  measures  in  the  proposal  build  on  or  strengthen  the  existing  framework  for  the 
regulation  of  medicinal  products.  This  proposal  directly  interfaces  with  five  existing 
Community  legislative  texts:  Directive  2001/83/EC  of  the  European  Parliament  and  of  the 
Council  of  6  November  20012  which  sets  the  framework  for  the  regulation  of  medicinal 
products;  Regulation  (EC)  No  726/2004  of  the  European  Parliament  and  of  the  Council  of 
31 March 20043 which establishes the European Medicines Agency (EMEA) and created the 
centralised  authorisation  procedure  for  medicinal  products;  Directive  2001/20/EC  of  the 
European Parliament and of the Council of 4 April 2001 which provides a framework for the 
regulation and conduct of clinical trials in the Community; Regulation (EC) No 141/2000 of 

2 
3 

OJ L 311, 28.11.2001 p. 67. 
OJ L 136, 30.4.2004 p. 1. 

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the  European  Parliament  and  of  the  Council  which  establishes  a  Community  system  for  the 
designation  of  medicinal  products  as  orphan  medicinal  products  and  incentives  to  stimulate 
their  development  and  authorisation4  and;  Council  Regulation  (EEC)  No  1768/92  of 
18 June 19925 which created the Supplementary Protection Certificate. 

This  proposal  for  a  regulation  establishes  a  precise  legal  framework,  however,  where  more 
detailed implementing provisions are required, a Commission regulation is foreseen and it is 
proposed that further provisions be adopted by the Commission as guidelines, in consultation 
with the Member States, the EMEA and the parties concerned. 

Consistency with other Community policies 

Consistency will be sought with activities in the areas of research and development and health 
and consumer protection. 

Outside consultation 

Interested  parties  have  been  widely  consulted  on  this  proposal.  Detail  on  the  consultation 
conducted  by  the  Commission  is  included  in  the  Extended  Impact  Assessment  that 
accompanies this proposal. 

Evaluation of the proposal: Extended impact assessment 

This proposal has been the subject of a Commission extended impact assessment, attached to 
this proposal, which is based on data collected by an independent contracted study. 

3. 

PRESENTATION 

A  brief  description  of  the  main  elements  of  the  proposal  is  hereby  provided.  For  a  more 
detailed  description,  we  refer  to  the  Commission’s  explanatory  document  attached  to  this 
proposal. 

Key measures included in the proposal 

The Paediatric Committee 

A  committee  with  expertise  in  all  aspects  related  to  medicines  for  children  is  central  to  the 
proposal  and  its  operation.  The  Paediatric  Committee  will  be  responsible  primarily  for  the 
assessment  and  agreement  of  paediatric  investigation  plans  and  requests  for  waivers  and 
deferrals described below. In addition it may assess compliance with paediatric investigation 
plans and be asked to assess the results of studies. In all its work it will consider the potential 
significant therapeutic benefits of studies in children including the need to avoid unnecessary 
studies,  it  will  follow  existing  Community  requirements  and  will  avoid  any  delay  in  the 
authorisation of medicines for other populations as a result of the requirements for studies in 
children. 

4 
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OJ L 18, 22.1.2000, p. 1. 
OJ L 182, 2.7.1992, p. 1. 

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Marketing authorisation requirements 

The paediatric investigation plan will be the document upon which the studies in children are 
based and will have to be agreed by the Paediatric Committee. When assessing such plans the 
Paediatric  Committee  will  have  to  take  into  consideration  two  overarching  principles:  that 
studies  should  only  be  performed  if  there  is  a  potential  therapeutic  benefit  to  children  (and 
avoiding duplication of studies) and that the requirements for studies in children should not 
delay the authorisation of medicines for other populations. 

A  core  measure  is  a  new  requirement  for  the  results  of  all  studies  performed  in  accordance 
with  a  completed,  agreed  paediatric  investigation  plan  to  be  presented  at  the  time  of 
applications, unless a waiver or a deferral has been granted. This core requirement has been 
included to ensure that medicines are developed for children based on their therapeutic needs. 
The  paediatric  investigation  plan  will  be  the  basis  upon  which  compliance  with  this 
requirement is judged. 

Waivers from the requirements 

Not all medicines being developed for adults will be suitable for children or will be needed to 
treat  children  and  unnecessary  studies  in  children  should  be  avoided.  To  deal  with  such 
situations  a  system  of  waivers  from  the  requirements  described  above  is  proposed.  The 
Paediatric  Committee  will  start  work  as  soon  as  it  is  set  up,  on  lists  of  waivers  of  specific 
medicinal  products  and  classes  of  medicinal  product.  For  products  not  included  in  the 
published lists, a simple procedure is proposed for companies to request waivers. 

Deferrals from the timing of initiation or completion of studies in children 

Sometimes  studies  in  children  will  be  more  appropriate  when  there  exists  some  initial 
experience on use of a product in adults or studies in children might take longer than studies 
in adults. This might apply to the entire paediatric population or just a subset. Therefore, to 
deal  with  this  situation,  a  system  of  deferrals  is  proposed  together  with  a  procedure  for 
agreeing them with the Paediatric Committee. 

Marketing authorisation procedures 

The procedures set out in existing pharmaceutical legislation are not altered by the proposals. 
The requirements above will require the Competent Authorities to check compliance with the 
agreed paediatric investigation plan at the existing validation step for marketing authorisation 
applications. The assessment of safety, quality and efficacy of medicines for children and the 
granting  of  marketing  authorisations  remain  the  remit  of  the  Competent  Authorities.  To 
increase  the  availability  of  medicines  for  children  across  the  Community,  because  the 
requirements  in  the  proposals  are  linked  to  Community-wide  rewards  and  to  prevent  the 
distortion  of  free  trade  within  the  Community,  it  is  proposed  that  an  application  for  a 
marketing authorisation including at least one paediatric indication based on the results of an 
agreed paediatric investigation plan will have access to the centralised Community procedure. 

The Paediatric Use Marketing Authorisation (PUMA) 

In order to establish a vehicle for providing incentives for off-patent medicines, a new type of 
marketing authorisation, the Paediatric Use Marketing Authorisation (PUMA) is proposed. A 

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PUMA  will  utilise  existing  marketing  authorisation  procedures  but  is  specifically  for 
medicinal products developed exclusively for use in children. 

The name of the medicinal product granted a PUMA can utilise the existing brand name of 
the  corresponding  product  authorised  for  adults  but  the  product  names  of  all  medicines 
granted a PUMA will include a superscript of the letter “P” to aid recognition and prescribing. 
Thus, pharmaceutical companies will be able to capitalise on existing brand recognition while 
benefiting from the data protection associated with a new marketing authorisation. The data 
protection period associated with the PUMA may prove more valuable in light of the recent 
case  law  of  the  European  Court  of  Justice  concerning  the  interpretation  of  data  protection 
rules6. 

An application for a PUMA will require the submission of data necessary to establish safety, 
quality and efficacy specifically in children, collected in accordance with an agreed paediatric 
investigation  plan.  However, an application  for  a  PUMA  may  refer  to  data  contained  in  the 
dossier of a medicinal product which is or has been authorised in the Community. 

Extension of the duration of the supplementary protection certificate 

For  new  medicines  and  for  products  covered  by  a  patent  or  a  Supplementary  Protection 
Certificate (SPC), if all the measures included in the agreed paediatric investigation plan are 
complied with, if the product is authorised in all Member States and if relevant information on 
the results of studies is included in product information, the six-month SPC extension will be 
granted.  The  mechanism  for  this  will  be  the  inclusion  of  a  statement  in  the  marketing 
authorisation that these measures have been met. Companies will then be able to present the 
marketing authorisation to patent offices that will then award the SPC extension. The need to 
have a marketing authorisation in all Member States is to prevent a Community-wide reward 
without  Community-wide  benefits  to  child-health.  Because  the  reward  is  for  conducting 
studies in children and not for demonstrating that a product is safe and effective in children, 
the reward will be granted even when a paediatric indication is not granted. However, relevant 
information  on  use  in  paediatric  populations  will  have  to  be  included  in  authorised  product 
information. 

Extended market exclusivity for orphan medicinal products 

Under the EU orphan regulation, medicinal products designated as orphan medicinal products 
gain ten-years of market exclusivity on the granting of a marketing authorisation in the orphan 
indication. As such products are frequently not patent protected the reward of SPC extension 
can not be applied and when they are patent-protected, SPC extension would provide a double 
incentive. Therefore it is proposed to extend the ten-year period of orphan market exclusivity 
to twelve-years if the requirements for data on use in children are fully met. 

Paediatric study programme: Medicines Investigation for the Children of Europe (MICE) 

An  additional  tool  for  promoting  high  quality,  ethical  research  that  may  lead  to  the 
development and authorisation of medicines for children should be the provision of funding 
for  studies  into  the  paediatric  use  of  medicines  not  covered  by  a  patent  or  a  supplementary 
protection  certificate.  The  Commission  intends  to  examine  the  possibility  of  setting  up  a 

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Case C-106/01, Novartis Pharmaceuticals UK, judgment of 29 April 2004, not yet reviewed. 

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paediatric study programme: Medicines Investigation for the Children of Europe, taking into 
consideration existing Community Programmes.  

Information on the use of medicines for children 

One  of  the  objectives  of  this  proposal  is  to  increase  the  information  available  on  the  use  of 
medicines for children. Through increased availability of information, the safe and effective 
use  of  medicines  for  children  can  be  increased  so  promoting  public  health.  In  addition, 
availability of this information with help prevent the duplication of studies in children and the 
conduct of unnecessary studies in children. 

The Clinical Trials Directive establishes a Community database of clinical trials (EudraCT). It 
is proposed to build onto this database an information resource of all ongoing and terminated 
paediatric studies conducted both in the Community and in third countries. 

In  addition,  based  on  a  survey  of  existing  use  of  medicines  in  Europe,  an  inventory  of 
therapeutic needs of children will be established by the Paediatric Committee. 

It  is  also  proposed  to  create  a  Community  network  to  link  together  national  networks  and 
clinical trial centres in order to build up the necessary competences at a European level and to 
facilitate the conduct of studies, to increase co-operation and avoid duplication of studies. 

Pharmaceutical companies have, in some cases, already conducted clinical trials in children. 
However,  frequently,  the  results  of  these  studies  have  not  been  submitted  to  Competent 
Authorities and have not resulted in updates to product information. To deal with this issue, it 
is proposed that any studies completed before this proposed legislation is adopted will not be 
eligible for the rewards and incentives proposed for the EU. They will, however, be taken into 
account  for  the  requirements  contained  in  the  proposals  and  it  will  be  mandatory  for 
companies to submit the studies to the competent authorities once this proposed legislation is 
adopted. 

Other measures 

The  interface  between  the  Committee  for  Medicinal  Products  for  Human  Use,  its  Scientific 
Advice Working Group and other Community committees and working groups on medicines 
and  the  Paediatric  Committee  will  be  managed  by  the  EMEA.  In  addition,  free  scientific 
advice from the EMEA to sponsors developing medicines for children is proposed. 

The proposals presented will place demands on competent authorities and particularly on the 
EMEA.  It  is  proposed  to  increase  the  Community  subsidy,  to  be  allocated  to  the  EMEA  to 
take account of the new tasks. A financial statement accompanies this proposal. 

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2004/0217 (COD) 

Proposal for a 

REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL 

on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, 
Directive 2001/83/EC and Regulation (EC) No 726/2004 

(Text with EEA relevance) 

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION, 

Having  regard  to  the  Treaty  establishing  the  European  Community,  and  in  particular 
Article 95 thereof, 

Having regard to the proposal from the Commission1, 

Having regard to the Opinion of the European Economic and Social Committee2, 

Having regard to the Opinion of the Committee of the Regions3, 

In accordance with the procedure referred to in Article 251 of the Treaty4, 

Whereas: 

(1) 

(2) 

(3) 

Before  a  medicinal  product  for  human  use  is  placed  on  the  market  of  one  or  more 
Member  States,  it  generally  has  to  have  undergone  extensive  studies,  including 
pre-clinical  tests  and  clinical  trials,  to  ensure  that  it  is  safe,  of  high  quality  and 
effective for use in the target population. 

Such studies may not have been done for use in children and many of the medicines 
currently  used  to  treat  children  have  not  been  studied  or  authorised  for  such  use. 
Market  forces  alone  have  proven  insufficient  to  stimulate  adequate  research, 
development and authorisation of medicines for children. 

Problems  resulting  from  the  absence  of  suitably  adapted  medicines  for  children 
include inadequate dosing information leading to increased risks of adverse reactions 
including  death,  ineffective  treatment  through  under-dosing,  non-availability  to 
children of therapeutic advances, as well as the use of extemporaneous formulations to 
treat children which may be of poor quality. 

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4 

OJ C […], […], p. […]. 
OJ C […], […], p. […]. 
OJ C […], […], p. […]. 
OJ C […], […], p. […]. 

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(4) 

The  aim  of  this  Regulation  is  to  increase  the  development  of  medicines  for  use  in 
children,  to  ensure  that  medicines  used  to  treat  children  are  subject  to  high  quality, 
ethical  research  and  are  appropriately  authorised  for  use  in  children,  and  to  improve 
the information available on the use of medicines in the various paediatric populations. 
These  objectives  should  be  achieved  without  subjecting  children  to  unnecessary 
clinical  trials  and  without  delaying  the  authorisation  of  medicinal  products  for  other 
populations. 

(5)  While taking into account the fact that any regulations on medicinal products must be 
fundamentally  aimed  at  safeguarding  public  health,  this  aim  must  be  achieved  by 
means  that  do  not  impede  the  free  movement  of  medicinal  products  within  the 
Community.  The  differences  between  the  national  legislative,  regulatory  and 
administrative provisions on medicinal products tend to hinder intra-Community trade 
and  therefore  directly  affect  the  operation  of  the  internal  market.  Any  action  to 
promote the development and authorisation of medicinal products for paediatric use is 
therefore justified with a view to preventing or eliminating these obstacles. Article 95 
of the Treaty is therefore the proper legal basis. 

(6) 

(7) 

(8) 

The  establishment  of  a  system  of  both  obligations  and  rewards  and  incentives  has 
proved necessary to achieve these objectives. The precise nature of the obligations and 
rewards  and  incentives  should  take  account  of  the  status  of  the  particular  medicinal 
product  concerned.  This  Regulation  should  apply  to  all  the  medicines  required  by 
children  and  therefore  its  scope  should  cover  products  in  development  and  yet  to  be 
authorised,  authorised  products  still  covered  by  intellectual  property  rights  and 
authorised products no longer covered by intellectual property rights. 

Any concerns about conducting trials in the paediatric population should be balanced 
by the ethical concerns about giving medicines to a population in which they have not 
been  tested.  The  public  health  threat  from  the  use  of  untested  medicines  in  children 
can be safely addressed through the study of medicines for children, which should be 
carefully controlled and monitored through the specific requirements for the protection 
of  children  who  take  part  in  clinical  trials  in  the  Community  laid  down  in 
Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 
on  the  approximation  of  the  laws,  regulations  and  administrative  provisions  of  the 
Member States relating to the implementation of good clinical practice in the conduct 
of clinical trials on medicinal products for human use5. 

It is appropriate to create a scientific committee, the Paediatric Committee, within the 
European Medicines Agency, hereinafter ‘the Agency’, with expertise and competence 
in  the  development  and  assessment  of  all  aspects  of  medicinal  products  to  treat 
paediatric populations. The Paediatric Committee should be primarily responsible for 
the assessment and agreement of paediatric investigation plans and for the system of 
waivers and deferrals thereof, and it should also be central to various support measures 
contained in this Regulation. In all its work the Paediatric Committee should consider 
the potential significant therapeutic benefits of studies in children including the need 
to  avoid  unnecessary  studies.  It  should  follow  existing  Community  requirements, 
including  Directive  2001/20/EC,  as  well  as 
International  Conference  on 
Harmonisation (ICH) guideline E11 on the development of medicines for children, and 

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OJ L 121, 1.5.2001, p. 34. 

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it should avoid any delay in the authorisation of medicines for other populations as a 
result of the requirements for studies in children. 

(9) 

Procedures  should  be  established  for  the  Agency  to  agree  and  modify  a  paediatric 
investigation  plan,  the  document  upon  which  the  development  and  authorisation  of 
medicines  for  children  should  be  based.  The  paediatric  investigation  plan  should 
include  details  of  the  timing  and  the  measures  proposed  to  demonstrate  the  quality, 
safety and efficacy of the medicinal product in the paediatric population. Because the 
paediatric population is in fact made up of a number of subpopulations, the paediatric 
investigation  plan  should  specify  which  subpopulations  need  to  be  studied,  by  what 
means and by when. 

(10)  The introduction of the paediatric investigation plan in the legal framework concerning 
medicinal products for human use aims at ensuring that development of medicines for 
children becomes an integral part of the development of medicinal products, integrated 
into  the  development  programme  for  adults.  Thus,  paediatric  investigation  plans 
should  be  submitted  early  during  product  development,  in  time  for  studies  to  be 
conducted in children before marketing authorisation applications are submitted. 

(11) 

It  is  necessary  to  introduce  a  requirement  for  new  medicinal  products  and  for 
authorised  medicinal  products  covered  by  a  patent  or  a  supplementary  protection 
certificate  to  present  the  results  of  studies  in  children  in  accordance  with  an  agreed 
paediatric investigation plan in order to obtain validation of a marketing authorisation 
application  or  an  application  for  a  new  indication,  new  pharmaceutical  form  or  new 
route  of  administration.  The  paediatric  investigation  plan  should  be  the  basis  upon 
which compliance with that requirement is judged. However, that requirement should 
not apply to generics or similar biological medicinal products and medicinal products 
authorised  through  the  well-established  medicinal  use  procedure,  or  to  homeopathic 
medicinal  products  and  traditional  herbal  medicinal  products  authorised  through  the 
simplified  registration  procedures  of  Directive  2001/83/EC  of 
the  European 
Parliament and of the Council of 6 November 2001 on the Community code relating to 
medicinal products for human use6. 

(12) 

In order to ensure that research in children is only conducted to meet their therapeutic 
needs, there is a need to establish procedures for the Agency to waive that requirement 
for specific products or for classes or part of classes of medicinal products, to be then 
published by the Agency. As knowledge on science and medicine evolves over time, 
provision should be made for the lists of waivers to be amended. However, if a waiver 
is revoked, the requirement should not apply for a given period in order to allow time 
for  at  least  a  paediatric  investigation  plan  to  be  agreed  and  studies  in  children  to  be 
initiated prior to marketing authorisation application. 

(13) 

In certain cases, the Agency should defer the initiation or completion of some or all of 
the measures contained in a paediatric investigation plan, with a view to ensuring that 
research is done only when it is safe and ethical to do so and that the requirement for 
study data in children does not block or delay the authorisation of medicines for other 
populations. 

6 

OJ L 311, 28.11.2001, p. 67. Directive as last amended by Directive 2004/27/EC (OJ L 136, 30.4.2004, 
p. 34.) 

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(14)  Free  scientific advice should be provided  by the Agency as  an  incentive  to  sponsors 
developing  medicines  for  children.  To  ensure  scientific  consistency,  the  Agency 
should  manage  the  interface  between  the  Paediatric  Committee  and  the  Scientific 
Advice Working Group of the Committee for Medicinal Products for Human Use , as 
well  as  the  interaction  between  the  Paediatric  Committee  and  the  other  Community 
committees and working groups concerning medicinal products. 

(15)  The  existing  procedures  for  the  marketing  authorisation  of  medicinal  products  for 
human use should not be changed. However, it follows from the requirement for the 
results of studies in children to be presented in accordance with an agreed paediatric 
investigation plan that competent authorities should check compliance with the agreed 
paediatric  investigation  plan  and  any  waivers  and  deferrals  at  the  existing  validation 
step  for  marketing  authorisation  applications.  The  assessment  of  safety,  quality  and 
efficacy of medicines for children and the granting of marketing authorisations should 
remain  the  remit  of  the  competent  authorities.  Provision  should  be  made  for  the 
possibility of asking the Paediatric Committee  for an opinion  on  compliance  and for 
an opinion on the safety, quality and efficacy of a medicine in children. 

(16)  To  provide  healthcare  professionals  and  patients  with  information  on  the  safe  and 
effective  use  of  medicines  in  children  and  as  a  transparency  measure,  information 
regarding  the  results  of  studies  in  children,  as  well  as  on  the  status  of  the  paediatric 
investigation plans, waivers and deferrals, should be included in product information. 
When all the measures in the paediatric investigation plan have been complied with, 
that  fact  should  be  recorded  in  the  marketing  authorisation,  and  should  then  be  the 
basis upon which companies can obtain the rewards for compliance. 

(17)  To  distinguish  medicines  authorised  for  use  in  children  following  completion  of  an 
agreed paediatric investigation plan and enable their prescription , provision should be 
made  for  the  name  of  medicinal  products  granted  an  indication  for  use  in  children 
following  an  agreed  paediatric  investigation  plan  to  include  the  letter  “P”  in  blue 
lettering surrounded by the outline of a star, also in blue. 

(18) 

In  order  to  establish  incentives  for  authorised  products  no  longer  covered  by 
intellectual  property  rights,  it  is  necessary  to  establish  a  new  type  of  marketing 
authorisation,  the  Paediatric  Use  Marketing  Authorisation.  A  Paediatric  Use 
Marketing  Authorisation  should  be  granted  through  existing  marketing  authorisation 
procedures but should apply specifically for medicinal products developed exclusively 
for use in children. It should be possible for the name of the medicinal product granted 
a  Paediatric  Use  Marketing  Authorisation  to  utilise  the  existing  brand  name  of  the 
corresponding  product  authorised  for  adults,  in  order  to  capitalise  on  existing  brand 
recognition  while  benefiting  from  the  data  exclusivity  associated  with  a  new 
marketing authorisation. 

(19)  An  application  for  a  Paediatric  Use  Marketing  Authorisation  should  include  the 
submission  of  data  concerning  use  of  the  product  in  the  paediatric  population, 
collected in accordance with an agreed paediatric investigation plan. These data may 
be  derived  from  the  published  literature  or  from  new  studies.  An  application  for  a 
Paediatric Use Marketing Authorisation should also be able to refer to data contained 
in  the  dossier  of  a  medicinal  product  which  is  or  has  been  authorised  in  the 
Community.  That  is  intended  to  provide  an  additional  incentive  to  attract  small  and 

EN 

11 

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medium  sized  enterprises,  including  generic  companies,  to  develop  off-patent 
medicines for children. 

(20)  This  Regulation  should  include  measures  to  maximise  access  of  the  Community 
population  to  new  medicinal  products  tested  and  adapted  for  paediatric  use,  and 
minimise  the  chance  of  Community-wide  rewards  and  incentives  being  granted 
without  sections  of  the  Community  paediatric  population  benefiting  from  the 
availability  of  a  newly  authorised  medicine.  An  application  for  a  marketing 
authorisation, including  an  application for a Paediatric Use Marketing Authorisation, 
which  contains  the  results  of  studies  conducted  in  compliance  with  an  agreed 
paediatric  investigation  plan  should  be  eligible  for  the  Community  centralised 
procedure set out in Articles 5 to 15 of 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 European Medicines Agency7. 

(21)  When  an  agreed  paediatric  investigation  plan  has  led  to  the  authorisation  of  a 
paediatric  indication  for  a  product  already  marketed  for  other  indications,  the 
marketing  authorisation  holder  should  be  obliged  to  place  the  product  on  the  market 
taking into account the paediatric information within two years following the date of 
approval  of  the  indication.  That  requirement  should  relate  only  to  products  already 
authorised,  but  not  to  medicines  authorised  via  a  Paediatric  Use  Marketing 
Authorisation. 

(22)  An  optional  procedure  should  be  established  to  make  it  possible  to  obtain  a  single 
Community-wide opinion for a nationally authorised medicinal product when data on 
children following an agreed paediatric investigation plan form part of the marketing 
authorisation application. To achieve this, the procedure set out in Articles 32 to 34 of 
Directive  2001/83/EC  may  be  used.  This  will  allow  the  adoption  of  a  Community 
harmonised Decision on use of the medicinal product in children and its introduction 
in all national product information. 

(23) 

It  is  essential  to  ensure  that  pharmacovigilance  mechanisms  are  adapted  to  meet  the 
specific  challenges  of  collecting  safety  data  in  children,  including  data  on  possible 
long-term  effects.  Efficacy  in  children  may  also  need  additional  study  following 
authorisation.  Therefore,  an  additional  requirement  for  applying  for  a  marketing 
authorisation  that  includes  the  results  of  studies  conducted  in  compliance  with  an 
agreed  paediatric  investigation  plan  should  be  an  obligation  for  the  applicant  to 
indicate  how  he  proposes  to  ensure  the  long-term  follow-up  of  possible  adverse 
reactions to the use of the medicinal product and efficacy in the paediatric population. 
Additionally, where there is a particular cause for concern, provision is made for the 
possibility  of  requiring  the  applicant  to  submit  and  implement  a  risk  management 
system and/or perform specific post-marketing studies as a condition of the marketing 
authorisation. 

(24)  For products falling within the scope of the requirement to submit paediatric data, if 
all the measures included in the agreed paediatric investigation plan are complied with, 
if  the  product  is  authorised  in  all  Member  States  and  if  relevant  information  on  the 

7 

OJ L 136, 30.4.2004, p. 1. 

EN 

12 

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results of studies is included in product information, a reward should be granted in the 
form  of  a  6-month  extension  of  the  Supplementary  Protection  Certificate  created  by 
Council Regulation (EEC) No 1768/928. 

(25)  Because the reward is for conducting studies in children and not for demonstrating that 
a product is safe and effective in children, the reward should be granted even when a 
paediatric indication is not authorised. However, to improve the information available 
on  the  use  of  medicines  in  the  paediatric  population,  relevant  information  on  use  in 
paediatric populations should be included in authorised product information. 

(26)  Under Regulation (EC) No 141/2000 of the European Parliament and of the Council of 
16 December 1999 on orphan medicinal products9, medicinal products  designated as 
orphan  medicinal  products  gain  ten  years  of  market  exclusivity  on  the  granting  of  a 
marketing authorisation for the orphan indication. As such products are frequently not 
patent-protected, the reward of Supplementary Protection Certificate extension cannot 
be  applied  and  when  they  are  patent-protected,  such  an  extension  would  provide  a 
double incentive. Therefore, for orphan medicinal products, instead of extension of the 
Supplementary Protection Certificate, the ten-year period of orphan market exclusivity 
should  be  extended  to  twelve  years  if  the  requirement  for  data  on  use  in  children  is 
fully met. 

(27)  The  measures  provided  for  in  this  Regulation  should  not  preclude  the  operation  of 
other  incentives  or  rewards.  To  ensure  transparency  on  the  different  measures 
available at Community and Member State levels, the Commission should draw up a 
detailed list of all the incentives available, on the basis of information provided by the 
Member  States.  The  measures  set  out  in  this  Regulation,  including  the  agreement  of 
paediatric  investigation  plans,  should  not  be  grounds  for  obtaining  any  other 
Community  incentives  to  support  research,  such  as  the  funding  of  research  projects 
under 
for  Research, 
Technological Development and Demonstration Activities. 

the  multi-annual  Community  Framework  Programmes 

(28) 

In order to increase the availability of information on the use of medicines in children, 
and  to  avoid  the  repetition  of  studies  in  children  which  do  not  add  to  the  collective 
knowledge, the European database provided for in Article 11 of Directive 2001/20/EC 
should  include  an  information  resource  of  all  ongoing,  prematurely  terminated,  and 
completed paediatric studies conducted both in the Community and in third countries. 

(29)  An  inventory  of  therapeutic  needs  of  children  should  be  adopted  by  the  Paediatric 
Committee after consultation with the Commission, the Member States and interested 
parties,  and  regularly  updated.  The  inventory  should  identify  the  existing  medicines 
used by children and highlight the therapeutic needs of children and the priorities for 
research  and  development.  In  this  way,  companies  should  be  able  to  identify  easily 
opportunities  for  business  development;  the  Paediatric  Committee  should  be  able  to 
better  judge  the  need  for  medicines  and  studies  when  assessing  draft  paediatric 
investigation  plans,  waivers  and  deferrals;  and  healthcare  professionals  and  patients 
should  have  an  information  source  available  to  support  their  decisions  as  to  which 
medicines to choose. 

8 
9 

OJ L 182, 2.7.1992, p. 1. Regulation as last amended by the Act of Accession 2003. 
OJ L 18, 22.1.2000, p. 1. 

EN 

13 

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(30)  Clinical  trials  in  the  paediatric  population  may  require  specific  expertise,  specific 
methodology  and,  in  some  cases,  specific  facilities  and  should  be  carried  out  by 
appropriately  trained  investigators.  A  network  linking  together  existing  national  and 
European initiatives and study centres in order to build up the necessary competences 
at a European level, would help facilitating co-operation and avoiding duplication of 
studies. This network should  contribute to the work of strengthening the foundations 
of the European Research Area in the context of Community Framework Programmes 
for  Research,  Technological  Development  and  Demonstration  Activities,  benefit  the 
paediatric population and provide a source of information and expertise for industry.  

(31)  For certain authorised products, pharmaceutical companies may already hold data on 
safety  or  efficacy  in  children.  To  improve  the  information  available  on  the  use  of 
medicines  in  the  paediatric  populations,  companies  holding  such  data  should  be 
required to submit them to all competent authorities where the product is authorised. 
In  this  way  the  data  can  be  assessed  and,  if  appropriate,  information  should  be 
included in the authorised product information aimed at healthcare professionals and 
patients. 

(32)  Community  funding  should  be  envisaged  to  cover  all  aspects  of  the  work  of  the 
Paediatric  Committee  and  of  the  Agency  resulting  from  the  implementation  of  this 
Regulation,  such  as  the  assessment  of  paediatric  investigation  plans,  fee  waivers  for 
scientific  advice,  and  information  and  transparency  measures,  including  the  database 
of paediatric studies and the network. 

(33)  The measures necessary for the implementation of this Regulation should be adopted 
in accordance with Council Decision 1999/468/EC of 28 June 1999 laying down the 
procedures for the exercise of implementing powers conferred on the Commission10. 

(34)  Regulation 

(EEC)  No 1768/92,  Directive  2001/83/EC  and  Regulation 

(EC) 

No 726/2004 should therefore be amended accordingly, 

HAVE ADOPTED THIS REGULATION: 

TITLE I 
Introductory provisions 

CHAPTER 1 
SUBJECT-MATTER AND DEFINITIONS 

Article 1 

This  Regulation  lays  down  rules  concerning  the  development  of  medicinal  products  for 
human use in order to meet the specific therapeutic needs of the paediatric population, without 
subjecting 
compliance  with 
children 
Directive 2001/20/EC. 

to  unnecessary 

clinical 

trials 

and 

in 

10 

OJ L 184, 17.7.1999, p. 23. 

EN 

14 

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In addition to the definitions laid down in Article 1 of Directive 2001/83/EC, the following 
definitions shall apply for the purposes of this Regulation: 

Article 2 

(1) 

(2) 

(3) 

1. 

2. 

3. 

paediatric  population  means  that  part  of  the  population  aged  between  birth  and 
18 years; 

paediatric  investigation  plan  means  a  research  and  development  programme  aimed 
at ensuring that the necessary data are generated determining the conditions in which 
a medicinal product may be authorised to treat the paediatric population. 

medicinal product authorised for a paediatric indication means a medicinal product 
which is authorised for use in part or all of the paediatric population and in respect of 
which  the  details  of  the  authorised  indication  are  specified  in  the  summary  of  the 
product 
accordance  with  Article  11  of 
in 
Directive 2001/83/EC. 

characteristics  drawn  up 

CHAPTER 2 
PAEDIATRIC COMMITTEE 

Article 3 

A Paediatric Committee is established within the European Medicines Agency set up 
under Regulation (EC) No 726/2004, hereinafter “the Agency”. 

The Agency shall act as the secretariat of the Paediatric Committee and shall provide 
it with technical and scientific support. 

Save  where  otherwise  provided  in  this  Regulation,  Regulation  (EC)  No 726/2004 
shall apply to the Paediatric Committee. 

The  Executive  Director  of  the  Agency  shall  ensure  appropriate  co-ordination 
between  the  Paediatric  Committee  and  the  Committee  for  Medicinal  Products  for 
Human  Use,  the  Committee  for  Orphan  Medicinal  Products,  their  working  parties 
and any other scientific advisory groups. 

The  Agency  shall  draw  up  specific  procedures  for  possible  consultations  between 
them. 

Article 4 

1. 

The Paediatric Committee shall be composed of the following members: 

(a) 

five  members  of  the  Committee  for  Medicinal  Products  for  Human  Use, 
appointed by the latter; 

EN 

15 

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(b)  one  person  appointed  by  each  Member  State  whose  national  competent 
authority is not represented through the members appointed by the Committee 
for Medicinal Products for Human Use; 

(c) 

six  persons  appointed  by  the  Commission,  on  the  basis  of  a  public  call  for 
expressions of interest, in order to represent paediatricians and the interests of 
patient associations. 

For  the  purposes  of  point  (b),  the  Member  States  shall  cooperate,  under  the 
coordination of the Executive Director of the Agency, in order to ensure that the final 
composition  of  the  Paediatric  Committee  covers  the  scientific  areas  relevant  to 
paediatric  medicinal  products,  and  including  at  least:  pharmaceutical  development, 
paediatric  medicine,  paediatric  pharmacy,  paediatric  pharmacology,  paediatric 
research, pharmacovigilance and ethics. 

The members of the Paediatric Committee shall be appointed for a renewable period 
of three years. At meetings of the Paediatric Committee, they may be accompanied 
by experts. 

The  Paediatric  Committee  shall  elect  its  Chairman  from  among  its  members  for  a 
term of three years renewable once. 

The  names  and  scientific  qualifications  of  the  members  shall  be  published  by  the 
Agency. 

Article 5 

When preparing its opinions, the Paediatric Committee shall use its best endeavours 
to  reach  a  scientific  consensus.  If  such  a  consensus  cannot  be  reached,  the  opinion 
shall consist of the position of the majority of members and divergent positions, with 
the grounds on which they are based.  

The  Paediatric  Committee  shall  draw  up  its  own  rules  of  procedure  for  the 
implementation  of  its  tasks.  The  rules  of  procedure  shall  enter  into  force  after 
receiving  a  favourable  opinion  from  the  Management  Board  of  the  Agency  and, 
subsequently, from the Commission. 

All meetings of the Paediatric Committee may be attended by representatives of the 
Commission, the Executive Director of the Agency or his representatives. 

2. 

3. 

4. 

1. 

2. 

3. 

Article 6 

Members  of  the  Paediatric  Committee  and  its  experts  shall  undertake  to  act  in  the  public 
interest and in an independent manner. They shall not have financial or other interests in the 
pharmaceutical industry that could affect their impartiality. 

All  indirect  interests  that  could  relate  to  the  pharmaceutical  industry  shall  be  entered  in  a 
register  held  by  the  Agency  which  the  public  may  consult.  The  register  shall  be  updated 
annually. 

EN 

16 

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Members  of  the  Paediatric  Committee  and  its  experts  shall  declare  at  each  meeting  any 
specific  interests  which  could  be  considered  to  be  prejudicial  to  their  independence  with 
respect to the points on the agenda. 

Members of the Paediatric Committee and its experts shall be required, even after their duties 
have  ceased,  not  to  disclose  any  information  of  the  kind  covered  by  the  obligation  of 
professional secrecy. 

1. 

The tasks of the Paediatric Committee shall include the following: 

Article 7 

(a) 

to  assess  the  content  of  any  paediatric  investigation  plan  for  a  medicinal 
product  submitted  to  it  in  accordance  with  this  Regulation  and  formulate  an 
opinion thereon; 

(b) 

to assess waivers and deferrals and formulate an opinion thereon; 

(c) 

(d) 

(e) 

(f) 

(g) 

(h) 

at  the  request  of  the  Committee  for  Medicinal  Products  for  Human  Use,  a 
competent  authority  or  the  applicant,  to  assess  compliance  of  the  application 
for  a  Marketing  Authorisation  with 
the  concerned  agreed  paediatric 
investigation plan and formulate an opinion thereon; 

at  the  request  of  the  Committee  for  Medicinal  Products  for  Human  Use  or  a 
competent authority, to assess any data generated in accordance with an agreed 
paediatric investigation plan and formulate an opinion on the quality, safety or 
efficacy of the medicinal product for use in the paediatric population; 

to  advise  on  the  content  and  format  of  data  to  be  collected  for  the  survey 
referred  to  in  Article  41  and  to  adopt  an  inventory  of  therapeutic  needs  as 
referred to in Article 42; 

to  support  and  advise  the  Agency  on  establishing  the  European  network 
referred to in Article 43; 

to  assist  scientifically  in  the  elaboration  of  any  documents  related  to  the 
fulfilment of the objectives of this Regulation; 

to provide advice on any question related to medicinal products for paediatric 
use, at the request of the Executive Director of the Agency or the Commission. 

2. 

When carrying out its tasks, the Paediatric Committee shall consider whether or not 
any proposed studies can be expected to be of significant therapeutic benefit to the 
paediatric population. 

EN 

17 

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TITLE II 
Marketing authorisation requirements 

CHAPTER 1 
GENERAL AUTHORISATION REQUIREMENTS 

Article 8 

1. 

An application for marketing authorisation under Article 6 of Directive 2001/83/EC 
in  respect  of  a  medicinal  product  for  human  use  which  is  not  authorised  in  the 
Community  at  the  time  of  entry  into  force  of  this  Regulation  shall  be  regarded  as 
valid  only  if  it  includes,  in  addition  to  the  particulars  and  documents  referred  to  in 
Article 8(3) of Directive 2001/83/EC, one of the following: 

(a) 

the  results  of  all  studies  performed  and  details  of  all  information  collected  in 
compliance with an agreed paediatric investigation plan; 

(b) 

a decision of the Agency granting a product-specific waiver; 

(c) 

a decision of the Agency granting a class waiver; 

(d) 

a decision of the Agency granting a deferral. 

For  the  purposes  of  point  (a),  the  decision  of  the  Agency  agreeing  the  paediatric 
investigation plan concerned shall also be included in the application. 

2. 

The  documents  submitted  pursuant  to  paragraph  1  shall,  cumulatively,  cover  all 
subsets of the paediatric population. 

Article 9 

In  the  case  of  authorised  medicinal  products  which  are  protected  either  by  a  supplementary 
protection certificate under Regulation (EEC) No 1768/92, or by a patent which qualifies for 
the  granting  of  the  supplementary  protection  certificate,  Article  8  of  this  Regulation  shall 
apply  to  applications  for  authorisation  of  new  indications,  including  paediatric  indications, 
new pharmaceutical forms and new routes of administration. 

Articles 8 and 9 shall not apply to products authorised under Articles 10, 10a, 13 to 16 or 16a 
to 16i of Directive 2001/83/EC. 

Article 10 

EN 

18 

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Article 11 

In  consultation  with  the  Member  States,  the  Agency  and  other  interested  parties,  the 
Commission  shall  draw  up  the  modalities  concerning  the  format  and  content  which 
applications for agreement or modification of a paediatric investigation plan and requests for 
waivers or deferrals must follow in order to be considered valid. 

CHAPTER 2 
WAIVERS 

Article 12 

1. 

Production of the information referred to in point (a) of Article 8(1) shall be waived 
for  specific  medicinal  products  or  for  classes  of  medicinal  products,  if  there  is 
evidence showing any of the following: 

(a) 

(b) 

(c) 

that the specific medicinal product or class of medicinal products is likely to be 
ineffective or unsafe in part or all of the paediatric population; 

that the disease or condition for which the specific medicinal product or class is 
intended occurs only in adult populations; 

that the specific medicinal product does not represent a significant therapeutic 
benefit over existing treatments for paediatric patients. 

2. 

The waiver provided for in paragraph 1 may be issued with reference only to one or 
more  specified  subsets  of  the  paediatric  population,  with  reference  only  to  one  or 
more specified therapeutic indications, or with reference to a combination of both. 

Article 13 

The Paediatric Committee may of its own motion adopt an opinion, on the grounds set out in 
Article  12(1),  to  the  effect  that  a  class  or  a  product-specific  waiver,  as  referred  to  in 
Article 12(1), should be granted. 

As soon as the Paediatric Committee adopts an opinion, the procedure laid down in Chapter 4 
shall apply. In the case of a class waiver, only Article 26(4) shall apply. 

Article 14 

1. 

2. 

The applicant may, on the grounds set out in Article 12(1), apply to the Agency for a 
product-specific waiver. 

Within 60 days of receipt of the application, the Paediatric Committee shall adopt an 
opinion as to whether or not a product-specific waiver should be granted. 

EN 

19 

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Either the applicant or the Paediatric Committee may request a meeting during that 
60-day period. 

Whenever  appropriate,  the  Paediatric  Committee  may  request  the  applicant  to 
supplement  the  particulars  and  documents  submitted.  Where  the  Paediatric 
Committee avails itself of this option, the 60-day time-limit shall be suspended until 
such time as the supplementary information requested has been provided. 

As soon as the Paediatric Committee adopts an opinion, the procedure laid down in 
Chapter  4  shall  apply.  The  Agency  shall  inform  the  applicant  accordingly  without 
delay. The applicant shall be informed of the reasons for the conclusion reached. 

The Agency shall maintain a list of all waivers. 

Article 15 

The Paediatric Committee may, at any time, adopt an opinion advocating the review 
of a granted waiver. 

In the case of a change affecting a product-specific waiver, the procedure laid down 
in Chapter 4 shall apply. 

In the case of a change affecting a class waiver, Article 26(5) shall apply. 

If a particular product-specific or class waiver is revoked, the requirement set out in 
Articles 8 and 9 shall not apply for 36 months from the date of its removal from the 
list of waivers. 

CHAPTER 3 
PAEDIATRIC INVESTIGATION PLAN 

SECTION 1 
REQUESTS FOR AGREEMENT 

Article 16 

Where the intention is to apply in accordance with points (a) or (d) of Article 8(1), a 
paediatric investigation plan shall be drawn up and submitted to the Agency with a 
request for agreement. 

The paediatric investigation plan shall specify the timing and the measures proposed 
to assess the quality, safety and efficacy of the medicinal product in all subsets of the 
paediatric  population  that  may  be  concerned.  In  addition,  it  shall  describe  any 
measures  to  adapt  the  formulation  of  the  medicinal  product  so  as  to  make  its  use 
more acceptable, easier, safer or more effective for different subsets of the paediatric 
population. 

3. 

1. 

2. 

3. 

1. 

2. 

EN 

20 

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1. 

2. 

3. 

1. 

2. 

Article 17 

In  the  case  of  applications  as  referred  to  in  Articles  8  and  9,  the  paediatric 
investigation plan shall be submitted with a request for agreement, unless otherwise 
justified,  not  later  than  upon  completion  of  the  human  pharmaco-kinetic  studies  in 
adults specified in Section 5.2.3 of Part I of Annex I to Directive 2001/83/EC, so as 
to ensure that an opinion on use in the paediatric population of the medicinal product 
concerned can be given at the time of the assessment of the marketing authorisation 
or other application concerned. 

Within 30 days of receiving the request referred to in paragraph 1, the Agency shall 
verify  the  validity  of  the  request  and  shall  prepare  a  summary  report  for  the 
Paediatric Committee. 

Whenever  appropriate,  the  Agency  may  ask  the  applicant  to  submit  additional 
particulars  and  documents,  in  which  case  the  time-limit  of  30  days  shall  be 
suspended  until  such  time  as  the  supplementary  information  requested  has  been 
provided. 

Article 18 

Within 60 days of receiving a proposed paediatric investigation plan which is valid, 
the  Paediatric  Committee  shall  adopt  an  opinion  as  to  whether  or  not  the  proposed 
studies will ensure the generation of the necessary data determining the conditions in 
which the medicinal product may be used to treat the paediatric population or subsets 
thereof, and as to whether or not the expected therapeutic benefits justify the studies 
proposed. 

Within the same period, either the applicant or the Paediatric Committee may request 
a meeting. 

Within the 60-day period referred to in paragraph 1, the Paediatric Committee may 
request  the  applicant  to  propose  modifications  to  the  plan,  in  which  case  the 
time-limit  referred  to  in  paragraph  1  for  the  adoption  of  the  final  opinion  shall  be 
extended  for  a  maximum  of  60  days.  In  such  cases,  the  applicant  or  the  Paediatric 
Committee  may  request  an  additional  meeting  during  this  period.  The  time-limit 
shall  be  suspended  until  such  time  as  the  supplementary  information  requested  has 
been provided. 

As  soon  as  the  Paediatric  Committee  adopts  an  opinion,  whether  positive  or  negative,  the 
procedure laid down in Chapter 4 shall apply. 

Article 19 

Article 20 

If, having considered a paediatric investigation plan, the Paediatric Committee concludes that 
Article  12(1)(a),  (b)  or  (c)  applies  to  the  medicinal  product  concerned,  it  shall  adopt  a 
negative opinion under Article 18(1). 

EN 

21 

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In  such  cases,  the  Paediatric  Committee  shall  adopt  an  opinion  in  favour  of  a  waiver  under 
Article 13, whereupon the procedure laid down in Chapter 4 shall apply. 

SECTION 2 
DEFERRALS 

Article 21 

1. 

2. 

1. 

At  the  same  time  as  the  paediatric  investigation  plan  is  submitted  under 
Article 17(1), a request  may be made for deferral of the initiation or completion of 
some  or  all  of  the  measures  set  out  in  that  plan.  Such  deferral  shall  be  justified  on 
scientific and technical grounds or on grounds related to public health.  

In any case, a deferral shall be granted when it is appropriate to conduct studies in 
adults  prior  to  initiating  studies  in  the  paediatric  population  or  when  studies  in  the 
paediatric population will take longer to conduct than studies in adults. 

On the basis of the experience acquired as a result of the operation of this Article, the 
Commission  may  adopt  provisions  in  accordance  with  the  procedure  referred  to  in 
Article 51(2) to define further the grounds for granting a deferral. 

Article 22 

At  the  same  time  as  the  Paediatric  Committee  adopts  a  positive  opinion  under 
Article 18(1),  it  shall,  of  its  own  motion  or  following  a  request  submitted  by  the 
applicant under Article 21, adopt an opinion, if the conditions specified in Article 21 
are  met,  in  favour  of  deferring  the  initiation  or  completion  of  some  or  all  of  the 
measures in the paediatric investigation plan. 

An  opinion  in  favour  of  a  deferral  shall  specify  the  time-limits  for  initiating  or 
completing the measures concerned. 

2. 

As  soon  as  the  Paediatric  Committee  adopts  an  opinion  in  favour  of  deferral,  as 
referred to in paragraph 1, the procedure laid down in Chapter 4 shall apply. 

SECTION 3 
MODIFICATION OF A PAEDIATRIC INVESTIGATION PLAN 

Article 23 

If,  after  the  decision  agreeing  the  paediatric  investigation  plan,  the  applicant  encounters 
difficulties  with  its  implementation  such  as  to  render  the  plan  unworkable  or  no  longer 
appropriate,  the  applicant  may  propose  changes  or  request  a  deferral  or  a  waiver,  based  on 
detailed grounds, to the Paediatric Committee. The Paediatric Committee shall review these 
changes and adopt an opinion proposing their refusal or acceptance. As soon as the Paediatric 
Committee  adopts  an  opinion,  whether  positive  or  negative,  the  procedure  laid  down  in 
Chapter 4 shall apply. 

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SECTION 4 
COMPLIANCE WITH THE PAEDIATRIC INVESTIGATION PLAN 

Article 24 

The Paediatric Committee may, in the following cases, be requested to give its opinion as to 
whether  studies  conducted  by  the  applicant  are  in  compliance  with  the  agreed  paediatric 
investigation plan: 

(a) 

(b) 

(c) 

by  the  applicant,  prior  to  submitting  an  application  for  marketing  authorisation  or 
variation as referred to in Articles 8 and 9, respectively; 

by  the  Agency,  or  the  competent  authority,  when  validating  an  application,  as 
referred  to  in  point  (a),  which  does  not  include  an  opinion  concerning  compliance 
adopted following a request under point (a); 

by  the  Committee  for  Medicinal  Products  for  Human  Use,  or  the  competent 
authority,  when  assessing  an  application,  as  referred  to  in  point  (a),  where  there  is 
doubt concerning compliance and an opinion has not been given already following a 
request under points (a) or (b). 

Member States shall take account of such an opinion. 

If the Paediatric Committee is asked to give an opinion under the first paragraph, it must do so 
within 60 days of receiving the request. 

Article 25 

If, when conducting the scientific assessment of a valid application, the competent authority 
concludes that the studies are not compliant with the agreed paediatric investigation plan, the 
product shall not be eligible for the rewards provided for in Articles 36 and 37. 

CHAPTER 4 
PROCEDURE 

Article 26 

1. 

2. 

Within 30 days of receiving the opinion  of the Paediatric Committee, the applicant 
may  submit  to  the  Agency  a  written  request,  on  detailed  grounds,  for  a 
re-examination of the opinion. 

Within 30 days of receiving a request for re-examination pursuant to paragraph 1, the 
Paediatric Committee, having appointed a new rapporteur, shall issue a new opinion 
confirming or revising its previous opinion. The opinion shall be duly reasoned and a 
statement of reasons for the conclusion reached shall be annexed to the new opinion, 
which shall become definitive. 

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3. 

4. 

5. 

If, within the 30-day period referred to in paragraph 1, the applicant does not request 
re-examination, the opinion of the Paediatric Committee shall become definitive. 

The  Agency  shall  adopt  a  decision  without  delay.  This  decision  shall  be 
communicated to the applicant. 

In  the  case  of  a  class  waiver  as  referred  to  in  Article  13,  the  Agency  shall  adopt  a 
decision, which shall be published. 

CHAPTER 5 
MISCELLANEOUS PROVISIONS 

Article 27 

The sponsor of a medicinal product intended for paediatric use may, prior to the submission 
of  a  paediatric  investigation  plan  and  during  its  implementation,  request  advice  from  the 
Agency on the design and conduct of the various tests and studies necessary to demonstrate 
the  quality,  safety  and  efficacy  of  the  medicinal  product  in  the  paediatric  population  in 
accordance with Article 57(1)(n) of Regulation (EC) No 726/2004. 

In addition, the sponsor may request advice on the design and conduct of pharmacovigilance 
and risk management systems as referred to in Article 35. 

The Agency shall provide advice under this Article free of charge. 

TITLE III 

Marketing authorisation procedures 

Article 28 

Save  where  otherwise  provided  in  this  Title,  marketing  authorisation  procedures  for  the 
marketing authorisations covered by this Title shall be governed by the provisions laid down 
in Regulation (EC) No 726/2004 or in Directive 2001/83/EC. 

CHAPTER 1 
MARKETING AUTHORISATION PROCEDURES FOR APPLICATIONS FALLING 
WITHIN THE SCOPE OF ARTICLES 8 AND 9 

Article 29 

1. 

Applications  may  be  submitted  in  accordance  with  the  procedure  laid  down  in 
Articles  5  to  15  of  Regulation  (EC)  No 726/2004  for  a  marketing  authorisation  as 
referred to in Article 8(1) of this Regulation which includes one or more paediatric 

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indications selected on the basis of studies conducted in compliance with an agreed 
paediatric investigation plan. 

Where  authorisation  is  granted,  the  results  of  those  studies  shall  be  included  in  the 
summary of product characteristics and, if appropriate, in the package leaflet of the 
medicinal  product,  whether  or  not  all  the  paediatric  indications  concerned  were 
approved. 

2. 

3. 

Where a marketing authorisation is granted or varied, any waiver or deferral which 
has  been  granted  pursuant  to  this  Regulation  shall  be  recorded  in  the  summary  of 
product  characteristics  and  if  appropriate,  the  package  leaflet  of  the  medicinal 
product concerned. 

If the application complies with all the measures contained in the agreed completed 
paediatric  investigation  plan  and  if  the  summary  of  product  characteristics  reflects 
the  results  of  studies  conducted  in  compliance  with  that  agreed  paediatric 
investigation  plan,  the  competent  authority  shall  include  within  the  marketing 
authorisation  a  statement  indicating  compliance  of  the  application  with  the  agreed 
completed paediatric investigation plan. 

Article 30 

In  the  case  of  medicinal  products  authorised  under  Directive  2001/83/EC,  an  application  as 
referred to in Article 9 of this Regulation may be submitted, in accordance with the procedure 
laid  down  in  Articles  32,  33  and  34  of  Directive  2001/83/EC,  for  authorisation  of  a  new 
indication, including the extension of an authorisation for use in the paediatric population, a 
new pharmaceutical form or a new route of administration. 

That application shall comply with the requirement laid down in point (a) of Article 8(1). 

The procedure shall be limited to the assessment of the specific sections of the summary of 
product characteristics to be varied. 

CHAPTER 2 
PAEDIATRIC USE MARKETING AUTHORISATION 

Article 31 

1. 

For  the  purposes  of  this  Regulation,  a  paediatric  use  marketing  authorisation  shall 
mean a marketing authorisation granted in respect of a medicinal product for human 
use  which  is  not  protected  by  a  supplementary  protection  certificate  under 
Regulation (EEC) No 1768/92 or by a patent which qualifies for the granting of the 
supplementary  protection  certificate,  covering  exclusively  therapeutic  indications 
which are relevant for use in the paediatric population, or subsets thereof, including 
the  appropriate  strength,  pharmaceutical  form  or  route  of  administration  for  that 
product. 

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2. 

3. 

4. 

5. 

Submission of an application for a paediatric use marketing authorisation shall in no 
way preclude the right to apply for a marketing authorisation for other indications. 

An application for a paediatric use marketing authorisation shall be accompanied by 
the  particulars  and  documents  necessary  to  establish  safety,  quality  and  efficacy  in 
children,  including  any  specific  data  needed  to  support  an  appropriate  strength, 
pharmaceutical form or route of administration of the product, in accordance with an 
agreed paediatric investigation plan. 

The application shall also include the decision of the Agency agreeing the paediatric 
investigation plan concerned. 

Where  a  medicinal  product  is  or  has  been  authorised  in  a  Member  State  or  in  the 
Community, data contained in the dossier on that product may, where appropriate, be 
referred  to,  in  accordance  with  Article  14(11)  of  Regulation  (EC)  No 726/2004  or 
Article 10 of Directive 2001/83/EC, in an application for a paediatric use marketing 
authorisation. 

The medicinal product in respect of which a paediatric use marketing authorisation is 
granted  may  retain  the  name  of  any  medicinal  product  which  contains  the  same 
active  substance  and  in  respect  of  which  the  same  holder  has  been  granted 
authorisation for use in adults. 

Article 32 

Without  prejudice  to  Article  3(2)  of  Regulation  (EC)  No 726/2004,  an  application  for  a 
paediatric  use  marketing  authorisation  may  be  made  in  accordance  with  the  procedure  laid 
down in Articles 5 to 15 of Regulation (EC) No 726/2004. 

CHAPTER 3 
IDENTIFICATION 

Article 33 

Where  a  medicinal  product  is  granted  a  marketing  authorisation  for  a  paediatric  indication 
based  on  the  results  of  studies  conducted  in  compliance  with  an  agreed  paediatric 
investigation  plan,  the  label  shall  display  the  name  of  the  medicinal  product  followed  by  a 
superscript of the letter “P” in blue lettering surrounded by the outline of a star, also in blue, 
for any paediatric presentation. 

The  first  paragraph  shall  apply  whether  the  name  of  the  medicinal  product  is  an  invented 
name  or  a  common  name  as  referred  to  in  Article  1(20)  and  (21),  respectively,  of 
Directive 2001/83/EC. 

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TITLE IV 

Post-authorisation requirements 

Article 34 

Where medicinal products are authorised for a paediatric indication following completion of 
an agreed paediatric investigation plan and those products have already been marketed with 
other  indications,  the  marketing  authorisation  holder  shall,  within  two  years  of  the  date  on 
which  the  paediatric  indication  is  authorised,  place  the  product  on  the  market  taking  into 
account the paediatric indication. 

1. 

2. 

Article 35 

In  the  following  cases,  the  applicant  shall  detail,  in  addition  to  the  normal 
requirements for post-marketing monitoring, the measures to ensure the follow-up of 
efficacy  and  of  possible  adverse  reactions  to  the  paediatric  use  of  the  medicinal 
product: 

(a) 

applications for a marketing authorisation that includes a paediatric indication; 

(b) 

applications  to  include  a  paediatric  indication  in  an  existing  marketing 
authorisation; 

(c) 

applications for a paediatric use marketing authorisation. 

Where there is particular cause for concern, the competent authority may require, as 
a condition for granting marketing authorisation, that a risk management system be 
set up or that specific post-marketing studies be performed and submitted for review. 
The  risk  management  system  shall  comprise  a  set  of  activities  and  interventions 
designed  to  prevent  or  minimise  risks  relating  to  medicinal  products,  including  the 
assessment of the effectiveness of those interventions. 

Assessment  of  the  effectiveness  of  any  risk  management  system  and  the  results  of 
any studies performed shall be included in the periodic safety update reports referred 
to  in  Article  104(6)  of  Directive  2001/83/EC  and  Article  24(3)  of  Regulation  (EC) 
No 726/2004. 

In  addition,  the  competent  authority  may  request  submission  of  additional  reports 
assessing  the  effectiveness  of  any  risk  minimisation  system  and  the  results  of  any 
such studies performed. 

3. 

In the case  of a  deferral,  the  marketing authorisation  holder  shall submit an annual 
report  to  the  Agency  providing  an  update  on  progress  with  paediatric  studies  in 
accordance  with  the  decision  of  Agency  agreeing  the  paediatric  investigation  plan 
and granting a deferral. 

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27 

   EN 

 
The  Agency  shall  inform  the  competent  authority  if  it  is  found  that  the  marketing 
authorisation holder has failed to comply with the decision of Agency agreeing the 
paediatric investigation plan and granting a deferral. 

4. 

The  Agency  shall  draw  up  detailed  guidelines  relating  to  the  application  of  this 
Article. 

TITLE V 

Rewards and incentives 

Article 36 

1. 

2. 

3. 

4. 

Where  an  application  under  Articles  8  or  9  includes  the  results  of  all  studies 
conducted in compliance with an agreed paediatric investigation plan, the holder of 
the  patent  or  supplementary  protection  certificate  shall  be  entitled  to  a  six-month 
extension of the period referred to in Articles 13(1) and 13(2) of Regulation (EEC) 
No 1768/92. 

The  first  subparagraph  shall  also  apply  where  completion  of  the  agreed  paediatric 
investigation plan fails to lead to the authorisation of a paediatric indication, but the 
results  of  the  studies  conducted  are  reflected  in  the  summary  of  product 
characteristics,  and  if  appropriate,  in  the  package  leaflet  of  the  medicinal  product 
concerned. 

The  inclusion  in  a  marketing  authorisation  of  the  statement  referred  to  in 
Article 29(3) shall be used for the purposes of applying paragraph 1 of this Article. 

Where  the  procedures  laid  down  in  Directive  2001/83/EC  have  been  used,  the 
six-month extension of the period referred to in paragraph 1 shall be granted only if 
the product is authorised in all Member States. 

Paragraphs 1, 2 and 3 shall apply to products that are protected by a supplementary 
protection  certificate  under  Regulation (EEC)  No 1768/92,  or  under  a  patent  which 
qualifies  for  the  granting  of  the  supplementary  protection  certificate.They  shall  not 
apply  to  medicinal  products  designated  as  orphan  medicinal  products  pursuant  to 
Regulation (EC) No 141/2000. 

Article 37 

Where  an  application  for  a  marketing  authorisation  is  submitted  in  respect  of  a  medicinal 
product designated as an orphan medicinal product pursuant to Regulation (EC) No 141/2000 
and that application includes the results of all studies conducted in compliance with an agreed 
paediatric investigation plan, and the statement referred to in Article 29(3) of this Regulation 
is subsequently included in the marketing authorisation granted, the ten-year period referred 
to in Article 8(1) of Regulation (EC) No 141/2000 shall be extended to twelve years. 

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28 

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The first paragraph shall also apply where completion of the agreed paediatric investigation 
plan fails to lead to the authorisation of a paediatric indication, but the results of the studies 
conducted are reflected in the summary of product  characteristics, and  if appropriate, in the 
package leaflet of the medicinal product concerned. 

1. 

2. 

1. 

2. 

3. 

Article 38 

Where  a  paediatric  use  marketing  authorisation  is  granted  in  accordance  with 
Articles 5 to 15 of Regulation (EC) No 726/2004, the data and marketing protection 
periods referred to in Article 14(11) of that Regulation shall apply. 

Where  a  paediatric  use  marketing  authorisation  is  granted  in  accordance  with  the 
procedures  laid  down  in  Directive  2001/83/EC,  the  data  and  marketing  protection 
periods referred to in Article 10(1) of that Directive shall apply. 

Article 39 

In  addition  to  the  rewards  and  incentives  provided  for  in  Articles  36,  37  and  38, 
medicinal products for paediatric use may be eligible for incentives provided by the 
Community or by the Member States to support research into, and the development 
and availability of, medicinal products for paediatric use. 

Within one year of the entry into force of this Regulation, the Member States shall 
communicate to the Commission detailed information concerning any measures they 
have  enacted  to  support  research  into,  and  the  development  and  availability  of, 
medicinal products for paediatric use. This information shall be updated regularly at 
the request of the Commission. 

Within  18  months  of  the  entry  into  force  of  this  Regulation,  the  Commission  shall 
publish  a  detailed  inventory  of  all  incentives  provided  by  the  Community  and 
Member  States  to  support  research  into,  and  the  development  and  availability  of, 
medicinal products for paediatric use. This inventory shall be updated regularly. 

TITLE VI 

Communication and coordination 

Article 40 

1. 

Appropriate details of trials that are contained within agreed paediatric investigation 
plans, including those that are carried out in third countries, shall be entered into the 
European database created by Article 11 of Directive 2001/20/EC. 

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29 

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2. 

The  Commission  shall,  on  a  proposal  by  the  Agency  and  in  consultation  with 
Member  States  and  interested  parties,  draw  up  guidance  on  the  nature  of  the 
information referred to in paragraph 1 to be entered in the European database created 
by Article 11 of Directive 2001/20/EC. 

Article 41 

Member  States  shall  collect  available  data  on  all  existing  uses  of  medicinal  products  in  the 
paediatric  population  and,  within  2  years  of  the  entry  into  force  of  this  Regulation,  shall 
communicate these data to the Agency. 

The Paediatric Committee shall provide guidance on the content and the format of the data to 
be collected. 

1. 

2. 

3. 

1. 

2. 

3. 

Article 42 

The Agency shall assess the data referred to in Article 41, in particular with a view to 
identifying research priorities. 

On  the  basis  of  the  assessment  under  paragraph  1  and  other  information  available, 
and following consultation with the Commission, the Member States and interested 
parties, the Paediatric Committee shall establish an inventory of therapeutic needs. 

The Agency shall publish the inventory within 3 years of the entry into force of this 
Regulation, and shall update it on a regular basis. 

In  establishing  the  inventory  of  therapeutic  needs,  account  shall  be  taken  of  the 
prevalence  of  the  conditions  in  the  paediatric  population,  the  seriousness  of  the 
conditions to  be treated,  the  availability and suitability of alternative treatments  for 
the  conditions  in  the  paediatric  population,  including  the  efficacy  and  the  adverse 
reaction profile of those treatments, including any unique paediatric safety issues. 

Article 43 

The Agency shall, with the scientific support of the Paediatric Committee, develop a 
European  network  of  existing  national  and  European  networks,  investigators  and 
centres  with  specific  expertise  in  the  performance  of  studies  in  the  paediatric 
population. 

The  objectives  of  the  European  network  shall  be,  inter  alia,  to  coordinate  studies 
relating  to  paediatric  medicinal  products,  to  build  up  the  necessary  scientific  and 
administrative  competences  at  European  level,  and  to  avoid  duplication  of  studies 
and testing in children. 

Within one year of the entry into force of this Regulation, the Management Board of 
the  Agency  shall,  on  a  proposal  from  the  Executive  Director  and  following 
consultation  with  the  Commission,  the  Member  States  and  interested  parties,  adopt 
an implementing strategy for the launching and operation of the European network. 
This network must, where appropriate, be compatible with the work of strengthening 

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the  foundations  of  the  European  Research  Area  in  the  context  of  the  Community 
and 
Framework  Programmes 
Demonstration Activities. 

for  Research,  Technological  Development 

Article 44 

1. 

Within  one  year  of  the  entry  into  force  of  this  Regulation,  any  paediatric  studies 
already completed, by the date of entry into force, in respect of products authorised 
in the Community shall be submitted for assessment to the competent authority. 

The  competent  authority  shall,  as  appropriate,  update  the  summary  of  product 
characteristics  and  package  leaflet,  and  shall  vary  the  marketing  authorisation 
accordingly. Competent authorities shall exchange information regarding the studies 
submitted and their implications for any marketing authorisations concerned. 

The Agency shall coordinate the exchange of information. 

2. 

3. 

All  existing  paediatric  studies,  as  referred  to  in  paragraph  1,  shall  be  taken  into 
consideration by the Paediatric Committee when assessing applications for paediatric 
investigation  plans,  waivers  and  deferrals  and  by  competent  authorities  when 
assessing applications submitted pursuant to Articles 8, 9 or 31. 

No paediatric studies, as referred to in paragraph 1, which have at the date of entry 
into  force  of  this  Regulation  already  been  submitted  for  assessment  in  a  third 
country, shall be taken into consideration for the rewards and incentives provided for 
in Articles 36, 37 and 38. 

Article 45 

Any  other  marketing  authorisation  holder  sponsored  studies  which  involve  the  use  in  the 
paediatric population of a medicinal product covered by a marketing authorisation, whether or 
not  they  are  conducted  in  compliance  with  an  agreed  paediatric  investigation  plan,  shall  be 
submitted  to  the  competent  authority  within  six  months  of  the  completion  of  the  studies 
concerned. 

The first paragraph shall apply whether or not the marketing authorisation holder intends to 
apply for a paediatric indication. 

The competent authority shall, as appropriate, update the summary of product characteristics 
and package leaflet, and shall vary the marketing authorisation accordingly. 

Competent  authorities  shall  exchange  information  regarding  the  studies  submitted  and  their 
implications for any marketing authorisations concerned. 

The Agency shall coordinate the exchange of information. 

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TITLE VII 

General and final provisions 

CHAPTER 1 
GENERAL 

SECTION 1 
FEES, COMMUNITY FUNDING, PENALTIES AND REPORTS 

Article 46 

1. 

2. 

3. 

Where  an  application  for  a  paediatric  use  marketing  authorisation  is  submitted  in 
accordance  with  the  procedure  laid  down  in  Regulation  (EC)  No 726/2004,  the 
amount  of  the  reduced  fees  for  the  examination  of  the  application  and  the 
maintenance  of  the  marketing  authorisation  shall  be  fixed  in  accordance  with 
Article 70 of Regulation (EC) No 726/2004. 

Council Regulation (EC) No 297/9511 shall apply. 

Assessments of the following by the Paediatric Committee shall be free of charge: 

(a) 

applications for waiver; 

(b) 

applications for deferral; 

(c) 

paediatric investigation plans; 

(d) 

compliance with the agreed paediatric investigation plan. 

Article 47 

The Community contribution provided for in Article 67 of Regulation (EC) No 726/2004 shall 
cover  all  aspects  of  the  work  of  the  Paediatric  Committee,  including  scientific  support 
provided by experts, and of the Agency, including the assessment of paediatric investigation 
plans, scientific advice and any fee waivers provided for in this Regulation, and shall support 
the Agency’s activities under Articles 40 and 43 of this Regulation. 

1. 

Without prejudice to the Protocol on the Privileges and Immunities of the European 
Communities,  each  Member  State  shall  determine  the  penalties  to  be  applied  for 

Article 48  

11 

OJ L 35, 15.2.1995, p. 1. 

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infringement  of  the  provisions  of  this  Regulation  or  the  implementing  measures 
adopted  pursuant  to  it  in  relation  to  medicinal  products  authorised  through  the 
procedures laid down in Directive 2001/83/EC and shall take all measures necessary 
for  their  implementation.  The  penalties  shall  be  effective,  proportionate  and 
dissuasive. 

Member States shall inform the Commission of these provisions no later than […]. 
They shall notify any subsequent alterations as soon as possible. 

Member States shall inform the Commission immediately of any litigation instituted 
for infringement of this Regulation. 

At  the  Agency's  request,  the  Commission  may  impose  financial  penalties  for 
infringement  of  the  provisions  of  this  Regulation  or  the  implementing  measures 
adopted  pursuant  to  it  in  relation  to  medicinal  products  authorised  through  the 
procedure  laid  down  in  Regulation  (EC)  No 726/2004.  The  maximum  amounts  as 
well  as  the  conditions  and  methods  for  collection  of  these  penalties  shall  be  laid 
down  in  accordance  with  the  procedure  referred  to  in  Article  51(2)  of  this 
Regulation. 

The  Commission  shall  publish  the  names  of  the  marketing  authorisation  holders 
involved and the amounts of and reasons for the financial penalties imposed. 

Article 49 

On  the  basis  of  a  report  from  the  Agency  and  at  least  on  an  annual  basis,  the 
Commission shall publish a list of the companies that have benefited from any of the 
rewards  and  incentives  in  this  Regulation  and  the  companies  that  have  failed  to 
comply  with  any  of  the  obligations  in  this  Regulation.  The  Member  States  shall 
provide this information to the Agency. 

Within six years of entry into force of this Regulation, the Commission shall publish 
a  general  report  on  experience  acquired  as  a  result  of  its  application,  including  in 
particular a detailed inventory of all medicinal products authorised for paediatric use 
since its entry into force. 

2. 

3. 

4. 

1. 

2. 

SECTION 2 
COMMITTEE 

Article 50 

The  Commission  shall,  after  consulting  the  Agency,  adopt  appropriate  provisions  for  the 
performance of the tasks of the Paediatric Committee referred to in Article 7 in the form of a 
Regulation in accordance with the procedure referred to in Article 51(2). 

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1. 

2. 

Article 51 

The Commission shall be assisted by the Standing Committee on Medicinal Products 
for Human Use set up by Article 121 of Directive 2001/83/EC. 

reference 

this  paragraph,  Articles  5  and  7  of 
Where 
Decision 1999/468/EC  shall  apply,  having  regard  to  the  provisions  of  Article  8 
thereof. 

is  made 

to 

The period laid down in Article 5(6) of Decision 1999/468/EC shall be set at three 
months. 

CHAPTER 2 
AMENDMENTS 

Article 52 

Regulation (EEC) No 1768/92 is amended as follows: 

(1) 

In Article 7, the following paragraph 3 is added: 

“3.  The application for an extension of the duration of a certificate already granted 
in  application  of  Article  13(3)  of  this  Regulation  and  of  Article  36  of 
Regulation  (EC)  No […/…  of  the  European  Parliament  and  of  the  Council 
(Paediatric  Regulation)*]  shall  be  lodged  not  later  than  two  years  before  the 
expiry of the certificate. 

_____________________ 
* 

OJ L […], […], p. […].” 

(2) 

Article 8 shall be amended as follows: 

(a) 

in paragraph 1, the following point (d) is added: 

“(d)  where the application for a certificate includes a request for an extended 
duration in application of Article 13(3) of this Regulation and Article 36 
of Regulation (EC) No […/…(Paediatric Regulation)]: 

(i) 

a  copy  of  the  statement  indicating  compliance  with  an  agreed 
completed  paediatric 
in 
Article 36(3) 
(EC)  No […/…(Paediatric 
Regulation)]; 

investigation  plan  as 

Regulation 

referred 

of 

to 

(ii)  where  necessary,  in  addition  to  the  copy  of  the  authorisations  to 
place the product on the market as referred to in point (b), copies of 
the  authorisations  to  place  the  product  on  the  market  of  all  other 
Member States, as referred to in Article 36(4) of Regulation  (EC) 
No […/… (Paediatric Regulation)] .” 

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34 

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(b) 

the following paragraph 1a is inserted: 

“1a.  The  application  for  an  extension  of  the  duration  of  a  certificate  already 

granted shall contain: 

(a) 

a copy of the certificate already granted; 

(b) 

a  copy  of  the  statement  indicating  compliance  with  an  agreed 
in 
to 
completed  paediatric 
Article 36(3) 
(Paediatric 
Regulation)]; 

investigation  plan  as 

(EC)  No […/… 

of  Regulation 

referred 

(c) 

copies  of  the  authorisations  to  place  the  product  on  the  market  of 
all Member States.” 

(c) 

paragraph 2 is replaced by the following: 

“2.  Member States may provide that a fee is to be payable upon application 
for a certificate and upon application for the extension of the duration of 
a certificate.” 

(3) 

Article 9 is amended as follows: 

(a) 

in paragraph 1, the following subparagraph is added: 

“The  application  for  an  extension  of  the  duration  of  a  certificate  already 
granted  shall  be  lodged  with  the  competent  industrial  property  office  of  the 
Member State which granted the certificate.” 

(b) 

the following paragraph 3 is added: 

“3.  Paragraph  2  shall  apply  to  the  notification  of  the  application  for  an 
extension  of  the  duration  a  certificate  already  granted.  The  notification 
shall  additionally  contain  the  request  for  an  extended  duration  of  the 
(EC) 
certificate 
No […/… (Paediatric Regulation)].” 

in  application  of  Article  36  of  Regulation 

(4) 

In Article 11, the following paragraph 3 is added: 

“3.  Paragraphs 1 and 2 shall apply to the notification of the fact that an extension 
of the duration of a certificate already granted has been granted or rejected.” 

(5) 

In Article 13, the following paragraph 3 is added: 

“3.  The periods laid down in paragraphs 1 and 2 shall be extended by six months 
in 
(EC) 
No […/… (Paediatric Regulation)]. In that case, the duration of the period laid 
down in paragraph 1 of this Article may be extended only once.” 

the  case  of  application  of  Article  36  of  Regulation 

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Article 53 

In Article 6 of Directive 2001/83/EC, the first subparagraph of paragraph 1 is replaced by the 
following: 

“No medicinal product may be placed on the market of a Member State unless a marketing 
authorisation has been issued by the competent authorities of that Member State in accordance 
with this Directive or an authorisation has been granted in accordance with Regulation (EC) 
No. 726/2004, read in conjunction with Regulation (EC) No […/of the European Parliament 
and of the Council (Paediatric Regulation)*]. 

___________________ 

* 

OJ L […], […], p. […].” 

Article 54 

Regulation (EC) No.726/2004 is amended as follows: 

(1) 

Article 56(1) is replaced by the following: : 

“1.  The Agency shall comprise: 

(a) 

(b) 

the  Committee  for  Medicinal  Products  for  Human  Use,  which  shall  be 
responsible  for  preparing  the  opinion  of  the  Agency  on  any  question 
relating to the evaluation of medicinal products for human use; 

the Committee for Medicinal Products for Veterinary Use, which shall be 
responsible  for  preparing  the  opinion  of  the  Agency  on  any  question 
relating to the evaluation of medicinal products for veterinary use; 

(c) 

the Committee on Orphan Medicinal Products; 

(d) 

the Committee on Herbal Medicinal Products; 

(e) 

the Paediatric Committee; 

(f) 

(g) 

(h) 

a Secretariat, which shall provide technical, scientific and administrative 
support for the committees and ensure appropriate coordination between 
them; 

an  Executive  Director,  who  shall  exercise  the  responsibilities  set  out  in 
Article 64; 

a Management Board, which shall exercise the responsibilities set out in 
Articles 65, 66 and 67.” 

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36 

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(2) 

The following Article 73a is inserted: 

“Article 73a 

Decisions  taken  by  the  Agency  under  Regulation  (EC)  No  […/…  of  the  European 
Parliament and of the Council (Paediatric Regulation)*] may form the subject of an 
action before the Court of Justice of the European Communities under the conditions 
laid down in Article 230 of the Treaty. 

___________________ 
* 

OJ L […], […], p. […].” 

CHAPTER 3 
FINAL PROVISIONS 

Article 55 

The requirement laid down in Article 8(1) shall not apply to valid applications pending at the 
time of entry into force of this Regulation. 

Article 56 

1. 

2. 

This  Regulation  shall  enter  into  force  on  the  thirtieth  day  following  that  of  its 
publication in the Official Journal of the European Union. 

Article 8 shall apply from … [18 months following the entry into force]. 

Article 9 shall apply from … [24 months following the entry into force]. 

Articles 31 and 32 shall apply from … [6 months following the entry into force]. 

This Regulation shall be binding in its entirety and directly applicable in all Member States. 

Done at Brussels, […] 

For the European Parliament 
The President 
[…] 

For the Council 
The President 
[…] 

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37 

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LEGISLATIVE FINANCIAL STATEMENT 

Policy area(s): Internal market 

Activities: The activities of the European Medicines Agency are included in the following policies: 

Improvement in the protection of public health and for consumers across the Community 

-  Support for the development of paediatric medicines ; 
- 
-  Maintaining a reliable and independent source of scientific advice and information, and 
-  Support and achievement of the internal market for the pharmaceutical sector. 

TITLE  OF  ACTION:  REGULATION  OF  THE  EUROPEAN  PARLIAMENT  AND  OF  THE  COUNCIL  ON 
MEDICINAL PRODUCTS FOR PAEDIATRIC USE AND AMENDING REGULATION (EEC) NO 1768/92, 
DIRECTIVE 2001/83/EC AND REGULATION (EC) NO 726/2004 

1. 

BUDGET LINE(S) + HEADING(S) 

02.040201  –  European  Agency  for  the  Evaluation  of  Medicinal  Products  —  Subsidy  under 
Titles 1 and 2 

02.040202  –  European  Agency  for  the  Evaluation  of  Medicinal  Products  —  Subsidy  under 
Title 3 

2. 

OVERALL FIGURES  

2.1. 

Total allocation for action (Part B): € million for commitment 

EUR 21 282 million 

2.2. 

Period of application: 

2007 to 2012 

2.3. 

Overall multiannual estimate of expenditure: 

(a) 

Schedule  of  commitment  appropriations/payment  appropriations 
intervention) (see point 6.1.1) 

(financial 

EUR million (to three decimal places) 

Year 
2007 

2008 

2009 

2010 

2011 

2012 
and 
subs. 
Years 

Total 

Commitments 

1,000 

3,039 

3,377 

3,598 

5,053 

5,215 

21,282 

Payments 

1,000 

3,039 

3,377 

3,598 

5,053 

5,215 

21,282 

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(b) 

Technical and administrative assistance and support expenditure(see point 6.1.2) 

Commitments 

Payments 

Subtotal a+b 

Commitments 

1,000 

3,039 

3,377 

3,598 

5,053 

5,215 

21,282 

Payments 

1,000 

3,039 

3,377 

3,598 

5,053 

5,215 

21,282 

(c) 

Overall  financial  impact  of  human  resources  and  other  administrative  expenditure 
(see points 7.2 and 7.3) 

Commitments/ 
payments 

TOTAL a+b+c 

Commitments 

1,000 

3,039 

3,377 

3,598 

5,053 

5,215 

21,282 

Payments 

1,000 

3,039 

3,377 

3,598 

5,053 

5,215 

21,282 

2.4. 

Compatibility with financial programming and financial perspective 

[X]  Proposal  will  entail  reprogramming  of  the  relevant  heading  in  the  financial 
perspective.  The  proposal  is  compatible  with  the  new  financial  framework 
the 
(2007-2013)  proposed  by 
Commission to the Council and the European Parliament COM(2004) 101). 

the  Commission  (Communication  from 

2.5. 

Financial impact on revenue1: 

[X]  Proposal  has  no  financial  implications  (involves  technical  aspects  regarding 

implementation of a measure) 

3. 

BUDGET CHARACTERISTICS 

Type of expenditure 

Budget 
line 

New  EFTA 
contrib
ution 

Contributions 
from 
applicant 
countries 

Heading in 
financial 
perspective

Non-comp  Non-diff  02.040201 NO 

Non-comp  Non-diff  02.040202 NO 

YES 

YES 

NO 

NO 

1 a 

1 a 

1 

For further information, see separate explanatory note. 

EN 

39 

   EN 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                 
4. 

LEGAL BASIS  

–  Treaty establishing the European Community and notably article 235. 

–  Draft Regulation of the European Parliament and of the Council on medicinal products for 
paediatric  use  (to  support  the  Agency’s  work  required  for  the  operation  of  the  draft 
Regulation  including  all  work  of  the  Paediatric  Committee,  scientific  advice  and  any  fee 
waivers provided for by virtue of the draft Regulation). 

–  Regulation (EC) No 726/2004 of the European parliament and of the Council of 30 May 
2004,  establishing  the  community  procedures  for  the  authorisation  and  follow  up  of 
medicines  for  human  and  veterinary  use,  and  establishing  the  European  Agency  for  the 
Evaluation of Medicinal Products (OJ L 136, 30.4.2004, p. 1). 

–  Council  Regulation  (EC)  No  297/95  of  10  February  1995  modified  by  Council 
Regulation (EC)  No 2743/98  of  14  December  1998  concerning  fees  payable  to  the 
European Agency for the Evaluation of Medicinal Products (OJ L 345, 19.12.1998, p. 3). 

5. 

DESCRIPTION AND GROUNDS 

5.1. 

Need for Community intervention  

5.1.1.  Objectives pursued 

It  is  estimated  that  between  50  and  90%  of  medicinal  products  used  in  the  paediatric 
population  have  never  been  specifically  studied  or  authorised  (licensed)  for  use  in  that  age 
group. This leaves no alternative to the prescriber than to use products “off-label” (i.e. use of 
product authorised for adults - products that have not been tested or authorised for paediatric 
use) or use of completely unauthorised products with the associated risks of inefficacy and/or 
adverse reactions (side effects). 

The overall policy objective is to improve the health of the children of Europe by increasing 
the research, development and authorisation of medicines for use in children. 

General objectives are to: 

•  increase the development of medicines for use in children; 

•  ensure that medicines used to treat children are subject to high quality research; 

•  ensure  that  medicines  used  to  treat  children  are  appropriately  authorised  for  use  in 

children; 

•  improve the information available on the use of medicines in children; 

•  achieve  these  objectives  without  subjecting  children  to  unnecessary  clinical  trials  and  in 

full compliance with the EU Clinical Trials Directive. 

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40 

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5.1.2.  Measures taken in connection with ex ante evaluation  

The draft Regulation of the European Parliament and of the Council on medicinal products for 
paediatric use was the subject of a Commission Extended Impact Assessment (EIA). The EIA 
accompanies  this  Financial  Statement.  The  Commission’s  EIA  is  based  on  an  independent, 
externally  contracted  study,  specifically  designed  to  estimate  the  economic,  social  and 
environmental impacts of the proposal. The EIA also draws on experience with the existing 
EU  pharmaceutical  market  and  regulatory  framework,  experience  with  legislation  on 
paediatric  medicines  in  the  US,  experience  with  orphan  medicines  in  the  EU,  extensive 
consultation with stakeholders, and the published literature.  

5.1.3.  Measures taken following ex post evaluation 

The draft Regulation of the European Parliament and of the Council on medicinal products for 
paediatric  use  is  a  new  legislative  proposal  and  no  interim  or  ex  post  evaluation  has  been 
conducted. 

5.2. 

Action envisaged and budget intervention arrangements 

The key measures included in the draft paediatric regulation are:  

•  the establishment of an expert committee, the Paediatric Committee within the EMEA;  

•  a  requirement  at  the  time  of  marketing  authorisation  applications  for  new  medicines  and 
line-extensions for existing patent-protected medicines for data on the use of the medicine 
in children resulting from an agreed paediatric investigation plan;  

•  a system of waivers from the requirement for medicines unlikely to benefit children;  

•  a  system  of  deferrals  of  the  requirement  to  ensure  medicines  are  tested  in  children  only 
when  it  is  safe  to  do  so  and  to  prevent  the  requirements  delaying  the  authorisation  of 
medicines for adults;  

•  excluding  orphan  medicines,  a  mixed  reward  and  incentive  for  compliance  with  the 
requirement  in  the  form  of  a  six-month  extension  to  the  supplementary  protection 
certificate (in effect, a six-month patent extension on the active moiety);  

•  for orphan medicines, a mixed reward and incentive for compliance with the requirement 
in the form of an additional two-years of market exclusivity added to the existing ten years 
awarded under the EU orphan regulation; 

•  a  new  type  of  marketing  authorisation,  the  PUMA,  which  allows  ten  years  of  data 

protection for innovation (new studies) on off-patent products;  

•  amended  data  requirements  for  PUMA  applications  to  attract  SMEs  including  generics 

companies; 

•  a reference in the explanatory memorandum to the establishment, via separate legislation 
of  an  EU  paediatric  study  programme  to  fund  research  leading  to  the  development  and 
authorisation of off-patent medicine for children;  

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41 

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•  access  to  an  optional  centralised  procedure  via  the  community  referral  procedure  for 
existing nationally authorised medicines to gain an EU-wide Commission Decision on use 
in children;  

•  measures to increase the robustness of pharmacovigilance for medicines for children;  

•  a requirement for industry to submit to the authorities study reports they already hold on 
use of their medicine in children, to maximise the utility of existing data and knowledge;  

•  an EU inventory of the therapeutic needs of children to focus research, development and 

authorisation of medicines;  

•  an EU network of investigators and trial centres to conduct the research and development 

required;  

•  a system of free scientific advice for the industry, provided by the EMEA;  

•  a database of paediatric studies (based on the existing database set up by the EU Directive 

on clinical trials (OJ L 121, 1.5.2001, p. 34). 

Populations affected by the activity: 

•  more  than  100  million  children  in  the  newly  enlarged  EU  stand  to  benefit  from  better 

medicines for children. Children will also be enrolled into clinical trials; 

•  healthcare  professionals  will  benefit  through  the  supply  of  medicines  specifically 
developed for children and may take part in clinical research on medicines for children; 

•  all pharmaceutical companies seeking to access the EU market will be affected by the draft 

Regulation; 

•  the  EMEA  and  all  National  competent  authorities  will  have  to  change  their  working 

practices as a result of the draft Regulation; 

Expense type 

Article  47  of  the  draft  Regulation  on  medicinal  products  for  paediatric  use  foresees  a 
contribution  from  the  Community  to  cover  the  work  resulting  from  the  draft  Regulation  on 
medicinal  products  for  paediatric  use,  incorporated  into  the  contribution  provided  for  in 
Article 67 of Regulation (EC) No 726/2004 and in Article 7 of Regulation (EC) No 141/2000 
to be allocated to the European Medicines Agency. This contribution should cover all aspects 
of  the  work  of  the  European  Medicines  Agency  to  implement  and  operate  the  draft 
Regulation, in particular: the operation of the Paediatric Committee including assessment of 
paediatric  investigation  plans,  requests  for  waivers  and  deferrals,  assessment  of  compliance 
with  paediatric  investigation  plans  and  assessment  of  the  safety,  quality  and  efficacy  of 
medicinal products for paediatric use; an EU inventory of the therapeutic needs of children; 
an EU network of investigators and trial centres to conduct the research; free scientific advice 
for the industry; a database of paediatric studies. 

The  explanatory  memorandum  of  the  draft  paediatric  regulation  makes  a  reference  to  the 
possible creation of a paediatric study programme: Medicines Investigation for the Children 

EN 

42 

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of  Europe  (MICE)2.  The  creation  of  the  funding  and  its  operation  would  be  included  in  a 
separate Commission initiative. A detailed assessment of the impacts of the programme will 
accompany  that  separate  initiative.  However,  given  the  interface  between  legislation  on  a 
paediatric  study  programme  and  the  draft  paediatric  Regulation  assessed  here,  some 
consideration  is  required.  An  EU  paediatric  study  programme,  focussed  on  funding  or  part 
funding  studies  on  off-patent  medicines  will  be  important  if  research  and  authorisation  for 
children of off-patent products are to occur for the majority of products needed by children. It 
is  envisaged  that  the  paediatric  study  programme  may  be  funded,  at  least  in  part,  from  the 
Community budget. The paediatric study programme would also need to take account of other 
relevant Community funding, including the 6th and 7th Framework Programmes operated  by 
the Commission Directorate General Research. Community funding for studies into off-patent 
medicines  for  children  (which  may  lead  to  the  authorisation  of  an  off-patent  medicine  for 
children)  may  only  be  partial,  e.g.  50%  funding:  the  remainder  of  the  funding  may  need  to 
come from industry, Member State governments or medical charities.  

An EU paediatric study programme has the potential to stimulate research and development of 
off-patent  medicines  for  children  and  could  have  a  major  beneficial  impact  on  EU 
pharmaceutical companies, including SMEs, and a major impact on clinical trials conducted 
in the EU including strengthening pharmaceutical R&D in Europe. 

Estimated resources and costs of the paediatric Regulation, based on the draft proposal 
released for consultation by the European Commission on 8 March 2004 

The  increased  contribution  will  cover:  increased  administration  costs  of  the  European 
Medicines Agency relating to all tasks of the Paediatric Committee; the costs of free scientific 
advice and fee reductions for paediatric use marketing authorisations. 

Justifications of the resources implications based on its coming into force in 2007 

As  of  2006,  the  EMEA  would  have  to  set  up  a  task  force  to  prepare  for  the  work  of  the 
Paediatric Committee and the procedures as laid out in the Regulation. It is estimated that the 
task force would require 1 A grade full time and 1 C grade half time. This will be covered by 
an internal redeployment. 

In 2007 

Activities  planned  for  the  first  year.  All  activities  are  based  on  the  EMEA’s  experience  of 
Committee activities, and in particular the experience gained in the last 3 years of activities on 
orphan medicinal products and the Committee for orphan medicinal products. Activities will 
start in full as soon as the Regulation is implemented due to the legal obligations created by it. 

2 

The impact of the referenced paediatric study programme will critically depend on its funding, size and 
awarding rules. A fund, set up under the United States Best Pharmaceuticals for Children Act 2002, is 
of $ 200 000 000 for fiscal year 2000 and such sums as are necessary for each of the succeeding five 
years for the study of the use in the paediatric population of medicinal products for which there is no 
patent  protection  or  market  exclusivity.  The  CHMP  Paediatric  Expert  Group  has  produced  a 
preliminary  list  of  sixty-five  off-patent  active  substances  considered  to  be  priorities  for  research  and 
development for children in the EU. 

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43 

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A. 

Paediatric Committee  

Functioning of the Paediatric Committee 

•  Meeting costs 

A  monthly  meeting  of  2-3  days  is  necessary.  Eleven  meetings  a  year  with  31  members  are 
envisaged,  representing  682-1023  expert  days.  In  addition,  it  is  anticipated  that  additional 
experts will be needed on an ad-hoc basis by the Paediatric Committee.  

•  Meeting Management and Conference services  

Eleven meetings a year of 31 members plus additional experts will have heavy implications 
on the Meeting Management & Conferences Sector of the EMEA which will have to organise 
travel and accommodation and meetings, as well as on the meeting room occupation.  

•  Secretariat costs 

The  secretariat  of  the  Paediatric  Committee  represents  a  full  time  position  all  year  round, 
therefore  taking  into  consideration  the  need  for  a  back-up,  this  represents  1.5  A  grade  and 
1.5 C grade positions. 

•  Expert costs 

Estimated  at  5-10  experts  per  Paediatric  Committee  meeting,  in  addition  to  members  of  the 
Paediatric Committee (i.e. 55-110 experts per year). 

Activities of the Paediatric Committee 

–  Paediatric Investigation Plans 

–  Deferrals 

–  Waiver of Paediatric Investigation Plans  

–  Paediatric needs 

–  Paediatric priorities  

–  Compliance  

–  Expert work 

In  the  draft  paediatric  Regulation,  there  is  an  obligation  to  submit  the  results  of  studies 
performed according to an agreed Paediatric Investigation Plan for applications for marketing 
authorisations  of  new  products  (Marketing  Authorisation  Applications)  and  variations  for 
patented  products.  The  best  estimate  of  the  number  of  Paediatric  Investigation  Plans  to  be 
submitted per year to the Agency in the first years is about 235-285.  

The activities related to the submission of Paediatric Investigation Plans are rather similar to 
the  work  done  for  orphan  drug  designation.  However  the  level  of  scientific  involvement  to 

EN 

44 

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judge the submitted plan is considered higher, more complex, and the number of procedures is 
2.5 times more than the current number of orphan applications. 

– 

Agreed Paediatric Investigation Plans revisions 

– 

Procedures 

It  is  not  expected  that  applications  for  the  revision  of  Paediatric  Investigation  Plans  would 
occur in the first year. Only procedures would have to be established. 

B. 

– 

Other activities created by the Regulation 

Paediatric scientific advice 

There will be an increase in scientific advice for paediatric development. It is expected that up 
to  60%  of  companies  may  seek  advice  (the  current  situation  is  about  30%  for  products 
submitted for Marketing Authorisation). This represents about three times the current number 
of  Scientific  Advice  requests  (currently  100  per  year).  See  section  6.2  for  details  of  the 
financial implications of fee waivers for paediatric scientific advice. 

– 

Information publication and management 

This has implications on the current development of the databases at the EMEA and on other 
forms of EMEA communication.  

– 

Survey of paediatric use and inventory of research priorities 

These activities will be performed by the staff in charge of other paediatric activities but will 
represent a significant part of the workload. 

– 

Establishment of a paediatric research network 

This is a new type of activity for the EMEA, which will require at least a full time position for 
an A and a C grade. 

C. 

Impact on the Agency 

In  addition  to  involving  specific  staff  all  activities  have  direct  implications  on  other  sectors 
such as Meeting Management and Conference, IT and administration. 

The activities will generate the need for regular training, workshops and will involve missions 
outside  the  Agency  (for  example  for  the  establishment  of  a  network  of  paediatric  clinical 
research). 

D. 

Need for Experts in Secondment 

To strengthen the collaboration between EMEA and Member States in particular in relation to 
paediatric  activities  on  national  products,  authorisations  and  pharmacovigilance,  the  EMEA 
will invite Experts in Secondment to join the Agency to facilitate the work. This will be done 
also at the stage of the preparatory work. 

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A typical stabilised year  

It  has  been  considered  that  year  2009  would  represent  a  typical  year,  when  the  number  of 
applications per year would be stable, and all activities provided for by the Regulation would 
be developed. 

A. 

Paediatric Committee 

Functioning of the Paediatric Committee 

–  Meeting costs 

No major changes in activities are anticipated. 

–  Meeting Management and Conference services  

No major changes in activities are anticipated. 

–  Secretariat costs 

No major changes in activities are anticipated. 

–  Experts costs 

Changes in activities may be needed. Estimates are however given for the same numbers. 

Activities of the Paediatric Committee 

Figures for new products (on patent) should remain stable. Variations capturing products that 
never  included  a  Paediatric  Investigation  Plan  should  slightly  decrease,  as  some  products 
would  have  been  captured  at  the  stage  of  marketing  authorisation  applications.  This  would 
however not be the case of variation applications in a new indication (new therapeutic area) 
for which a new Paediatric Investigation Plan may have to be submitted. 

There should not be any more products undergoing purely national procedures in respect of 
the obligation to submit a Paediatric Investigation Plan. 

The  ‘stable’  number  of  Paediatric  Use  Marketing  Authorisation  procedures  cannot  be 
estimated. It is judged that the initial figure of 15 per year should be kept.  

Overall the level of activities should remain around 235-285 procedures per year. 

The  additional  (fully  developed)  tasks  will  include  in  particular  the  Annual  Reports  on 
deferrals,  and  the  revision  of  agreed  Paediatric  Investigation  Plans.  Once  a  Paediatric 
Investigation Plan is agreed, the draft Regulation offers the possibility to amend it as often as 
needed on request from the sponsor. It is estimated that 30% of the Paediatric Investigation 
Plans  may  need  revision  at  some  point  in  time.  This  may  represent  a  minimum  of  80 
additional applications a year. 

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46 

   EN 

 
B. 

Activities created by the Regulation 

–  Scientific Advice 

Paediatric  Scientific  Advice  and  follow  up  procedures  would  increase  progressively  over 
time. 

–  Pharmacovigilance and risk management 

This activity will be fully developed. 

–  Information publication and management 

Modifications or developments of the current structures will take place over several years.  

–  Inventory of research priorities 

Regular updates are forecasted for in the Regulation. 

–  Establishment of a paediatric research network 

The implementation and running of the network should be in place.  

C. 

Impact on the Agency  

In  addition  to  involving  specific  staff  all  activities  and  their  related  increases  have  direct 
implications on other sectors. 

5.3.  Methods of implementation 

The  draft  Regulation  will  be  implemented  and  operated  primarily  by  the  existing  European 
Medicines  Agency.  Certain  aspects  will  also  be  operated  by  the  National  Competent 
Authorities.  The  Commission  will  be  responsible  for  an  implementing  regulation  and  a 
number of supporting guidelines. 

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6. 

FINANCIAL IMPACT 

6.1. 

Total financial impact on Part B - (over the entire programming period) 

(The method of calculating the total amounts set out in the table below must be explained by 
the breakdown in Table 6.2. ) 

6.1.1.  Financial intervention 

Commitments (in EUR million to three decimal places) 

Breakdown 

2007 

2008 

2009 

2010 

2011 

Total 

2012 
and 
subs. 
Years 

0,800 

2,397

2,688

2,881

4,280 

4,409

17,455

0,200 

0,642

0,689

0,717

0,773 

0,806

3,827

02.040201 – European 

Agency for the Evaluation of 

Medicinal Products — 

Subsidy under Titles 1 and 2 

02.040202 – European 

Agency for the Evaluation of 

Medicinal Products — 

Subsidy under Title 3 

Action 2 

etc. 

TOTAL 

1,000 

3,039

3,377

3,598

5,053 

5,215

21,282

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48 

   EN 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.1.2.  Technical  and  administrative  assistance,  support  expenditure  and  IT  expenditure 

(commitment appropriations) 

2007 

2008 

2009 

2010 

2011 

Total 

2012 
and 
subs. 
Years 

1) Technical and 
administrative assistance 

N.A. 

a) Technical assistance 
offices

b) Other technical and 
administrative assistance: 

- intra muros: 

- extra muros: 

of which for construction 
and maintenance of 
computerised management 
systems 

Subtotal 1 

2) Support expenditure 

a) Studies 

b) Meetings of experts 

c) Information and 
publications 

Subtotal 2 

TOTAL 

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6.2. 

Calculation  of  costs  by  measure  envisaged  in  Part  B  (over  the  entire 
programming period)3 

(Where  there  is  more  than  one  action,  give  sufficient  detail  of  the  specific  measures  to  be 
taken for each one to allow the volume and costs of the outputs to be estimated.) 

Commitments (in EUR million to three decimal places) 

Breakdown  

Type  
of outputs 
(projects, files ) 

Number of 
outputs 

Average unit 
cost 

(total for years 
2007-2012)  

Total cost 

(total for years 
2007-2012)  

1 

2 

3 

4=(2X3) 

Paediatric medicines management 

- Measure 1 

Paediatric 
activities costs 
for the EMEA 
general subsidy 

Staff 

Expenditure 
other. 

TOTAL COST 

17,455 

3,827 

21,282 

These costs are mainly due to: 1. the supplementary staff needed to perform the tasks induced 
by  the  new  regulation  on  medicinal  products  for  paediatric  use,  2.  scientific  advice  being 
given without a fee, and, 3. fee reductions for marketing authorisation applications.  

Staff  will  be  required  to:  provide  the  secretariat  of  the  new  expert  committee  the  Paediatric 
Committee,  administer  requests  for  opinions  from  the  Paediatric  Committee,  create  and 
maintain an inventory of the therapeutic needs of the children of Europe, create and maintain 
an  EU  network  of  clinical  trial  centres  to  conduct  tests  of  medicines  for  children,  and, 
collation  and  publication  of  information  about  medicines  for  children.  Projections  for  2011 
foresee that 24 people (14,5 A and 9,5 C) will be necessary to support the EMEA work related 
to the paediatric regulation. Support staff will bring the overall figure to 26. 

Regarding  scientific  advice,  currently,  requests  for  such  advice  command  a  fee  from  the 
EMEA. This fee is used mainly to pay experts from the National agencies who conduct the 
scientific evaluation of the requests (with their accompanying dossiers). The draft paediatric 
regulation  will  lead  to  such  scientific  advice  being  given  without  the  payment  of  fees. 
Therefore the EMEA will have to pay money to the National agencies and this will have to be 

3 

For further information, see separate explanatory note. 

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50 

   EN 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                 
covered.  Furthermore,  the  total  number  of  requests  for  scientific  advice  is  predicted  to 
increase  dramatically  as  a  result  of  the  paediatric  regulation.  The  current  average  fee  for 
scientific advice is about 40 000 € and it is predicted that, For the period of six years starting 
in 2007, about 330 free pieces of scientific advice will be given.  

Regarding  fee  reductions  for  marketing  authorisation  applications,  the  current  fee  is 
approximately 200 000 €. This pays mainly for the scientific evaluation conducted by experts 
from the National agencies. The fee reduction foreseen in the paediatric regulation is 50% and 
this will apply to a small proportion of all paediatric marketing authorisations (the so called 
Paediatric  Use  Marketing  Authorisations  –  PUMAs).  For  the  period  of  six-years  starting  in 
2007 it is estimated that about 30 paediatric use marketing authorisation applications will be 
made that will attract the 50% fee reduction. Hence the EMEA will have to pay the National 
agencies but this will not be covered by adequate fees. 

Staff requirement 

2007 

2008 

2009 

2010 

2011 

2012 
and 
subs. 
Years 

Secretariat Paediatric 

Committee Paediatric 

Investigation Plan 

applications 

Paediatric Research Network 

Funding of studies 

Support staff 

1 

1 

1 

3

3

3

3 

3

10

10

10

14 

14

1

2

1

1

2

1

2

2

3 

2 

4 

3

2

4

TOTAL 

3 

16

17

18

26 

26

Expenditure costs will mostly cover the reimbursement of the experts in relation with the new 
committee  ‘Paediatric  Committee’,  as  well  as  other  missions  and  trainings.  Some  IT 
developments  will  also  be  necessary  in  order  to  include  this  new  category  of  medicinal 
products in the several existing databases. 

EN 

51 

   EN 

 
 
 
 
 
 
 
 
Expenditure Other  

2007 

2008 

2009 

2010 

2011 

2012 
and 
subs. 
Years 

Meetings Paediatric 

Committee  

31 members and 5 experts 

0,050 

0,413

0,452

0,474

0,498 

0,523

11 x 2-day meetings 

Workshops, trainings and 

missions 

IT development and web 

publication 

0,100 

0,119

0,127

0,133

0,165 

0,173

0,050 

0,110

0,110

0,110

0,110 

0,110

TOTAL 

0,200 

0,642

0,689

0,717

0,773 

0,806

7 

IMPACT ON STAFF AND ADMINISTRATIVE EXPENDITURE  

7.1. 

Impact on human resources 

Staff to be assigned to management of the 
action using existing resources 

Description of tasks deriving from the 
action 

Types of post 

Total 

Number of 
permanent posts 

Number of 
temporary posts 

Officials or 
temporary staff 

A 

N.A. 

B 

C 

Other human resources 

Total 

If necessary, a fuller description of the 
tasks may be annexed. 

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52 

   EN 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7.2. 

Overall financial impact of human resources 

Type of human resources 

Amount (€) 

Method of calculation *  

Officials 

Temporary staff 

Other human resources 

N.A. 

(specify budget line) 

Total 

The amounts are total expenditure for twelve months. 

7.3. 

Other administrative expenditure deriving from the action 

Amount € 

Method of calculation 

N.A. 

Budget line 

(number and heading) 

Overall allocation (Title A7) 

ex A0701 – Missions 

ex A07030 – Meetings 

ex A07031 – Compulsory committees 1 

Paediatric Committee  

A07032 – Non-compulsory committees 1 

A07040 – Conferences 

ex A0705 – Studies and consultations 

Other expenditure (specify) 

Training 

Information systems (A-5001/A-4300) 

Other expenditure - Part A (specify) 

IT developments 

Total 

The amounts are total expenditure for twelve months. 

1 Specify the type of committee and the group to which it belongs. 

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53 

   EN 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I. 

II. 

Annual total (7.2 + 7.3) in 2011 

Duration of action 

III. 

Total cost of action (2007 to 2012) 

The  needs  for  human  and  administrative  resources  shall  be  covered  within  the  allocation 
granted to the managing DG in the framework of the annual allocation procedure 

8. 

FOLLOW-UP AND EVALUATION 

8.1. 

Follow-up arrangements 

Many of the effects of the draft paediatric legislation lend themselves to measurement. Others, 
including the overall objective of improved child health will be more difficult to measure due 
to a lack of robust EU-wide data. Collection of the following data is possible. 

•  The  dates  on  which  the  Paediatric  Committee  and  EU  network  of  clinical  trialists  are 

established and guidelines and first inventory of therapeutic needs are adopted. 

•  The date on which the database of paediatric studies becomes operational. 

•  The number of clinical trials in children initiated and completed (broken down by country 

and type of trial). 

•  The number of children enrolled into clinical trials. 

•  The  number  of  draft  paediatric  investigation  plans  submitted  for  assessment  and  the 

number of paediatric investigation plans agreed by the Paediatric Committee. 

•  The number of requests for waivers and the number of waivers granted by the Paediatric 

Committee. 

•  The number of requests for deferrals and the number of deferrals granted by the Paediatric 

Committee. 

•  The number of requests for scientific advice. 

•  The  numbers  of  marketing  authorisation  applications  made  and  granted  for  adults  and 

children. 

•  The  number  of  PUMA  applications  made  and  PUMAs  (with  their  associated  data 

protection) granted. 

•  The  number  of  requests  for  post-marketing  studies,  pharmacovigilance  plans  and  risk 

management systems and the delivery against those plans. 

•  The  number  of  existing  studies  in  children  submitted  and  the  number  of  marketing 

authorisations updated as a result. 

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54 

   EN 

 
 
•  The  number  of  times  marketing  authorisations  record  that  a  paediatric  investigation  plan 
has  been  complied  with.  This  provides  a  measure  of  the  number  of  supplementary 
protection certificates that can be extended. 

•  Impact on the budget of the EMEA. 

These data would provide a robust measure of the impact of the draft paediatric regulation in 
terms  of  stimulating  research,  development  and  authorisation  of  medicines  for  children  and 
any collateral effect on the authorisation of medicines for other populations. They would also 
provide a measure of the financial impacts on the EMEA. 

Prospective  measurement  of  the  costs  to  industry  and  on  the  price  of  medicines  is  not 
proposed as such measurement lends itself better to a post-hoc study.  

Section  4  of  the  extended  impact  assessment  points  out  that  the  impact,  both  financial  and 
social, of improved health of the children of Europe is very difficult to measure. Unless there 
is major investment in the central collection of indices of EU child health, this difficulty will 
remain  when  attempting  to  measure,  in  the  future,  the  impact  of  the  draft  paediatric 
Regulation. 

8.2. 

Arrangements and schedule for the planned evaluation 

The draft paediatric regulation includes proposals for: a database of paediatric studies; annual 
reports  from  the  Member  States  to  the  Commission  on  problems  encountered  with  the 
implementation of the draft paediatric regulation; annual publication of lists of companies that 
have benefits from the rewards / incentives or companies that have failed to comply with the 
obligations, and; within six years of entry into force, a general report on experienced acquired 
as  a  result  of  the  application  of  the  draft  paediatric  Regulation,  including  in  particular  a 
detailed  inventory  of  all  medicinal  products  authorised  for  paediatric  use  since  it  came  into 
force. 

Through  these  measures,  specifically  proposed  in  the  draft  paediatric  Regulation,  ex  post 
evaluation is already planned. The general report will likely be based on the indices listed in 
section 8.1. Furthermore, the need for a designated independent study to support the general 
report  should  be  considered.  Such  an  independent  study  could  include  within  its  scope  the 
financial and social impacts for which prospective data collection is problematic. 

9. 

ANTI-FRAUD MEASURES 

The European Medicines Agency has specific budgetary control mechanisms and procedures. 
The  Management  Board,  which  comprises  representatives  of  the  Member  States,  the 
Commission  and  the  European  Parliament,  adopts  the  draft  budget  (Article  57.5)  as  well  as 
the final budget (Article 57.6). The European Court of Auditors examines the execution of the 
budget each year (Article 57.9) and the Management Board gives a discharge to the Director 
regarding  the  budget  (Article  57.10).  In  addition  the  Agency  adopted  on  1  June  1999  a 
decision concerning co-operation with the European Anti-Fraud Office (EMEA/D/15007/99). 

The Quality Management System applied by the Agency supports a continuous review with 
the  intention  of  ensuring  that  the  correct  procedures  are  followed  and  that  these  procedures 
and  policies  are  pertinent  and  efficient.  Several  internal  audits  are  undertaken  each  year  as 
part of this process. 

EN 

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