Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004   (Text with EEA relevance)
Date: 2006-12-12
Institutions: Council of the European Union, European Parliament
Subjects: European Medicines Agency, drug surveillance, market approval, medical research, medicinal product, paediatrics, testing

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I

(Acts whose publication is obligatory)

REGULATION (EC) No 1901/2006 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

of 12 December 2006

on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive
2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004

(Text with EEA relevance)

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EURO-
PEAN UNION,

(4)

Having regard to the Treaty establishing the European Com-
munity, and in particular Article 95 thereof,

Having regard to the proposal from the Commission,

Having regard to the Opinion of the European Economic and
Social Committee (1),

Having consulted the Committee of the Regions,

Acting in accordance with the procedure referred to in
Article 251 of the Treaty (2),

Whereas:

(1)

(2)

(3)

Before a medicinal product for human use is placed on
the market in 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 undertaken for use in
the paediatric population and many of
the medicinal
products currently used to treat the paediatric population
have not been studied or authorised for such use. Market
to stimulate
forces
adequate research into, and the development and authori-
sation of, medicinal products for the paediatric popula-
tion.

alone have proven insufficient

Problems resulting from the absence of suitably adapted
medicinal products for the paediatric population include
inadequate dosage information which leads to increased
risks of adverse reactions including death,
ineffective
treatment through under-dosage, non-availability to the
paediatric population of
therapeutic advances, suitable
formulations and routes of administration, as well as use
of magistral or officinal formulations to treat the paedia-
tric population which may be of poor quality.

(1) OJ C 267, 27.10.2005, p. 1.
(2) Opinion of the European Parliament of 7 September 2005 (OJ C 193 E,
17.8.2006, p. 225), Council Common Position of 10 March 2006
(OJ C 132 E, 7.6.2006, p. 1) and Position of the European Parliament of
1 June 2006 (not yet published in the Official Journal). Council Deci-
sion of 23 October 2006.

the paediatric population are subject

This Regulation aims to facilitate the development and
accessibility of medicinal products for use in the paedia-
tric population, to ensure that medicinal products used to
treat
to ethical
research of high quality and are appropriately authorised
for use in the paediatric population, and to improve the
information available on the use of medicinal products in
the various paediatric populations. These objectives
should be achieved without subjecting the paediatric
population to unnecessary clinical
trials and without
delaying the authorisation of medicinal products for
other age populations.

(5) While taking into account the fact that the regulation of
medicinal products must be fundamentally aimed at safe-
guarding public health, this aim must be achieved by
means that do not impede the free movement of safe
medicinal products within the Community. The differ-
legislative, regulatory and
ences between the national
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)

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

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(7)

(8)

Any concerns about conducting trials in the paediatric
population should be balanced by the ethical concerns
about giving medicinal products to a population in
which they have not been appropriately tested. Public
health threats
from the use of untested medicinal
products in the paediatric population can be safely
addressed through the study of medicinal products for
the paediatric population, which should be carefully
controlled and monitored through the specific require-
ments for the protection of the paediatric population
who take part in clinical trials in the Community laid
down in Directive 2001/20/EC of the European Parlia-
ment and of the Council of 4 April 2001 on the approxi-
mation of the laws, regulations and administrative provi-
sions of the Member States relating to the implementa-
tion of good clinical practice in the conduct of clinical
trials on medicinal products for human use (1).

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 popula-
tions. The rules on scientific committees of the Agency,
as laid down in Regulation (EC) No 726/2004 (2), should
apply to the Paediatric Committee. Members of
the
Paediatric Committee should therefore not have financial
or other interests in the pharmaceutical industry which
could affect their impartiality, should undertake to act in
the public interest and in an independent manner, and
should make an annual declaration of
their financial
interests. The Paediatric Committee should be primarily
responsible for the scientific assessment and agreement
of paediatric investigation plans and for the system of
waivers and deferrals thereof; it should also be central to
various support measures contained in this Regulation. In
its work, the Paediatric Committee should consider the
potential significant therapeutic benefits for the paediatric
patients involved in the studies or the paediatric popula-
tion at large including the need to avoid unnecessary
studies. The Paediatric Committee should follow existing
Community requirements, including Directive 2001/20/
EC, as well as International Conference on Harmonisation
(ICH) guideline E11 on the development of medicinal
products for the paediatric population, and it should
avoid any delay in the authorisation of medicinal
products for other populations deriving from the require-
ments for studies in the paediatric population.

(9)

Procedures should be established for the Agency to agree
and modify a paediatric investigation plan, which is the
document upon which the development and authorisa-

(1) OJ L 121, 1.5.2001, p. 34.
(2) 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 Agency (OJ L
136, 30.4.2004, p. 1).

(10)

(11)

tion of medicinal products for the paediatric population
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. Since the
paediatric population is in fact composed of a number of
population subsets,
the paediatric investigation plan
should specify which population subsets need to be
studied, by what means and by when.

The introduction of the paediatric investigation plan in
the legal framework concerning medicinal products for
human use aims at ensuring that the development of
medicinal products that are potentially to be used for the
paediatric population 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 the paediatric population, where appropriate, before
marketing authorisation applications are submitted. It is
appropriate to set a deadline for the submission of a
paediatric investigation plan in order to ensure early
dialogue between the
and the Paediatric
Committee. Furthermore, early submission of a paediatric
investigation plan, combined with the submission of a
deferral request as described below, will avoid delaying
the authorisation for other populations. As the develop-
ment of medicinal products is a dynamic process depen-
dent on the result of ongoing studies, provision should
be made for modifying an agreed plan where necessary.

sponsor

It is necessary to introduce a requirement for new medic-
inal products and for authorised medicinal products
covered by a patent or a supplementary protection certifi-
cate to present either the results of studies in the paedia-
tric population in accordance with an agreed paediatric
investigation plan or proof of having obtained a waiver
or deferral, at the time of filing 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
judged.
However, that requirement should not apply to generics
or similar biological medicinal products and medicinal
products authorised through the well-established medic-
inal use procedure, nor
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 use (3).

requirement

is

(3) 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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Provision should be made for research into the paediatric
use of medicinal products which are not protected by a
patent or supplementary protection certificate to be
financed under Community research programmes.

should be included in product information. When all the
measures in the paediatric investigation plan have been
complied with,
fact should be recorded in the
marketing authorisation, and should then be the basis
upon which companies can obtain the rewards
for
compliance.

that

(12)

(13)

(14)

(15)

(16)

(11)

In order to ensure that research in the paediatric popula-
tion is only conducted to meet their therapeutic needs,
there is a need to establish procedures for the Agency to
for
waive the requirement referred to in Recital
specific products or for classes or part of classes of
medicinal products, these waivers being then made public
by the Agency. As knowledge of science and medicine
evolves over time, provision should be made for the lists
is
of waivers to be amended. However,
revoked, that 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 the paedia-
tric population to be initiated before an application for
marketing authorisation is submitted.

if a waiver

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 conducted only when safe and ethical and that
the requirement for study data in the paediatric popula-
tion does not block or delay the authorisation of medic-
inal products for other populations.

an incentive

Free scientific advice should be provided by the Agency
as
to sponsors developing medicinal
products for the paediatric population. To ensure scien-
tific 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 Com-
munity committees and working groups concerning
medicinal products.

The existing procedures for the marketing authorisation
of medicinal products for human use should not be
changed. However, from the requirement referred to in
Recital (11) it follows that competent authorities should
check compliance with the agreed paediatric investigation
plan and any waivers and deferrals at the existing valida-
tion step for marketing authorisation applications. The
assessment of quality, safety and efficacy of medicinal
products for the paediatric population and the granting
of marketing authorisations should remain the remit of
the competent authorities. Provision should be made for
the Paediatric Committee to be asked for its opinion on
compliance and on the quality, safety and efficacy of a
medicinal product in the paediatric population.

(17)

To provide healthcare professionals and patients with
information on the safe and effective use of medicinal
products in the paediatric population and as a transpar-
ency measure,
information on the results of studies in
the paediatric population, as well as on the status of the
paediatric investigation plans, waivers and deferrals,

(18)

(19)

In order to identify medicinal products authorised for use
in the paediatric population and enable their prescription,
provision should be made for the labels of medicinal
products granted an indication for use in the paediatric
population to display a symbol which will be selected by
the Commission on a recommendation by the Paediatric
Committee.

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 authorisa-
tion,
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 devel-
oped exclusively for use in the paediatric population. It
should be possible for the name of the medicinal product
that has been granted a Paediatric Use Marketing Author-
isation to retain the existing brand name of the corre-
sponding product authorised for adults, in order to capi-
talise on existing brand recognition, while benefiting
from the data exclusivity associated with a new marketing
authorisation.

(20) An application for a Paediatric Use Marketing Authorisa-
tion 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 medic-
inal product which is or has been authorised in the Com-
munity. This is intended to provide an additional incen-
tive to encourage small and medium-sized enterprises,
including generic
to develop off-patent
medicinal products for the paediatric population.

companies,

(21)

This Regulation should include measures to maximise
access by the Community population to new medicinal
products tested and adapted for paediatric use, and to
minimise the chance of Community-wide rewards and
incentives being granted without sections of the Com-
munity paediatric population benefiting from the avail-
ability 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.

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(22) 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 of the date of approval of
the indication. That requirement should relate only to
products
to medicinal
products authorised via a Paediatric Use Marketing
Authorisation.

already authorised, but not

with, if the product is authorised in all Member States
and if relevant information on the results of studies is
information, a reward should be
included in product
granted in the form of a 6-month extension of
the
supplementary protection certificate created by Council
Regulation (EEC) No 1768/92 (1). Any decisions by
Member States' authorities as regards the setting of prices
for medicinal products or their inclusion in the scope of
national health insurance schemes have no bearing on
the granting of this reward.

(23) 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
the paediatric population following an agreed paediatric
investigation plan form part of the marketing authorisa-
tion application. To achieve this, the procedure set out in
Articles 32, 33 and 34 of Directive 2001/83/EC could be
used. This will allow the adoption of a Community
harmonised Decision on use of that medicinal product in
the paediatric population and its inclusion in all national
product information.

(24)

It is essential to ensure that pharmacovigilance mechan-
isms are adapted to meet
the specific challenges of
collecting safety data in the paediatric population,
including data on possible long-term effects. Efficacy in
the paediatric population may also need additional study
following authorisation. Therefore, an additional require-
ment
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,
the applicant should
submit and implement a risk management system and/or
perform specific post-marketing studies as a condition
for the granting of the marketing authorisation.

(27) An application for an extension of the duration of the
certificate pursuant to this Regulation should only be
admissible where a certificate is granted pursuant
to
Regulation (EEC) No 1768/92.

(28)

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

(29) Under Regulation (EC) No 141/2000 of the European
Parliament and of the Council of 16 December 1999 on
orphan medicinal products (2), medicinal products desig-
nated as orphan medicinal products gain ten years of
market exclusivity on the granting of a marketing author-
isation for the orphan indication. As such products are
frequently not patent-protected, the reward of supple-
mentary protection certificate
extension cannot be
applied; when they are patent-protected, such an exten-
sion would provide a double incentive. Therefore,
for
instead of an extension of
orphan medicinal products,
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 the
paediatric population is fully met.

(25)

It is necessary in the interests of public health to ensure
the continuing availability of safe and effective medicinal
products authorised for paediatric indications developed
as a result of this Regulation. If a marketing authorisation
holder intends to withdraw such a medicinal product
from the market then arrangements should be in place so
that
the paediatric population can continue to have
access to the medicinal product in question. In order to
help achieve this, the Agency should be informed in
good time of any such intention and should make that
intention public.

(30)

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 avail-
information provided by the
able, on the basis of
Member States. The measures set out in this Regulation,
including the agreement of paediatric investigation plans,
should not be grounds for obtaining any other Com-
munity incentives
the
such as
the multi-annual
funding of
Community Framework Programmes for Research, Tech-
nological Development and Demonstration Activities.

to support
research projects under

research,

(26)

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

(1) OJ L 182, 2.7.1992, p. 1. Regulation as last amended by the 2003 Act

of Accession.

(2) OJ L 18, 22.1.2000, p. 1.

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(31)

In order to increase the availability of information on the
use of medicinal products in the paediatric population,
and to avoid unnecessary repetition of studies in the
paediatric population which do not add to the collective
knowledge, the European database provided for in Article
11 of Directive 2001/20/EC should include a European
register of clinical trials of medicinal products for paedia-
tric use comprising all ongoing, prematurely terminated,
and completed paediatric studies conducted both in the
Community and in third countries. Part of the informa-
tion concerning paediatric clinical trials entered into the
database, as well as details of the results of all paediatric
clinical
trials submitted to the competent authorities,
should be made public by the Agency.

(32) An inventory of the therapeutic needs of the paediatric
population should be established by the Paediatric
Committee after consultation with the Commission, the
Member States and interested parties, and should be regu-
larly updated. The inventory should identify the existing
medicinal products used by the paediatric population and
highlight the therapeutic needs of that population and
the priorities for research and development. In this way,
companies should be able easily to identify opportunities
for business development;
the Paediatric Committee
should be able better to judge the need for medicinal
products 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
medicinal products to choose.

(33)

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, which
links existing national and Community initiatives and
study centres in order to build up the necessary compe-
tences at Community level, and which takes account of
Community and third country data, would help facilitate
cooperation and avoid unnecessary duplication of studies.
This network should contribute to the work of strength-
ening 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.

(35)

(36)

(37)

(38)

Community funding should be provided 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 investiga-
tion plans, fee waivers for scientific advice, and informa-
tion and transparency measures, including the database
of paediatric studies and the network.

The measures necessary for the implementation of this
adopted in accordance with
Regulation should be
Council Decision 1999/468/EC of 28 June 1999 laying
down the procedures for the exercise of implementing
powers conferred on the Commission (1).

Regulation (EEC) No 1768/92, Directive 2001/20/EC,
Directive 2001/83/EC and Regulation (EC) No 726/2004
should therefore be amended accordingly.

Since the objective of this Regulation, namely improving
availability of medicinal products tested for paediatric
use, cannot be sufficiently achieved by the Member States
and can therefore be better achieved at Community level,
given that this will make it possible to take advantage of
the widest possible market and avoid the dispersion of
limited resources, the Community may adopt measures,
in accordance with the principle of subsidiarity as set out
in Article 5 of the Treaty. In accordance with the prin-
ciple of proportionality, as set out in that Article, this
is necessary in
Regulation does not go beyond what
order to achieve this objective,

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
the paediatric population, without
therapeutic needs of
subjecting the paediatric population to unnecessary clinical or
other trials and in compliance with Directive 2001/20/EC.

(34)

For certain authorised products, pharmaceutical compa-
nies may already hold data on safety or efficacy in the
paediatric population. To improve the information avail-
able on the use of medicinal products 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
could be assessed and, if appropriate, information should
be included in the authorised product information aimed
at healthcare professionals and patients.

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

1) ‘paediatric population’ means that part of the population

aged between birth and 18 years;

(1) OJ L 184, 17.7.1999, p. 23. Decision as amended by Decision

2006/512/EC (OJ L 200, 22.7.2006, p. 11).

Article 2

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2) ‘paediatric investigation plan’ means a research and develop-
ment programme aimed at ensuring that the necessary data
are generated determining the conditions in which a medic-
inal product may be authorised to treat the paediatric popu-
lation;

3) ‘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 product characteristics drawn up in
the summary of
accordance with Article 11 of Directive 2001/83/EC;

4) ‘paediatric use marketing authorisation’ means 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 supple-
mentary protection certificate, covering exclusively thera-
peutic 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.

CHAPTER 2

Paediatric committee

Article 3

1.
By 26 July 2007, a Paediatric Committee shall be estab-
lished within the European Medicines Agency set up under
Regulation (EC) No 726/2004, hereinafter ‘the Agency’. The
Paediatric Committee shall be considered as established once the
members referred to in Article 4(1)(a) and (b) have been
appointed.

The Agency shall fulfil the secretariat functions for the Paediatric
Committee and shall provide it with technical and scientific
support.

2.
Save where otherwise provided for in this Regulation,
Regulation (EC) No 726/2004 shall apply to the Paediatric
Committee, including the provisions on the independence and
impartiality of its members.

The Executive Director of the Agency shall ensure appro-
3.
priate coordination between the Paediatric Committee and the
Committee
the
Committee for Orphan Medicinal Products,
their working
parties and any other scientific advisory groups.

for Medicinal Products

for Human Use,

(a) five members, with their alternates, of the Committee for
Medicinal Products for Human Use, having been appointed
to that Committee in accordance with Article 61(1) of Regu-
lation (EC) No 726/2004. These five members with their
alternates shall be appointed to the Paediatric Committee by
the Committee for Medicinal Products for Human Use;

(b) one member and one alternate 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) three members and three alternates appointed by the
Commission, on the basis of a public call for expressions of
interest, after consulting the European Parliament, in order
to represent health professionals;

(d) three members and three alternates appointed by the
Commission, on the basis of a public call for expressions of
interest, after consulting the European Parliament, in order
to represent patient associations.

The alternates shall represent and vote for the members in their
absence.

For the purposes of points (a) and (b), 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, including members and alternates, covers
the scientific areas relevant to paediatric medicinal products,
and including at least: pharmaceutical development, paediatric
medicine, general practitioners, paediatric pharmacy, paediatric
pharmacology, paediatric research, pharmacovigilance, ethics
and public health.

For the purposes of points (c) and (d), the Commission shall
take into account
the expertise provided by the members
appointed under points (a) and (b).

The members of

the Paediatric Committee shall be
2.
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

3.
among its members for a term of three years, renewable once.

The names and qualifications of the members shall be

4.
made public by the Agency.

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

Article 4

The Paediatric Committee shall be composed of

1.
following members:

the

Article 5

1. 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 Paediatric Committee
shall adopt an opinion consisting of the position of the majority
of the members. The opinion shall mention the divergent posi-
tions, with the grounds on which they are based. This opinion
shall be made accessible to the public pursuant to Article 25(5)
and (7).

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The Paediatric Committee shall draw up its rules of proce-
2.
dure 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.

3.
All meetings of the Paediatric Committee may be attended
by representatives of the Commission, the Executive Director of
the Agency or his representatives.

Article 6

The tasks of the Paediatric Committee shall

1.
following:

include the

(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) 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 agreed paediatric investigation plan
concerned and formulate an opinion thereon;

(d) 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 investiga-
tion plan and formulate an opinion on the quality, safety or
efficacy of the medicinal product for use in the paediatric
population;

(e) to advise on the content and format of data to be collected

for the survey referred to in Article 42;

(f) to support and advise the Agency on establishing the Euro-

pean network referred to in Article 44;

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 and/or fulfil
a therapeutic need of the paediatric population. The Paediatric
Committee shall take into account any information available to
including any opinions, decisions or advice given by the
it,
competent authorities of third countries.

TITLE II

MARKETING AUTHORISATION REQUIREMENTS

CHAPTER 1

General authorisation requirements

Article 7

An application for marketing

1.
authorisation under
Article 6 of Directive 2001/83/EC in respect of a medicinal
product for human use which is not authorised in the Com-
munity at the time of entry into force of this Regulation shall
be regarded as valid only if it includes, in addition to the parti-
culars and documents referred to in Article 8(3) of Direc-
tive 2001/83/EC, one of the following:

(a) the results of all studies performed and details of all infor-
mation 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 pursuant to

Article 11;

(d) a decision of the Agency granting a deferral.

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

the decision of

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

The documents submitted pursuant to paragraph 1 shall,

2.
cumulatively, cover all subsets of the paediatric population.

(h) to provide advice on any question related to medicinal
products for use in the paediatric population, at the request
of the Executive Director of the Agency or the Commission;

(i) to establish a specific inventory of paediatric medicinal
product needs and update it on a regular basis, as referred
to in Article 43;

(j) to advise the Agency and the Commission regarding the
communication of arrangements available for conducting
research into medicinal products for use in the paediatric
population;

(k) to make a recommendation to the Commission on the

symbol referred to in Article 32(2).

Article 8

In the case of authorised medicinal products which are protected
either by a supplementary protection certificate under Regu-
lation (EEC) No 1768/92, or by a patent which qualifies for the
granting of the supplementary protection certificate, Article 7 of
this Regulation shall apply to applications for authorisation of
new indications, including paediatric indications, new pharma-
ceutical forms and new routes of administration.

the first subparagraph,

For the purposes of
the documents
referred to in Article 7(1) shall cover both the existing and the
new indications, pharmaceutical forms and routes of administra-
tion.

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Article 9

Articles 7 and 8 shall not apply to products authorised under
Articles 10, 10a, 13 to 16 or 16a to 16i of Directive 2001/83/
EC.

Article 10

In consultation with the Member States, the Agency and other
interested parties, the Commission shall draw up the detailed
arrangements concerning the format and content which applica-
tions for agreement or modification of a paediatric investigation
plan and requests for waivers or deferrals must follow in order
to be considered valid and concerning the operation of the
compliance check referred to in Articles 23 and 28(3).

CHAPTER 2

Waivers

Article 11

1.
Production of the information referred to in point (a) of
Article 7(1) shall be waived for specific medicinal products or
for classes of medicinal products, if there is evidence showing
any of the following:

(a) 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;

(b) that the disease or condition for which the specific medic-
inal product or class is intended occurs only in adult popu-
lations;

(c) 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 either to one or more specified subsets of the
paediatric population, or to one or more specified therapeutic
indications, or to a combination of both.

Article 12

The Paediatric Committee may of its own motion adopt an
opinion, on the grounds set out in Article 11(1), to the effect
that a class or a product-specific waiver, as referred to in
Article 11(1), should be granted.

As soon as the Paediatric Committee adopts an opinion, the
procedure laid down in Article 25 shall apply. In the case of a
class waiver, only paragraphs 6 and 7 of Article 25 shall apply.

Article 13

The applicant may, on the grounds set out in Article 11

1.
(1), apply to the Agency for a product-specific waiver.

Following receipt of

the Paediatric
the
2.
Committee shall appoint a rapporteur and shall within 60 days
adopt an opinion as to whether or not a product-specific waiver
should be granted.

application,

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

to supplement

Whenever appropriate, the Paediatric Committee may request
the particulars and documents
the applicant
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,

3.
the procedure laid down in Article 25 shall apply.

Article 14

1.
The Agency shall maintain a list of all waivers. The list
shall be regularly updated (at least every year) and made avail-
able to the public.

The Paediatric Committee may, at any time, adopt an

2.
opinion advocating the review of a granted waiver.

In the case of a change affecting a product-specific waiver, the
procedure laid down in Article 25 shall apply.

In the case of a change affecting a class waiver, paragraphs 6
and 7 of Article 25 shall apply.

3.
If a particular product-specific or class waiver is revoked,
the requirement set out in Articles 7 and 8 shall not apply for
from the list of
36 months from the date of
waivers.

the removal

CHAPTER 3

Paediatric investigation plan

S e c t i o n 1

R e q u e s t s f o r a g r e e m e n t

Article 15

1. Where the intention is to apply for a marketing authorisa-
tion in accordance with Article 7(1)(a) or (d), Article 8 or
Article 30, 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
2.
and the measures proposed to assess the quality, safety and effi-
cacy 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.

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Article 16

1.
In the case of the applications for marketing authorisation
referred to in Articles 7 and 8 or the applications for waiver
referred to in Articles 11 and 12, the paediatric investigation
plan or the application for waiver shall be submitted with a
request for agreement, except in duly justified cases, 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 Direc-
tive 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 authori-
sation or other application concerned.

2. Within 30 days following receipt of the request referred to
in paragraph 1 and in Article 15(1), the Agency shall verify the
validity of the request and prepare a summary report for the
Paediatric Committee.

3. 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 17

1.
Following receipt of a proposed paediatric investigation
plan which is valid in accordance with the provisions of
Article 15(2), the Paediatric Committee shall appoint a rappor-
teur and shall within 60 days adopt an opinion as to whether or
not
the
the proposed studies will ensure the generation of
necessary data determining the conditions in which the medic-
inal product may be used to treat the paediatric population or
subsets thereof, and as to whether or not the expected thera-
peutic benefits justify the studies proposed. When adopting its
opinion,
the
measures proposed to adapt the formulation of the medicinal
product for use in different subsets of the paediatric population
are appropriate.

the Committee shall consider whether or not

to the medicinal product concerned, it shall adopt a negative
opinion under Article 17(1).

In such cases, the Paediatric Committee shall adopt an opinion
in favour of a waiver under Article 12, whereupon the proce-
dure laid down in Article 25 shall apply.

S e c t i o n 2

D e f e r r a l s

Article 20

At the same time as the paediatric investigation plan is
1.
submitted under Article 16(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 event, 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 popula-
tion will take longer to conduct than studies in adults.

2.
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 21

following a request

1.
At the same time as the Paediatric Committee adopts a
positive opinion under Article 17(1), it shall, of its own motion
submitted by the applicant under
or
the conditions specified in
Article 20, adopt an opinion,
Article 20 are met,
in favour of deferring the initiation or
completion of some or all of the measures in the paediatric
investigation plan.

if

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

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

the applicant

2. Within the 60-day period referred to in paragraph 1, the
Paediatric Committee may request
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 appli-
cant 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.

Article 18

As soon as the Paediatric Committee adopts an opinion,
whether positive or negative,
the procedure laid down in
Article 25 shall apply.

Article 19

If, having considered a paediatric investigation plan, the Paedia-
tric Committee concludes that Article 11(1)(a), (b) or (c) applies

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 Article 25 shall apply.

S e c t i o n 3

M o d i f i c a t i o n o f a p a e d i a t r i c i n ve s t i g a t i o n p l a n

Article 22

If, following the decision agreeing the paediatric investigation
plan, the applicant encounters such difficulties with its imple-
mentation 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. Within 60 days,
the Paediatric Committee shall
review these changes or the request for a deferral or a waiver
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 Article 25 shall
apply.

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S e c t i o n 4

C o m p l i a n c e w i t h t h e p a e d i a t r i c

i n ve s t i g a t i o n

p l a n

Article 23

The

authority

competent

responsible

1.
granting
marketing authorisation shall verify whether an application for
marketing authorisation or variation complies with the require-
ments laid down in Articles 7 and 8 and whether an application
to Article 30 complies with the agreed
submitted pursuant
paediatric investigation plan.

for

Where the application is submitted in accordance with the
procedure set out in Articles 27 to 39 of Directive 2001/83/EC,
the verification of
appropriate,
requesting an opinion of the Paediatric Committee in accord-
ance with paragraph 2(b) and (c) of
this Article, shall be
conducted by the reference Member State.

compliance,

including,

as

2.
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 inves-
tigation plan:

(a) by the applicant, prior to submitting an application for
marketing authorisation or variation as referred to in Arti-
cles 7, 8 and 30, respectively;

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

include

CHAPTER 4

Procedure

Article 25

1. Within ten days of its receipt, the Agency shall transmit
the opinion of the Paediatric Committee to the applicant.

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

to paragraph 2,

3. Within 30 days following receipt of a request for re-exami-
nation pursuant
the Paediatric Committee,
having appointed a new rapporteur, shall issue a new opinion
confirming or revising its previous opinion. The rapporteur
shall be able to question the applicant directly. The applicant
may also offer to be questioned. The rapporteur shall inform
the Paediatric Committee without delay in writing about details
of contacts with the applicant. 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 defini-
tive.

4.
If, within the 30-day period referred to in paragraph 2, the
applicant does not request re-examination, the opinion of the
Paediatric Committee shall become definitive.

5.
The Agency shall adopt a decision within a period not
exceeding 10 days following receipt of the Paediatric Commit-
tee's definitive opinion. This decision shall be communicated to
the applicant in writing and shall annex the definitive opinion
of the Paediatric Committee.

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

6.
In the case of a class waiver as referred to in Article 12,
the Agency shall adopt a decision within ten days following
receipt of the opinion of the Paediatric Committee as referred to
in Article 13(3). This decision shall annex the opinion of the
Paediatric Committee.

In the case of point (a), the applicant shall not submit its appli-
cation until the Paediatric Committee has adopted its opinion,
and a copy thereof shall be annexed to the application.

Decisions of the Agency shall be made public after dele-

7.
tion of any information of a commercially confidential nature.

3.
If the Paediatric Committee is requested to give an opinion
under paragraph 2, it shall do so within 60 days of receiving
the request.

Member States shall take account of such an opinion.

CHAPTER 5

Miscellaneous provisions

Article 26

Article 24

If, when conducting the scientific assessment of a valid applica-
tion for Marketing Authorisation,
the competent authority
concludes that the studies are not in conformity with the agreed
paediatric investigation plan, the product shall not be eligible
for the rewards and incentives provided for in Articles 36, 37
and 38.

Any legal or natural person developing 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
in the
paediatric population in accordance with Article 57(1)(n) of
Regulation (EC) No 726/2004.

the medicinal product

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In addition, this legal or natural person may request advice on
the design and conduct of pharmacovigilance and risk manage-
ment systems as referred to in Article 34.

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

Article 29

In the case of medicinal products authorised under Directive
2001/83/EC, an application as referred to in Article 8 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.

TITLE III

MARKETING AUTHORISATION PROCEDURES

That application shall comply with the requirement laid down
in point (a) of Article 7(1).

Article 27

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

Save where otherwise provided in this Title, marketing authori-
sation 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 2

Paediatric use marketing authorisation

CHAPTER 1

Article 30

Marketing authorisation procedures for applications falling
within the scope of Articles 7 and 8

Article 28

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 7(1) of this Regulation which includes one or more
paediatric indications on the basis of studies conducted in
compliance with an agreed paediatric investigation plan.

Where authorisation is granted, the results of all those studies
shall be included in the summary of product characteristics and,
if appropriate, in the package leaflet of the medicinal product,
provided that the competent authority deems the information to
be of use to patients, whether or not all the paediatric indica-
tions concerned were approved by the competent authority.

2. 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 charac-
teristics and, if appropriate, in the package leaflet of the medic-
inal product concerned.

the competent authority shall

If the application complies with all the measures contained
3.
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 investiga-
include within the
tion plan,
marketing authorisation a statement indicating compliance of
the application with the agreed completed paediatric investiga-
tion plan. For the purpose of the application of Article 45(3),
this statement shall also indicate whether significant studies
contained in the agreed Paediatric Investigation Plan have been
completed after the entry into force of this Regulation.

Submission of

1.
a paediatric use
marketing authorisation shall in no way preclude the right to
apply for a marketing authorisation for other indications.

an application for

An application for a paediatric use marketing authorisa-
2.
tion shall be accompanied by the particulars and documents
necessary to establish quality, safety and efficacy in the paedia-
tric population, including any specific data needed to support
route of
an appropriate strength, pharmaceutical
form or
administration for 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.

3. 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.

4.
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 31

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

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CHAPTER 3

Identification

Article 32

1. Where a medicinal product is granted a marketing authori-
sation for a paediatric indication, the label shall display the
symbol agreed in accordance with paragraph 2. The package
the
leaflet shall contain an explanation of
symbol.

the meaning of

By 26 January 2008,

2.
symbol
Committee. The Commission shall make the symbol public.

the Commission shall select a
Paediatric

recommendation of

following

the

a

3.
The provisions of this Article shall also apply to medicinal
products authorised before the entry into force of this Regu-
lation, and to medicinal products authorised after the entry into
force of this Regulation but before the symbol has been made
public, if they are authorised for paediatric indications.

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 minimi-
sation system and the results of any such studies performed.

3.
In addition to paragraphs 1 and 2, the provisions on phar-
macovigilance as laid down in Regulation (EC) No 726/2004
and in Directive 2001/83/EC shall apply to marketing authorisa-
tions for medicinal products which include a paediatric indica-
tion.

In the case of a deferral,

4.
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 the Agency agreeing the paediatric investi-
gation plan and granting a deferral.

In this case, the symbol and the explanation referred to in para-
graph 1 shall be included in the labelling and package leaflet
respectively of the medicinal products concerned not later than
two years after the symbol has been made public.

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

TITLE IV

POST-AUTHORISATION REQUIREMENTS

Article 33

Where medicinal products are authorised for a paediatric indica-
tion 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. A register, coordinated by the Agency,
and made publicly available, shall mention these deadlines.

Article 34

In the following cases,

1.
the
measures to ensure the follow-up of efficacy and of possible
adverse reactions to the paediatric use of the medicinal product:

the applicant shall detail

(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.

2. Where there is particular cause for concern, the competent
authority shall 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
pharmacovigilance activities and interventions designed to iden-
tify, characterise, prevent or minimise risks relating to medicinal
products, including the assessment of the effectiveness of those
interventions.

The Agency shall draw up guidelines relating to the appli-

5.
cation of this Article.

Article 35

If a medicinal product is authorised for a paediatric indication
and the marketing authorisation holder has benefited from
rewards or incentives under Article 36, 37 or 38, and these
periods of protection have expired, and if the marketing authori-
sation holder
intends to discontinue placing the medicinal
product on the market, the marketing authorisation holder shall
transfer the marketing authorisation or allow a third party,
which has declared its intention to continue to place the medic-
inal product in question on the market, to use the pharmaceu-
tical, pre-clinical and clinical documentation contained in the
file of the medicinal product on the basis of Article 10c of
Directive 2001/83/EC.

The marketing authorisation holder shall inform the Agency of
its intention to discontinue the placing on the market of the
product no less than six months before the discontinuation. The
Agency shall make this fact public.

TITLE V

REWARDS AND INCENTIVES

Article 36

1. Where an application under Article 7 or 8 includes the
results of all studies conducted in compliance with an agreed
paediatric investigation plan, the holder of the patent or supple-
mentary 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.

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

2.
The inclusion in a marketing authorisation of the state-
ment referred to in Article 28(3) shall be used for the purposes
of applying paragraph 1 of this Article.

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

the product

4.
Paragraphs 1, 2 and 3 shall apply to products that are
protected by a supplementary protection certificate under Regu-
lation (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.

5.
In the case of an application under Article 8 which leads
to the authorisation of a new paediatric indication, paragraphs
1, 2 and 3 shall not apply if the applicant applies for, and
obtains, a one-year extension of the period of marketing protec-
tion for the medicinal product concerned, on the grounds that
this new paediatric indication brings a significant clinical benefit
in comparison with existing therapies,
in accordance with
Article 14(11) of Regulation (EC) No 726/2004 or the fourth
subparagraph of Article 10(1) of Directive 2001/83/EC.

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 28(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.

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

Article 38

1. 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.

2. 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

1.
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 develop-
ment and availability of, medicinal products for paediatric use.

2.
By 26 January 2008, the Member States shall communi-
cate to the Commission detailed information concerning any
measures they have enacted to support research into, and the
development and availability of, medicinal products for paedia-
tric use. This information shall be updated regularly at the
request of the Commission.

3.
By 26 July 2008, the Commission shall make publicly
available a detailed inventory of all rewards and 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 and the updates shall also be made publicly available.

Article 40

1.
Funds for research into medicinal products for the paedia-
tric population shall be provided for in the Community budget
in order to support studies relating to medicinal products or
active substances not covered by a patent or a supplementary
protection certificate.

2.
The Community funding referred to in paragraph 1 shall
be delivered through the Community Framework Programmes
for Research, Technological Development and Demonstration
Activities or any other Community initiatives for the funding of
research.

TITLE VI

COMMUNICATION AND COORDINATION

Article 41

include clinical

trials carried out

The European database created by Article 11 of Directive
1.
2001/20/EC shall
in third
countries which are contained in an agreed paediatric investiga-
tion plan, in addition to the clinical trials referred to in Articles
1 and 2 of that Directive. In the case of such clinical trials
carried out in third countries, the details listed in Article 11 of
that Directive shall be entered into the database by the addressee
of the Agency's decision on a paediatric investigation plan.

By way of derogation from the provisions of Article 11 of
Directive 2001/20/EC, the Agency shall make public part of the
information on paediatric clinical trials entered in the European
database.

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Details of the results of all the trials referred to in para-
2.
graph 1 and of any other trials submitted to competent authori-
ties in compliance with Articles 45 and 46 shall be made public
by the Agency, whether or not the trial was terminated prema-
turely. These results shall be submitted without delay to the
Agency by the clinical trial sponsor, the addressee of the Agen-
cy's decision on a paediatric investigation plan, or by the
marketing authorisation holder as appropriate.

In consultation with the Agency, Member States and inter-
3.
ested parties, the Commission shall 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 Direc-
tive 2001/20/EC, on which information shall be made accessible
to the public in application of paragraph 1, on how clinical trial
results shall be submitted and be made public in application of
paragraph 2, and on the Agency's responsibilities and tasks in
this regard.

Article 42

Member States shall collect available data on all existing uses of
medicinal products
in the paediatric population and shall
communicate these data to the Agency by 26 January 2009.

The Paediatric Committee shall provide guidance on the content
and the format of the data to be collected by 26 October 2007.

to build up the necessary scientific and administrative compe-
tences at European level, and to avoid unnecessary duplication
of studies and testing in the paediatric population.

By 26 January 2008,

the Management Board of

the
3.
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 the foundations of the European Research Area
in the context of the Community Framework Programmes for
Research, Technological Development and Demonstration Activ-
ities.

Article 45

1.
By 26 January 2008, any paediatric studies already
completed, by the date of entry into force, in respect of products
authorised in the Community shall be submitted by the
marketing authorisation holder for assessment to the competent
authority.

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

Article 43

The Agency shall coordinate the exchange of information.

1.
On the basis of the information referred to in Article 42
and after consulting the Commission, the Member States and
the interested parties, the Paediatric Committee shall establish
an inventory of therapeutic needs, in particular with a view to
identifying research priorities.

The Agency shall make the inventory public at the earliest by
26 January 2009 and at the latest by 26 January 2010 and shall
update it regularly.

2.
In establishing the inventory of therapeutic needs, account
shall be taken of the prevalence of the conditions in the paedia-
tric 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, and any data resulting from
studies in third countries.

2.
All existing paediatric studies, as referred to in paragraph
1, and all paediatric studies initiated prior to the entry into
force of this Regulation shall be eligible to be included in a
paediatric investigation plan, and shall be taken into considera-
tion by the Paediatric Committee when assessing applications
for paediatric investigation plans, waivers and deferrals and by
competent authorities when assessing applications submitted
pursuant to Article 7, 8 or 30.

3. Without prejudice to the previous paragraph, the rewards
and incentives of Articles 36, 37 and 38 shall only be granted
provided that significant studies contained in an agreed Paedia-
tric Investigation Plan are completed after the entry into force
of this Regulation.

In consultation with the Agency, the Commission shall
4.
draw up guidelines to establish assessment criteria for the signif-
icance of studies for the purposes of applying paragraph 3.

Article 44

1.
The Agency shall, with the scientific support of the Paedia-
tric 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,
2.
to coordinate studies relating to paediatric medicinal products,

Article 46

Any other marketing authorisation holder-sponsored
1.
studies which involve the use in the paediatric population of a
covered by a marketing authorisation,
medicinal product
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 completion of the
studies concerned.

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Paragraph 1 shall apply independent of whether or not
intends to apply for a

2.
the marketing authorisation holder
marketing authorisation of a paediatric indication.

3.
The competent authority may update the summary of
product characteristics and package leaflet, and may vary the
marketing authorisation accordingly.

shall determine the penalties to be applied for infringement of
the provisions of this Regulation or the implementing measures
adopted pursuant
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.

to it

Competent

4.
information
regarding the studies submitted and, as appropriate, their impli-
cations for any marketing authorisations concerned.

authorities

exchange

shall

5.

The Agency shall coordinate the exchange of information.

TITLE VII

GENERAL AND FINAL PROVISIONS

CHAPTER 1

General provisions

S e c t i o n 1

F e e s , c o m m u n i t y f u n d i n g , p e n a l t i e s a n d r e p o r t s

Article 47

1. 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.

2.
Council Regulation (EC) No 297/95 of 10 February 1995
on fees payable to the European Medicines Agency (1) shall
apply.

Assessments of the following by the Paediatric Committee

3.
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 48

The Community contribution provided for in Article 67 of
Regulation (EC) No 726/2004 shall cover the work of
the
Paediatric Committee, including scientific support provided by
experts, and of the Agency, including the assessment of paedia-
tric investigation plans, scientific advice and any fee waivers
provided for in this Regulation, and shall support the Agency's
activities under Articles 41 and 44 of this Regulation.

Article 49

1. Without prejudice to the Protocol on the Privileges and
Immunities of the European Communities, each Member State

(1) OJ L 35, 15.2.1995, p. 1. Regulation as last amended by Regulation

(EC) No 1905/2005 (OJ L 304, 23.11.2005, p. 1).

Member States shall inform the Commission of these provisions
by 26 October 2007. They shall notify any subsequent altera-
tions as soon as possible.

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

3.
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 Regu-
lation.

The Commission shall make public the names of anyone
4.
infringing the provisions of this Regulation or of any imple-
menting measures adopted pursuant to it and the amounts of,
and reasons for, the financial penalties imposed.

Article 50

1.
On the basis of a report from the Agency, and at least on
an annual basis, the Commission shall make public a list of the
companies and of the products 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.

2.
By 26 January 2013, the Commission shall present to the
European Parliament and the Council a general report on
experience acquired as a result of the application of this Regu-
lation. This shall include in particular a detailed inventory of all
medicinal products authorised for paediatric use since its entry
into force.

By 26 January 2017,

3.
the Commission shall present a
to the European Parliament and the Council on the
report
experience acquired as a result of the application of Articles 36,
37 and 38. The report shall include an analysis of the economic
impact of the rewards and incentives, together with an analysis
of the estimated consequences for public health of this Regu-
lation, with a view to proposing any necessary amendments.

4.
Provided that there are sufficient data available to allow
robust analyses to be made, the provisions of paragraph 3 shall
be fulfilled at the same time as the provisions of paragraph 2.

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S e c t i o n 2

(a) in paragraph 1, the following point shall be added:

S t a n d i n g c o m m i t t e e

Article 51

1.
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, hereinafter referred to as
‘the Committee’.

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

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

3.

The Committee shall adopt its rules of procedure.

CHAPTER 2

Amendments

Article 52

‘(d) where the application for a certificate includes a

request for an extension of the duration:

(i) a copy of the statement indicating compliance
with an agreed completed paediatric investiga-
tion plan as referred to in Article 36(1) of
Regulation (EC) No 1901/2006;

(ii) where necessary, in addition to the copy of the
authorisations to place the product on the
market as referred to in point (b), proof that it
has authorisations to place the product on the
market of all other Member States, as referred
to in Article 36(3) of Regulation (EC)
No 1901/2006.’;

(b) the following paragraphs shall be inserted:

‘1a. Where an application for a certificate is pending,
an application for an extended duration in accord-
ance with Article 7(3) shall include the particulars
referred to in paragraph 1(d) and a reference to the
application for a certificate already filed.

1b. The application for an extension of the duration of
a certificate already granted shall contain the parti-
culars referred to in paragraph 1(d) and a copy of
the certificate already granted.’;

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

(c) paragraph 2 shall be replaced by the following:

1) in Article 1, the following definition shall be added:

‘(e) “Application for an extension of the duration” means
an application for an extension of the duration of the
certificate pursuant to Article 13(3) of this Regulation
and of Article 36 of Regulation (EC) No 1901/2006 of
the Council of 12
the European Parliament and of
December 2006 on medicinal products for paediatric
use (*).

‘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 certi-
ficate.’;

4) Article 9 shall be amended as follows:

(a) in paragraph 1, the following subparagraph shall be

(*) OJ L 378, 27.12.2006, p. 1.’

added:

2) in Article 7, the following paragraphs shall be added:

‘3.
The application for an extension of the duration may
be made when lodging the application for a certificate or
when the application for the certificate is pending and the
appropriate requirements of Articles 8(1)(d) or 8(1a),
respectively, are fulfilled.

The application for an extension of the duration of a
4.
certificate already granted shall be lodged not later than
two years before the expiry of the certificate.

5.
Notwithstanding paragraph 4, for five years following
the entry into force of Regulation (EC) No 1901/2006, the
application for an extension of the duration of a certificate
already granted shall be lodged not later than six months
before the expiry of the certificate.’;

3) Article 8 shall be amended as follows:

‘The application for an extension of the duration of a
certificate shall be lodged with the competent authority
of the Member State concerned.’;

(b) in paragraph 2, the following point shall be added:

‘(f) where applicable, an indication that the application
includes an application for an extension of
the
duration.’;

(c) the following paragraph shall be added:

‘3.
Paragraph 2 shall apply to the notification of the
application for an extension of the duration of a certifi-
cate already granted or where an application for a certi-
ficate is pending. The notification shall additionally
contain an indication of the application for an extended
duration of the certificate.’;

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5) in Article 10, the following paragraph shall be added:

Paragraphs 1 to 4 shall apply mutatis mutandis to

‘6.
the application for an extension of the duration.’;

6) in Article 11, the following paragraph shall be added:

‘3.
Paragraphs 1 and 2 shall apply to the notification of
the fact that an extension of the duration of a certificate
has been granted or of the fact that the application for an
extension has been rejected.’;

7) in Article 13, the following paragraph shall be added:

‘3.
The periods laid down in paragraphs 1 and 2 shall be
extended by six months in the case where Article 36 of
Regulation (EC) No 1901/2006 applies. In that case, the
duration of the period laid down in paragraph 1 of this
Article may be extended only once.’;

8) the following Article shall be inserted:

‘Article 15a

Revocation of an extension of the duration

1.
The extension of the duration may be revoked if it
was granted contrary to the provisions of Article 36 of
Regulation (EC) No 1901/2006.

2.
Any person may submit an application for revocation
of the extension of the duration to the body responsible
under national law for the revocation of the corresponding
basic patent.’;

By way of derogation from paragraph 1, the Agency
‘4.
shall make public part of the information on paediatric clin-
ical trials entered in the European database in accordance
with the provisions of Regulation (EC) No 1901/2006 of
the Council of 12
the European Parliament and of
for paediatric
December 2006 on medicinal products
use (*).

(*) OJ L 378, 27.12.2006, p. 1.’

Article 54

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

‘1.
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 unless an authori-
sation has been granted in accordance with Regulation (EC)
No 726/2004, read in conjunction with Regulation (EC) No
1901/2006 of the European Parliament and of the Council
of 12 December 2006 on medicinal products for paediatric
use (*).

(*) OJ L 378, 27.12.2006, p. 1.’

Article 55

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

9) Article 16 shall be amended as follows:

1) Article 56(1) shall be replaced by the following:

(a) the text of Article 16 becomes that Article's para-

graph 1;

‘1.

The Agency shall comprise:

(b) the following paragraph shall be added:

‘2.
If the extension of the duration is revoked in
accordance with Article 15a, notification thereof shall
be published by the authority referred to in Article 9
(1).’;

10) Article 17 shall be replaced by the following:

‘Article 17

Appeals

The decisions of the authority referred to in Article 9(1) or
of the bodies referred to in Articles 15(2) and 15a(2) taken
under this Regulation shall be open to the same appeals as
those provided for in national law against similar decisions
taken in respect of national patents.’.

Article 53

(a) 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;

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

(g) an Executive Director, who shall exercise the responsibil-

ities set out in Article 64;

In Article 11 of Directive 2001/20/EC, the following paragraph
shall be added:

(h) a Management Board, which shall exercise the responsi-

bilities set out in Articles 65, 66 and 67.’;

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2) in Article 57(1), the following point shall be added:

‘(t) taking decisions as referred to in Article 7(1) of Regu-
lation (EC) No 1901/2006 of the European Parliament
and of the Council of 12 December 2006 on medicinal
products for paediatric use (*).

(*) OJ L 378, 27.12.2006, p. 1.’

CHAPTER 3

Final provisions

Article 56

The requirement laid down in Article 7(1) shall not apply to
valid applications pending at the time of entry into force of this
Regulation.

3) the following Article shall be inserted:

Article 57

‘Article 73a

1.
This Regulation shall enter into force on the thirtieth day
following that of its publication in the Official Journal of the Euro-
pean Union.

Decisions taken by the Agency under Regulation (EC) No
1901/2006 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.’.

2.

Article 7 shall apply from 26 July 2008.

Article 8 shall apply from 26 January 2009.

Articles 30 and 31 shall apply from 26 July 2007.

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

Done at Strasbourg, 12 December 2006.

For the European Parliament

The President

J. BORRELL FONTELLES

For the Council

The President

M. PEKKARINEN

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COMMISSION STATEMENT

In view of the risks of carcinogens, mutagens and substances toxic to reproduction, the Commission will
request the Committee for Medicinal Products for Human Use of the European Medicines Agency to draw
up an opinion on the use of these categories of substances as excipients of medicinal products for human
use, on the basis of Articles 5(3) and 57(1)(p) of Regulation (EC) No 726/2004 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 Agency.

The Commission will transmit the opinion of the Committee for Medicinal Products for Human Use to the
European Parliament and the Council.

Within six months of the opinion of the Committee for Medicinal Products for Human Use, the Commis-
sion will inform the European Parliament and the Council of any necessary action it intends to take to
follow-up on this opinion.