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 (Text with EEA relevance)
Date: 2004-03-31
Institutions: Council of the European Union, European Parliament
Subjects: European Medicines Agency, drug surveillance, marketing, medicinal product, veterinary drug

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I

(Acts whose publication is obligatory)

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

(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 and Article
152(4)(b) thereof,

Having regard to the proposal from the Commission (1),

Having regard to the Opinion of the European Economic and
Social Committee (2),

(3)

After consulting the Committee of the Regions,

In accordance with the procedure laid down in Article 251 of
the Treaty (3),

Whereas:

(1)

Article 71 of Council Regulation (EEC) No 2309/93 of
22 July 1993 laying down Community procedures for
the authorisation and supervision of medicinal products
for human and veterinary use and establishing a
European Agency for
the Evaluation of Medicinal
Products (4) provides that, within six years of the entry
the Commission is to
into force of
publish a general report on the experience acquired as
a result of the operation of the procedures laid down in
the Regulation.

the Regulation,

(2)

In the
report on the
the Commission's
experience gained, it has proved necessary to improve

light of

(1) OJ C 75 E, 26.3.2002, p. 189 and OJ C . . . (not yet published in

the Official Journal).

(2) OJ C 61, 14.3.2003, p. 1.
(3) Opinion of the European Parliament of 23 October 2002 (OJ C
300 E, 11.12.2003, p. 308), Council Common Position of
29 September 2003 (OJ C 297 E, 9.12.2003, p. 1), Position of
the European Parliament of 17 December 2003 (not yet
published in the Official
Journal) and Council Decision of
11 March 2004.

the operation of the authorisation procedures for the
in the
placing of medicinal products on the market
Community
and to amend certain administrative
aspects of the European Agency for the Evaluation of
Medicinal Products.
that
In addition,
Agency should be simplified and changed to the
European Medicines Agency, (hereinafter referred to as
the ‘Agency’).

the name of

It emerges from the conclusions of that report that the
amendments to be made to the centralised procedure set
up by Regulation (EEC) No 2309/93 consist of
corrections to some of the operating procedures and
the probable devel-
adaptations to take account of
science and technology and the future
opment of
enlargement of the European Union.
It also emerges
from the report that the general principles previously
established which govern the centralised procedure
should be maintained.

have

since the European Parliament and the
Moreover,
Council
2001/83/EC of
adopted Directive
6 November 2001 on the Community code relating to
medicinal products for human use (5) and Directive
2001/82/EC of 6 November 2001 on the Community
code relating to veterinary medicinal products (6), all the
references to the codified Directives in Regulation (EEC)
No 2309/93 should be updated.

For the sake of clarity, it is necessary to replace the said
Regulation with a new Regulation.

It is appropriate to preserve the Community mechanism
set up by the repealed Community legislation for
concertation prior to any national decision relating to
a high-technology medicinal product.

(4)

(5)

(6)

(4) OJ L 214, 24.8.1993, p. 1. Regulation as last amended by Regu-

(6) OJ L 311, 28.11.2001, p. 1. Directive as amended by Council

lation (EC) No 1647/2003 (OJ L 245, 29.9.2003, p. 19).

Directive 2004/28/EC (see p. 58 of this Official Journal).

(5) OJ L 311, 28.11.2001, p. 67. Directive as last amended by Council

Directive 2004/27/EC (see p. 34 of this Official Journal).

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(7)

the

adoption of Council
Experience gained since
Directive 87/22/EEC of 22 December 1986 on the
approximation of national measures relating to the
placing on the market of high-technology medicinal
products, particularly those derived from biotech-
nology (1) has shown that it is necessary to create a
centralised authorisation procedure that is compulsory
for high-technology medicinal products, particularly
those resulting from biotechnical processes, in order to
maintain the high level of scientific evaluation of these
medicinal products in the European Union and thus to
preserve the confidence of patients and the medical
professions
is particularly
important
the emergence of new
therapies, such as gene therapy and associated cell
therapies,
This
approach should be maintained, particularly with a
view to ensuring the effective operation of the internal
market in the pharmaceutical sector.

in the context of

evaluation. This

xenogenic

therapy.

somatic

in the

and

for human use

(8) With a view to harmonising the internal market for new
medicinal products, this procedure should also be made
compulsory for orphan medicinal products and any
medicinal product
containing an
entirely new active substance, i.e. one that has not yet
been authorised in the Community, and for which the
therapeutic indication is
the treatment of acquired
immune deficiency syndrome, cancer, neurodegenerative
disorder or diabetes. Four years after the date of entry
into force of this Regulation, the procedure should also
become compulsory for medicinal products for human
use containing a new active substance, and for which
the therapeutic indication is for the treatment of auto-
immune diseases and other immune dysfunctions and
viral diseases.
should be possible to review the
provisions in point 3 of the Annex via a simplified
decision-making procedure not earlier than four years
after the entry into force of this Regulation.

It

(9)

to

the

not

belonging

As regards medicinal products for human use, optional
access
to the centralised procedure should also be
provided for in cases where use of a single procedure
produces added value for the patient. This procedure
should remain optional for medicinal products which,
although
abovementioned
categories, are nevertheless therapeutically innovative.
It is also appropriate to allow access to this procedure
for medicinal products which, although not innovative,
may be of benefit to society or to patients if they are
authorised from the outset at Community level, such as
certain medicinal products which can be supplied
without a medical prescription. This option may be
extended to generic medicinal products authorised by
in no way
this
the Community, provided that
the harmonisation achieved when
undermines either

(1) OJ L 15, 17.1.1987, p. 38. Directive repealed by Directive

93/41/EEC (OJ L 214, 24.8.1993, p. 40).

(10)

(11)

(12)

(13)

(14)

the reference medicinal product was evaluated or the
results of that evaluation.

In the field of veterinary medicinal products, adminis-
trative measures should be laid down in order to take
account of the specific features of this field, particularly
those due to the regional distribution of certain diseases.
It should be possible to use the centralised procedure for
the authorisation of veterinary medicinal products used
within the
framework of Community provisions
regarding prophylactic measures for epizootic diseases.
Optional access to the centralised procedure should be
maintained for veterinary medicinal products containing
a new active substance.

For medicinal products for human use, the period for
tests and
protection of data relating to pre-clinical
clinical trials should be the same as that provided for
in Directive 2001/83/EC. For medicinal products for
veterinary use,
the period for protection of data
relating to pre-clinical tests and clinical trials as well
as safety and residue tests should be the same as that
provided for in Directive 2001/82/EC.

In order to reduce the cost for small and medium-sized
enterprises of marketing medicinal products authorised
via the centralised procedure, provisions
should be
adopted to allow for a reduction of fees, deferring the
payment of fees, taking over responsibility for trans-
lations and offering administrative assistance in respect
of these enterprises.

economic

and other

the use in their

In the interest of public health, authorisation decisions
under the centralised procedure should be taken on the
basis of the objective scientific criteria of quality, safety
and efficacy of the medicinal product concerned, to the
exclusion of
considerations.
However, Member States should be able exceptionally
territory of medicinal
to prohibit
products
for human use which infringe objectively
defined concepts of public policy and public morality.
Moreover, a veterinary medicinal product is not to be
its use would
authorised by
contravene the rules laid down within the framework
of the Common Agricultural Policy or if presented for
a use prohibited under other Community provisions,
inter alia Directive 96/22/EC (2).

the Community

if

criteria

2001/83/EC

Provision should be made for the quality, safety and
efficacy
and
in Directives
2001/82/EC to apply to medicinal products authorised
by the Community and it should be possible to assess
the risk-benefit balance of all medicinal products when
they are placed on the market, at
the
renewal of the authorisation and at any other time the
competent authority deems appropriate.

the time of

(2) Council Directive 96/22/EC of 29 April 1996 concerning the
prohibition on the use in stockfarming of certain substances
having a hormonal or thyrostatic action and of β-agonists (OJ L
125, 23.5.1996, p. 3).

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(15)

(16)

(17)

(18)

fit

The Community is required, pursuant to Article 178 of
the Treaty, to take account of the development policy
aspects of any measure and to promote the creation of
conditions
for human beings worldwide. Phar-
maceutical law should continue to ensure that only effi-
cacious, safe and top-quality medicinal products are
exported,
consider
the Commission
creating further incentives to carry out research into
medicinal products against widespread tropical diseases.

should

and

is also a need to provide for

There
the ethical
requirements of Directive 2001/20/EC of 4 April 2001
of the European Parliament and of the Council on the
approximation of
the laws, regulations and adminis-
trative provisions of the Member States relating to the
implementation of good clinical practice in the conduct
of clinical trials on medicinal products for human use (1)
to apply to medicinal products authorised by the
Community. In particular, with respect to clinical trials
the Community on medicinal
conducted outside
products
the
to
destined
the
Community, at
application for authorisation, it should be verified that
these trials were conducted in accordance with the prin-
ciples of
ethical
requirements equivalent to the provisions of the said
Directive.

authorised within
the evaluation of

good clinical practice

the time of

and the

be

a

legislation in the
single

best possible scientific opinions so as to enable them
to exercise the powers regarding the authorisation and
supervision of medicinal products conferred on them by
field of medicinal
Community
evaluation
scientific
products. Only after
procedure addressing the quality, safety and efficacy of
high-technology medicinal products has been conducted
by the Agency, applying the highest possible standards,
should marketing authorisation be granted by the
Community, and this should be done by means of a
rapid procedure ensuring close cooperation between
the Commission and Member States.

(20)

In order
to ensure close cooperation between the
Agency and scientists operating in Member States, the
composition of the Management Board should be such
as to guarantee that the competent authorities of the
Member States are closely involved in the overall
management of the Community system for authorising
medicinal products.

(21)

The Agency's budget should be composed of fees paid
by the private sector and contributions paid out of the
Community budget to implement Community policies.

The Community should have the means to carry out a
scientific assessment of the medicinal products presented
in accordance with the decentralised Community auth-
orisation procedures. Moreover, with a view to ensuring
the effective harmonisation of administrative decisions
taken by Member States with regard to medicinal
products presented in accordance with decentralised
authorisation procedures,
it is necessary to endow the
Community with the means to resolve disagreements
between Member States concerning the quality, safety
and efficacy of medicinal products.

(22)

(23)

The structure and operation of
the various bodies
making up the Agency should be designed in such a
the need constantly to
way as to take into account
renew scientific expertise,
the need for cooperation
between Community and national bodies, the need for
adequate involvement of civil society, and the future
the European Union. The various
enlargement of
the Agency should establish and develop
bodies of
in
appropriate contacts with the parties concerned,
particular
representatives of patients and health-care
professionals.

the Interinstitutional Agreement of
Paragraph 25 of
the
6 May 1999 between the European Parliament,
Council and the Commission on budgetary discipline
and improvement of budgetary procedure (2) provides
for the Financial Perspective to be adjusted in order to
cover the new needs resulting from enlargement.

all

questions

responsibility for preparing the Agency's
Exclusive
concerning medicinal
on
opinions
products
should be vested in a
for human use
Committee for Medicinal Products for Human Use. As
far as veterinary medicinal products are concerned, such
responsibility should be vested in a Committee for
regards
Medicinal Products
orphan medicinal products, the task should fall to the
Committee on Orphan Medicinal Products set up under
Regulation (EC) No 141/2000 of
European
Parliament and of the Council of 16 December 1999
on orphan medicinal products (3). Lastly, as regards
herbal medicinal products, this responsibility should be
vested in the Committee on Herbal Medicinal Products
set up under Directive 2001/83/EC.

for Veterinary Use. As

the

(19)

The chief
the Agency should be to provide
Community institutions and Member States with the

task of

(24)

The creation of the Agency will make it possible to
reinforce the scientific role and independence of the
committees, particularly through the setting-up of a
permanent technical and administrative secretariat.

(1) OJ L 121, 1.5.2001, p. 34.

(2) OJ C 172, 18.6.1999, p. 1.
(3) OJ L 18, 22.1.2000, p. 1.

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(25)

(26)

(27)

(28)

(29)

and

their

enlarged

operating methods

The field of activity of the Scientific Committees should
be
and
composition modernised. Scientific advice for future
applicants seeking marketing authorisation should be
provided more generally and in greater depth. Similarly,
structures allowing the development of advice for
companies, in particular small and medium-sized enter-
prises, should be put in place. The committees should be
able to delegate some of
their evaluation duties to
standing working parties open to experts from the
scientific world appointed for
this purpose, whilst
retaining total responsibility for the scientific opinions
issued. The
should be
re-examination procedures
amended to provide a better guarantee for applicants'
rights.

The number of members of the Scientific Committees
participating in the centralised procedure should be
established with a view to ensuring that the committees
remain of an efficient size after the enlargement of the
European Union.

It is also necessary to reinforce the role of the Scientific
Committees in such a way as to enable the Agency to
participate actively in international scientific dialogue
and to develop certain activities that will be necessary,
in particular regarding international scientific harmon-
isation and technical
cooperation with the World
Health Organisation.

Furthermore, in order to create greater legal certainty it
is necessary to define the responsibilities regarding the
transparency rules for the Agency's work, to set certain
conditions for the marketing of medicinal products auth-
orised by the Community, to confer on the Agency
the distribution of medicinal
powers
products authorised by the Community and to specify
the sanctions and the procedures for implementing them
in the event of failure to observe the provisions of this
Regulation and the conditions contained in the author-
isations granted under the procedures it establishes.

to monitor

It is also necessary to take measures for the supervision
of medicinal products authorised by the Community,
and in particular for the intensive supervision of unde-
sirable effects of these medicinal products within the
framework of Community pharmacovigilance activities,
so as to ensure the rapid withdrawal from the market of
any medicinal product presenting a negative risk-benefit
balance under normal conditions of use.

(30)

In order to enhance the efficiency of market surveillance,
the Agency should be responsible for coordinating
Member States' pharmacovigilance activities. A number
of provisions need to be introduced to put in place

(31)

(32)

(33)

stringent and efficient pharmacovigilance procedures,
to allow the competent authority to take provisional
including the introduction of
emergency measures,
amendments
authorisation and,
finally, to permit a reassessment to be made at any
time of the risk-benefit balance of a medicinal product.

to the marketing

It is also appropriate to entrust the Commission, in close
cooperation with the Agency and after consultations
with the Member States, with the task of coordinating
the execution of the various supervisory responsibilities
vested in the Member States, and in particular with the
tasks of providing information on medicinal products
and of checking the observance of good manufacturing,
laboratory and clinical practices.

It is necessary to provide for the coordinated implemen-
tation of Community procedures for the authorisation of
medicinal products, and of the national procedures of
Member States which have already been harmonised to a
considerable degree by Directives 2001/83/EC and
2001/82/EC. It is appropriate that the operation of the
procedures laid down by this Regulation be re-examined
by the Commission every ten years on the basis of
experience gained.

account of

and to take

in particular, the legitimate expec-
In order to meet,
tations of patients
the
increasingly rapid progress of science and therapies,
accelerated assessment procedures should be set up,
reserved for medicinal products of major therapeutic
interest, and procedures for obtaining temporary auth-
reviewable
orisations
conditions.
for
human use, a common approach should also be
followed, whenever possible, regarding the criteria and
conditions for the compassionate use of new medicinal
products under Member States' legislation.

subject
to certain annually
In the field of medicinal products

(34) Member States have developed an evaluation of

emphasised

the
comparative efficacy of medicinal products aimed at
positioning a new medicinal product with respect to
those that already exist in the same therapeutic class.
Similarly, the Council, in its Conclusions on medicinal
products and public health (1), adopted on 29 June
2000,
identifying
medicinal products that presented an added therapeutic
value. However this evaluation should not be conducted
in the context of the marketing authorisation, for which
the fundamental criteria should be
it
retained.
in this respect to allow for the
possibility of gathering information on the methods
used by the Member States to determine the therapeutic
benefit obtained by each new medicinal product.

importance of

is agreed that

It is useful

the

(1) OJ C 218, 31.7.2000, p. 10.

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(35)

(36)

current provisions of Directives
In line with the
2001/83/EC and 2001/82/EC, the term of validity of a
Community marketing authorisation should be limited
initially to a period of five years, upon the expiry of
which it should be renewed. Thereafter the marketing
authorisation should normally be of unlimited validity.
Furthermore, any authorisation not used for
three
consecutive years, that is to say, one which has not
led to the placing on the market of a medicinal
product in the Community during that period, should
be considered invalid, in order,
in particular, to avoid
the administrative burden of maintaining such authoris-
ations. However,
to
rule
exemptions when these are justified on public health
grounds.

should be

subject

this

Environmental risks may arise from medicinal products
genetically modified
containing
such
organisms.
products
risk-assessment
to the procedure under Directive
procedure similar

consisting
is
an

thus necessary

environmental

to subject

or
It
to

of

the

the European Parliament and of

the
2001/18/EC of
Council of 12 March 2001 on the deliberate release
into
genetically modified
organisms (1),
to be conducted in parallel with the
evaluation, under a single Community procedure, of
the quality, safety and efficacy of the product concerned.

environment

of

(37)

(38)

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 Commission (2).

The provisions of Regulation (EC) No 1647/2003 (3)
amending Regulation (EC) No 2309/93 as regards the
budgetary and financial rules applicable to the Agency
and access to the Agency's documents should be fully
incorporated into this Regulation,

HAVE ADOPTED THIS REGULATION:

TITLE I

DEFINITIONS AND SCOPE

Article 1

Article 3

for

The purpose of this Regulation is to lay down Community
procedures
supervision and phar-
macovigilance of medicinal products for human and veterinary
use, and to establish a European Medicines Agency (hereinafter
referred to as ‘the Agency’).

authorisation,

the

The provisions of this Regulation shall not affect the powers of
Member States' authorities as regards setting the prices of
medicinal products or their inclusion in the scope of
the
national health system or social security schemes on the
basis of health, economic and social conditions. In particular,
Member States shall be free to choose from the particulars
shown in the marketing authorisation those therapeutic indi-
cations and pack sizes which will be covered by their social
security bodies.

Article 2

1.
No medicinal product appearing in the Annex may be
placed on the market within the Community unless a
marketing authorisation has been granted by the Community
in accordance with the provisions of this Regulation.

2.
Any medicinal product not appearing in the Annex may
be granted a marketing authorisation by the Community in
accordance with the provisions of this Regulation, if:

(a) the medicinal product contains a new active substance
which, on the date of entry into force of this Regulation,
was not authorised in the Community; or

(b) the applicant shows that the medicinal product constitutes
a significant therapeutic, scientific or technical innovation
or that the granting of authorisation in accordance with
this Regulation is in the interests of patients or animal
health at Community level.

The definitions laid down in Article 1 of Directive 2001/83/EC
and those laid down in Article 1 of Directive 2001/82/EC shall
apply for the purposes of this Regulation.

Immunological veterinary medicinal products for the treatment
of animal diseases that are subject to Community prophylactic
measures may also be granted such authorisation.

The holder of a marketing authorisation for medicinal products
covered by this Regulation must be established in the
Community. The holder shall be responsible for the placing
on the market of those medicinal products, whether he does
it himself or via one or more persons designated to that effect.

___________
(1) OJ L 106, 17.4.2001, p. 1. Directive as last amended by Regulation
(EC) No 1830/2003 of the European Parliament and of the Council
(OJ L 268, 18.10.2003, p. 24).

(2) OJ L 184, 17.7.1999, p. 23.
(3) OJ L 245, 29.9.2003, p. 19.

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A generic medicinal product of a reference medicinal
3.
product authorised by the Community may be authorised by
the competent authorities of the Member States in accordance
with Directive 2001/83/EC and Directive 2001/82/EC under
the following conditions:

After the competent committee of the Agency has been
4.
consulted,
the Annex may be re-examined in the light of
technical and scientific progress, with a view to making any
necessary amendments without extending the scope of
the
centralised procedure. Such amendments shall be adopted in
accordance with the procedure referred to in Article 87(2).

(a) the application for authorisation is submitted in accordance
with Article 10 of Directive 2001/83/EC or Article 13 of
Directive 2001/82/EC;

(b) the summary of the product characteristics is in all relevant
respects consistent with that of the medicinal product auth-
orised by the Community except for those parts of the
summary of product characteristics referring to indications
or dosage forms which were still covered by patent law at
the time when the generic medicine was marketed; and

(c) the generic medicinal product is authorised under the same
name in all the Member States where the application has
been made. For the purposes of this provision, all the
linguistic versions of the INN (international non-proprietary
name) shall be considered to be the same name.

Article 4

Applications for the marketing authorisations referred to

1.
in Article 3 shall be submitted to the Agency.

The Community shall grant and supervise marketing
for human use in

for medicinal products

2.
authorisations
accordance with Title II.

3.
The Community shall grant and supervise marketing
authorisations for veterinary medicinal products in accordance
with Title III.

AUTHORISATION AND SUPERVISION OF MEDICINAL PRODUCTS FOR HUMAN USE

TITLE II

C h a p t e r 1

Article 6

Submission and examination of applications —
Authorisations

Article 5

1.
A Committee for Medicinal Products for Human Use is
hereby established. The Committee shall be part of the Agency.

2. Without prejudice to Article 56 or to other tasks which
Community law may confer on it, the Committee for Medicinal
Products for Human Use shall be responsible for drawing up
the Agency on any matter concerning the
the opinion of
admissibility of
the files submitted in accordance with the
centralised procedure, the granting, variation, suspension or
revocation of an authorisation to place a medicinal product
for human use on the market
in accordance with the
provisions of this Title, and pharmacovigilance.

concerning the

At the request of the Executive Director of the Agency or
3.
the Commission representative, the Committee for Medicinal
Products for Human Use shall also draw up an opinion on any
evaluation of medicinal
scientific matter
take due
for human use. The Committee shall
products
account of any requests by Member States for an opinion.
The Committee shall also formulate an opinion whenever
there is disagreement in the evaluation of medicinal products
through the mutual recognition procedure. The opinion of the
Committee shall be made publicly accessible.

for human use shall

Each application for the authorisation of a medicinal
1.
specifically and completely
product
referred to in
include the particulars and documents as
to,
Articles 8(3), 10, 10a, 10b or 11 of, and Annex I
a
include
Directive 2001/83/EC. The documents must
statement to the effect that clinical trials carried out outside
the European Union meet the ethical requirements of Directive
2001/20/EC. These particulars and documents
take
account of the unique, Community nature of the authorisation
requested and, otherwise than in exceptional cases relating to
the application of the law on trade marks, shall include the use
of a single name for the medicinal product.

shall

The application shall be accompanied by the fee payable to the
Agency for the examination of the application.

In the case of a medicinal product

2.
for human use
containing or consisting of genetically modified organisms
within the meaning of Article 2 of Directive 2001/18/EC, the
application shall be accompanied by:

(a) a copy of the competent authorities' written consent to the
deliberate release into the environment of the genetically
modified organisms for research and development purposes
where provided for in Part B of Directive 2001/18/EC or in
Part B of Council Directive 90/220/EEC of 23 April 1990
environment of
on the deliberate
genetically modified organisms (1);

into the

release

(1) OJ L 117, 8.5.1990, p. 15. Directive repealed by Directive

2001/18/EC, but continues to have certain legal effects.

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(b) the complete technical dossier supplying the information
required by Annexes III and IV to Directive 2001/18/EC;

(c) the environmental risk assessment in accordance with the
principles set out in Annex II to Directive 2001/18/EC; and

(d) the results of any investigations performed for the purposes

of research or development.

Articles 13 to 24 of Directive 2001/18/EC shall not apply to
medicinal products for human use containing or consisting of
genetically modified organisms.

The Agency shall ensure that

the
3.
Committee for Medicinal Products for Human Use is given
within 210 days after receipt of a valid application.

the opinion of

The duration of the analysis of the scientific data in the file
concerning the application for marketing authorisation must be
at least 80 days, except in cases where the rapporteur and
co-rapporteur
their
that
assessment before that time.

they have

completed

declare

(b) may request that an Official Medicines Control Laboratory
or a laboratory that a Member State has designated for that
its
purpose test
starting materials
intermediate
products or other constituent materials in order to ensure
that the control methods employed by the manufacturer
and described in the application documents are satisfactory;

the medicinal product

for human use,

if need be,

and,

its

(c) may request that the applicant supplement the particulars
accompanying the application within a specific time period.
Where the said Committee avails itself of this option, the
time-limit laid down in Article 6(3),
first subparagraph,
shall be suspended until such time as the supplementary
this
information requested has been provided. Likewise,
time-limit shall be suspended for the time allowed for the
applicant to prepare oral or written explanations.

Article 8

1.
Upon receipt of a written request from the Committee for
Medicinal Products for Human Use, a Member State shall
forward the information showing that the manufacturer of a
medicinal product or the importer from a third country is able
to manufacture the medicinal product concerned and/or carry
out
in accordance with the
tests
particulars and documents supplied pursuant to Article 6.

the necessary control

On the basis of a duly reasoned request, the said Committee
may call for the duration of the analysis of the scientific data in
the file concerning the application for marketing authorisation
to be extended.

2. Where it considers it necessary in order to complete its
examination of an application, the said Committee may require
the applicant to undergo a specific inspection of the manu-
facturing site of
the medicinal product concerned. Such
inspections may be made unannounced.

the

shall

respect

environmental

In the case of a medicinal product for human use containing or
consisting of genetically modified organisms, the opinion of the
said Committee
safety
requirements laid down by Directive 2001/18/EC. During the
process of evaluating applications for marketing authorisations
for medicinal products for human use containing or consisting
of genetically modified organisms, the rapporteur shall carry
out necessary consultations of bodies that the Community or
Member States have set up in accordance with Directive
2001/18/EC.

4.
The Commission shall, in consultation with the Agency,
Member States and interested parties, draw up a detailed guide
regarding the form in which applications for authorisation are
to be presented.

The inspection shall be carried out within the time-limit laid
down in the first subparagraph of Article 6(3) by inspectors
from the Member State holding the appropriate qualifications;
they may be accompanied by a rapporteur or an expert
appointed by the Committee.

Article 9

The Agency shall forthwith inform the applicant if the
1.
opinion of the Committee for Medicinal Products for Human
Use is that:

(a) the application does not satisfy the criteria for author-

isation set out in this Regulation;

Article 7

In order to prepare its opinion, the Committee for Medicinal
Products for Human Use:

(b) the summary of the product characteristics proposed by the

applicant needs to be amended;

(a) shall verify that the particulars and documents submitted in
accordance with Article 6 comply with the requirements of
Directive 2001/83/EC, and shall examine whether
the
conditions specified in this Regulation for granting a
marketing authorisation are satisfied;

(c)

the labelling or package leaflet of the product is not in
compliance with Title V of Directive 2001/83/EC;

(d) the authorisation needs to be granted subject
conditions provided for in Article 14(7) and (8).

to the

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2. Within 15 days after receipt of the opinion referred to in
paragraph 1, the applicant may give written notice to the
Agency that he wishes to request a re-examination of the
opinion.
forward to the
Agency the detailed grounds for the request within 60 days
after receipt of the opinion.

the applicant shall

In that case,

Within 60 days following receipt of
the grounds for the
request, the said Committee shall re-examine its opinion in
accordance with the conditions laid down in the fourth
subparagraph of Article 62(1). The reasons for the conclusion
reached shall be annexed to the final opinion.

3. Within 15 days after its adoption, the Agency shall send
the final opinion of the said Committee to the Commission, to
the Member States and to the applicant, together with a report
describing the assessment of the medicinal product by the
Committee and stating the reasons for its conclusions.

4.
If an opinion is favourable to the granting of the relevant
authorisation to place the medicinal product concerned on the
the following documents shall be annexed to the
market,
opinion:

(a) a draft summary of the product characteristics, as referred

to in Article 11 of Directive 2001/83/EC;

(b) details of any conditions or restrictions which should be
imposed on the supply or use of the medicinal product
including the conditions under which the
concerned,
medicinal product may be made available to patients,
in
accordance with the criteria laid down in Title VI of
Directive 2001/83/EC;

(c) details of any recommended conditions or restrictions with
the medicinal

regard to the safe and effective use of
product;

(d) the draft text of the labelling and package leaflet proposed
by the applicant, presented in accordance with Title V of
Directive 2001/83/EC;

(e) the assessment report.

Article 10

1. Within 15 days after receipt of the opinion referred to in
Article 5(2),
the
decision to be taken in respect of the application.

the Commission shall prepare a draft of

Where a draft decision envisages the granting of a marketing
authorisation,
include or make reference to the
documents mentioned in Article 9(4)(a), (b), (c) and (d).

shall

it

Where the draft decision is not in accordance with the opinion
of the Agency, the Commission shall annex a detailed expla-
nation of the reasons for the differences.

The draft decision shall be forwarded to Member States and the
applicant.

The Commission shall take a final decision in accordance
the procedure

2.
with, and within 15 days after the end of,
referred to in Article 87(3).

3.
for
The Standing Committee on Medicinal Products
Human Use referred to in Article 87(1) shall adjust its rules
of procedure so as to take account of the tasks incumbent
upon it under this Regulation.

The adjustments shall provide that:

(a) the opinion of the said Standing Committee is to be given

in writing;

(b) Member States shall have 22 days to forward their written
observations on the draft decision to the Commission.
However, if a decision has to be taken urgently, a shorter
time-limit may be set by the Chairman according to the
degree of urgency involved. This time-limit shall not,
otherwise than in exceptional circumstances, be shorter
than 5 days;

(c) Member States may request

the draft
decision referred to in paragraph 1 be discussed by a
plenary meeting of the said Standing Committee, stating
their reasons in detail.

in writing that

4. Where,
in the opinion of the Commission, a Member
State's written observations raise important new questions of
a scientific or technical nature which the opinion delivered by
the Agency has not addressed, the Chairman shall suspend the
procedure and refer the application back to the Agency for
further consideration.

5.
The Commission shall adopt the provisions necessary for
the implementation of paragraph 4 in accordance with the
procedure referred to in Article 87(2).

The Agency shall disseminate the documents referred to

6.
in Article 9(4)(a), (b), (c) and (d).

Article 11

If an applicant withdraws an application for a marketing auth-
orisation submitted to the Agency before an opinion has been
given on the application, the applicant shall communicate its
reasons for doing so to the Agency. The Agency shall make
this information publicly accessible and shall publish the
assessment report, if available, after deletion of all information
of a commercially confidential nature.

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Article 12

The marketing authorisation shall be refused if, after
1.
the particulars and documents submitted in
verification of
accordance with Article 6,
it appears that the applicant has
not properly or sufficiently demonstrated the quality, safety
or efficacy of the medicinal product.

likewise be refused if particulars or
Authorisation shall
documents provided by the applicant
in accordance with
Article 6 are incorrect or if the labelling and package leaflet
proposed by the applicant are not in accordance with Title V
of Directive 2001/83/EC.

2.
The refusal of a Community marketing authorisation shall
constitute a prohibition on the placing on the market of the
medicinal product concerned throughout the Community.

After a marketing authorisation has been granted, the
4.
inform the Agency of the
holder of the authorisation shall
dates of actual marketing of
for
human use in the Member States, taking into account the
various presentations authorised.

the medicinal product

The holder shall also notify the Agency if the product ceases to
be placed on the market, either temporarily or permanently.
Such notification shall, otherwise than in exceptional circum-
stances, be made no less than 2 months before the interruption
in the placing on the market of the product.

Upon request by the Agency, particularly in the context of
pharmacovigilance,
the marketing authorisation holder shall
provide the Agency with all data relating to the volume of
sales of the medicinal product at Community level, broken
down by Member State, and any data in the holder's possession
relating to the volume of prescriptions.

Information about all refusals and the reasons for them

3.
shall be made publicly accessible.

Article 14

Article 13

4(4)

prejudice

to Article

1. Without
of Directive
2001/83/EC, a marketing authorisation which has been
granted in accordance with this Regulation shall be valid
throughout the Community. It shall confer the same rights
and obligations in each of the Member States as a marketing
authorisation granted by that Member State in accordance with
Article 6 of Directive 2001/83/EC.

Authorised medicinal products for human use shall be entered
in the Community Register of Medicinal Products and shall be
given a number, which shall appear on the packaging.

1. Without prejudice to paragraphs 4, 5 and 7 a marketing
authorisation shall be valid for five years.

2.
The marketing authorisation may be renewed after five
years on the basis of a re-evaluation by the Agency of the
risk-benefit balance.

To this end, the marketing authorisation holder shall provide
the Agency with a consolidated version of the file in respect of
quality, safety and efficacy, including all variations introduced
since the marketing authorisation was granted, at
least six
months before the marketing authorisation ceases to be valid
in accordance with paragraph 1.

Journal of

Notification of marketing authorisation shall be published
2.
the European Union, quoting in
in the Official
the date of authorisation and the registration
particular
number
International
Non-proprietary Name (INN) of the active substance of the
medicinal
any
its
Anatomical Therapeutic Chemical Code (ATC).

in the Community Register,

pharmaceutical

product,

form,

and

any

The Agency shall

3.
immediately publish the assessment
report on the medicinal product for human use drawn up by
the Committee for Medicinal Products for Human Use and the
reasons for its opinion in favour of granting authorisation, after
deletion of any information of a commercially confidential
nature.

The European Public Assessment Report (EPAR) shall include a
summary written in a manner that is understandable to the
public. The summary shall contain in particular a section
relating to the conditions of use of the medicinal product.

3.
Once renewed, the marketing authorisation shall be valid
for an unlimited period, unless the Commission decides, on
justified grounds relating to pharmacovigilance,
to proceed
in accordance with
with one additional
paragraph 2.

five-year

renewal

4.
Any authorisation which is not followed by the actual
for human use on the
placing of
Community market within three years after authorisation
shall cease to be valid.

the medicinal product

5. When an authorised medicinal product previously placed
on the market is no longer actually present on the market for
three consecutive years, the authorisation shall cease to be
valid.

In exceptional

circumstances and on public health
6.
grounds
from
paragraphs 4 and 5. Such exemptions must be duly justified.

the Commission may

exemptions

grant

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Following consultation with the applicant, an author-
7.
isation may be granted subject to certain specific obligations,
to be reviewed annually by the Agency. The list of these obli-
gations shall be made publicly accessible.

By way of derogation from paragraph 1, such authorisation
shall be valid for one year, on a renewable basis.

The provisions for granting such authorisation shall be laid
down in a Commission Regulation adopted in accordance
with the procedure referred to in Article 87(2).

requirement

to introduce

the
for
in particular

applicant
concerning the

8.
In exceptional circumstances and following consultation
with the applicant, the authorisation may be granted subject to
specific
a
the
procedures,
medicinal product, notification to the competent authorities
of any incident relating to its use, and action to be taken.
This authorisation may be granted only for objective, verifiable
reasons and must be based on one of the grounds set out in
Annex I to Directive 2001/83/EC. Continuation of the author-
isation shall be linked to the annual reassessment of these
conditions.

safety of

9. When an application is submitted for a marketing auth-
orisation in respect of medicinal products for human use which
are of major interest from the point of view of public health
and in particular from the viewpoint of therapeutic innovation,
the applicant may request an accelerated assessment procedure.
The request shall be duly substantiated.

If
the Committee for Medicinal Products for Human Use
accepts the request, the time-limit laid down in Article 6(3),
first subparagraph, shall be reduced to 150 days.

its opinion,

10. When adopting
Medicinal Products for Human Use shall
concerning the criteria for the prescription or use of
medicinal products
Directive 2001/83/EC.

for
include a proposal
the
in accordance with Article 70(1) of

the Committee

this Regulation shall benefit

11. Without prejudice to the law on the protection of
industrial and commercial property, medicinal products for
human use which have been authorised in accordance with
from an
the provisions of
eight-year period of data protection and a ten-year period of
marketing protection,
in which connection the latter period
shall be extended to a maximum of 11 years if, during the
first eight years of those ten years, the marketing authorisation
holder obtains an authorisation for one or more new thera-
peutic indications which, during the scientific evaluation prior
to their authorisation, are held to bring a significant clinical
benefit in comparison with existing therapies.

marketing authorisation pursuant to the applicable national law
in Member States.

C h a p t e r 2

Supervision and penalties

Article 16

1.
After an authorisation has been granted in accordance
with this Regulation, the holder of the marketing authorisation
for a medicinal product for human use shall, in respect of the
methods of manufacture and control provided for in Article
8(3)(d) and (h) of Directive 2001/83/EC,
take account of
technical and scientific progress and make any variations that
may be required to enable the medicinal products to be manu-
factured and checked by means of generally accepted scientific
methods. He shall apply for approval of such variations in
accordance with this Regulation.

The holder of the marketing authorisation shall forthwith
2.
supply to the Agency, to the Commission and to the Member
States any new information which might entail the variation of
the particulars or documents referred to in Articles 8(3), 10,
10a, 10b and 11 of Directive 2001/83/EC, in Annex I thereto,
or in Article 9(4) of this Regulation.

forthwith inform the Agency,

the
In particular, he shall
Commission and the Member States of any prohibition or
restriction imposed by the competent authorities of any
country in which the medicinal product for human use is
marketed and of any other new information which might
the
influence the evaluation of
medicinal product for human use concerned.

the benefits and risks of

In order that the risk-benefit balance may be continuously
assessed, the Agency may at any time ask the holder of the
marketing authorisation to forward data demonstrating that the
risk-benefit balance remains favourable.

If the holder of the authorisation for a medicinal product
3.
for human use proposes
the
particulars and documents referred to in paragraph 2, he
shall submit the relevant application to the Agency.

to make any variation of

4.
The Commission shall, after consulting the Agency, adopt
appropriate provisions for the examination of variations to
marketing authorisations
in the form of a regulation in
accordance with the procedure referred to in Article 87(2).

Article 15

The granting of authorisation shall not affect
the civil or
criminal liability of the manufacturer or of the holder of the

The applicant or the holder of a marketing authorisation shall
be responsible for the accuracy of the documents and of the
data submitted.

Article 17

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Article 18

1.
In the case of medicinal products for human use manu-
factured within the Community, the supervisory authorities
shall be the competent authorities of the Member State or
Member States which granted the manufacturing authorisation
provided for in Article 40(1) of Directive 2001/83/EC in
respect of the medicinal product concerned.

2.
In the case of medicinal products imported from third
countries, the supervisory authorities shall be the competent
authorities of the Member State or Member States that granted
the authorisation provided for in Article 40(3) of Directive
2001/83/EC to the importer, unless appropriate agreements
have been made between the Community and the exporting
country to ensure that those controls are carried out in the
exporting country and that the manufacturer applies standards
of good manufacturing practice at least equivalent to those laid
down by the Community.

A Member State may request assistance from another Member
State or from the Agency.

Article 19

The supervisory authorities

1.
shall be responsible for
verifying on behalf of the Community that the holder of the
marketing authorisation for the medicinal product for human
use or the manufacturer or importer established within the
Community satisfies the requirements laid down in Titles IV,
IX and XI of Directive 2001/83/EC.

in accordance with Article 122 of Directive
2. Where,
2001/83/EC, the Commission is informed of serious differences
of opinion between Member States as to whether the holder of
the marketing authorisation for the medicinal product
for
human use or a manufacturer or importer established within
the Community satisfies
referred to in
paragraph 1,
the Commission may, after consultation with
the Member States concerned, request an inspector from the
supervisory authority to undertake a new inspection of the
the
marketing authorisation holder,
importer; the inspector in question shall be accompanied by
two inspectors from Member States which are not party to the
dispute or by two experts nominated by the Committee for
Medicinal Products for Human Use.

the manufacturer or

the requirements

Subject

3.
to any agreements which may have been
concluded between the Community and third countries in
the Commission may,
accordance with Article 18(2),
following a reasoned request from a Member State or from
the said Committee, or on its own initiative, require a manu-
facturer established in a third country to submit
to an
inspection.

The inspection shall be undertaken by inspectors from the
Member States who possess the appropriate qualifications;
expert
they may be

accompanied by a

rapporteur or

appointed by the said Committee. The report of the inspectors
shall be made available to the Commission, the Member States
and the said Committee.

Article 20

1. Where the supervisory authorities or the competent auth-
orities of any other Member State are of the opinion that the
manufacturer or importer established within the Community
territory is no longer fulfilling the obligations laid down in
Title IV of Directive 2001/83/EC, they shall forthwith inform
the Committee for Medicinal Products for Human Use and the
Commission, stating their reasons in detail and indicating the
course of action proposed.

shall

same

apply where

a Member State or

The
the
Commission considers that one of the measures envisaged in
Titles IX and XI of Directive 2001/83/EC should be applied in
respect of the medicinal product concerned or where the said
Committee has delivered an opinion to that
in
accordance with Article 5 of this Regulation.

effect

the matter,

2.
The Commission shall request the opinion of the Agency
within a time-limit which it shall determine in the light of the
to examine the reasons
in order
urgency of
advanced. Whenever practicable,
the author-
isation for placing the medicinal product for human use on
the market shall be invited to provide oral or written expla-
nations.

the holder of

3.
Following an opinion by the Agency, the Commission
shall adopt the necessary provisional measures, which shall
be applied immediately.

A final decision shall be adopted within six months,
accordance with the procedure referred to in Article 87(3).

in

4. Where urgent action is essential to protect human health
or the environment, a Member State may, on its own initiative
or at the Commission's request, suspend the use in its territory
of a medicinal product for human use which has been auth-
orised in accordance with this Regulation.

When it does so on its own initiative,
inform the
Commission and the Agency of the reasons for its action at
the latest on the next working day following the suspension.
inform the other Member States without
The Agency shall
the
immediately
delay. The Commission shall
procedure provided for in paragraphs 2 and 3.

it shall

initiate

case,

In this

the Member State

that
5.
health-care professionals are rapidly informed of
its action
and the reasons for the action. Networks set up by professional
associations may be used to this effect. The Member States
shall
inform the Commission and the Agency of actions
taken for this purpose.

ensure

shall

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The suspensive measures referred to in paragraph 4 may
6.
be maintained in force until such time as a definitive decision
has been reached in accordance with the procedure referred to
in Article 87(3).

which are reported to the personnel of the company and
to medical
is collected, evaluated and
collated so that
it may be accessed at a single point
within the Community;

representatives

The Agency shall, upon request,

7.
concerned of
publicly accessible immediately after it has been taken.

inform any person
the final decision and make the decision

C h a p t e r 3

Pharmacovigilance

Article 21

For the purposes of this Chapter, Article 106(2) of Directive
2001/83/EC shall apply.

Article 22

The Agency, acting in close cooperation with the national
pharmacovigilance systems established in accordance with
Article 102 of Directive 2001/83/EC, shall receive all relevant
information concerning
to
suspected
medicinal products for human use which have been authorised
by the Community in accordance with this Regulation. Where
appropriate, the Committee for Medicinal Products for Human
Use shall, in accordance with Article 5 of this Regulation, draw
up opinions on the measures necessary. These opinions shall
be made publicly accessible.

reactions

adverse

The measures referred to in the first paragraph may include
amendments
to the marketing authorisation granted in
accordance with Article 10. They shall be adopted in
accordance with the procedure referred to in Article 87(3).

The holder of the marketing authorisation and the competent
authorities of Member States shall ensure that all relevant
information concerning suspected adverse reactions to the
medicinal products authorised under
this Regulation are
brought to the attention of the Agency in accordance with
the provisions of this Regulation. Patients shall be encouraged
to
health-care
adverse
professionals.

communicate

reaction

any

to

Article 23

The holder of an authorisation for a medicinal product for
human use granted in accordance with the provisions of this
Regulation shall have permanently and continuously at his
disposal an appropriately qualified person responsible for phar-
macovigilance.

That qualified person shall reside in the Community and shall
be responsible for the following:

(b) preparing the reports referred to in Article 24(3) for the
competent authorities of
the Member States and the
Agency in accordance with the requirements of this Regu-
lation;

(c) ensuring that any request from the competent authorities
information necessary for
for the provision of additional
the evaluation of the risks and benefits of a medicinal
product
including the
provision of information regarding the volume of sales or
prescriptions for the medicinal product concerned;

is answered fully and promptly,

(d) providing the

competent

authorities with any other
information relevant
to the evaluation of the risks and
benefits of a medicinal product, particularly information
concerning post-authorisation safety studies.

Article 24

reactions

1.
The holder of the marketing authorisation for a medicinal
product for human use shall ensure that all suspected serious
adverse
to a medicinal product authorised in
accordance with this Regulation occurring within the
Community which a health-care professional brings to his
attention are recorded and reported promptly to Member
States within the territory of which the incident occurred,
and no later
the
information.

than 15 days following the receipt of

The holder of the marketing authorisation shall record any
other suspected serious adverse reactions occurring within
the Community, in accordance with the guide referred to in
Article 26, of which he may reasonably be expected to be
aware, and promptly notify the competent authority of
Member States
incident
in the
occurred and the Agency, and no later
than 15 days
following receipt of the information.

territory of which the

2.
The holder of the marketing authorisation for a medicinal
product for human use shall ensure that all suspected serious
unexpected adverse reactions and any suspected transmission
via a medicinal product of any infectious agent occurring in
the territory of a third country are reported promptly to
Member States and the Agency, and no later than 15 days
following receipt of the information. The provisions for the
reporting of suspected unexpected adverse reactions which
are not serious, whether occurring in the Community or in a
third country,
shall be adopted in accordance with the
procedure referred to in Article 87(2).

(a) establishing and managing a system which ensures that
suspected adverse reactions

information concerning all

Save in exceptional circumstances,
these reactions shall be
transmitted electronically in the form of a report and in
accordance with the guide referred to in Article 26.

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The holder of the marketing authorisation for a medicinal
3.
product for human use shall maintain detailed records of all
suspected adverse reactions within or outside the Community
which are reported to him by a health-care professional.

the granting of

Unless other requirements have been laid down as a condition
for
the marketing authorisation by the
Community, these records shall be submitted, in the form of
a periodic safety update report, to the Agency and Member
States immediately upon request or at least every six months
after authorisation until the placing on the market. Periodic
safety update reports shall also be submitted immediately
upon request or at least every six months during the first
two years following the initial placing on the Community
market and once a year for the following two years. Thereafter,
the reports shall be submitted at
three-yearly intervals, or
immediately upon request.

These reports shall be accompanied by a scientific evaluation,
particularly of
the medicinal
the risk-benefit balance of
product.

4.
The Commission may lay down provisions to amend
paragraph 3 in view of experience gained with its operation.
The Commission shall adopt any such provisions in accordance
with the procedure referred to in Article 87(2).

information relating

The holder of a marketing authorisation may not
5.
communicate
to pharmacovigilance
concerns to the general public in relation to its authorised
medicinal product without giving prior or simultaneous notifi-
cation to the Agency.

In any case, the marketing authorisation holder shall ensure
that such information is presented objectively and is not
misleading.

Member States shall take the necessary measures to ensure that
a marketing authorisation holder who fails to discharge these
obligations is subject to effective, proportionate and dissuasive
penalties.

Article 25

reactions occurring within their

Each Member State shall ensure that all suspected serious
adverse
territory to a
medicinal product for human use authorised in accordance
with this Regulation which are brought to their attention are
recorded and reported promptly to the Agency and the
marketing authorisation holder, and no later than 15 days
following receipt of the information.

Article 26

The Commission,
in consultation with the Agency, Member
States and interested parties, shall draw up a guide on the
collection, verification and presentation of adverse-reaction
reports. This guide shall contain, in particular, for the benefit
of health-care professionals, recommendations concerning the
communication of information on adverse reactions.

In accordance with this guide, holders of marketing authoris-
ations shall use the medical terminology accepted at inter-
national level for the transmission of adverse-reaction reports.

of

transmission

The Agency,
in consultation with Member States and the
Commission, shall set up a data-processing network for the
competent
rapid
Community authorities in the event of an alert relating to
faulty manufacture, serious adverse reactions and other phar-
macovigilance data regarding medicinal products authorised in
accordance with Article 6 of Directive 2001/83/EC. Such data
shall be made publicly accessible, if relevant, after evaluation.

information

the

to

For a period of five years following the initial placing on the
market in the Community, the Agency may request that the
marketing authorisation holder arrange for
specific phar-
macovigilance data to be collected from targeted groups of
patients. The Agency shall state the reasons for the request.
The marketing authorisation holder shall collate and assess the
data collected and submit it to the Agency for evaluation.

Article 27

The Agency shall collaborate with the World Health Organi-
sation in matters of international pharmacovigilance and shall
take the necessary steps to submit to it, promptly, appropriate
and adequate information regarding the measures taken in the
Community which may have a bearing on public health
protection in third countries; it shall send a copy thereof to
the Commission and the Member States.

Article 28

The Agency and Member States' competent authorities shall
cooperate to continuously develop pharmacovigilance systems
capable of achieving high standards of public health protection
for all medicinal products, regardless of routes of authorisation,
including the use of collaborative approaches, to maximise use
of resources available within the Community.

Article 29

The Agency shall forward the information to the national phar-
macovigilance systems set up in accordance with Article 102
of Directive 2001/83/EC.

Any amendment which may be necessary to update the
provisions of this Chapter in order to take account of scientific
and technical progress shall be adopted in accordance with the
procedure referred to in Article 87(2).

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AUTHORISATION AND SUPERVISION OF VETERINARY MEDICINAL PRODUCTS

TITLE III

C h a p t e r 1

Submission and examination of applications —
Authorisations

Article 30

(a) a copy of the written consent of the competent authorities
to the deliberate release into the environment of
the
genetically modified organisms for research and devel-
opment purposes, as provided for in Part B of Directive
2001/18/EC or in Part B of Directive 90/220/EEC;

1.
A Committee for Medicinal Products for Veterinary Use is
hereby established. The Committee shall be part of the Agency.

2. Without prejudice to Article 56 and other tasks which
Community law may confer on it, in particular under Regu-
lation (EEC) No 2377/90 (1),
the Committee for Medicinal
Products for Veterinary Use shall be responsible for drawing
up the opinion of the Agency on any question concerning the
admissibility of
submitted in accordance with the
centralised procedure, the granting, variation, suspension or
revocation of an authorisation to place a veterinary medicinal
product on the market arising in accordance with the
provisions of this Title, and pharmacovigilance.

files

3.
At the request of the Executive Director of the Agency or
the Commission representative, the Committee for Medicinal
Products for Veterinary Use shall also draw up opinions on any
scientific matters concerning the evaluation of veterinary
medicinal products. The Committee shall take due account of
for an opinion. The
any requests
Committee shall also formulate an opinion whenever there is
in the assessment of a veterinary medicinal
disagreement
product
recognition procedure. The
opinion of the Committee shall be made publicly accessible.

from Member States

through the mutual

Article 31

1.
Each application for the authorisation of a medicinal
product for veterinary use shall specifically and exhaustively
referred to in
include the particulars and documents as
Articles 12(3), 13, 13a, 13b and 14 of, and Annex I
to,
Directive 2001/82/EC. These particulars and documents shall
take account of the unique, Community nature of the author-
isation requested and, otherwise than in exceptional cases
relating to the application of the law on trade marks, shall
include the use of a single name for the medicinal product.

The application shall be accompanied by the fee payable to the
Agency for the examination of the application.

In the case of a veterinary medicinal product containing
2.
or consisting of genetically modified organisms within the
meaning of Article 2 of Directive 2001/18/EC, the application
shall also be accompanied by:

(b) the complete technical

required
2001/18/EC;

under Annexes

file supplying the information
IV to Directive

and

III

(c)

the environmental risk assessment in accordance with the
principles set out in Annex II to Directive 2001/18/EC; and

(d) the results of any investigations performed for the purposes

of research or development.

Articles 13 to 24 of Directive 2001/18/EC shall not apply to
veterinary medicinal products containing or consisting of
genetically modified organisms.

The Agency shall ensure that

3.
the
Committee for Medicinal Products for Veterinary Use is given
within 210 days after the receipt of a valid application.

the opinion of

In the case of a veterinary medicinal product containing or
consisting of genetically modified organisms, the opinion of
the said Committee must respect
the environmental safety
requirements laid down by Directive 2001/18/EC. During the
process of evaluating applications for marketing authorisations
for veterinary medicinal products containing or consisting of
genetically modified organisms, necessary consultations shall be
set up by the
held by the rapporteur with the bodies
Community or
in accordance with
Directive 2001/18/EC.

the Member States

4.
The Commission shall, in consultation with the Agency,
Member States and interested parties, draw up a detailed guide
regarding the form in which applications for authorisation are
to be presented.

Article 32

In order

1.
Medicinal Products for Veterinary Use:

to prepare its opinion,

the Committee for

(1) Council Regulation (EEC) No 2377/90 of 26 June 1990 laying
down a Community procedure for the establishment of maximum
residue limits of veterinary medicinal products in foodstuffs of
animal origin (OJ L 224, 18.8.1990, p. 1). Regulation as last
amended by Commission Regulation (EC) No 1029/2003 (OJ L
149, 17.6.2003, p. 15).

(a) shall verify that the particulars and documents submitted in
accordance with Article 31 comply with the requirements
of Directive 2001/82/EC and examine whether
the
conditions specified in this Regulation for granting a
marketing authorisation are satisfied;

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(b) may request that an Official Medicines Control Laboratory
or a laboratory that a Member State has designated for that
purpose test the veterinary medicinal product, its starting
materials and, where appropriate, its intermediate products
or other constituent materials in order to ensure that the
control methods employed by the manufacturer and
described in the application are satisfactory;

that

laboratory

(c) may request a Community reference laboratory, Official
Medicines Control Laboratory or
a
Member State has designated for that purpose to verify,
using samples provided by the applicant, that the analytical
the
detection method proposed by the applicant
purposes of Article 12(3)(j), second indent, of Directive
2001/82/EC is satisfactory and is suitable for use to
the presence of residue levels, particularly those
reveal
above
accepted by the
the maximum residue
Community in accordance with the provisions of Regu-
lation (EEC) No 2377/90;

level

for

(d) may request the applicant to supplement the particulars
accompanying the application within a specific time-limit.
Where the said Committee avails itself of this option, the
time-limit laid down in Article 31(3), first subparagraph
shall be suspended until such time as the supplementary
the
information requested has been provided. Likewise,
time-limit shall be suspended for the time allowed to the
applicant to prepare oral or written explanations.

Article 34

The Agency shall forthwith inform the applicant if the
for

for Medicinal Products

the Committee

1.
opinion of
Veterinary Use is that:

(a) the application does not satisfy the criteria for author-

isation set out in this Regulation;

(b) the summary of

the product characteristics should be

amended;

(c)

the labelling or package leaflet of the product is not in
compliance with Title V of Directive 2001/82/EC;

(d) the

authorisation should be granted subject

to the

conditions provided for in Article 39(7).

2. Within 15 days after receipt of the opinion referred to in
paragraph 1, the applicant may provide written notice to the
Agency that he wishes to request a re-examination of the
forward to the
opinion.
Agency the detailed grounds for the request within 60 days
after receipt of the opinion.

In that case the applicant shall

2.
In those cases where the analytical method has not been
subject to verification by one of the abovementioned labora-
tories under the procedures established by Regulation (EEC)
No 2377/90, the verification shall be carried out within the
framework of this Article.

Within 60 days after receipt of the grounds for the request, the
said Committee shall re-examine its opinion in accordance with
the conditions laid down in Article 62(1), fourth subparagraph.
The reasons for the conclusion reached shall be annexed to the
final opinion.

Article 33

1.
Upon receipt of a written request from the Committee for
Medicinal Products for Veterinary Use, a Member State shall
forward the information establishing that the manufacturer of a
veterinary medicinal product or the importer from a third
country is able to manufacture the veterinary medicinal
product concerned and/or carry out
the necessary control
tests
in accordance with the particulars and documents
supplied pursuant to Article 31.

2. Where it considers it necessary in order to complete its
examination of
the said Committee may
require the applicant to undergo a specific inspection of the
the veterinary medicinal product
manufacturing site of
concerned. Such inspections may be made unannounced.

the application,

The inspection, which shall be completed within the time-limit
subparagraph,
referred to in Article 31(3),
shall be
from the Member State who
undertaken by inspectors
possess the appropriate qualifications;
they may be accom-
panied by a rapporteur or expert appointed by the said
Committee.

first

the Agency shall
3. Within 15 days after its adoption,
forward the final opinion of
the said Committee to the
Commission, to Member States and to the applicant, together
with a report describing the assessment of
the veterinary
medicinal product by the Committee and stating the reasons
for its conclusions.

4.
If an opinion is favourable to the granting of the relevant
authorisation to place the relevant veterinary medicinal product
on the market, the following documents shall be annexed to
the opinion:

(a) a draft summary of the product characteristics, as referred
to in Article 14 of Directive 2001/82/EC; where appro-
priate, this draft shall reflect differences in the veterinary
conditions in the Member States;

(b) in the case of a veterinary medicinal product intended for
administration to food-producing animals, a statement of
the maximum residue level which may be accepted by the
Community
(EEC)
No 2377/90;

accordance with Regulation

in

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(c) details of any conditions or restrictions which should be
imposed on the supply or use of the veterinary medicinal
product concerned, including the conditions under which
the veterinary medicinal product may be made available to
users, in conformity with the criteria laid down in Directive
2001/82/EC;

(d) details of any recommended conditions or restrictions with
the medicinal

regard to the safe and effective use of
product;

(e) the draft text of the labelling and package leaflet proposed
by the applicant, presented in accordance with Title V of
Directive 2001/82/EC;

(f)

the assessment report.

Article 35

1. Within 15 days after receipt of the opinion referred to in
Article 30(2), the Commission shall prepare a draft of the
decision to be taken in respect of the application.

Where a draft decision envisages the granting of marketing
authorisation,
include or make reference to the
documents mentioned in Article 34(4)(a) to (e).

shall

it

Where the draft decision is not in accordance with the opinion
of the Agency, the Commission shall annex a detailed expla-
nation of the reasons for the differences.

The draft decision shall be forwarded to Member States and the
applicant.

The Commission shall take a final decision in accordance
the procedure

2.
with, and within 15 days after the end of,
referred to in Article 87(3).

The

Standing Committee

for Veterinary Medicinal
3.
Products referred to in Article 87(1) shall adjust its rules of
procedure so as to take account of the tasks assigned to it by
this Regulation.

The adjustments shall provide that:

(a) the opinion of the said Standing Committee is to be given

in writing;

(b) Member States shall have 22 days to forward their written
observations on the draft decision to the Commission;
however, if a decision has to be taken urgently, a shorter
time-limit may be set by the Chairman according to the
degree of urgency involved. This time-limit shall not,
otherwise than in exceptional circumstances, be shorter
than 5 days;

(c) Member States may request

the draft
decision referred to in paragraph 1 be discussed at a
plenary meeting of the said Standing Committee, stating
their reasons in detail.

in writing that

4. Where,
in the opinion of the Commission, the written
observations of a Member State raise important new questions
technical nature which have not been
of a scientific or
the
addressed in the opinion delivered by the Agency,
Chairman shall suspend the procedure and refer the application
back to the Agency for further consideration.

The provisions necessary for

5.
paragraph 4 shall be
accordance with the procedure referred to in Article 87(2).

the implementation of
adopted by the Commission in

The Agency shall disseminate the documents referred to

6.
in Article 34(4) (a) to (e).

Article 36

If an applicant withdraws an application for a marketing auth-
orisation submitted to the Agency before an opinion has been
given on the application, the applicant shall communicate its
reasons for doing so to the Agency. The Agency shall make
this information publicly accessible and shall publish the
assessment report, if available, after deletion of all information
of a commercially confidential nature.

Article 37

The marketing authorisation shall be refused if, after
the particulars and documents submitted in

1.
verification of
accordance with Article 31, it appears that:

(a) the applicant has not properly or sufficiently demonstrated
the quality, safety or efficacy of the veterinary medicinal
product;

(b) in the case of zootechnical veterinary medicinal products
and performance enhancers, when the safety and welfare of
safety have not been
the animals and/or
sufficiently taken into account;

consumer

(c)

the withdrawal period recommended by the applicant is
not long enough to ensure that foodstuffs obtained from
treated animals do not contain residues which might
constitute a health hazard for the consumer or is insuf-
ficiently substantiated;

(d) the veterinary medicinal product is presented for a use

prohibited under other Community provisions.

likewise be refused if particulars or
Authorisation shall
in accordance with
documents provided by the applicant
Article 31 are incorrect or
the labelling and package
if
leaflets proposed by the applicant are not in accordance with
Title V of Directive 2001/82/EC.

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The refusal of a Community marketing authorisation shall
2.
constitute a prohibition on the placing on the market of the
veterinary medicinal product
the
Community.

concerned throughout

Upon request by the Agency, particularly in the context of
pharmacovigilance,
the marketing authorisation holder shall
provide the Agency with all data relating to the volume of
sales of the medicinal product at Community level, broken
down by Member State, and any data in the holder's possession
relating to the volume of prescriptions.

Information about all refusals and the reasons for them

3.
shall be made publicly accessible.

Article 39

Article 38

1. Without prejudice to paragraphs 4 and 5, a marketing
authorisation shall be valid for five years.

1. Without prejudice to Article 71 of Directive 2001/82/EC,
a marketing authorisation which has been granted in
accordance with this Regulation shall be valid throughout the
Community. It shall confer the same rights and obligations in
each of
the Member States as a marketing authorisation
granted by that Member State in accordance with Article 5
of Directive 2001/82/EC.

Authorised veterinary medicinal products shall be entered in
the Community Register of Medicinal Products and shall be
given a number which shall appear on the packaging.

2.
The marketing authorisation may be renewed after five
years on the basis of a re-evaluation by the Agency of the
risk-benefit balance.

To this end, the marketing authorisation holder shall submit a
consolidated list of all documents submitted in respect of
quality, safety and efficacy, including all variations introduced
least six
since the marketing authorisation was granted, at
months before the marketing authorisation ceases to be valid
in accordance with paragraph 1. The Agency may require the
applicant to submit the listed documents at any time.

Journal of

Notification of marketing authorisation shall be published
2.
in the Official
the European Union, quoting in
particular the date of authorisation and the number in the
Community Register, any International Non-proprietary Name
its
(INN) of the active substance of the medicinal product,
pharmaceutical
any Anatomical Therapeutic
Chemical Veterinary Code (ATC Vet Code).

form,

and

3.
Once renewed, the marketing authorisation shall be valid
for an unlimited period, unless the Commission decides, on
to proceed
justified grounds relating to pharmacovigilance,
with one additional
in accordance with
paragraph 2.

five-year

renewal

The Agency shall

3.
immediately publish the assessment
report on the veterinary medicinal product drawn up by the
Committee for Medicinal Products for Veterinary Use and the
reasons for its opinion in favour of granting authorisation, after
deletion of any information of a commercially confidential
nature.

The European Public Assessment Report (EPAR) shall include a
summary written in a manner that is understandable to the
public. The summary shall contain in particular a section
relating to the conditions of use of the medicinal product.

After a marketing authorisation has been granted, the
4.
inform the Agency of the
holder of the authorisation shall
the veterinary
dates of actual placing on the market of
medicinal product in Member States, taking into account the
various presentations authorised.

The holder shall also notify the Agency if the product ceases to
be placed on the market, either temporarily or permanently.
Such notification shall, other
than in exceptional circum-
stances, be made no less than 2 months before the interruption
in the placing of the product on the market.

Any authorisation which is not followed by the actual
4.
placing of the medicinal product for veterinary use on the
Community market within three years after authorisation
shall cease to be valid.

5. When an authorised medicinal product previously placed
on the market is no longer actually present on the market for
three consecutive years, the authorisation shall cease to be
valid.

In exceptional circumstances and on public and/or animal
6.
health grounds the Commission may grant exemptions from
the provisions of paragraphs 4 and 5. Such exemptions must
be duly justified.

7.
In exceptional circumstances and following consultation
with the applicant, authorisation may be granted subject to a
requirement for the applicant to introduce specific procedures,
in particular concerning product safety, notification to the
relevant authorities of any incident relating to its use, and
action to be taken. This authorisation may be granted only
for objective, verifiable reasons. Continuation of the author-
isation shall be linked to the annual reassessment of these
conditions.

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8. When an application is submitted for a marketing auth-
orisation in respect of veterinary medicinal products of major
interest, particularly from the point of view of animal health
and from the viewpoint of
the
applicant may request an accelerated assessment procedure.
The request shall be duly substantiated.

innovation,

therapeutic

If the Committee for Medicinal Products for Veterinary Use
accepts the request, the time-limit laid down in Article 31(3),
first subparagraph, shall be reduced to 150 days.

9. When adopting its opinion,
include
for
concerning
prescription or use of the veterinary medicinal products.

the said Committee shall
the
the

a proposal

conditions

10.
Veterinary medicinal products which have been auth-
orised in accordance with the provisions of this Regulation
shall benefit from the provisions on protection in Articles 13
and 13a of Directive 2001/82/EC.

the analytical method for detecting residues of
tation of
veterinary medicinal products by the Community reference
laboratory or, where appropriate, national reference labora-
tories designated in accordance with Council Directive
96/23/EC of 29 April 1996 on measures to monitor certain
substances and residues thereof
in live animals and animal
products (1).

4.
The holder of the marketing authorisation shall forthwith
supply to the Agency, the Commission and the Member States
any new information which might entail the variation of the
particulars or documents referred to in Articles 12(3), 13, 13a,
13b and 14 of Directive 2001/82/EC, in Annex I thereto, or in
Article 34(4) of this Regulation.

He shall forthwith inform the Agency, the Commission and the
Member States of any prohibition or restriction imposed by the
competent authorities of any country in which the veterinary
is marketed and of any other new
medicinal product
influence the evaluation of
information which might
the
the veterinary medicinal product
benefits
concerned.

and risks of

Article 40

the civil or
The granting of authorisation shall not affect
criminal
liability of the manufacturer or the holder of the
marketing authorisation pursuant to the applicable national
law in Member States.

In order that the risk-benefit balance may be continuously
assessed, the Agency may at any time ask the holder of the
marketing authorisation to forward data justifying that the risk-
benefit balance remains favourable.

C h a p t e r 2

Supervision and sanctions

Article 41

in Article 12(3)(d)

1.
After an authorisation has been granted in accordance
with this Regulation, the holder of the marketing authorisation
shall, in respect of the methods of manufacture and control
provided for
and (i) of Directive
2001/82/EC, take account of technical and scientific progress
and make any variations that may be required to enable the
medicinal products to be manufactured and checked by means
of generally accepted scientific methods. He shall apply for
approval of these variations in accordance with this Regulation.

2.
The competent authority of a Member State or the
Agency may require the holder of the marketing authorisation
to provide
the
performance of tests to detect the presence of residues of the
veterinary medicinal products concerned in foodstuffs of
animal origin.

in sufficient

substances

quantities

for

If

the holder of

5.
the marketing authorisation for the
veterinary medicinal product proposes to make any variation
of the particulars and documents referred to in paragraph 4, he
shall submit the relevant application to the Agency.

6.
The Commission shall, after consulting the Agency, adopt
appropriate provisions for the examination of variations to
marketing authorisations
in the form of a regulation in
accordance with the procedure referred to in Article 87(2).

Article 42

The applicant or the holder of a marketing authorisation shall
be responsible for the accuracy of the documents and of the
data submitted.

Article 43

1.
In the case of veterinary medicinal products manu-
factured within the Community, the supervisory authorities
shall be the competent authorities of the Member State or
Member States which granted the manufacturing authorisation
provided for in Article 44(1) of Directive 2001/82/EC in
respect of the manufacture of the medicinal product concerned.

3.
At the request of the competent authority of a Member
State or the Agency, the holder of the marketing authorisation
shall provide technical expertise to facilitate the implemen-

(1) OJ L 125, 23.5.1996, p. 10. Directive as amended by Regulation

(EC) No 806/2003 (OJ L 122, 16.5.2003, p. 1).

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In the case of veterinary medicinal products imported
2.
from third countries, the supervisory authorities shall be the
competent authorities of the Member State or Member States
that granted the authorisation provided for in Article 44(3) of
Directive 2001/82/EC to the importer, unless appropriate
agreements have been made between the Community and the
exporting country to ensure that those controls are carried out
in the exporting country and that the manufacturer applies
standards of good manufacturing practice at least equivalent
to those laid down by the Community.

A Member State may request assistance from another Member
State or the Agency.

Article 44

The supervisory authorities

shall be responsible for
1.
verifying on behalf of the Community that the holder of the
marketing authorisation for the veterinary medicinal product or
the manufacturer
the
importer
Community satisfies the requirements laid down in Titles IV,
VII and VIII of Directive 2001/82/EC.

established within

or

2. Where,
in accordance with Article 90 of Directive
2001/82/EC, the Commission is informed of serious differences
of opinion between Member States as to whether the holder of
the marketing authorisation for
the veterinary medicinal
product or a manufacturer or importer established within the
Community satisfies the requirements referred to in paragraph
1, the Commission may, after consultation with the Member
States concerned, request an inspector from the supervisory
authority to undertake a new inspection of the holder of the
marketing authorisation, the manufacturer or the importer; the
inspector in question shall be accompanied by two inspectors
from Member States which are not party to the dispute and/or
by two experts nominated by the Committee for Medicinal
Products for Veterinary Use.

Subject

3.
to any agreements which may have been
concluded between the Community and third countries in
accordance with Article 43(2), the Commission may, upon
receipt of a reasoned request from a Member State or from
the said Committee, or on its own initiative, require a manu-
facturer established in a third country to submit
to an
inspection.

The inspection shall be undertaken by inspectors from the
Member State who possess the appropriate qualifications;
they may be
expert
appointed by the said Committee. The report of the inspectors
shall be made available to the Commission, the Member States
and the said Committee.

accompanied by a

rapporteur or

no longer fulfilling the obligations laid down in Title VII of
Directive 2001/82/EC,
forthwith inform the
Committee for Medicinal Products for Veterinary Use and the
Commission, stating their reasons in detail and indicating the
course of action proposed.

shall

they

shall

same

apply where

a Member State or

The
the
Commission considers that one of the measures envisaged in
Title VIII of Directive 2001/82/EC should be applied in respect
of the veterinary medicinal product concerned or where the
said Committee has delivered an opinion to that effect
in
accordance with Article 30 of this Regulation.

2.
The Commission shall request the opinion of the Agency
within a time-limit which it shall determine in the light of the
urgency of
to examine the reasons
in order
advanced. Whenever practicable, the holder of the marketing
authorisation for the medicinal product shall be invited to
provide oral or written explanations.

the matter,

3.
Following an opinion by the Agency, the Commission
shall adopt the necessary provisional measures, which shall
be applied immediately.

A final decision shall be adopted within six months,
accordance with the procedure referred to in Article 87(3).

in

4. Where urgent action is essential to protect human or
animal health or the environment, a Member State may, on
its own initiative or at the Commission's request, suspend the
use on its territory of a veterinary medicinal product which has
been authorised in accordance with this Regulation.

When it does so on its own initiative, the Member State shall
inform the Commission and the Agency of the reasons for its
action at the latest on the next working day following the
inform the other Member
suspension. The Agency shall
States without delay. The Commission shall
immediately
initiate the procedure provided for in paragraphs 2 and 3.

case,

In this

the Member State

that
5.
health-care professionals are rapidly informed of
its action
and the reasons for the action. Networks set up by professional
associations may be used to this effect. Member States shall
inform the Commission and the Agency of actions taken for
this purpose.

ensure

shall

6.
The suspensive measures referred to in paragraph 4 may
be maintained until such time as a definitive decision has been
reached in accordance with the procedure referred to in Article
87(3).

Article 45

1. Where the supervisory authorities or the competent auth-
orities of any other Member State are of the opinion that the
manufacturer or importer established within the Community is

The Agency shall, upon request,

7.
concerned of
publicly accessible, immediately after it has been taken.

inform any person
the final decision and make the decision

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C h a p t e r 3

Pharmacovigilance

Article 46

For the purpose of this Chapter, Article 77(2) of Directive
2001/82/EEC shall apply.

Article 47

The Agency, acting in close cooperation with the national
pharmacovigilance systems established in accordance with
Article 73 of Directive 2001/82/EC, shall receive all relevant
information about suspected adverse reactions to veterinary
medicinal products which have been authorised by the
Community in accordance with this Regulation. Where appro-
priate the Committee for Medicinal Products for Veterinary Use
shall, in accordance with Article 30 of this Regulation, draw up
opinions on the measures necessary. These opinions shall be
made publicly accessible.

These measures may include amendments to the marketing
authorisation granted in accordance with Article 35. They
shall be adopted in accordance with the procedure referred
to in Article 87(3).

The holder of the marketing authorisation and the competent
authorities of
the Member States shall ensure all relevant
information about suspected adverse reactions to the veterinary
medicinal products authorised under this Regulation is brought
to the attention of
the Agency in accordance with the
provisions of this Regulation. Animal owners and breeders
shall be encouraged to communicate any adverse reaction to
health-care professionals or to the competent national auth-
orities responsible for pharmacovigilance.

Article 48

The holder of the marketing authorisation for a veterinary
medicinal product granted in accordance with the provisions
of this Regulation shall have permanently and continuously at
his disposal an appropriately qualified person responsible for
pharmacovigilance.

That qualified person shall reside in the Community and shall
be responsible for the following:

(a) establishing and managing a system which ensures that
information about all suspected adverse reactions which
are reported to the personnel of
the company and to
medical representatives is collected, evaluated and collated
so that it may be accessed at a single point within the
Community;

Agency in accordance with the requirements of this Regu-
lation;

(c) ensuring that any request from the competent authorities
for the provision of additional
information necessary for
the evaluation of the risks and benefits of a veterinary
medicinal product
and promptly,
including the provision of information about the volume
of
the veterinary medicinal
for
product concerned;

sales or prescriptions

answered fully

is

(d) providing the

competent

authorities with any other
information relevant
to the evaluation of the risks and
benefits of a veterinary medicinal product, particularly
information concerning post-authorisation safety studies,
including information regarding the validity of the with-
drawal period or lack of expected efficacy or potential
environmental problems.

Article 49

The holder of

the marketing authorisation for

1.
a
veterinary medicinal product shall ensure that all suspected
serious adverse reactions, and adverse human reactions to a
veterinary medicinal product authorised in accordance with
the provisions of
this Regulation occurring within the
Community which a health-care professional brings to his
attention are recorded and reported promptly to the Member
States in the territory of which the incident occurred no later
than 15 days following receipt of the information.

The holder of the marketing authorisation shall record any
other suspected serious adverse reactions and human adverse
reactions occurring within the Community, in accordance with
the guidelines referred to in Article 51, of which he may
reasonably be expected to be aware, and promptly notify
Member States
incident
in the
occurred and the Agency, and no later
than 15 days
following receipt of the information.

territory of which the

The holder of

the marketing authorisation for

2.
a
veterinary medicinal product shall ensure that all suspected
serious unexpected adverse reactions, and adverse human
reactions, and any suspected transmission via a medicinal
product of any infectious agent occurring in the territory of
a third country are reported promptly to the Member States
and the Agency, and no later than 15 days following receipt of
the information. The provisions for the reporting of suspected
unexpected adverse reactions which are not serious, whether
occurring in the Community or in a third country, shall be
adopted in accordance with the procedure referred to in Article
87(2).

(b) preparing the reports referred to in Article 49(3) for the
the Member States and the

competent authorities of

Save in exceptional circumstances,
these reactions shall be
transmitted electronically in the form of a report and in
accordance with the guide referred to in Article 51.

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The holder of

the marketing authorisation for

a
3.
veterinary medicinal product shall maintain detailed records
of all suspected adverse reactions occurring within or outside
the Community which are reported to him.

the granting of

Unless other requirements have been laid down as a condition
for
the marketing authorisation by the
Community, these records shall be submitted, in the form of
a periodic safety update report, to the Agency and Member
States immediately upon request or at least every six months
after authorisation until the placing on the market. Periodic
safety update reports shall also be submitted immediately
upon request or at least every six months during the first
two years following the initial placing on the Community
market and once a year for the following two years. Thereafter,
the reports shall be submitted at
three-yearly intervals, or
immediately upon request.

These reports shall be accompanied by a scientific evaluation,
the medicinal
the risk-benefit balance of
particularly of
product.

The Commission may lay down provisions to amend
4.
paragraph 3 in view of experience gained with its operation.
The Commission shall adopt any such provisions in accordance
with the procedure referred to in Article 87(2).

The Agency shall forward the information to the national phar-
macovigilance systems set up in accordance with Article 73 of
Directive 2001/82/EC.

Article 51

The Commission,
in consultation with the Agency, Member
States and interested parties, shall draw up a guide on the
collection, verification and presentation of adverse-reaction
reports. This guide shall contain, in particular, for the benefit
of health-care professionals, recommendations concerning the
communication of information on adverse reactions.

In accordance with this guide, holders of marketing authoris-
ations shall use the medical terminology accepted at inter-
national level for the transmission of adverse-reaction reports.

of

transmission

The Agency, in consultation with the Member States and the
Commission, shall set up a data-processing network for the
rapid
competent
data
Community authorities in the event of an alert relating to
faulty manufacture, serious adverse reactions and other phar-
macovigilance data regarding veterinary medicinal products
authorised in accordance with Article 5 of Directive
2001/82/EC.

between

the

information relating

The holder of a marketing authorisation may not
5.
communicate
to pharmacovigilance
concerns to the general public in relation to its authorised
medicinal product without giving prior or simultaneous notifi-
cation to the Agency.

For a period of five years following the initial placing on the
market in the Community, the Agency may request that the
marketing authorisation holder arrange for
specific phar-
macovigilance data to be collected from targeted groups of
animals. The Agency shall state the reasons for the request.
The marketing authorisation holder shall collate and assess
the data collected and submit it to the Agency for evaluation.

In any case, the marketing authorisation holder shall ensure
that such information is presented objectively and is not
misleading.

Article 52

The Agency shall cooperate with international organisations
concerned with veterinary pharmacovigilance.

Member States shall take the necessary measures to ensure that
a marketing authorisation holder who fails to discharge these
obligations is subject to effective, proportionate and dissuasive
penalties.

Article 50

Each Member State shall ensure that all suspected serious
adverse reactions, and adverse human reactions, occurring
within its territory to a veterinary medicinal product authorised
in accordance with the provisions of this Regulation which are
brought to its attention are recorded and reported promptly to
the Agency and the holder of the marketing authorisation for
the veterinary medicinal product, and no later than 15 days
following receipt of the information.

Article 53

The Agency and the Member States' competent authorities shall
cooperate to continuously develop pharmacovigilance systems
capable of achieving high standards of public health protection
for all medicinal products, regardless of routes of authorisation,
including the use of collaborative approaches, to maximise use
of resources available within the Community.

Article 54

Any amendment which may be necessary to update the
provisions of this Chapter in order to take account of scientific
and technical progress shall be adopted in accordance with the
procedure referred to in Article 87(2).

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THE EUROPEAN MEDICINES AGENCY — RESPONSIBILITIES AND ADMINISTRATIVE STRUCTURE

TITLE IV

C h a p t e r 1

Tasks of the Agency

Article 55

A European Medicines Agency is hereby established.

The Agency shall be responsible for coordinating the existing
scientific resources put at its disposal by Member States for the
evaluation, supervision and pharmacovigilance of medicinal
products.

Article 56

1.

The Agency shall comprise:

(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) a Secretariat, which shall provide technical, scientific and
the committees and ensure

administrative support
appropriate coordination between them;

for

(f) an Executive Director, who shall exercise the responsi-

bilities set out in Article 64;

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

bilities set out in Articles 65, 66 and 67.

2.
The committees referred to in paragraph 1(a) to (d) may
each establish standing and temporary working parties. The
referred to in paragraph 1(a) and (b) may
committees
establish scientific advisory groups in connection with the
evaluation of
types of medicinal products or
treatments, to which the committee concerned may delegate
certain tasks associated with drawing up the scientific opinions
referred to in Articles 5 and 30.

specific

When establishing working parties and scientific advisory
groups,
in their rules of procedures
the committees shall
referred to in Article 61(8) provide for:

(a) the appointment of members of these working parties and
scientific advisory groups on the basis of the lists of experts
referred to in the second subparagraph of Article 62(2);
and

(b) consultation of these working parties and scientific advisory

groups.

The Executive Director,

3.
in close consultation with the
Committee for Medicinal Products for Human Use and the
Committee for Medicinal Products for Veterinary Use, shall
set up the administrative structures and procedures allowing
the development of advice for undertakings, as referred to in
Article 57(1)(n), particularly regarding the development of new
therapies.

Each committee shall establish a standing working party with
the sole remit of providing scientific advice to undertakings.

4.
The Committee for Medicinal Products for Human Use
and the Committee for Medicinal Products for Veterinary Use
may,
seek guidance on
important questions of a general scientific or ethical nature.

it appropriate,

they consider

if

Article 57

1.
The Agency shall provide the Member States and the
institutions of the Community with the best possible scientific
advice on any question relating to the evaluation of the quality,
safety and efficacy of medicinal products
for human or
veterinary use which is referred to it in accordance with the
provisions of Community legislation relating to medicinal
products.

To this end,
committees, shall undertake the following tasks:

the Agency, acting particularly through its

(a)

(b)

(c)

coordination of the scientific evaluation of the quality,
safety and efficacy of medicinal products which are
subject to Community marketing authorisation procedures;

transmitting on request and making publicly available
assessment reports, summaries of product characteristics,
labels and package leaflets or inserts for these medicinal
products;

coordination of the supervision, under practical conditions
of use, of medicinal products which have been authorised
within the Community and the provision of advice on the
measures necessary to ensure the safe and effective use of
these products, in particular by evaluation, coordination of
the implementation of pharmacovigilance obligations and
the monitoring of such implementation;

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(d) ensuring the dissemination of

to medicinal products

information on adverse
authorised in the
reactions
Community, by means of
a database permanently
accessible to all Member States; health-care professionals,
marketing authorisation holders and the public shall have
appropriate levels of access
to these databases, with
personal data protection being guaranteed;

the general public about medicinal products evaluated by
the Agency;

(n) advising undertakings on the conduct of the various tests
and trials necessary to demonstrate the quality, safety and
efficacy of medicinal products;

(e)

assisting Member States with the rapid communication of
information concerning pharmacovigilance to health-care
professionals.

(f)

distributing appropriate pharmacovigilance information to
the general public;

(g) advising on the maximum limits for residues of veterinary
medicinal products which may be accepted in foodstuffs of
animal origin in accordance with Regulation (EEC)
No 2377/90;

(h) providing scientific advice on the use of antibiotics in
food-producing
the
occurrence of bacterial resistance in the Community; this
advice shall be updated when needed;

to minimise

in order

animals

(i)

(j)

(k)

(l)

coordinating the verification of compliance with the prin-
ciples of good manufacturing practice, good laboratory
practice, good clinical practice and the verification of
compliance with pharmacovigilance obligations;

upon request, providing technical and scientific support in
order to improve cooperation between the Community, its
Member States,
international organisations and third
countries on scientific and technical issues relating to the
evaluation of medicinal products,
in the
context of discussions organised in the framework of inter-
national conferences on harmonisation;

in particular

recording the status of marketing authorisations
medicinal
granted
Community procedures;

for
accordance with

products

in

creating a database on medicinal products, to be accessible
to the general public, and ensuring that it is updated, and
managed independently of pharmaceutical companies; the
database shall facilitate the search for information already
authorised for package leaflets; it shall include a section on
medicinal products
treatment of
authorised for
children; the information provided to the public shall be
worded in an appropriate and comprehensible manner;

the

(m) assisting the Community and Member States

in the
provision of information to health-care professionals and

(o) checking that the conditions laid down in Community
legislation on medicinal products and in the marketing
case of parallel
authorisations
in
distribution
accordance with this Regulation;

are observed in the

of medicinal

authorised

products

(p) drawing up, at

the Commission's request, any other
scientific opinion concerning the evaluation of medicinal
products or the starting materials used in the manufacture
of medicinal products;

(q) with a view to the protection of public health, compilation
of scientific information concerning pathogenic agents
which might be used in biological warfare, including the
and other medicinal products
existence of vaccines
available to prevent, or to treat, the effects of such agents;

(r)

coordination of the supervision of the quality of medicinal
products placed on the market by requesting testing of
compliance with their authorised specifications by an
Official Medicines Control Laboratory or by a laboratory
that a Member State has designated for that purpose;

(s)

forwarding annually to the budgetary authority any
to the outcome of the evaluation
information relevant
procedures.

The database provided for in paragraph 1(l) shall include
2.
the summaries of product characteristics, the patient or user
package leaflet and the information shown on the labelling.
The database shall be developed in stages, priority being
given to medicinal products authorised under this Regulation
and those authorised under Chapter 4 of Title III of Directive
2001/83/EC and of Directive 2001/82/EC respectively. The
database shall
subsequently be extended to include any
medicinal product placed on the market within the
Community.

Where appropriate, the database shall also include references to
data on clinical trials currently being carried out or already
completed, contained in the clinical trials database provided
for in Article 11 of Directive 2001/20/EC. The Commission
shall, in consultation with the Member States, issue guidelines
on data fields which could be included and which may be
accessible to the public.

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Article 58

Article 61

1.
The Agency may give a scientific opinion, in the context
of cooperation with the World Health Organisation, for the
evaluation of certain medicinal products
for human use
intended exclusively for markets outside the Community. For
this purpose, an application shall be submitted to the Agency
in accordance with the provisions of Article 6. The Committee
for Medicinal Products for Human Use may, after consulting
the World Health Organisation, draw up a scientific opinion in
accordance with Articles 6 to 9. The provisions of Article 10
shall not apply.

2.
The said Committee shall establish specific procedural
rules for the implementation of paragraph 1, as well as for
the provision of scientific advice.

Article 59

The Agency shall take care to ensure early identification
1.
of potential sources of conflict between its scientific opinions
and those of other bodies established under Community law
carrying out a similar task in relation to issues of common
concern.

source of
2. Where the Agency identifies a potential
the body concerned in order to
conflict,
ensure that any relevant scientific information is shared and
to identify the scientific points which potentially conflict.

it shall contact

3. Where there is a fundamental conflict over scientific
points and the body concerned is a Community agency or a
scientific committee, the Agency and the body concerned shall
work together either to resolve the conflict or to submit a joint
document to the Commission clarifying the scientific points of
conflict. This document shall be published immediately after its
adoption.

Save as otherwise provided in this Regulation,

in
4.
Directive 2001/83/EC or
in Directive 2001/82/EC, where
there is a fundamental conflict over scientific points and the
body concerned is a body in a Member State, the Agency and
the national body concerned shall work together either to
resolve the conflict or to prepare a joint document clarifying
the scientific points of conflict. This document
shall be
published immediately after its adoption.

Article 60

authorised medicinal products,

At the request of the Commission, the Agency shall, in respect
of
available
information on methods that Member States' competent auth-
orities use to determine the added therapeutic value that any
new medicinal product provides.

collect

any

Each Member State shall, after consultation of

the
1.
Management Board, appoint,
term which
may be renewed, one member and one alternate to the
Committee for Medicinal Products for Human Use and one
member and one alternate to the Committee for Medicinal
Products for Veterinary Use.

for a three-year

The alternates shall represent and vote for the members in their
absence and may act as rapporteurs in accordance with Article
62.

Members and alternates shall be chosen for their role and
experience
for
human and veterinary use as appropriate and shall represent
the competent national authorities.

evaluation of medicinal products

in the

The

five
2.
committees may co-opt
additional members chosen on the basis of
their specific
scientific competence. These members shall be appointed for
a term of three years, which may be renewed, and shall not
have alternates.

a maximum of

With a view to the co-opting of such members, the committees
shall identify the specific complementary scientific competence
of
shall be
chosen among experts nominated by Member States or the
Agency.

the additional member(s). Co-opted members

The members of each Committee may be accompanied

3.
by experts in specific scientific or technical fields.

4.
The Executive Director of the Agency or his represen-
tative and representatives of the Commission shall be entitled
to attend all meetings of the committees, working parties and
scientific advisory groups and all other meetings convened by
the Agency or its committees.

In addition to their task of providing objective scientific
5.
opinions
to the Community and Member States on the
questions which are referred to them, the members of each
committee shall ensure that there is appropriate coordination
between the tasks of the Agency and the work of competent
national
bodies
concerned with the marketing authorisation.

consultative

authorities,

including

the

shall

6. Members of the committees and experts responsible for
evaluating medicinal products
rely on the scientific
evaluation and resources available to national marketing auth-
orisation bodies. Each competent national authority shall
monitor the scientific level and independence of the evaluation
carried out and facilitate the activities of nominated committee
members and experts. Member States shall refrain from giving
committee members and experts any instruction which is
incompatible with their own individual
tasks or with the
tasks and responsibilities of the Agency.

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7. When preparing the opinion, each 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 opinion
procedure may deal only with the points of
initially identified by the applicant and may be based only
on the scientific data available when the Committee adopted
the initial opinion. The applicant may request
the
Committee consult a scientific advisory group in connection
with the re-examination.

that

8.

Each committee shall establish its own rules of procedure.

These rules shall, in particular, lay down:

(a) procedures for appointing and replacing the Chairman;

(b) procedures

relating to working parties and scientific

advisory groups; and

(c) a procedure

adoption of opinions,
particularly in relation to the provisions of this Regulation
on market surveillance and pharmacovigilance.

the urgent

for

2. Member States shall transmit to the Agency the names of
national experts with proven experience in the evaluation of
medicinal products who would be available to serve on
the
working parties
Committee for Medicinal Products
the
Committee on Herbal Medicinal Products or the Committee
for Medicinal Products for Veterinary Use, together with an
indication of their qualifications and specific areas of expertise.

groups of
for Human Use,

scientific

advisory

or

The Agency shall keep an up-to-date list of accredited experts.
The list shall
include the experts referred to in the first
subparagraph and other experts appointed directly by the
Agency. The list shall be updated.

They shall enter into force after receiving a favourable opinion
from the Commission and the Management Board.

The provision of services by rapporteurs or experts shall
3.
be governed by a written contract between the Agency and the
person concerned, or where appropriate between the Agency
and his employer.

Article 62

1. Where, in accordance with the provisions of this Regu-
lation, the Committee for Medicinal Products for Human Use,
the Committee on Herbal Medicinal Products or the Committee
for Medicinal Products for Veterinary Use is required to
its
evaluate a medicinal product,
it shall appoint one of
members to act as rapporteur for the coordination of
the
evaluation. The Committee concerned may appoint a second
member to act as co-rapporteur.

report(s) drawn up by the rapporteur or

When consulting the scientific advisory groups referred to in
Article 56(2), the Committee shall forward to them the draft
assessment
the
co-rapporteur. The opinion issued by the scientific advisory
the relevant
group shall be forwarded to the chairman of
Committee in such a way as to ensure that the deadlines laid
down in Article 6(3) and Article 31(3) are met.

The substance of
assessment report published pursuant
Article 38(3).

the opinion shall be included in the
to Article 13(3) and

If there is a request for re-examination of one of its opinions,
the Committee concerned shall appoint a different rapporteur
and, where necessary, a different co-rapporteur from those
re-examination
appointed

initial opinion. The

the

for

The person concerned, or his employer, shall be remunerated
in accordance with a scale of
fees to be included in the
financial arrangements established by the Management Board.

The performance of scientific services for which there are
4.
for an
several potential providers may result
expression of interest,
if the scientific and technical context
allows, and if it is compatible with the tasks of the Agency,
in particular to ensure a high level of public health protection.

in a call

The Management Board shall adopt the appropriate procedures
on a proposal from the Executive Director.

The Agency or any of the committees referred to in
5.
Article 56(1) may use
the
discharge of other specific tasks for which they are responsible.

services of experts

the

for

Article 63

The membership of the committees referred to in Article
is
shall be made public. When each appointment
the professional qualifications of each member

1.
56(1)
published,
shall be specified.

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the Management Board, members of

the
2. Members of
committees, rapporteurs and experts shall not have financial
or other interests in the pharmaceutical industry which could
affect their impartiality. They shall undertake to act in the
public interest and in an independent manner, and shall
make an annual declaration of their financial
interests. All
indirect interests which could relate to this industry shall be
entered in a register held by the Agency which is accessible to
the public, on request, at the Agency's offices.

The Agency's code of conduct shall provide for the implemen-
tation of this Article with particular reference to the acceptance
of gifts.

rapporteurs

and experts who participate

the Management Board, members of

the
Members of
committees,
in
meetings or working groups of the Agency shall declare, at
each meeting, any specific interests which could be considered
to be prejudicial to their independence with respect to the
items on the agenda. These declarations
shall be made
available to the public.

Article 64

The Executive Director

shall be appointed by the
1.
Management Board, on a proposal from the Commission, for
a period of five years on the basis of a list of candidates
proposed by the Commission following a call for expressions
of interest published in the Official Journal of the European Union
and elsewhere. Before appointment, the candidate nominated
by the Management Board shall be invited forthwith to make a
statement
to the European Parliament and to answer any
questions put by its Members. His mandate may be renewed
once. The Management Board may, upon a proposal from the
Commission, remove the Executive Director from his post.

The Executive Director shall be the legal representative of

2.
the Agency. He shall be responsible:

(a)

for the day-to-day administration of the Agency;

(b) for managing all

the Agency resources necessary for
conducting the activities of the committees referred to in
Article 56(1),
appropriate
scientific and technical support;

including making available

(c)

for ensuring that the time-limits laid down in Community
legislation for the adoption of opinions by the Agency are
complied with;

(d) for

ensuring

appropriate

coordination between

the

committees referred to in Article 56(1);

(f)

for all staff matters;

(g) for providing the secretariat for the Management Board.

3.
Each year the Executive Director shall submit a draft
report covering the activities of the Agency in the previous
year and a draft work programme for the coming year to
the Management Board for approval, making a distinction
between
concerning medicinal
activities
products for human use, those concerning herbal medicinal
products and those concerning veterinary medicinal products.

the Agency's

The draft report covering the activities of the Agency in the
previous year shall include information about the number of
applications evaluated within the Agency, the time taken for
completion of the evaluation and the medicinal products auth-
orised, rejected or withdrawn.

Article 65

The Management Board shall consist of one represen-
the
European

1.
tative of each Member State,
Commission and two representatives of
Parliament.

two representatives of

the

In addition, two representatives of patients' organisations, one
representative of doctors' organisations and one representative
of veterinarians' organisations
shall be appointed by the
Council in consultation with the European Parliament on the
basis of a list drawn up by the Commission which includes
appreciably more names than there are posts to be filled. The
list drawn up by the Commission shall be forwarded to the
European Parliament, together with the relevant background
documents. As quickly as possible, and within three months
of notification, the European Parliament may submit its views
for consideration to the Council, which shall then appoint the
Management Board.

The members of the Management Board shall be appointed in
such a way as to guarantee the highest levels of specialist
qualifications, a broad spectrum of relevant expertise and the
broadest possible geographic spread within the European
Union.

The members of
2.
appointed on the basis of
management and,
medicinal products for human or veterinary use.

the Management Board shall be
in
relevant
if appropriate, experience in the field of

expertise

their

(e)

for the preparation of the draft statement of estimates of
the Agency's revenue and expenditure, and execution of its
budget;

Each Member State and the Commission shall appoint
3.
their members of
the Management Board as well as an
alternate who will replace the member in his absence and
vote on his behalf.

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The term of office of the representatives shall be three

4.
years. The term of office may be renewed.

(g) adopt the internal financial provisions (Article 67);

The Management Board shall elect its Chairman from

5.
among its members.

(h) adopt provisions
(Article 75);

implementing the Staff Regulations

The term of office of the Chairman shall be three years and
the
shall expire when he
Management Board. The term of office may be renewed once.

to be a member of

ceases

Decisions of the Management Board shall be adopted by a

6.
majority of two-thirds of its members.

7.

The Management Board shall adopt its rules of procedure.

8.
The Management Board may invite the chairmen of the
scientific committees to attend its meetings, but they shall not
have the right to vote.

9.
The Management Board shall approve the annual work
programme of the Agency programme and forward it to the
European Parliament, the Council, the Commission and the
Member States.

10.
The Management Board shall adopt the annual report
on the Agency's activities and forward it by 15 June at the
latest
the
Commission, the European Economic and Social Committee,
the Court of Auditors and the Member States.

the Council,

Parliament,

European

the

to

Article 66

The Management Board shall:

(a) adopt an opinion on the rules of procedures of

the
Committee for Medicinal Products for Human Use and
the Committee for Medicinal Products for Veterinary Use
(Article 61);

(b) adopt procedures for the performance of scientific services

(Article 62);

(c) appoint the Executive Director (Article 64);

(d) adopt the annual work programme and forward it to the
European Parliament, the Council, the Commission and the
Member States (Article 65);

(e) approve the annual report on the Agency's activities and
to the European
forward it by 15 June at
the Commission, the European
Parliament,
Economic and Social Committee, the Court of Auditors
and the Member States (Article 65);

the Council,

the latest

(f) adopt the budget of the Agency (Article 67);

(i) develop contacts with stakeholders and stipulate

the

conditions applicable (Article 78);

(j) adopt provisions for providing assistance to pharmaceutical

companies (Article 79);

(k) adopt rules to ensure the availability to the public of
information concerning the authorisation or supervision
of medicinal products (Article 80).

C h a p t e r 2

Financial Provisions

Article 67

Estimates of all

the revenue and expenditure of

1.
the
Agency shall be prepared for each financial year, corresponding
to the calendar year, and shall be shown in the budget of the
Agency.

The revenue and expenditure shown in the budget shall

2.
be in balance.

3.
The Agency's revenue shall consist of a contribution from
the Community and fees paid by undertakings for obtaining
and maintaining Community marketing authorisations and for
other services provided by the Agency.

‘the budgetary authority’)

The European Parliament and the Council (hereinafter referred
to as
re-examine, when
necessary, the level of the Community contribution on the
basis of an evaluation of needs and taking account of the
level of fees.

shall

4.
Activities relating to pharmacovigilance, to the operation
of communications networks and to market surveillance shall
receive adequate public funding commensurate with the tasks
conferred.

5.
The expenditure of the Agency shall include staff remun-
eration, administrative and infrastructure costs, and operating
expenses as well as expenses resulting from contracts entered
into with third parties.

Each year the Management Board, on the basis of a draft
6.
drawn up by the Executive Director, shall produce an estimate
of revenue and expenditure for the Agency for the following
financial year. This estimate, which shall include a draft estab-
lishment plan, shall be forwarded by the Management Board to
the Commission by 31 March at the latest.

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The estimate shall be forwarded by the Commission to
7.
the budgetary authority together with the preliminary draft
general budget of the European Union.

8.
On the basis of the estimate, the Commission shall enter
in the preliminary draft general budget of the European Union
the estimates it deems necessary for the establishment plan and
the amount of the subsidy to be charged to the general budget,
the budgetary authority in
shall place before
which it
accordance with Article 272 of the Treaty.

The budgetary authority shall authorise the appro-

9.
priations for the subsidy to the Agency.

By 31 March at the latest following each financial year,
3.
the Commission's accounting officer shall submit the Agency's
provisional accounts to the Court of Auditors, together with a
report on the budgetary and financial management for that
financial year. The report on the budgetary and financial
management for the financial year shall also be forwarded to
the European Parliament and the Council.

4.
On receipt of the Court of Auditors' observations on the
Agency's provisional accounts, pursuant to Article 129 of the
general Financial Regulation, the Executive Director shall draw
up the Agency's final accounts under his own responsibility
and submit them to the Management Board for an opinion.

The budgetary authority shall adopt the establishment plan for
the Agency.

The Management Board of the Agency shall deliver an

5.
opinion on the Agency's final accounts.

10.
The budget shall be adopted by the Management Board.
It shall become final following final adoption of the general
budget of the European Union. Where appropriate, it shall be
adjusted accordingly.

11.
Any modification of the establishment plan and of the
budget shall be the subject of an amending budget, which is
forwarded for the purposes of information to the budgetary
authority.

The Management Board shall, as soon as possible, notify
12.
the budgetary authority of
its intention to implement any
project which may have significant financial implications for
the funding of its budget, in particular any projects relating to
property such as the rental or purchase of buildings. It shall
inform the Commission thereof.

The Executive Director shall, by 1 July at

6.
the latest
following each financial year, forward the final accounts to
the European Parliament, the Council, the Commission and
the Court of Auditors, together with the Management Board's
opinion.

7.

The final accounts shall be published.

8.
The Agency's Executive Director shall send the Court of
Auditors a reply to its observations by 30 September at the
latest. He shall also send this reply to the Management Board.

Where a branch of the budgetary authority has notified its
it shall forward its opinion
intention to deliver an opinion,
to the Management Board within a period of six weeks from
the date of notification of the project.

The Executive Director shall submit

9.
to the European
Parliament, at the latter's request, any information required
the discharge procedure for
for the smooth application of
the financial year in question, as laid down in Article 146(3)
of the general Financial Regulation.

Article 68

The Executive Director shall implement the budget of the

1.
Agency.

10.
The European Parliament, on a recommendation from
the Council acting by a qualified majority, shall, before 30 April
of year N + 2, give a discharge to the Executive Director in
respect of the implementation of the budget for year N.

2.
By 1 March at the latest following each financial year, the
Agency's accounting officer shall communicate the provisional
accounts to the Commission's accounting officer together with
a report on the budgetary and financial management for that
shall
financial year. The Commission's accounting officer
consolidate the provisional accounts of the institutions and
decentralised bodies in accordance with Article 128 of the
Financial Regulation applicable to the general budget of the
European Communities (1)
the
‘general Financial Regulation’).

referred to as

(hereinafter

(1) Council Regulation (EC, Euratom) No 1605/2002 of 25 June 2002
on the Financial Regulation applicable to the general budget of the
European Communities (OJ L 248, 16.9.2002, p. 1).

11.
The financial rules applicable to the Agency shall be
adopted by the Management Board after the Commission has
been consulted. They may not depart from Commission Regu-
lation (EC, Euratom) No 2343/2002 of 19 November 2002 on
the framework Financial Regulation for the bodies referred to
in Article 185 of Council Regulation (EC,
Euratom)
No 1605/2002 on the Financial Regulation applicable to the
the European Communities (2), unless
general budget of
specifically required for the Agency's operation and with the
Commission's prior consent.

(2) OJ L 357, 31.12.2002, p. 72.

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Article 69

1.
In order to combat fraud, corruption and other unlawful
activities the provisions of Regulation (EC) No 1073/1999 of
the European Parliament and of the Council of 25 May 1999
European
concerning
Anti-Fraud Office (OLAF) (1) shall apply without restriction.

investigations

conducted

the

by

shall

The Agency

2.
Interinstitutional
accede
Agreement of 25 May 1999 concerning internal investigations
by the European Anti-Fraud Office (OLAF) and shall
issue,
without delay, the appropriate provisions applicable to all the
employees of the Agency.

to the

Article 70

1.
The structure and the level of the fees referred to in
Article 67(3) shall be established by the Council acting under
the conditions provided for by the Treaty on a proposal from
the Commission, once the Commission has consulted organi-
sations
the pharmaceutical
industry at Community level.

representing the

interests of

2.
However, provisions shall be adopted in accordance with
the procedure referred to in Article 87(2), establishing the
circumstances in which small and medium-sized enterprises
may pay reduced fees, defer payment of the fee, or receive
administrative assistance.

The Court of
relating to compensation for any such damage.

Justice shall have jurisdiction in any dispute

The personal liability of its servants towards the Agency
3.
shall be governed by the relevant rules applying to the staff of
the Agency.

Article 73

Regulation (EC) No 1049/2001 of the European Parliament and
of the Council of 30 May 2001 regarding public access to
European Parliament, Council and Commission documents (2)
shall apply to documents held by the Agency.

The Agency shall set up a register pursuant to Article 2(4) of
Regulation (EC) No 1049/2001 to make
all
documents that are publicly accessible pursuant to this Regu-
lation.

available

The Management Board shall adopt
the arrangements for
implementing Regulation (EC) No 1049/2001 within six
months of entry into force of this Regulation.

Decisions taken by the Agency pursuant to Article 8 of Regu-
lation (EC) No 1049/2001 may give rise to the lodging of a
complaint with the Ombudsman or form the subject of an
action before the Court of Justice, under the conditions laid
down in Articles 195 and 230 of the Treaty respectively.

C h a p t e r 3

General Provisions governing the Agency

Article 71

Article 74

The Protocol on the Privileges and Immunities of the European
Communities shall apply to the Agency.

The Agency shall have legal personality. In all Member States it
shall enjoy the most extensive legal capacity accorded to legal
persons under their laws.
It may in particular acquire or
dispose of movable and immovable property and may be a
party to legal proceedings.

Article 72

1.
The contractual liability of the Agency shall be governed
by the law applicable to the contract in question. The Court of
Justice of the European Communities shall have jurisdiction
pursuant
to any arbitration clause contained in a contract
concluded by the Agency.

Article 75

The staff of the Agency shall be subject to the rules and regu-
lations applicable to officials and other staff of the European
Communities. In respect of its staff, the Agency shall exercise
the powers which have been devolved to the appointing
authority.

The Management Board, in agreement with the Commission,
shall adopt the necessary implementing provisions.

Article 76

2.
In the case of non-contractual liability, the Agency shall,
in accordance with the general principles common to the laws
of the Member States, make good any damage caused by it or
by its servants in the performance of their duties.

the Management Board, members of

Members of
the
committees referred to in Article 56(1), and experts and
officials and other servants of the Agency, shall be required,
even after their duties have ceased, not to disclose information
of the kind covered by the obligation of professional secrecy.

(1) OJ L 136, 31.5.1999, p. 1.

(2) OJ L 145, 31.5.2001, p. 43.

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Article 77

in agreement with the Management
The Commission may,
invite representatives of
Board and the relevant committee,
international organisations with an interest
in the harmon-
isation of regulations applicable to medicinal products to
participate as observers in the work of
the Agency. The
conditions for participation shall be determined beforehand
by the Commission.

Article 78

in agreement with the
1.
The Management Board shall,
contacts between the
Commission, develop appropriate
the industry, consumers
Agency and the representatives of
and patients and the health professions. These contacts may
include the participation of observers in certain aspects of the
Agency's work, under conditions determined beforehand by the
Management Board, in agreement with the Commission.

2.
The committees referred to in Article 56(1) and any
working parties and scientific advisory groups established in
accordance with that Article shall in general matters establish
contacts, on an advisory basis, with parties concerned with the
use of medicinal products, in particular patient organisations
and
associations. Rapporteurs
appointed by these committees may, on an advisory basis,

professionals'

health-care

establish contacts with representatives of patient organisations
and health-care professionals' associations relevant to the indi-
cation of the medicinal product concerned.

Article 79

The Management Board shall,
in the case of veterinary
medicinal products which have limited markets, or in the
case of veterinary medicinal products intended for diseases
with a regional distribution, adopt the necessary measures to
provide assistance to companies at the time of submission of
their applications.

Article 80

level of

transparency,

an appropriate

To ensure
the
Management Board, on the basis of a proposal by the
Executive Director and in agreement with the Commission,
shall adopt rules to ensure the availability to the public of
regulatory, scientific or technical
information concerning the
authorisation or supervision of medicinal products which is not
of a confidential nature.

rules

internal

The
its
committees and its working groups shall be made available
to the public at the Agency and on the Internet.

and procedures of

the Agency,

TITLE V

GENERAL AND FINAL PROVISIONS

Article 81

a marketing

All decisions to grant, refuse, vary, suspend, withdraw or
1.
taken in
revoke
the
accordance with this Regulation shall
reasons on which they are based. Such decisions shall be
notified to the party concerned.

authorisation which are

state in detail

2.
An authorisation to place a medicinal product governed
by this Regulation on the market shall not be granted, refused,
varied, suspended, withdrawn or revoked except through the
procedures and on the grounds set out in this Regulation.

Article 82

Only one authorisation may be granted to an applicant

1.
for a specific medicinal product.

However, the Commission shall authorise the same applicant to
submit more than one application to the Agency for that
medicinal product when there are objective verifiable reasons
relating to public health regarding the availability of medicinal
products to health-care professionals and/or patients, or for
co-marketing reasons.

2.
As regards medicinal products for human use, Article
98(3) of Directive 2001/83/EC shall apply to medicinal
products authorised under this Regulation.

3. Without prejudice to the unique, Community nature of
the content of the documents referred to in Article 9(4)(a), (b),
(c) and (d) and in Article 34(4)(a) to (e), this Regulation shall
not prohibit the use of two or more commercial designs for a
given medicinal product covered by a single authorisation.

Article 83

1.
By way of exemption from Article 6 of Directive
2001/83/EC Member States may make a medicinal product
for human use belonging to the categories referred to in
Article 3(1) and (2) of this Regulation available for compas-
sionate use.

For the purposes of this Article, ‘compassionate use’ shall
2.
mean making a medicinal product belonging to the categories
referred to in Article 3(1) and (2) available for compassionate
reasons to a group of patients with a chronically or seriously
debilitating disease or whose disease is considered to be life-
threatening, and who can not be treated satisfactorily by an
authorised medicinal
product
concerned must either be the subject of an application for a
marketing authorisation in accordance with Article 6 of this
Regulation or must be undergoing clinical trials.

The medicinal

product.

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3. When a Member State makes use of
provided for in paragraph 1 it shall notify the Agency.

the possibility

obligations laid down in connection with the authorisations.
The maximum amounts as well as the conditions and methods
for collection of
shall be laid down in
accordance with the procedure referred to in Article 87(2).

these penalties

4. When compassionate use is envisaged, the Committee for
Medicinal Products for Human Use, after consulting the manu-
the applicant, may adopt opinions on the
facturer or
conditions for use,
the conditions for distribution and the
patients targeted. The opinions shall be updated on a regular
basis.

5. Member States
opinions.

shall

take account of any available

The Agency shall keep an up-to-date list of the opinions
6.
adopted in accordance with paragraph 4, which shall be
published on its website. Article 24(1) and Article 25 shall
apply mutatis mutandis.

The opinions referred to in paragraph 4 shall not affect
liability of the manufacturer or of the

7.
the civil or criminal
applicant for marketing authorisation.

8. Where a compassionate use programme has been set up,
the applicant shall ensure that patients taking part also have
access to the new medicinal product during the period between
authorisation and placing on the market.

This Article shall be without prejudice to Directive

9.
2001/20/EC and to Article 5 of Directive 2001/83/EC.

Article 84

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 infringement of
the provisions of this Regulation or the regulations adopted
pursuant to it and shall take all measures necessary for their
implementation. The penalties shall be effective, proportionate
and dissuasive.

Member States
provisions no later
notify any subsequent alterations as soon as possible.

these
than 31 December 2004. They shall

inform the Commission of

shall

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

Article 85

This Regulation shall not affect the competences vested in the
European Food Safety Authority created by Regulation (EC)
No 178/2002 (1).

Article 86

At least every ten years, the Commission shall publish a general
report on the experience acquired as a result of the operation
of the procedures laid down in this Regulation, in Chapter 4 of
Title III of Directive 2001/83/EC and in Chapter 4 of Title III of
Directive 2001/82/EC.

Article 87

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 and by the Standing
Committee on Veterinary Medicinal Products
set up by
Article 89 of Directive 2001/82/EC.

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. Where reference is made to this paragraph, Articles 4 and
7 of Decision 1999/468/EC shall apply, having regard to the
provisions of Article 8 thereof.

The period laid down in Article 4(3) of Decision 1999/468/EC
shall be set at one month.

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

4.

The committees shall adopt their Rules of Procedure.

3.
At the Agency's request, the Commission may impose
financial penalties on the holders of marketing authorisations
granted under this Regulation if they fail to observe certain

(1) Regulation (EC) No 178/2002 of the European Parliament and of
the Council of 28 January 2002 laying down the general principles
and requirements of
food law, establishing the European Food
Safety Authority and laying down procedures in matters of food
safety (OJ L 31, 1.2.2002, p. 1).

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Article 88

Regulation (EEC) No 2309/93/EC is hereby repealed.

which an application for authorisation has been submitted
before the date referred to in Article 90, second paragraph.

References to the repealed Regulation shall be construed as
references to this Regulation.

Article 89

The periods of protection provided for in Articles 14(11) and
39(10) shall not apply to reference medicinal products for

Article 90

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

By way of derogation from the first paragraph, Titles I, II, III
and V shall apply from 20 November 2005 and point 3, fifth
and sixth indent of the Annex shall apply from 20 May 2008.

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

Done at Strasbourg 31 March 2004.

For the European Parliament

The President

P. COX

For the Council

The President

D. ROCHE

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MEDICINAL PRODUCTS TO BE AUTHORISED BY THE COMMUNITY

ANNEX

1. Medicinal products developed by means of one of the following biotechnological processes:

— recombinant DNA technology,

— controlled expression of genes coding for biologically active proteins in prokaryotes and eukaryotes including

transformed mammalian cells,

— hybridoma and monoclonal antibody methods.

2. Medicinal products for veterinary use intended primarily for use as performance enhancers in order to promote the

growth of treated animals or to increase yields from treated animals.

3. Medicinal products for human use containing a new active substance which, on the date of entry into force of this
Regulation, was not authorised in the Community, for which the therapeutic indication is the treatment of any of the
following diseases:

— acquired immune deficiency syndrome,

— cancer,

— neurodegenerative disorder,

— diabetes,

and with effect from 20 May 2008

— auto-immune diseases and other immune dysfunctions,

— viral diseases.

After 20 May 2008, the Commission, having consulted the Agency, may present any appropriate proposal modifying
this point and the Council shall take a decision on that proposal by qualified majority.

4. Medicinal products that are designated as orphan medicinal products pursuant to Regulation (EC) No 141/2000.