Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use (Text with EEA relevance)
Date: 2004-03-31
Institutions: Council of the European Union, European Parliament
Subjects: approximation of laws, consolidation of EU law, legal code, medicinal product, pharmaceutical legislation, public health, single market

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Official Journal of the European Union

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DIRECTIVE 2004/27/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

of 31 March 2004

amending Directive 2001/83/EC on the Community code relating to medicinal products for human
use

(Text with EEA relevance)

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE
EUROPEAN UNION,

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

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

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

After consulting the Committee of the Regions,

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

Whereas:

(1)

(2)

(3)

Directive 2001/83/EC of the European Parliament and of
the Council of 6 November 2001 on the Community
code relating to medicinal products for human use (4),
codified and consolidated in a single text the texts of
Community legislation on medicinal products for human
use, in the interests of clarity and rationalisation.

The Community legislation so far adopted has made a
major contribution to the achievement of the objective
of the free and safe movement of medicinal products for
human use and the elimination of obstacles to trade in
such products. However, in the light of the experience
acquired,
it has become clear that new measures are
necessary to eliminate the remaining obstacles to free
movement.

It is therefore necessary to align the national laws, regu-
lations and administrative provisions which contain
differences with regard to the basic principles in order
to promote the operation of the internal market while
realising a high level of human health protection.

(1) OJ C 75 E, 26.3.2002, p. 216 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. 353), Council Common Position of
29 September 2003 (OJ C 297 E, 9.12.2003, p. 41), Position of
the European Parliament of 17 December 2003 (not yet published
in the Official Journal) and Council Decision of 11 March 2004.
(4) OJ L 311, 28.11.2001, p. 67. Directive as last amended by
Commission Directive 2003/63/EC (OJ L 159, 27.6.2003, p. 46).

(4)

(5)

(6)

(7)

The main purpose of any regulation on the manufacture
and distribution of medicinal products for human use
should be to safeguard public health. However,
this
objective should be achieved by means which do not
hinder the development of the pharmaceutical industry
or trade in medicinal products in the Community.

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 (5) provided that, within six years of its entry
into force, the Commission was required to publish a
general report on the experience acquired as a result of
the operation of the marketing authorisation procedures
laid down in that Regulation and in other Community
legal provisions.

light of

the Commission's

report on the
In the
experience
to
improve the operation of the marketing authorisation
procedures for medicinal products in the Community.

it has proved necessary

acquired,

the

sectors,

the definitions

the definition of

growing number of

scientific and technical
Particularly as a result of
progress,
and scope of Directive
2001/83/EC should be clarified in order to achieve
high standards for the quality, safety and efficacy of
medicinal products for human use.
In order to take
account both of the emergence of new therapies and
of
so-called ‘borderline’
products between the medicinal product sector and
‘medicinal product’
other
should be modified so as to avoid any doubt as to the
applicable legislation when a product, whilst fully falling
within the definition of a medicinal product, may also
fall within the definition of other regulated products.
This definition should specify the type of action that
the medicinal product may exert on physiological
functions. This enumeration of actions will also make
it possible to cover medicinal products such as gene
as
as well
radiopharmaceutical products
therapy,
certain medicinal products for topical use. Also,
in
view of the characteristics of pharmaceutical legislation,
provision should be made for such legislation to apply.
With the same objective of clarifying situations, where a
given product comes under the definition of a medicinal
product but could also fall within the definition of other
regulated products, it is necessary, in case of doubt and
in order to ensure legal certainty,
to state explicitly
which provisions have to be complied with. Where a
product comes clearly under the definition of other
product categories, in particular food, food supplements,

(5) OJ L 214, 21.8.1993, p. 1. Regulation repealed by Regulation (EC)

No 726/2004 (see p. 1 of this Official Journal).

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this Directive
medical devices, biocides or cosmetics,
should not apply. It is also appropriate to improve the
consistency of the terminology of pharmaceutical legis-
lation.

(13)

(8) Wherever it is proposed to change the scope of the
it should no longer be possible
centralised procedure,
to opt
for the mutual-recognition procedure or the
decentralised procedure in respect of orphan medicinal
products and medicinal products which contain new
active substances and for which the therapeutic indi-
cation is the treatment of acquired immune deficiency
or
syndrome,
diabetes. Four years after the date of entry into force
of Regulation (EC) No 726/2004 (1),
should no
longer be possible to opt for the mutual-recognition
procedure or the decentralised procedure in respect of
medicinal products which contain new active substances
and for which the therapeutic indication is the treatment
of
immune
dysfunctions and viral diseases.

neurodegenerative

auto-immune

disorder

diseases

cancer,

other

and

it

(9)

(10)

(11)

On the other hand,
in the case of generic medicinal
products of which the reference medicinal product has
been granted a marketing authorisation under
the
seeking marketing
centralised procedure,
authorisation should be able to choose either of the
two procedures, on certain conditions. Similarly,
the
mutual-recognition or decentralised procedure should
be available as an option for medicinal products which
represent a therapeutic innovation or which are of
benefit to society or to patients.

applicants

In order to increase availability of medicinal products, in
particular on smaller markets, it should, in cases where
an applicant does not apply for an authorisation for a
medicinal product in the context of the mutual-recog-
nition procedure in a given Member State, be possible
for that Member State, for justified public health reasons,
to authorise the placing on the market of the medicinal
product.

Evaluation of the operation of marketing authorisation
procedures has revealed the need to revise, in particular,
the mutual-recognition procedure in order to improve
the opportunities
for cooperation between Member
States. This cooperation process should be formalised
by setting up a coordination group for this procedure
and by
to settle
disagreements within the framework of a revised decen-
tralised procedure.

its operation so as

defining

(12) With regard to referrals, the experience acquired reveals
the need for an appropriate procedure, particularly in
the case of referrals relating to an entire therapeutic
class or to all medicinal products containing the same
active substance.

There is a need to provide for the ethical requirements
of Directive 2001/20/EC of the European Parliament and
the Council of 4 April 2001 on the approximation of
the laws, regulations and administrative provisions of
the Member States relating to the implementation of
good clinical practice in the conduct of clinical trials
on medicinal products for human use (2) to apply to
all medicinal
the
Community. In particular, with respect to clinical trials
the Community on medicinal
conducted outside
products
the
to
destined
it should be verified, at the time of the
Community,
evaluation of
that
these trials were conducted in accordance with the prin-
ethical
ciples of
requirements
that
Directive.

the application for authorisation,

good clinical practice

to the provisions of

authorised within

authorised within

equivalent

and the

products

be

(14)

(15)

(16)

in medicinal products,

Since generic medicines account for a major part of the
market
to the
Community market should be facilitated in the light of
the period for
the experience acquired. Furthermore,
protection of data relating to pre-clinical
tests and
clinical trials should be harmonised.

their access

to manufacturing process

Biological medicinal products similar
to a reference
medicinal product do not usually meet all the conditions
to be considered as a generic medicinal product mainly
due
raw
materials used, molecular characteristics and therapeutic
modes of action. When a biological medicinal product
does not meet all the conditions to be considered as a
the results of appropriate
generic medicinal product,
tests
the
requirements related to safety (pre-clinical tests) or to
efficacy (clinical tests) or to both.

should be provided in order

characteristics,

to fulfil

The criteria of quality, safety and efficacy should enable
the risk-benefit balance of all medicinal products to be
assessed both when they are placed on the market and
at any other time the competent authority deems this
is necessary to
appropriate.
harmonise and adapt the criteria for refusal, suspension
and revocation of marketing authorisations.

In this connection,

it

(17) A marketing authorisation should be renewed once five
years after the granting of the marketing authorisation.
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
in the Member States concerned
medicinal product
during that period, should be considered invalid,
in
order, in particular, to avoid the administrative burden
However,
of maintaining
exemptions from this rule should be granted when
these are justified on public health grounds.

authorisations.

such

(1) See p. 1 of this Official Journal.

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

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(18)

(19)

(20)

The environmental impact should be assessed and, on a
case-by-case basis,
it
should be envisaged. In any event this impact should
not constitute a criterion for refusal of a marketing
authorisation.

specific arrangements

to limit

The quality of medicinal products for human use manu-
factured or available in the Community should be
guaranteed by requiring that the active substances used
in their composition comply with the principles of good
manufacturing practice in relation to those medicinal
products.
It has proved necessary to reinforce the
Community provisions on inspections and to compile
a Community register of the results of those inspections.

and, more

generally, market
Pharmacovigilance
surveillance and sanctions in the event of
failure to
comply with the provisions should be stepped up. In
the field of pharmacovigilance, account
should be
taken of the facilities offered by new information tech-
nologies to improve exchanges between Member States.

(21) As part of the proper use of medicinal products, the
rules on packaging should be adapted to take account
of the experience acquired.

(22)

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

the

(23) Directive 2001/83/EC should be amended accordingly,

HAVE ADOPTED THIS DIRECTIVE:

Article 1

Directive 2001/83/EC is hereby amended as follows:

1) Article 1 shall be amended as follows:

(a) point 1 shall be deleted;

(b) point 2 shall be replaced by the following:

‘2. Medicinal product:

human beings either with a view to restoring,
correcting or modifying physiological functions
by exerting a pharmacological, immunological
or metabolic action, or to making a medical
diagnosis.’

(c) point 5 shall be replaced by the following:

‘5. Homeopathic medicinal product:

Any medicinal product prepared from substances
called homeopathic stocks in accordance with a
homeopathic manufacturing procedure described
by the European Pharmacopoeia or,
in the
absence thereof, by the pharmacopoeias currently
used officially in the Member States. A homeo-
pathic medicinal product may contain a number
of principles.’;

(d) the Title of point 8 shall be replaced by ‘Kit’;

(e)

the following point shall be inserted:

‘18a Representative of the marketing authorisation holder:

The person, commonly known as local represen-
tative, designated by the marketing authorisation
holder to represent him in the Member State
concerned’.

(f) point 20 shall be replaced by the following:

‘20. Name of the medicinal product:

The name, which may be either an invented name
not liable to confusion with the common name,
or a common or scientific name accompanied by
a trade mark or the name of the marketing auth-
orisation holder.’;

(g) the heading of point 26 shall be replaced by the

following:

(only concerns the Portuguese version);

(h) point 27 shall be replaced by the following:

(a) Any substance or combination of substances
presented as having properties for treating or
preventing disease in human beings; or

‘27. Agency:

(b) Any substance or combination of substances
which may be used in or administered to

(1) OJ L 184, 17.7.1999, p. 23.

The European Medicines Agency established by
Regulation (EC) No 726/2004 (*);

___________
(*) OJ L 136, 30.4.2004, p. 1.’;

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(i) point 28 shall be replaced by the following points:

‘28. Risks related to use of the medicinal product:

2001 on the approximation of the laws, regulations
and administrative provisions of the Member States
relating to the implementation of good clinical
practice
trials on
medicinal products for human use (*).

conduct of clinical

in the

— any risk relating to the quality, safety or
efficacy of the medicinal product as regards
patients' health or public health;

___________
(*) OJ L 121, 1.5.2001, p. 34.’;

— any risk of undesirable

effects on the

environment;

(c) point 6 shall be replaced by the following:

28a. Risk-benefit balance:

‘6. Whole blood, plasma or blood cells of human
origin, except for plasma which is prepared by a
method involving an industrial process.’;

An evaluation of the positive therapeutic effects
of the medicinal product in relation to the risks
as defined in point 28, first indent.’;

4) Article 5 shall be replaced by the following:

2) Article 2 shall be replaced by the following:

‘Article 5

‘Article 2

This Directive shall apply to medicinal products for
1.
human use intended to be placed on the market
in
Member States and either prepared industrially or manu-
factured by a method involving an industrial process.

2.
In cases of doubt, where, taking into account all its
characteristics, a product may fall within the definition of
a “medicinal product” and within the definition of a
product covered by other Community legislation the
provisions of this Directive shall apply.

3.
Notwithstanding paragraph 1 and Article 3(4), Title
this Directive shall apply to medicinal products
IV of
intended only for export and to intermediate products.’;

3) Article 3 shall be amended as follows:

(a) point 2 shall be replaced by the following:

‘2. Any medicinal product which is prepared in a
pharmacy in accordance with the prescriptions of
a pharmacopoeia and is intended to be supplied
directly to the patients served by the pharmacy in
the officinal
question (commonly known as
formula).’

(b) point 3 shall be replaced by the following:

‘3. Medicinal products intended for research and devel-
to the
opment
provisions
the
European Parliament and of the Council of 4 April

trials, but without prejudice

2001/20/EC of

of Directive

1.
A Member State may, in accordance with legislation
in force and to fulfil special needs, exclude from the
provisions of this Directive medicinal products supplied
in response to a bona fide unsolicited order, formulated
in accordance with the specifications of an authorised
health-care professional and for use by an individual
patient under his direct personal responsibility.

temporarily

the
2. Member States may
distribution of an unauthorised medicinal product
in
response to the suspected or confirmed spread of path-
ogenic
agents or nuclear
toxins,
radiation any of which could cause harm.

authorise

chemical

agents,

in order

lay down provisions
authorisation

to ensure
holders, manufacturers

3. Without prejudice to paragraph 1, Member States
that
shall
marketing
and
health professionals are not subject to civil or adminis-
trative liability for any consequences resulting from the
use of a medicinal product otherwise than for the auth-
orised indications or from the use of an unauthorised
medicinal product, when such use is recommended or
required by a competent authority in response to the
suspected or confirmed spread of pathogenic agents,
toxins, chemical agents or nuclear
radiation any of
which could cause harm. Such provisions shall apply
whether or not national or Community authorisation has
been granted.

Liability for defective products, as provided for by
4.
Council Directive 85/374/EEC of 25 July 1985 on the
approximation of the laws, regulations and administrative
provisions of the Member States, concerning liability for
defective products (*), shall not be affected by paragraph 3.

___________
(*) OJ L 210, 7.8.1985, p. 29. Directive as last amended
by Directive 1999/34/EC of the European Parliament
and of the Council (OJ L 141, 4.6.1999, p. 20).’;

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5) Article 6 shall be amended as follows:

(a)

in paragraph 1, the following subparagraph shall be
added:

‘When a medicinal product has been granted an initial
marketing authorisation in accordance with the first
subparagraph, any additional strengths, pharmaceutical
forms, administration routes, presentations, as well as
any variations and extensions shall also be granted an
authorisation
first
accordance
subparagraph or be included in the initial marketing
authorisation. All these marketing authorisations shall
same global
be
marketing authorisation, in particular for the purpose
of the application of Article 10(1).’;

considered as belonging to the

with

the

in

(b) the following paragraph shall be inserted:

‘1a
The marketing authorisation holder shall be
responsible for marketing the medicinal product. The
designation of a representative shall not relieve the
marketing authorisation holder of his legal responsi-
bility.’;

(c)

in paragraph 2, ‘radionuclide kits’ shall be replaced by
‘kits’;

6) in Article 7,

‘radionuclide kits’ shall be replaced by ‘kits’;

7) Article 8(3) shall be amended as follows:

with an indication of potential risks presented by
the medicinal product for the environment.

(h) Description of the control methods employed by

the manufacturer.

(i)

Results of:

— pharmaceutical

(physico-chemical, biological

or microbiological) tests,

— pre-clinical

(toxicological

and pharmaco-

logical) tests,

— clinical trials.

(ia) A detailed description of the pharmacovigilance
and, where appropriate, of the risk-management
system which the applicant will introduce.

(ib) A statement

to the effect

trials
carried out outside the European Union meet
the ethical requirements of Directive 2001/20/EC.

that clinical

(j) A summary, in accordance with Article 11, of the
product characteristics, a mock-up of the outer
packaging, containing the details provided for in
Article 54, and of the immediate packaging of
the medicinal product, containing the details
provided for
together with a
in Article 55,
package leaflet in accordance with Article 59.’;

(a) points (b) and (c) shall be replaced by the following:

(d) the following points shall be added:

‘(b) Name of the medicinal product.

(c) Qualitative and quantitative particulars of all the
constituents of the medicinal product,
including
the reference to its international non-proprietary
name (INN) recommended by the WHO, where an
INN for
the medicinal product exists, or a
reference to the relevant chemical name;’;

(b) the following point shall be inserted:

‘(ca) Evaluation of the potential environmental risks
posed by the medicinal product. This impact
shall be assessed and, on a case-by-case basis,
specific
shall be
envisaged.’;

arrangements

to limit

it

‘(m) A copy of any designation of

the medicinal
product as an orphan medicinal product under
Regulation (EC) No 141/2000 of the European
Parliament and of the Council of 16 December
1999 on orphan medicinal products (*), accom-
panied by a copy of the relevant Agency opinion.

the applicant has the services of a
(n) Proof that
qualified
phar-
person
macovigilance and has the necessary means for
the
reaction
suspected of occurring either in the Community
or in a third country.

notification

responsible

adverse

any

for

of

___________
(*) OJ L 18, 22.1.2000, p. 1.’;

(c) points (g),

(h),

(i) and (j) shall be replaced by the

(e) the following subparagraph shall be added:

following points:

‘(g) Reasons

for

any precautionary

safety
measures to be taken for the storage of
the
medicinal product, its administration to patients
and for the disposal of waste products, together

and

‘The documents and information concerning the results
of the pharmaceutical and pre-clinical tests and the
(i) of
clinical
the first
subparagraph shall be
accompanied by detailed
summaries in accordance with Article 12.’;

trials referred to in point

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8) Article 10 shall be replaced by the following:

‘Article 10

By way of derogation from Article 8(3)(i), and
1.
without prejudice to the law relating to the protection of
industrial and commercial property, the applicant shall not
be required to provide the results of pre-clinical tests and
of clinical trials if he can demonstrate that the medicinal
product
is a generic of a reference medicinal product
which is or has been authorised under Article 6 for not
less
in the
Community.

in a Member State or

than eight years

A generic medicinal product authorised pursuant to this
provision shall not be placed on the market until ten years
have elapsed from the initial authorisation of the reference
product.

an authorised active substance must be supplied by
the applicant. The various immediate-release oral phar-
maceutical forms shall be considered to be one and the
same pharmaceutical form. Bioavailability studies need
not be required of the applicant if he can demonstrate
that the generic medicinal product meets the relevant
criteria
detailed
in the
as
guidelines.

appropriate

defined

3.
In cases where the medicinal product does not fall
within the definition of a generic medicinal product as
provided in paragraph 2(b) or where the bioequivalence
cannot be demonstrated through bioavailability studies or
in case of changes in the active substance(s), therapeutic
indications, strength, pharmaceutical
form or route of
administration, vis-à-vis the reference medicinal product,
the results of the appropriate pre-clinical tests or clinical
trials shall be provided.

In this case,

is submitted.
in the

application form the name of

The first subparagraph shall also apply if the reference
medicinal product was not authorised in the Member
State in which the application for the generic medicinal
the applicant shall
product
indicate
the
Member State in which the reference medicinal product
is or has been authorised. At
the
competent authority of the Member State in which the
application is submitted, the competent authority of the
other Member State shall transmit within a period of one
month, a confirmation that
reference medicinal
product is or has been authorised together with the full
the reference product and if necessary
composition of
other relevant documentation.

request of

the

the

The ten-year period referred to in the second subparagraph
shall be extended to a maximum of eleven years if, during
the first eight years of those ten years,
the marketing
authorisation holder obtains an authorisation for one or
more new therapeutic indications which, during the
scientific evaluation prior to their authorisation, are held
to bring a significant clinical benefit in comparison with
existing therapies.

2.

For the purposes of this Article:

(a) “reference medicinal product” shall mean a medicinal
product authorised under Article 6, in accordance with
the provisions of Article 8;

the

form as

(b) “generic medicinal product” shall mean a medicinal
product which has the same qualitative and quanti-
tative composition in active substances and the same
pharmaceutical
reference medicinal
product, and whose bioequivalence with the reference
medicinal product has been demonstrated by appro-
salts,
priate bioavailability
esters,
isomers,
isomers, mixtures
complexes or derivatives of an active substance shall
be considered to be the same active substance, unless
they differ significantly in properties with regard to
additional
safety and/or
information providing proof of
the safety and/or
efficacy of the various salts, esters or derivatives of

studies. The different

In such cases,

efficacy.

ethers,

of

4. Where a biological medicinal product which is
similar to a reference biological product does not meet
the conditions in the definition of generic medicinal
in particular, differences relating to
products, owing to,
raw materials or differences in manufacturing processes
of
the biological medicinal product and the reference
biological medicinal product, the results of appropriate
pre-clinical
relating to these
conditions must be provided. The type and quantity of
supplementary data to be provided must comply with
the relevant criteria stated in Annex I and the related
detailed guidelines. The results of other tests and trials
from the reference medicinal product's dossier shall not
be provided.

tests or

clinical

trials

5.
In addition to the provisions laid down in paragraph
1, where an application is made for a new indication for a
well-established substance, a non-cumulative period of one
year of data exclusivity shall be granted, provided that
significant pre-clinical or clinical studies were carried out
in relation to the new indication.

6.
Conducting the necessary studies and trials with a
view to the application of paragraphs 1, 2, 3 and 4 and
the consequential practical
shall not be
regarded as contrary to patent rights or to supplementary
protection certificates for medicinal products.’;

requirements

9) the following Articles shall be inserted:

‘Article 10a

trials

the applicant

if he can demonstrate that

By way of derogation from Article 8(3)(i), and without
prejudice to the law relating to the protection of industrial
shall not be
and commercial property,
tests or
required to provide the results of pre-clinical
clinical
the active
substances of the medicinal product have been in well-
established medicinal use within the Community for at
least ten years, with recognised efficacy and an acceptable
level of safety in terms of the conditions set out in Annex
I. In that event, the test and trial results shall be replaced
by appropriate scientific literature.

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Article 10b

composition of

In the case of medicinal products containing active
substances used in the
authorised
medicinal products but not hitherto used in combination
for therapeutic purposes, the results of new pre-clinical
tests or new clinical trials relating to that combination
shall be provided in accordance with Article 8(3)(i), but
it shall not be necessary to provide scientific references
relating to each individual active substance.

Article 10c

Following the granting of a marketing authorisation, the
authorisation holder may allow use to be made of the
pharmaceutical, pre-clinical and clinical documentation
contained in the file on the medicinal product, with a
view to examining subsequent applications relating to
other medicinal products possessing the same qualitative
and quantitative composition in terms of active substances
and the same pharmaceutical form.’;

10) Article 11 shall be replaced by the following:

‘Article 11

The summary of the product characteristics shall contain,
in the order indicated below, the following information:

1. name of

the medicinal product

followed by the

strength and the pharmaceutical form.

2. qualitative and quantitative composition in terms of
the active substances and constituents of the excipient,
knowledge of which is essential for proper adminis-
tration of the medicinal product. The usual common
name or chemical description shall be used.

4.5.

interaction with other medicinal products and
other forms of interactions,

4.6. use during pregnancy and lactation,

4.7. effects on ability to drive and to use machines,

4.8. undesirable effects,

4.9. overdose

(symptoms,

emergency procedures,

antidotes).

5. pharmacological properties:

5.1. pharmacodynamic properties,

5.2. pharmacokinetic properties,

5.3. preclinical safety data.

6. pharmaceutical particulars:

6.1.

list of excipients,

6.2. major incompatibilities,

6.3. shelf life, when necessary after reconstitution of
the medicinal product or when the immediate
packaging is opened for the first time,

6.4. special precautions for storage,

6.5. nature and contents of container,

6.6. special precautions

a used
medicinal product or waste materials derived
from such medicinal product, if appropriate.

for disposal of

3. pharmaceutical form.

4. clinical particulars:

4.1. therapeutic indications,

7. marketing authorisation holder.

8. marketing authorisation number(s).

9. date of the first authorisation or renewal of the auth-

orisation.

4.2. posology and method of administration for

adults and, where necessary for children,

10. date of revision of the text.

4.3. contra-indications,

4.4. special warnings and precautions for use and, in
the case of immunological medicinal products,
any special precautions to be taken by persons
handling such products and administering them
to patients, together with any precautions to be
taken by the patient,

11. for

radiopharmaceuticals,

full details of

internal

radiation dosimetry.

12. for

for

radiopharmaceuticals,

detailed
additional
extemporaneous preparation and
instructions
quality control of such preparation and, where appro-
priate, maximum storage time during which any inter-
mediate preparation such as an eluate or the ready-
to-use pharmaceutical will conform with its specifi-
cations.

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For authorisations under Article 10, those parts of the
summary of product characteristics of
the reference
medicinal product
referring to indications or dosage
forms which were still covered by patent law at the time
when a generic medicine was marketed need not be
included.’;

14) Article 15 shall be amended as follows:

(a) the second indent shall be replaced by the following:

11) Article 12 shall be replaced by the following:

‘Article 12

The applicant shall ensure that, before the detailed
1.
summaries referred to in the last subparagraph of Article
8(3) are submitted to the competent authorities, they have
been drawn up and signed by experts with the necessary
technical or professional qualifications, which shall be set
out in a brief curriculum vitae.

Persons having the technical and professional qualifi-
justify any use
in

2.
cations referred to in paragraph 1 shall
made of
accordance with the conditions set out in Annex I.

literature under Article 10a

scientific

‘— dossier describing how the homeopathic stock or
stocks
and
justifying its/their homeopathic use, on the basis
of an adequate bibliography,’;

controlled,

obtained

is/are

and

(b) the sixth indent shall be replaced by the following:

‘— one or more mock-ups of the outer packaging and
the medicinal

immediate packaging

of

the
products to be registered,’;

15) Article 16 shall be amended as follows:

(a)

in paragraph 1,
replaced by ‘Articles 8, 10, 10a, 10b, 10c and 11’.

‘Articles 8, 10 and 11’ shall be

The detailed summaries shall form part of the file
3.
which the applicant submits to the competent authorities.’;

(b) in paragraph 2,

‘toxicological and pharmacological

tests’ shall be replaced by ‘pre-clinical tests’;

12) Article 13 shall be replaced by the following:

16) Articles 17 and 18 shall be replaced by the following:

‘Article 13

‘Article 17

shall

States

ensure

1. Member
that homeopathic
medicinal products manufactured and placed on the
market within the Community are registered or authorised
in accordance with Articles 14, 15 and 16, except where
such medicinal products are covered by a registration or
authorisation granted in accordance with national
legis-
lation on or before 31 December 1993. In case of regis-
trations, Article 28 and Article 29(1) to (3) shall apply.

2. Member States shall establish a special simplified
registration procedure for
the homeopathic medicinal
products referred to in Article 14.’;

13) Article 14 shall be amended as follows:

1. Member States shall take all appropriate measures to
ensure that the procedure for granting a marketing auth-
orisation for medicinal products is completed within a
maximum of 210 days after the submission of a valid
application.

Applications for marketing authorisations in two or more
Member States in respect of the same medicinal product
shall be submitted in accordance with Articles 27 to 39.

2. Where a Member State notes that another marketing
authorisation application for the same medicinal product is
being examined in another Member State, the Member
State concerned shall decline to assess the application
and shall advise the applicant that Articles 27 to 39 apply.

(a)

in paragraph 1, the following second subparagraph
shall be inserted:

Article 18

‘If new scientific evidence so warrants, the Commission
may amend the third indent of the first subparagraph
by the procedure referred to in Article 121(2).’;

(b) paragraph 3 shall be deleted;

Where a Member State is informed in accordance with
Article 8(3)(1) that another Member State has authorised
a medicinal product which is the subject of a marketing
authorisation application in the Member State concerned,
it shall reject the application unless it was submitted in
compliance with Articles 27 to 39.’;

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17) Article 19 shall be amended as follows:

(a)

in the introductory sentence,
‘Articles 8 and 10(1)’
shall be replaced by ‘Articles 8, 10, 10a, 10b and 10c’;

(b) in point 1, ‘Articles 8 and 10(1)’ shall be replaced by

‘Articles 8, 10, 10a, 10b and 10c’;

(c)

in point 2,
‘a State laboratory or a laboratory
designated for that purpose’ shall be replaced by ‘an
Official Medicines Control Laboratory or a laboratory
that a Member State has designated for that purpose’;

(d) in point 3, ‘Articles 8(3) and 10(1)’ shall be replaced by

‘Articles 8(3), 10, 10a, 10b and 10c’;

18) in point (b) of Article 20,

‘in exceptional and justifiable

cases’ shall be replaced by ‘in justifiable cases’;

19) in Article 21, paragraphs 3 and 4 shall be replaced by the

following:

objective, verifiable reasons and must be based on one
of the grounds set out in Annex I. Continuation of the
authorisation shall be linked to the annual reassessment of
these conditions. The list of these conditions shall be made
publicly accessible without delay, together with deadlines
and dates of fulfilment.’;

21) in Article 23, the following paragraphs shall be added:

‘The authorisation holder shall
forthwith supply to the
competent authority any new information which might
the particulars or documents
entail
referred to in Articles 8(3), 10, 10a, 10b and 11, or
32(5), or Annex I.

the amendment of

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

The

authorities

competent

shall make publicly
‘3.
available without delay
authorisation
together with the summary of the product characteristics
for each medicinal product which they have authorised.

the marketing

The

competent

the pharmaceutical and pre-clinical

4.
shall draw up an
authorities
assessment report and comments on the file as regards
tests
the results of
and the clinical trials of the medicinal product concerned.
The assessment report shall be updated whenever new
information becomes available which is of
importance
for the evaluation of the quality, safety or efficacy of the
medicinal product concerned.

The competent authorities shall make publicly accessible
without delay the assessment report, together with the
reasons for their opinion, after deletion of any information
of a commercially confidential nature. The justification
shall be provided separately for each indication applied
for.’;

20) Article 22 shall be replaced by the following:

‘Article 22

to a requirement

In exceptional circumstances and following consultation
the authorisation may be granted
with the applicant,
subject
to meet
the applicant
certain conditions, in particular concerning the safety of
the medicinal product, notification to the competent auth-
orities of any incident relating to its use, and action to be
taken. This authorisation may be granted only for

for

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

risk-benefit balance

the

22) the following Article shall be inserted:

‘Article 23a

the
After a marketing authorisation has been granted,
holder of the authorisation shall
inform the competent
authority of the authorising Member State of the date of
actual marketing of the medicinal product for human use
in that Member State,
the various
presentations authorised.

taking into account

The holder shall also notify the competent authority if the
product ceases to be placed on the market of the Member
State, either temporarily or permanently. Such notification
shall, otherwise than in exceptional circumstances, be
made no less than 2 months before the interruption in
the placing on the market of the product.

Upon request by the competent authority, particularly in
the context of pharmacovigilance, the marketing author-
isation holder shall provide the competent authority with
all data relating to the volume of sales of the medicinal
product, and any data in his possession relating to the
volume of prescriptions.’;

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23) Article 24 shall be replaced by the following:

(c)

its qualitative and quantitative composition is not as
declared.

‘Article 24

1. Without prejudice
marketing authorisation shall be valid for five years.

to paragraphs 4 and 5,

a

2.
The marketing authorisation may be renewed after
five years on the basis of a re-evaluation of the risk-benefit
balance by the competent authority of
the authorising
Member State.

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

including all variations

Once renewed, the marketing authorisation shall be
3.
valid for an unlimited period, unless
the competent
authority decides, on justified grounds relating to phar-
macovigilance, to proceed with one additional five-year
renewal in accordance with paragraph 2.

4.
Any authorisation which within three years of its
granting is not followed by the actual placing on the
market of
in the authorising
the authorised product
Member State shall cease to be valid.

5. When an authorised product previously placed on
the market in the authorising Member State is no longer
actually present on the market
three
consecutive years,
that product
shall cease to be valid.

the authorisation for

for a period of

Authorisation shall

any
refused if
2.
particulars or documents submitted in support of
the
application do not comply with Articles 8, 10, 10a, 10b
and 10c.

likewise be

The applicant or the holder of a marketing author-
the

3.
isation shall be responsible for
documents and the data submitted.’;

the accuracy of

25) the heading of Chapter 4 of Title III shall be replaced by

the following:

‘CHAPTER 4

Mutual
procedure’;

recognition procedure

and decentralised

26) Articles 27 to 32 shall be replaced by the following:

‘Article 27

1.
A coordination group shall be set up for the exam-
ination of any question relating to marketing authorisation
of a medicinal product in two or more Member States in
accordance with the procedures laid down in this Chapter.
The Agency shall provide the secretariat of
this coor-
dination group.

2.
The coordination group shall be composed of one
representative per Member State appointed for a renewable
period of three years. Members of the coordination group
may arrange to be accompanied by experts.

6.
The competent authority may, in exceptional circum-
stances and on public health grounds grant exemptions
from paragraphs 4 and 5. Such exemptions must be
duly justified.’;

The coordination group shall draw up its own Rules
3.
of Procedure, which shall
into force after a
favourable opinion has been given by the Commission.
These Rules of Procedure shall be made public.

enter

24) Article 26 shall be replaced by the following:

Article 28

‘Article 26

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

1.
verification of
Articles 8, 10, 10a, 10b and 10c, it is clear that:

(a) the risk-benefit balance is not considered to be

favourable; or

(b) its therapeutic efficacy is insufficiently substantiated by

the applicant; or

1. With a view to the granting of a marketing author-
isation for a medicinal product in more than one Member
State, an applicant shall submit an application based on an
identical dossier in these Member States. The dossier shall
contain the information and documents referred to in
Articles 8, 10, 10a, 10b, 10c and 11. The documents
submitted
States
a
shall
concerned by the application.

list of Member

include

The applicant shall request one Member State to act as
“reference Member State” and to prepare an assessment
report on the medicinal product
in accordance with
paragraphs 2 or 3.

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reference Member

2. Where the medicinal product has already received a
marketing authorisation at the time of application,
the
concerned Member States shall recognise the marketing
authorisation granted by the reference Member State. To
this end, the marketing authorisation holder shall request
an
the
State
assessment
if
necessary, to update any existing assessment report. The
reference Member State shall prepare or update the
assessment report within 90 days of receipt of a valid
together with the
application. The assessment
approved summary of product characteristics,
labelling
and package leaflet
to the concerned
shall be sent
Member States and to the applicant.

report on the medicinal product or,

to prepare

report

either

shall

In cases where the medicinal product has not
3.
the
time of
received a marketing authorisation at
the reference
request
the applicant
application,
Member State to prepare a draft assessment report, a
draft summary of product characteristics and a draft of
the labelling and package leaflet. The reference Member
State shall prepare these draft documents within 120
days after receipt of a valid application and shall send
them to the concerned Member States and to the
applicant.

4. Within 90 days of receipt of the documents referred
to in paragraphs 2 and 3, the Member States concerned
shall approve the assessment report,
the summary of
product characteristics and the labelling and package
inform the reference Member State
leaflet and shall
accordingly. The reference Member State shall record the
agreement of all parties, close the procedure and inform
the applicant accordingly.

5.
Each Member State in which an application has been
submitted in accordance with paragraph 1 shall adopt a
decision in conformity with the approved assessment
report, the summary of product characteristics and the
labelling and package leaflet as approved, within 30 days
after acknowledgement of the agreement.

Article 29

1.
If, within the period laid down in Article 28(4), a
Member State cannot approve the assessment report, the
summary of product characteristics, the labelling and the
package leaflet on the grounds of potential serious risk to
public health,
it shall give a detailed exposition of the
reasons for its position to the reference Member State, to
the other Member States concerned and to the applicant.
The points of disagreement shall be forthwith referred to
the coordination group.

Guidelines to be adopted by the Commission shall

2.
define a potential serious risk to public health.

to reach agreement on the action to be taken. They shall
allow the applicant the opportunity to make his point of
view known orally or in writing. If, within 60 days of the
communication of the points of disagreement, the Member
States reach an agreement, the reference Member State
shall
record the agreement, close the procedure and
inform the applicant accordingly. Article 28(5) shall apply.

If

the Member States fail

to reach an agreement
4.
within the 60-day period laid down in paragraph 3, the
Agency shall be immediately informed, with a view to the
application of the procedure under Articles 32, 33 and 34.
The Agency shall be provided with a detailed statement of
the matters on which the Member States have been unable
to reach agreement and the reasons for their disagreement.
A copy shall be forwarded to the applicant.

As soon as the applicant is informed that the matter
5.
has been referred to the Agency, he shall
forthwith
forward to the Agency a copy of the information and
subparagraph of
documents
Article 28(1).

referred to in the first

6.
In the circumstances referred to in paragraph 4,
Member States that have approved the assessment report,
the draft summary of product characteristics and the
labelling and package leaflet of
the reference Member
State may, at the request of the applicant, authorise the
medicinal product without waiting for the outcome of the
procedure laid down in Article 32.
the
authorisation granted shall be without prejudice to the
outcome of that procedure.

In that event,

Article 30

If two or more applications submitted in accordance
1.
with Articles 8, 10, 10a, 10b, 10c and 11 have been made
for marketing authorisation for a particular medicinal
product, and if Member States have adopted divergent
decisions concerning the authorisation of the medicinal
product or its suspension or revocation, a Member State,
the Commission or the applicant or the marketing auth-
orisation holder may refer the matter to the Committee for
Medicinal Products for Human Use, hereinafter referred to
as “the Committee”, for the application of the procedure
laid down in Articles 32, 33 and 34.

2.
In order to promote harmonisation of authorisations
for medicinal products authorised in the Community,
Member States shall, each year,
forward to the coor-
dination group a list of medicinal products for which a
harmonised summary of product characteristics should be
drawn up.

3. Within the coordination group, all Member States
referred to in paragraph 1 shall use their best endeavours

The coordination group shall lay down a list taking into
account the proposals from all Member States and shall
forward this list to the Commission.

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The Commission or a Member State, in agreement with
the Agency and taking into account the views of interested
parties, may refer these products to the Committee in
accordance with paragraph 1.

Before issuing its opinion,

the Committee shall
3.
provide the applicant or
the marketing authorisation
holder with an opportunity to present written or oral
explanations within a time limit which it shall specify.

Article 31

the Commission or

The Member States or

1.
the
applicant or the marketing authorisation holder shall, in
specific cases where the interests of the Community are
involved, refer the matter to the Committee for application
of the procedure laid down in Articles 32, 33 and 34
before any decision is
for a
marketing authorisation or on the suspension or revo-
cation of an authorisation, or on any other variation to
the terms of a marketing authorisation which appears
necessary, in particular to take account of the information
collected in accordance with Title IX.

reached on a request

The Member State concerned or the Commission shall
clearly identify the question which is referred to the
inform the
Committee
applicant or the marketing authorisation holder.

consideration and shall

for

The Member States and the applicant or the marketing
authorisation holder shall supply the Committee with all
available information relating to the matter in question.

2. Where the referral
to the Committee concerns a
range of medicinal products or a therapeutic class, the
Agency may limit the procedure to certain specific parts
of the authorisation.

In that event, Article 35 shall apply to those medicinal
products only if they were covered by the authorisation
procedures referred to in this Chapter.

Article 32

1. When reference is made to the procedure laid down
in this Article, the Committee shall consider the matter
concerned and shall issue a reasoned opinion within 60
days of the date on which the matter was referred to it.

in cases

submitted to the Committee

However,
in
accordance with Articles 30 and 31, this period may be
extended by the Committee for a further period of up to
90 days, taking into account the views of the applicants or
the marketing authorisation holders concerned.

In an emergency, and on a proposal from its Chairman,
the Committee may agree to a shorter deadline.

In order to consider the matter, the Committee shall
2.
appoint one of its members to act as rapporteur. The
Committee may also appoint individual experts to advise
it on specific questions. When appointing experts,
the
Committee
tasks and specify the
time-limit for the completion of these tasks.

shall define

their

The opinion of the Committee shall be accompanied by a
draft summary of product characteristics for the product
and a draft text of the labelling and package leaflet.

If necessary,
the Committee may call upon any other
person to provide information relating to the matter
before it.

The Committee may suspend the time-limits referred to in
paragraph 1 in order
the
marketing authorisation holder to prepare explanations.

to allow the applicant or

4.
The Agency shall forthwith inform the applicant or
the marketing authorisation holder where the opinion of
the Committee is that:

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

isation; or

(b) the summary of the product characteristics proposed
by the applicant or the marketing authorisation holder
in accordance with Article 11 should be amended; or

(c) the authorisation should be granted subject to certain
conditions, in view of conditions considered essential
for the safe and effective use of the medicinal product
including pharmacovigilance; or

(d) a marketing authorisation should be suspended, varied

or revoked.

Within 15 days after receipt of the opinion, the applicant
or the marketing authorisation holder may notify the
Agency in writing of his intention to request a re-exam-
ination of the opinion. In that case, he shall forward to the
Agency the detailed grounds for the request within 60
days after receipt of the opinion.

Within 60 days following receipt of the grounds for the
request, the Committee shall re-examine its opinion in
accordance with the fourth subparagraph of Article 62(1)
of Regulation (EC) No 726/2004. The reasons for the
conclusion reached shall be annexed to the assessment
report referred to in paragraph 5 of this Article.

5. Within 15 days after its adoption, the Agency shall
forward the final opinion of the Committee to the Member
States, to the Commission and to the applicant or the
marketing authorisation holder,
together with a report
describing the assessment of the medicinal product and
stating the reasons for its conclusions.

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In the event of an opinion in favour of granting or main-
taining an authorisation to place the medicinal product
concerned on the market, the following documents shall
be annexed to the opinion:

(c) Member States shall have the option of submitting a
written request that the draft Decision be discussed in
a plenary meeting of the Standing Committee.

(a) a draft summary of

the product characteristics, as

referred to in Article 11;

(b) any conditions affecting the authorisation within the

meaning of paragraph 4(c);

(c) details of any recommended conditions or restrictions
with regard to the safe and effective use of
the
medicinal product;

(d) the proposed text of the labelling and leaflet.’

27) Article 33 shall be amended as follows:

(a)

in the first paragraph, ‘30 days’ shall be replaced by ‘15
days’;

(b) in the second paragraph, ‘Article 32(5)(a) and (b)’ shall
be replaced by ‘Article 32(5), second subparagraph’;

(c)

in the fourth paragraph, the words ‘or the marketing
authorisation holder’ shall be added after the word
‘applicant’;

28) Article 34 shall be replaced by the following:

‘Article 34

The Commission shall

1.
take a final decision in
accordance with, and within 15 days after the end of,
the procedure referred to in Article 121(3).

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

The provisions necessary for the implementation of this
paragraph shall be adopted by the Commission in
accordance with the procedure referred to in Article
121(2).

States

The decision as referred to in paragraph 1 shall be
3.
addressed to all Member
and reported for
information to the marketing authorisation holder or
applicant. The
the
concerned Member
reference Member State shall either grant or revoke the
marketing authorisation, or vary its terms as necessary to
comply with the decision within 30 days following its
notification, and they shall refer to it. They shall inform
the Commission and the Agency accordingly.’;

States

and

29) the third subparagraph of Article 35(1) shall be deleted;

30) in Article 38, paragraph 2 shall be replaced by the

following:

At

least every ten years

the Commission shall
‘2.
publish a report on the experience acquired on the basis
of
the procedures described in this Chapter and shall
propose any amendments which may be necessary to
improve those procedures. The Commission shall submit
to the European Parliament and to the
this
Council.’;

report

The rules of procedure of the Standing Committee
2.
established by Article 121(1) shall be adjusted to take
account of
this
Chapter.

incumbent upon it under

the tasks

31) Article 39 shall be replaced by the following:

‘Article 39

Those adjustments shall entail the following provisions:

(a) except in cases referred to in the third paragraph of
Article 33, the opinion of the Standing Committee
shall be given in writing;

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

Article 29(4), (5) and (6) and Articles 30 to 34 shall not
apply to the homeopathic medicinal products referred to
in Article 14.

Articles 28 to 34 shall not apply to the homeopathic
medicinal products referred to in Article 16(2).’;

32) the following paragraph shall be added to Article 40:

‘4.
The Member States shall forward to the Agency a
copy of the authorisation referred to in paragraph 1. The
Agency shall enter that information on the Community
database referred to in Article 111(6).’;

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33) in Article 46, point (f) shall be replaced by the following:

39) in Article 51(1), point

(b)

shall be replaced by the

following:

‘(f)

to comply with the principles and guidelines of good
manufacturing practice for medicinal products and to
use as starting materials only active substances, which
have been manufactured in accordance with the
detailed guidelines on good manufacturing practice
for starting materials.

shall

also be

applicable

This point
to certain
excipients, the list of which as well as the specific
conditions of application shall be established by a
Directive adopted by the Commission in accordance
with the procedure referred to in Article 121(2).’;

34) the following Article shall be inserted:

‘Article 46a

1.
For the purposes of this Directive, manufacture of
active substances used as starting materials shall include
both total and partial manufacture or import of an active
substance used as a starting material as defined in Part I,
point 3.2.1.1 (b) Annex I, and the various processes of
dividing up, packaging or presentation prior to its incor-
poration into a medicinal product, including repackaging
or re-labelling, such as are carried out by a distributor of
starting materials.

2.
Any amendments necessary to adapt paragraph 1 to
new scientific and technical developments shall be laid
down in accordance with the procedure referred to in
Article 121(2).’;

‘(b)

in the case of medicinal products coming from third
irrespective of whether the product has
countries,
been manufactured in the Community,
that each
production batch has undergone in a Member State
a full qualitative analysis, a quantitative analysis of at
least all the active substances and all the other tests or
checks necessary to ensure the quality of medicinal
products in accordance with the requirements of the
marketing authorisation.’;

40) Article 54 shall be amended as follows:

(a) point (a) shall be replaced by the following:

‘(a)

the name of the medicinal product followed by its
strength and pharmaceutical form, and,
if appro-
priate, whether it is intended for babies, children
or adults; where the product contains up to three
active substances, the international non-proprietary
name (INN) shall be included, or, if one does not
exist, the common name;’;

(b) in point (d),
guidance’;

‘guidelines’ shall be replaced by ‘detailed

(c) Point (e) shall be replaced by the following:

‘(e)

the method of administration and, if necessary, the
route of administration. Space shall be provided
for the prescribed dose to be indicated.’;

(d) point (f) shall be replaced by the following:

35) in Article 47, the following paragraphs shall be added:

‘(f) a special warning that the medicinal product must
be stored out of the reach and sight of children;’;

‘The principles of good manufacturing practice for active
substances used as starting materials referred to in point (f)
of Article 46 shall be adopted in the form of detailed
guidelines.

The Commission shall also publish guidelines on the form
and content of the authorisation referred to in Article
40(1), on the reports referred to in Article 111(3) and
on the form and content of the certificate of good manu-
facturing practice referred to in Article 111(5).’;

36) in Article 49(1), ‘minimum’ shall be deleted;

37) in Article 49(2), fourth subparagraph, first indent ‘Applied
physics’ shall be replaced by ‘Experimental physics’;

(e) Point (j) shall be replaced by the following:

‘(j) specific precautions relating to the disposal of
unused medicinal products or waste derived from
medicinal products, where appropriate, as well as
reference to any appropriate collection system in
place;’;

(f) point (k) shall be replaced by the following:

‘(k)

the name and address of the marketing author-
isation holder and, where applicable,
the name
of the representative appointed by the holder to
represent him;’;

(g) point (n) shall be replaced by the following:

38) in Article 50(1), ‘in the State concerned’ shall be replaced

‘(n)

by ‘within the Community’;

the

in
products, instructions for use’;

case

of

non-prescription medicinal

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41) Article 55 shall be amended as follows:

(b) the therapeutic indications;

(a)

in paragraph 1,
replaced by ‘in Article 54’;

‘in Articles 54 and 62’ shall be

(c) a list of information which is necessary before the

medicinal product is taken:

(b) the first indent of paragraph 2 shall be replaced by the

following:

(i) contra-indications;

‘— the name of the medicinal product as laid down in

point (a) of Article 54,’;

(c) the first indent of paragraph 3 shall be replaced by the

following:

(ii) appropriate precautions for use;

(iii) forms of interaction with other medicinal products
interaction (e.g. alcohol,
and other
tobacco, foodstuffs) which may affect the action
of the medicinal product;

forms of

‘— the name of the medicinal product as laid down in
point (a) of Article 54 and, if necessary, the route
of administration,’;

(iv) special warnings;

42) the following Article shall be inserted:

‘Article 56a

and in particular:

(i) the dosage,

(d) the necessary and usual

instructions for proper use,

the medicinal product, as referred to in
The name of
Article 54, point (a) must also be expressed in Braille
format on the packaging. The marketing authorisation
holder shall ensure that the package information leaflet
is made available on request from patients' organisations
in formats appropriate for the blind and partially-sighted.’

43) in Article 57, the following paragraph shall be added:

‘For medicinal products authorised under Regulation (EC)
No 726/2004, Member States shall, when applying this
Article, observe the detailed guidance referred to in
Article 65 of this Directive.’;

44) Article 59 shall be replaced by the following:

‘Article 59

1.
The package leaflet shall be drawn up in accordance
with the summary of the product characteristics; it shall
include, in the following order:

(a)

for the identification of the medicinal product:

(i) the name of the medicinal product followed by its
strength and pharmaceutical form, and, if appro-
priate, whether it is intended for babies, children or
adults. The common name shall be included where
the product contains only one active substance and
if its name is an invented name;

(ii) the pharmaco-therapeutic group or type of activity
in terms easily comprehensible for the patient;

(ii) the method and, if necessary, route of adminis-

tration;

(iii) the frequency of administration, specifying if
necessary the appropriate time at which the
medicinal product may or must be administered;

and, as appropriate, depending on the nature of the
product:

(iv) the duration of treatment, where it should be

limited;

(v) the action to be taken in case of an overdose
(such as symptoms, emergency procedures);

(vi) what to do when one or more doses have not

been taken;

(vii) indication, if necessary, of the risk of withdrawal

effects;

(viii) a specific recommendation to consult the doctor
or the pharmacist, as appropriate, for any clari-
fication on the use of the product;

(e) a description of the adverse reactions which may occur
under normal use of the medicinal product and,
if
necessary, the action to be taken in such a case; the
patient should be expressly asked to communicate any
adverse reaction which is not mentioned in the
package leaflet to his doctor or pharmacist;

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(f) a reference to the expiry date indicated on the label,

45) Article 61(1) shall be replaced by the following:

with:

(i) a warning against using the product after that

date;

(ii) where appropriate, special storage precautions;

(iii) if necessary, a warning concerning certain visible

signs of deterioration;

(iv) the

full

qualitative

composition (in

active
substances and excipients) and the quantitative
composition in active substances, using common
names,
the medicinal
product;

for each presentation of

‘1.
One or more mock-ups of the outer packaging and
the immediate packaging of a medicinal product, together
with the draft package leaflet, shall be submitted to the
authorities competent for authorising marketing when the
marketing authorisation is
results of
assessments
in cooperation with target
patient groups shall also be provided to the competent
authority.’;

requested. The

carried out

46) in Article 61(4),

‘or as appropriate’ shall be replaced by

‘and’;

47) in Article 62,

‘for health education’ shall be replaced by

‘for the patient’;

48) Article 63 shall be amended as follows:

(v) for each presentation of the product, the phar-
maceutical form and content in weight, volume
or units of dosage;

(a) the

following

subparagraph shall be

added to

paragraph 1:

(vi) the name and address of the marketing author-
isation holder and, where applicable, the name of
his appointed representatives
in the Member
States;

‘In the case of certain orphan medicinal products, the
listed in Article 54 may, on reasoned
particulars
request, appear in only one of the official
languages
of the Community.’;

(vii) the name and address of the manufacturer;

(b) paragraphs 2 and 3 shall be replaced by the following:

(g) where

the medicinal product

in
accordance with Articles 28 to 39 under different
names in the Member States concerned, a list of the
names authorised in each Member State;

authorised

is

(h) the date on which the package leaflet was last revised.

2.

The list set out in point (c) of paragraph 1 shall:

(a) take into account the particular condition of certain
categories of users (children, pregnant or breastfeeding
women, the elderly, persons with specific pathological
conditions);

(b) mention, if appropriate, possible effects on the ability

to drive vehicles or to operate machinery;

(c)

list those excipients knowledge of which is important
for the safe and effective use of the medicinal product
and which are included in the detailed guidance
published pursuant to Article 65.

The package leaflet shall reflect the results of consul-
is

3.
tations with target patient groups to ensure that
legible, clear and easy to use.’;

it

‘2.
The package leaflet must be written and designed
to be clear and understandable, enabling the users to
act appropriately, when necessary with the help of
health professionals. The package leaflet must be
clearly legible in the official language or languages of
the Member State in which the medicinal product is
placed on the market.

from being printed in several

The first subparagraph shall not prevent the package
leaflet
languages,
provided that the same information is given in all
the languages used.

3. When the product is not intended to be delivered
directly to the patient, the competent authorities may
grant an exemption to the obligation that certain
particulars should appear on the labelling and in the
package leaflet and that the leaflet must be in the
official language or languages of the Member State in
which the product is placed on the market.’;

49) Article 65 shall be replaced by the following:

‘Article 65

In consultation with the Member States and the parties
concerned, the Commission shall draw up and publish
detailed guidance concerning in particular:

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30.4.2004

(a) the wording of certain special warnings for certain

53) Article 74 shall be replaced by the following:

categories of medicinal products;

‘Article 74

(b) the

particular

information

needs

relating

to

non-prescription medicinal products;

(c) the legibility of particulars on the labelling and

package leaflet;

the
When new facts are brought
competent authorities shall examine and, as appropriate,
amend the classification of a medicinal product by
applying the criteria listed in Article 71.’;

to their attention,

54) the following Article shall be inserted:

(d) the methods for the identification and authentication

of medicinal products;

‘Article 74a

(e) the list of excipients which must

feature on the
labelling of medicinal products and the way in which
these excipients must be indicated;

(f) harmonised provisions

for

the implementation of

Article 57.’;

50) Article 66(3), fourth indent shall be replaced by:

Where a change of classification of a medicinal product
has been authorised on the basis of significant pre-clinical
tests or clinical trials, the competent authority shall not
refer to the results of those tests or trials when examining
an application by another applicant
for or holder of
marketing authorisation for a change of classification of
the same substance for one year after the initial change
was authorised.’;

55) Article 76 shall be amended as follows:

(a) the existing text shall become paragraph 1;

‘— the name and address of the manufacturer,’;

(b) the following paragraphs shall be added:

51) Article 69(1) shall be amended as follows:

(a) the first indent shall be replaced by the following:

‘— the scientific name of the stock or stocks followed
by the degree of dilution, making use of
the
symbols of the pharmacopoeia used in accordance
with Article 1(5);
if the homeopathic medicinal
product is composed of two or more stocks, the
scientific names of the stocks on the labelling may
be supplemented by an invented name’;

(b) the last indent shall be replaced by the following:

‘2.
In the case of wholesale distribution and storage,
medicinal products shall be covered by a marketing
authorisation granted pursuant
to Regulation (EC)
No 726/2004 or by the competent authorities of a
Member State in accordance with this Directive.

3.
Any distributor, not being the marketing author-
isation holder, who imports a product from another
Member State shall notify the marketing authorisation
holder and the competent authority in the Member
State to which the product will be imported of his
intention to import it. In the case of products which
have not been granted an authorisation pursuant to
Regulation (EC) No 726/2004, the notification to the
competent authority shall be without prejudice to
additional procedures provided for in the legislation
of that Member State.’;

‘— a warning advising the user to consult a doctor if

the symptoms persist’;

56) the second indent of point
replaced by the following:

(e) of Article 80 shall be

52) Article 70(2) shall be amended as follows:

‘— name of the medicinal product,’;

(a) point (a) shall be replaced by the following:

‘(a) medicinal products on medical prescription for

renewable or non-renewable delivery;’;

(b) point (c) shall be replaced by the following:

‘(c) medicinal

products

“restricted” medical
on
prescription, reserved for use in certain specialised
areas.’;

57) Article 81 shall be replaced by the following:

‘Article 81

With regard to the supply of medicinal products to phar-
macists and persons authorised or entitled to supply
medicinal products to the public, Member States shall
not impose upon the holder of a distribution authorisation
which has been granted by another Member State any
obligation,
in particular public service obligations, more
stringent than those they impose on persons whom they
have
in equivalent
activities.

themselves authorised to engage

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The holder of a marketing authorisation for a medicinal
product and the distributors of the said medicinal product
actually placed on the market in a Member State shall,
within the limits of their responsibilities, ensure appro-
priate and continued supplies of that medicinal product
to
supply
persons
medicinal products so that the needs of patients in the
Member State in question are covered.

pharmacies

authorised

and

to

The arrangements for implementing this Article should,
moreover, be justified on grounds of public health
protection and be proportionate
in relation to the
in compliance with the
objective of such protection,
free
concerning the
Treaty rules, particularly those
movement of goods and competition.’;

58) in Article 82, the second indent of the first paragraph shall

be replaced by the following:

‘— the name and pharmaceutical form of the medicinal

product,’;

59) Article 84 shall be replaced by the following:

‘Article 84

The Commission shall publish guidelines on good
distribution practice. To this end,
the
Committee for Medicinal Products for Human Use and
the Pharmaceutical Committee established by Council
Decision 75/320/EEC (*).
___________
(*) OJ L 147, 9.6.1975, p. 23.’;

it shall consult

60) Article 85 shall be replaced by the following:

‘Article 85

This Title shall apply to homeopathic medicinal products.’;

61) the fourth indent of Article 86(2) shall be replaced by the

following:

‘— information relating to human health or diseases,
provided that there is no reference, even indirect, to
medicinal products’;

62) Article 88 shall be replaced by the following:

(b) contain substances defined as psychotropic or narcotic
the United
convention,

by international
such as
Nations Conventions of 1961 and 1971.

2. Medicinal products may be advertised to the general
public which, by virtue of their composition and purpose,
are intended and designed for use without the intervention
of a medical practitioner for diagnostic purposes or for the
prescription or monitoring of treatment, with the advice of
the pharmacist, if necessary.

3. Member States shall be entitled to ban, on their
territory, advertising to the general public of medicinal
products the cost of which may be reimbursed.

4.
The prohibition contained in paragraph 1 shall not
apply to vaccination campaigns carried out by the industry
and approved by the competent authorities of the Member
States.

The prohibition referred to in paragraph 1 shall
to Article 14 of Directive

5.
apply without prejudice
89/552/EEC.

6. Member States shall prohibit the direct distribution
of medicinal products to the public by the industry for
promotional purposes.’;

63) the following text is inserted after Article 88:

‘TITLE VIIIa

INFORMATION AND ADVERTISING

Article 88a

the Commission shall,

Within three years of the entry into force of Directive
2004/726/EC,
following consul-
tations with patients'
and consumers' organisations,
doctors' and pharmacists' organisations, Member States
and other
to the European
Parliament and the Council a report on current practice
with regard to information provision — particularly on the
Internet — and its risks and benefits for patients.

interested parties, present

the above data,

if appropriate, put

the Commission
Following analysis of
shall,
forward proposals setting out
an information strategy to ensure good-quality, objective,
information on medicinal
reliable and non-promotional
products and other
the
question of the information source's liability.’;

treatments and shall address

‘Article 88

64) Article 89 shall be amended as follows:

1. Member States shall prohibit the advertising to the
general public of medicinal products which:

(a) the first indent of point (b) of paragraph 1 shall be

replaced by the following:

(a) are

available on medical prescription only,

in

accordance with Title VI;

(does not affect the English version);

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Official Journal of the European Union

30.4.2004

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

71) Article 100 shall be replaced by the following:

‘2. Member States may decide that the advertising of
to the general public may,
a medicinal product
notwithstanding paragraph 1, include only the name
international
of
product
non-proprietary name, where
the
exists, or
trademark if it is intended solely as a reminder.’;

the medicinal

or
this

its

65) in Article 90, point (l) shall be deleted;

‘Article 100

the homeopathic medicinal products
Advertising of
referred to in Article 14(1)
to the
provisions of this Title with the exception of Article 87(1).

shall be subject

However, only the information specified in Article 69(1)
may be used in the advertising of
such medicinal
products.’;

66) in Article 91, paragraph 2 shall be replaced by the

following:

72) in Article 101, the second paragraph shall be replaced by

the following:

‘2. Member States may decide that the advertising of a
medicinal product
to persons qualified to prescribe or
supply such products may, notwithstanding paragraph 1,
include only the name of the medicinal product, or its
international non-proprietary name, where this exists, or
the trademark, if it is intended solely as a reminder.’;

‘The Member States may impose specific requirements on
doctors and other health-care professionals in respect of
the reporting of suspected serious or unexpected adverse
reactions.’;

73) Article 102 shall be replaced by the following:

67) Article 94(2) shall be replaced by the following:

‘Article 102

‘2.
Hospitality at sales promotion events shall always be
strictly limited to their main purpose and must not be
extended to persons other than health-care professionals.’;

68) Article 95 shall be replaced by the following:

‘Article 95

The provisions of Article 94(1) shall not prevent hospi-
tality being offered, directly or indirectly, at events for
purely professional and scientific purposes; such hospi-
tality shall always be strictly limited to the main scientific
objective of the event; it must not be extended to persons
other than health-care professionals.’;

69) point

(d) of Article 96(1)

shall be replaced by the

following:

decisions

regulatory

concerning

to ensure the adoption of appropriate and
In order
harmonised
the
medicinal products authorised within the Community,
having regard to information obtained about adverse
reactions to medicinal products under normal conditions
of use,
a phar-
macovigilance system. This
system shall be used to
collect information useful in the surveillance of medicinal
products, with particular reference to adverse reactions in
human beings, and to evaluate such information scien-
tifically.

the Member States

shall operate

shall ensure that

suitable information
Member States
collected within this
system is communicated to the
other Member States and the Agency. The information
shall be recorded in the database referred to in point (l)
of the second subparagraph of Article 57(1) of Regulation
(EC) No 726/2004 and shall be permanently accessible to
all Member States and without delay to the public.

This system shall also take into account any available
information on misuse and abuse of medicinal products
which may have an impact on the evaluation of their
benefits and risks.’;

‘(d) each sample shall be no larger than the smallest pres-

entation on the market;’;

74) the following Article shall be inserted:

70) in Article 98, the following paragraph shall be added:

‘Article 102a

States

The Member

‘3.
the
co-promotion of a medicinal product by the holder of
the marketing authorisation and one or more companies
nominated by him.’;

prohibit

shall

not

The management of funds intended for activities connected
with pharmacovigilance, the operation of communication
networks and market surveillance shall be under
the
permanent control of the competent authorities in order
to guarantee their independence.’;

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75) in Article 103,

the introductory phrase of
paragraph shall be replaced by the following:

the second

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

76) Articles 104 to 107 shall be replaced by the following:

‘Article 104

The marketing authorisation holder shall be required
1.
to maintain detailed records of all suspected adverse
reactions occurring either in the Community or in a
third country.

Save in exceptional circumstances, these reactions shall be
communicated electronically in the form of a report in
accordance with the guidelines
referred to in Article
106(1).

2.
The marketing authorisation holder shall be required
to record all suspected serious adverse reactions which are
brought to his attention by a health-care professional and
to report them promptly to the competent authority of the
Member State on whose territory the incident occurred,
and no later than 15 days following the receipt of the
information.

3.
The marketing authorisation holder shall be required
to record and report all other suspected serious adverse
reactions which meet
in
the
referred to in Article
accordance with the guidelines
106(1), of which he can reasonably be expected to have
knowledge, promptly to the competent authority of the
Member State in whose territory the incident occurred,
and no later than 15 days following the receipt of the
information.

notification

criteria

4.
The marketing authorisation holder 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 in accordance with the
so that
guidelines
the
referred to in Article 106(1),
Agency and the competent authorities of
the Member
States in which the medicinal product is authorised are
informed of them, and no later than 15 days following
the receipt of the information.

By way of derogation from paragraphs 2, 3 and 4, in
5.
the case of medicinal products which are covered by
the
Directive 87/22/EEC or which have qualified for
procedures laid down in Articles 28 and 29 of
this
Directive or which have been the subject of the procedures
under Articles 32, 33 and 34 of
the
marketing authorisation holder shall also ensure that all
suspected serious adverse reactions occurring in the
Community are reported in such a way as to be accessible
to any competent
to the reference Member State or

this Directive,

acting

State. The
authority
reference Member State shall assume the responsibility of
analysing and monitoring such adverse reactions.

reference Member

as

6.
Unless other requirements have been laid down as a
condition for the granting of the marketing authorisation,
or subsequently as indicated in the guidelines referred to in
Article 106(1), reports of all adverse reactions shall be
submitted to the competent authorities in the form of a
periodic safety update report, immediately upon request or
at least every six months after authorisation and 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 market and once a year for the
following two years. Thereafter,
shall be
submitted at three-yearly intervals, or immediately upon
request.

the reports

The periodic safety update reports shall include a scientific
evaluation of
the medicinal
the risk-benefit balance of
product.

7.
The Commission may lay down provisions to amend
paragraph 6 in view of experience gained through its
operation. The Commission shall adopt the provisions in
accordance with the procedure referred to in Article
121(2).

Following the granting of a marketing authorisation,
8.
the marketing authorisation holder may request
the
amendment of the periods referred to in paragraph 6 in
accordance with the procedure laid down by Commission
Regulation (EC) No 1084/2003 (*).

9.
The holder of a marketing authorisation may not
communicate information relating to pharmacovigilance
concerns to the general public in relation to its authorised
medicinal product without giving prior or simultaneous
notification to the competent authority.

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

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

these obligations

subject

is

Article 105

The Agency, in collaboration with the Member States
1.
and the Commission,
set up a data-processing
network to facilitate the exchange of pharmacovigilance
information regarding medicinal products marketed in
the Community in order to allow all competent authorities
to share the information at the same time.

shall

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2. Making use of the network referred to in paragraph
1, Member States shall ensure that reports of suspected
serious adverse reactions that have taken place on their
territory are promptly made available to the Agency and
the other Member States, and in any case within 15 days
after their notification at the latest.

The Member States shall ensure that

3.
reports of
suspected serious adverse reactions that have taken place
on their territory are promptly made available to the
marketing authorisation holder, and in any case within
15 days after their notification at the latest.

Article 106

the

within

Community,

In order to facilitate the exchange of information on
1.
the
pharmacovigilance
Commission, after consulting the Agency,
the Member
States and interested parties, shall draw up guidelines on
the collection, verification and presentation of adverse
reaction reports, including technical requirements for elec-
tronic exchange of pharmacovigilance information in
accordance with internationally agreed formats, and shall
publish a reference to an internationally agreed medical
terminology.

Acting in accordance with the guidelines, marketing auth-
orisation holders shall use internationally agreed medical
terminology for the reporting of adverse reactions.

These guidelines shall be published in Volume 9 of The
in the European
Rules governing Medicinal Products
international
Community and shall
harmonisation work carried out
in the field of phar-
macovigilance.

take account of

For the interpretation of the definitions referred to in
2.
points (11) to (16) of Article 1 and of the principles
outlined in this Title, the marketing authorisation holder
and the competent authorities shall follow the guidelines
referred to in paragraph 1.

Article 107

the evaluation of phar-
1. Where, as a result of
macovigilance data, a Member State considers that a
marketing authorisation should be suspended, revoked or
varied in accordance with the guidelines referred to in
Article 106(1), it shall forthwith inform the Agency, the
other Member States and the marketing authorisation
holder.

2. Where urgent action to protect public health is
necessary, the Member State concerned may suspend the
marketing authorisation of a medicinal product, provided
that the Agency, the Commission and the other Member
States are informed no later than the following working
day.

the

first

subparagraph of

informed in accordance with
When the Agency is
paragraph 1 in relation to suspensions and revocation,
or
the
Committee shall prepare an opinion within a time-frame
to be determined depending on the urgency of the matter.
In relation to variations, the Committee may upon request
from a Member State prepare an opinion.

this paragraph,

Acting on the basis of this opinion, the Commission may
request all Member States in which the product is being
marketed to take temporary measures immediately.

The final measures shall be adopted in accordance with the
procedure referred to in Article 121(3).

___________
(*) OJ L 159, 27.6.2003, p. 1.’;

77) Article 111 shall be amended as follows:

(a) paragraph 1 shall be replaced by the following:

ensure, by means of

The competent authority of the Member State
‘1.
concerned shall
repeated
inspections, and if necessary unannounced inspections,
an Official
and, where
laboratory
Medicines Control
tests on
designated for that purpose to carry out
samples,
governing
the
medicinal products are complied with.

asking
or

requirements

appropriate,

Laboratory

legal

that

by

a

The competent authority may also carry out unan-
nounced inspections at the premises of manufacturers
of active substances used as starting materials, or at the
premises of marketing authorisation holders whenever
there are grounds for suspecting
it considers that
non-compliance with the principles and guidelines of
good manufacturing practice referred to in Article 47.
These inspections may also be carried out at
the
request of a Member State, the Commission or the
Agency.

In order to verify whether the data submitted in order
to obtain a conformity certificate comply with the
monographs of the European Pharmacopoeia, the stan-
dardisation body of the nomenclatures and the quality
norms within the meaning of the Convention relating
to the elaboration of the European Pharmacopoeia (*)
(European Directorate for the quality of Medicinal
Products) may ask the Commission or the Agency to
request such an inspection when the starting material
concerned is the subject of a European Pharmacopoeia
monograph.

competent

authority of

the Member State
The
concerned may carry out
starting
material manufacturers at the specific request of the
manufacturer himself.

inspections of

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Such inspections shall be carried out by officials repre-
senting
authority who shall be
empowered to:

competent

the

(a)

the manufacturing or commercial estab-
inspect
lishments of manufacturers of medicinal products
or of active substances used as starting materials,
and any laboratories employed by the holder of the
manufacturing authorisation to carry out checks
pursuant to Article 20;

(b) take samples including with a view to independent
tests being carried out by an Official Medicines
Control Laboratory or a laboratory designated for
that purpose by a Member State;

(c) examine any documents relating to the object of
the inspection, subject to the provisions in force in
the Member States on 21 May 1975 placing
restrictions on these powers with regard to the
description of the manufacturing method;

(d) inspect the premises, records and documents of
marketing authorisation holders or any firms
employed by the marketing authorisation holder
to perform the activities described in Title IX,
and in particular Articles 103 and 104.

___________
(*) OJ L 158, 25.6.1994, p. 19.’;

(b) paragraph 3 shall be replaced by the following:

After

every

referred

to in
inspection as
‘3.
paragraph 1, the officials representing the competent
authority shall report on whether the manufacturer
complies with the principles and guidelines of good
manufacturing practice laid down in Article 47 or,
where appropriate, with the requirements laid down
in Articles 101 to 108. The content of such reports
shall be
communicated to the manufacturer or
marketing authorisation holder who has undergone
the inspection.’;

(c) the following paragraphs shall be added:

‘4. Without prejudice to any arrangements which
may have been concluded between the Community
and third countries, a Member State, the Commission
or the Agency may require a manufacturer established
to an inspection as
in a third country to submit
referred to in paragraph 1.

5. Within 90 days of an inspection as referred to in
paragraph 1, a certificate of good manufacturing
practice shall be issued to a manufacturer
the
if
outcome of
the manu-
the inspection shows that
facturer complies with the principles and guidelines
of good manufacturing practice as provided for by
Community legislation.

If inspections are performed as part of the certification
procedure for the monographs of the European Phar-
macopoeia, a certificate shall be drawn up.

6. Member States shall enter the certificates of good
manufacturing practice which they
in a
Community database managed by the Agency on
behalf of the Community.

issue

7.
If the outcome of the inspection as referred to in
paragraph 1 is that the manufacturer does not comply
with the principles and guidelines of good manufac-
turing practice as provided for by Community legis-
lation,
entered in the
Community database as referred to in paragraph 6.’;

information shall be

the

78) in Article 114(1) and (2), the terms ‘by a State laboratory
or a laboratory designated for that purpose’ shall be
replaced by the terms ‘by an Official Medicines Control
Laboratory or a laboratory that a Member State has
designated for that purpose’;

79) Article 116 shall be replaced by the following:

‘Article 116

The competent authorities shall suspend, revoke, withdraw
or vary a marketing authorisation if the view is taken that
the product is harmful under normal conditions of use, or
that it lacks therapeutic efficacy, or that the risk-benefit
balance is not positive under the normal conditions of use,
or that its qualitative and quantitative composition is not
is
as declared. Therapeutic efficacy is lacking when it
concluded that
therapeutic results cannot be obtained
from the medicinal product.

also be

suspended,

An authorisation shall
revoked,
withdrawn or varied where the particulars supporting
the application as provided for in Article 8 or Articles
10, 10a, 10b, 10c and 11 are incorrect or have not
been amended in accordance with Article 23, or where
the controls referred to in Article 112 have not been
carried out.’;

80) Article 117(1) shall be replaced by the following:

‘1. Without prejudice to the measures provided for in
Article 116, Member States shall take all appropriate steps
to ensure that
is
prohibited and the medicinal product withdrawn from
the market, if the view is taken that:

the supply of the medicinal product

(a) the medicinal product
conditions of use; or

is harmful under normal

(b) it lacks therapeutic efficacy; or

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(c) the risk-benefit balance is not favourable under the

authorised conditions of use; or

(d) its qualitative and quantitative composition is not as

declared; or

(e) the controls on the medicinal product and/or on the
ingredients and the controls at an intermediate stage of
the manufacturing process have not been carried out
or if some other requirement or obligation relating to
the grant of the manufacturing authorisation has not
been fulfilled.’;

81) Article 119 shall be replaced by the following:

‘Article 119

The provisions of this Title shall apply to homeopathic
medicinal products.’;

82) Articles 121 and 122 shall be replaced by the following:

‘Article 121

1.
The Commission shall be assisted by the Standing
Committee on Medicinal Products for Human Use, here-
inafter called “the Standing Committee”,
in the task of
the directives on the
adapting to technical progress
removal of technical barriers to trade in the medicinal
products sector.

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.

The Standing Committee shall adopt its own rules of

4.
procedure which shall be made public.

Article 122

the

that

competent

1. Member States shall take all appropriate measures to
concerned
ensure
communicate to each other such information as is appro-
priate to guarantee that the requirements placed on the
authorisations referred to in Articles 40 and 77, on the
certificates
referred to in Article 111(5) or on the
marketing authorisations are fulfilled.

authorities

Upon

reasoned

shall
2.
forthwith communicate the reports referred to in Article
111(3) to the competent authorities of another Member
State.

request, Member

States

The conclusions reached in accordance with Article

3.
111(1) shall be valid throughout the Community.

However, in exceptional cases, if a Member State is unable,
relating to public health,
for
the
reasons
conclusions
an inspection under
following
reached
Article 111(1), that Member State shall forthwith inform
the Commission and the Agency. The Agency shall inform
the Member States concerned.

to accept

When the Commission is informed of these divergences of
it may, after consulting the Member States
opinion,
concerned, ask the inspector who performed the original
inspection to perform a new inspection; the inspector may
be accompanied by two other inspectors from Member
States which are not parties to the disagreement.’;

83) in Article 125, the third subparagraph shall be replaced by

the following:

‘Decisions to grant or revoke a marketing authorisation
shall be made publicly available.’;

84) the following Article shall be inserted:

‘Article 126a

In the absence of a marketing authorisation or of a
1.
pending application for a medicinal product authorised in
another Member State in accordance with this Directive, a
Member State may for justified public health reasons
said
the placing on the market of
authorise
medicinal product.

the

2. When a Member State avails itself of this possibility,
it shall adopt the necessary measures in order to ensure
that the requirements of this Directive are complied with,
in particular those referred to in Titles V, VI, VIII, IX and
XI.

Before granting such an authorisation a Member

3.
State shall:

(a) notify the marketing authorisation holder,

in the
Member State
in which the medicinal product
concerned is authorised, of the proposal to grant an
authorisation under
the
product concerned; and

this Article in respect of

(b) request the competent authority in that State to furnish
a copy of the assessment report referred to in Article
21(4) and of the marketing authorisation in force in
respect of the said medicinal product.

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L 136/57

authorised

of medicinal

The Commission shall set up a publicly accessible
4.
register
under
products
paragraph 1. Member States shall notify the Commission
if any medicinal product is authorised, or ceases to be
including the name or
authorised, under paragraph 1,
corporate name and permanent address of the author-
isation holder. The Commission shall amend the register
of medicinal products accordingly and make this register
available on their website.

No later than 30 April 2008, the Commission shall
5.
present a report
to the European Parliament and the
Council concerning the application of this provision with
a view to proposing any necessary amendments.’;

85) the following Article 126b is inserted:

‘Article 126b

In order to guarantee independence and transparency, the
Member States shall ensure that members of staff of the
competent authority responsible for granting authoris-
ations, rapporteurs and experts concerned with the auth-
orisation and surveillance of medicinal products have no
financial or other interests in the pharmaceutical industry
which could affect their impartiality. These persons shall
make an annual declaration of their financial interests.

the Member States shall ensure that

In addition,
the
competent authority makes publicly accessible its rules of
procedure and those of its committees, agendas for its
meetings and records of
its meetings, accompanied by
decisions
taken, details of votes and explanations of
votes, including minority opinions.’;

86) the following Article shall be inserted:

‘Article 127a

is

When a medicinal product
to be authorised in
accordance with Regulation (EC) No 726/2004 and the
Scientific Committee in its opinion refers to recommended
conditions or restrictions with regard to the safe and
effective use of the medicinal product as provided for in
Article 9(4)(c) of that Regulation, a decision addressed to
the Member States shall be adopted in accordance with the
procedure provided for in Articles 33 and 34 of
this
Directive, for the implementation of those conditions or
restrictions.’;

87) the following Article shall be inserted:

‘Article 127b

Member States shall ensure that appropriate collection
systems are in place for medicinal products that are
unused or have expired.’

Article 2

The periods of protection provided for in Article 1, point 8,
which amends Article 10(1) of Directive 2001/83/EC, shall not
apply to reference medicinal products for which an application
for authorisation has been submitted before the date of trans-
position referred to in Article 3 first paragraph.

Article 3

Member States shall bring into force the laws, regulations and
administrative provisions necessary to comply with this
than 30 October 2005. They shall
Directive no later
immediately inform the Commission thereof.

When Member States adopt these measures, they shall contain
a reference to this Directive or shall be accompanied by such a
reference on the occasion of their official publication. The
methods of making such reference shall be laid down by the
Member States.

Article 4

This Directive shall enter into force on the day of its publi-
cation in the Official Journal of the European Union.

Article 5

This Directive is addressed to the Member States.

Done at Strasbourg, 31 March 2004.

For the European Parliament

The President

P. COX

For the Council

The President

D. ROCHE