Opinion of the Economic and Social Committee on the 'Proposal for a European Parliament and Council Directive on the approximation of provisions laid down by law, regulation or administrative action relating to the implementation of Good Clinical Practice in the conduct of clinical trials on medicinal products for human use'
Date: 1998-01-28
Institutions: European Economic and Social Committee
Subjects: approximation of laws, market approval, pharmaceutical product, testing, therapeutics

30.3.98

EN

Official Journal of the European Communities

C 95/1

II

(Preparatory Acts)

ECONOMIC AND SOCIAL COMMITTEE

Opinion of the Economic and Social Committee on the ‘Proposal for a European Parliament
and Council Directive on the approximation of provisions laid down by law, regulation or
administrative action relating to the implementation of Good Clinical Practice in the conduct
of clinical trials on medicinal products for human use’ (1)

(98/C 95/01)

On 4 December 1997 the Council decided to consult the Economic and Social Committee,
under Article 100a of the Treaty establishing the European Community, on the above-mentioned
proposal.

The Section for Protection of the Environment, Public Health and Consumer Affairs, which
was responsible for preparing the Committee’s work on the subject, adopted its opinion on
6 January 1998. The rapporteur was Mr Colombo.

At its 351st plenary session (meeting of 28 January 1998), the Economic and Social Committee
adopted the following opinion by 82 votes to four, with one abstention.

1.

Introduction

The proposal is based on Article 100a. It is
1.1.
designed to align the principles and guidelines concerning
clinical trials of medicinal products for human use. The
aim is to reinforce existing practice and align procedures
for the commencement of clinical trials on human
subjects, through consistent application of the guidelines
of the International Conference on Harmonization
(ICH) (2).

The matter has been codified at Community
1.2.
level since 1990 in the European Union guideline on
Good Clinical Practice (GCP), and was harmonized
internationally in January 1997 by the ICH.

The GCP standards are used by the pharmaceuti-
1.3.
cal industry when it undertakes clinical trials with a
view to obtaining authorization to market a proprietary
medicinal product, or with a view to confirming the
therapeutic effect of proprietary products that have
already been authorized.

(1) OJ C 306, 8.10.1997, p. 9.
(2) International Conference on Harmonization of Technical
Requirements for Registration of Pharmaceuticals for
Human Use.

1.4.
The codified GCP guidelines only provide a
yardstick at present and are not applied uniformly in
the Member States, which have hitherto been responsible
for legislation in this area.

1.5.
This situation often causes serious delays in the
start of clinical trials, both because of the red tape
generated by differing procedures and the differences
between Member States’ requirements and practices.

1.6.
A uniform procedure is becoming increasingly
necessary in multi-centre clinical trials, so as to attain a
sufficient number of cases for the statistical validation
of the data collected.

1.7.
These are the main reasons why it is desirable to
convert the principles and guidelines into a binding piece
of EU legislation, so as to regulate an activity which
now involves a large number of trials centres, often in
various Member States. This procedure will become
much more important from 1 January 1998, when

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the national procedure will be supplemented by the
decentralized procedure for most marketing author-
izations.

2.2.
In assessing the proposal, the Committee feels it
desirable to seek to strike a balance between the need
to:

The main objectives of the proposal are as

1.8.
follows:

— protection of persons taking part in trials, based on
the revised text of the Helsinki declaration and with
reference to the Council of Europe Convention on
the protection of human rights and dignity of the
human being (1);

— maximum safety throughout the procedure, to be
obtained inter alia by introducing an inspection
system;

— a more rigorous role for ethics committees by
making a proper distinction between the ‘lead’ ethics
committee which issues the opinion on whether to
authorize the trial, and the ethics committees of each
site, which are responsible for the launch of the trial
at their site;

— speeding-up of the administrative procedures needed
to begin a trial, which must always be referred to an
ethics committee for its opinion and notified to the
competent authority of the Member State; this
authority has 30 days to provide the sponsor with
reasoned grounds for non-acceptance of an appli-
cation;

— more thorough exchange of information between

the Member States involved in the trial.

2. General comments

In its own-initiative opinion on the free move-
2.1.
ment of medicines in the European Union (2),
the
Committee emphasized the importance of having a
pharmaceutical sector which draws its strength from
the existence of a competitive, highly innovative industry
within the EU.

2.1.1.
The opinion pointed out that the availability
of innovative, safe and effective medicines plays an
important role in protecting public health and extending
average life expectancy.

Trials on human subjects are essential for
2.1.2.
assessing whether new products are effective and safe.
Such trials must be conducted according to scientific
and ethical principles, while at the same time avoiding
pointless and expensive studies which cover no new
ground.

(1) Council of Europe, European Treaty Series No 164, Oviedo

4.4.1997.

(2) OJ C 97, 1.4.1996.

— simplify red tape;

— respect the deadlines for commencement of the

clinical trial;

and the need to

— provide the utmost guarantees for trial subjects;

— coordinate findings so that the efficacy and safety of
a new medicinal product can be rigorously assessed.

2.3.
Article 1(3) of the proposal states that ‘the
principles and guidelines of Good Clinical Practice shall
be adopted in the form of a directive’. The Committee
sees this as a positive step forward, as it means that
these principles and guidelines will be binding in all
Member States. The proposal will approximate the
national legislative provisions adopted recently in vari-
ous Member States. Failure to harmonize these pro-
visions would result in existing discrepancies remaining
unaltered.

The Committee endorses the approximation of
2.4.
provisions, on condition that this does not in practice
create further bureaucratic or administrative obstacles
but promotes high-quality pharmacological research in
the EU. The EU must remain a magnet for trials and
innovation, as this will help to improve health protection.

2.5.
In order to ensure that the principles and guide-
lines governing clinical trials are followed consistently,
the provisions of the directive should also apply to
independent research on new drugs conducted outside
the industry (at universities, hospitals and research
centres).

2.6.
The Committee understands and endorses the
cautious way in which the Commission intends to
proceed towards the aim of a single procedure for the
commencement of clinical trials, valid throughout the
EU. It notes the Commission’s statement (point 5 of the
explanatory memorandum) regarding the inadequate
cooperation at present between Member States and the
difficulty of submitting a single application to the
European Agency for the Evaluation of Medicinal
Products (EMEA), as the agency is not yet properly
equipped for this.

2.7. However, the Committee thinks that forms of
cooperation should be encouraged for the purpose of
gradually moving towards a single EU procedure. Use
should be made here of the scientific skills and knowhow
available at the EMEA, especially as regards ‘orphan’

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medicinal products and gene and cell therapy. The
following opportunities could, for example, be explored:

— at some future stage, the EMEA could be made
responsible for authorizing trials on products which
have to be registered under the centralized procedure;

— the Committee for Proprietary Medicinal Products
(CPMP) could act as the technical body for arbi-
tration in the event of disagreement and/or differing
interpretations between Member States.

ology. It asks the Commission to align the terminology
on that of the ICH, which has become a reference point
for the international scientific community and to which
the Commission has also actively contributed. In particu-
lar, it asks the Commission to check on the various
translations of the term ‘non-interventional clinical
trials’, as the present translations could give rise to
misunderstandings.

3.2. Article 2

2.8.
In order to boost cooperation, it is essential that
an EU database be provided as part of EudraNet
(a telematic network linking the relevant national
authorities, the EMEA and the Commission). This
would be used to coordinate and circulate information
between the Member States involved in a multi-centre
international trial, with an access key to guarantee the
utmost confidentiality and the safeguarding of industrial
protection.

3.2.1.
The definition of a ‘serious adverse event or
serious adverse reaction’ should also mention the ICH
provision on the advisability of seeking a medical
opinion on other possible risks.

It would be helpful to include a definition of
3.2.2.
‘research coordinator’, this being the person in charge
of the clinicians involved in a multi-centre trial.

The goal must be a clear and simple legal
2.9.
framework which allows trials to be launched simul-
taneously in different countries. This presupposes
respect for the deadlines laid down for the favourable
opinion from the ethics committees and for the accept-
ance of any requests from the relevant authorities for
modifications (these authorities have 30 days to notify
their opinion to the sponsor).
is also essential
that persons undergoing trials are guaranteed the best
possible risks-benefits ratio.

It

2.10.
A harmonized EU framework which is consist-
ent with the documents of the International Conference
on Harmonization, Good Clinical Practice, pharmacovi-
gilance standards and Good Manufacturing Practice can
ensure that studies carried out in the EU are fully
consistent, making it easier to check and compare the
data obtained.

2.11.
To this end, the Commission must obtain
greater guarantees regarding the participation of third
countries in multi-centre trials. The sponsor should be
asked to ascertain that third countries involved in trails
on a particular medicinal product are familiar with the
Community guidelines and are therefore able to apply
them properly.

3. Specific comments

The Committee notes that various articles of the
3.1.
directive contain incorrect or incorrectly used termin-

3.3. Article 4

The current wording does not make it clear
3.3.1.
that the opinion of the ethics committee is mandatory.
This weakens the position of trial subjects. The Com-
mittee therefore suggests that Article 4(2) be amended
to read ‘... must be delivered ...’.

3.4. Article 7

3.4.1.
This is the central article of the proposal. The
Committee feels that respect for GCP, the mandatory
nature of the favourable opinion from the ethics com-
mittee, and the possibility for Member States to inter-
vene, together provide sufficient guarantees for trial
subjects and ensure a standard procedure in all Member
States.

3.4.2.
A special exemption from this procedure could
be allowed for gene and cell therapy products, given the
recognized sensitivity of these sectors. Since centralized
registration is mandatory for such products, the Com-
mission could, as of now, make the start of trials
contingent on the opinion of the EMEA as the body in
charge of the centralized authorization procedure for
high-tech products.

In order to avoid unnecessary red tape,

3.4.3.
it
should be made clear that the scientific data to be
presented to the Member State and to the ethics
committee are to be the same.

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3.5. Article 8

3.7. Article 10

Explicit provision should be made for rigorous
3.5.1.
respect for the confidentiality of data and the utmost
discretion regarding research under way.

For

investigational medicinal products,

3.7.1.
it
would seem best to use the provisions on Good Manufac-
turing Practice (Directive 91/356/EEC) (1).

3.6. Article 9

3.8. Article 13

3.6.1.
In cases where a trial is suspended or prohibited,
the Member State should inform not only the Com-
mission and the other Member States, but also the
sponsor, before taking any decision.

3.8.1.
and definitions be made consistent with the ICH text.

The Committee recommends that procedures

(1) OJ L 193, 17.7.1991.

Brussels, 28 January 1998.

The President

of the Economic and Social Committee

Tom JENKINS

Opinion of the Economic and Social Committee on the ‘Proposal for a Council Regulation
(EC) amending Council Regulation (EEC) No 1210/90 of 7 May 1990 on the establishment of
the European Environment Agency and the European Environment Observation Network’

(98/C 95/02)

On 18 November 1997 the Council decided to consult the Economic and Social Committee,
under Article 130s of the Treaty establishing the European Community, on the above-mentioned
proposal.

The Section for Protection of the Environment, Public Health and Consumer Affairs, which
was responsible for preparing the Committee’s work on the subject, adopted its opinion on
6 January 1998. The rapporteur, working without study group, was Mrs Sa´nchez Miguel.

At its 351st plenary session (meeting of 28 January 1998), the Economic and Social Committee
adopted the following opinion by 109 votes, with three abstentions.

1.

Introduction

1.1.
In application of the principle of transparency in
the budgetary workings of EU bodies, the Commission
proposes to amend nine regulations covering the so-
called ‘second-generation’ agencies which, when created,
were given different budgetary rules to those in force
for the ‘first-generation’ agencies.

The first-generation agencies (1) have a budget
1.2.
management and approval system under which the

(1) Bodies set up in 1975: CEDEFOP (Thessaloniki) and the
European Foundation for the Improvement of Living and
Working Conditions (Dublin).

European Parliament grants discharge to the Manage-
ment Board, after consulting the Council. In the second-
generation agencies (2), on the other hand, the Manage-
ment Board grants discharge to the Executive Director,
who is responsible for implementing the budget.

After reviewing the operation of these second-
1.3.
generation agencies, once established in their functions,

(2) The European Environment Agency, the European Train-
ing Foundation, the European Monitoring Centre for
Drugs and Drug Addiction, the European Agency for
Safety and Health at Work, the Translation Centre for
Bodies of the European Union, the Office for Harmon-
ization in the Internal Market, the European Agency for
the Evaluation of Medicinal Products, the Community
Plant Variety Rights Office and the European Monitoring
Centre on Racism and Xenophobia.