European Parliament legislative resolution on the Council common position for adopting a European Parliament and Council directive 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 (8878/1/2000 - C5-0424/2000 - 1997/0197(COD))
Date: 2000-12-12
Institutions: European Parliament
Subjects: approximation of laws, experiment on humans, medicinal product, scientific research, testing, therapeutics

C 232/52

Official Journal of the European Communities

EN

17.8.2001

Tuesday 12 December 2000

TEXTS ADOPTED

1. Training of seafarers ***I (procedure without report)

C5-0285/2000

Proposal for a European Parliament and Council directive on the minimum level of training of
seafarers (consolidated version) (COM(2000) 313 * C5-0285/2000 * 2000/0131(COD))

(Codecision procedure: first reading)

The proposal was approved.

2. Coffee and chicory extracts ***I (procedure without report)

C5-0485/2000

Proposal for a European Parliament and Council directive amending Directive 80/232/EEC as
regards the range of nominal weights for coffee extracts and chicory extracts (COM(2000) 568 *
C5-0485/2000 * 2000/0235(COD))

(Codecision procedure: first reading)

The proposal was approved.

3. Clinical trials on medicinal products for human use ***II

A5-0349/2000

European Parliament legislative resolution on the Council common position for adopting a Eur-
opean Parliament and Council directive on the approximation of the laws, regulations and admin-
istrative 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 (8878/1/2000 * C5-0424/
2000 * 1997/0197(COD))

(Codecision procedure: second reading)

The European Parliament,

(cid:25) having regard to the Council common position 8878/1/2000 (cid:25) C5-0424/2000) (1),

(cid:25) having regard to its position at first reading (2) on the Commission proposal to Parliament and the

Council (COM(1997) 369) (3),

(cid:25) having regard to the Commission’s amended proposal (COM(1999) 193 (4),

(cid:25) having regard to Article 251(2) of the EC Treaty,

(cid:25) having regard to Rule 80 of its Rules of Procedure,

(cid:25) having regard to the recommendation for second reading of the Committee on the Environment,

Public Health and Consumer Policy (A5-0349/2000),

(1) OJ C 300, 20.10.2000, p. 32.
(2) OJ C 379, 7.12.1998, p. 27.
(3) OJ C 306, 8.10.1997, p. 9.
(4) OJ C 161, 8.6.1999, p. 5.

17.8.2001

EN

Official Journal of the European Communities

C 232/53

Tuesday 12 December 2000

1.

Amends the common position as follows;

2.

Instructs its President to forward its position to the Council and Commission.

COUNCIL
COMMON POSITION

AMENDMENTS
BY PARLIAMENT

(Amendment 28)
Recital 3

(3)
It is incumbent on Member States to lay down rules to safe-
guard the protection of individuals who are incapable of giving their
consent, such as minors and incapacitated adults. Since such persons
are incapable of giving their free consent to taking part in a clinical
trial, consent to their participation must be given by a person or body
provided for by law.

Persons who are incapable of giving legal consent to
(3)
clinical trials should be given special protection.
It is
incumbent on the Member States to lay down rules to
this effect. Such persons may not be included in clinical
trials if the same results can be obtained using persons
capable of giving consent. Normally these persons should
only be included in clinical trials when there are grounds
for expecting that the administering of the medicinal pro-
duct would be of direct benefit to the patient, thereby
outweighing the risks. However, there is a need for clini-
cal trials involving children to improve the treatment
available to them. Children represent a vulnerable popula-
tion with developmental, physiological and psychological
differences from adults, which make age- and develop-
ment-related research important for their benefit. Medic-
inal products, including vaccines, for children need to be
tested scientifically before widespread use. This can only
be achieved by ensuring that medicinal products which
are likely to be of significant clinical value for children
are fully studied. The clinical trials required for this pur-
pose should be carried out under conditions affording the
best possible protection for the subjects. Criteria for the
protection of children in clinical trials therefore need to
be laid down.

(Amendment 2)
Recital 3a (new)

inclusion in clinical

(3a)
In the case of other persons incapable of giving their
consent,
such as persons with dementia, psychiatric
trials in such cases
patients etc.,
should be on an even more restrictive basis. Medicinal
products for trial may be administered to all such indivi-
duals when there are grounds for assuming that the direct
benefit to the patient outweighs the risks. Moreover, in
such cases the written agreement of the patient’s legal
representative, given in cooperation with the treating doc-
tor, is necessary before participation in any such clinical
trial.

(Amendment 29)
Recital 3b (new)

(3b) The notion of legal representative refers back to
existing national law and consequently may include nat-
ural or legal persons, an authority and/or a body provided
for by national law.

C 232/54

Official Journal of the European Communities

EN

17.8.2001

Tuesday 12 December 2000

COUNCIL
COMMON POSITION

AMENDMENTS
BY PARLIAMENT

(Amendment 3)
Recital 8a (new)

(8a) As a rule authorisation should be implicit,
if
there has been a vote in favour by the Ethics committee
and the competent authority has not objected within a
given period, it should be possible to begin the clinical
trials. In exceptional cases raising especially complex pro-
blems, explicit written authorisation shall however be
required.

i.e.

(Amendment 30)
Recital 10a (new)

(10a) Non-commercial clinical trials conducted by re-
searchers without the participation of the pharmaceuticals
industry may be of great benefit to the patients con-
cerned. The Directive should therefore take account of
the special position of trials whose planning does not
require particular manufacturing or packaging processes,
if these trials are carried out with medicinal products
with a marketing authorisation within the meaning of
Directive 65/65/EEC, manufactured or imported in accor-
dance with the provisions of Directives 75/319/EEC and
91/356/EEC, and on patients with the same characteristics
as those covered by the indication specified in this mar-
keting authorisation. Labelling of the investigational med-
icinal products for trials of this nature should be subject
to simplified provisions laid down in the good manufac-
turing practice guidelines on investigational products and
in Directive 91/356/EEC.

(Amendment 31)
Article 2(f)

(f)

‘Investigator’: A person responsible for the conduct of a
is conducted by a
clinical trial at a trial site. If a trial
team of individuals at a trial site, the investigator is the
leader responsible for the team and may be called the prin-
cipal investigator;

(f)

‘Investigator’: A doctor or a person following a profes-
sion agreed in the Member State for investigations
because of the scientific background and the experi-
ence in patient care it requires. The investigator is
responsible for the conduct of a clinical trial at a trial
site. If a trial is conducted by a team of individuals at a
trial site, the investigator is the leader responsible for the
team and may be called the principal investigator;

(Amendment 32)
Article 2(j)

(j)

‘Informed consent’: decision to take part in a clinical trial,
taken freely after being duly informed of the details and
appropriately documented, by any person capable of giv-
ing consent or, where the person is not capable of giving
consent, by his or her legal representative and/or an author-
ity and/or a person and/or body provided for by law.

(j)

‘Informed written consent’: decision, which must be
dated and signed, to take part in a clinical trial, taken
freely after being duly informed of its nature, signifi-
cance, implications and risks and appropriately docu-
mented, by any person capable of giving consent or,
where the person is not capable of giving consent, by his

17.8.2001

EN

Official Journal of the European Communities

C 232/55

COUNCIL
COMMON POSITION

Tuesday 12 December 2000

AMENDMENTS
BY PARLIAMENT

or her legal representative. If the person concerned is
unable to write, oral consent in the presence of at
least one witness may be given in exceptional cases,
as provided for in national legislation;

(Amendment 7)
Article 3(1)

1.
This Directive shall apply without prejudice to the
national provisions on the protection of clinical trial subjects
if they are more comprehensive than the provisions of this
Directive and consistent with the procedures and time-scales
specified therein.

1.
This Directive shall apply without prejudice to the
national provisions on the protection of clinical trial subjects
if they are more comprehensive than the provisions of this
Directive and consistent with the procedures and time-scales
in so far as they
specified therein. Member States shall,
have not already done so, adopt detailed rules to protect
from abuse individuals who are incapable of giving their
informed consent.

(Amendment 33)
Article 3(2)(a)

(a)

foreseeable

the
risks and inconveniences have been
weighed against the anticipated benefit for the individual
trial subject and society. A clinical trial may be initiated
and continued only if anticipated benefits justify the risks;

(a)

foreseeable

the
risks and inconveniences have been
weighed against the anticipated benefit for the individual
trial subject and other present and future patients.
A clinical trial may be initiated only if the Ethics com-
mittee and/or the competent authority comes to the
conclusion that the anticipated therapeutic and public
health benefits justify the risks and continued only if
compliance with this requirement
is permanently
monitored;

(Amendment 34)
Article 3(2)(aa) (new)

(aa)

the trial subject or, when the person is not able to
give informed consent, his legal representative has
had the opportunity, in a prior interview with the
investigator or a member of the investigating team,
to understand the objectives, risks and inconveniences
of the trial, and the conditions under which it is to be
conducted. The subject will also be informed of his
right to withdraw from the trial at any time;

(Amendment 35)
Article 3(2)(c)

(c)

informed consent in the appropriate form has been obtained;

(c)

the trial subject or, when the person is not able to
give informed consent, his legal representative has
given his written consent after being informed of the
nature, significance, implications and risks of the clin-
ical trial. If the individual is unable to write, oral con-
sent in the presence of at least one witness may be
given in exceptional cases, as provided for in national
legislation;

C 232/56

Official Journal of the European Communities

EN

17.8.2001

Tuesday 12 December 2000

COUNCIL
COMMON POSITION

AMENDMENTS
BY PARLIAMENT

(Amendment 11)
Article 3(2)(da) (new)

(da) provision has been made for insurance or indemnity
to cover the liability of the investigator and sponsor;

(Amendment 36)
Article 3a (new)

Article 3a

Clinical trials on minors

In addition to any other relevant restriction, a clinical trial
on minors may be undertaken only if

(a)

the informed consent of the parents or legal represen-
tative has been obtained; consent must represent the
minor’s presumed will and may be revoked at any
time, without detriment to the minor;

(b) the minor has received information according to its
capacity of understanding, from staff with experience
with minors, regarding the trial, the risks and the ben-
efits;

(c)

the explicit wish of a minor who is capable of form-
ing an opinion and assessing this information to
refuse participation or to be withdrawn from the clin-
ical trial at any time is considered by the investigator
or where appropriate the principal investigator;

(d) no incentives or financial

inducements are given

except compensation;

(e) some direct benefit

for the group of patients is
obtained from the clinical trial and only where such
research is essential to validate data obtained in clini-
cal trials on persons able to give informed consent or
by other
such
research should either relate directly to a clinical con-
dition from which the minor concerned suffers or be
of such a nature that it can only be carried out on
minors;

research methods. Additionally,

(f)

the corresponding scientific guidelines of the Agency
have been followed;

(g) clinical trials have been designed to minimise pain,
discomfort, fear and any other foreseeable risk in rela-
tion to the disease and developmental stage; both the
risk threshold and the degree of distress have to be
specially defined and constantly monitored;

(h) the Ethics committee, with paediatric expertise or
after taking advice in clinical, ethical and psychosocial
matters in the field of paediatrics, has endorsed the
protocol;

(i)

the interests of the patient always prevail over those
of science and society.

17.8.2001

EN

Official Journal of the European Communities

C 232/57

COUNCIL
COMMON POSITION

Tuesday 12 December 2000

AMENDMENTS
BY PARLIAMENT

(Amendment 37)

Article 3b (new)

Article 3b

Clinical trials on incapacitated adults not able to give
informed legal consent

In the case of other persons incapable of giving informed
legal consent, all relevant requirements listed for persons
capable of giving consent shall apply. In addition to these
requirements, inclusion in clinical trials of incapacitated
adults who have not given or not refused informed con-
sent prior to the onset of their incapacity shall be allowed
only if:

(a)

the informed consent of the legal representative has
been obtained; consent shall represent the subject’s
presumed will and may be revoked at any time, with-
out detriment to the subject;

(b) the person not able to give legal informed consent has
received information according to his/her capacity of
understanding regarding the trial, the risks and the
benefits;

(c)

the explicit wish of a subject who is capable of form-
ing an opinion and assessing this information to
refuse participation or to be withdrawn from the clin-
ical trial at any time is considered by the investigator
or where appropriate the principal investigator;

(d) no incentives or financial

inducements are given

except compensation;

(e) such research is essential to validate data obtained in
clinical trials on persons able to give informed con-
sent or by other research methods and which relates
directly to a life-threatening or debilitating clinical
condition from which the incapacitated adult con-
cerned suffers;

(f) clinical trials have been designed to minimise pain,
discomfort, fear and any other foreseeable risk in rela-
tion to the disease and developmental stage; both the
risk threshold and the degree of distress have to be
specially defined and constantly monitored;

(g)

the Ethics committee, with expertise in the relevant
disease and the patient population concerned or after
taking advice in clinical, ethical and psychosocial ques-
tions in the field of the relevant disease and patient
population concerned, has endorsed the protocol;

(h) the interests of the patient always prevail over those

of science and society;

C 232/58

Official Journal of the European Communities

EN

17.8.2001

Tuesday 12 December 2000

COUNCIL
COMMON POSITION

AMENDMENTS
BY PARLIAMENT

(i)

there are grounds for expecting that administering the
medicinal product to be tested will produce a benefit
to the patient outweighing the risks or produce no
risk at all.

(Amendment 14)
Article 4(3)(aa) (new)

(aa) whether the evaluation of the anticipated benefits
and risks as required under Article 3(2)(a) is satisfac-
tory and whether the conclusions are justified;

(Amendment 38)
Article 4(3)(f)

(f)

the adequacy and completeness of the written information
to be given and the procedure to be used for the purpose
of obtaining informed consent;

(f)

the adequacy and completeness of the written information
to be given and the procedure to be used for the purpose
of obtaining informed consent and the justification for
the research on persons incapable of giving informed
consent as regards the specific restrictions laid down
in Article 3;

(Amendment 39)
Article 4(7)

No extension to the time period referred to in paragraph 5
7.
shall be permissible except in the case of trials involving med-
icinal products for gene therapy and somatic cell
therapy,
including xenogenic cell therapy.

No extension to the 60-day period referred to in para-
7.
graph 5 shall be permissible except in the case of trials invol-
ving medicinal products for gene therapy or somatic cell ther-
apy or medicinal products containing genetically modified
organisms,
for which an extension of a maximum of
this
30 days shall be permitted. For these products,
90-day period may be extended by a further 90 days in
the event of consultation of a group or a committee in
accordance with the Member State regulations and proce-
dures. In the case of xenogenic cell therapy there shall be no
time limit to the authorisation period.

(Amendment 40)
Article 7(4)

4.
Consideration of a valid request for authorisation by the
competent authority as stated in paragraph 2 must not exceed
60 days. After those 60 days, the sponsor can consider that the
competent authority does not object
the
trial if it has not notified the sponsor of any grounds for non-accep-
tance.

to the commencement of

4.
Consideration of a valid request for authorisation by the
competent authority as stated in paragraph 2 shall be carried
out as rapidly as possible and may not exceed 60 days. The
Member States may lay down a shorter period than
60 days within their area of responsibility if that is in
compliance with current practice. The competent author-
ity can nevertheless notify the sponsor before the end of
this period that it has no grounds for non-acceptance.

No extensions to the period referred to in the first subpara-
graph shall be permissible except in the case of trials involving
the medicinal products listed in paragraph 6.

No further extensions to the period referred to in the first sub-
paragraph shall be permissible except in the case of trials invol-
ving the medicinal products listed in paragraph 6, for which

17.8.2001

EN

Official Journal of the European Communities

C 232/59

COUNCIL
COMMON POSITION

Tuesday 12 December 2000

AMENDMENTS
BY PARLIAMENT

an extension of a maximum of 30 days shall be permitted.
For these products, the 90-day period may be extended by
a further 90 days in the event of consultation of a group
or a committee in accordance with the Member State reg-
ulations and procedures. In the case of xenogenic cell
therapy there shall be no time limit to the authorisation
period.

(Amendment 41)
Article 7(5)

5. Without prejudice to paragraph 6, written authorisation
may be required before the commencement of clinical trials
for such trials on medicinal products which do not have a mar-
keting authorisation within the meaning of Directive 65/65/
EEC and are referred to in Part A of the Annex to Regulation
(EEC) No 2309/93, and other medicinal products with special
characteristics the list of which is adopted in accordance with the
procedure referred to in Article 19(2) of this Directive.

Until the said list is adopted, Member States shall continue to apply
their national procedures.

5. Without prejudice to paragraph 6, written authorisation
may be required before the commencement of clinical trials
for such trials on medicinal products which do not have a mar-
keting authorisation within the meaning of Directive 65/65/
EEC and are referred to in Part A of the Annex to Regulation
(EEC) No 2309/93, and other medicinal products with special
characteristics, such as medicinal products whose active
ingredient(s) is a biological product of human or animal
origin, or contains biological components of human or
animal origin, or manufacturing of which requires such
components.

(Amendment 42)
Article 7(6)

6. Written authorisation shall be required before commen-
cing clinical trials involving medicinal products for gene ther-
apy, somatic cell therapy including xenogenic cell therapy and
all medicinal products containing genetically modified organ-
isms.

6. Written authorisation shall be required before commen-
cing clinical trials involving medicinal products for gene ther-
apy, somatic cell therapy including xenogenic cell therapy and
all medicinal products containing genetically modified organ-
isms. No gene therapy trials may be carried out which
result in modifications to the subject’s germ line genetic
identity.

(Amendment 21)
Article 10(1), first subparagraph a (new)

Before the Member State reaches its decision it shall ask
the sponsor and/or the investigator for their opinion, to
be delivered within one week * except where delay
involves risk.

(Amendment 43)
Article 12, second paragraph (new)

In addition, these guidelines shall lay down adapted provi-
sions relating to labelling for investigational medicinal
products for clinical trials with the following characteris-
tics:

* the planning of the trial does not require particular

manufacturing or packaging processes;

* the trial is conducted with medicinal products with,
in the Member States concerned by the study, a mar-
keting authorisation within the meaning of Directive
65/65/EEC, manufactured or imported in accordance
with the provisions of Directive 75/319/EEC;

C 232/60

Official Journal of the European Communities

EN

17.8.2001

Tuesday 12 December 2000

COUNCIL
COMMON POSITION

AMENDMENTS
BY PARLIAMENT

* the patients participating in the trial have the same
characteristics as those covered by the indication spe-
cified in the abovementioned authorisation.

(Amendment 23)
Article 15(3)(a)

(a) Each Member State shall ensure that all suspected unex-
pected serious adverse reactions to an investigational med-
icinal product which are brought
to its attention are
reported immediately to the Agency by the sponsor of the clin-
ical trial.

(a) Each Member State shall ensure that all suspected unex-
pected serious adverse reactions to an investigational med-
icinal product which are brought
to its attention are
immediately entered in a European database to which,
in accordance with Article 9(1), only the competent
authorities of the Member States, the Agency and the
Commission, shall have access.

4. Summer-time ***I

A5-0356/2000

Proposal

for a European Parliament and Council directive on summer-time arrangements

(COM(2000) 302 * C5-0322/2000 * 2000/0140(COD))

The proposal was amended as follows:

TEXT PROPOSED
BY THE COMMISSION (1)

AMENDMENTS
BY PARLIAMENT

(Amendment 3)
Recital 4

(4) The proper functioning of certain sectors, not only trans-
port and communications, but also other sectors of industry,
requires stable, long-term planning. Provisions concerning sum-
mer-time should therefore be laid down for an unlimited period.
Article 4 of Directive 97/44/EC provides, in that respect, that
the European Parliament and the Council are to adopt, by 1 Jan-
uary 2001, the arrangements to apply from 2002 onwards.

(4) The proper functioning of certain sectors, not only trans-
port and communications, but also other sectors of industry,
requires stable, long-term planning. Provisions concerning sum-
mer-time should therefore be laid down for an unspecified
period. Article 4 of Directive 97/44/EC provides,
in that
respect, that the European Parliament and the Council are to
adopt, by 1 January 2001, the arrangements to apply from
2002 onwards.

(Amendment 4)
Article 5, 2nd paragraph (new)

The Commission shall, if necessary and following the con-
clusions of the report, make appropriate proposals.

(1) OJ C 337 E, 28.11.2000, p. 136.