Source: EURLEX
Language: en
Format: md

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,_

�
having regard to the Council common position 8878/1/2000 �C5-0424/2000) ( [1] ),

�
having regard to its position at first reading ( [2] ) on the Commission proposal to Parliament and the
Council (COM(1997) 369) ( [3] ),

�
having regard to the Commission’s amended proposal (COM(1999) 193 ( [4] ),

�
having regard to Article 251(2) of the EC Treaty,

�
having regard to Rule 80 of its Rules of Procedure,

�
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._

(3) **Persons who are incapable of giving legal consent to**
**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)_

**(3a)** **In the case of other persons incapable of giving their**
**consent,** **such** **as** **persons** **with** **dementia,** **psychiatric**
**patients etc., inclusion in clinical trials in such cases**
**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, i.e. 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.**

(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
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;

(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 giving 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 documented, 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

**Tuesday 12 December 2000**

COUNCIL

COMMON POSITION

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
specified therein. **Member States shall, in so far as they**
**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) the foreseeable 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) the foreseeable 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** **research** **methods.** **Additionally,** **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;**

**(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

**Tuesday 12 December 2000**

COUNCIL

COMMON POSITION

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)_

7. No extension to the _time_ period referred to in paragraph 5
shall be permissible except in the case of trials involving medicinal products for gene therapy _and_ somatic cell therapy _,_
_including_ xenogenic cell therapy.

7. No extension to the **60-day** period referred to in paragraph 5 shall be permissible except in the case of trials involving medicinal products for gene therapy **or** somatic cell therapy **or medicinal products containing genetically modified**
**organisms, for which an extension of a maximum of**
**30 days shall be permitted. For these products, this**
**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 to the commencement of the_
_trial if it has not notified the sponsor of any grounds for non-accep-_
_tance._

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

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 **further** extensions to the period referred to in the first subparagraph shall be permissible except in the case of trials involving the medicinal products listed in paragraph 6 **, for which**

17.8.2001 EN Official Journal of the European Communities C 232/59

**Tuesday 12 December 2000**

COUNCIL

COMMON POSITION

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 marketing 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 marketing 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 commencing clinical trials involving medicinal products for gene therapy, somatic cell therapy including xenogenic cell therapy and
all medicinal products containing genetically modified organisms.

6. Written authorisation shall be required before commencing clinical trials involving medicinal products for gene therapy, somatic cell therapy including xenogenic cell therapy and
all medicinal products containing genetically modified organisms. **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 unexpected serious adverse reactions to an investigational medicinal product which are brought to its attention are
_reported_ immediately _to_ the Agency _by the sponsor of the clin-_
_ical trial_ .

**4.** **Summer-time ***I**

**A5-0356/2000**

(a) Each Member State shall ensure that all suspected unexpected serious adverse reactions to an investigational medicinal 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** .

**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 transport and communications, but also other sectors of industry,
requires stable, long-term planning. Provisions concerning summer-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 January 2001, the arrangements to apply from 2002 onwards.

(4) The proper functioning of certain sectors, not only transport and communications, but also other sectors of industry,
requires stable, long-term planning. Provisions concerning summer-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.