Directive 2001/20/EC of the European Parliament and of the CouncilShow full title

Directive 2001/20/EC of the European Parliament and of 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

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 from the Commission(1),

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

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

Whereas:

(1) Council Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation or administrative action relating to medicinal products(4) requires that applications for authorisation to place a medicinal product on the market should be accompanied by a dossier containing particulars and documents relating to the results of tests and clinical trials carried out on the product. Council Directive 75/318/EEC of 20 May 1975 on the approximation of the laws of Member States relating to analytical, pharmaco-toxicological and clinical standards and protocols in respect of the testing of medicinal products(5) lays down uniform rules on the compilation of dossiers including their presentation.

(2) The accepted basis for the conduct of clinical trials in humans is founded in the protection of human rights and the dignity of the human being with regard to the application of biology and medicine, as for instance reflected in the 1996 version of the Helsinki Declaration. The clinical trial subject's protection is safeguarded through risk assessment based on the results of toxicological experiments prior to any clinical trial, screening by ethics committees and Member States' competent authorities, and rules on the protection of personal data.

(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 be included in clinical trials only when there are grounds for expecting that the administering of the medicinal product would be of direct benefit to the patient, thereby outweighing the risks. However, there is a need for clinical trials involving children to improve the treatment available to them. Children represent a vulnerable population with developmental, physiological and psychological differences from adults, which make age- and development- related research important for their benefit. Medicinal 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 purpose 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.

(4) 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 individuals only when there are grounds for assuming that the direct benefit to the patient outweighs the risks. Moreover, in such cases the written consent of the patient's legal representative, given in cooperation with the treating doctor, is necessary before participation in any such clinical trial.

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

(6) In order to achieve optimum protection of health, obsolete or repetitive tests will not be carried out, whether within the Community or in third countries. The harmonisation of technical requirements for the development of medicinal products should therefore be pursued through the appropriate fora, in particular the International Conference on Harmonisation.

(7) For medicinal products falling within the scope of Part A of the Annex to 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(6), which include products intended for gene therapy or cell therapy, prior scientific evaluation by the European Agency for the Evaluation of Medicinal Products (hereinafter referred to as the ‘Agency’), assisted by the Committee for Proprietary Medicinal Products, is mandatory before the Commission grants marketing authorisation. In the course of this evaluation, the said Committee may request full details of the results of the clinical trials on which the application for marketing authorisation is based and, consequently, on the manner in which these trials were conducted and the same Committee may go so far as to require the applicant for such authorisation to conduct further clinical trials. Provision must therefore be made to allow the Agency to have full information on the conduct of any clinical trial for such medicinal products.

(8) A single opinion for each Member State concerned reduces delay in the commencement of a trial without jeopardising the well-being of the people participating in the trial or excluding the possibility of rejecting it in specific sites.

(9) Information on the content, commencement and termination of a clinical trial should be available to the Member States where the trial takes place and all the other Member States should have access to the same information. A European database bringing together this information should therefore be set up, with due regard for the rules of confidentiality.

(10) Clinical trials are a complex operation, generally lasting one or more years, usually involving numerous participants and several trial sites, often in different Member States. Member States' current practices diverge considerably on the rules on commencement and conduct of the clinical trials and the requirements for carrying them out vary widely. This therefore results in delays and complications detrimental to effective conduct of such trials in the Community. It is therefore necessary to simplify and harmonise the administrative provisions governing such trials by establishing a clear, transparent procedure and creating conditions conducive to effective coordination of such clinical trials in the Community by the authorities concerned.

(11) 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 problems, explicit written authorisation should, however, be required.

(12) The principles of good manufacturing practice should be applied to investigational medicinal products.

(13) Special provisions should be laid down for the labelling of these products.

(14) Non-commercial clinical trials conducted by researchers without the participation of the pharmaceuticals industry may be of great benefit to the patients concerned. 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 accordance 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 marketing authorisation. Labelling of the investigational medicinal products intended for trials of this nature should be subject to simplified provisions laid down in the good manufacturing practice guidelines on investigational products and in Directive 91/356/EEC.

(15) The verification of compliance with the standards of good clinical practice and the need to subject data, information and documents to inspection in order to confirm that they have been properly generated, recorded and reported are essential in order to justify the involvement of human subjects in clinical trials.

(16) The person participating in a trial must consent to the scrutiny of personal information during inspection by competent authorities and properly authorised persons, provided that such personal information is treated as strictly confidential and is not made publicly available.

(17) This Directive is to apply without prejudice to Directive 95/46/EEC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data(7).

(18) It is also necessary to make provision for the monitoring of adverse reactions occurring in clinical trials using Community surveillance (pharmacovigilance) procedures in order to ensure the immediate cessation of any clinical trial in which there is an unacceptable level of risk.

(19) 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 the procedures for the exercise of implementing powers conferred on the Commission(8),

HAVE ADOPTED THIS DIRECTIVE:

(1)

OJ C 306, 8.10.1997, p. 9 and

OJ C 161, 8.6.1999, p. 5.

(2)

OJ C 95, 30.3.1998, p. 1.

(3)

Opinion of the European Parliament of 17 November 1998 (OJ C 379, 7. 12. 1998, p. 27). Council Common Position of 20 July 2000 (OJ C 300, 20.10.2000, p. 32) and Decision of the European Parliament of 12 December 2000. Council Decision of 26 February 2001.

(4)

OJ 22, 9.2.1965, p. 1/65. Directive as last amended by Council Directive 93/39/EEC (OJ L 214, 24.8.1993, p. 22).

(5)

OJ L 147, 9.6.1975, p. 1. Directive as last amended by Commission Directive 1999/83/EC (OJ L 243, 15.9.1999, p. 9).

(6)

OJ L 214, 24.8.1993, p. 1. Regulation as amended by Commission Regulation (EC) No 649/98 (OJ L 88, 24.3.1998, p. 7)

(7)

OJ L 281, 23.11.1995, p. 31.

(8)

OJ L 184, 17.7.1999, p. 23.