Implementation of EU Directive on Good Clinical Practice in Clinical Trials

The then Minister for Health and Children made Regulations implementing the EU Clinical Trials Directive in this country (European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations, 2004. (S.I. No. 190 of 2004) These Regulations came into force on 1st May 2004.

The Regulations set out measures relating to the conduct of clinical trials on medicinal products for human use and replace those controls that previously applied to such trials under the Control of Clinical Trials Acts, 1987 and 1990.

Aspects dealt with in the Regulations include:

  • procedures for obtaining a favourable ethics committee opinion (a single ethics committee opinion is required in the case of multi-centre trials);
  • procedures for obtaining authorisations for the conduct of clinical trials from the Irish Medicines Board;
  • controls that are to apply to the manufacture, supply and importation of investigational medicinal products;
  • obligations for the reporting of various adverse events encountered in subjects participating in clinical trials, including the recording, reporting and notifying of such events;
  • obligations for compliance with standards of good clinical practice (GCP) and good manufacturing practice (GMP).

Recognised Ethics Committees

The Regulations contain provisions for the establishment of, recognition of and operation of ethics committees. These committees are required to be independent, consisting of healthcare professionals and lay members and to have responsibility to protect the rights, safety and wellbeing of human subjects involved in a trial. They are also required to provide a public assurance of that protection by, among other things, expressing an opinion on the trial protocol, on the suitability of the investigators, on the adequacy of the facilities, on the availability of insurance, indemnity or compensation and on the methods and documents to be used to inform trial subjects and to obtain their informed consent.

Appointment and Recognition of New Ethics Committees

Since 1st May 2004, (with the exception of those trials that are covered by the transitional arrangements), ethics committees have had to comply with criteria set out in the Regulations before being entitled to approve clinical trials for medicinal products. All such committees are required to be established and recognised by the Ethics Committee Supervisory Body under Part 2 of the Regulations. The function of the Supervisory Body under the Regulations is to be discharged for the time being by the Department of Health and Children pending the transfer of the function from the Department, following restructuring and the reform of the health services.

Under the Regulations, it will also be a matter for the appointing authority to collect fees (as set out in Regulations) and to provide an appropriate administrative structure and premises to enable the committees to carry out their functions within the strict timelines imposed by the Directive.

Other Ethics Committees

The implementation of the Directive only imposes controls in relation to clinical trials for medicinal products and does not impact on activities that have traditionally been carried out by other ethics committees (including trials not involving medicines).

Single Ethics Committee Opinion

It is obligatory under the Directive (and the Regulations) that, in the case of multi-centre clinical trials, a single ethics committee opinion be given for each Member State. This means that once an ethics committee opinion is given by a recognised ethics committee for a clinical trial in this country, that opinion must prevail at all centres where the trial is to be conducted. This does not mean that such a trial must be carried out at a particular centre. Obviously a local centre may decide, on a case by case basis, whether or not it would permit a particular trial to be carried out at its site.

In the context of the single ethics committee opinion, it is necessary that the ethics committee takes into account the suitability of the investigator and supporting staff and the quality and adequacy of the facilities available at each of the proposed trial sites. Any subsequent decisions that may be taken locally at these trial sites can only be taken on a yes/no basis.

Ethics Committee Supervisory Body

The implementation of the Directive only imposes controls in relation to clinical trials for medicinal products and does not impact on activities that have traditionally been carried out by other ethics committees (including trials not involving medicines).

Composition of New Ethics Committees

The Regulations provide, in Schedule 2, for ethics committees to have a membership of not more than 21 members, of which at least one-third are to be lay members and at least half of those are to be persons that have never been health care professionals. There is also provision for the appointment of two vice-chairpersons and for the appointment of deputies who may attend in the absence of a member.

The framework for these committees has been designed in such a way as to provide maximum flexibility for their operation as ethics committees and to enable them to properly discharge their functions under the Regulations in a timely manner.

Clinical Indemnity Scheme

An ethics committee established by an agency covered by the Clinical Indemnity Scheme will also be covered by that Scheme. This cover extends to individual committee members whether or not they are employees of the agency concerned. The same situation would prevail if an ethics committee were to be established by a number of agencies covered by the Clinical Indemnity Scheme, acting conjointly.

In view of the nature of the Clinical Indemnity Scheme, no particular provision has been included in the Regulations in respect of indemnity.

Responsibility for Consideration of Insurance and Indemnity

Responsibility for considering the availability of insurance, indemnity or compensation in the context of clinical trials for medicinal products will be carried out by the new ethics committees.

Exemption for Academic Research

The Directive requires that investigational medicinal products and the devices for the administration of such products should be made available free of charge by sponsors. An exemption has been incorporated in the Regulations for academic researchers whereby this requirement will not apply to non-commercial clinical trials that are conducted by investigator-sponsors, without the participation of the pharmaceutical industry, in circumstances where the investigator-sponsors have no commercial or financial interest in the outcome of the trial insofar as such products or devices have not been obtained free of charge by the investigator-sponsor.

Further information

See the Health Product’s Regulatory Authority¬†website for information on the procedures for obtaining HPRA approval for clinical trials.