Good clinical practice (GCP) is an international ethical and scientific quality standard for designing, recording and reporting trials that involve the participation of human subjects. Compliance with this standard provides public assurance that the rights, safety and wellbeing of trial subjects are protected and that clinical-trial data are credible.
The protection of clinical trial subjects is consistent with the principles set out in the Declaration of Helsinki. This is a statement of ethical principles developed by the World Medical Association.
Requirements for the conduct of clinical trials in the European Union (EU), including GCP and good manufacturing practice (GMP) and GCP or GMP inspections, are implemented in:
Information concerning the activities in EU Member States can be found via the Heads of Medicines Agencies.
The European Medicines Agency plays an important role in the harmonisation and co-ordination of GCP-related activity at an EU level. It is involved in:
- co-ordinating GCP inspections for the centralised procedure;
- preparing guidance on GCP topics through the work of the GCP Inspectors Working Group;
- co-ordinating advice on the interpretation of EU GCP requirements and related technical issues;
- developing of EU-wide guidelines on GCP inspections and related procedures for the centralised procedure.
For more information on clinical trial authorisation, safety monitoring, GCP inspections, and GCP and GMP requirements for clinical trials in the European Economic Area (EEA), see volume 10: clinical-trial guidelines of the rules governing medicinal products in the EU.
International clinical trials
Regardless of where they are conducted, all clinical trials included in applications for marketing authorisation in the EEA must be in accordance with:
- Directive 2001/83/EC Annex I, as amended by Directive 2003/63/EC;
- the ethical standards of the Clinical Trials Directive (Directive 2001/20/EC).
In July 1996, the EU adopted the guideline for good clinical practice, which lays out unified GCP standards for Europe, the United States of America and Japan.
For more information, see:
- the Council for International Organizations of Medical Science (CIOMS);
- the World Medical Association.
Clinical trials conducted in countries outside the EU
The number of clinical trials and clinical-trial subjects outside Western Europe and North America has been increasing for a number of years. The Agency has been tracking the geographic origins of patients included in pivotal trials submitted in marketing authorisations to the centralised procedure.
- For more information, see the overview of patient recruitment and the geographical location of investigator sites.
In April 2012, the Agency published the final version of the reflection paper on ethical and GCP aspects of clinical trials of medicinal products for human use conducted outside of the EU / EEA and submitted in marketing authorisation applications to the EU regulatory authorities. The aim of the paper is to strengthen existing processes to provide assurance to regulators and stakeholders that clinical trials meet the required ethical and GCP standards, no matter where in the world they have been conducted.
The reflection paper is part of the Agency’s strategy developed to address the challenges arising from the increasing globalisation of clinical research. These challenges are addressed in a two-fold manner, by:
- putting forward concrete steps for international cooperation between regulatory authorities in the regulation of clinical trials, with a specific emphasis on capacity-building initiatives for a common approach to oversight of trials and to ensure a robust framework for the oversight and conduct of clinical trials;
- clarifying and determining the practical steps by which EU regulators will gain assurance that ethical and GCP standards are applied to clinical trials for human medicines, both during the development and during the marketing-authorisation-application phase.
The development of this paper followed on from the publication of the strategy paper on acceptance of clinical trials conducted in third countries and an international workshop in September 2010.
Working Group on Clinical Trials conducted outside of the EU / EEA
The Agency's Working Group on Clinical Trials Conducted Outside of the EU / EEA was established in 2009 to develop practical proposals for tasks and procedures or guidance in the four areas identified in the strategy paper on the acceptance of clinical trials conducted outside of the EU/EEA:
- clarify the practical application of ethical standards for clinical trials, in the context of the Agency's activities;
- determine the practical steps to be undertaken during the provision of guidance and advice in the drug-development phase;
- determine the practical steps to be undertaken during the marketing-authorisation phase;
- international cooperation in the regulation of clinical trials, their review and inspection and capacity building in this area and to develop a reflection paper on ethical and GCP aspects of clinical trials conducted outside the EU / EEA.
The Working Group includes representatives of the Committee for Medicinal Products for Human Use (CHMP), Paediatric Committee (PDCO), Committee for Orphan Medicinal Products (COMP), Coordination Group for Mutual Recognition and Decentralised Procedures (CMD), Clinical Trials Facilitation Group, GCP inspectors, Patients' and Consumers' Working Party, Healthcare Professionals' Working Group, Agency secretariat and European Commission.
The Working Group meets on a regular basis at the Agency.
Collaboration with the Food and Drug Administration
1. EMA-FDA GCP initiative
The Agency and the United States Food and Drug Administration (FDA) agreed to launch a joint initiative to collaborate on international GCP inspection activities in July 2009.
The initiative forms an important contribution to ensuring the protection of clinical-trial subjects in the context of the increasing globalisation of clinical research. The initiative comes under the scope of the confidentiality arrangements between the European Commission, the European Medicines Agency (EMA) and the FDA. For more information on these arrangements, see United States.
The initiative's main objectives are to:
- conduct periodic information exchanges on GCP-related information, to streamline sharing of GCP inspection planning information, and to communicate on inspection outcomes effectively and in a timely manner;
- conduct collaborative GCP inspections by sharing information, experience and inspection procedures, co-operating in the conduct of inspections and sharing knowledge of best practice;
- share information on the interpretation of GCP, by keeping each other informed of GCP-related legislation, regulatory guidance and related documents, and to identify and act together to benefit the clinical research process.
The initiative began with a pilot phase that ran between September 2009 and March 2011. During the pilot, the EMA and the FDA exchanged more than 250 documents relating to 54 different medicines. They also organised 13 joint inspections of clinical trials in conjunction with the GCP inspectors of the EU Member States.
A report and question-and-answer document on the outcomes of the pilot are available, which detail the success of the information-sharing and collaboration on inspections relating to clinical trials:
The pilot has laid the foundation for a more efficient use of limited resources, improved inspection coverage and better understanding of each agency’s inspection procedures. It demonstrates how the agencies can work together to improve human subject protection and better ensure the integrity of data submitted as the basis for drug approvals.
Based on the positive experience, the EMA and the FDA intend to continue with the initiative, incorporating lessons learned during the pilot. The agencies are updating the terms of engagement and procedures for participating authorities to reflect this.
Applicants interested in volunteering to take part in a collaborative inspection during the pilot phase should contact the EMA or the FDA.
2. EMA-EU MSs-FDA initiative on inspections for generic applications
In light of the successful implementation of the initiative mentioned in the previous section, the EMA, the FDA and the regulatory authorities in some EU Member States agreed to launch a joint initiative to collaborate on the sharing of information and conduct of inspections of bioequivalence studies submitted in support of marketing-authorisation applications for generic medicines. The objectives and the list of EU Member States involved are described in the Terms of engagement for this initiative.
The initiative will begin with an 18-month pilot phase that will run between January 2014 and June 2015. A report on its outcome would be made available after the pilot phase.
- Good clinical practice compliance (veterinary)
- Directive 2001/20/EC
- Directive 2005/28/EC
- Volume 10: clinical trial guidelines
- Guideline for good clinical practice
- European Medicines Agency strategy paper: Acceptance of clinical trials conducted in third countries, for evaluation in marketing-authorisation applications (04/12/2008)
- Reflection paper on ethical and good-clinical-practice aspects of clinical trials of medicinal products for human use conducted outside of the European Union (EU) / European Economic Area and submitted in marketing-authorisation applications to the EU regulatory authorities (16/04/2012)
- Draft reflection paper on ethical and good-clinical-practice aspects of clinical trials of medicinal products for human use conducted in third countries and submitted in marketing authorisation applications to the European Medicines Agency (28/05/2010)
- European Medicines Agency-Food and Drug Administration good-clinical-practice initiative: Terms of engagement and procedures for participating authorities (29/07/2009)