Good clinical practice
HumanCompliance and inspections
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:
- the 'Clinical Trial Directive' (Directive 2001/20/EC);
- the 'GCP Directive' (Directive 2005/28/EC).
- Clinical Trials Regulation' (Regulation 536/2014)
- Commission Implementing (Regulation 2017/556)
Information concerning the activities in EU Member States can be found via the Heads of Medicines Agencies.
Guidance on clinical trial management during the COVID-19 pandemic
Guidance on adjusting themanagement of clinical trials has been available for sponsors of clinical trials during the COVID-19 pandemic:
It covered:
- how to deal with extraordinary situations such as the self-isolation or quarantine of trial participants, limited access to public places including hospitals due to the risk of infection and reallocation of healthcare professionals;
- how to communicate these changes to national competent authorities;
- distribution of medicines to trial participants, remote verification of source datain the context of social distancing and notifying authorities of urgent actions taken to protect trial participants;
- clinical trials for COVID-19 treatments, including the need for large, multi-national trial protocols.
The guidance was drafted by representatives of the Clinical Trials Expert Group (CTEG) of the European Commission, supported by European Medicines Agency (EMA), the Clinical Trials Facilitation and Coordination Group (CTFG) of HMA and the GCP Inspectors’ Working Group, with the aim of ensuring the safety of trial participants across the EU while preserving data quality. It was first published in March 2020.
The guidance also advised sponsors to check relevant national legislation andguidelines, as clinical trials are overseen at national level in the EU.
The CHMP urged the EU research community to prioritise large randomised controlled clinical studies to support the rapid development and approval of COVID-19 medicines. It also emphasised the need to include all EU countries in these trials:
A scientific guideline has also been available for sponsors of clinical trials affected by the COVID-19 pandemic, to help ensure theintegrity of studies and the interpretation of their results while safeguarding the safety of trial participants:
This guidance is no longer relevant in relation to COVID-19, except to help evaluate the clinical trials affected by the pandemic. It can still apply in the context of other major disruptions, such as the war in Ukraine.
EMA role
The European Medicines Agency (EMA) 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.
Marketing authorisation holders and applicants need to use EMA's IRIS system to communicate with EMA on GCP inspections requested by the Agency’s scientific committees.
Using IRIS for GCP inspections improves efficiency by harmonising and automating processes and re-using master data held by EMA. It also simplifies retrieving and reporting data.
More information on the use of EMA's IRIS system:
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:
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 Clinical trials submitted in marketing-authorisation applications to the European Medicines Agency: 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 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-autho.... 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 European Medicines Agency strategy paper: Acceptance of clinical trials conducted in third countries, for evaluation in marketing-authorisation applications 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 Coordination Group (CTCG), 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
Good clinical practice initiative
EMA and the United States Food and Drug Administration (FDA) have initiated a collaboration on international GCP inspection activities.
The initiative helps protect clinical trial subjects in the context of the increasing globalisation of clinical research.
It is in line with the confidentiality arrangements between the European Commission, EMA and FDA.
- European Medicines Agency-Food and Drug Administration good-clinical-practice initiative
- United States Food and Drug Administration - European Medicines Agency: Good-clinical-practice initiative: Frequently asked questions and answers
The 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:
- Report on the pilot European Medicines Agency-Food and Drug Administration good-clinical-practice initiative
- Questions and answers: European Medicines Agency-Food and Drug Administration good-clinical-practice initiative
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, EMA and the FDA intend to continue with the initiative, incorporating lessons learned during the pilot. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) is an observer of the collaboration as of June 2017.
For more information, see:
Inspections for generic applications
EMA, FDA, the World Health Organisation (WHO) and regulatory authorities in certain EU Member States uphold a joint initiative consisting in sharing information and conducting inspections.
The inspections involve bioequivalence studies supporting marketing authorisation applications for generic medicines.
Terms of engagement for this initiative and the list of EU member states involved are available in the documents below: