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.
Guidance on adjusting the management of clinical trials has been available for sponsors of clinical trials during the COVID-19 pandemic:
It covered:
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 and guidelines, 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 the integrity 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.
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:
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:
Regardless of where they are conducted, all clinical trials included in applications for marketing authorisation in the EEA must be in accordance with:
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 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.
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:
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.
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:
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.
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.
The main objectives are to:
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, 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:
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: