Clinical trial authorisations: Legislation and guidance documents

From 1 November 2007, letters from the MHRA relating to clinical trial submissions will not be signed. The wording and format of letters from the MHRA relating to clinical trial submissions will also be modified from this date. This is in line with MHRA policy.

Legislation
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.
› Directive 2001/20/EC (external link)

Commission Directive 2003/63/EC of 25 June 2003 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use (Text with EEA relevance).
› Directive 2003/63/EC (external link)

Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use.
› Directive 2001/83/EC (external link)

The Medicines for Human Use (Clinical Trials) Regulations 2004.
› The Medicines for Human Use (Clinical Trials) Regulations 2004: SI 2004/1031 (external link)

The MHRA has produced a description, which aims to help those involved in the conduct of clinical trials to follow and understand the Regulations.
› Description of the Medicines for Human use (Clinical Trials) regulations 2004 (236Kb)

The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006.
› The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 - SI 2006/1928 (external link)

The Medicines for Human Use (Clinical Trials) Amendment (No.2) Regulations 2006.
› The Medicines for Human Use (Clinical Trials) Amendment Regulations (No.2) 2006 - SI 2006/2984 (external link)

The consultation exercise on the Amendment Regulations (MLX 328 (see below)) ran from November 2005 to February 2006.
› MLX 328: consultation on implementation of the European Commission’s Directive on Good Clinical Practice (2005/28/EC) (548Kb)

A summary of responses to the consultation exercise MLX 328.
› The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 - Summary of responses to consultation document MLX 328 (143Kb)

Guidance documents
EC The rules governing medicinal products in the European Union, VOLUME 10. Notice to applicants. Clinical Trials.
› EudraLex: The Rules Governing Medicinal Products in the European Union: Volume 10 - Clinical Trials (external link)

EC The rules governing medicinal products in the European Union, Volume 10 Notice to applicants. Questions & Answers. Clinical Trial Documents April 2006.
› EudraLex: The Rules Governing Medicinal products in the European Union: Volume 10- Questions & Answers (external link)

EC The rules governing medicinal products in the European Union, VOLUME 4. Notice to applicants. EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use.
› EudraLex: The Rules Governing Medicinal Products in the European Union: Volume 4 - Good Manufacturing Practice (external link)

EC Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial October 2005.
› Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial - October 2005 (external link)

EMEA/CHMP/SWP/28367/07.
› Guideline on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products (external link)

For guidance on EudraCT.
› EudraCT supporting documentation (external link)

HMP/QWP/185401/2004 final.
› Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials (external link)

Labelling requirements. EC The rules governing medicinal products in the European Union, VOLUME 4. Notice to applicants.
› ANNEX 13 Manufacture of investigational medicinal products JULY 2003

Databases
The European Clinical Trials database, EudraCT, established in accordance with Directive 2001/20/EC.
› EudraCT: European Clinical Trials Database (external link)

EudraVigilance, a data processing network and management system for reporting and evaluating suspected adverse reactions during the development and following the marketing authorisation of medicinal products in the European Economic Area (EEA).
› EudraVigilance (external link)

Information from the MHRA
The Commission on Human Medicines provides advice to the Ministers and the MHRA on human medicinal products: Commission on Human Medicines

› The final report of the expert scientific group (ESG) on phase 1 clinical trials (external link)

Following the publication of the final report of the independent expert working group on phase 1 clinical trials, the MHRA issued the following response.
› TGN1412: MHRA response to final report by independent expert working group on phase 1 clinical trials.

Time based performance measures for licensing.
› Licensing time-based performance measures

The Department of Health and Universities UK have issued a joint statement, 'Responsibilities, liabilities and risk management in clinical trials of medicines'. It recognises the Regulations do not change the underlying allocation of responsibilities in the partnership between universities and the NHS.
› Responsibilities, liabilities and risk management in clinical trials of medicines (163Kb)

A Memorandum of Understanding being agreed and signed by the MHRA, the Central Office for Research Ethics Committee (COREC) and the Gene Therapy Advisory Committee (GTAC) to allow sharing of information.
› Medicines for Human Use (Clinical Trials) Regulations 2004 - Memorandum of understanding between MHRA, COREC and GTAC (91Kb)

› Good Clinical Practice (GCP)
› Good Laboratory Practice (GLP)
› Good Manufacturing and Distribution Practice

Useful sites
The Department of Health and the Medical Research Council (MRC) have established a joint project to address a range of important issues raised by the academic trials community about the implementation of the Directive in the UK.
› Clinical Trial toolkit (external link)

The Council for International Organizations of Medical Sciences (CIOMS) is an international, non-governmental, non-profit organization established jointly by World Health Orgainization (WHO) and United Nations Educational, Scientific and Cultural Organization (UNESCO) in 1949.
› Council for International Organisations of Medical Sciences (external link)

Gene Therapy Advisory Committee (GTAC) is the UK national research Ethics Committee (REC) for gene therapy clinical research according to the Medicines for Human Use (Clinical Trials) Regulations 2004.
› Gene Therapy Advisory Committee (GTAC) (external link)

The Department of Health provides health and social care policy, guidance and publications.
› Department of Health (external link)

The Research Governance Framework for health and social care defines the broad principles of good research governance.
› Department of Health - Research governance (external link)

The National Research Ethics Service, Central Office.
› Central Office for Research Ethics Committees (COREC) (external link)

Health & Safety Executive (HSE) regulate contained use activities of genetically modified organisms.
› Genetically modified organisms (external link)

The Department for Environment, Food and Rural Affairs (DEFRA) regulate releases of genetically modified organisms into the environment.
› Genetically Modified Organism Regulations (external link)

The Administration of Radioactive Substances Advisory Committee (ARSAC) advises the Department of Health (DH) on matters relating to the granting of certificates to practice nuclear medicine in the UK, and radiological safety issues.
› The Administration of Radioactive Substances Advisory Committee (ARSAC)

The Stationery Office (TSO) publishes UK legislation and guidance documents.
› The Stationery Office (TSO) (external link)

The Office of Public Sector Information (OPSI) provides information on re-use of public sector information.
› Office of Public Sector Information (OPSI) (external link)