Regulatory Authority
Regulatory Authority
Scope of Assessment
Regulatory Fees
Ethics Committee
Ethics Committee
Scope of Review
Ethics Committee Fees
Authorizing Body
Clinical Trial Lifecycle
Submission Process
Submission Content
Timeline of Review
Trial Initiation
Safety Reporting
Progress Reporting
Sponsorship
Definition of Sponsor
Trial Authorization
Insurance
Compensation
Quality, Data & Records Management
Site/Investigator Selection
Informed Consent
Documentation Requirements
Required Elements
Compensation Disclosure
Participant Rights
Special Circumstances/Emergencies
Vulnerable Populations
Children/Minors
Pregnant Women, Fetuses & Neonates
Prisoners
Mentally Impaired
Investigational Products
Definition of Investigational Product
Manufacturing & Import
IMP/IND Quality Requirements
Labeling & Packaging
Product Management
Specimens
Definition of Specimen
Import & Export
Consent for Specimens
United Kingdom
QUICK FACTS
Clinical trial application languageEnglish
Parallel regulatory and ethical review permittedYes
Clinical trial registration requiredYes
In-country sponsor presence/representation requiredYes
Age of minorsUnder 16
Specimens export allowedYes
Regulatory Authority > Regulatory Authority
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Last content review/update: April 26, 2017. Submit updates or comments.
SUMMARY
Overview
As per the MHCTR and the MHCTR2006, the Medicines and Healthcare Products Regulatory Agency (MHRA) is the regulatory authority responsible for clinical trial approvals, oversight, and inspections in the United Kingdom (UK). The MHRA grants permission for clinical trials to be conducted in the UK in accordance with the MHCTR and the MHCTR2006.
 
According to Additional Resource (A), the MHRA is an executive agency within the Department of Health (DOH). The MHRA is granted authority by the DOH to regulate and license all medicines and medical devices within the UK. Per the G-MHRA-CTAuth and Additional Resource (B), the agency’s Clinical Trials Unit (CTU) is specifically focused on reviewing applications to conduct clinical trials of medicinal products.
 
Contact Information
MHRA
151 Buckingham Palace Road
Victoria
London
SW1W 9SZ
UK
 
Phone: 020-3080-6000
Fax: 0203-118-9803
General Email: info@mhra.gsi.gov.uk
 
Application Submissions Contact Information
MHRA
151 Buckingham Palace Road
Victoria
London
SW1W 9SZ
UK
 
*Clinical Research Office:
Phone: 020-3080-6456
 
*In addition, the G-MHRA-CTAuth includes several email addresses for specific purposes related to submissions.
 
ADDITIONAL RESOURCES
(A) (Website) MHRA – About Us (Current as of February 20, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(B) (Website) Health Research Authority – MHRA – Clinical Trial Authorisation (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(C) (Website) Contact MHRA (Last Updated October 13, 2016)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(D) (Website) Clinical Trials ToolkitCTA Submission (Current as of February 20, 2017)
National Institute for Health Research, National Health Service England, Department of Health, UK Government
 
European Parliament and Council of the European Union
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1(4) and Part 3 (12, 17 and 18)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Section: Part 2 (Conditions Based on Article 3 of the Directive)
 
(3) (Guidance) Guidance: Clinical Trials for Medicines: Manage Your Authorisation, Report Safety Issues (G-MHRA-CTAuth) (Last Updated March 31, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
Relevant Sections: Clinical Trials Named Contact; and Report an Urgent Safety Issue
Regulatory Authority > Scope of Assessment
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Last content review/update: February 22, 2017. Submit updates or comments.
SUMMARY
Overview
In accordance with the MHCTR and the MHCTR2006, the Medicines and Healthcare Products Regulatory Agency (MHRA) is responsible for reviewing, evaluating, and approving applications for clinical trials using registered or unregistered investigational products (IPs). (Note: IPs are known as investigational medicinal products (IMPs) in the United Kingdom (UK)). The MPHFR and the G-MHRA-CTApp specify that the scope of the MHRA’s assessment includes all clinical trials (Phases I-IV). As delineated in Additional Resources (A) and (B), the MHRA’s review process may be conducted in parallel with the ethics committee (EC) review. However, pursuant to the MHCTR and the MHCTR2006, the clinical trial must be authorized by the MHRA, and an EC established and recognized by the United Kingdom Ethics Committee Authority (UKECA) must provide a favorable opinion in relation to the trial prior to the trial’s commencement. (See the Ethics Committee topic for detailed information on the EC review and approval process.)
 
According to Additional Resources (A) and (C), the sponsor or his/her designated representative must also apply for a European Clinical Trials Database (EudraCT) number by registering a clinical trial in the EudraCT database. (See Clinical Trial Lifecycle topic, Submission Process subtopic for additional details.)
 
Clinical Trial Review Process
Application Submission
The MHCTR and Additional Resources (A) and (E) specify that the MHRA coordinates the clinical trial application process. Per Additional Resource (G), upon receipt of a clinical trial application, the MHRA’s Clinical Trials Unit (CTU) conducts an application validation and the sponsor or his/her designated legal representative is sent an acknowledgement letter. If the application is valid, the CTU assessment period begins from the date of receipt (Day 0). If the application is not valid, the sponsor or his/her designated representative will be informed of the deficiencies, and he/she must provide a full new application. According to the MHCTR, if the sponsor or his/her designated representative does not receive a request for additional information from the MHRA within 30 days, the application is treated as authorized. (See the Clinical Trial Lifecycle topic, Timeline of Review subtopic for additional details.)
 
In addition, as stated in the G-MHRA-CTApp, certain first-in-human (Phase I) trials with specific risk factors may require the MHRA’s CTU to seek advice from an Expert Advisory Group/the Commission on Human Medicines before giving approval. See the G-MHRA-CTApp for examples of which trials require expert advice and for detailed requirements.
 
Notification Scheme Submission
As set forth in the G-MHRA-CTApp and Additional Resources (A), (E), (F), (G), and (H), in lieu of a standard application, a sponsor or his/her designated representative may submit a notification of a clinical trial to the MHRA under the Notification Scheme when conducting “Type A” trials. Type A trials are those in which the potential risk associated with an IP is determined to be no higher than that of standard medical care, and involve medicinal products licensed in any EU Member State that meet the following criteria:
  • they relate to the licensed range of indications, dosage and form, or,
  • they involve off-label use established by practice and supported by published evidence and/or guidelines
See the G-MHRA-CTApp and Additional Resources (E), (F), (G) and (H) for detailed Notification Scheme requirements.
 
Upon receipt of a valid notification, the MHRA will send an acknowledgement letter to the sponsor or his/her designated representative stating that the trial may proceed if an objection is not raised within 14 days. If the MHRA does not send a Notification Objection letter, the acknowledgement letter serves as the authorization.
 
If the MHRA raises objections, the submission is assessed as a standard request for authorization (refer to information under the Application Submission heading above), and the CTU initial assessment is performed within 30 days of receipt of valid application.
 
(See the Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics for detailed submission requirements.)
 
ADDITIONAL RESOURCES
Health Research Authority, National Health Service England, Department of Health, UK Government
 
European Forum on Good Clinical Practice
 
(C) (EU Website) EudraCT – Help: Overview of EudraCT (Current as of February 20, 2017)
European Medicines Agency, European Union
 
(D) (Website) EudraCT Results Multi-Media Tutorials (Last Updated February 20, 2017)
European Medicines Agency, European Union
 
(E) (Flowchart) Clinical Trial Authorisation (CTA) Application Flowchart (Current as of February 20, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(F) (Website) Health Research Authority – MHRA – Clinical Trial Authorisation (Current as of February 20, 2017)
Health Research Authority,  National Health Service  England, Department of Health, UK Government
 
(G) (Website) Clinical Trials ToolkitCTA Submission (Current as of February 20, 2017)
National Institute for Health Research, National Health Service England, Department of Health, UK Government
 
(H) (Document) Clinical Trials Toolkit – Trial Supplies (Updated March 2015)
Gupta, Oliver (MODEPHARMA)
 
European Parliament and Council of the European Union
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (2), Part 2 (5, 6, and 7), Part 3 (12, 14, 15, 17, and 18), and Schedule 2
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
 
(3) (Regulation) The Medicines (Products for Human Use) (Fees) Regulations 2013 (MPHFR) (Effective March 11, 2013)
Department of Health, UK Government
 
Relevant Section: Schedule 2
(Part 1(1))
 
(4) (Guidance) Guidance: Clinical Trials for Medicines: Apply for Authorisation in the UK (G-MHRA-CTApp) (Last Updated March 31, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
Relevant Section: Clinical Trial Phases
 
Regulatory Authority > Regulatory Fees
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Last content review/update: February 22, 2017. Submit updates or comments.
SUMMARY
Overview
As per the MHCTR, the MHCTR2006, the G-MHRA-CTApp, and the G-MHRAFees, the sponsor or his/her designated representative is responsible for paying a fee to the Medicines and Healthcare Products Regulatory Agency (MHRA) to submit a clinical trial application for authorization. According to the G-MHRA-CTApp, the sponsor or his/her designated representative must provide proof of payment in the cover letter and/or as a separate document (e.g., a photocopy of a check or confirmation of a bank transfer).
 
Effective April 1, 2016, the MHRA levies the following processing fees as delineated in the G-MHRAFees:
  • 3,060 British Pounds – Applications with an Investigational Medicinal Product (IMP) dossier
  • 225 British Pounds – Applications without an Investigational Medicinal Product (IMP) dossier
  • 225 British Pounds – Clinical trial variation/amendment
  • No cost – Phase IV notification
The G-MHRA-CTApp further indicates that no fees are required for applications submitted and authorized under the Notification Scheme. However, a fee will be charged to assess an application if an objection to the notification is raised and the application is not authorized by the MHRA.
 
Instructions for Payment of Clinical Trial Application Fee
According to the G-MHRAPaymt, payment information should be sent to the attention of the MHRA Cashier via one of the following routes:
 
Postal Address:
MHRA Cashiers
5th Floor
151 Buckingham Palace Road
London
SW1W 9SZ
UK
 
Bank transfers should be sent to:
Account Name: MHRA
Account Number: 10004386
Sort code: 60-70-80
Swift code: NWBKGB2L
Iban: GB68NWBK60708010004386
Bank: National Westminster Bank
 
Bank address:
National Westminster Bank
RBS, London Corporate Service Centre, 2nd Floor
280 Bishopsgate
London
EC2M 4RB
UK
 
Further information can be obtained from the Cashiers Department by email: cashiers@mhra.gsi.gov.uk.
 
ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Section: Part 3 (17)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: 11, 13, and Explanatory Note
 
(3) (Guidance) Guidance: Clinical Trials for Medicines: Apply for Authorisation in the UK (G-MHRA-CTApp) (Last Updated March 31, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(4) (Guidance) Statutory Guidance: Current MHRA Fees (G-MHRAFees) (Last Updated April 1, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
Relevant Section: 8 (Clinical trials: application fees)
 
(5) (Guidance) Guidance: Make a Payment to MHRA (G-MHRAPaymt) (Last Updated January 26, 2016)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
Ethics Committee > Ethics Committee
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Last content review/update: February 22, 2017. Submit updates or comments.
SUMMARY
Overview
As set forth in GAfREC and Additional Resource (A), the United Kingdom (UK) has a centralized recognition process for ethics committees (ECs), (known as research ethics committees (RECs) in the UK). Per Additional Resource (A), the UK Health Departments’ Research Ethics Service (UKRES) has authorized England’s Health Research Authority (HRA) to serve as the lead administrative body to coordinate the development of operational systems for ECs recognized or established by the United Kingdom Ethics Committee Authority (UKECA), the HRA, or, the Ministers or Health Departments of the four (4) UK nations (England, Northern Ireland, Scotland, and Wales).
 
As stated in GAfREC, the UKRES encompasses England’s Department of Health (DOH), Northern Ireland’s Department of Health, the Scottish Government Health and Social Care Directorates, the Wales Department for Health and Social Services as well as the ECs that are collectively recognized or established by these authorizing bodies. The National Research Ethics Service (NRES), now known as the Research Ethics Service (RES) and a core function of the HRA, formerly played the lead administrative role for the UKRES. A list of recognized ECs within the UKRES is available through Additional Resource (B).
 
All recognized UKRES ECs are required to comply with the provisions delineated in GAfREC and Additional Resource (A). However, specific ECs within the UKRES are recognized, or otherwise designated, to review certain types of research proposals. In accordance with the MHCTR and the MHCTR2006, ECs recognized to conduct reviews of clinical trials for investigational medicinal products (CTIMPs) are authorized by the statutory body, the UKECA, and are of central importance in this topic. Please refer to the Ethics Committee topic, Authorizing Body subtopic for additional details on the UKRES and the UKECA.
 
UKRES EC Composition
As delineated in the MHCTR, GAfREC, and Additional Resource (C), a UKRES recognized EC, which includes those recognized by UKECA, may consist of up to 18 members. However, per Additional Resource (E), the HRA has determined that the ideal number of members is 15.Collectively, members must encompass the qualifications and experience required to review and evaluate the scientific, medical, and ethical aspects of a proposed clinical trial. The ECs should include a diverse mixture of members in terms of age, disability, gender, race, religion, and sexual orientation. One third of the committee must also be lay members. Additionally, GAfREC states that a quorate meeting must be attended by at least seven (7) members and include the chair, at least one (1) expert member, and one (1) lay member.
 
Per Additional Resource (A), in order to accommodate the United States’ (US) quorum definition pursuant to its 45 CFR 46, the UKRES also makes special arrangements to review UK based research that is funded by US Federal Government departments and their agencies. In such cases, the quorum is a majority of the EC. See the ClinRegs United States page, Ethics Committee topic for more information on ethics review requirements in the US.
 
As indicated in GAfREC, committee member appointments are valid for up to five (5) years. Appointments may be renewed; however, members should not normally serve more than two (2) consecutive terms of five (5) years on the same EC, and members may resign at any time. Members must maintain confidentiality regarding all ethical review related matters and refuse any projects in which they have a conflict of interest. See the MHCTR and the GAfREC for additional EC composition requirements.
 
Terms of Reference and Review Procedures
In addition to complying with composition requirements, GAfREC and Additional Resource (A) state that an EC must also adopt written standard operating procedures (SOPs). The SOPs should cover the entire review process from application submission to opinion and notification, amendments, and annual reporting. For detailed EC procedures and information on other administrative processes, see GAfREC and Additional Resource (A).
 
ADDITIONAL RESOURCES
(A) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Introduction (Purpose and Scope), Implementation, Terminology (Glossary), and Sections 1, 2, and 3
 
(B) (Website) NHS Research Ethics Committee (REC) - Where to Book (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
European Forum on Good Clinical Practice
 
European Parliament and Council of the European Union
 
(E) (Website) Health Research Authority – Research Ethics Committees (RECs) (Current as of February 21, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
REQUIREMENTS
(1) (Guidance) Governance Arrangements for Research Ethics Committees: A Harmonised Edition (GAfREC) (May 2011) (Updated April 2012)
UK Health Departments
 
Relevant Sections: 1, 2, 3, 4, 5, 6, Glossary, Annex C, Annex E, and Annex F
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 2 , Part 3 (11, 12, 14, 15, 17, and 18), and Schedule 2
 
(3) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Ethics Committee > Scope of Review
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
According to GAfREC and Additional Resource (A), the primary scope of information assessed by ethics committees (ECs) recognized by the United Kingdom Health Departments’ Research Ethics Service (UKRES) relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial. (Note: ECs are known as research ethics committees (RECs) in the UK).
 
As per GAfREC, the MHCTR, the MHCTR2006, and the MHCTR2006-No2, ECs must pay special attention to reviewing informed consent and to protecting the welfare of certain classes of participants deemed to be vulnerable. (See Informed Consent topic, and the subtopics of Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired for additional information about these populations).
 
As indicated in GAfREC, the MHCTR, the MHCTR2006, and Additional Resource (A), ECs are responsible for ensuring an independent, timely, and competent review of all ethical aspects of the clinical trial protocol. They must act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants; confirming the suitability of the investigator(s), facilities, and methods; and verifying the adequacy of confidentiality and privacy safeguards. See GAfREC, the MHCTR, the MHCTR2006 and Additional Resource (A) for detailed ethics review guidelines.
 
Role in Clinical Trial Approval Process
As described in Additional Resources (A), (B), (C), (D), (E), and (F), the type of EC responsible for approval within the UKRES depends on the type of research being conducted. As discussed in the preceding subtopic, ECs recognized to conduct reviews of clinical trials for investigational medicinal products (CTIMPs) must be authorized by the United Kingdom Ethics Committee Authority (UKECA). Per GAfREC and Additional Resource (E), research studies other than CTIMPs are reviewed by UKRES recognized ECs that are established under Health Department policy within each of the four (4) UK nations (England, Northern Ireland, Scotland, and Wales).
 
As indicated in the MHCTR, the MHCTR2006, GAfREC, and Additional Resource (G), CTIMP applications require the favorable opinion of a UKECA recognized EC, and approval by the Medicines and Healthcare Products Regulatory Agency (MHRA) prior to the sponsor or his/her designated legal representative initiating the trial. Per Additional Resources (E) and (G), the MHRA’s review process may be conducted in parallel with the EC review. The G-MHRA-CTApp also states that an EC opinion may be obtained before, during, or after the MHRA application has been electronically submitted to the Integrated Research Application System (IRAS). Therefore to prepare an EC application, an IRAS account must be created.
 
Prior to submitting an application, the trial must first be registered in the EU Clinical Trials Register, which provides a EudraCT number. According to Additional Resources (A) and (C), the chief investigator (CI) must submit the electronic application to IRAS on the same day that a booking is made to schedule an EC review through the National Health Service (NHS) Research Ethics Committee (REC)’s Central Booking Service (CBS). The EudraCT number should also be included with the application. (See the Clinical Trial Lifecycle topic, Trial Initiation subtopic for additional information.)
 
According to the MHCTR, GAfREC, and Additional Resource (A), for all studies, the UKRES requires the CI to obtain only one EC review (referred to as the “main EC”) for a project taking place in the UK, regardless of the number of sites. Furthermore, Additional Resource (A) states that the CI should be based in the UK and that the REC may agree exceptionally to an application being submitted by a CI based outside the UK, but should consider as part of the ethical review whether adequate arrangements are in place for supervision of the study in the UK. Per Additional Resource (A), a site-specific assessment (SSA) may be necessary for multicenter clinical trials. The SSA is not a separate ethical review, but forms part of the single ethical review of the research. In the case of international studies, an application must be made to an EC in the UK, whether or not the study has a favourable ethical opinion from a committee outside the UK, and whether or not it has started outside the UK.
 
GAfREC, the MHCTR, and Additional Resource (A) also state that the EC must, in general, give its opinion within 60 calendar days of receipt of a valid application. When an EC requires further information before confirming its opinion, it may give a provisional opinion and may make one written request for further information, clarification, or changes to documentation. The time it takes for the EC to receive a complete response to its request does not count against the 60-day timeline. Certain studies, including gene therapy studies, will take 90 days, or 180 days if a specialist group or committee is consulted. For other exceptions, see GAfREC and the MHCTR. (See the Clinical Trial Lifecycle topic, Submission Process subtopic and Timeline of Review subtopic for detailed submission process requirements.)
 
There is no stated expiration date for an EC approval in the MHCTR, GAfREC, or the Additional Resources.
 
England's Health Research Authority (HRA) Approval
In addition to serving as the lead administrative body for all recognized ECs within the UKRES, per Additional Resources (B), (C), (J), (K), and (L), effective March 31, 2016, the HRA is authorized to approve all research studies led from England and which involve England’s National Health Service (NHS).
 
Per Additional Resources (B), (J), (K), and (L), these research studies now only require a single HRA approval to commence. The HRA approval process consists of an independent EC review provided through England’s Research Ethics Service (RES) (known as a regulatory compliance assessment conducted by HRA staff in accordance with established standard operating procedures (SOPs) and assessment criteria (Additional Resources (A) and (M)).
 
The new system replaces the need for NHS permission (also known as R&D Approval) to be obtained by each participating organization in England, and as such, replaces the requirement for local R&D approval processes. Instead, the sponsor and local research team conduct a site-specific assessment to ensure the suitability of the study site and investigative team.
 
Additionally, per Additional Resource (A), the HRA approval provides an initial step in preparing for the implementation of the EU Clinical Trials Regulation that will require applicants to submit a single clinical trial application via the EU portal. The regulation will become operational in October 2018.
 
ADDITIONAL RESOURCES
(A) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Introduction (Purpose and Scope), Terminology (Glossary), and Sections 1 and 5
 
(B) (Website) Determine Which Review Body Approvals are Required (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: 1, 3, and 4
 
(C) (Website) Health Research Authority - Research Ethics Committee (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(D) (Website) NHS Research Ethics Committee (REC) – Where to Book (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
European Forum on Good Clinical Practice
 
(F) (Website) Health Research Authority – Glossary (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Definitions of Authorised REC and Recognized REC
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(H) (Website) Integrated Research Application System (IRAS) (Version 5.4.0) (Last Updated December 20, 2016)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
European Parliament and Council
 
(J) (Website) HRA Approval: Questions and Answers (Last Updated January 8, 2015)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: 1, 2, and 3
 
(K) (Website) Health Research Authority - HRA Approval (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(M) (Guidance) HRA Approval: Assessment Criteria and Standards Document (March 30, 2016) (Version 4.0)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: 6
 
(N) (Website) EudraCT – European Clinical Trials Database (Current as of February 20, 2017)
European Medicines Agency, European Union
 
REQUIREMENTS
(1) (Guidance) Governance Arrangements for Research Ethics Committees: A Harmonised Edition (GAfREC) (May 2011) (Updated April 2012)
UK Health Departments
 
Relevant Sections: 2.3, 3, 4.3, and 5.4
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (2 and 3), Part 3 (11, 12, 14, 15, 17, and 18), Schedule 2, and Schedule 3 (Part 1)
 
(3) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
 
(4) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment (No.2) Regulations 2006
(S.I. 2006/2984) (MHCTR2006-No2) (December 12, 2006)
Department of Health, UK Government
 
Relevant Sections: Amendment of the Clinical Trials Regulations; Amendment of the Adults with Incapacity (Scotland) Act 2000
 
(5) (Guidance) Guidance: Clinical Trials for Medicines: Apply for Authorisation in the UK (G-MHRA-CTApp) (Last Updated March 31, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
Relevant Section: Clinical Trial Phases
 
Ethics Committee > Ethics Committee Fees
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Last content review/update: February 22, 2017. Submit updates or comments.
SUMMARY
Overview
As set forth in GAfREC and Additional Resource (A), ethics committees (ECs) are not permitted to charge an application fee or seek any other financial contribution or donation for reviewing research proposals. Additionally, per GAfREC, EC members receive no payment for contributing to the application review process at scheduled meetings or for attending these meetings.
 
ADDITIONAL RESOURCES
European Forum on Good Clinical Practice
 
REQUIREMENTS

(1) (Guidance) Governance Arrangements for Research Ethics Committees: A Harmonised Edition (GAfREC) (May 2011) (Updated April 2012)
UK Health Departments

Relevant Section: 4.3

 

Ethics Committee > Authorizing Body
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Last content review/update: February 22, 2017. Submit updates or comments.
SUMMARY
Overview
UK Health Departments’ Research Ethics Service (RES)
As stated in GAfREC, the United Kingdom (UK) Health Departments’ Research Ethics Service (UKRES) encompasses England’s Department of Health (DOH), Northern Ireland’s Department of Health, the Scottish Government Health and Social Care Directorates, the Wales Department for Health and Social Services, as well as the ethics committees (ECs) (known as research ethics committees (RECs) in the UK) collectively recognized or established by these authorizing bodies.
 
Each of the health departments within the four (4) UK nations (England, Northern Ireland, Scotland, and Wales) is represented by a head office that serves as the appointing authority for the recognized ECs. Per GAfREC and Additional Resource (A), within England’s DOH, the Health Research Authority (HRA) is the head office with appointing authority for the Research Ethics Service (RES), formerly the National Research Ethics Service (NRES). The official RES head offices (i.e., appointing authorities) for the other nations are represented by the Health and Social Care Research and Development (HSC R&D) Division within Northern Ireland’s HSC Public Health Agency (Additional Resource (B)); the Chief Scientist Office (CSO) within the Scottish Government Health and Social Care Directorates (Additional Resource (C)); and the Ethics Service within Health and Care Research Wales (Additional Resource (D)). The head offices work together to maintain a consistent approach in operating the UKRES ECs.
 
UK Ethics Committee Authority (UKECA)
As set forth in the MHCTR, the MHCTR2006, and GAfREC, the United Kingdom Ethics Committee Authority (UKECA) is responsible for establishing, recognizing, and monitoring ECs that review applications for clinical trials of investigational medicinal products (CTIMPs). As indicated in the MHCTR and Additional Resources (E) and (F), the UKECA recognizes two (2) types of ECs for new CTIMPs applications:
  • Type 1: Reviews Phase 1 clinical trials in healthy volunteers taking place anywhere in the UK
  • Type 3: Reviews clinical trials in patients taking place anywhere in the UK
New applications are no longer allocated for review by ECs with Type 2 recognition. Additionally, per Additional Resource (F), when the UKECA recognizes an EC it must specify the following:
  • Whether the EC may act for the entire UK, or, only for a particular area of the UK
  • The description/class of clinical trial for which the EC may provide ethics review
Per the GAfREC and Additional Resources (E) and (F), the HRA is responsible for providing advice, assistance and operational support to all UK ECs recognized by the UKECA.
 
As indicated in Additional Resource (G), UKECA business is chaired by the HRA and reviewed at the bimonthly Four Nations’ Meeting, which brings together England’s DOH, Northern Ireland’s HSC, Scotland’s CSO, and the Health and Care Research Wales.
 
Registration, Auditing, and Accreditation
As delineated in the GAfREC and Additional Resource (E), the UKRES is responsible for ensuring the quality of the ECs, including the UKECA ECs, through regular monitoring, auditing and accrediting their operations and performance.
 
England’s Health Research Authority (HRA)
In accordance with the CareAct2014 and Additional Resource (H), the HRA was established in 2015 as a non-departmental public body, sponsored by England’s DOH to standardize regulatory practices relating to health and social care research, and to encourage safe and ethical research conducted across the UK. According to GAfREC and Additional Resource (E), the UKRES has authorized England’s HRA to serve as the lead administrative body to coordinate the development of operational systems for ECs recognized or established by the UKECA, the HRA, or, the Ministers or Health Departments of the four (4) UK nations (including their respective head offices). The RES is a core function of the HRA and formerly played the lead administrative role for the UKRES.
 
As indicated in GAfREC and Additional Resources (I) and (J), the HRA, in support of the UKRES and UKECA, supports two (2) main types of ECs in the UK:
  • Authorized ECs – those authorized by the UKRES to review all applications except those relating to CTIMPs
  • Recognized ECs – those recognized by the UKECA, a statutory body established under the MHCTR, to review applications relating to CTIMPs. Recognized ECs may also review non-CTIMP research.
ADDITIONAL RESOURCES
(A) (Website) Health Research Authority - Research Ethics Service (RES) (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
HSC R&D Division, Public Health Agency, Department of Health, Northern Ireland Government
 
(C) (Website) Scottish Government Health Directorates – Chief Scientist Office (Current as of February 20, 2017)
Chief Scientist Office, National Health Service Scotland, Scottish Government Health Directorates, Scottish Government
 
(D) (Website) Health and Care Research Wales – Gaining Ethical Approval (Current as of February 20, 2017)
Health and Care Research Wales, National Health Service Wales, Department of Welsh Government
 
(E) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Introduction (Purpose and Scope), Implementation, Terminology (Glossary), and Sections 1, 2, and 3
 
European Forum on Good Clinical Practice
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(G) (Website) Health Research Authority – Four Nations and UKECA – Resource Page (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(H) (Website) Health Research Authority – Who We Are (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(I) (Website) Determine Which Review Body Approvals are Required (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: 1, 3, and 4
 
(J) (Website) Health Research Authority – Glossary (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Definitions of Authorised REC and Recognized REC
 
REQUIREMENTS
(1) (Guidance) Governance Arrangements for Research Ethics Committees: A Harmonised Edition (GAfREC) (May 2011) (Updated April 2012)
UK Health Departments
 
Relevant Sections: 1.3, 2.1, 2.3, 3.3, 5.4, Glossary, Annex C, Annex D, Annex E, and Annex F
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 2, Part 3 (12), and Schedule 2
 
(3) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Section: Part 2 (Conditions Based on Article 3 of the Directive)
 
(4) (Legislation) Care Act 2014 (Chapter 23) (CareAct2014) (May 14, 2014)
Parliament, UK Government
 
Relevant Sections: Part 3 (Chapter 2, Section 109) and Part 4 (Sections 109-115)
 
Clinical Trial Lifecycle > Submission Process
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SUMMARY
Overview
In accordance with the MHCTR, the MHCTR2006, and Additional Resources (A), (B), and (C), the United Kingdom (UK) requires the sponsor or his/her designated legal representative to obtain clinical trial authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA) prior to initiating the trial. The MHCTR, the G-MHRA-CTApp, and Additional Resource (D) also state that if the sponsor is not based in the European Economic Area (EEA), he/she must appoint a legal representative located in the EEA.
 
Per Additional Resources (C) and (E), the sponsor may submit an application for clinical trial authorization to the MHRA in parallel with the chief investigator’s (CI) submission to a recognized ethics committee (EC) for a favorable ethics opinion.
 
According to the G-MHRA-CTApp and Additional Resources (F) and (G), the sponsor or his/her designated representative must apply for a EudraCT number, which is a prerequisite to creating a clinical trial application as well as submitting an EC application to the Integrated Research Application System (IRAS). The EudraCT number is a unique European Union (EU)-wide reference number assigned to a trial that is used by the review bodies (the MHRA and ECs) to exchange trial-related information. Only after receiving a EudraCT number can the sponsor or his/her designated representative generate a clinical trial application electronically via the EU’s EudraCT database or the UK’s IRAS database. Both systems provide a saved data file in the form of an XML file, which is stored on the sponsor’s or his/her designated representative’s local hard drive, can be shared across both systems, and can be generated into PDF files. However, per Additional Resource (H), IRAS is the most efficient submission option because it enables researchers to enter the information required by the UK review bodies only once, rather than having to complete several separate applications forms to obtain these permissions and approvals.
(See Clinical Trial Lifecycle topic, Submission Content subtopic for detailed submission requirements).
 
Delivery Address for Clinical Trial Application
MHRA
Information Processing Unit
Area 6
Medicines & Healthcare Products Regulatory Agency
151 Buckingham Palace Road
Victoria
London
SW1W 9SZ
UK
 
Assembly and Number of Copies
Based on information provided in the G-MHRA-CTApp, and Additional Resources (F), (G), (I), (J), and (K), once the sponsor or his/her designated representative obtains a EudraCT number by registering his/her clinical trial application in the EudraCT database, he/she must download and complete the clinical trial application form on EudraCT or IRAS. Per the G-MHRA-CTApp, XML and PDF versions must be created for the form, and all documents to be included in the application package must have copy and paste functionality. When completed, the form should be saved and signed electronically, and submitted along with the rest of the required documents.
 
Application files may be saved and prepared on a local computer prior to uploading to EudraCT, IRAS, or the Heads of Medicines Agencies (HMA) Common European Submission Portal (CESP) for submission to the MHRA. Information included in the submission package will be used to validate the application; incomplete applications will be rejected. Per the G-MHRA-CTApp and Additional Resources (J) and (K), the CESP is only used to submit files, not to download files to a local computer. Refer to Additional Resources (F), (G), (I), and (O) for detailed EudraCT application submission instructions, Additional Resource (H) for IRAS submission information, and the G-MHRA-CTApp and Additional Resources (J) and (K) for CESP submission information. (See Clinical Trial Lifecycle topic, Submission Content subtopic for documentation to be included in the application package.)
 
According to the G-HRA-REC-Bkg, effective May 2014, all EC forms and their associated supporting documentation should be submitted electronically via IRAS, thereby eliminating the need to submit any hard copies. Detailed instructions about submitting EC applications through IRAS are available at Additional Resources (H) and (N).
 
Clinical Trial Application Language Requirements
As delineated in the MHCTR, the clinical trial application and accompanying material must be provided in English.
 
ADDITIONAL RESOURCES
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(B) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Terminology
(Glossary) and Section 14
 
European Forum on Good Clinical Practice
 
(D) (Website) Health Research Authority – Sponsor’s Legal Representative (Current as of February 20, 2017)
Health Research Authority, National Health Service  England, Department of Health, UK Government
 
(E) (Website) Health Research Authority - Research Ethics Service (RES) (Current as of February 20, 2017)
Health Research Authority, National Health Service  England, Department of Health, UK Government
 
(F) (Website) EudraCT – European Clinical Trials Database (Current as of February 20, 2017)
European Medicines Agency, European Union
 
(G) (Website) EudraCT – Overview of the EudraCT Public and Secure Applications (Last Updated October 14, 2016)
European Medicines Agency, European Union
 
(H) (Website) Integrated Research Application System (Version 5.4.0) (Current as of December 20, 2016)
Health Research Authority, Department of Health, National Health Service, UK Government
 
Enterprise Directorate-General, European Commission
 
Heads of Medicines Agencies, European Economic Area
 
(K) (Document) CESP Demonstration (Date unavailable)
Heads of Medicines Agencies, European Economic Area
 
(L) (Website) Clinical Trials Toolkit – CTA Submission (Current as of February 20, 2017)
National Institute for Health Research, National Health Service England, Department of Health, UK Government
 
European Parliament and Council
 
Health Research Authority, National Health Service  England, Department of Health, UK Government
 
(O) (Website) EudraCT – Protocol Related Documentation (Last Updated January 4, 2017)
European Medicines Agency, European Union
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (3) and Part 3 (12, 14, 17, and 18)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
 
(3) (Guidance) Guidance: Clinical Trials for Medicines: Apply for Authorisation in the UK (G-MHRA-CTApp) (Last Updated March 31, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(4) (Guideline) Research Ethics Committee (REC) - New Booking & Submission Processes: A Step by Step Guide (G-HRA-REC-Bkg) (May 19, 2014)
Health Research Authority, Department of Health, National Health Service, UK Government
 
Clinical Trial Lifecycle > Submission Content
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SUMMARY
Overview
As set forth in the MHCTR, the MHCTR2006, and Additional Resources (A), (B), and (C), the Medicines and Healthcare Products Regulatory Agency (MHRA) requires the sponsor or his/her designated legal representative to apply for clinical trial authorization, and the chief investigator (CI) or principal investigator (PI) to apply for a favorable opinion from a recognized ethics committee (EC). (See the Ethics Committee topic for detailed coverage of EC operations and responsibilities.)
 
MHRA Requirements
As specified in the MHCTR and the G-MHRA-CTApp, a clinical trial application submission should contain PDF and XML files for each of the following documents sent to the MHRA:
  • Cover letter (when applicable, this should include a statement that the submission is for a Phase I trial eligible for the shortened assessment time)
  • Sponsor or designated representative name and contact information
  • Investigator(s) contact information
  • Clinical Trial Application
  • Protocol and description of proposed trial
  • Copy of EC opinion, if available
  • Investigator’s Brochure (IB) or document replacing the IB
  • Investigational Medicinal Product Dossier (IMPD) or simplified IMPD
  • Non-Investigational Medicinal Product (NIMP) Dossier (if required)
  • Informed Consent Form (ICF)
  • Scientific advice - A summary of scientific advice from any Member State or the European Medicines Agency (EMA) regarding the trial (if available)
  • EMA Decision - A copy of the EMA’s Decision on the Pediatric Investigation Plan and the opinion of the Pediatric Committee (if applicable)
  • Investigational Medicinal Product (IMP) labeling content (or justification for its absence)
  • Proof of payment (not required for applications made under the Notification Scheme)
  • Manufacturer’s Authorization for Investigational Medicinal Products (MIA(IMP)) plus Qualified Person (QP) declaration on Good Manufacturing Practice (GMP) for each manufacturing site
  • Manufacturer or importer contact information
Refer to the MHCTR and the G-MHRA-CTApp for detailed submission information.
 
EC Requirements
As per the MHCTR and Additional Resource (E), ECs require the CI to submit the following documentation for ethics approval:
  • Application for an EC opinion (including EudraCT number)
  • A summary of the trial, including justification, relevance, and methodology to be used
  • Research hypothesis
  • Statistical analysis and justification for the numbers of participants to be recruited
  • Protocol
  • IB
  • Peer review process details
  • Sponsor name and contact information
  • Financial arrangements for the trial (e.g., funding sources, participant reimbursement, compensation provisions in the event of trial-related injury or death, and insurance or indemnity coverage for sponsor and investigator(s)) (see Sponsorship topic, Compensation subtopic for additional information)
  • Terms of agreement between sponsor and participating institution(s)
  • Material to be used (including advertisements) to recruit potential research participants
  • Informed consent form (ICF) and copies of materials to be provided to participants (See Informed Consent topic, Required Elements subtopic for additional information)
  • Participant treatment plans
  • Benefit/risk assessment for participants
  • Investigator(s) Curriculum Vitaes (CVs)
  • Trial design and suitability of facilities
Additionally, according to the G-HRA-REC-Bkg and Additional Resource (H), the CI must submit the electronic application to the Integrated Research Application System (IRAS) on the same day that a booking is made to schedule an EC review through the National Health Service (NHS) Research Ethics Committee’s Central Booking Service (CBS). All EC reviews must be booked through the CBS with the exception of social care adult research application submissions, which are booked directly with the Social Care ECs. Refer to the G-HRA-REC-Bkg and Additional Resource (H) for detailed submission and booking instructions.
 
Clinical Protocol
According Additional Resources (I) and (J), the clinical protocol should contain the following elements:
  • Protocol Summary
  • Sponsor or designated representative name and contact information
  • Investigator(s) CV(s) and contact information
  • Investigational Product description (See Investigational Products topic for detailed coverage of this subject)
  • Form, dosage, route, method, and frequency of administration; treatment period
  • Trial objectives and purpose
  • Trial design, random selection method, and blinding level
  • Participant selection/withdrawal
  • Participant treatment
  • Summary of potential risks and known benefits to research participants
  • Safety and efficacy assessments
  • Adverse event reporting requirements (See Clinical Trial Lifecycle topic, Safety Reporting subtopic for additional information)
  • Statistics and methods to track trial data
  • Sponsor specifications for direct access to source data/documents
  • Quality control/quality assurance procedures and practices
  • Ethical considerations
  • Data management and recordkeeping
  • Financing and insurance details
  • Publication policy
For complete protocol requirements, refer to Additional Resources (I) and (J).
 
ADDITIONAL RESOURCES
Health Research Authority, Department of Health, National Health Service  England, Department of Health, UK Government
 
(B) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Terminology (Glossary) and Section 14
 
European Forum on Good Clinical Practice
 
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(G) (Website) Integrated Research Application System (Version 5.4.0) (Current as of December 20, 2016)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Enterprise and Industry Directorate-General, European Commission
 
Relevant Sections: 4 and Attachments 1 and 2
 
(J) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Section: 6
 
(K) (Website) EudraCT – European Clinical Trials Database (Last Updated January 4, 2017)
European Medicines Agency, European Union
 
(L) (Website) EudraCT – Overview of the EudraCT Public and Secure Applications (Last Updated October 14, 2016)
European Medicines Agency, European Union
 
(M) (Website) EudraCT – Help: Overview of EudraCT (Current as of February 20, 2017)
European Medicines Agency, European Union
 
(N) (EU Form) Annex 1 - Clinical Trial Application Form (Volume 10) (November 30, 2009)
Eudralex, Enterprise Directorate-General, European Commission
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 3 (12, 14, 15, 17, and 18) and Schedule 3 (Parts 1 and 2)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
 
(3) (Guidance) Guidance: Clinical Trials for Medicines: Apply for Authorisation in the UK (G-MHRA-CTApp) (Last Updated March 31, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(4) (Guideline) Research Ethics Committee (REC) - New Booking & Submission Processes: A Step by Step Guide (G-HRA-REC-Bkg) (May 19, 2014)
Health Research Authority, Department of Health, National Health Service, UK Government
 
Clinical Trial Lifecycle > Timeline of Review
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SUMMARY
Overview
Based on the MHCTR, the MHCTR2006, GAfREC, and Additional Resources (A), (B), and (C), the sponsor or his/her designated representative must submit an application for clinical trial authorization to the Medicines and Healthcare Products Regulatory Agency's (MHRA), and the chief investigator (CI) must submit an application to a recognized ethics committee (EC) to obtain a favorable opinion prior to the trial’s commencement. Additional Resources (C) and (D) indicate that these submissions may be conducted in parallel. The G-MHRA-CTApp also states that an EC opinion may be obtained before, during, or after the MHRA application has been electronically submitted to the Integrated Research Application System (IRAS), EudraCT, or the Heads of Medicines Agencies (HMA) Common European Submission Portal (CESP).
 
MHRA Approval
Clinical Trial Application Submission
As per the MHCTR, the G-MHRA-CTApp, and Additional Resource (E), the MHRA review and approval process for a clinical trial application takes 30 days. For Phase 1 trials, the average is 14 days. According to Additional Resource (E), if the sponsor or his/her designated representative is required to submit an amended application, the MHRA provides a response to the amendment within 60 days of receipt of the original application. Additionally, responses for Phase 1 healthy volunteer studies will be reviewed within an average of 14 days, and studies using gene therapy, somatic cell therapy (including xenogenic cell therapy) products or products containing genetically modified organisms will be reviewed within 90 days or receipt of the original application.
 
The MHCTR and Additional Resource (E) specify that the MHRA coordinates the clinical trial application process. Upon receipt, the MHRA’s Information Processing Unit conducts an application validation. If the application is validated, the sponsor or his/her designated legal representative is sent an acknowledgement letter. The MHRA’s Clinical Trials Unit (CTU) assessment period begins from the date of receipt (Day 0) of a valid application. According to the MHCTR, if the sponsor or his/her designated representative does not receive a request for additional information from the MHRA within 30 days, the clinical trial application is treated as authorized.
 
In addition, as stated in Additional Resource (F), certain first-in-human (Phase I) trials with specific risk factors require the MHRA’s CTU to seek advice from an Expert Advisory Group/the Commission on Human Medicines before approval for the trial can be given. See Additional Resource (F) for detailed requirements.
 
Notification Scheme Submission
The G-MHRA-CTApp and Additional Resources (E) and (G) indicate that in place of a standard application, a notification of a clinical trial may be submitted for “Type A” trials. This includes trials involving medicinal products licensed in any EU Member State that meet the following criteria:
  • they relate to the licensed range of indications, dosage and form, or,
  • they involve off-label use established by practice and supported by published evidence and/or guidelines
Type A trials include studies in which the potential risk associated with an investigational medicinal product is determined to be no higher than that of standard medical care. See the G-MHRA-CTApp and Additional Resources (E) and (G) for detailed Notification Scheme requirements.
 
Upon receipt of the notification, the MHRA sends an acknowledgement letter to the sponsor or his/her designated representative stating that the trial may proceed if an objection is not raised within 14 days. If the MHRA does not send a Notification Objection letter, the acknowledgement letter serves as the authorization. If the MHRA raises objections, the submission is treated as a standard request for authorization, and the CTU initial assessment is performed within 30 days. For the purposes of this calculation, the day of receipt of the valid notification by the Clinical Trials Unit is day 0.
 
Ethics Committee Approval
As specified in the MHCTR, GAfREC, and Additional Resource (B), an EC must give its opinion within 60 calendar days of receipt of a valid application. When an EC requires further information before confirming its opinion, it may give a provisional opinion, and it is permitted to make one written request for further information, clarification, or changes to documentation. The time it takes for the EC to receive a complete response to the request does not count against the 60-day timeline. Studies using gene therapy, somatic cell therapy (including xenogenic cell therapy) products or products containing genetically modified organisms will take 90 days, or 180 days if a specialist group or committee is consulted. For other exceptions, see GAfREC and the MHCTR.
 
As delineated in Additional Resource (B), the CI is responsible for submitting an application to an EC via IRAS. The G-HRA-REC-Bkg and Additional Resources (B) and (H) indicate that the CI must submit the electronic application to IRAS on the same day that a booking is made to schedule an EC review through the National Health Service (NHS) Research Ethics Committee’s Central Booking Service (CBS).
 
Per Additional Resource (B), a site-specific assessment (SSA) is required for multicenter clinical trials. The “site specific assessment” (SSA) is not a separate ethical review, but forms part of the single ethical review of the research.
 
In the case of international studies, an application must be made to an EC in the UK, whether or not the study has a favourable ethical opinion from a committee outside the UK, and whether or not it has started outside the UK. According to Additional Resource (H), some projects taking place outside the NHS require a site specific assessment, which is undertaken by the REC reviewing the study application. See the Ethics Committee topic, Scope of Assessment subtopic for additional information on the “main EC.”
 
ADDITIONAL RESOURCES
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(B) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Terminology (Glossary), Section 1, and Section 14
 
European Forum on Good Clinical Practice
 
(D) (Website) Health Research Authority - Research Ethics Service (RES) (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: United Kingdom
 
(E) (Website) Health Research Authority – MHRA – Clinical Trial Authorisation (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(F) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012)
Association for the British Pharmaceutical Industry
 
Relevant Section: 3
 
(G) (Website) Clinical Trials ToolkitCTA Submission (Current as of February 20, 2017)
National Institute for Health Research, Department of Health, UK Government
 
(H) (Website) Health Research Authority – Research Ethics Committee (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(I) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
(J) (Website) Integrated Research Application System (Version 5.4.0) (Current as of December 20, 2016)
Health Research Authority, Department of Health, National Health Service, UK Government
 
(K) (Website) EudraCT – European Clinical Trials Database (Last Updated January 4, 2017)
European Medicines Agency, European Union
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 2 (5 and 7), Part 3 (12, 14, 15, 17, and 18)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
 
(3) (Guidance) Governance Arrangements for Research Ethics Committees: A Harmonised Edition (GAfREC) (May 2011) (Updated April 2012)
UK Health Departments
 
Relevant Section: 3
 
(4) (Guidance) Guidance: Clinical Trials for Medicines: Apply for Authorisation in the UK (G-MHRA-CTApp) (Last Updated March 31, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(5) (Guideline) Research Ethics Committee (REC) - New Booking & Submission Processes: A Step by Step Guide (G-HRA-REC-Bkg) (May 19, 2014)
Health Research Authority, Department of Health, National Health Service, UK Government
 
Clinical Trial Lifecycle > Trial Initiation
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
In accordance with the MHCTR, the MHCTR2006, GAfREC, and Additional Resources (A), (B), and (C), a clinical trial can only commence after the sponsor or his/her designated representative receives authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA) and the Chief Investigator (CI) receives a favorable opinion from a recognized ethics committee (EC). No waiting period is required following the applicant’s receipt of these approvals.
 
The MHCTR, the G-MHRA-CTApp, and Additional Resource (D) also state that if the sponsor is not based in the European Economic Area (EEA), it is a statutory requirement for the sponsor to appoint a legal representative located in the EEA. Per Additional Resources (C) and (E), the sponsor may submit an application for clinical trial authorization to the MHRA in parallel with the Chief Investigator’s (CI) submission to an EC. Furthermore, Additional Resource (B) states that the CI should be based in the United Kingdom (UK). In rare cases when this is not required, adequate arrangements must be in place for supervision of the study in the UK.
 
In addition, per the MHCTR, the G-MHRA-CTApp, and Additional Resource (F), a Manufacturer’s Authorization for Investigational Medicinal Products (MIA(IMP)) must be obtained by the person responsible for the manufacture or importation of any investigational product (IP) (known as investigational medicinal product (IMP) in the UK) to be used in the trial. The sponsor or his/her designated representative must include a copy of the MIA(IMP) in the clinical trial application submission to the MHRA. (See Clinical Trial Lifecycle topic, Submission Content subtopic, and the Investigational Products topic, Manufacturing & Import subtopic for detailed submission and IMP requirements respectively).
 
As stated in the MHCTR and Additional Resource (G), which comply with the European Medicines Agency’s implementation of the International Council for Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs), all investigators must possess appropriate qualifications, training, and experience. The trials should be conducted in compliance with the EU-ICH-GCPs, and laboratory practices must comply with the UK-GLPs.
 
Clinical Trial Agreement
According to Additional Resources (I) and (J), which implement the EU-ICH-GCPs, the sponsor or his/her designated representative is required to sign a letter of agreement with the participating institution(s) before the trial begins. In addition, the investigators and the sponsor or his/her designated representative must sign an agreement specific to the clinical trial.
 
EC Confirmation of Review and Approval
The MHCTR and the MHCTR2006 mandate that the sponsor or his/her designated representative is responsible for ensuring that the CI has obtained confirmation of the EC’s favorable opinion. Per the G-MHRA-CTApp, an EC opinion may be obtained before, during, or after the MHRA application has been electronically submitted to the Integrated Research Application System (IRAS), the EudraCT database, or the Common European Submission Portal (CESP). The final favorable opinion letter can be obtained from IRAS. The MHRA Clinical Trials Unit is also automatically notified of all EC opinions as soon as they are issued.
 
As per the MHCTR, and Additional Resources (B) and (C), the sponsor or his/her designated representative should also notify the EC of any substantial amendments to the protocol, and submit all relevant documents in support of such amendments. These amendments may not be implemented without a favorable opinion from the EC. (See Ethics Committee topic, Scope of Review subtopic and Clinical Trial Lifecycle topic, Submission Content subtopic for additional details on the EC review and approval process).
 
EU Clinical Trials Register
As per Additional Resources (K), (L), and (M), effective September 30, 2013, the sponsor or investigator are required to register the clinical trial in the EU Clinical Trials Register by applying for a EudraCT number as a condition of the favorable ethical opinion. Failure to register in this database will be treated as a breach of good research practice.
 
ADDITIONAL RESOURCES
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(B) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Terminology (Glossary), Section 1, and Section 14
 
European Forum on Good Clinical Practice
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(E) (Website) Health Research Authority - Research Ethics Service (RES) (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(F) (Website) Manufacturing, Wholesaling, Importing and Exporting Medicines (Current as of February 20, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(H) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
(I) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012)
Association for the British Pharmaceutical Industry
 
Relevant Sections: 3 and 8
 
Enterprise and Industry Directorate-General, European Commission
 
Relevant Sections: 1, 5, and 7
 
(K) (Website) Health Research Authority - Transparency (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Clinical Trial Registration
 
(L) (Website) Health Research Authority - Transparency, Registration and Publication (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
European Commission
 
Relevant Section: Chapter 3
 
European Commission
 
European Commission
 
Enterprise Directorate-General, European Commission
 
(R) (Website) Integrated Research Application System (Version 5.4.0) (Current as of December 20, 2016)
Health Research Authority, Department of Health, National Health Service, UK Government
 
(S) (Website) EU Clinical Trials Register (Current as of February 20, 2017)
European Medicines Agency, European Union
 
(T) (Website) EudraCT – European Clinical Trials Database (Last Updated January 4, 2017)
European Medicines Agency, European Union
 
(U) (Website) EudraCT – Overview of the EudraCT Public and Secure Applications (Last Updated October 14, 2016)
European Medicines Agency, European Union
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (3), Part 3 (12, 13, 14, 17, 18, 22, and 24) and Part 6 (36 and 38)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
 
(3) (Guidance) Governance Arrangements for Research Ethics Committees: A Harmonised Edition (GAfREC) (May 2011) (Updated April 2012)
UK Health Departments
 
Relevant Section: 3.2
 
(4) (Guidance) Guidance: Clinical Trials for Medicines: Apply for Authorisation in the UK (G-MHRA-CTApp) (Last Updated March 31, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(5) (Regulation) The Good Laboratory Practice Regulations 1999 (S.I. 1999/3106) (UK-GLPs) (December 14, 1999)
UK Parliament
 
Relevant Section: 7
 
 
Clinical Trial Lifecycle > Safety Reporting
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
According to Additional Resources (A), (B), and (C), the following definitions provide a basis for a common understanding of the United Kingdom’s (UK’s) safety reporting requirements:
  • Adverse Event (or Adverse Experience) (AE) – Any untoward medical occurrence in a participant, including occurrences which are not necessarily caused by or related to that product
  • Adverse Drug Reaction (ADR) – Any untoward and unintended response in a participant to an investigational medicinal product which is related to any dose administered to that participant
  • Serious Adverse Event (SAE), Serious Adverse Drug Reaction (SADR), or Unexpected Serious ADR – Any AE, ADR, or unexpected ADR that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or a congenital anomaly/birth defect
  • Unexpected Adverse Drug Reaction (ADR) – An adverse reaction where the nature or severity is inconsistent with the applicable product information
  • Suspected unexpected serious adverse reaction (SUSAR) – A suspected serious adverse reaction which is also “unexpected,” meaning that its nature and severity are not consistent with the information about the medicinal product in question.
Reporting Requirements for AEs/ADRs
Investigator Responsibilities
As specified in the MHCTR, the G-MHRA-SafetyRpting, and Additional Resources (A), (B), and (D), the investigator is responsible for reporting all SAEs/SADRs immediately to the sponsor. The report may be made orally or in writing, and followed by a detailed report no later than 24 hours after the event. When the reported event results in a participant’s death, the investigator must provide the sponsor with any requested information. For fatal events/reactions, the investigator must also supply the ethics committee (EC) with any requested information. According to the MHCTR and Additional Resource (A), in cases where reporting is not immediately required according to the protocol or the Investigator’s Brochure (IB), the investigator should report an SAE/SADR within the appropriate timeframe based on the trial requirements, the seriousness of the SAE/SADR, and protocol or Investigator’s Brochure (IB) guidelines.
 
Sponsor Responsibilities
According to the MHCTR, the G-MHRA-SafetyRpting, and Additional Resource (A), the sponsor is required to record and report all relevant information about fatal or life-threatening SUSARs as soon as possible, but no later than seven (7) calendar days, to the Medicines and Healthcare Products Regulatory Agency (MHRA), to the competent authorities of any other European Economic Area (EEA) Member State, other than the UK, in which the trial is being conducted, and to the EC. Any additional relevant information should be sent within eight (8) days of the initial report. The sponsor must also report any non-fatal or non-life-threatening SUSARs no later than 15 calendar days following first awareness of the event.
 
As per the MHCTR, the G-MHRA-SafetyRpting, and Additional Resources (A), (B), and (D), the sponsor or his/her designated representative must also provide the MHRA and the EC with an annual list of SUSARs related to all trials both within and outside of the UK, and within 60 days of the reporting date. This annual report is referred to as a Development Safety Update Report (DSUR). According to Additional Resource (E), the Development International Birth Date (DIBD) is used to determine the start of the annual period for the DSUR. This date is the sponsor’s first authorisation to conduct a clinical trial in any country worldwide. The start of the annual period for the DSUR is the month and date of the DIBD. See the G-MHRA-SafetyRpting for detailed DSUR submission instructions.
 
See the MHCTR and Additional Resources (A), (B), and (D) for detailed reporting requirements for the Investigator and Sponsor.
 
Form Completion & Delivery Requirements
As per the MHCTR, the G-MHRA-SafetyRpting, and Additional Resource (A), all SUSARs must be reported electronically by the sponsor or his/her designated representative and the institutions responsible for trial safety reporting by using the MHRA’s eSUSAR website or the EudraVigilance System. See the G-MHRA-SafetyRpting and Additional Resources (B), (E), (F), (G), and (H) for detailed reporting requirements.
 
Data Monitoring Committee (DMC)
Although there is no statutory requirement under the MHCTR for a Data Monitoring Committee (DMC), according to Additional Resource (I), some form of monitoring interim data should always be considered. The sponsor or his/her designated representative is generally required to establish a DMC for trials involving participants with life-threatening illnesses or those representing vulnerable populations. (See Informed Consent topic, Vulnerable Populations subtopic for additional information.)
 
ADDITIONAL RESOURCES
Enterprise Directorate-General, European Commission
 
Relevant Sections: 3, 4, and 7
 
Health Research Authority, Department of Health, National Health Service, UK Government
 
(C) (Website) Health Research Authority – Glossary – SUSAR (Current as of January 13, 2017)
Health Research Authority, Department of Health, National Health Service, UK Government
 
Health Research Authority, Department of Health, National Health Service, UK Government
 
(E) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Sections: 1, 4.11, 5.16, and 5.17
 
(F) (Website) eSUSAR (Current as of January 13, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, National Health Service, UK Government
 
(G) (Website) EudraVigilance (Current as of January 13, 2017)
European Medicines Agency,European Union
 
(H) (Website) EudraVigilance System Overview (Current as of January 13, 2017)
European Medicines Agency, European Union
 
National Patient Safety Agency, Health Research Authority, National Health Service England, Department of Health, UK Government
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Section: Part 5
 
(2) (Guidance) Guidance: Clinical Trials for Medicines: Manage your Authorisation, Report Safety Issues (G-MHRA-SafetyRpting) (Last Updated January 24, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, National Health Service, UK Government
Clinical Trial Lifecycle > Progress Reporting
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Last content review/update: July 19, 2017. Submit updates or comments.
SUMMARY
Overview
As indicated in the G-MHRA-SafetyRpting and Additional Resources (A), (B), (C), and (D), the investigator and the sponsor share responsibility for submitting progress reports on the status of a clinical trial and for submitting a final study report upon the trial’s completion. These requirements comply with the progress and final reporting requirements delineated in the European Medicines Agency’s implementation of the International Council for Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs).
 
Interim/Progress Reports
As stated in Additional Resource (A), the investigator is required to send progress reports to interested parties, including the sponsor and the ethics committee (EC), throughout the trial. In accordance with Additional Resources (A), (B), (C), and (D), the chief investigator (CI) is responsible for submitting progress reports annually, or more frequently if requested by the EC, on the status of a clinical trial. The CI must complete the annual progress report form listed in Additional Resource (E) and send it to the main EC, or, the EC reviewing the original application. See Ethics Committee topic, Scope of Assessment subtopic for additional information on the “main EC.”
 
Final Report
According to the G-MHRA-SafetyRpting, the sponsor must upload the end of trial summary results to EudraCT. The sponsor does not need to submit the clinical trial summary report to the MHRA. However, the sponsor must send a short confirmation email to CT.Submission@mhra.gsi.gov.uk once the results have been uploaded to EudraCT with ‘End of trial: result-related information: EudraCT XXXX-XXXXXX-XX’ as the subject line. The report may only be submitted following the MHRA’s receipt of the Declaration of the End of a Clinical Trial Form. End of trial declarations must be submitted via the Common European Submission Portal (CESP).
 
As per Additional Resource (C), which complies with the EU-ICH-GCPs, the investigator is also required to submit a summary of the final study report to the main EC within one (1) year of the trial’s conclusion. There is no standard format for final reports. However, the minimum information to be provided to the EC should include whether the trial achieved its objectives, the main findings, and arrangements for publication or dissemination of research.
 
ADDITIONAL RESOURCES
(A) (Website) Clinical Trials ToolkitProgress Reporting (Current as of February 20, 2017)
National Institute for Health Research, Department of Health, UK Government
 
(B) (Website) Health Research Authority - Progress Reports (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(C) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Terminology (Glossary), Section 1, and Section 14
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(F) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Sections: 4.10 and 4.13
 
REQUIREMENTS
(1) (Guidance) Guidance: Clinical Trials for Medicines: Manage your Authorisation, Report Safety Issues (G-MHRA-SafetyRpting) (Last Updated January 24, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, National Health Service, UK Government
Sponsorship > Definition of Sponsor
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
As per the MHCTR, the MHCTR2006, and Additional Resources (A), (B), (C), and (D), the sponsor is defined as an individual, company, institution, or organization who takes ultimate responsibility for the initiation, management, and financing (or arranging the financing) of a trial. The sponsor must ensure that the trial design meets appropriate standards, and arrange for the trial to be properly conducted and reported.
 
The MHCTR also permits two (2) or more parties to take responsibility for the sponsor’s functions. When this applies, the MHCTR requires one (1) of the parties to submit the clinical trial application for authorization to the Medicines and Healthcare Products Regulatory Agency (MHRA), and to specify who is responsible for carrying out the following functions:
  • communications relating to substantial amendments, modified amendments, and the conclusion of the trial
  • communications relating to urgent safety measures
  • pharmacovigilance reporting
As stated in the MHCTR, the sponsor must either be established in the European Economic Area (EEA), or designate a legal representative who is established in the EEA. The MHCTR and Additional Resources (A) and (C) also specify that the sponsor may delegate any or all of his/her trial-related duties and functions to a contract research organization (CRO). However, the sponsor must ensure that this arrangement is formally agreed upon and documented.
 
ADDITIONAL RESOURCES
(A) (Website) Health Research Authority – Sponsor – Resource Page (Current as of February 20, 2017)
Health Research Authority, Department of Health, National Health Service, UK Government
 
(B) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Terminology (Statutory Definitions Relating to CTIMPS)
 
(C) (Document) Sponsorship Principles (Version 5) (Last Updated June 2016)
Research and Development Forum, National Health Service
 
Relevant Sections: Basic Principles and Table 1
 
(D) (Website) Clinical Trials Toolkit – Sponsorship (Current as of February 20, 2017)
National Institute for Health Research, Department of Health, UK Government
 
Health Research Authority, Department of Health, National Health Service, UK Government
 
(F) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
European Commission
 
Relevant Section: Chapter 2 (3)
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (3) and Schedule 3, Part 2 (1)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 3 of the Principal Regulations; Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Sponsorship > Trial Authorization
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Last content review/update: August 30, 2017. Submit updates or comments.
SUMMARY
Overview
In accordance with the MHCTR, the MHCTR2006, the G-MHRA-CTApp, and Additional Resources (A), (B), and (C), the sponsor or his/her designated representative is responsible for submitting a clinical trial application to the Medicines and Healthcare Products Regulatory Agency (MHRA) to obtain  authorization to conduct a clinical trial. The MHCTR, the G-MHRA-CTApp, and Additional Resource (B) also state that if the sponsor is not based in the European Economic Area (EEA), it is a statutory requirement for the sponsor to appoint a legal representative located in the EEA.
 
As delineated in the G-MHRA-CTApp, and Additional Resources (D) and (E), to complete the clinical trial application package, the sponsor or his/her designated representative must apply for a EudraCT number, which is a prerequisite to creating a clinical trial application. The EudraCT number is a unique European Union-wide reference number assigned to a trial that is used by the review bodies (the MHRA and the ethics committees (ECs)) to exchange trial-related information. Only after receiving a EudraCT number can the sponsor or his/her designated representative generate a clinical trial application via the EU’s EudraCT database or the UK’s Integrated Research Application System (IRAS)'s database. Both systems provide a saved data file in the form of an XML file, which is stored on the sponsor’s or his/her designated representative’s local hard drive, can be shared across both systems, and can be generated into PDF files. However, per Additional Resource (F), IRAS is the most efficient submission option because it enables researchers to enter the information required by all UK review bodies only once, rather than having to complete several separate application forms to obtain these permissions and approvals.
 
The submission package may then be uploaded to EudraCT, IRAS, or the Heads of Medicines Agencies (HMA) Common European Submission Portal (CESP) for submission to the MHRA. Per the G-MHRA-CTApp and Additional Resource (H), the CESP is only used to submit files, not to download files to a local computer. Refer to Additional Resources (D), (E), (G), and (K) for detailed EudraCT application submission instructions, and Additional Resource (H) for CESP submission information. (See the Clinical Trial Lifecycle topic, Submission Content subtopic for documentation to be included in the application package.)
In addition to the completed application, per the MHCTR and the G-MHRA-CTApp, the sponsor or his/her designated representative must provide the MHRA with a copy of the EC opinion (if available), the clinical protocol, the investigator’s brochure, a signed declaration by the investigators, a certificate of good manufacturing practice for the manufacture of the trial medicine, and other documentation covered in the Clinical Trial Lifecycle topic, Submission Content subtopic.
 
ADDITIONAL RESOURCES
(A) (Document) Sponsorship Principles (Version 5) (June 2016)
Research and Development Forum, National Health Service
 
Relevant Sections: Introduction and Table 1
 
(B) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Section 14
 
European Forum on Good Clinical Practice
 
(D) (Website) EudraCT – European Clinical Trials Database (Current as of January 11, 2017)
European Medicines Agency, European Union
 
(E) (Website) EudraCT –Overview of the EudraCT Public and Secure Applications (Current as of February 20, 2017)
European Medicines Agency, European Union
 
(F) (Website) Integrated Research Application System (Version 5.4.0) (Current as of December 20, 2016)
Health Research Authority, Department of Health, National Health Service, UK Government
 
Enterprise Directorate-General,European Commission
 
Heads of Medicines Agencies, European Economic Area
 
(Current as of February 20, 2017)
National Institute for Health Research, Department of Health, UK Government
 
European Parliament and Council
 
(K) (Website) EudraCT – Protocol Related Documentation (Last Updated January 4, 2017)
European Medicines Agency, European Union
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (3), Part 3 (12, 17, and 18), and Schedule 3 (Part 2)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Section: Part 2 (Conditions Based on Article 3 of the Directive)
 
(3) (Guidance) Guidance: Clinical Trials for Medicines: Apply for Authorisation in the UK (G-MHRA-CTApp) (Last Updated March 31, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
Sponsorship > Insurance
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
As set forth in the MHCTR and the MHCTR2006, it is a legal requirement for an insurance and indemnity provision to be made to cover the liability of the investigator and sponsor for trial related injuries. The MHCTR does not ascribe responsibility to the sponsor or his/her designated representative to obtain insurance and indemnity. However, Additional Resources (A) and (B) state that the sponsor or his/her designated representative is responsible for ensuring adequate insurance and indemnity arrangements are in place to cover the sponsor’s and the investigator’s potential liability, and for providing a copy of this coverage in the clinical trial application submission.
 
In addition, according to Additional Resource (A), the sponsor or his/her designated representative must ensure that the research covered by the National Health Service’s (NHS) indemnity policy is in place for each publicly funded participating study site. See Additional Resource (C) for detailed information on the NHS indemnity responsibilities for clinical negligence involving investigators and participants. Additional Resource (D), in turn, specifically addresses the sponsor’s or his/her designated representative’s requirement to insure or indemnify the investigator participating in industry-sponsored Phase I clinical trials.
 
See the Sponsorship topic, Compensation subtopic and Informed Consent topic, Compensation Disclosure subtopic for specific details related to sponsorship compensation obligations.
 
 
ADDITIONAL RESOURCES
(A) (Document) Sponsorship Principles (Version 5) (June 2016)
Research and Development Forum, National Health Service
 
Relevant Sections: Introduction, Basic Principles, and Table 1
 
(B) (Website) Health Research Authority – Sponsor – Resource Page (Current as of February 20, 2017)
Health Research Authority, Department of Health, National Health Service, UK Government
 
Association for the British Pharmaceutical Industry, BioIndustry Association, Clinical Contract Research Association
 
Relevant Section: 6
 
(D) (Website) Clinical Trials Toolkit – Sponsorship (Current as of February 20, 2017)
National Institute for Health Research, Department of Health, UK Government
 
(E) (Website) NHS Litigation Authority (Current as of February 20, 2017)
National Health Service Litigation Authority
 
European Parliament and Council
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 3 (15) and Schedule 1 (Part 1 (16))
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Section: Part 2 (Conditions Based on Article 3 of the Directive)
 
Sponsorship > Compensation
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Last content review/update: February 23, 2017. Submit updates or comments.
SUMMARY
Overview
As specified in the MHCTR and Additional Resource (A), the sponsor or his/her designated representative is responsible for providing compensation to research participants and/or their legal heirs in the event of Phase I trial-related injuries or death.
 
According to Additional Resource (A), the sponsor or his/her designated representative must follow the principles set forth in the Association of the British Pharmaceutical Industry (ABPI)’s guidelines  to comply with the United Kingdom (UK)’s participant compensation and treatment requirements due to Phase I trial-related injuries.
 
The guidelines state that the sponsor should furnish written assurance to the investigator that the sponsor will agree to pay compensation to participants and/or his/her legal heirs in the event of trial-related injuries or death whenever a causal relationship with participation is demonstrated. The investigator, in turn, communicates this information to the relevant ethics committees (ECs).
 
The sponsor or his/her designated representative must provide the details of insurance for each trial to the main EC using the Statement of Insurance Cover form which requires the following information:
  • Aggregate limit of the sponsor’s indemnity for the trial and for the individual participant (It is recommended that sponsors purchase a minimum for 5 million British Pounds indemnity cover for any first-in-human Phase 1 trial, or 2.5 million British Pounds for other Phase 1 trials)
  • Policy type (trial-specific or block), length, exclusions or other conditions
  • Insurer name and address
  • Copy of insurance certificate
See the Informed Consent topic, Compensation Disclosure subtopic for additional information.
 
ADDITIONAL RESOURCES
Association for the British Pharmaceutical Industry, BioIndustry Association, Clinical Contract Research Association
 
Relevant Sections: 3, 4, and 5
 
Health Research Authority, Department of Health, National Health Service, UK Government
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 3 (15), Part 4 (8), and Schedule 1 (Part 1 (1))
 
Sponsorship > Quality, Data & Records Management
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
As stated in the MHCTR, the MHCTR2006, and Additional Resource (A), the sponsor is responsible for maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol and the European Medicines Agency’s implementation of the International Council for Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs). The sponsor is required to obtain agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed.
 
The sponsor must also obtain the investigator(s) and the institution(s) agreement to:
  • conduct the trial in compliance with the EU-ICH-GCPs and the protocol agreed to by the sponsor and approved by the ethics committee (EC)
  • comply with data recording and reporting procedures
  • permit monitoring, auditing, and inspection
  • retain essential documents until the sponsor informs them that they are no longer needed
Electronic Data Processing System
According to the EU-ICH-GCPs and Additional Resource (A), when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance, and that he/she maintains SOPs for using these systems. Refer to the EU-ICH-GCPs and Additional Resource (A) for detailed information on electronic trial data systems.
 
Record Management
As set forth in the EU-ICH-GCPs and Additional Resource (A), sponsor-specific essential documents should be retained until at least two (2) years after the last approval of a marketing application, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of the investigational product’s clinical development. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.
 
However, per the MHCTR2006, the sponsor and the chief investigator must ensure that the documents contained in the trial master file are retained for at least five (5) years following the trial’s completion. The documents must be readily available to the Medicines and Healthcare Products Regulatory Agency (MHRA) upon request, and be complete and legible. The sponsor should ensure that trial participant medical files are also retained for at least five (5) years after the trial’s conclusion.
 
Moreover, the EU Clinical Trials Regulation states that the sponsor and the investigator must archive the content of the clinical trial master file for at least 25 years following the end of the trial.
 
Audit Requirements
As part of its QA system, the EU-ICH-GCPs and Additional Resource (A) state that the sponsor may choose to perform a clinical trial audit. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, and other applicable regulatory requirements. The sponsor should appoint auditors to review the clinical trial. The sponsor should ensure that the auditors are qualified by training and experience, and the auditor’s qualifications should be documented. The sponsor must also ensure that the audit is conducted in accordance with his/her own SOPs, the auditor observations are documented, and data are available as needed for the MHRA. No specific timeframe is provided for the audit process.
 
Premature Study Termination/Suspension
The EU-ICH-GCPs states that if the sponsor or his/her designated representative chooses, or is required to terminate a study, the investigator(s) should promptly inform the institution, and the investigator or institution should also immediately inform the EC and provide a detailed explanation of the termination or suspension.
 
Multicenter Studies
As delineated in the EU-ICH-GCPs, in the event of a multicenter clinical trial, the sponsor must ensure that:
  • All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor
  • The case report forms (CRFs) are designed to capture the required data at all multicenter trial sites
  • Investigator responsibilities are documented prior to the start of the trial
  • All investigators are given instructions on following the protocol, complying with a uniform set of standards to assess clinical and laboratory findings, and completing the CRFs
  • Communication between investigators is facilitated
Data Monitoring Committee (DMC)
Although there is no statutory requirement under the MHCTR for a Data Monitoring Committee (DMC), according to Additional Resource (C), some form of monitoring interim data should always be considered. The sponsor or his/her designated representative is generally required to establish a DMC for trials involving participants with life-threatening illnesses or those representing vulnerable populations. (See Informed Consent topic, Vulnerable Populations subtopic for additional information.)
 
ADDITIONAL RESOURCES
(A) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012)
Association for the British Pharmaceutical Industry
 
Relevant Sections: 8, 12, 13, 23, and 25
 
(B) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Sections: 5.5, 5.19, 5.21, and 5.23
 
European Parliament and the Council of the European Union
 
Relevant Section: Chapter VIII (Article 58)
 
National Patient Safety Agency, Health Research Authority, Department of Health, National Health Service, UK Government
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 3 (15), Part 4 (28), Part 6 (36 and 38), and Schedule 7 (Parts 2 and 3)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 31 of the Principal Regulations and Part 2 (Principles Based on Articles 2 to 5 of the GCP Directive)
 
Sponsorship > Site/Investigator Selection
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
As set forth in the European Medicines Agency’s implementation of the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) and Additional Resources (A) and (B), the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial, taking into account the appropriateness and availability of the study site and facilities. The MHCTR2006 and Additional Resource (A) indicate that the sponsor must also ensure that the investigator(s) are qualified by training and experience. Additionally, the sponsor must define and allocate all study related duties and responsibilities to the relevant parties participating in the study.
 
As delineated in the MHCTR, the MHCTR2006, the EU-ICH-GCPs, and Additional Resources (B) and (C), prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an investigator’s brochure. Per the EU-ICH-GCPs, if a multicenter trial is going to be conducted, the sponsor must organize a coordinating committee or select coordinating investigators.
 
Although there is no statutory requirement under the MHCTR for a Data Monitoring Committee (DMC), according to Additional Resource (D), some form of monitoring interim data should always be considered.
 
Foreign Sponsor Responsibilities
As per the MHCTR and Additional Resource (E), if the sponsor is not based in the European Economic Area (EEA), it is a statutory requirement for the sponsor to appoint a legal representative located in the EEA. According to the EU-ICH-GCPs and Additional Resource (B), the sponsor may also transfer any or all of his/her study related duties and functions to a (contract research organization (CRO). However, the sponsor is ultimately responsible for the study data’s quality and integrity. Any study related duties, functions or responsibilities transferred to and assumed by a local representative or CRO must be specified in writing. Other duties, functions, or responsibilities not specifically transferred shall be deemed to have been retained by the sponsor. Additional foreign sponsor requirements are listed in Section 5.2 of the EU-ICH-GCPs.
 
ADDITIONAL RESOURCES
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(B) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012)
Association for the British Pharmaceutical Industry
 
Relevant Sections: 5 and 8
 
European Commission
 
Relevant Section: Chapter 2 (Section 4)
 
National Patient Safety Agency, Health Research Authority, Department of Health, National Health Service, UK Government
 
Health Research Authority, Department of Health, National Health Service, UK Government
 
Health Research Authority, Department of Health, National Health Service, UK Government
 
(G) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Sections: 5.6, 6, and 7
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (3) and Part 3 (15)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Insertion of Regulation 3A of the Principal Regulations, Insertion of Regulation 29A of the Principal Regulations, and Part 2 (Principles based on Articles 2 to 5 of the GCP Directive)
 
 
Informed Consent > Documentation Requirements
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
In all United Kingdom (UK) clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the MHCTR and the MHCTR2006. As per the MHCTR, the MHCTR2006, and Additional Resources (E), (F), and (G), the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an ethics committee (EC) recognized by the United Kingdom Ethics Committee Authority (UKECA) (henceforth referred to as a “recognized EC”) and operating according to Standard Operating Procedures issued by the England’s Health Research Authority (HRA), formerly the National Research Ethics Service (Additional Resource (E)). The ICF must be provided to the EC with the clinical trial application. (See the Informed Consent topic, Required Elements subtopic for details on what should be included in the form.)
 
The MHCTR and Additional Resources (A) and (B), state that the investigator(s) must provide detailed research study information to the participant and/or his/her legal representative(s) or guardian(s). The MHCTR and Additional Resources (A) and (B) also specify that the oral and written information concerning the trial, including the ICF, should be easy to understand and presented without coercion or unduly influencing a potential participant to enroll in the clinical trial. The participant, and his/her legal representative(s) or guardian(s), should also be given adequate time to consider whether to participate.
 
Re-Consent
According to Additional Resource (G), any change in the ICF due to a protocol modification should be approved by the EC before such changes are implemented. The participant and/or his/her legal representative(s) or guardian(s) will also be required to re-sign the revised ICF and receive a copy of any amended documentation.
 
Language Requirements
As stated in the MHCTR, applications to the EC and the Medicines and Healthcare Products Regulatory Agency (MHRA) and any accompanying material, such as the ICF content, should be presented in English.
 
Documentation Copies
The MHCTR states that the participant and/or the participant’s legal representative(s) or guardian(s), and the investigator(s) must sign and date the ICF. Where the participant is illiterate, and/or his/her legal representative(s) or guardian(s) is illiterate, verbal consent should be obtained in the presence of and countersigned by an impartial witness.
 
ADDITIONAL RESOURCES
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Definition of Informed Consent and Capable Adults
 
(B) (Document) Consent and Participant Information Sheet Preparation Guidance (Current as of February 20, 2017)
Medical Research Council, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Principles, Content, and Examples and Templates
 
(C) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Section: 4.8
 
European Parliament and Council
 
Relevant Sections: 23, 27, Chapter I (Article 2 (21)), and Chapter V (Articles 28 and 29)
 
(E) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Introduction (Purpose and Scope), Terminology (Glossary), and Section 1: New Applications for Ethical Review Special Allocations to Flagged RECs (Allocation of CTIMPs to Recognised Ethics Committees)
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Enterprise and Industry Directorate-General, European Commission
 
Relevant Section: 4
 
(H) (Website) Clinical Trials Toolkit – Informed Consent (Current as of February 20, 2017)
National Institute for Health Research, Department of Health, UK Government
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (3), Part 3 (12, 15, 17, and 18), Schedule 1 (Part 1 (3) and Part 2), and Schedule 3 (Parts 1 and 3)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 3 of the Principal Regulations; Amendment of Regulation 12 of the Principal Regulations; Amendment of Regulation 15 of the Principal Regulations; Amendment of Schedule 1 to the Principal Regulations; Amendment of Schedule 3 to the Principal Regulations; and Part 2 (Principles Based on Articles 2 to 5 of the GCP Directive and Conditions Based on Article 3 of the Directive)
 
Informed Consent > Required Elements
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
As delineated in the MHCTR and the MHCTR2006, prior to beginning a clinical trial, the Chief Investigator (CI) is required to obtain a favorable opinion from a recognized ethics committee (EC) for the written informed consent form (ICF) and any other information being provided to the research participant and/or his/her legal representative(s) or guardian(s).
 
No Coercion
As per Additional Resource (C), none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant and/or his/her legal representative(s) and/or guardian(s) to waive or to appear to waive his/her legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.
 
ICF Required Elements
Based on the MHCTR and Additional Resource (C), the ICF should include the following statements or descriptions, as applicable:
  • The study purpose, procedures, and duration
  • Approximate number of participants involved in the trial
  • The participant’s responsibilities in participating in the trial
  • Trial treatment schedule and the probability for random assignment to each treatment
  • Experimental aspects of the study
  • Any foreseeable risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
  • Any benefits or prorated payment to the participant or to others that may reasonably be expected from the research; if no benefit is expected, the participant should also be made aware of this
  • A disclosure of appropriate alternative procedures or treatments, and their potential benefits and risks
  • Compensation and/or medical treatment available to the participant in the event of a trial-related injury
  • Any additional costs to the participant that may result from participation in the research
  • That participation is voluntary, the participant may withdraw at any time, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled
  • The extent to which confidentiality of records identifying the participant will be maintained, and the possibility of record access by the Medicines and Healthcare Products Regulatory Agency (MHRA), the ECs, the auditor(s), and the monitor(s)
  • That the participant and/or his/her legal representative(s) or guardian(s) will be notified if significant new findings developed during the study may affect the participant's willingness to continue
  • Individuals to contact for further information regarding the trial, the rights of trial participants, and whom to contact in the event of trial-related injury
  • Foreseeable circumstances under which the investigator(s) may remove the participant without his/her consent
(See the Informed Consent topic, Compensation Disclosure subtopic and Vulnerable Populations subtopic and the Specimens topic, Consent for Specimens subtopic for further information.)
 
ADDITIONAL RESOURCES
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Enterprise and Industry Directorate-General, European Commission
 
Relevant Section: 4
 
(C) (Document) Consent and Participant Information Sheet Preparation Guidance (Current as of February 20, 2017)
Medical Research Council, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Principles
 
(D) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Section: 4.8
 
European Parliament and Council
 
Relevant Section: Chapter V
(Article 29)
 
Health Research Authority, National Health Service  England, Department of Health, UK Government
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (3), Part 3 (12 and 15), and Schedule 3 (Parts 1 and 3)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 3 of the Principal Regulations; Amendment of Regulation 12 of the Principal Regulations; and Amendment of Schedule 3 to the Principal Regulations
 
Informed Consent > Compensation Disclosure
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Last content review/update: February 23, 2017. Submit updates or comments.
SUMMARY
Overview
In accordance with the MHCTR and Additional Resources (A) and (B), the informed consent form (ICF) should contain a statement describing the compensation or medical treatment a participant can receive for participating in a clinical trial.
 
Compensation for Participation in Research
As stated in the MHCTR and the EU-ICH-GCPs, ethics committees should consider, in particular, the provision of indemnity or compensation in the event of injury or death attributable to the trial.
 
Compensation for Injury
As per Additional Resource (B), the MHCTR, and the EU-ICH-GCPs, the ICF should contain a statement advising the participant of available compensation and medical treatment in the event of any trial-related injury in a clinical trial.
 
(See the Informed Consent topic, Required Elements subtopic for additional details on what should be included in the ICF, and the Sponsorship topic, Compensation subtopic for information on sponsor requirements.)
 
ADDITIONAL RESOURCES
(A) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012)
Association for the British Pharmaceutical Industry
 
Relevant Section: 19
 
Health Research Authority, Medical Research Council, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Principles
 
(C) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Sections: 4.8 and 5.8
 
European Parliament and Council
 
Relevant Section: Chapter V (Article 29)
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Schedule 1 (Parts 4 and 5)
Informed Consent > Participant Rights
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
In accordance with the MHCTR, the MHCTR2006, and Additional Resource (C), the United Kingdom’s (UK’s) ethical standards promote respect for all human beings and safeguard the rights of research participants. The MHCTR and Additional Resources (C) and (D) state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process.
 
The Right to Participate, Abstain, or Withdraw
As set forth in the MHCTR and Additional Resource (C), the participant or his/her legal representative(s) or guardian(s) should be informed that participation is voluntary, that he/she may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.
 
The Right to Information
As delineated in the MHCTR, and Additional Resource (C), a potential research participant and/or his/her legal representative(s) or guardian(s) has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study.
 
The Right to Privacy and Confidentiality
As per the MHCTR, the EU Clinical Trials Regulation, and Additional Resource (C), the arrangements to protect participants’ privacy should be provided in the application to the ethics committee, and the ICF should inform potential participants of any potential risk to their confidentiality.
 
The Right of Inquiry/Appeal
The MHCTR and Additional Resource (C) state that the research participant and/or his/her legal representative(s) or guardian(s) should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries.
 
The Right to Safety and Welfare
The MHCTR and the MHCTR2006, state that a research participant’s rights, safety and well-being must take precedence over the interests of science and society.
 
ADDITIONAL RESOURCES
European Parliament and Council
 
Relevant Sections: 27 and Chapter V (Articles 28 and 29)
 
(B) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Section: 4.8
 
Health Research Authority, Medical Research Council, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Principles and Content
 
Enterprise and Industry Directorate-General, European Commission
 
Relevant Section: 4
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (3 and 15), Schedule 1 (Parts 1, 2, and 5)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 3 of the Principal Regulations; Amendment of Schedule 1 to the Principal Regulations;  and Part 2 (Principles Based on Articles 2 to 5 of the GCP Directive and Conditions Based on Article 3 of the Directive)
 
Informed Consent > Special Circumstances/Emergencies
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Last content review/update: April 26, 2017. Submit updates or comments.
SUMMARY
Overview
The MHCTR, the MHCTR-2, the MHCTR-BSQ, and Additional Resource (A) make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by special circumstances. Special circumstances include medical emergencies and when a participant is mentally incapacitated.
 
Medical Emergencies
As delineated in Additional Resources (A), (D) and (E), in an emergency, if the signed informed consent form (ICF) cannot be obtained from the research participant, the consent of his/her legal representative(s) or guardian(s) should be obtained. If the prior consent of the participant or his/her legal representative(s) or guardian(s) cannot be obtained, the participant’s enrollment should follow measures specified in the protocol, and the ethics committee (EC) must provide documented approval in order to protect the participant’s rights, safety, and well-being. The participant or his/her legal representative(s) or guardian(s) should provide consent as soon as possible.
 
The MHCTR-BSQ amends the MHCTR and creates an exception for minors participating in a trial where urgent treatment is required and prior consent cannot be obtained. This situation also requires the EC to issue its approval beforehand.
 
Mentally Incapacitated Persons
The MHCTR-2 amends the MHCTR and creates an exception to the general rule in England, Northern Ireland, and Wales that incapacitated adults cannot be included in a clinical trial under medical emergencies. If the treatment to be provided is a matter of urgency and obtaining prior consent is not possible, incapacitated adult participants may be included in the trial once EC approval has been obtained. However, in Scotland, the inclusion of adults lacking capacity in research is governed by the provisions of Section 51 of the AIA2000.
 
ADDITIONAL RESOURCES
Medical Research Council, UK
 
Relevant Section: 4.3
 
European Parliament and Council
 
Relevant Sections: 19, 27, 36, Chapter I (Article 2), and Chapter V (Articles 28 and 31)
 
(C) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Section: 4.8.15
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Emergency Situations
 
Medical Research Council, UK
 
Relevant Section: 5.5.4
 
(F) (Document) Consent and Participant Information Sheet Preparation Guidance (Current as of February 20, 2017)
Medical Research Council, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Principles
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Section: Schedule 1 (Parts 4 and 5)
 
(2) (Regulation) Medicines for Human Use (Clinical Trials) Amendment (No.2) Regulations 2006 (S.I. 2006/2984) (MHCTR-2) (December 12, 2006)
Department of Health, UK Government
 
Relevant Sections: 2 and Explanatory Note
 
(3) (Regulation) The Medicines for Human Use (Clinical Trials) and Blood Safety and Quality (Amendment) Regulations 2008 (S.I. 2008/941) (MHCTR-BSQ) (May 1, 2008)
 
Relevant Sections: 4 and Explanatory Note
 
(4) (Legislation) Adults with Incapacity (Scotland) Act 2000 (AIA2000) (May 9, 2000)
Scottish Parliament, Scotland
 
Relevant Section: Section 51
 
Informed Consent > Vulnerable Populations
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Last content review/update: February 23, 2017. Submit updates or comments.
SUMMARY
Overview
As per the MHCTR and Additional Resources (C), (D) and (E), in all United Kingdom (UK) clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. Additional Resources (C), (D), (E) and (F) characterize vulnerable populations as those who are dependent on others and are unable to express their opinion freely or make their own decisions. These participants may include children, persons with mental or physical incapacities, persons with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, prisoners, detainees, refugees, members of a group with a hierarchical structure, such as students, subordinate hospital and laboratory personnel, pharmaceutical industry employees, members of the armed forces, and persons kept in detention.
 
See the Informed Consent topic, and the subtopics of Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired for additional information about these vulnerable populations.
 
ADDITIONAL RESOURCES
European Parliament and Council
 
Relevant Sections: 19, 27, and Chapter II (Article 10)
 
(B) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Section: 1.61
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Principles of the EU Directive
 
Medical Research Council, UK
 
Relevant Section: 4.3
 
Medical Research Council, UK
 
Relevant Section: 1.3
 
(F) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012)
Association for the British Pharmaceutical Industry
 
Relevant Section: 9
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Schedule 1 (Parts 1, 4, and 5)
 
Informed Consent > Children/Minors
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
According to the MHCTR, a minor is an individual under 16 years of age. However, per Additional Resource (C), in situations where the MHCTR does not apply, a minor is an individual under 18 years of age.
 
As set forth in the MHCTR, the MHCTR2006, and Additional Resources (C), (D), and (E), when the research participant is a minor, informed consent should be obtained from his/her legal representative(s) and/or guardian(s). As per Additional Resource (C), legally, the researcher needs only to obtain consent from one (1) person with parental responsibility; however, consent from all legal representative(s) and/or guardians is encouraged.
 
Additionally, precautions against possible physical and mental harms should be exercised. All pediatric participants should be informed to the fullest extent possible about the study in language and terms that they are easily able to understand. The rights of the minors should also be respected for their voluntary decision to participate in a clinical study.
 
The MHCTR, the MHCTR2006, and Additional Resources (C), (D), and (E) state that a study may only be conducted on minors if several conditions are fulfilled including:
  • An ethics committee (EC), following consultation with pediatric experts, has endorsed the protocol
  • The legal representative(s) and/or guardian(s) has had an interview with the investigator(s) to understand the trial objectives and risks, been provided with a contact point for further information, and been informed of the right to withdraw the minor from the trial at any time
  • No incentives or financial inducements are given to the minor or his/her legal representative(s) and/or guardian(s) except in the event of trial-related injury or loss
  • The trial relates directly to a condition from which the minor suffers, or, is of such a nature that it can only be carried out on minors
  • The participant(s) will derive some direct benefit from their participation in the trial
  • The trial is necessary to validate data obtained in other trials involving persons able to give informed consent, or, by other research methods
  • The trial has been designed to minimize pain, discomfort, fear, and any other foreseeable risk in relation to the disease and the minor’s stage of development
See the MHCTR, the MHCTR2006, and Additional Resources (C), (D), and (E) for detailed requirements.
 
Assent and Minor Privacy Requirements
As delineated in Additional Resource (C), if a minor is deemed competent to give assent to decisions about participation in research, the investigator(s) must obtain that assent in addition to the consent of his/her legal representative(s) and/or guardian(s). If the child does not assent, this should be respected.
 
Furthermore, Additional Resource (C) states that a minor’s ability to assent is based on his/her ability to understand and assess options, rather than on his/her age. For a minor to be able to give his/her assent, he/she must be able to:
  • Comprehend and retain information material to the decision, especially the consequences of having or not having any intervention
  • Use and weigh this information in a decision-making process
  • Reach and communicate a decision
In addition, Additional Resource (C) specifies that if the competent minor specifically asks for the family not to be involved, and they cannot be persuaded otherwise, his/her privacy should be respected.
 
ADDITIONAL RESOURCES
European Parliament and
Council
 
Relevant Section: Chapter V (Article 32)
 
(B) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Section: 4.8.12
 
Medical Research Council, UK
 
Relevant Section: 5
 
(D) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments' Research Ethics Service, Health Research Authority, Natoinal Health Service England, Department of Health, UK Government
 
Relevant Section: Section 2 (CTIMPs Involving Minors or Adults with Incapacity)
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Principles of the EU Directive
 
(F) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012)
Association for the British Pharmaceutical Industry
 
Relevant Section: 11
 
(G) (Document) Consent and Participant Information Sheet Preparation Guidance (Current as of February 20, 2017)
Medical Research Council, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Principles (Children and Young People)
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (2) and Schedule 1 (Part 4)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Schedule 1 to the Principal Regulations; Amendment of Regulation 15 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Informed Consent > Pregnant Women, Fetuses & Neonates
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Last content review/update: February 23, 2017. Submit updates or comments.
SUMMARY
Overview
As set forth in Additional Resource (A) any research studies involving women capable of becoming pregnant and breastfeeding women require additional safeguards to ensure the research conforms to appropriate ethical standards and upholds societal values.
 
Per the EU Clinical Trials Regulation, specific expertise should be considered where appropriate to assess clinical trials involving female participants who are pregnant, or, capable of becoming pregnant, and breastfeeding women. Specific provisions should also be delineated to protect this vulnerable population, particularly when the trial does not have the potential to produce results that will directly benefit a woman or her embryo, fetus, or child following birth.
 
According to Additional Resource (A), the following conditions are required for research to be conducted with this population:
  • Reproductive toxicology studies have been completed and the results support conducting a trial, or, there is a good reason not to conduct the reproductive toxicology studies
  • The female participant is not pregnant according to her menstrual history and a pregnancy test, and is not at risk of becoming pregnant during, and for a specified interval, after the trial
  • The female participant is warned about the potential risks to the developing child should she become pregnant, and she is tested for pregnancy during the trial, as appropriate
  • Women using a hormonal contraceptive, such as “the pill,” should use an alternative method of contraception until the possibility of an interaction with the investigational medicinal product has been excluded
ADDITIONAL RESOURCES
(A) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012)
Association for the British Pharmaceutical Industry
 
Relevant Section: 9
 
European Parliament and Council
 
Relevant Sections: 19, 27, 34, Chapter II (Article 10), and Chapter V (Articles 28 and 33)
 
REQUIREMENTS

No applicable regulatory requirements

Informed Consent > Prisoners
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SUMMARY

No relevant provisions

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

No applicable regulatory requirements

Informed Consent > Mentally Impaired
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SUMMARY
Overview
As per the MHCTR and Additional Resources (B) and (C), a recognized ethics committee (EC) within the Health Research Authority (HRA), formerly the National Research Ethics Service, must approve the participation of adult research participants who are incapable by reason of physical and mental capacity to give consent, and must obtain advice from professionals with expertise in handling this patient population.
 
The MHCTR and Additional Resource (C) specify that when a study involves adult participants with mental incapacities, informed consent should be obtained from his/her legal representative (s) and/or guardian(s). This consent should only be provided once the legal representative(s) or guardian(s) has had an interview with the investigator(s) to understand the trial objectives and risks, been provided with a contact point for further information, and been informed of the right to withdraw the participant from the trial at any time.
 
As delineated in the MHCTR, and Additional Resource (C), a research study may involve participants with mental incapacities under the following conditions:
  • The participant has received information according to his/her capacity of understanding regarding the trial, its risks, and its benefits
  • No incentives or financial inducements are given to the participant or his/her legal representative(s) and/or guardian(s) except in the event of trial-related injury or loss
  • The trial relates directly to a condition from which the participant suffers, or, is of such a nature that it can only be carried out on participants with mental incapacities
  • The participant(s) will derive some direct benefit from their participation in the trial, or produce no risk at all
  • The trial is necessary to validate data obtained in other trials involving persons able to give informed consent, or, by other research methods
  • The trial has been designed to minimize pain, discomfort, fear, and any other foreseeable risk in relation to the disease and the participant’s stage of development
See the MHCTR and Additional Resource (C) for detailed requirements.
 
ADDITIONAL RESOURCES
European Parliament and Council
 
Relevant Sections: 19, 27, Chapter I (Article 2), Chapter II (Article 10), and Chapter V (Articles 28 and 31)
 
(B) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Section 2 (CTIMPs Involving Minors or Adults with Incapacity) and Section 13 (Ethical Review)
 
Health Research Authority, National Health Service  England, Department of Health, UK Government
 
Relevant Sections: Incapacitated Adults, Responsibilities of Ethics Committees in Trials Involving Minors or Incapacitated Adults, and Annex B
 
(D) (Website) Health Research Authority – Adults Unable to Consent for Themselves (Current as of February 20, 2017)
Health Research Authority, National Health Service England, Department of Health, UK Government
 
(E) (Document) Consent and Participant Information Sheet Preparation Guidance (Current as of February 20, 2017)
Medical Research Council, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Principles (Adults Lacking Capacity)
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (15), Schedule 1 (Parts 1 and 5)
Investigational Products > Definition of Investigational Product
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SUMMARY
Overview
As delineated in the MHCTR and Additional Resources (A) and (B), an investigational product (IP), referred to as an investigational medicinal product (IMP) in the United Kingdom (UK), is defined as a pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial. This includes a product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form; when used for an unapproved indication; or when used to gain further information about an approved use.
ADDITIONAL RESOURCES
(A) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Terminology (Statutory Definitions Relating to CTIMPs)
 
(B) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012)
Association for the British Pharmaceutical Industry
 
Relevant Section: Appendix 5
 
European Parliament and Council of the European Union
 
Relevant Section: Chapter I (Article 2 (5))
 
REQUIREMENTS

(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC

Relevant Section: Part 1 (2)

 

Investigational Products > Manufacturing & Import
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SUMMARY
Overview
According to the MHCTR, the MHCTR2006, the G-MHRA-CTApp, and the G-MHRA-GMP/GDP, the Medicines and Healthcare Products Regulatory Agency (MHRA) is responsible for authorizing the manufacture or import of investigational products (IPs) (known as investigational medicinal products (IMPs) in the United Kingdom (UK)) to be used in a trial. A Manufacturer’s Authorization for Investigational Medicinal Products (MIA (IMP)) must be obtained by the person responsible for the manufacture or importation of any IP to be used in the trial. The sponsor or his/her designated representative must include a copy of the MIA (IMP) in the clinical trial application submission to the MHRA. The applicant must complete the form listed in Additional Resource (C) to obtain an MIA (IMP) from the MHRA. The MHRA will approve the manufacture or import of an IP after the clinical trial application has been approved.
 
As per the MHCTR, the MHCTR2006, the G-MHRA-GMP/GDP, Additional Resources (D) and (E), and the EU Good Manufacturing Practice Directive, the MIA (IMP) holder must also comply with the Good Manufacturing Practice (GMP) guidelines and provide an IMP Certificate of Analysis. In addition, the MHCTR, the MHCTR2006, the G-MHRA-GMP/GDP, Additional Resources (D) and (E),the EU Good Manufacturing Practice Directive, and the EU Good Clinical Practice Directive, specify that the holder of an MIA (IMP) must always have the services of at least one Qualified Person (QP) at his/her disposal. The QP must satisfy the qualification and experience requirements delineated in the aforementioned sources. The QP’s primary legal responsibility is to certify batches of IPs prior to using in a clinical trial, or prior to releasing for sale and placing on the market. See Part 6 and Schedule 6 of the MHCTR for detailed applicant requirements.
 
ADDITIONAL RESOURCES
European Commission
 
Relevant Section: Chapter 3
 
European Parliament and Council of the European Union
 
Relevant Sections: Chapters IX and X
 
(C) (Forms) Medicines: Application Forms for a Manufacturer Licence (Current as of February 20, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(D) (Website) Clinical Trials Toolkit – Trial Supplies (Current as of February 20, 2017)
National Institute for Health Research, National Health Service, Department of Health, UK Government
 
Relevant Section: Trials Supplies Guide (PDF)
 
European Commission
 
Relevant Section: Annex 2
 
(F) (Website) Manufacturing, Wholesaling, Importing and Exporting Medicines (Current as of February 20, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
European Commission, European Parliament and European Council
 
Relevant Section: Title IV
 
(H) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (2), Part 3 (13), Part 6, Schedul1 1 (Part 2), Schedule 3 (Part 2), Schedule 6, and Schedule 7
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Amendment of Regulation 13 of the Principal Regulations; Amendment of Regulation 42 of the Principal Regulations; Amendment of Regulation 44 of the Principal Regulations; and Part 2 (Principles based on Articles 2 to 5 of the GCP Directive, Conditions Based on Article 3 of the Directive and Amendment of Schedule 6 to the Principal Regulations)
 
(3) (Guidance) Guidance: Clinical Trials for Medicines: Apply for Authorisation in the UK (G-MHRA-CTApp) (Last Updated March 31, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
(4) (Guidance) Guidance: Good Manufacturing Practice and Good Distribution Practice (G-MHRA-GMP/GDP) (Last Updated January 18, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
Investigational Products > IMP/IND Quality Requirements
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SUMMARY
Overview
In accordance with the MHCTR, the MHCTR2006, the EU Good Clinical Practice Directive, and the EU Clinical Trials Regulation, the sponsor or his/her designated representative is responsible for complying with the principles of good clinical practice (GCP) as specified in the European Medicines Agency’s implementation of the International Council for Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs), and for providing investigators with an Investigator’s Brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs) (known as investigational medicinal products (IMPs) in the United Kingdom (UK)) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse events data. The sponsor or his/her designated representative should also update the IB as significant new information becomes available.
 
IB Content Requirements
As specified in the EU-ICH-GCPs, the IB must provide coverage of the following areas:
  • Physical, chemical, and pharmaceutical properties and formulation parameters
  • Non-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
  • Effects of IMPs in humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; regulatory and post marketing experiences)
  • Summary of data and guidance for the investigator(s)
  • Bibliography
See Section 7 of the EU-ICH-GCPs for detailed content guidelines.
 
As defined in the EU-ICH-GCPs, the sponsor is also accountable for supplying the IMP, including the comparator(s) and placebo, if applicable. The MHCTR, the MHCTR2006, the G-MHRA-GMP/GDP, and Additional Resources (D) and (E) also specify that the sponsor or his/her designated representative must ensure that the products are manufactured in accordance with current Good Manufacturing Practice (GMP) guidelines. (See Investigational Products topic, Product Management subtopic for additional information on IP supply, storage, and handling requirements).
 
Certificate of Analysis and Drug Manufacturing Certificate Requirements
As stated in Additional Resource (F), the Manufacturer’s Authorization for Investigational Medicinal Products (MIA(IMP)) holder must provide the Medicines and Healthcare Products Regulatory Agency (MHRA) with documentation including the following:
  • MIA(IMP) license of final Qualified Person (QP) releasing site
  • MIA(IMP) license of placebo manufacturing site (if different from final QP releasing site)
  • Certified QP release statement
  • Import QP release certificate (if applicable)
  • QP declaration
  • IP certificate of analysis
ADDITIONAL RESOURCES
European Commission
 
Relevant Section: Chapter 2 (Section 4)
 
European Parliament and Council of the European Union
 
Relevant Sections: Chapters IX and X
 
(C) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Sections: 5.12, 5.13, 5.14, 5.15, 5.5, and 7
 
European Commission
 
European Commission
 
(F) (Website) Clinical Trials Toolkit – Trial Supplies (Current as of February 20, 2017)
National Institute for Health Research, Department of Health, UK Government
 
Relevant Section: Trials Supplies Guide (PDF)
 
(G) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012)
Association for the British Pharmaceutical Industry
 
Relevant Sections: 8, 12, 13, 16, and 25
 
Enterprise Directorate-General, European Commission
 
Relevant Section: 4.4
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (2), Part 3 (13), Part 6, Schedule 6, and Schedule 7
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Insertion of Regulation 3A of the Principal Regulations; Amendment of Regulation 13 of the Principal Regulations; Amendment of Regulation 15 of the Principal Regulations;  Amendment of Regulation 42 of the Principal Regulations, Amendment of Regulation 44 of the Principal Regulations; and Part 2 (Principles based on Articles 2 to 5 of the GCP Directive
 
(3) (Guidance) Guidance: Good Manufacturing Practice and Good Distribution Practice (G-MHRA-GMP/GDP) (Last Updated January 18, 2017)
Medicines and Healthcare Products Regulatory Agency, Department of Health, UK Government
 
Investigational Products > Labeling & Packaging
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
Labeling for investigational products (IPs) (known as investigational medicinal products (IMPs) in the United Kingdom (UK)) must comply with the requirements set forth in the MHCTR, the MHCTR2006, Additional Resource (A), the EU Good Manufacturing Practice Directive, and the European Medicines Agency’s implementation of the International Council for Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs). As specified in Additional Resources (A) and (B), for an IP to be used in a clinical trial, it must be properly labeled in the official language of the country where the trial is being conducted.
 
As set forth in Additional Resources (A) and (B), the following labeling information must be included on the primary package label (or any intermediate packaging), and the outer packaging:
  • Name, address and telephone number of the sponsor, contract research organisation (CRO), or investigator
  • Pharmaceutical dosage form, route of administration, quantity of dosage units, and in the case of open trials, the name/identifier and strength/concentration
  • Batch and/or code number to identify the contents and packaging operation
  • Trial reference code allowing identification of the trial, site, investigator, and sponsor (if not given elsewhere)
  • Trial participant identification number/treatment number and where relevant, the visit number
  • Investigator name (if not already included above)
  • Instructions for use (reference may be made to a leaflet or other explanatory document intended for the trial participant or person administering the product)
  • “For clinical trial use only” or similar wording indicating the IP is clinical trial material
  • Storage conditions
  • Expiration date (use by date, expiration date, or re-test date as applicable), in month/year format and in a manner that avoids any ambiguity
  • “Keep Out of Reach of Children” except when the product is not going to be taken home by participants
As per the MHCTR and Additional Resource (B), a sample of the labeling is required as part of the clinical trial application submission. (See Clinical Trial Lifecycle topic, Submission Content subtopic for detailed clinical trial application submission requirements). In addition, Additional Resource (B) states that the IP should be coded and labeled in a manner that protects the blinding, if applicable. Furthermore, according to Additional Resource (A), the IP must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.
 
ADDITIONAL RESOURCES
European Commission (Date Varies by Guidance)
 
Relevant Section: Annex 13 – Investigational Medicinal Products – Packaging, Labelling, and Table 1
 
(B) (Document) Clinical Trials Toolkit: Trial Supplies (Current as of February 20, 2017)
National Institute for Health Research, National Health Service, Department of Health, UK Government
 
Relevant Section: Trials Supplies Guide (PDF), Labelling of Investigational Medicinal Products and Checklist of IMP-Related Documents
 
European Commission
 
Relevant Section: Article 15
 
European Parliament and Council of the European Union
 
Relevant Section: Chapter X
 
(E) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Section: 5.13
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 1 (2) and Part 7, and Schedule 3, Part 2 (12)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Section: Amendment of Regulation 46 of the Principal Regulations
Investigational Products > Product Management
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Last content review/update: June 07, 2017. Submit updates or comments.
SUMMARY
Overview
In accordance with the MHCTR, the MHCTR2006, the EU Good Clinical Practice Directive, and the EU Clinical Trials Regulation, the sponsor or his/her designated representative is responsible for complying with the principles of good clinical practice (GCP) as specified in the European Medicines Agency’s implementation of the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) and for providing investigators with an Investigator’s Brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs) (known as investigational medicinal products (IMPs) in the United Kingdom (UK)) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse event data. The sponsor should also update the IB as significant new information becomes available.
 
Investigational Product Supply, Storage, and Handling Requirements
As defined in the MHCTR, the EU-ICH-GCPs, and Additional Resource (D), the sponsor must supply the investigator(s)/institution(s) with the IMP(s), including the comparator(s) and placebo, if applicable. The sponsor should not supply either party with the IMP(s) until obtaining the Medicines and Healthcare Products Regulatory Agency (MHRA) approval and a favorable opinion from a recognized ethics committee (EC).
 
The sponsor must ensure the following:
  • IP product quality and stability over the period of use
  • IP manufactured according to EU good manufacturing practices (GMPs) as per EU Good Manufacturing Practice Directive
  • Proper coding, packaging and labeling of the IMP(s)
  • IP use record including information on the quantity, loading, shipment, receipt, dispensing, handling, reclamation and destruction of the unused IP
  • Acceptable storage temperatures, conditions, and times for the IMP
  • Written procedures including instructions for handling and storage of the IP, adequate and safe receipt, dispensing, retrieval of unused IP(s), and return of unused IMP(s) to the sponsor
  • Timely delivery of the IP(s)
  • Establishment of management and filing systems for the IPs
Refer to the MHCTR, the EU-ICH-GCPs, and Additional Resource (D) for detailed sponsor-related IP requirements.
 
Record Requirements
As per the Additional Resource (D) and the EU-ICH-GCPs, the sponsor should inform the investigator(s) and institution(s) in writing of the need for record retention and should notify the investigator(s) and institution(s) in writing when the trial-related pharmacy records are no longer needed. Additionally, the sponsor must ensure sufficient quantities of the IP(s) used in the trial to reconfirm specifications, should this become necessary, and should maintain records of batch samples analyses and characteristics.
 
As set forth in the EU-ICH-GCPs and the EU Good Clinical Practice Directive, sponsor-specific essential documents should be retained until at least two (2) years after the last approval of a marketing application, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of the IP’s clinical development. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.
 
However, per the MHCTR2006, the sponsor and the chief investigator must ensure that the documents contained in the trial master file are retained for at least five (5) years following the trial’s completion. The documents must be readily available to the MHRA upon request, and be complete and legible. The sponsor should ensure that trial participant medical files are also retained for at least five (5) years after the trial’s conclusion.
 
Moreover, the EU Clinical Trials Regulation states that the sponsor and the investigator must archive the content of the clinical trial master file for at least 25 years following the end of the trial.
 
ADDITIONAL RESOURCES
European Commission
 
Relevant Section: Chapter 2 (Section 4)
 
European Parliament and Council
 
Relevant Section: Chapter VIII (Article 51)
 
(C) (EU ICH Guidance) Guideline for Good Clinical Practice E6 (R2) (EU-ICH-GCPs) (Step 5 Version) (December 1, 2016)
EMA/CHMP/ICH/135/1995
Committee for Human Medicinal Products, European Medicines Agency, European Union
 
Relevant Sections: 5.12, 5.13, 5.14, 5.15, 5.5, and 7
 
(D) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012)
Association for the British Pharmaceutical Industry
 
Relevant Sections: 8, 12, 13, and 22
 
European Parliament and Council of the European Union
 
Relevant Section: Chapter VIII (Article 58)
 
Enterprise Directorate-General, European Commission
 
Relevant Section: 4.4
 
European Commission
 
European Commission
 
REQUIREMENTS
(1) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health, National Health Service, UK Government
Implements EU Clinical Trials Directive 2001/20/EC
 
Relevant Sections: Part 3 (13 and 15), Part 4 (28), Part 6 (36 and 38), and Schedule 7 (Parts 2 and 3)
 
(2) (Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health, UK Government
Implements EU Good Clinical Practice Directive 2005/28/EC
 
Relevant Sections: Insertion of Regulation 3A of the Principal Regulations; Amendment of Regulation 15 of the Principal Regulations; and Amendment of Regulation 31 of the Principal Regulations
 
Specimens > Definition of Specimen
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Last content review/update: April 26, 2017. Submit updates or comments.
SUMMARY
Overview
The term “specimen” is not referenced within the United Kingdom (UK). However, the following terms are used relating to specimens:
 
  • Relevant material: As per the UK-HTA, CODE E, and Additional Resources (A) and (B), “relevant material” or “human tissue” is any material from a human body, other than gametes, that consists of, or includes, cells. This also includes blood (except where held for transplantation). Hair and nails from living persons are specifically excluded from this definition, as are gametes and embryos outside the body.
  • Substance/active substance: The EU Community Code Directive defines “substance” as any matter regardless of origin which may be human (e.g., blood and blood products), animal, vegetable, or chemical.

 

ADDITIONAL RESOURCES
Health Research Authority, NHS England, Department of Health, UK Government
 
Relevant Section: Definition of Relevant Material
 
(B) (Website) Relevant Material Under the Human Tissue Act 2004 (Updated February 2014)
Health Tissue Authority, Department of Health, UK Government
 
European Parliament and European Council
 
Relevant Section: Title I (Article 1)
 
REQUIREMENTS
(1) (Legislation) Human Tissue Act 2004 (UK-HTA) (November 15, 2004)
UK Parliament
 
Relevant Sections: Part 3 (53)
 
(2) (Guidance) Code E: Research and Standards (CODE E) (April 2017)
Human Tissue Authority, Department of Health, UK Government
 
Relevant Section: Glossary
 
 
Specimens > Import & Export
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Last content review/update: August 30, 2017. Submit updates or comments.
SUMMARY
Overview
As set forth in the UK-HTA, the HTRegs, and Additional Resource (A), the UK-HTA regulates the storage and use of specimens (known as “relevant materials” or “human tissue” in the United Kingdom (UK)) from the living, and the removal, storage, use, and licensing of relevant materials/human tissue from the deceased for specified health-related purposes in the UK. The UK-HTA refers to specified purposes as “scheduled purposes.”
 
Per Additional Resource (E), the HTRegs transposed the European Union Tissue and Cells Directive (EUTCD) into UK law on July 5, 2007. The HTRegs extended the HTA’s sphere of regulatory responsibility to include procurement, testing, processing, storage, distribution, and import/export.
 
Per the UK-HTA, the G-HTA-QAHumanTissue, and CODE E, the scope of the UK-HTA provisions specifically cover England, Northern Ireland, and Wales. The UK-HTA licensing requirements do not apply in Scotland, with the exception of those provisions relating to the use of DNA. Scotland complies with the Scotland-AnatAct and the Scotland-HTA for the removal, retention, use, licensing, and import of human organs, tissue, and tissue samples specifically removed post mortem, and subsequently used for research. Per Additional Resource (B), the Scotland-HTA does not regulate the use of tissue from the living for research.
 
Relevant Materials/Human Tissue
As specified in the UK-HTA, the Human Tissue Authority (HTA) has jurisdiction regarding the import and export of relevant materials/ human tissue, and complies with the Code of Practice on import and export set forth in CODE E. According to the UK-HTA, CODE E, and Additional Resource (C), the import and export of relevant material/human tissue is not in itself a licensable activity under the UK-HTA. However, once the material is imported, storage of this material may be licensable if it is deemed to be for a specified or scheduled purpose.
 
If relevant material/human tissue is being imported or exported for an application, the HTRegs specify that this must be carried out under the authority of a license or third party agreement with an establishment licensed by the HTA to store material for human application.
 
CODE E requires imported material to be procured, used, handled, stored, transported, and disposed of in accordance with the donor’s consent. In addition, due regard should be given to safety considerations, and with the dignity and respect accorded to human bodies, body parts, and tissue as delineated in CODE E. Any individual or organization wishing to import human bodies, body parts and tissue into England, Wales or Northern Ireland must comply with the guidelines set forth in CODE E.
 
Exported material should also be procured, used, handled, stored, transported and disposed of, in accordance with the donor’s consent, with due regard for safety considerations, and with the dignity and respect accorded to human bodies, body parts and tissue as stated in CODE E. This includes providing donors with adequate information upon taking consent, that their samples may be transported as exported samples for use abroad. It is the responsibility of the recipient country to ensure that, prior to export, the material is handled appropriately and that the required country standards have been met.
 
ADDITIONAL RESOURCES
(A) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Section 12 and Annex H
 
(B) (Website) Summary of Legal Requirements for Research with Human Tissues in Scotland (V2) (June 2016) (Research and Human Tissue Legislation Series)
MRC Regulatory Support Centre, Medical Research Council, UK
 
Relevant Sections: 1 and 3
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Section: Import and Export of Tissue
 
European Parliament and European Council
 
Relevant Sections: Chapter II (Articles 8 and 9)
 
(E) (Website) EU Tissue and Cells Directives (Current as of February 20, 2017)
Health Tissue Authority, National Health Service England, Department of Health, UK Government
 
REQUIREMENTS
(1) (Legislation) Human Tissue Act 2004 (Chapter 30) (UK-HTA) (November 15, 2004)
UK Parliament
 
Relevant Sections: Part 2 (13, 14, 16, 26, and 41)
 
(2) (Legislation) Anatomy Act 1984 (Scotland-AnatAct) (May 24, 1984)
UK Parliament
 
Relevant Sections: Section 3: Licenses and Section 7: Licenses: general provisions
 
(3) (Legislation) Human Tissue (Scotland) Act 2006 (Scotland-HTA) (2006)
Scottish Parliament
 
Relevant Section: Part 5 (53 (6))
 
(4) (Guidance) Guide to Quality and Safety Assurance for Human Tissues and Cells for Patient Treatment (G-HTA-QAHumanTissue) (Version 1.1) (June 2015)
Human Tissue Authority, Department of Health, UK Government
 
Relevant Sections: Glossary/Definitions, Import and Export
 
(5) (Guidance) Code E: Research and Standards (CODE E) (April 2017)
Human Tissue Authority, Department of Health, UK Government
 
Relevant Sections: Introduction to the Human Tissue Authority Codes of Practice, Licensing – Import and Export, Licensing – HTA Licensing Standards, and Annex A
 
(6) (Regulation) The Human Tissue (Quality and Safety for Human Application) Regulations 2007 (S.I. 2007/1523) (HTRegs) (May 25, 2007)
UK Parliament
 
Relevant Sections: Part 1 (6) and Part 2 (7), and Part 3
Specimens > Consent for Specimens
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Last content review/update: February 23, 2017. Submit updates or comments.
SUMMARY
Overview
In accordance with the UK-HTA, CODE1, and Additional Resources (A), (B), and (C), prior to collecting, storing, or using a research participant’s specimens (known as relevant material/human tissue in the United Kingdom (UK)), consent from the participant and/or his/her legal representative(s) and ethics committee (EC) approval must be obtained. The scope of the UK-HTA provisions specifically cover England, Northern Ireland, and Wales. The UK-HTA licensing requirements do not apply in Scotland, with the exception of those provisions relating to the use of DNA. Scotland complies with the Scotland-AnatAct and the Scotland-HTA for the removal, retention, use, licensing, and import of human organs, tissue, and tissue samples specifically removed post mortem, and subsequently used for research.
 
Human Genetic Research Consent Requirements
As set forth in the UK-HTA, CODE1, and Additional Resources (C) and (D), the UK-HTA considers it a UK-wide offense to have relevant material/human tissue with the intention of conducting a DNA analysis or using the results of this analysis without “qualifying consent” from a participant and/or his/her legal representative(s), unless the information is being used for an “excepted purpose.” The UK-HTA and CODE1 state that “qualifying consent” is consent required in relation to the analysis of DNA manufactured by the human body. An “excepted purpose” is defined as the following:
  • Medical diagnosis/treatment
  • Coroner purposes
  • Crime prevention/detection
  • Prosecution
  • National security
  • Court/tribunal order
  • An existing holding to be used for research
In addition to participant consent, EC approval is required for the use of DNA tissue. Please refer to the UK-HTA, CODE1, and Additional Resources (C) and (D) for detailed DNA analysis consent requirements.
 
Human Tissue/Relevant Material Consent Requirements
In accordance with the UK-HTA, CODE1, and Additional Resources (A), (B), and (C), prior to removing, storing, or using any living or deceased person’s organs, tissues, or cells for the purpose of research in connection with disorders in, or the functioning of the human body, investigators must obtain “appropriate consent” from the trial participants and/or their legal representative(s) as well as EC approval. The UK-HTA and CODE1 define “appropriate consent” in terms of the person who may give consent. This person may be either the trial participant, his/her legal representative (referred to as “nominated representative” in the UK-HTA), or, in the absence of either of these, the consent of a person in a “qualifying relationship” with the participant immediately before he/she dies.
 
As indicated in the UK-HTA and CODE1, in the case of a living child donor, “appropriate consent” must be obtained from the child’s legal representative(s). If the child has died, the written consent must be obtained prior to the child’s death in the presence of at least one (1) witness, or, it must be signed at the direction of the child concerned, in his/her presence, and in the presence of at least one (1) witness.
 
As indicated in the UK-HTA and CODE1, in the case of an adult donor, 18 years or older, his/her consent must be obtained prior to removing any materials from his/her body. If the adult has died, his/her written consent is only valid when it is signed by the person prior to his/her death in the presence of at least one (1) witness at his/her direction, or it is contained in the person’s will. An adult donor may also appoint one (1) or more people (“nominated representative(s)”) to consent on his/her behalf in the event of his/her death. This consent may be obtained orally or in writing. If the deceased donor has neither provided consent nor an appointed or nominated representative, appropriate consent may be given by someone in a “qualifying relationship” with the donor immediately prior to his/her death. Refer to the UK-HTA and CODE1 to obtain a complete list of relatives in hierarchical order who may qualify to provide this consent.
 
In the case of obtaining materials from an adult donor who lacks the capacity to consent, and neither a decision to consent or not consent is in force, the UK-HTA, the MCA2005, and Additional Resources (C) and (D) state that approval by an EC is required. In addition, a living person’s organs, tissues, or cells may be stored and used without consent if the investigator is unable to identify the individual and it is being used for an EC-approved research project. Please refer to the UK-HTA and CODE1 for detailed consent requirements.
 
See the Informed Consent topic, Required Elements and Participant Rights subtopics for additional information on informed consent.
 
ADDITIONAL RESOURCES
(A) (Industry Guidance) Guidelines for Phase I Clinical Trials (2012 Edition) (Last Updated November 12, 2014))
Association for the British Pharmaceutical Industry, UK
 
Relevant Section: 18
 
General Medical Council, UK
 
Relevant Section: Areas Requiring Special Consideration (Research Involving Human Tissue)
 
(C) (Document) Standard Operating Procedures for Research Ethics Committees (Version 7.2) (January 2017)
UK Health Departments’ Research Ethics Service, Health Research Authority, National Health Service England, Department of Health, UK Government
 
Relevant Sections: Section 12 and Annex H
 
Royal College of Physicians, Royal College of Pathologists, and The British Society for Human Genetics
 
Relevant Sections: 1, 2, 3, 4, and Appendices A, B and C
 
(E) (Website) Human Tissue Act 2004 (Updated January 2016)
Human Tissue Authority, UK Government
 
Health Research Authority, National Health Service England, Department of Health, UK Government
 
REQUIREMENTS
(1) (Legislation) Human Tissue Act 2004 (UK-HTA) (November 15, 2004)
UK Parliament
 
Relevant Sections: Part 1 (1, 2, 3, 4, 6, and 7), Part 3 (54), and Schedules 1 and 4
 
(2) (Guidance) Code of Practice 1: Consent (CODE1) (Version 14.0) (July 2014)
Human Tissue Authority, Department of Health, UK Government
 
Relevant Sections: Introduction, Consent: the Fundamental Principle, Consent Requirements - Part 1: General provisions, Consent Requirements - Part 2: Tissue from the Deceased, Consent Requirements - Part 3: Tissue from the Living
 
(3) (Legislation) Mental Capacity Act 2005 (Chapter 9) (MCA2005) (April 7, 2005)
UK Parliament
 
Relevant Section: Research
 
(4) (Legislation) Anatomy Act 1984 (Scotland-AnatAct) (May 24, 1984)
UK Parliament
 
Relevant Sections: Introductory (3) and Miscellaneous (7)
 
(5) (Legislation) Human Tissue (Scotland) Act 2006 (Scotland-HTA) (2006)
Scottish Parliament
 
Relevant Section: Part 5 (53 (6))
 
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Expiration Date: 2/28/2019