United Kingdom
United Kingdom

Quick facts

Clinical trial application language English
Regulatory authority & ethics committee review may be conducted at the same time Yes
Clinical trial registration required Yes
In-country sponsor presence/representation required Yes
Age of minors Under 16
Specimens export allowed Yes

Regulatory Authority > Regulatory Authority

Last content review/update: January 13, 2023

Medicines and Healthcare Products Regulatory Agency (MHRA)

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 GBR-57, the MHRA is an executive agency within the Department of Health and Social Care (DHSC). MHRA’s responsibilities are to:

  • Ensure that medicines, medical devices, and blood components for transfusion meet applicable standards of safety, quality, and efficacy
  • Ensure that the supply chain for medicines, medical devices, and blood components is safe and secure
  • Promote international standardization and harmonization to assure the effectiveness and safety of biological medicines
  • Help to educate the public and healthcare professionals about the risks and benefits of medicines, medical devices, and blood components
  • Support innovation and research and development that is beneficial to public health
  • Influence UK and international regulatory frameworks so that they are risk-proportionate and effective at protecting public health

Per the G-CTAuth-GBR, the agency’s Clinical Trials Unit (CTU) focuses specifically on reviewing applications to conduct clinical trials of medicinal products.

Pursuant to the MMDAct, the Secretary of State for DHSC is authorized to make clinical trials regulations and amend or supplement the law relating to human medicines, taking into consideration the safety of human medicines, the availability of human medicines, and the likelihood of the UK being seen as a favorable place to carry out research relating to human medicines, conduct clinical trials, or manufacture or supply human medicines.

Please note: The UK is party to the Nagoya Protocol on Access and Benefit-sharing (GBR-5), which may have implications for studies of investigational products developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see GBR-48.

Contact Information

Per GBR-58, the following is the MHRA’s contact information:

Medicines and Healthcare Products Regulatory Agency
10 South Colonnade
Canary Wharf
LONDON
E14 4PU
UK

Main Phone: +44 020-3080-6000
Fax: +44 0203-118-9803
General Email: info@mhra.gov.uk
Data Protection Email: DataProtection@mhra.gov.uk
Importing Investigational Products from Approval Countries Email: gmpinspectorate@mhra.gov.uk

Clinical Research Office:
Email: clintrialhelpline@mhra.gov.uk
Phone: +44 020-3080-6456

In addition, the G-CTAuth-GBR includes other email addresses for specific purposes related to submissions.

Clinical Trials Named Contact and Urgent Safety Measures
Part 1(4) and Part 3 (12, 17, and 18)
Amendment of Schedule 1 to the Principal Regulations (27 - Part 2, Conditions Based on Article 3 of the Directive)
Part 2 (Chapter 1)
Our Responsibilities
Customer Services, Enquiries about new guidance and procedures in place since 1 January 2021, Clinical trials of medicines, and Data protection

Regulatory Authority > Scope of Assessment

Last content review/update: January 13, 2023

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-CTApp specify that the scope of the MHRA’s assessment includes all clinical trials (Phases 1-4). Per G-CTApp and G-IRASCombRev, all new clinical trial applications must be prepared, submitted, and reviewed via the combined review process (formerly known as Combined Ways of Working (CWoW), which offers a single application route and parallel/coordinated review from MHRA and the ethics committee (EC) leading to a single UK decision for clinical trials.

Regarding licensing of biosimilars (i.e., generic biotech medicines), see the G-Biosimilars for details on the UK’s recent regulatory changes to ease or remove clinical trial requirements for the MHRA’s review and approval of biosimilars.

Clinical Trial Review Process

Per GBR-72, under combined review, research teams make a single application using a new part (GBR-125) of the Integrated Research Application System (IRAS) (GBR-78), which goes to both the MHRA and an EC at the same time. The regulatory and ethics reviews are done in parallel and any requests for further information are raised jointly. A single response to these requests leads to a single decision from both reviews. The G-CTApp states that the initial combined review assessment will be completed within 30 days of application submission. Applications for healthy volunteer trials and sponsor-determined phase 1 trials in non-oncology participants may qualify for a shortened assessment time and the MHRA will work with the EC to expedite these applications. When applications need expert advice, the MHRA will seek advice from the Clinical Trials, Biologicals and Vaccines Expert Advisory Group (CTBV EAG) of the Commission on Human Medicines (CHM). In addition, the CHM will then discuss the trial at their meeting, which will take place later in the same week as the CTBV EAG meeting. See the G-CTApp for examples of which trials require expert advice and for detailed requirements. The MHRA also supports the conduct of trials with complex innovative designs such as umbrella, basket, platform, and master protocol plus submodules. These trial designs are characterized by the presence of prospective major adaptations, such as the addition of new IPs or introducing new trial populations. Before submitting a clinical trial application with a complex innovative design and/or an amendment requesting approval of major adaptations, sponsors are recommended to establish a dialogue with the MHRA and seek advice.

Pursuant to the combined review process, the MHRA will inform applicants of the outcome of the submission along with the EC’s review and decision. The outcomes could be one (1) of the following:

  • Acceptance of the request for a clinical trial authorization
  • Acceptance of the request for a clinical trial authorization subject to conditions
  • Grounds for non-acceptance of the request for a clinical trial authorization

With respect to grounds for non-acceptance, applicants will have the opportunity to respond, usually within 14 days; however, this may be extended on request. A communication informing the applicant of the combined MHRA and EC decision will usually be sent within 60 days of receiving the original valid application. If an extension to the response date has been agreed to, then this will impact the final decision timeline. Notification of a decision relating to a gene therapy, somatic cell therapy (including xenogenic cell therapy) product, tissue engineered product, or products containing genetically modified organisms will be sent within 90 days of receiving the original application, unless otherwise advised. Communications will be sent electronically via email from MHRA_CT_Ecomms@mhra.gov.uk. The MHRA will only send official correspondence to the named applicant email address. According to the MHCTR, if the sponsor or the designated representative does not receive a request for additional information from the MHRA within 30 days, the application is considered authorized. (See the Timeline of Review section for additional details.)

Per GBR-9, the EC’s ethical opinion applies for the duration of the study, which was stated in the clinical trial application and protocol. An extension of the study period is not in itself a substantial amendment, except where it is related to other amendments that would be substantial, such as an increase in target recruitment, addition of new procedures or sub-studies, or extension of follow-up. Where the duration of the study is to be extended beyond the period specified in the application form, the EC should be notified.

IRAS (GBR-78) is a single system for applying for the permissions and approvals for health and social care/community care research in the UK. It generates the IRAS ID and uses filters to ensure that the data collected and collated is appropriate to the type of study, and consequently the permissions and approvals required. The system helps applicants meet the regulatory and governance requirements. As described in GBR-67, approval from the Health Research Authority (HRA) is required for all National Health Service (NHS) project-based research led from England or Wales. HRA and Health and Care Research Wales (HCRW) approval brings together the assessment of governance and legal compliance. For any new studies led from Scotland or Northern Ireland but have English and/or Welsh NHS sites, the national research and development coordinating function of the lead nation will share information with the HRA and HCRW assessment teams, who can issue HRA and HCRW approval for English and Welsh sites and thereby retain existing compatibility arrangements. Studies led from England or Wales with sites in Northern Ireland or Scotland will be supported through existing UK-wide compatibility systems, by which each country accepts the centralized assurances, as far as they apply, from national coordinating functions without unnecessary duplication. For details on HRA’s assessment criteria and standards for approval, see GBR-29.

Brexit Background

Per the G-MHRASubmiss, Brexit, the EUCouncil-Brexit, the WithdrlAgrmt, and the G-AfterTransition, the UK withdrew from the European Union (EU) on January 31, 2020. The MHRA updated and published clinical trials guidance that became effective on January 1, 2021. G-AfterTransition summarizes the guidance to sponsors and researchers. Furthermore, the G-MHRASubmiss describes how to make certain regulatory submissions to the MHRA (substantial amendments, end-of-trial notifications, and developmental safety update reports (DSURs)). Per the MHCTR-EUExit and as explained in GBR-115, the new guidance went into force via the MHCTR-EUExit (also known as the "Exit Regulations"). The Exit Regulations also update existing UK legislation by, for example, replacing references to EU databases with newly established UK databases. The G-IPsNIreland delineates that the supply and use of IPs in Northern Ireland must follow EU laws as per the Northern Ireland Protocol. For policy papers and details on the Northern Ireland Protocol, see GBR-119. For broader information and a comprehensive Brexit “checker” of new rules in the UK, see GBR-60.

To help ensure the continuity of supply of IPs for clinical trials the BrexitLtr-IPs indicates that the UK will unilaterally recognize certain EU regulatory processes for a time-limited period. This recognition is known as “standstill.”

GBR-115 indicates that the UK is committed to being as aligned as possible with the EU Clinical Trials Regulation (GBR-21). The MMDAct grants authority for regulations to be made that correspond or are similar to GBR-21.

6
10.9
Help (Preparing and Submitting Applications)
When a clinical trial authorization (CTA) is needed, Trial Sponsor and legal Representative, Registration of your clinical trial, Combined review of clinical trials of investigational medicinal products, Documents to send with your application, Assessment of your submission, Requesting approval of trials with complex innovative designs, and Applications that need expert advice
Part 4 (Article 126)
Part 2 (Chapter 1)
Introduction and Article 1
Schedule 2 (Part 1(1))
Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 1 (2), Part 2 (5, 6, and 7), Part 3 (12, 14, 15, 17, and 18), and Schedule 2

Regulatory Authority > Regulatory Fees

Last content review/update: January 13, 2023

Medicines and Healthcare Products Regulatory Agency (MHRA)

As per the MHCTR, the MHCTR2006, the G-CTApp, and the G-MHRAFees, the sponsor or the 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-MHRAPaymt, applicants will receive an invoice to make a payment for the outstanding amount after validation of the application. Applicants must pay invoices upon receipt or they will incur penalty fees.

As delineated in the G-MHRAFees, the MHRA levies the following clinical trial processing fees:

  • 3,060 British Pounds – Applications with an Investigational Medicinal Product (IMP) dossier
  • 225 British Pounds – Applications without an IMP dossier
  • 225 British Pounds – Clinical trial variation/amendment
  • No cost – Phase 4 notification

The G-CTApp further indicates that no fees are required for applications submitted and authorized under the Notification Scheme.

Payment Instructions

According to the G-MHRAPaymt, the MHRA does not accept checks. Payments can be made electronically by bank transfer, credit card, or debit card. 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

As per G-MHRAPaymt, credit or debit card payments may be made securely online using MHRA’s payments service (GBR-26). Remittance advice notices can be sent to sales.invoices@mhra.gov.uk and should include the relevant invoice number on the remittance advice. MHRA cannot accept any documentation sent by postal mail service. Further information can be obtained by emailing sales.invoices@mhra.gov.uk. G-MHRAPaymt further provides that clinical trial application invoice disputes/queries should be emailed to ctdhelpline@mhra.gov.uk and cc: sales.invoices@mhra.gov.uk.

The G-CTApp indicates that invoices for clinical trial authorization applications and substantial amendment applications are sent directly to the applicant shortly after a valid submission has been established. The applicant’s cover letter should clearly highlight the purchase order (PO) number where available. It is the responsibility of the applicant to ensure timely payment of invoices for their submissions. Invoices must be settled on receipt of invoice. For additional information, applicants may contact the MHRA Finance Department at 020 3080 6533 or sales.invoices@mhra.gov.uk.

Fees
8 (Clinical trials: application fees)
11, 13, and Explanatory Note
Part 3 (17)

Ethics Committee > Ethics Committee

Last content review/update: January 13, 2023

Overview

As set forth in GAfREC, the United Kingdom (UK) has a centralized recognition process for ethics committees (ECs), known as research ethics committees (RECs) in the UK. ECs are part of an accountable and independent Research Ethics Service (RES) (GBR-62).

As described in GBR-51 and GBR-62, the RES has a dual mission to protect the rights, safety, dignity, and well-being of research participants and to facilitate and promote ethical research that is of potential benefit to participants, science, and society. To achieve this, GBR-62 states that the RES works with the devolved administrations to conduct the following activities:

  • Provide robust, proportionate, and responsive ethical review of research through ECs
  • Provide ethical guidance to ECs
  • Provide and deliver a managed structure to support ECs
  • Deliver a quality assurance (QA) framework
  • Deliver a training program
  • Work with colleagues across the UK to maintain a UK-wide framework for ethical review
  • Work with colleagues in the wider regulatory environment to streamline the processes for approving research
  • Promote and support transparency in research

As stated in GAfREC, the RES encompasses England’s Department of Health and Social Care (DHSC), Northern Ireland’s Department of Health, the Scottish Government Health and Social Care Directorates (SGHSC), the Welsh Government’s Department of Health and Social Care as well as the ECs that are collectively recognized or established by these authorizing bodies. The UK Health Departments have authorized the head office of the RES in England, within the Health Research Authority (HRA), to perform some UK-wide functions on behalf of the other head offices, including performing some of the functions of the UK Ethics Committee Authority (UKECA), which is the statutory body that recognizes ECs for the review of clinical trials of investigational medicinal products (CTIMPs). (See Oversight of Ethics Committees section for more details on RES and UKECA functions.) In accordance with the MHCTR and the MHCTR2006, ECs recognized to conduct reviews of clinical trials for CTIMPs are authorized by the UKECA.

All recognized RES ECs are required to comply with the provisions delineated in GAfREC, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), and GBR-9. However, specific ECs within the RES are recognized, or otherwise designated, to review certain types of research proposals. A list of recognized ECs within the RES is available through GBR-111. Also see GBR-64 for EC definitions.

Ethics Committee Composition

As delineated in the MHCTR and GAfREC, a RES-recognized EC, which includes those recognized by UKECA, may consist of up to 18 members. 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, and half of the lay members must be persons who are not and never have been health care professionals, clinical researchers, or managers of clinical research (also known as 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. GBR-9 mirrors this requirement, but adds that when investigational products are reviewed, a lay member must be present. See GBR-113 for additional recommendations for composition.

Per GBR-9, in order to accommodate the United States’ (US) quorum definition pursuant to regulations for the protection of human subjects in research (45 CFR 46) and the Common Rule (45 CFR 46 Subpart A), the RES also makes special arrangements to review UK-based research 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 GAfREC for additional EC composition requirements.

Terms of Reference, Review Procedures, and Meeting Schedule

In addition to complying with composition requirements, GAfREC, GBR-113, and GBR-9 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.

Per GBR-9, applications that have been submitted via the CTIMP combined review service will be validated by the MHRA, and EC staff do not need to undertake a formal validation check. ECs should check the application against the validation checklist and request any missing information or clarifications from the applicant if required. All validated clinical trial applications for an ethical opinion should be reviewed at a full meeting of an EC. An EC should normally hold at least 10 scheduled full meetings in each year for the purposes of ethical review of applications. Additional meetings may be held where necessary to ensure that an ethical opinion on an application is given within the relevant time limit (or to discuss matters relating to the establishment or operating procedures of the EC or for training purposes). Meetings to review applications should normally be held at intervals of one (1) month, unless there are holidays. The schedule of EC meetings for the financial year commencing on April 1st should be agreed to by December 1st in the previous financial year. The schedule should set out the dates, times, and venues of meetings, and the closing date for applications to each meeting. All members and deputy members of the EC should receive details of the schedule. The closing dates for full applications should normally be 14 calendar days prior to each EC meeting. In the case of applications for Phase 1 clinical trials in healthy volunteers, Type 1 ECs may adopt a later closing date for applications not less than seven (7) calendar days prior to the meeting and may accept applications booked in advance of the closing date which are submitted up to seven (7) days before the date of the meeting.

According to GBR-9, the EC Chair is responsible for ensuring that the EC reaches clearly agreed to decisions on all matters. If the Chair is unavailable, then the meeting should normally be chaired by the vice-Chair or, if the vice Chair is also unavailable, by the alternate vice-Chair. The EC meeting should reach unanimous decisions by consensus wherever possible. Where a consensus is not achievable, a formal vote should be taken by a counting of hands. The decision of the EC should be determined by a simple majority of those members present and entitled to vote. A record should be kept of the number of votes, including abstentions, in the minutes. Where the vote is tied, the Chair may give a casting vote, but should first consider any other options to arrive at a more consensual decision. Where any member wishes to record a formal dissent from the decision of the committee, this should be recorded in the minutes but should not be included in the opinion letter. An agenda should be prepared for an EC meeting. EC staff must prepare minutes of the EC meetings. See GBR-9 for additional requirements on the agenda, meeting conduct/decisions, and minutes during full EC meetings.

As per GBR-9, documents for EC meetings should be distributed as soon as possible after the agenda is finalized and applications have been validated, and in any case no later than 10 calendar days prior to the meeting (with the exception of expedited, proportionate review, and Phase 1 applications where there has been prior agreement). Under no circumstances should full applications be tabled at the meeting. Applications should be made available to members via the HRA Assessment and Review Portal (HARP) as soon as the application is validated, and an email sent to the EC members to inform them the application is now viewable.

GBR-9 requires ECs to retain all the documentation relating to a CTIMP on which it gives an opinion:

  • Where the trial proceeds, for at least three (3) years from the conclusion or early termination of the trial
  • Where the trial does not proceed (e.g., it is given an unfavorable opinion, or does not start following a favorable opinion), for at least three (3) years from the date of the opinion

In accordance with GBR-9, documentation should be retained on all invalid applications for at least one (1) year from the date of invalidation; and for three (3) years where the application is withdrawn by the EC, the chief investigator, or the sponsor after the EC review but before a final opinion is given. Signed final copies of the minutes of full EC meetings and sub-committee business should be retained electronically for at least 20 years. Where paper records are destroyed in accordance with this policy, they should be shredded and disposed of as confidential waste. Electronic records of studies will be retained indefinitely.

For detailed EC procedures and information on other administrative processes, see GAfREC, GBR-113, and GBR-9. Also see GBR-8 for a summary of changes to GBR-9.

Introduction (Purpose and Scope, and Implementation), Terminology (Glossary), and Sections 1, 2, 3, and 15
Foreword, Introduction, 1.24, 1.27, 2.6, 3, and 5.11
Definitions of Authorised REC and Recognized REC
Search Research Ethics Committee
1-6, Glossary, Annex C, Annex E, and Annex F
Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 2, Part 3 (11, 12, 14, 15, 17, and 18), and Schedule 2

Ethics Committee > Scope of Review

Last content review/update: January 13, 2023

Overview

According to GAfREC, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), and GBR-9, the primary scope of information assessed by ethics committees (ECs) within the United Kingdom (UK) Health Departments’ Research Ethics Service (RES) (GBR-62) 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). GAfREC specifies that ethical review is required for research proposals that involve investigational products (IPs), material consisting of human cells, and other situations that are described in GAfREC.

As per GAfREC, the MHCTR, the MHCTR2006, the MHCTR2006-No2, and GBR-113, ECs must pay special attention to reviewing informed consent and to protecting the welfare of certain classes of participants deemed to be vulnerable. (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations).

As indicated in GAfREC, the MHCTR, the MHCTR2006, GBR-113, and GBR-9, 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 GBR-9 for detailed ethics review guidelines.

GBR-112 indicates that certain ECs are flagged for special expertise including gene therapy or stem tell clinical trials; Phase 1 studies in healthy volunteers; Phase 1 studies in participants; research involving adults lacking capacity; research involving children; research involving prisoners or prisons; or fast-track ECs.

Role in Clinical Trial Approval Process

As described in GBR-9, GBR-66, and GBR-95, the type of EC responsible for approval (known as a “favorable opinion” in the UK) within the RES depends on the type of research being conducted. Per GAfREC and GBR-9, ECs are recognized or established by the United Kingdom Ethics Committee Authority (UKECA) to conduct reviews of clinical trials for IPs (known as clinical trials for investigational medicinal products (CTIMPs) in the UK). Per GAfREC, RES-recognized ECs established under Health Department policy within each of the four (4) UK nations (England, Northern Ireland, Scotland, and Wales) review research studies other than IP clinical trials. Also see GBR-64 for definitions of EC terminology and GBR-111 and GBR-112 to search for ECs within the RES.

As indicated in the MHCTR, the MHCTR2006, and GAfREC, IP 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 the designated legal representative initiating the trial. The G-CTApp states that all new clinical trial applications must be prepared, submitted, and reviewed via the combined review process, wherein a single application route and coordinated review by MHRA and the EC leads to a single UK decision. New clinical trial applications for combined review are prepared and electronically submitted to the new combined review section of Integrated Research Application System (IRAS) (GBR-125). Per GBR-78, IRAS does not change the requirements for review, including authorizations or signatures, of any regulatory authority or National Health Service (NHS) body. Therefore, it requires different authorizations depending on the type of study and the applicable review bodies. According to GBR-9, submissions of the electronic application must be made to IRAS on the same day that a booking is made to schedule an EC review through the NHS REC’s Online Booking Service (GBR-95).

According to the MHCTR, GAfREC, and GBR-9, for all studies, only one (1) EC review (referred to as the “main EC”) is needed for a project taking place in the UK, regardless of the number of sites. Furthermore, GBR-9 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. The ethical review includes an assessment of the suitability of each site or sites at which the research is to be conducted in the UK. The site assessment is not a separate ethical review, but forms part of the single ethical review of the research. Management permission is still required from the organization responsible for hosting the research before it commences at any site. In the case of international studies, an application must be made to an EC in the UK, whether or not the study has a favorable ethical opinion from a committee outside the UK, and whether or not it has started outside the UK.

Per GBR-68, unless an application is being processed under the proportionate review service, the applicant should attend the EC meeting if possible. The EC will notify the sponsor of its decision, usually within 10 working days of the EC meeting. GBR-9 indicates that the EC should reach one (1) of the following decisions on any application reviewed at a full meeting or a proportionate review sub-committee meeting:

  • A final opinion, which may be either favorable with standard conditions, favorable with additional conditions, or unfavorable
  • Provisional opinion with request for further information, which means the EC may decide that a final opinion cannot be issued until further information or clarification has been received from the applicant

The MHCTR, GBR-9, and GBR-68 state that the 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 may make one (1) written request for further information, clarification, or changes to documentation. The time required 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 Submission Process and Timeline of Review sections for detailed submission process requirements.)

Per GBR-116, the Health Research Authority (HRA), on behalf of the UK, offers a fast-track research ethics review. Fast-track ethics review is open to global clinical trials and Phase 1 trials, whether the sponsor is commercial or non-commercial. This includes:

  • Any clinical trial of an investigational medicinal product (CTIMP) led from UK with at least one (1) other country participating
  • Any CTIMP led from outside the UK which could be placed in any country and the UK is competing for participation (including any only taking place in the UK)
  • Any Phase 1 or Phase 1/2 CTIMP in healthy volunteers or participants

Fast-track ethics review is not available for any CTIMP involving a gene therapy medicinal product, any CTIMP funded by the US Department of Health and Human Services, and any other type of clinical trial or research study.

Per GBR-9, the EC’s favorable ethical opinion applies for the stated duration of the study, except where action is taken to suspend or terminate the opinion. The MHCTR, GAfREC, and IRAS (GBR-78) require the applicant to identify an expected end date for the study. A change to the definition of the end of the study is a substantial amendment. Extension of the study beyond the period specified in the application form is a non-substantial amendment.

GBR-9 describes EC processes related to reviewing and approving clinical trial amendments and any related notifications. The sponsor of a CTIMP may make an amendment to a clinical trial authorization, other than a substantial amendment, at any time after the trial has started. These do not need to be notified. If the amendment is substantial, the sponsor is required to submit a valid amendment to the MHRA and/or the REC that gave the favorable opinion of the trial. Where the sponsor requests an ethical opinion on a CTIMP, the EC should provide this in all cases within 35 calendar days of receiving a valid amendment. If the opinion is unfavorable, the sponsor may then modify the proposed amendment. A written notice of the modification should be sent to the main EC at least 14 calendar days before it is due to be implemented. The EC may then give an unfavorable opinion on the modified amendment within 14 calendar days, otherwise it may be implemented. See GBR-9 and GBR-98 for guidance on what changes qualify as a substantial amendment, which requires notification to the EC and MHRA. GBR-9 states that while the EC is not responsible for proactive monitoring, it has a duty to keep the favorable ethical opinion under review in the light of progress reports and significant developments and may review the opinion at any time. If information raises concerns about the suitability of the site or investigator, the favorable opinion may be reviewed.

Introduction (Purpose and Scope), Terminology (Glossary), and Sections 1, 3, 5, 6, and 10.9
Foreword, 1.27, 2, and 3
Search Research Ethics Committee
Combined review of clinical trials of investigational medicinal products
2.3, 3, 4.3, and 5.4
Amendment of the Clinical Trials Regulations; Amendment of the Adults with Incapacity (Scotland) Act 2000
Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 1 (2 and 3), Part 3 (11, 12, 14, 15, 17, and 18), Schedule 2, and Schedule 3 (Part 1)

Ethics Committee > Ethics Committee Fees

Last content review/update: January 13, 2023

As set forth in GAfREC, ethics committees (ECs) are not permitted to charge an application fee or seek any other financial contribution or donation for reviewing research proposals. Additionally, EC members receive no payment for contributing to the application review process at scheduled meetings or for attending these meetings.

4.3

Ethics Committee > Oversight of Ethics Committees

Last content review/update: January 13, 2023

Overview

As stated in GAfREC and GBR-9, the United Kingdom (UK)-wide Research Ethics Service (RES) (GBR-62) provides proportionate and responsive ethical review of research through its “recognized” ethics committees (ECs), known as research ethics committees (RECs) in the UK. Per the MHCTR, the MHCTR2006, and GAfREC, the UK Ethics Committee Authority (UKECA) is the statutory body that recognizes ECs for the review of clinical trials of investigational products (CTIMPs). The UK Health Departments have authorized England’s Health Research Authority (HRA) to perform some of the RES functions (more details below).

As indicated in the MHCTR and GBR-9, the UKECA recognizes two (2) types of ECs for new CTIMPs:

  • Type 1: Reviews Phase 1 clinical trials of investigational products (IPs) taking place at any site in the UK, where the sponsor has no knowledge of any evidence that the product has effects likely to be beneficial to the participants of the trial, and the participants are healthy and not suffering from the disease or condition to which the trial relates.
  • Type 3: Reviews clinical trials of IPs taking place at any site in the UK, including first-in-person studies involving people with the target disease or condition to which the trial relates.

As stated in GAfREC, the HRA performs the following EC oversight activities on behalf of the UKECA:

  • Develops and manages a national training program for ECs
  • Develops, implements, and maintains standard operating procedures for ECs and provides advice and support to ECs on procedural issues
  • Develops a quality assurance program, including accreditation of ECs, based on regular monitoring and audit of their operation and performance
  • Provides guidance and advice to assist ECs in their work and encourage consistency of approach to common issues in research ethics
  • Acts for UKECA to provide a national mechanism for operational advice and assistance to ECs recognized to review and approve clinical trials
  • Acts for UKECA to handle appeals against the unfavorable opinions of ECs in respect of CTIMPs
  • Acts for UKECA to transfer to a successor EC the functions of an EC that has ceased to operate or that has been varied, abolished, or had its recognition revoked
  • Acts for UKECA to reallocate to ECs applications made to the Gene Therapy Advisory Committee which do not require its review

The following oversight functions are the responsibility of UKECA for the purposes of clinical trials:

  • Establishes or recognizes ECs
  • Establishes or recognizes ECs to act in relation to such descriptions or classes of research as it considers appropriate
  • Abolishes or revokes the recognition of ECs that it has established or recognized
  • Monitors the extent to which ECs adequately perform their functions, including through annual reports from ECs it has recognized
  • Approves standing orders and standard operating procedures for EC business and operations, as well as variations and revocations to these orders and procedures

Registration, Auditing, and Accreditation

Per GAfREC, HRA, acting for UKECA, develops a quality assurance program to encourage a consistently high level of service to applicants, including accreditation of ECs, based on regular monitoring and audit of their operation and performance.

GBR-123 indicates that HRA implements a rolling accreditation program to audit UK ECs against standards as detailed in GAfREC and GBR-9. ECs are issued with an audit decision: full accreditation, accreditation with conditions (low-risk non-compliance identified requiring an action plan), or provisional accreditation (high- and low-risk issues requiring an action plan). Published bi-annually, HRA’s latest accreditation report is at GBR-124. In addition, quality control checks are undertaken, and results are shared with management teams. For example, operational managers observe EC meetings and provide a check against agreed-upon standards relating to meeting conduct and minute taking. Findings from the meeting observations are shared with the EC chair and staff and collated to identify common themes to inform improvements. For more information about quality assurance, contact quality.assurance@hra.nhs.uk.

Introduction (Purpose and Scope), Implementation, Terminology (Glossary), and Sections 1, 2, and 3
Accreditation Scheme for Research Ethics Committees and Quality Control
1.3, 2.1, 2.3, 3.3, 5.4, Glossary, Annex C, Annex D, Annex E, and Annex F
Part 2 (Conditions Based on Article 3 of the Directive)
Part 2, Part 3 (12), and Schedule 2

Clinical Trial Lifecycle > Submission Process

Last content review/update: January 13, 2023

Overview

In accordance with the MHCTR, the MHCTR2006, the G-CTApp, and GBR-9, the United Kingdom (UK) requires the sponsor or the designated legal representative to obtain clinical trial authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA) prior to initiating the trial. Per G-CTApp and G-IRASCombRev, the UK’s combined review process offers a single application route and coordinated/parallel review from MHRA and the ethics committee (EC) leading to a single UK decision for clinical trials.

Note: G-CTApprovedCountries and the MHCTR-EUExit list the countries where a clinical trial sponsor or their legal representative may be established; these countries are initially European Union (EU) and European Economic Area (EEA) countries.

Combined Review Submission

Per G-CTApp and G-IRASCombRev, all new clinical trials applications of investigational products (CTIMPs) must be prepared, submitted, and reviewed via the combined review process using the Integrated Research Application System (IRAS) (GBR-125). For support and getting started, users should review GBR-72 and contact the combined review team at cwow@hra.nhs.uk. Step-by-step instructions are provided in G-IRASCombRev. As delineated in GBR-9, applications submitted via the combined review service are submitted jointly by the chief investigator and the sponsor. Per GBR-116, applicants seeking fast-track review of clinical trial applications must also apply via combined review on GBR-125. See Scope of Assessment section for fast-track eligibility criteria.

Per GBR-122, for studies that were submitted before combined review, these applicants should continue to submit amendments and reports for these studies at IRAS via GBR-78’s log-in. HRA will update sponsors and applicants with full instructions and plenty of notice for any planned changes in the future, such as the migration of existing, ongoing studies. See GBR-122, for additional details on the migration of existing materials in IRAS. GBR-72 includes learning resources and a video on the combined review process.

G-IRASCombRev contains a step-by-step guide to combined review submission. The following is an overview of the steps:

  • Finalize protocol and supporting documents
  • New users create IRAS account and create a new project and allocate roles
  • Complete project details, study information, and clinical trial dataset in IRAS and upload supporting documentation
  • Send application to the sponsor to review and authorize
  • Book an EC online and submit application

Note that when selecting an EC meeting that is not the first available meeting, the 60-day regulatory clock for both the EC and the MHRA will start on the cutoff date for the meeting that is chosen, which is 14 days before the meeting date. Once booked, the EC booking page will update to show the confirmed booking details. The applicant will then be able to scroll down the page to select the option to “submit to the regulators.” See G-IRASCombRev for detailed step-by-step instructions.

Other regulatory information aside from new clinical trial applications are to be submitted pursuant to the G-MHRASubmiss. These submittals include substantial amendments for existing clinical trials, end-of-trial notifications, and developmental safety update reports (DSURs). The G-CTAuth-GBR also states that clinical trials not approved or yet transitioned over to the combined review process should continue to use the online MHRA Submissions portal (GBR-13). The steps for gaining access to the UK portal MHRA Submissions (GBR-13) are contained in the G-MHRASubmiss and GBR-11. For overviews of submittals to MHRA, see GBR-18 and GBR-17.

Per GBR-18, all CTIMPs that have sites in the EU must be registered on the EudraCT database (GBR-87) and issued with a unique EudraCT number.

As described in GBR-78, other relevant approvals can be sought on the IRAS site. For example, applicants can request inclusion in the National Institute for Health and Care Research Clinical Research Network (NIHR CRN) Portfolio, which comprises high-quality clinical research studies that receive support services from the Clinical Research Network in England.

Per G-CTApp, MHRA supports the conduct of trials with complex innovative designs such as umbrella, basket, platform, and master protocol plus submodules. When submitting a clinical trial application for a trial with innovative designs that involve prospective major adaptations, the sponsor must justify the choice of a complex trial design, ensure that each adaptation as well as the entire trial are safe and scientifically sound, and describe how the integrity of trial results will be maintained throughout the conduct of the trial. See G-CTApp for example scenarios of when it is appropriate to propose major adaptations via submission of a substantial amendment request. Before submitting an application for authorization of a trial with a complex innovative design and/or an amendment requesting approval of major adaptations, sponsors are recommended to establish a dialogue with the MHRA and seek advice.

As delineated in the MHCTR, the clinical trial application and accompanying material must be provided in English.

3
Terminology (Glossary) and Sections 1.1-1.2 and 14
CI Checklist Before Seeking Approval, CTA Submission, Unique Trial Number, EudraCT Number
Combined Review: What will happen to ongoing CTIMP studies submitted in the standard system?
Help (Preparing and Submitting Applications)
Trial Sponsor and legal Representative, Combined review of clinical trials of investigational medicinal products, Documents to send with your application, and Requesting approval of trials with complex innovative designs
Amending your trial protocol or other documentation
2
2
Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 1 (3) and Part 3 (12, 14, 17, and 18)

Clinical Trial Lifecycle > Submission Content

Last content review/update: January 13, 2023

Regulatory Authority Requirements

As specified in the G-CTApp, a clinical trial submission package to the Medicines and Healthcare Products Regulatory Agency (MHRA) should contain the following documents:

  • Cover letter (when applicable, the subject line should state that the submission is for a Phase 1 trial and is eligible for a shortened assessment time, or if it is submitted as part of the notification scheme); this letter should clearly highlight the Purchase Order (PO) number to help the MHRA invoice and allocate payments promptly and efficiently
  • Clinical trial application form in PDF and XML versions
  • Protocol document
  • Investigator’s brochure (IB)
  • Investigational medical product dossier (IMPD) or a simplified IMPD
  • Summary of scientific advice obtained from the MHRA or any other regulatory authority, if available
  • Manufacturer’s authorization, including the importer’s authorization and Qualified Person declaration on good manufacturing practice for each manufacturing site if the product is manufactured outside the European Union (EU) (See G-ImportIMPs and the Manufacturing & Import section for more information)
  • Copy of the United Kingdom (UK) or the European Medicines Agency’s decision on the pediatric investigation plan and the opinion of the pediatric committee, if applicable
  • Content of the labelling of the investigational product (IP) (known as investigational medicinal product (IMP) in the UK) (or justification for its absence)

Ethics Committee Requirements

As per the MHCTR, the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GBR-113), ECs require the chief investigator (CI) to submit the following documentation for ethics approval:

  • Application for an EC opinion
  • 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 the Insurance & Compensation section 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 and copies of materials to be provided to participants (See the Required Elements section for additional information)
  • Participant treatment plans
  • Benefit/risk assessment for participants
  • Investigator(s) Curriculum Vitaes (CVs)
  • Trial design and suitability of facilities

Further, to help with planning before seeking EC approval, GBR-18 provides a checklist for CIs.

Clinical Protocol

Per GBR-9, the protocol describes the objectives, design, methodology, statistical considerations and organization of a clinical trial. According to GBR-113, 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
  • IP description (See the 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 the Safety Reporting section 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 GBR-113.

Documents to send with your application
Part 3 (12, 14, 15, 17, and 18) and Schedule 3 (Parts 1 and 2)
3.1 and 6
CI Checklist Before Seeking Approval
Terminology (Statutory Definitions Relating to CTIMPs)

Clinical Trial Lifecycle > Timeline of Review

Last content review/update: January 13, 2023

Overview

Per G-CTApp and G-IRASCombRev, all new clinical trials applications for investigational products (CTIMPs) must be prepared, submitted, and reviewed via the combined review process. Combined review offers a single application route and coordinated/parallel review from the Medicines and Healthcare Products Regulatory Agency (MHRA) and the ethics committee (EC) leading to a single United Kingdom (UK) decision for clinical trials.

Combined Review

Per the G-CTApp and GBR-72, the initial combined review assessment will be completed within 30 days of being submitted. The G-CTApp indicates that applications for healthy volunteer trials and sponsor-determined phase 1 trials in non-oncology participants may qualify for a shortened assessment time and MHRA will work with the EC to expedite these applications. The MHRA and the EC will inform applicants of the outcome of a submission. If there are grounds for non-acceptance of the application, the applicant will have the opportunity to respond--usually within 14 days, though this may be extended on request. Communication informing the applicant of the MHRA and EC decisions following receipt of the responses will usually be sent within 60 days of receiving the original valid application. If an extension to the response date has been agreed to, then this will impact the final decision timeline. Notification of the decision relating to a gene therapy, somatic cell therapy (including xenogenic cell therapy) product, tissue engineered product, or products containing genetically modified organisms will be sent within 90 days of receiving the original application unless otherwise advised.

The G-CTApp states that the MHRA uses automated electronic communication. To ensure receipt of MHRA correspondence, applicants should add MHRA_CT_Ecomms@mhra.gov.uk to their safe sender email list. MHRA will only send official correspondence to the named applicant email address. According to the MHCTR, if the sponsor or the 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 the G-CTApp, certain first-in-human (Phase 1) trials of investigational products with higher risk or greater elements of uncertainty require the MHRA to seek advice from the Clinical Trials, Biologicals, and Vaccines Expert Advisory Group (CTBV EAG) of the Commission on Human Medicines before approval for the trial can be given. See the G-CTApp for detailed requirements.

Combined review of clinical trials of investigational medicinal products, Assessment of your submission, and Applications that need expert advice
Initial Process Review and Timelines

Clinical Trial Lifecycle > Initiation, Agreements & Registration

Last content review/update: January 13, 2023

Overview

In accordance with the MHCTR, the MHCTR2006, and GAfREC, a clinical trial can only commence after the sponsor or the designated representative receives authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA) and the chief investigator (CI) receives an approval from a recognized ethics committee (EC). In addition, GBR-9 clarifies that a favorable EC opinion does not imply that research activity at sites can begin. Confirmation of management permission or approval from relevant care organization(s) to proceed with the research also needs to be in place. In addition, if the EC issued a favorable opinion with additional conditions, the clinical trial cannot start until these conditions are met. Finally, per the MHCTR and GBR-18, specific documentation, including MHRA licensing, must be in place before an investigational product (IP) can be released for a clinical trial.

As stated in the MHCTR, clinical trials should be conducted in compliance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), and laboratory practices for IPs must comply with the UK-GLPs.

Per GBR-78, all project-based research must also have governance and legal compliance approvals from the appropriate lead United Kingdom (UK) Health Department. The Integrated Research Application System (IRAS) (GBR-78) facilitates this process. As described in GBR-67, approval from the Health Research Authority (HRA) is required for all National Health Service (NHS) project-based research led from England or Wales. HRA and Health and Care Research Wales (HCRW) approval brings together the assessment of governance and legal compliance. For any new studies that are led from Scotland or Northern Ireland but have English and/or Welsh NHS sites, the national research and development coordinating function of the lead nation will share information with the HRA and HCRW assessment teams, who can issue HRA and HCRW approval for English and Welsh sites and thereby retain existing compatibility arrangements. Studies led from England or Wales with sites in Northern Ireland or Scotland will be supported through existing UK-wide compatibility systems, by which each country accepts the centralized assurances, as far as they apply, from national coordinating functions without unnecessary duplication. For more information on HRA’s assessment criteria and standards for approval, see GBR-29.

Clinical Trial Agreement

According to GBR-107 and GBR-70, contracts and agreements should be in place prior to the initiation of a trial. GBR-107 provides model templates for industry-sponsored clinical trials with the NHS/Department of Health and Social Care (DHSC) participants in hospitals throughout the UK Health Services, which encompasses England, Northern Ireland, Scotland, and Wales. Applicants are advised to use the templates without modification. Any proposed modifications will not be accepted unless first agreed to by the UK Contracting Leads. Proposing modifications to the templates is likely to result in significant delay. Feedback on the content of the templates and their use by sponsors should be provided to mCTA@hra.nhs.uk.

GBR-107 also provides the model non-commercial agreement (mNCA) template to meet the requirements of non-commercial sponsors and the NHS/DHSC bodies undertaking the research. This agreement has been developed as a single, UK-wide agreement template, meaning that it can be used irrespective of where the sponsor and research site are established. It is designed to be used without modification or negotiation. The mNCA has been developed for a range of interventional research scenarios, including clinical trials, medical device studies, research using participant data, and research using human tissue. The terms and conditions are suitable for all such scenarios and only the completion of highlighted sections, including the schedules of the agreement, will differ depending on the study involved.

Additional details and templates are available in GBR-107 and GBR-70.

Clinical Trial Registration

As per the GBR-102 and the G-CTApp, the sponsor or investigator is required to register the clinical trial in a publicly accessible database as a condition of a favorable ethical opinion. Registration should occur before the first participant is recruited and no later than six (6) weeks after recruitment of the first participant. To help researchers meet the UK’s transparency requirements, GBR-102 indicates that the HRA will automatically register approved clinical trials with the International Standard Randomised Controlled Trial Number (ISRCTN) Registry (GBR-47) to ensure that information is publicly available. ISRCTN is the UK's preferred clinical trials registry. HRA’s commitment to register clinical trials on behalf of sponsors and researchers is in line with the “Make It Public” research transparency strategy (see GBR-55). Per GBR-102, HRA also recognizes any registry covered by the World Health Organization (WHO) or the International Committee of Medical Journal Editors (ICMJE), such as clinical trials.gov (GBR-49). For any submissions prior to December 31, 2021, the applicant should have registered their clinical trial on an established international register. If deferral of registration is needed, then contact the HRA at study.registration@hra.nhs.uk. The registry number(s), if available, should continue to be used in section A.5. of the application form in IRAS (GBR-78) when preparing the application. If this number is not available at the time of application, email the MHRA at clintrialhelpline@mhra.gov.uk with subject line “Clinical Trial Registration” within six (6) weeks of recruiting the first research participant. The applicant should also let the EC know the registration number as soon as possible.

6
Terminology (Glossary) and Sections 1, 3, and 14
1.17, 5.1.2, and 8.2.6
CI Checklist Before Seeking Approval and Final Trial Management Documentation
Help (Preparing and Submitting Applications)
Registration of your clinical trial, Combined review of clinical trials of investigational medicinal products, Documents to send with your application, and Assessment of your submission
3.2
7
Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 3 (12, 13, and 18)

Clinical Trial Lifecycle > Safety Reporting

Last content review/update: January 13, 2023

Safety Reporting Definitions

According to GBR-1 and GBR-64, 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 SADR – 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.

Per the G-CTAuth-GBR, the Medicines and Healthcare Products Regulatory Agency (MHRA) advises that the guidance on reference safety information (RSI) contained in GBR-30 (developed by the Clinical Trials Facilitation Group of the Heads of Medicines Agencies (HMA)) remains applicable. For clinical trials that are being conducted in the UK, an RSI cannot be used for expectedness until the RSI has been approved by the MHRA. Additional SUSARs that occur before the new RSI is approved should be reported in the usual expedited manner. If sponsors wish to harmonize the implementation date of an RSI in a trial that includes European Union (EU) and UK sites, then they can use the date when approval is granted in all member states and the UK. In the interest of efficiency and harmonization for multinational trials, the MHRA recommends that amendments including changes to the RSI are submitted to the UK and EU at the same time. The RSI in place at the time the SUSAR occurred should be used to assess expectedness for follow-up reports.

Safety Reporting Requirements

Per GBR-99, a sponsor or investigator may take appropriate urgent safety measures (USMs) to protect research participants against any immediate hazard to their health or safety, without prior authorization from a regulatory body. The main ethics committee (EC), and the MHRA for clinical trials for investigational medicinal products (CTIMPs), must be notified immediately (no later than three (3) days) in the form of a substantial amendment that such measures have been taken and the reasons why. GBR-9 states that for trials which have been via the combined review service, one USM notification is made via of the Integrated Research Application System (IRAS) (GBR-125) and received by the MHRA. No additional notification is required directly to the REC. In addition, the G-CTAuth-GBR states that the sponsor should call the MHRA’s Clinical Trials Unit at 020 3080 6456 to discuss the issue with a safety scientist, ideally within 24 hours of measures being taken, but no later than three (3) days. If key details are not available during the initial call, then the sponsor should inform the MHRA no later than three (3) days from the date the measures are taken by email to clintrialhelpline@mhra.gov.uk. Written notification in the form of a substantial amendment is also required. The substantial amendment covering the changes made as part of the USM is anticipated within approximately two (2) weeks of notification to the MHRA. Any potential reason for delay of substantial amendment submission should be discussed and agreed upon with the MHRA at the time of initial notification or through a follow-up call. Submission of the substantial amendment must not be delayed by additional changes outside of those taken and required as an urgent safety measure. Unrelated and unacceptable changes may result in rejection. For more details on how submissions should be made using MHRA Submissions, see G-CTAuth-GBR.

Investigator Responsibilities

As specified in the MHCTR, GBR-1, and GBR-30, 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. According to the MHCTR, 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 IB guidelines. Per GBR-1, the investigator and the sponsor share responsibility for the assessment and evaluation of adverse events with regard to seriousness, causality, and expectedness.

Sponsor Responsibilities

According to the MHCTR, the G-CTAuth-GBR, and the MHCTR-EUExit, 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 MHRA, to the institution 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. Per GBR-1, the investigator and the sponsor share responsibility for the assessment and evaluation of adverse events with regard to seriousness, causality, and expectedness. Per the G-CTAuth-GBR, sponsors must report all UK-relevant SUSARs to the MHRA. The agency’s definition of ‘UK-relevant’ includes:

  • SUSARs originating in the UK for a trial
  • SUSARs originating outside the UK for a trial
  • If the sponsor is serving as a sponsor of another ongoing trial outside the UK involving the same medicinal product
  • SUSARs involving the same medicinal product if the sponsor of the trial outside the UK is either part of the same mother company or develops the medicinal product jointly, on the basis of a formal agreement, with the UK sponsor

Other Safety Reports

Per the G-CTAuth-GBR, sponsors must submit Development Safety Update Reports (DSURs) to the MHRA. The DSUR should consider all new available safety information received during the reporting period. The DSUR should include:

  • A cover letter listing all relevant clinical trial numbers of trials covered by the DSUR and an email address for correspondence (Note: per GBR-18, every clinical trial with a European site must include a unique European Clinical Trials Database (EudraCT) number (GBR-87))
  • An analysis of the participant’s safety in the concerned clinical trial(s) with an appraisal of its ongoing risk/benefit
  • A listing of all suspected serious adverse reactions (including all SUSARs) that occurred in the trial(s)
  • An aggregate summary tabulation of SUSARs that occurred in the concerned trial(s)

At the end of the DSUR reporting period, the sponsor may assess the new safety information that has been generated and submit any proposed safety changes to the IB as a substantial amendment. This amendment must be supported by the DSUR and approved before the RSI is changed.

A shortened DSUR is available for approved trials under MHRA’s notification scheme that are not part of a multi-study development program. Phase 4 national (UK only) trials of licensed products, which commanded a low fee from the MHRA, and where all participants have completed treatment and are only in the follow-up stage will also be suitable for submission of a short format DSUR. As an alternative to producing a full DSUR for these trials, the Health Research Authority Annual Progress Report (GBR-27) may be used.

The MHRA and Health Canada jointly released DSUR-UK_Canada to strengthen participant safety in clinical trials by improving the quality of DSURs. To increase the transparency of the data included in DSURs, the MHRA and Health Canada are requiring that the region-specific section of the DSUR explain how safety data were reviewed during the reporting period. Specifically, the region-specific section of the DSUR should include a summary description of the processes used by the sponsor to review the worldwide safety data of the investigational product (IP) (e.g., regular analyses of accumulating data, in-house safety review meetings, proposal of specific pharmacovigilance activities, or substantial modifications of the protocol). In addition, the region-specific section must describe how each safety signal (i.e., an event with an unknown causal relationship to the IP) identified during the reporting period was evaluated, as well as how a decision was made regarding the signal itself.

See the G-CTAuth-GBR, the MHCTR, GBR-1, GBR-30, and GBR-99 for detailed reporting requirements for the investigator and sponsor.

Form Completion & Delivery Requirements

Per the G-CTAuth-GBR, SUSARs during clinical trials should be reported to the MHRA in one (1) of the following ways:

  • Individual Case Safety Reports (ICSR) Submissions (GBR-126) (which replaces the EudraVigilance website (EVWEB)) - The ICSR Submissions route is used to submit single reports. (Note that per GBR-127, MHRA also decommissioned the eSUSAR reporting platform.)
  • MHRA Gateway (which replaces the EudraVigilance Gateway) - To gain access to the MHRA Gateway, which is used to submit bulk reports, users must first register via MHRA Submissions (GBR-13). The steps for gaining access to MHRA Submissions are contained within the G-MHRASubmiss and GBR-11.

If applicable, the user will need to dual report UK-relevant SUSARs to the Clinical Trial Module in the European Medicines Agency’s EudraVigilance Clinical Trial Module, as well as to other national competent authorities, using the European submission routes.

See the G-CTAuth-GBR and GBR-99 for more details on submittal and delivery requirements.

4 and 5
10
CI Checklist Before Seeking Approval, Safety Reporting, and Urgent Safety Measures
SUSAR
Reference Safety Information - updated guidance, Suspected Unexpected Serious Adverse Reactions (SUSARs), Development Safety Update Reports (DSURs), and Urgent Safety Measures
14
Part 5

Clinical Trial Lifecycle > Progress Reporting

Last content review/update: January 13, 2023

Interim and Annual Progress Reports

As indicated in the G-CTAuth-GBR, GBR-65, and GBR-9 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 International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113).

In accordance with GBR-65 and GBR-9, the chief investigator (CI) is responsible for submitting progress reports annually, or more frequently if requested by the ethics committee (EC), on the status of a clinical trial. Per GBR-65, a progress report should be submitted to the EC 12 months after the date on which the favorable opinion was given. Progress reports are only required for studies that are more than two (2) years in duration and for Research Tissue Bank and Research Databases. There is no requirement to submit a progress report for proportionate review studies and where the study is two (2) years or less in duration. The form (GBR-27) should be completed in typescript and signed by the CI. An electronic copy should be emailed to the EC within 30 days of the end of the reporting period.

Health Research Authority (HRA)-approved research projects that have also been reviewed by an EC should submit regular progress reports to the HRA using the guidance outlined for ECs above. See GBR-18 for additional information on clinical trial progress reporting.

Final Report

As per the MHCTR and the G-CTAuth-GBR, the sponsor must notify the Medicines and Healthcare Products Regulatory Agency (MHRA) and the EC in writing that a clinical trial has ended within 90 days of the conclusion of the trial. As indicated in GBR-128, all project-based research (not research tissue banks or research databases) that has been reviewed by an EC needs to submit a final report within 12 months of the end of the study. The final report should be completed and submitted in the combined review part of Integrated Research Application System (IRAS) (GBR-125). When completing the final report form, IRAS guides the user with instructions next to each question.

The G-CTAuth-GBR further specifies that a declaration of the end of a clinical trial should be sent to the MHRA within 90 days of the global end of the trial and within 15 days of the global premature end of the trial. The submission must include an end of trial form (GBR-133) and a cover letter. Note that only the global end-of-trial notification is required to be submitted. However, a facility may inform the MHRA of the local (UK) end of trial via the end-of-trial notification form, but these local notifications will not be officially acknowledged and the MHRA Submissions automatic email confirmation should be considered as evidence of submission. If a local end of trial is submitted, MHRA would still expect to receive relevant safety updates and substantial amendments for the ongoing trial until the global end of trial notification is received. An exemption to this requirement must be requested via a substantial amendment for approval. The amendment must clearly state to what documents the proposal relates and provide a robust rationale for the request. All safety documentation must be submitted unless there are no other trials ongoing with the same product in the UK. Any trial activities (such as follow-ups, visits) must be completed before the submission of the global end-of-trial declaration form. It is not possible to submit amendments to the trial or the Development Safety Update Report (DSUR) once the global end-of-trial declaration form has been received by the MHRA. If the end-of-trial declaration has been received within a reporting period, or within 60 days following the data lock point, the corresponding DSUR will not be required.

Per the G-CTAuth-GBR, the timeframe for publishing the summary of results is within one (1) year of the end of trial. Sponsors should publish summary results within this timeframe in the public register(s) where they registered the clinical trial. While it is not required to submit this clinical trial summary report to the MHRA, sponsors must send a short confirmation email to CT.Submission@mhra.gov.uk once the results-related information has been uploaded to the public register and provide the relevant link. The G-CTAuth-GBR specifies that the subject line of the email notification must state ‘End of trial: result-related information: EudraCT XXXX-XXXXXX-XX’ once the result-related information has been uploaded to the public register. If the clinical trial is not on a public register or the results will not be published in the register (for example an adult phase 1 study), summary results should be submitted to MHRA via MHRA Submissions (GBR-13). An acknowledgement letter will not be sent for this submission. Sponsors of trials conducted in the UK that are already registered in the European Union (EU) Register may submit results to EudraCT (GBR-87). The MHRA will not be able to update the status of the study in the EU system.

As per GBR-9 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. GBR-20 clarifies that the form in GBR-20 should be used for this submittal, which includes submitting a lay summary of results. This is a UK-wide final report for all project-based research studies that have been reviewed by an EC within the UK Health Departments' Research Ethics Service (GBR-62). The information contained in this final report helps the Research Ethics Service to monitor whether the research was conducted in accordance with the EC’s favorable opinion and applicable transparency requirements. Per the GBR-120, sponsors should include a plain language summary of their findings in the final report, which will be published on HRA’s website alongside the study research summaries. See GBR-120 for guidance on writing a good plain language summary for a general audience.

Per the G-PIPs, UK marketing authorization holders who sponsor a study that involves the use of the authorized medicinal product in the pediatric population, must submit to the MHRA results of the study within six (6) months after the trial ended. Additional requirements and submittal details are in the G-PIPs and the G-PIPsProcess.

Terminology (Glossary), and Sections 1 and 14
4.10 and 4.13
Progress Reporting
Final report on the research
End of Trial
Legal Background and Scope
Part 3 (Section 27)

Sponsorship > Definition of Sponsor

Last content review/update: January 13, 2023

As per the MHCTR, the MHCTR2006, the G-CTApp, GBR-103, GBR-9, GBR-2, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), 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. In addition, per GBR-101, the sponsor is the individual, organization, or partnership that takes on overall responsibility for proportionate, effective arrangements being in place to set up, run, and report a research project.

In accordance with GBR-113, the United Kingdom (UK) also permits a sponsor to transfer any or all of its trial-related duties and functions to a contract research organization (CRO) and/or institutional site(s). However, the ultimate responsibility for the trial data’s quality and integrity always resides with the sponsor. Any trial-related responsibilities transferred to a CRO should be specified in a written agreement. The CRO should implement quality assurance and quality control. Per the G-CTApp, G-SubtlAmndmt, and the GBR-103, a the clinical trial sponsor or legal representative needs to be established in the UK or a country on an approved country list which initially includes the European Union (EU)/European Economic Area (EEA) countries per G-CTApprovedCountries. A change in sponsor or legal representative for a UK trial is a substantial amendment requiring submission to both the MHRA and the ethics committee. The GBR-103 specifies that the legal representative:

  • May be an individual person or a representative of a corporate entity
  • Does not have to be a legally qualified person
  • Should be willing to act as the agent of the sponsor in the event of any legal proceedings instituted (e.g., for service of legal documents)
  • Should be established at an address in the UK or a country on the approved country list
  • Does not assume any of the legal liabilities of the sponsor(s) for the trial by virtue of the role of legal representative and does not therefore require insurance or indemnity to meet such liabilities; but may, in some cases, enter into specific contractual arrangements to undertake some or all of the statutory duties of the sponsor in relation to the trial, in which case the legal representative would also be regarded as a co-sponsor and would then require insurance or indemnity cover

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

Per the G-SubtlAmndmt, the UK requires the sponsor or legal representative of a clinical trial to be in the UK or a country on an approved country list that will initially include the EU and EEA countries. A change in sponsor or legal representative for a UK trial is a substantial amendment requiring submission to both the MHRA and the ethics committee.

Trial Sponsor and legal Representative
2
Changes to the trial sponsor/legal representative
Part 1 (3)
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)
Responsibilities (9.10)
5.1 and 5.2
Basic Principles
Terminology (Statutory Definitions Relating to CTIMPs)

Sponsorship > Site/Investigator Selection

Last content review/update: January 13, 2023

Overview

As set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), 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 indicates 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. GBR-9 states that the chief investigator (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.

As delineated in the MHCTR, the MHCTR2006, and GBR-113, 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 GBR-113, if a multicenter trial is going to be conducted, the sponsor must organize a coordinating committee or select coordinating investigators. Per GBR-18, for clinical trials of investigational products (CTIMPs) conducted at National Health Service (NHS) sites, the addition of a new site and/or addition or change of a principal investigator (PI) is no longer considered a substantial amendment. No changes have been made to the classification of amendments relating to new sites/change of PI at non-NHS sites. If a site is added in a nation not previously involved in a study, this should be indicated in the combined review section (GBR-125) of the Integrated Research Application System (IRAS) (GBR-78) for CTIMPs, and made clear in a cover letter when submitting the amendment to the lead nation.

GBR-113 recommends establishing a Data Monitoring Committee (DMC) to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial.

Per GBR-63, researchers working with NHS/Health and Social Care in Northern Ireland (HSC) organizations across England, Northern Ireland, Scotland, and Wales should use the UK Local Information Pack, which provides one (1) consistent package to support study setup and delivery across the UK. For help with preparing and submitting these packages and site-specific information, see GBR-106.

Foreign Sponsor Responsibilities

GBR-103 provides that if a sponsor(s) is not established in the UK or on an approved country list (which initially includes European Union (EU)/European Economic Area (EEA) countries), it is a statutory requirement to appoint a legal representative based in the UK or a country on the approved country list for the purposes of the trial. Per the G-CTApprovedCountries, the UK published a list of countries where a sponsor of a clinical trial, or their legal representative, may be established; currently listed countries are those in the EU and EEA. The G-SubtlAmndmt delineates that a change in sponsor or legal representative for a UK trial is a substantial amendment requiring submission to both the Medicines and Healthcare Products Regulatory Agency (MHRA) and the ethics committee (EC), pursuant to the guidelines in the G-CTAuth-GBR. Where the sponsor is from the rest of the world, and the legal representative is established in the UK, and there are sites in the EU/EEA, the sponsor will need to assign an EU/EEA legal representative for these sites via a substantial amendment to the relevant EU/EEA competent authorities. No amendment submission to the MHRA is required where the sponsor or legal representative for an ongoing trial is established in the EU/EEA as the UK will continue to accept this approval. Further, no amendment will need to be submitted in the UK if the sponsor retains the UK legal representative for the UK study. Similarly, no amendment will need to be submitted in the UK if a sponsor remains in the UK and a legal representative is added to cover EU/EEA sites.

Additional foreign sponsor requirements are listed in Section 5.2 of GBR-113.

Data Safety and Monitoring Board

Per GBR-18, the chief investigator should ensure that arrangements are made for a data safety and monitoring board (known as a data monitoring committee (DMC) in the UK). GBR-113 recommends establishing a DMC to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial.

Multicenter Studies

As delineated in GBR-113, 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
2
Amending your trial protocol or other documentation
Changes to the trial sponsor/legal representative
Part 1 (3) and Part 3 (15)
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)
Preparing and Submitting Application (Site-specific information)
5.23, 5.5, 5.6, 6, and 7
CI Checklist Before Seeking Approval and Addition of New Sites & Investigators
1.1

Sponsorship > Insurance & Compensation

Last content review/update: January 13, 2023

Insurance

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 the designated representative to obtain insurance and indemnity. However, GBR-2, GBR-103, GBR-101, and GBR-18, state that the sponsor or the 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 GBR-2, the sponsor or the designated representative must ensure that the research covered by the National Health Service (NHS)'s indemnity policy is in place for each publicly funded participating study site. See GBR-33 for detailed information on the NHS indemnity responsibilities for clinical negligence involving investigators and participants. GBR-33, specifically addresses the sponsor’s or the designated representative’s requirement to insure or indemnify the investigator participating in industry-sponsored Phase 1 clinical trials.

The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113) also guides sponsors on providing insurance.

Compensation

Injury or Death

As specified in the MHCTR, the sponsor or the designated representative is responsible for providing compensation to research participants and/or their legal heirs in the event of Phase 1 trial-related injuries or death. According to GBR-33, the sponsor must have agreed with the research participant to provide compensation for injury whenever a causal relationship with participation is demonstrated. This undertaking can be provided directly by the sponsor through the consent process, or through authorizing the contract research organization (CRO) or investigator on behalf of the sponsor. In addition, the sponsor should follow these practices:

  • If the health or wellbeing of the participant deteriorates significantly as a result of taking part in the study, the sponsor will compensate the volunteer, irrespective of the ability of the participant to prove fault on the part of the sponsor or anyone else connected with the study.
  • The amount of compensation should be calculated by reference to the amount of damages that would commonly have been awarded for similar injuries by an English court had liability been proven. The amount of compensation may be reduced if the volunteer is partly responsible for the injury or if the volunteer is separately compensated under any other insurance policy.
  • The sponsor and participant agree to refer any dispute about whether compensation is payable or the amount of such compensation to an arbitrator with power to consult a barrister of 10 years’ standing on any issue of law, including the amount of damages to be paid.
  • Participants should be given a copy of the relevant Association of the British Pharmaceutical Industry (ABPI) guidelines and should be invited to seek clarification of any aspect of the undertaking that is not clear to them.
  • Participants may make a claim through the investigator, and the sponsor should aim to respond sympathetically and promptly.

GBR-113 also provides guidance for sponsors on providing compensation to research participants in the event of trial-related injuries or death. The sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries.

3, 4, and 6
Introduction and Basic Principles
5.8
CI Checklist Before Seeking Approval (Trial Planning Phase) and Final Trial Management Documentation
Responsibilities
Part 2 (Conditions Based on Article 3 of the Directive)
Part 3 (15), Part 4 (8), and Schedule 1 (Part 1 (1) and (16))

Sponsorship > Risk & Quality Management

Last content review/update: January 13, 2023

Quality Assurance/Quality Control

As stated in the MHCTR, the MHCTR2006, and GBR-92, 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 International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113). 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 GBR-113 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

MHCTR2006 requires the sponsor to notify the Medicines and Healthcare Products Regulatory Agency (MHRA) of serious breaches of good clinical practice (GCP) or the trial protocol. A serious breach is defined as one that is likely to affect to a significant degree: the safety or physical or mental integrity of the trial participants; or the scientific value of the trial. Per G-MHRA-SeriousBreaches, the sponsor, or delegated party, should notify the MHRA GCP Inspectorate within seven (7) days of becoming aware of a serious breach. Further, the sponsor should investigate and take action simultaneously after the MHRA notification. Notifications should primarily be sent to the following email address: GCP.SeriousBreaches@mhra.gov.uk.

Per the G-RiskAssmt, MHRA recommends that a risk assessment is undertaken for all clinical trials. Phase 1 trials are required to have a documented risk assessment process and to produce a risk assessment for all proposed trials. The risk assessment should be done as early as possible to help the sponsor identify whether the sponsor wishes to proceed with sponsorship and also the potential category of IP for eventual marketing authorization. An early risk assessment will also identify the study management requirements, which can assist in the planning and resourcing aspects of the trial (e.g., identification of trial monitoring requirements so that these can be budgeted for in any funding application). There is no requirement to submit risk assessments to the MHRA or the ethics committee (EC). However, any safety monitoring produced as a result of the risk assessment must be described in the protocol. Finally, information contained in the risk assessment may prove useful in completing the application form for approvals, particularly for the EC application. See the G-RiskAssmt for details on how to conduct the risk assessment.

Monitoring Requirements

Per GBR-18, the sponsor must develop an audit plan to assess and assure the reliability and integrity of the clinical trial systems against all relevant written standards. The following activities and checks could include the following:

  • Interview staff to assess whether they are appropriately trained, understand their role(s), and are working to all relevant standards, the protocol and procedures SOPs.
  • Tour the facility to assess if there are adequate resources and if the equipment is fit for its intended use.
  • Review documents to evaluate whether data reported is verifiable from source data and that written records confirm that the trial was conducted appropriately.

Auditors must be independent of the trial team and appropriately trained for their role. Their findings and observations must be documented in a formal audit report. Any deficiencies identified during an audit must be followed up with appropriate corrective and preventive actions wherever possible.

Per GBR-18, the MHRA may conduct inspections to ensure the clinical trial is being conducted in compliance with good clinical practice (GCP) as prescribed in GBR-92 and GBR-113. The MHRA takes a risk-based approach to inspections depending on the type of trials and risk rating. Once an inspection has been completed, a formal report outlining the findings will be sent to the inspected organization. A response to this report (describing any corrective and preventive actions) must be produced. Per G-RiskAssmt, GCP Inspectors will review risk assessments. The risk assessment should provide the rationale behind trial management/monitoring and GCP activities applied, or not, to the trial.

Finally, the sponsor’s audits and inspections should be conducted in compliance with GBR-113, which calls for a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose on-site monitoring, a combination of on-site and centralized monitoring, or where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan). The G-Ovrsight provides additional guidance to assist sponsors and those conducting trials on implementing adequate oversight and monitoring processes for clinical trials.

Premature Study Termination/Suspension

The G-CTAuth-GBR states that the MHRA has the authority to suspend or terminate a trial. In addition, the sponsor can contact the MHRA to put a trial on temporary halt or terminate a trial. If a sponsor suspends a trial temporarily, the MHRA must be notified. Sponsors of clinical trials of investigational products (CTIMPs) must use the combined review part of the Integrated Research Application System (IRAS) (GBR-125) to submit this notification as a substantial amendment. Per GBR-122, for studies that were submitted before combined review, these applicants should continue to submit this notification at IRAS via GBR-78. The G-CTAuth-GBR indicates the notification should be made as a substantial amendment using the amendment tool, clearly explaining what has been stopped and the reasons for the suspension. To restart a trial that has been temporarily suspended, you must make the request as a substantial amendment using the notification of amendment form, providing evidence that it is safe to restart the trial.

Per the G-CTAuth-GBR and GBR-18, to terminate a CTIMP, the sponsor must notify (as a substantial amendment) the MHRA and the EC via the combined review part of IRAS (GBR-125). For studies that were submitted before combined review, the submission should be made at GBR-78, using the end-of-trial form (GBR-133). GBR-128 specifies that for CTIMPs, the declaration of end of trial must be sent to the MHRA within 15 days of the global premature end of trial. Before declaring an end of the study, sponsors should review the plans that were approved by the EC for use of tissue and data collected in the course of the study, providing information to participants, and dissemination of results. If changes need to be made to these agreed arrangements, the sponsor should consider whether an amendment is required before submitting the end of study notification.

According to GBR-113, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the sponsor should also inform the EC promptly and provide the reason(s) for the termination or suspension.

5.0, 5.1, 5.2, 5.18, 5.19, 5.21, and 6.10
Ongoing Management & Monitoring, MHRA Inspection, Audit, Temporary Halt, Early Termination, and End of Trial Declaration
Suspend or Terminate a Trial and End of Trial
Amendment of Regulation 31 of the Principal Regulations and Part 2 (Principles Based on Articles 2 to 5 of the GCP Directive)
Part 3 (15), Part 4 (28), Part 6 (36 and 38), and Schedule 7 (Parts 2 and 3)

Sponsorship > Data & Records Management

Last content review/update: January 13, 2023

Electronic Data Processing System

To safeguard personal data within electronic health record (EHR) systems, G-EHRAccess provides guidance on updating these systems to ensure access by sponsors and their representatives (e.g., monitors and investigators) is limited to only the records of clinical trial participants and that this access is auditable. See G-EHRAccess for details on system security, remote access, document sharing, consent, and other considerations.

According to GBR-113, when using electronic trial data handling processing systems, the sponsor must ensure and document that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. To validate such systems, the sponsor should use a risk assessment approach that takes into consideration the system’s intended use and potential to affect human participant protection and reliability of trial results. In addition, the sponsor must maintain standard operating procedures (SOPs) that cover system setup, installation, and use. The SOPs should describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. With respect to the use of these computerized systems, the responsibilities of the sponsor, investigator, and other parties should be clear, and the users should receive relevant training.

Records Management

As set forth in GBR-113, 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.

In addition, GBR-113 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

1.65, 5.18, and 8
Part 2 (Principles Based on Articles 2 to 5 of the GCP Directive)

Sponsorship > Personal Data Protection

Last content review/update: January 13, 2023

Responsible Parties

For purposes of data protection requirements, the UK-GDPR, the UK-DPAct, and the G-GDPR delineate that the sponsor acts as the “controller” in relation to research data. This is because the sponsor determines what data is collected for the research study through the protocol, case report form, and/or structured data fields in a database. GBR-7 provides guidance on key data protection requirements to consider in the post-Brexit environment. Among other things, it describes how data can continue to flow to and from the United Kingdom (UK), as well as controller responsibilities.

Data Protection

Per the UK-GDPR, the UK-DPAct, the G-GDPR, and GBR-89, the sponsor (known as the “controller” in data protection legislation) must comply with the following principles of the data protection legislation:

  • Lawfulness, fairness, and transparency
  • Purpose limitation
  • Data minimization
  • Accuracy
  • Storage limitation
  • Integrity and confidentiality (security)
  • Accountability

The sponsor must show that each data processing activity has a lawful basis under this legislation, in addition to the common law basis. For health and social care research, the lawful basis is determined by the data controller’s organization type:

  • For universities, National Health Service (NHS) organizations, Research Council institutes, or other public authority, the processing of personal data for research should be a “task in the public interest.”
  • For commercial companies and charitable research organizations, the processing of personal data for research should be undertaken within “legitimate interests.”

As described in the G-GDPR, with regard to transparency, the sponsor should understand whether personal data is collected indirectly from a third party or directly, as these determine the actions to take to comply with data protection requirements. In most cases, the sponsor will need to provide transparency information about the legal basis and other details of processing personal data. See the table in G-GDPR, which sets out the specific transparency requirements for personal data. In addition, GBR-100 contains a series of templates by the Health Research Authority (HRA) with suggested transparency language. Further, the sponsor should take measures to ensure data is processed securely, giving consideration to security, storage, and pseudonymization/anonymization when possible. For details on complying with security and storage requirements, see GBR-100.

Per the UK-GDPR and the UK-DPAct, the data protection legislation introduces a duty requiring public authorities or bodies to appoint a data protection officer (DPO); a DPO may be required for non-public entities if they carry out certain types of processing activities. The DPO assists the sponsor with monitoring internal compliance, informs and advises on data protection obligations, provides advice regarding Data Protection Impact Assessments (DPIAs), and is a point of contact for participants and the supervisory authority. See G-GDPR for guidance related to DPIAs.

For more information on data protection requirements following the UK’s transition out of the European Union (EU), see GBR-7.

Consent for Processing Personal Data

Per the UK-GDPR, UK-DPAct, and G-GDPR, consent to participate in research is not the same as consent as the legal basis for processing personal data under the data protection legislation. Per the G-GDPR, for the purposes of the UK-GDPR, the legal basis for processing data for health and social care research should not be consent. This means that requirements in the UK-GDPR relating to consent do not apply to health and care research. Per the G-GDPR, even though consent is not the legal basis for processing personal data for research, the common law duty of confidentiality still applies, so consent is still needed for people outside the care team to access and use confidential information for research.

As delineated in the UK-GDPR, the UK-DPAct, the G-GDPR, and GBR-89, participants have the right to be informed about the collection and use of their personal data. This is a key transparency requirement under the data protection legislation. The UK-GDPR specifies what data individuals have the right to be informed about (i.e., privacy information). In addition, as delineated in the UK-GDPR, the UK-DPAct, the G-GDPR, and GBR-89, the participant has certain data rights, which are limited by a range of exemptions. These exemptions must be balanced with what is fair to participants. As indicated in the G-GDPR, exemptions to data subject rights are not automatic, but must be considered on a study-by-study basis. It is important, therefore, to take into account the relevance of data rights to a particular study in the Participant Information Sheet (PIS) when offering or limiting the rights available to research participants. If data rights have been previously offered or limited to participants that are not appropriate under UK-GDPR, then the PIS may need to be revised as a non-substantial amendment.

As indicated in the G-GDPR and GBR-100, the HRA has developed a series of templates with transparency language to help organizations comply with the data protection legislation. The requirements vary depending on the point of collection of personal data (directly or indirectly) and the timing of the study. Also see GBR-129 for guidance from the UK Information Commissioner’s Office.

Principles, Lawful Basis for Processing, Individual Rights, Accountability and Governance
What the Law Says (Consent in Research) and What You Need to do
Part 1, Part 2 (Chapter 2), and Schedules 2-4
Chapter II (Articles 5 and 6), Chapter III (Articles 12-23), and Chapter IV (Articles 24-43)

Informed Consent > Documentation Requirements

Last content review/update: January 13, 2023

Obtaining Consent

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, the MHCTR2006, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113). As per the MHCTR, the MHCTR2006, and GBR-9, 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 (GBR-9) issued by England’s Health Research Authority (HRA).) Refer to GBR-18 and GBR-69 for more on informed consent in the UK.

The MHCTR and G-ConsentPIS, state that the investigator(s) must provide detailed research study information to the participant and/or the legal representative(s) or guardian(s). The MHCTR and G-ConsentPIS 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 the legal representative(s) or guardian(s), should also be given adequate time to consider whether to participate. Per G-ConsentPIS, the Participant Information Sheet (PIS) supports the consent process to help ensure participants have been adequately informed. In addition, the PIS forms part of the transparency information that must be provided to participants under the data protection legislation for the use and processing of personal data. (See the Personal Data Protection section for more information on data protection requirements.)

Per GBR-31, the HRA guides researchers and ECs in taking a proportionate approach to seeking consent. A proportionate approach adopts procedures commensurate with the balance of risk and benefits so that potential participants are not overwhelmed by unnecessarily lengthy, complex, and inaccessible information sheets. Participants should be provided with succinct, relevant, truthful information in a user-friendly manner that promotes their autonomy. Specifically, the methods and procedures used to seek informed consent and the level of information provided should be proportionate to:

  • The nature and the complexity of the research
  • The risks, burdens, and potential benefits (to the participants and/or society)
  • The ethical issues at stake

Per GBR-113, none of the oral and written information concerning the clinical trial, including the written ICF, should contain any language that causes the participant and/or the participant’s legal representative(s) or guardian(s) to waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution, the sponsor, or their agents from liability for negligence.

Re-Consent

According to GBR-113, the EC should approve any change in the ICF due to a protocol modification before such changes are implemented. The participant and/or the legal representative(s) or guardian(s) will also be required to re-sign the revised ICF and receive a copy of any amended documentation.

Per GBR-18, during a clinical trial, researchers should periodically reaffirm the willingness of participants to continue. If significant new information becomes available, participants should be reconsented using revised (and re-approved) consent documents so that their continued consent is confirmed.

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.

Documenting Consent

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 the legal representative(s) or guardian(s) is illiterate, verbal consent should be obtained in the presence of and countersigned by an impartial witness. As provided in G-ConsentPIS, consent can be documented electronically or in writing. A physical or electronic copy of the signed consent form will still need to be provided to the participant. To record consent electronically, electronic signatures will be needed. Because there are different forms and classifications of electronic signatures, the researcher should determine what is appropriate for the particular study. GBR-6 sets out the legal and ethical requirements for seeking and documenting consent using electronic methods (also known as eConsent in the UK), as well as expectations regarding the use of electronic signatures. eConsent enables potential research participants to be provided with the information they need to make a decision via a tablet, smartphone, or digital multimedia. It also enables their informed consent to be documented using electronic signatures. This approach can supplement the traditional paper-based approach or, where appropriate, replace it.

Waiver of Consent

No information is currently available.

1 and 2
2, 4.4, 4.8, 8.2, and 8.3
Informed Consent
Principles of consent: General principles and Role of Participant Information Sheets; Content: Participant Information Sheet and Consent Form, and Examples and Templates
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)
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)

Informed Consent > Required Elements

Last content review/update: January 13, 2023

Based on the MHCTR, the G-ConsentPIS, and International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

  • The study purpose, procedures, and duration
  • Study title and the study Integrated Research Application System (IRAS) ID are clearly displayed
  • 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 ethics committees (ECs), the auditor(s), and the monitor(s)
  • That the participant and/or the 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 consent

ICF examples and templates are provided in the G-ConsentPIS.

For more information about informed consent required elements, see GBR-18, GBR-113, GBR-100, GBR-31, and GBR-69.

1 and 2
4.4 and 4.8
Informed Consent
Principles of consent: General principles and Role of Participant Information Sheets; Content: Participant Information Sheet and Consent Form
Part 1 (3), Part 3 (12 and 15), and Schedule 3 (Parts 1 and 3)

Informed Consent > Participant Rights

Last content review/update: January 13, 2023

Overview

In accordance with the MHCTR, the MHCTR2006, the G-ConsentPIS, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), the United Kingdom’s (UK’s) ethical standards promote respect for all human beings and safeguard the rights of research participants. The MHCTR states 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, the G-ConsentPIS, and GBR-113, the participant or the 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, the G-ConsentPIS, and GBR-113, a potential research participant and/or the 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.

Also see GBR-117 for an interactive web-based communications toolkit to help researchers and participants keep in touch after participation in a research study.

The Right to Privacy and Confidentiality

As per the MHCTR and GBR-113, 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 GBR-113 state that the research participant and/or the 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, the MHCTR2006, and GBR-113 state that a research participant’s rights, safety, and well-being must take precedence over the interests of science and society.

Principles and Content
Part 1 (3 and 15), Schedule 1 (Parts 1, 2, and 5)
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)
4.8

Informed Consent > Emergencies

Last content review/update: January 13, 2023

The MHCTR, the MHCTR2006-No2, the MHCTR-BSQ, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113) make provisions to protect the rights of a research participant during the informed consent process when a clinical trial of an investigational product (IP) is complicated by medical emergencies. As delineated in the G-ConsentPIS and GBR-18, in an emergency, if the signed informed consent form (ICF) cannot be obtained from the research participant, the consent of the legal representative(s) or guardian(s) should be obtained. If the prior consent of the participant or the 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 the 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.

The MHCTR2006-No2 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. In Scotland, the provisions of Section 51 of the AIA2000 govern the inclusion of adults lacking capacity in research.

The G-ConsentPIS states that the United Kingdom allows adults not able to consent for themselves to be recruited into clinical trials without prior consent in emergency situations if the following conditions exist:

  • Treatment needs to be given urgently
  • It is also necessary to take urgent action to administer the drug (IP) for the purposes of the trial
  • It is not reasonably practicable to obtain consent from a legal representative
  • The procedure is approved by an EC
  • Consent is sought from a legal representative as soon as possible
4.8.15
Informed Consent
Principles of Consent: Emergency Research
Section 51
2 and Explanatory Note
Schedule 1 (Parts 4 and 5)
4 and Explanatory Note

Informed Consent > Vulnerable Populations

Last content review/update: January 13, 2023

Overview

As per the MHCTR and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), 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.

Per GBR-131, vulnerability may be defined in different ways and may arise as a result of being in an abusive relationship, vulnerability due to age, potential marginalization, disability, and due to disadvantageous power relationships within personal and professional roles. Participants may not be conventionally vulnerable but may be in a dependent relationship that means they can feel coerced or pressured into taking part.

As stated in GBR-131, researchers must assess potential vulnerability within the context of the research, in terms of potential consequences from their participation (immediate and long-term) or lack of positive impact where this is immediately needed or expected. Further, researchers should make the participants aware of the limits to confidentiality and decide whether verbal or written consent will be more appropriate and protective of the participants’ interests. In addition, researchers should consider the following:

  • Participants’ vulnerability
  • Potential negative consequences or lack of personal benefits from their involvement in research where these are expected
  • Providing appropriate information to elicit freely-given informed consent for participation as well as information regarding data deposit and data re-use (where deposit is possible)
  • Limits to confidentiality and occasions where this may occur
  • Legal requirements of working with the specific population
  • Incentives and compensation for participation

In addition, GBR-131 states that when working with participants who are considered vulnerable, researchers may find themselves in a position of increased responsibilities or expectations. Researchers should endeavor to assess the likelihood of additional ethics issues and develop strategies and a framework of clear responsibilities they can refer to should such issues arise. They should also use their research ethics committee as a resource for advice and guidance. Researchers should be able to justify the approach they take in dealing with unforeseen ethics issues and maintain the integrity of the research.

As per GBR-131, in cases where research involves potentially vulnerable groups, every effort should be made to secure freely given informed consent that participants have actively provided. Every effort should be made to ensure that they have the time and opportunity to access support in their decision-making, for example by discussing their choice with a trusted adult or relative. Passive assent, including group assent (with consent given by a gatekeeper) should be avoided wherever possible, and every effort should be made to develop methods of seeking consent that are appropriate to the groups studied, using expert advice, support, and training, where necessary. Vulnerability should be considered on a case-by-case basis; many groups or individuals not traditionally considered as vulnerable could be exposed to issues from participating in research that make them vulnerable. See GBR-131 for additional resources and case studies.

See the Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these vulnerable populations.

Schedule 1 (Parts 1, 4, and 5)
1.61, 3.1, and 4.8

Informed Consent > Children/Minors

Last content review/update: January 13, 2023

According to the MHCTR and GBR-4, a minor in the United Kingdom (UK) is an individual under 16 years of age.

As set forth in the MHCTR, the MHCTR2006, the G-ConsentPIS, GBR-4, GBR-9, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GBR-113), when the research participant is a minor, informed consent should be obtained from the legal representative(s) and/or guardian(s). As per GBR-4, the researcher needs only to obtain consent from one (1) person with parental responsibility. GBR-130 further indicates that the legal representative(s) and/or guardian(s) must not be connected with the conduct of the trial, is suitable to act by virtue of their relationship with the child/young person, and is available and willing to do so. A legal representative(s) and/or guardian(s) should only ever be approached if someone with parental responsibility cannot be contacted prior to the proposed inclusion of the child/young person due to the urgent nature of the treatment provided as part of the trial. In this situation, if a legal representative(s) or guardian(s) is not available, then a professional legal representative (e.g., a doctor) can be responsible for the medical treatment of the child/young person if they are independent of the study, or a person nominated by the healthcare provider.

Additionally, GBR-130 states that researchers must ensure that the parent(s), legal representative(s), or guardian(s):

  • Understand that they are being asked to give consent on behalf of the child/young person
  • Understand the objectives, risks, and inconveniences of the trial and the conditions under which it is to be conducted
  • Have been informed of the right to withdraw the child/young person from the trial at any time
  • Have a contact point where further information about the trial can be obtained

The MHCTR, the MHCTR2006, and GBR-4, 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 point of contact 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 the 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

GBR-4 provides additional best practices:

  • Children and their parents (or those with parental responsibility) should be involved in the decision-making process around consent to take part in research, regardless of whether the child or young person is legally competent to give consent. This includes involving children or young people who are not considered competent to give consent.
  • Assent should be sought from a child who is not considered competent as long as this is practicable and the child is not too young.
  • In some situations, a young person who is competent may object to the involvement of their parents and their confidentiality should be respected.
  • Before giving consent, children and young people should be provided with age-appropriate information that enables them to understand participation in research. Information may be provided using a layered, or staged, approach so that it is more easily understood.
  • Children and young people should be given the opportunity to ask questions and to get support in their decision-making, such as talking to a trusted adult.
  • Good records should be kept of any discussions about consent and of the final decision.
  • Inducements and coercion must be avoided.
  • Seeking consent is a process and it is good practice to engage regularly with the child and family over the course of research to confirm they are willing to continue. In studies in which children who are not competent will become competent during the study period, then consent from young people should be sought as soon as possible after competency is reached. A decision about how this will be managed should be made at the start of the study and included in the protocol.

See the MHCTR, the MHCTR2006, GBR-4, and GBR-9 for detailed requirements. The G-ConsentPIS provides style guidance and suggestions for presenting age-appropriate information in the participant information sheet. Also see GBR-8 for a summary of changes to GBR-9.

Assent Requirements

As indicated in GBR-4, whenever practical and appropriate, a child's assent should be sought before including them in research. Even when a child or young person is competent, it is still normally good practice to involve the family in the decision-making process; however, if the young person objects, researchers should respect their privacy.

As per GBR-4, for clinical trials of investigational products (IPs), it is usually inappropriate to ask very young children (e.g., under five (5) years old) to sign an assent form; however, their views should be considered. Researchers must make an informed judgment to determine when seeking assent is appropriate; the age of a child can only be taken as a guide. The child's developmental stage, knowledge of illness and experience of health care should also be considered. Although there is a danger that children can be asked to exercise greater autonomy than normal, this must be balanced with the potential loss of trust associated with denying their assent. Such judgment needs a framework of considerations for analysis, a record of observations, and discussions and a documented decision. In circumstances where seeking assent at the outset is not appropriate, the researcher could provide the child with information as and when required.

Guidance (Consent)
2.51-2.58
4.8.12
Clinical Trial of an Investigational Medicinal Product (Consent for under 16)
Style and Examples & Templates
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)
Part 1 (2) and Schedule 1 (Part 4)

Informed Consent > Pregnant Women, Fetuses & Neonates

Last content review/update: January 13, 2023

The G-ConsentPIS states that researchers must give a clear warning to potential participants when there is a risk of harm to an unborn child and/or risk when breastfeeding. The Participant Information Sheet (PIS) should provide specific advice to potential participants about the risks of becoming pregnant, of fathering a child, or of breastfeeding while taking part in the research including the need for pregnancy testing, contraceptive requirements, and how to report a pregnancy during the study. The PIS should also provide information about what will happen if a participant becomes pregnant, including whether and how the researcher will monitor the pregnancy. This would include access to the mother's and/or child's notes, and any possible follow up of the child including post-natal examinations. For men, researchers must provide clear warnings and advice if the research treatment could damage sperm and consequently pose a risk to possible pregnancies. Specific advice for pregnant partners may be needed, including information on any compensation arrangements.

Further, the G-ConsentPIS finds that the risk of harm caused during pregnancy is most likely when recruiting young people to a clinical trial for an investigational medicinal product (CTIMP). In this case, there should be consent from someone over the age of 16, and the following should be done:

  • Discuss the risk of pregnancy, pregnancy testing, and the use of appropriate contraception with their parents (or the legal representative(s) and/or guardian(s)) during the consent process and with young potential participants as part of the assent process
  • Consider local social beliefs
  • Involve pediatricians and the ethics committee in preliminary discussions if this is a concern
  • Consult young people when designing consent and writing information
  • Respect the young person's autonomy but encourage involvement of the parents
  • Be aware that in CTIMPs, it is the parents of children under 16 who legally provide consent, and this will include consent to pregnancy testing and discussion of contraception
  • Information needs to go beyond "We will do a pregnancy test…" to include what will happen in broad terms

In accordance with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), informed consent requirements for conducting clinical trials with pregnant or nursing women or fetuses follow the general requirements listed in the Required Elements section. Specifically, the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant.

As set forth in GBR-35, 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. According to GBR-35, 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 and/or the risk of pregnancy is minimized (e.g., because she agrees to adhere to a highly effective method of contraception); 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 product has been excluded
  • 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
  • The female is tested for pregnancy before dosing starts and possibly during the trial, as appropriate
Content – Participant Information Sheet

Informed Consent > Prisoners

Last content review/update: January 13, 2023

Per the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. A research study involving prisoners should ensure that these prospective participants are informed and are given the opportunity to make their own decisions without any interference from a higher authority. The ethics committee must also ensure that the study will be independently monitored to assure the dignity and rights of the prisoners involved in the research.

1.61

Informed Consent > Mentally Impaired

Last content review/update: January 13, 2023

As per the MHCTR and GBR-9, a recognized ethics committee (EC) within the Health Research Authority (HRA), 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 population.

The MHCTR and the G-ConsentPIS, specify that when a study involves adult participants with mental incapacities, informed consent should be obtained from the 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 point of contact for further information, and been informed of the right to withdraw the participant from the trial at any time. The G-ConsentPIS provides additional country-specific information on legal representative requirements.

As delineated in the MHCTR, a clinical trial of an investigational product 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 the 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, G-ConsentPIS, and GBR-3 for detailed requirements.

2.51-2.58
Principles of Consent - Adults Who Are Not Able to Consent for Themselves
Part 1 (15), Schedule 1 (Parts 1 and 5)

Investigational Products > Definition of Investigational Product

Last content review/update: January 13, 2023

As delineated in the MHCTR, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), and GBR-9, 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.

Part 1 (2)
1.3
Terminology (Statutory Definitions Relating to CTIMPs)

Investigational Products > Manufacturing & Import

Last content review/update: January 13, 2023

According to the MHCTR, the MHCTR2006, the G-CTApp, and the G-GMP-GDP, the Medicines and Healthcare Products Regulatory Agency (MHRA) is responsible for authorizing the manufacture 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 of any IP to be used in the trial. The sponsor or the 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 GBR-28 to obtain an MIA(IMP) from the MHRA. The MHCTR defines “manufacturing authorization” to include importing and assembly authorizations, as applicable. The G-CTApp states that if an IP is manufactured outside the European Union (EU), the clinical trial application should include an MIA(IMP), importer authorization, and qualified person (QP) declaration on good manufacturing practice (GMP) for each site. 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-GMP-GDP, and GBR-15, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), the MIA(IMP) holder must also comply with the GMP guidelines and provide an IMP Certificate of Analysis. In addition, the MHCTR and the MHCTR2006 specify that the holder of an MIA(IMP) must always have the services of at least one (1) 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 use in a clinical trial, or prior to release for sale and placement in the market. See Part 6 and Schedule 6 of the MHCTR for detailed applicant requirements.

In accordance with the G-ImportIMPs, IPs that have been QP-certified in countries on the list of approved countries (initially, EU and European Economic Area (EEA) countries per G-CTApprovedCountries) do not need to be re-certified when importing to the UK. However, the sponsor must require the MIA(IMP) holder to put in place an assurance system to check these IMPs have been certified by a QP in a listed country before release to the trial. A sponsor may perform verification of QP certification in a listed country themselves if they are the holder of a UK MIA(IMP). Alternatively, they may outsource this verification to a third party who holds a UK MIA(IMP). IPs coming to Great Britain from Northern Ireland do not require this additional oversight. IPs coming directly to the UK from third-party countries that are not on the list of approved countries will continue to require import and QP certification in the UK by the MIA(IMP) holder as per the existing requirements. See the G-ImportIMPsAuth, for additional details on the authorizations and procedures. For additional details on what is new from Brexit, see the Scope of Assessment section.

The G-IPsNIreland delineates that the supply and use of IPs in Northern Ireland must follow EU laws as per the Northern Ireland Protocol. For policy papers and details on the Northern Ireland Protocol, see GBR-119.

Per the G-SubtlAmndmt, for any change to IP manufacturing, importation, or certification relevant to the supply of IPs in an ongoing UK trial, a substantial amendment must be submitted to the MHRA. However, if the sponsor chooses to retain an existing UK release site for the ongoing UK trial but includes an additional EU/EEA site for trials in the EU/EEA only, then no substantial amendment to the MHRA will be required.

Please note: The UK is party to the Nagoya Protocol on Access and Benefit-sharing (GBR-5), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see GBR-48.

Documents to send with your application
Overview
Part 1 (2), Part 3 (13), Part 6, Schedule 1 (Part 2), Schedule 3 (Part 2), Schedule 6, and Schedule 7
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)
Annex 2
Application for New Manufacturer’s Authorization for Investigational Medicinal Products MIA (IMP) (Human Use)

Investigational Products > Quality Requirements

Last content review/update: January 13, 2023

Investigator’s Brochure

In accordance with the MHCTR, the MHCTR2006, and GBR-92, the sponsor or the designated representative is responsible for providing investigators with an Investigator’s Brochure (IB), which 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 the designated representative should also update the IB as significant new information becomes available.

As specified in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), 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 IPs 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 GBR-113 for detailed content guidelines.

Quality Documentation

Per GBR-113, the sponsor must maintain a Certificate of Analysis to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

Part 1 (2), Part 3 (13), Part 6, Schedule 6, and Schedule 7
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
5.12 and 7
Overview

Investigational Products > Labeling

Last content review/update: January 13, 2023

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, GBR-15, the EU Good Manufacturing Practice Directive (GBR-12), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113). Per GBR-12, labeling for IPs must ensure protection of the participant and traceability, to enable identification of the product and trial, and to facilitate proper use of the IP. As specified in GBR-15, 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 GBR-15, 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 organization (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, a sample of the labeling is required as part of the clinical trial application submission. (See the Submission Content section for detailed clinical trial application submission requirements). Furthermore, according to GBR-15, the IP must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

Part 1 (2) and Part 7, and Schedule 3, Part 2 (12)
Amendment of Regulation 46 of the Principal Regulations
5.13
Article 15
Annex 13 - Investigational Medicinal Products - Packaging, Labelling, and Table 1

Investigational Products > Product Management

Last content review/update: January 13, 2023

Supply, Storage, and Handling Requirements

As defined in the MHCTR and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), the sponsor must supply the investigator(s)/institution(s) with the investigational product(s) (IPs) (known as investigational medicinal products (IMPs) in the United Kingdom (UK)), including the comparator(s) and placebo, if applicable. The sponsor should not supply either party with the IP(s) until obtaining Medicines and Healthcare Products Regulatory Agency (MHRA) approval and a favorable opinion from a recognized ethics committee (EC).

Per the MHCTR and GBR-113, the sponsor must ensure the following: (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.)

  • IP product quality and stability over the period of use
  • IP manufactured according to good manufacturing practice guidance (G-GMP-GDP and GBR-15)
  • Proper coding, packaging, and labeling of the IP(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 IP
  • 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 IP(s) to the sponsor
  • Timely delivery of the IP(s)
  • Establishment of management and filing systems for the IPs
  • Sufficient quantities of the IP for the trial

As delineated in GBR-15, IPs should remain under the control of the sponsor until after completion of a two-step procedure: certification by the Qualified Person (QP) and release by the sponsor for use in a clinical trial. Both steps should be recorded and retained in the relevant trial files held by or on behalf of the sponsor. Shipping of IPs should be conducted according to instructions given by or on behalf of the sponsor in the shipping order. De-coding arrangements should be available to the appropriate responsible personnel before IPs are shipped to the investigator site. A detailed inventory of the shipments made by the manufacturer or importer should be maintained and include the addressees’ identification.

Refer to the MHCTR and GBR-113 for detailed, sponsor-related IP requirements.

To help ensure the continuity of supply of medicines for clinical trials from January 1, 2021, the BrexitLtr-IPs indicates that the UK will unilaterally recognize certain European Union (EU) regulatory processes for a time-limited period. This recognition is known as “standstill.”

Record Requirements

As per GBR-113, 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 sample analyses and characteristics.

As set forth in GBR-113, 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.

Part 3 (13 and 15), Part 4 (28), Part 6 (36 and 38), and Schedule 7 (Parts 2 and 3)
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
5.12, 5.13, 5.14, 5.15, 5.5, and 7
Annex 13 – Investigational Medicinal Products – Packaging, Labelling

Specimens > Definition of Specimen

Last content review/update: January 13, 2023

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, GBR-73, and GBR-76, “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.
  • Bodily material: UK-HTA and GBR-64 defines “bodily material” as material from a human body that consists of, or includes, human cells. Unlike relevant material, this includes gametes, embryos outside the human body, and hair and nails from the body.
  • Tissue: GBR-64 defines “tissue” as any human material (e.g., blood, biopsies, urine) and includes relevant and bodily material.
Glossary
Part 3 (45 and 53)
Bodily Material and Tissues
Definition of Relevant Material

Specimens > Specimen Import & Export

Last content review/update: January 13, 2023

Import/Export

As specified in the UK-HTA, the Human Tissue Authority (HTA) has jurisdiction regarding the import and export of specimens (known as “relevant materials” or “human tissue” in the United Kingdom (UK)) and complies with the Code of Practice on import and export set forth in Code-E. According to the UK-HTA, Code-E, GBR-56, GBR-73, and GBR-52, 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 unless it is for a specific research project with ethical approval from an ethics committee (EC). GBR-73 explains that it is preferable for imported human tissue to be stored in a licensed establishment where possible, and if so, there is no requirement for EC approval to undertake research. However, if the premises where the human tissue will be held are not covered by a HTA license, each research project using the human tissue will require EC approval.

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. See G-Tissues-Brexit for guidance on Brexit-related regulatory changes that apply to the movement of human tissues and cells between Great Britain, Northern Ireland, and Europe. Establishments importing or exporting human tissues and cells intended for human application may require an HTA license covering these activities. For additional help, clinical trial staff should contact the HTA at enquiries@hta.gov.uk. For more information about Brexit, see the Scope of Assessment section.

Code-E requires imported and exported 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. For exports, donors should be provided with adequate information upon providing 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.

In addition, the G-QualityBlood lists the quality and safety standards when importing or exporting blood into or from the EU/European Economic Area (EEA). The UK maintains the existing quality and safety standards for the collection, testing, processing, storage, and distribution of human blood and blood components. The Medicines and Healthcare Products Regulatory Agency (MHRA) should be consulted before importing or exporting blood or blood components. See the G-QualityBlood for relevant EU quality and safety directives.

Other Considerations

As set forth in the UK-HTA, the HTRegs, and GBR-9, the HTA also regulates the storage and use of specimens 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 GBR-9, the HTA and the Health Research Authority (HRA) have agreed to collaborative arrangements in a Memorandum of Understanding. See GBR-8 for a summary of changes to GBR-9.

Note that per GBR-9 and GBR-105, an HTA license is not needed for the storage of specimens for certain research projects that have been approved by an ethics committee (EC). The HTA and the UK Health Departments’ Research Ethics Service (RES) (GBR-62) have agreed that an EC can give generic ethical approval for a research tissue bank’s arrangements for collection, storage, and release of specimens, provided the specimens in the bank are stored on HTA-licensed premises. This approval can extend to specific projects receiving non-identifiable tissue from the bank. The specimens do not then need to be stored on HTA-licensed premises, nor do they need project-specific ethical approval. However, a license is required for specimens stored for which there is no ethical approval (e.g., in large biobanks).

Per the UK-HTA, the G-QAHumTissue, 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 GBR-52, the Scotland-HTA does not regulate the use of tissue from the living for research.

Section 12 and Annex H
1 and 3
Import and Export of Tissue
Introduction to the Human Tissue Authority Codes of Practice, Licensing – Import and Export, Licensing – HTA Licensing Standards, and Annex A
Glossary/Definitions, Import and Export
Section 3: Licenses and Section 7: Licenses: general provisions
Part 5 (53 (6))
Part 2 (13, 14, 16, 26, and 41)
Part 1 (6), and Part 2 (7), and Part 3

Sources > Requirements

(Legislation) Adults with Incapacity (Scotland) Act 2000 (AIA2000) (May 9, 2000)
Scottish Parliament, Scotland
(Legislation) Anatomy Act 1984 (Scotland-AnatAct) (May 24, 1984)
UK Parliament
(Legislation) Data Protection Act 2018 (UK-DPAct) (Current through January 12, 2023)
UK Parliament
(Legislation) European Union (Withdrawal Agreement) Act of 2020 (c. 1) (Brexit) (January 23, 2020)
UK Parliament
(Legislation) Human Tissue (Scotland) Act 2006 (Scotland-HTA) (2006)
Scottish Parliament
(Legislation) Human Tissue Act 2004 (UK-HTA) (Current through January 13, 2023)
UK Parliament
(Legislation) Medicines and Medical Devices Act 2021 (MMDAct) (February 11, 2021)
UK Parliament
(Legislation) Mental Capacity Act 2005 (Chapter 9) (MCA2005) (April 7, 2005)
UK Parliament
(Legislation) On the Conclusion of the Agreement on the Withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community (Council Decision (EU) 2020/135) (EUCouncil-Brexit) (January 30, 2020)
EU Council
(Regulation) The Good Laboratory Practice Regulations 1999 (S.I. 1999/3106) (UK-GLPs) (December 14, 1999)
UK Parliament
(Regulation) The Human Tissue (Quality and Safety for Human Application) Regulations 2007 (S.I. 2007/1523) (HTRegs) (Effective July 5, 2007)
UK Parliament
(Regulation) The Medicines (Products for Human Use) (Fees) Regulations 2013 (MPHFR) (Effective April 1, 2013)
Department of Health and Social Care
(Regulation) The Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations 2019 (No. 744) (MHCTR-EUExit) (Effective January 1, 2021)
Department of Health and Social Care
(Regulation) The Medicines for Human Use (Clinical Trials) Amendment (No.2) Regulations 2006 (S.I. 2006/2984) (MHCTR2006-No2) (Effective December 12, 2006)
Department of Health and Social Care
(Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (Effective August 29, 2006)
Department of Health and Social Care, Implements EU Good Clinical Practice Directive 2005/28/EC
(Regulation) The Medicines for Human Use (Clinical Trials) and Blood Safety and Quality (Amendment) Regulations 2008 (S.I. 2008/941) (MHCTR-BSQ) (Effective May 1, 2008)
Department of Health and Social Care
(Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (Effective May 1, 2004)
Department of Health and Social Care, Implements EU Clinical Trials Directive 2001/20/EC
(Regulation) UK General Data Protection Regulation (UK-GDPR) (Effective January 1, 2021)
UK Parliament
(Guidance) Access to Electronic Health Records by Sponsor Representatives in Clinical Trials (G-EHRAccess) (September 8, 2021)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Authorizations and Procedures Required for Importing Investigational Medicinal Products to Great Britain from Approved Countries (G-ImportIMPsAuth) (Last Updated December 22, 2021)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Clinical Trials for Medicines: Apply for Authorisation in the UK (G-CTApp) (Last Updated July 18, 2022)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Clinical Trials for Medicines: Manage Your Authorisation, Report Safety Issues (G-CTAuth-GBR) (Last Updated November 8, 2022)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Code A: Guiding Principles and the Fundamental Principle of Consent (Code-A) (May 20, 2020)
Human Tissue Authority
(Guidance) Code E: Research - Code of Practice and Standards (Code-E) (April 3, 2017)
Human Tissue Authority
(Guidance) Completed Pediatric Studies - Submission, Processing, and Assessment (G-PIPs) (December 31, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Consent and Participant Information Guidance (G-ConsentPIS) (Version 11) (March 2021)
Medical Research Council, Health Research Authority
(Guidance) GDPR Guidance for Researchers and Study Coordinators (G-GDPR) (Current as of January 13, 2023)
Health Research Authority
(Guidance) Good Manufacturing Practice and Good Distribution Practice (G-GMP-GDP) (Last Updated December 27, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Governance Arrangements for Research Ethics Committees: 2020 Edition (GAfREC) (Version 2.1) (July 20, 2021)
UK Health Departments
(Guidance) Guidance for Health and Social Care Researchers at the End of the Transition Period (G-AfterTransition) (Last Updated December 30, 2021)
Health Research Authority
(Guidance) Guidance for the Notification of Serious Breaches of GCP or the Trial Protocol (G-MHRA-SeriousBreaches) (Version 6) (July 8, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Guidance on Submitting Clinical Trial Safety Reports (G-SftyRpts) (December 31, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Guidance on Substantial Amendments to a Clinical Trial (G-SubtlAmndmt) (December 31, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Guidance on the Licensing of Biosimilar Products (G-Biosimilars) (Last Updated November 7, 2022)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Guideline on How to Increase Transparency when Presenting Safety Information in the Development Safety Update Report (DSUR): Region-specific Requirements for Canada and the United Kingdom (DSUR-UK_Canada) (July 6, 2021)
Medicines and Healthcare Products Regulatory Agency
(Guidance) HTA Guide to Quality and Safety Assurance for Human Tissues and Cells for Patient Treatment (G-QAHumTissue) (January 2021)
Human Tissue Authority
(Guidance) Importing Investigational Medicinal Products into Great Britain from Approved Countries (G-ImportIMPs) (Last Updated December 22, 2021)
Medicines and Healthcare Products Regulatory Agency
(Guidance) List of Approved Countries for Clinical Trials and Investigational Medicinal Products (G-CTApprovedCountries) (Last Updated December 22, 2021)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Make a Payment to MHRA (G-MHRAPaymt) (Last Updated September 15, 2021)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Oversight and Monitoring of Investigational Medical Product Trials (G-Ovrsight) (January 28, 2022)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Procedures for UK Paediatric Investigation Plan (PIPs) (G-PIPsProcess) (December 31, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Quality and Safety of Human Blood and Blood Products (G-QualityBlood) (Last Updated May 27, 2021)
Department of Health and Social Care
(Guidance) Register to Make Submissions to the MHRA (G-MHRASubmiss) (Last Updated May 4, 2021)
Medicines and Healthcare Products Regulatory Agency, Department of Health and Social Care
(Guidance) Risk-Adapted Approach to Clinical Trials and Risk Assessments (G-RiskAssmt) (January 28, 2022)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Statutory Guidance: Current MHRA Fees (G-MHRAFees) (Last Updated September 5, 2022)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Step-by-step Guide to Using IRAS for Combined Review (G-IRASCombRev) (Last Updated January 5, 2023)
Health Research Authority
(Guidance) Supplying Investigational Medicinal Products to Northern Ireland (G-IPsNIreland) (Last Updated December 22, 2021)
Medicines and Healthcare Products Regulatory Agency
(Guidance) UK Transition Guidance (G-Tissues-Brexit) (Last Updated September 13, 2021)
Human Tissue Authority
(Correspondence) Letter to Medicines and Medical Product Suppliers: 17 November 2020 (BrexitLtr-IPs) (Last Updated December 28, 2020)
Department of Health and Social Care
(International Agreement) Agreement on the Withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community (WithdrlAgrmt) (Current consolidated version: February 22, 2022)
European Union, European Atomic Energy Community, and the United Kingdom of Great Britain and Northern Ireland

Sources > Additional Resources

(Document) Applying a Proportionate Approach to the Process of Seeking Consent (GBR-31) (Version 1.02) (May 3, 2018)
Health Research Authority
(Document) Consent and Confidentiality in Clinical Genetic Practice: Guidance on Genetic Testing and Sharing Genetic Information: A Report of the Joint Committee on Medical Genetics (GBR-37) (Second Edition) (September 2011)
Royal College of Physicians, Royal College of Pathologists, and The British Society for Human Genetics
(Document) Explanatory Memorandum to the Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations 2019 (No. 744) (GBR-115) (2019)
Department of Health and Social Care
(Document) Governance Review Check Guidelines (GBR-29) (Version 5.0) (November 21, 2021)
Health Research Authority
(Document) Guide to the UK General Data Protection Regulation (UK GDPR) (GBR-89) (October 14, 2022)
Information Commissioner’s Office
(Document) Guidelines for Phase I Clinical Trials (2018 Edition) (GBR-35) (May 29, 2018)
Association for the British Pharmaceutical Industry, UK
(Document) Insurance and Compensation in the Event of Injury in Phase I Clinical Trials (GBR-33) (June 27, 2012)
Association for the British Pharmaceutical Industry, BioIndustry Association, Clinical Contract Research Association
(Document) Involving Children in Research: MRC and ESRC Joint Guidance (GBR-4) (September 11, 2021)
Medical Research Council and Economic Social Research Council, UK
(Document) Joint Statement on Seeking Consent by Electronic Methods (GBR-6) (Version 1.2) (September 2018)
Medicines and Healthcare Products Regulatory Agency (MHRA), Health Research Authority
(Document) MRC Ethics Guide 2007 – Medical Research Involving Adults Who Cannot Consent (GBR-3) (2007)
Medical Research Council, UK
(Document) MRC/DH Joint Project to Codify Good Practice in Publicly-Funded UK Clinical Trials with Medicines - Workstream 6: Pharmacovigilance (GBR-1) (July 2012)
Health Research Authority
(Document) Nagoya Protocol on Access and Benefit-sharing (GBR-5) (2011)
Convention on Biological Diversity, United Nations
(Document) RES SOPs (Version 7.6) Summary of Changes (GBR-8) (September 2022)
UK Health Departments’ Research Ethics Service, Health Research Authority
(Document) Research and the Human Tissue Act 2004 - Consent (GBR-59) (Version 3) (January 2019)
Medical Research Council
(Document) SOP – Submitting a CTA Application to the MHRA (GBR-17) (Version 13.0) (Effective November 2, 2021)
Imperial College London, National Health Service
(Document) Sponsorship Principles (Research and Development Forum) (GBR-2) (Version 1.0) (February 2021)
Research and Development Forum, National Health Service
(Document) Standard Operating Procedures for Research Ethics Committees (GBR-9) (Version 7.6) (Effective September 26, 2022)
UK Health Departments’ Research Ethics Service, Health Research Authority
(Document) Summary of Legal Requirements for Research with Human Tissues in Scotland (GBR-52) (V2) (June 2016)
Medical Research Council
(Document) User Reference Guide – Gaining Access to MHRA Submissions (GBR-11) (Date Unavailable)
Medicines and Healthcare Products Regulatory Agency
(Document) Clinical Trials Facilitation Group (CTFG) Q&A document – Reference Safety Information (GBR-30) (November 2017)
Heads of Medicines Agencies (in cooperation with the European Medicines Agency and the European Commission)
(International Guidance) Commission Directive 2003/94/EC of 8 October 2003 Laying Down the Principles and Guidelines of Good Manufacturing Practice in Respect of Medicinal Products for Human Use and Investigational Medicinal Products for Human Use (GBR-12) (EU Good Manufacturing Practice Directive) (October 8, 2003)
European Commission, European Parliament and European Council
(International Guidance) EudraLex - Volume 4 - Good Manufacturing Practice (GMP) Guidelines (GBR-15) (Date Varies by Guidance)
European Commission
(International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (Step 4 Version) (GBR-113) (November 9, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(International Guidance) Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on Clinical Trials on Medicinal Products for Human Use, and Repealing Directive 2001/20/EC (GBR-21) (EU Clinical Trials Regulation) (April 16, 2014)
European Parliament and Council
(Not Available Online) NIAID Communication with Health Research Authority (December 2021) (GBR-118)
(Webpage) Applying to a Research Ethics Committee (GBR-68) (Last Updated October 27, 2022)
Health Research Authority
(Webpage) Brexit Guidance (GBR-60) (March 28, 2022)
Government of United Kingdom
(Webpage) Clinical Trials - Regulation EU No 536/2014 (GBR-86) (Current as of January 13, 2023)
European Commission
(Webpage) Clinical Trials in the European Union (GBR-121) (Current as of January 13, 2023)
European Union
(Webpage) Clinical Trials Regulation (GBR-54) (Current as of January 13, 2023)
European Medicines Agency
(Webpage) Clinical Trials Toolkit – Routemap (GBR-18) (Current as of January 13, 2023)
Medicines and Healthcare Products Regulatory Agency, Department of Health and Social Care
(Webpage) ClinicalTrials.gov (GBR-49) (Current as of January 13, 2023)
U.S. National Library of Medicine
(Webpage) Combined Review (GBR-72) (Last Updated December 9, 2022)
Health Research Authority
(Webpage) Contact MHRA (GBR-58) (Last Updated February 14, 2022)
Medicines and Healthcare Products Regulatory Agency
(Webpage) Country Profile: United Kingdom (GBR-48) (Current as of January 13, 2023)
Access and Benefit-sharing Clearing-house, Convention on Biological Diversity, United Nations
(Webpage) Decommission of eSUSAR (GBR-127) (August 3, 2022)
Medicines and Healthcare Products Regulatory Agency
(Webpage) Ending Your Project (GBR-128) (Last Updated May 10, 2022)
Health Research Authority
(Webpage) eSUSAR (GBR-50) (Current as of February 23, 2022)
Medicines and Healthcare Products Regulatory Agency
(Webpage) EudraCT – European Union Drug Regulating Authorities Clinical Trials Database (GBR-87) (Last Updated December 15, 2022)
European Medicines Agency
(Webpage) Examples of Substantial and Non-Substantial Amendments (GBR-98) (Last Updated March 25, 2021)
Health Research Authority
(Webpage) Fast-track Research Ethics Review (GBR-116) (Last Updated December 20, 2022)
Health Research Authority
(Webpage) Four Nations Policy Leads Group (GBR-97) (Last Updated September 20, 2021)
Health Research Authority
(Webpage) Good Clinical Practice for Clinical Trials (GBR-92) (Last Updated January 11, 2023)
Medicines and Healthcare Products Regulatory Agency
(Webpage) Health Research Authority - Glossary (GBR-64) (Current as of January 13, 2023)
Health Research Authority
(Webpage) Help - Using IRAS - New Users (GBR-106) (Current as of January 13, 2023)
Health Research Authority
(Webpage) HRA and Devolved Administrations Accreditation Scheme Report (GBR-124) (Last Updated December 6, 2022)
Health Research Authority
(Webpage) HRA Approval (GBR-67) (Last Updated November 22, 2021)
Health Research Authority
(Webpage) Human Tissue Act 2004 (GBR-75) (Current as of January 13, 2023)
Human Tissue Authority
(Webpage) ICSR Submissions Login Page (GBR-126) (Current as of January 13, 2023)
Medicines and Healthcare Products Regulatory Agency
(Webpage) Informing Participants and Seeking Consent (GBR-69) (Last Updated September 4, 2019)
Health Research Authority
(Webpage) Integrated Research Application System (IRAS) Login Page (GBR-78) (Version 6.3.3) (Last Updated November 14, 2022)
Health Research Authority
(Webpage) Integrated Research Application System (IRAS): Collated Question-Specific Guidance for NHS REC Form (GBR-77) (Version 14) (Last Updated July 27, 2017)
Health Research Authority
(Webpage) International Standardized Randomized Controlled Trial Number (ISRCTN) Registry (GBR-47) (Current as of January 13, 2023)
BioMed Central
(Webpage) IRAS - Templates for Supporting Documents (GBR-107) (Last Updated December 20, 2022)
Health Research Authority, Department of Health and Social Care
(Webpage) IRAS Development Questions and Answers (GBR-122) (Last Updated May 12, 2022)
Health Research Authority
(Webpage) IRAS for Combined Review Login Page (GBR-125) (Current as of January 13, 2023)
Health Research Authority
(Webpage) Launch of the UK Local Information Pack: Supporting the Set-up of NHS/HSC Research in the UK (GBR-63) (Last Updated June 4, 2019)
Health Research Authority
(Webpage) MHRA - About Us (GBR-57) (Current as of January 13, 2023)
Medicines and Healthcare Products Regulatory Agency
(Webpage) MHRA Account Request – MHRA Submissions (GBR-13) (Current as of January 13, 2023)
Medicines and Healthcare Products Regulatory Agency
(Webpage) MHRA Pay (GBR-26) (Current as of January 13, 2023)
Medicines and Healthcare Products Regulatory Agency
(Webpage) Model Agreements (GBR-70) (Last Updated July 31, 2019)
Health Research Authority
(Webpage) Online Booking Service (GBR-95) (Last Updated February 25, 2022)
Health Research Authority
(Webpage) Overview - Data Protection and the EU (GBR-7) (Current as of January 13, 2023)
Information Commissioner’s Office
(Webpage) Progress Reports (GBR-65) (Last Updated July 28, 2022)
Health Research Authority
(Webpage) Quality Assurance (GBR-123) (Last Updated August 31, 2022)
Health Research Authority
(Webpage) Relevant Material Under the Human Tissue Act 2004 (GBR-76) (Current as of January 13, 2023)
Health Tissue Authority
(Webpage) Research Ethics Committees Overview (GBR-111) (Last Updated February 4, 2020)
Health Research Authority
(Webpage) Research Ethics Service and Research Ethics Committees (GBR-51) (Current as of January 13, 2023)
Health Research Authority
(Webpage) Research Ethics Service (GBR-62) (Last Updated August 31, 2022)
Health Research Authority
(Webpage) Research FAQs (GBR-105) (Last Updated April 20, 2021)
Human Tissue Authority
(Webpage) Research Involving Children (GBR-130) (Last Updated September 6, 2021)
Health Research Authority
(Webpage) Research Registration and Research Project Identifiers (GBR-102) (Last Updated May 25, 2022)
Health Research Authority, Department of Health and Social Care
(Webpage) Research Transparency (GBR-55) (Last Updated December 19, 2022)
Health Research Authority
(Webpage) Research with Potentially Vulnerable People (GBR-131) (Last Updated June 16, 2022)
UK Research and Innovation
(Webpage) Roles and Responsibilities (GBR-103) (Last Updated May 26, 2021)
Health Research Authority
(Webpage) Safety Reporting (GBR-99) (Last Updated October 7, 2022)
Health Research Authority
(Webpage) Search RECs (GBR-112) (Current as of January 13, 2023)
Health Research Authority
(Webpage) Staying Connected with Your Participants (GBR-117) (Current as of January 13, 2023)
Parkinson’s UK
(Webpage) Templates: Recommended Wording to Help You Comply with GDPR (GBR-100) (Current as of January 13, 2023)
Health Research Authority
(Webpage) The Northern Ireland Protocol - Details of the agreement reached by Withdrawal Agreement Joint Committee regarding the implementation of the Northern Ireland Protocol (GBR-119) (Last Updated January 5, 2021)
United Kingdom Cabinet Office
(Webpage) UK Policy Framework for Health and Social Care Research (GBR-101) (Last Updated November 4, 2022)
Health Research Authority (England), the Department of Health and Social Care (Northern Ireland), the Scottish Government Health and Social Care Directorates, and the Department for Health and Social Services (Wales)
(Webpage) UK Transition Licensing FAQs (GBR-56) (Last Updated September 13, 2021)
Human Tissue Authority
(Webpage) Use of Human Tissue in Research (GBR-73) (Last Updated November 16, 2021)
Health Research Authority
(Webpage) What Approvals and Decisions Do I Need? (GBR-66) (Current as of January 13, 2023)
Health Research Authority
(Webpage) What is Valid Consent? (GBR-129) (October 14, 2022)
Information Commissioner’s Office
(Webpage) Writing a Plain Language (Lay) Summary of Your Research Findings (GBR-120) (Last Updated November 9, 2021)
Health Research Authority

Sources > Forms

(Form) Clinical Trial of an Investigational Medicinal Product (CTIMP), Annual Progress Report to Research Ethics Committee (GBR-27) (Version 4.5) (Last Updated January 2021)
Health Research Authority
(Form) Declaration of the End of Trial Form (GBR-24) (Revision 3, June 2010) (EudraLex, Volume 10, Clinical Trials Guidelines)
European Commission
(Form) Medicines: Application Forms for a Manufacturer License (GBR-28) (May 14, 2020)
Medicines and Healthcare Products Regulatory Agency
(Form) Notification of the End of a Clinical Trial of a Medicine for Human Use to the UK Competent Authority (GBR-133) (September 29, 2021)
Medicines and Healthcare Products Regulatory Agency
(Form) Submit your Final Report - Health Research Authority (GBR-20) (Current as of January 13, 2023)
Health Research Authority
(Form) Substantial Amendment Notification Form (GBR-25) (Revision 3, June 2010) (EudraLex, Volume 10, Clinical Trials Guidelines)
European Commission
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This message was updated on January 13, 2023