Ministry of Health and Public Hygiene (MSHP)

As delineated in PharmLaw-GIN, the Ministry of Health and Public Hygiene (Ministère de la Santé et de l'Hygiène Publique (MSHP)) is the regulatory authority responsible for national drug marketing authorization. Per DecreeNoD218, the MSHP is responsible for the regulation of clinical trials in the Republic of Guinea. Per GIN-1, the two (2) branches within the MSHP directly involved with the clinical trial approval process are the National Ethics Committee for Health Research (Comité National d'Ethique pour la Recherche en Santé (CNERS)) and the National Directorate of Pharmacy and Medicine (Direction Nationale de la Pharmacie et du Médicament (DNPM)). Per DecreeNoD218, CNERS is in charge of the clinical trial application review and approval process for studies conducted in humans, and per GIN-1, the DNPM is responsible for drug product registration, authorization, and importation.

National Directorate of Pharmacy and Medicine (DNPM)

Per GIN-20, the DNPM’s mission is to develop and monitor the implementation of government policy in the area of pharmacy and medicine. The DNPM’s responsibilities associated with this mission are as follows:

• Developing the elements of the drug and pharmacy policy
• Monitoring the implementation of the policy at all levels of the country's health system
• Developing regulatory texts relating to pharmacy and medicine
• Organizing a rational and sustainable supply system for the supply of essential medicines for all health structures in the country
• Organizing the quality control of drugs and biological products
• Organizing and supervising pharmacovigilance to safeguard public health
• Monitoring the application of international conventions on narcotic drugs and psychotropic substances
• Developing information and continuing education documents for health professionals
• Promoting essential research in the field of pharmacy and medicine

Per GIN-20 and GIN-9, to carry out its mission, the DNPM is comprised of two (2) divisions: the Medicines Division and the Division of Pharmaceutical Establishments & Laboratories.

As indicated in GIN-9, the Medicines Division’s responsibilities include managing the approval and import of drug products; overseeing drug economics including the supply and production of drug products; addressing pharmacovigilance and other vigilance activities; and monitoring narcotics and psychotropics on the national level. The Pharmaceutical Establishments and Laboratories Division’s responsibilities include overseeing regulations, standards, and approvals relating to pharmaceutical establishments and laboratories; managing the promotion and development of the pharmaceutical industry; addressing quality assurance and the fight against falsified medicines and illicit marketing; and implementing programs to address pharmaceutical logistics in Guinea. See GIN-9 for detailed division information.

National Ethics Committee for Health Research (CNERS)

For detailed information on CNERS’ responsibilities, composition, procedures, and fees, please refer to the Ethics Committee topic.

Other Considerations

According to GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7).

Please note: Guinea is party to the Nagoya Protocol on Access and Benefit-sharing (GIN-3), 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 GIN-10.

Contact Information

Medicines and Healthcare Products Regulatory Agency

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. For a listing of MHRA services and information, see GBR-36.

G-ATMP states that MHRA is also the competent authority for advanced therapy medicinal products (ATMPs) and for UK manufacturers or importers of ATMPs. An ATMP is a medicinal product which is either a gene therapy medicinal product, a somatic cell therapy medicinal product, or a tissue engineered product.

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 Medical Products from Approval Countries Email: for queries, complete this contact form and email to gmpinspectorate@mhra.gov.uk

Clinical Trials of Medicines:
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.

Overview

According to DecreeNoD218, Guinea-PHC, and GIN-5, the National Ethics Committee for Health Research (Comité National d'Ethique pour la Recherche en Santé (CNERS)) must approve the health research protocol involving human participants before a clinical trial can commence. Furthermore, according to GIN-1, the National Directorate of Pharmacy and Medicine (Direction Nationale de la Pharmacie et du Médicament (DNPM)) must issue a drug import license prior to the sponsor or the representative (typically the principal investigator (PI)) initiating the clinical trial.

According to GIN-1, CNERS must approve the clinical trial protocol before the drug import license application is submitted to the DNPM. Therefore, the CNERS and DNPM reviews may not be conducted in parallel.

Clinical Trial Review Process

According to GIN-1, the sponsor or the designated representative (typically the PI) is responsible for hand delivering the drug import license application to the DNPM’s Pharmacovigilance, Drugs and Quality Control section for review and approval. The DNPM may request drug samples for testing and evaluation even if the PI or the sponsor provides detailed proof of testing and licensing from regulatory authorities based abroad. (See the Submission Process and Submission Content sections for submission requirements, and the Timeline of Review section for review timelines.)

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 G-CTApp specifies 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, 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.

The G-CTApp states that under 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

As indicated in the G-CTApp, 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 product, 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.

UK-wide Research

The UKwide-Rsrch specifies that the four (4) UK nations take a consistent approach to study-wide reviews with one (1) application for all relevant UK sites. Each UK nation will take assurances from the study-wide review conducted by the lead nation (the nation conducting the initial review). The following outlines key differences in approvals from UK nations:

• England and Wales – For any research taking place in England and/or Wales, the sponsor will receive an HRA and HCRW approval letter, which will detail any further requirements before beginning the research
• Northern Ireland – Each participating Northern Ireland Health and Social Care body will confirm their capacity and capability after the relevant study-wide reviews and participating site assessments and arrangements are complete
• Scotland – For any research taking place in Scotland, the sponsor will receive Research & Development permission after the relevant study-wide reviews and site assessments and arrangements are complete

Notification Scheme

Per the G-CTApp, MHRA’s notification scheme enables a more streamlined and risk-proportionate approach to processing clinical trial authorization for “initial” applications. The scheme only applies to clinical trial applications for Phase 4 and certain Phase 3 clinical trials deemed to be of lower risk. Interest in the notification scheme should be registered via the combined review process described above (GBR-125). MHRA acceptance of an application under the notification scheme will be confirmed within 14 calendar days from the application received effective date and authorization by the MHRA will be granted unless any criterion is not suitably met. If the MHRA determines the application does not meet the notification scheme criteria, an objection decision will be communicated within 14 calendar days from the application received effective date, and the application will continue under full clinical trial assessment with a decision communicated within the 30-day statutory timeframe.

As indicated in the G-CTApp, the notification scheme acceptance criteria are as follows:

Phase 4 trials must meet both of the following criteria:

• All IPs are licensed and used according to the relevant UK, United States of America (USA), or European Union (EU) marketing authorization (except for placebo)
• There are no ongoing safety concerns with the IP(s) that the sponsor is aware of, for example other trials on temporary halt/clinical hold, other trials with unresolved urgent safety measures or post-marketing regulatory restrictions

Phase 3 trials must meet at least one (1) of the following criteria:

• The trial is already approved in the USA or EU based on the same protocol and Investigator’s Brochure (IB) versions submitted to MHRA, and for EU approvals, the same version of the IP dossier. For trials approved in the USA only, the IP dossier submitted to the MHRA must document the same IP manufacturing process
• The MHRA has approved in the last two (2) years a previous Phase 3 clinical trial of the IP(s) at the same dose (or a higher dose), dosing frequency (or a higher frequency) and route of administration, and for the same indication (even if the trial was with a different sponsor) and utilizing the same manufacturing process
• IPs are licensed and used according to the relevant UK, USA, or EU marketing authorization (except for placebo)

In addition, the G-CTApp states that to be eligible for the scheme, a Phase 3 trial must not include any of the following:

• Complex, innovative trial design (e.g., basket, umbrella, and platform) that allows for prospective major adaptations such as the addition of indications or IPs via future amendments
• Includes pediatric participants
• Includes pregnant or breastfeeding participants
• IP is first in class
• IP is an advanced therapy medicinal product (ATMP)

Brexit Background

Per the G-MHRASubmiss, Brexit, the EUCouncil-Brexit, the WithdrlAgrmt, and the G-AfterTransition, the UK withdrew from the 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. For more information about GBR-21, see GBR-54.

National Directorate of Pharmacy and Medicine (DNPM)

Per GIN-1, the National Directorate of Pharmacy and Medicine (Direction Nationale de la Pharmacie et du Médicament (DNPM)) does not charge a fee to review the drug import license application. However, at times there may be related processes that the applicant must follow, which may include fees. Contact the DNPM for more information.

Medicines and Healthcare Products Regulatory Agency

As per the MHCTR, the MHCTR2006, and the G-CTApp, 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. Non-payment may also result in suspension of any license or authorization, followed by legal proceedings for any unpaid amounts.

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

• 3,366 British Pounds – Applications with an Investigational Medicinal Product (IMP) dossier (higher fee for phase 1, full and simplified IMP dossier)
• 248 British Pounds – Applications without an IMP dossier (lower fee for phase IV, cross referral, additional protocol)
• 248 British Pounds – Clinical trial variation/amendment
• No cost – Phase 4 notification
• 248 British Pounds – Assessment of annual safety reports

Note per the G-MHRAFees, there is no annual clinical trials fee and no fee for Phase IV notifications. For a cross-referral or additional protocol submission, no new IMP dossier or investigators brochure data should be provided; however, copies of the relevant manufacturer’s authorization(s) and qualified person declaration (if applicable) should be provided since these are study specific.

Per the G-CTAuth-GBR, the fees for the annual safety reports are applicable to annual progress reports and Development Safety Update Reports (DSURs). From June 1, 2024, MHRA will only accept online payment of this fee via MHRA’s payments service (GBR-26) prior to submission of an annual safety report. Receipts generated will be sent by email and must be included in the report submission as proof of payment. Failure to provide evidence of payment will result in the submission being made invalid.

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. The relevant invoice and customer number should be quoted when making payments. 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, 2^nd Floor
280 Bishopsgate
London
EC2M 4RB
UK

As per G-MHRAPaymt, credit or debit card payments may be made securely online using 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.

Overview

According to DecreeNoD218, Guinea-PHC, and GIN-5, the principal investigator (PI) must obtain ethics committee (EC) approval to conduct health research involving human participants from the National Ethics Committee for Health Research (Comité National d'Ethique pour la Recherche en Santé (CNERS)) before a clinical trial can commence. As per DecreeNoD218, CNERS operates under the Ministry of Health and Public Hygiene (Ministère de la Santé et de l'Hygiène Publique (MSHP)). According to the Guinea-PHC and GIN-5, CNERS is responsible for reviewing and approving clinical research protocols for studies conducted in humans. Per GIN-13, CNERS is also responsible for ensuring research is conducted in accordance with the provisions of the Code of Ethics for Health Research which have been incorporated into Guinea-PHC, for proposing amendments, and for examining ethical issues related to health research submitted by institutions or individuals. In addition to conducting research in compliance with the Guinea-PHC, per GIN-5, CNERS must also comply with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GIN-7), the Declaration of Helsinki (GIN-23), the Council for International Organizations of Medical Science (CIOMS)’ International Ethical Guidelines for Biomedical Research Involving Human Subjects (GIN-24), and the World Health Organization (WHO)’s Operational Guidelines for Ethics Committees that Review Biomedical Research (GIN-25).

Ethics Committee Composition

As specified in DecreeNoD218, CNERS consists of 17 members appointed by the MSHP Minister, including an executive office responsible for coordinating committee activities, ensuring its proper functioning, and holding regular meetings. The executive office is comprised of a president, a vice president, and two (2) secretaries. However, GIN-13 states that the executive office is comprised of five (5) members elected within CNERS: a president, a vice-president, a secretary general (held by the Section Head in charge of Research at the MSHP), a secretary in charge of following up on protocol implementation, and a treasurer. Committee members are selected for their interest in research ethics, and for their qualifications and experience in reviewing and evaluating the scientific, medical, and ethical aspects of proposed clinical trials. CNERS strives to bring together health professionals, as well as non-specialists, to represent the social strata and moral values of the national community, and may include doctors, epidemiologists, pharmacists, statisticians, public health specialists, representatives of ministries of health and justice, training and research institutions, religious denominations, non-governmental organizations (NGOs), and patient associations.

As delineated in DecreeNoD218, CNERS composition specifically includes:

• Two (2) members representing Guinea’s main religions (Islam and Christianity)
• Eight (8) members with professional health research qualifications including doctors, clinicians, epidemiologists, biologists, chemists, statisticians, and methodology and research ethics experts
• Seven (7) members representing organizations including health professional associations, relevant ministerial departments, research institutions, non-governmental organizations, and human rights organizations

Per GIN-13, the committee’s activities include the following:

• Receive research protocols and correspondence for CNERS’s review
• Manage the documentation and archives of CNERS
• Help the committee prepare for its sessions
• Write committee meeting minutes
• Disseminate CNERS recommendations and decisions

CNERS has three (3) technical working committees: one (1) committee deals with advocacy, communication, and awareness actions; one (1) committee is responsible for training activities; and one (1) committee is responsible for monitoring and evaluating CNERS’s achievements.

Terms of Reference, Review Procedures, and Meeting Schedule

According to DecreeNoD218, the CNERS committee is required to follow standard operating procedures (SOPs) specifying the conditions for organizing and convening committee meetings and delineating member rights and responsibilities. See GIN-5 for the SOPs.

As specified in DecreeNoD218, the president (also known as the chairman) shall convene CNERS committee sessions, appoint rapporteurs to present the files/protocols submitted to the committee, and determine the matters to be discussed in the session. While DecreeNoD218 specifies that the CNERS committee meets in regular sessions two (2) times a year, the more current GIN-6 indicates that the committee meets in regular sessions on the last Thursday of each month. Per DecreeNoD218 and GIN-12, additional sessions are convened by the president as necessary.

GIN-6 indicates that applications submitted during the first week of each month will be discussed at the regular monthly meeting. It also explains that a minimum of three (3) weeks is required between the submission and its review by CNERS. The CNERS Administrative Assistant will provide the applicant an acknowledgement of receipt and keep all files in the CNERS archives. GIN-12 states that committee members should have a copy of the protocol for review at least six (6) working days before the committee session.

DecreeNoD218 states that the appointment of CNERS committee members is valid for three (3) years and is renewable. Members must have no conflict of interest with the protocols under review. GIN-5 indicates that the quorum required for voting is nine (9) members. Per GIN-5, if necessary, CNERS may use independent consultants to provide specific expertise in reviewing the proposed research protocols. These consultants may be specialists in ethics, law, in a particular disease or methodology, or be representatives of specific communities, patients, or special interest groups. If necessary, CNERS can also invite the PI. Further, GIN-13 recommends changing one-third of the membership at a time, which helps to train new members and remain efficient during the transition.

For detailed CNERS procedures and information on other administrative processes, see DecreeNoD218 and GIN-5.

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, Finance, Digital and Governance Directorates, 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. The UKwide-Rsrch reaffirms that GAfREC is the UK policy document governing the RES function and EC reviews in each country.

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 purpose 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 1^st should be agreed to by December 1^st in the previous financial year. The schedule should set out the dates, times, and venues of meetings, and the closing date for applications for 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 and 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.

Overview

According to DecreeNoD218, the Guinea-PHC, and GIN-5, the mission of the National Ethics Committee for Health Research (Comité National d’Ethique pour la Recherche en Santé (CNERS)) is to ensure the scientific quality and ethical conduct of health research in the Republic of Guinea. As per the Guinea-PHC and GIN-5, the primary scope of information assessed by CNERS relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial. GIN-6 requires the principal investigator (PI) to respect the fundamental ethical principles of research involving human beings.

As per the Guinea-PHC and GIN-5, CNERS must also pay special attention to reviewing informed consent and to protecting the welfare of certain classes of participants deemed to be vulnerable. DecreeNoD218, the Guinea-PHC, and GIN-5 also state that CNERS is 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, and they must verify the adequacy of confidentiality and privacy safeguards. See the Guinea-PHC and GIN-5 for detailed ethical review guidelines.

Role in Clinical Trial Approval Process

As per the Guinea-PHC, GIN-6, and GIN-5, the PI or the representative is responsible for submitting a research application to CNERS for review and approval. According to GIN-1, CNERS must approve the clinical trial protocol before the sponsor or the representative (typically the PI) submits the drug import license application to the National Directorate of Pharmacy and Medicine (Direction Nationale de la Pharmacie et du Médicament (DNPM)). Therefore, the CNERS and DNPM reviews may not be conducted in parallel.

GIN-6 and GIN-5 provide specific requirements for the submission of research by the PI, as well as the details pertaining to the CNERS review and decision-making process. Please refer to the Timeline of Review section for additional ethics committee (EC) timeline information.

Per GIN-5 and GIN-12, CNERS approval is valid for one (1) year and is renewable upon request by the PI/sponsor. Additionally, per GIN-12 and GIN-6, any amendments to protocols currently being implemented must also be submitted to CNERS.

Guinea-PHC states that when research is related to an epidemic or calamity, the proposal must be submitted within 30 days from the project’s filing date. GIN-5 further states that in emergencies (e.g., epidemics or disasters), an accelerated procedure is adopted without prejudice to the requirements of submitting the protocol and including the following:

• Reduction of the minimum and maximum periods of review and decision to 48 hours and one (1) week respectively
• Reduction of the required quorum of the members of CNERS to five (5)
• Possibility of calling on other national and international experts
• Acceptances of online submission and evaluation
• Sending the response letter within 48 hours after evaluation

Per GIN-5, the EC should conduct a monitoring and evaluation visit for all approved research projects. Urgent follow-up visits may also be prompted by the following:

• Any protocol amendment likely to affect the rights, safety, and/or well-being of the participants or the conduct of the research
• Serious or unexpected adverse events related to the conduct of the research or the product tested
• Actions taken by investigators, sponsors, and regulatory bodies
• Any event or new information likely to modify the benefit/risk ratio of the research
• A decision of an independent safety committee

Furthermore, in the event of serious shortcomings observed in the field (non-compliance with the protocol or modification of the latter), CNERS may suspend the implementation of the project. In this case, a new protocol will be submitted to CNERS for review.

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 cell 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 Chief Investigator (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 CTIMP led from the 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.

National Ethics Committee for Health Research (CNERS)

As per GIN-6, the principal investigator is responsible for paying a fee of 5,000,000 Guinean Francs to the National Ethics Committee for Health Research (Comité National d’Ethique pour la Recherche en Santé (CNERS)) to review and approve the clinical trial protocol and related documents. For protocol amendments or extension of approval validation, the fee is 3,000,000 Guinean Francs. For doctoral students, the fee for amending a protocol or extending the validation of approval is 1,500,000 Guinean Francs.

Payment Instructions

Per GIN-17, payment to CNERS can be made by bank transfer, check, or cash depending on the options available to the applicant. GIN-5 further notes that when the investigator submits the documents to be examined to the CNERS secretariat, an acknowledgement of receipt and a payment receipt will be sent to the investigator.

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.

Overview

Per DecreeNoD218, the Ministry of Health and Public Hygiene (Ministère de la Santé et de l’Hygiène Publique (MSHP)) is the authorizing body of the National Ethics Committee for Health Research (Comité National d’Ethique pour la Recherche en Santé (CNERS)). CNERS is responsible for reviewing and approving clinical research protocols for studies conducted in humans at the national level.

Registration, Auditing, and Accreditation

According to GIN-1, CNERS is accredited by the MSHP.

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 (SOPs) 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

Further, per GAfREC, 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 SOPs 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.

Overview

In accordance with DecreeNoD218, Guinea-PHC, and GIN-5, the principal investigator (PI) must obtain approval to conduct health research involving human participants from the National Ethics Committee for Health Research (Comité National d'Ethique pour la Recherche en Santé (CNERS)) before a clinical trial can commence. In addition, per GIN-1, the sponsor or the representative (typically the PI) is responsible for obtaining a drug import license from the National Directorate of Pharmacy and Medicine (Direction Nationale de la Pharmacie et du Médicament (DNPM)) prior to initiating a study.

According to GIN-1, CNERS must approve the clinical trial protocol before the drug import license application is submitted to the DNPM. Therefore, the CNERS and DNPM reviews may not be conducted in parallel. Additionally, according to GIN-12 and GIN-6, any amendments to protocols currently being implemented must also be submitted to CNERS.

Regulatory Submission

According to GIN-1, the sponsor or the representative (typically the PI) should hand deliver one (1) hard copy of the drug import license application along with other required documentation to the DNPM’s Division of Pharmaceutical Products. (Refer to the Submission Content section for submission documentation information.)

Ethics Review Submission

As per GIN-6, eight (8) hard copies and an electronic copy of the clinical trial application and accompanying materials should be submitted to CNERS. The application and supporting materials text must be in Arial 12 font. Each hard copy must have all the materials bound together, and the electronic copy must be transmitted in a single file. See GIN-6 for the application form and the Submission Content section for detailed documentation requirements.

According to GIN-6, the clinical trial application and accompanying materials, must be provided in French.

Per GIN-6 and GIN-21, the CNERS application and all related documents must be submitted to the CNERS headquarters located within the Dixinn BlueZone, next to the Kenien bridge on the highway. Contact Ms. Diallo Aissatou BAH, by phone at +224 622 25 31 27 or +224 628 77 72 23, email: aissatou_dalaba07@yahoo.fr.

Please refer to the Ethics Committee section for more information regarding CNERS requirements.

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. Per the G-CTApp, MHRA’s notification scheme enables a more streamlined and risk-proportionate approach to processing clinical trial authorization for “initial” applications. The scheme only applies to clinical trial applications for Phase 4 and certain Phase 3 clinical trials deemed to be of lower risk. Interest in the notification scheme should be registered via the combined review process (GBR-125). Per G-ATMP, all advanced therapy medicinal products must submit clinical trial applications using the same processes as all other medicines. See Scope of Review 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

G-IRASCombRev indicates 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.

For overall help during the submission process, see the CTapp-Issues which identifies common issues with validation and assessment of clinical trial applications and how to avoid them.

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 GBR-13 are contained in the G-MHRASubmiss and GBR-11.

For overviews of submittals to MHRA, see GBR-18. Also see the Initiation, Agreements & Registration section for information on obtaining a trial identification number during trial registration.

The UKwide-Rsrch provides guidance and requirements for research in more than one (1) United Kingdom (UK) nation, and specifies that the four (4) nations of the UK take a consistent approach to study-wide reviews so that sponsors only need to submit one (1) application on GBR-125 in most circumstances. Each UK nation will take assurances from the site-wide review conducted by the lead nation (the nation conducting the initial review).

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.

Regulatory Authority Requirements

Per GIN-1, the National Directorate of Pharmacy and Medicine (Direction Nationale de la Pharmacie et du Médicament (DNPM)) does not have a drug import license application form. Rather, the application is comprised of the materials submitted by the sponsor or the representative (typically the principal investigator (PI)) along with a request to obtain a drug import license.

Per GIN-1, along with the application, the sponsor or the representative must submit the following:

• One (1) copy of the protocol
• Ethical approval
• Informed consent form (ICF)
• Investigator(s) curriculum vitaes (CVs)
• Investigator’s Brochure (IB)
• All investigational product (IP) documentation
• Product license request

Ethics Committee Requirements

According to GIN-6, the National Ethics Committee for Health Research (Comité National d’Ethique pour la Recherche en Santé (CNERS)) requires eight (8) hard copies and an electronic copy of each of the documents listed below:

• Research protocol submission letter, dated and signed by the PI
• Completed ethics review application form, dated and signed by the PI (see GIN-6)
• Protocol
• ICF and/or assent form
• Data collection instruments
• IB
• Detailed project budget in Guinean francs
• Profile of investigators in five (5) lines
• CVs for all investigators (four (4) pages maximum per CV)
• Previous related decisions from CNERS and/or other countries
• Letters from associated partners
• Other documents

In addition to the documents indicated by GIN-6, GIN-5 also states that CNERS requires the following documents:

• Table of contents
• Acronyms and abbreviations
• Project summary in a maximum of 10 lines
• Research problem, objectives, and hypotheses
• Research sponsor(s) profile(s) and CV(s)
• Methodology including sampling
• Ethical considerations
• Data collection tools (including material(s) used to inform and recruit participants (e.g., posters, messages, image boxes, etc.) dated and with a version number, and translated into the relevant languages according to the target population of the study)
• Participant compensation mechanism as well as the benefits related to the research
• Measures taken to mitigate research-related risks
• Measures taken to ensure participant(s) compensation in the event of injury
• Data analysis techniques and tools
• Documents relating to free and informed consent including: description of the strategies for recruiting participants and obtaining consent; participant protection and data privacy measures; presentation of risks faced by individuals and communities
• Methods for sharing results (including publications), data, and biological materials collected in Guinea and transferred outside
• Involvement of health authorities and communities
• Methods for sharing research benefits with research populations
• Activities schedule
• Bibliographic references
• IB, if applicable, together with published data and a summary of product characteristics
• Details of changes made to the protocol since the last notice was issued
• Sponsor and PI declaration to respect ethical principles and standards

See GIN-6 for detailed requirements related to corrections, amendments, and renewal of approvals.

Clinical Protocol

As indicated in the Guinea-PHC, any clinical research protocol must contain the following elements:

• Identity of the sponsor and investigator
• Research objectives and hypotheses
• Methodology
• Calculation of the number of participants necessary, and inclusion/exclusion criteria
• Method of data analysis
• Criteria to decide end of study
• Potential risks to participants
• Ethical aspects
• Informed consent procedures

See the Guinea-PHC for additional details regarding protocol elements.

In addition, per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7). Accordingly, GIN-7 requires the following protocol contents:

• General information (protocol title, identifying number, and date; contact information for the sponsor, medical expert, investigator(s), trial site(s), qualified physician(s), and laboratory and/or institutions involved in the study)
• Background information
• Objectives and purpose
• Trial design
• Selection, withdrawal, and treatment of participants
• Assessment of efficacy
• Assessment of safety
• A description of the statistical methods to be used in the trial
• Direct access to source data and documents
• Quality control and quality assurance
• Ethical considerations
• Data handling and recordkeeping
• Publication policy

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 (See the Initiation, Agreements & Registration section for additional information on participant recruitment)
• 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.

Overview

According to GIN-1, the National Ethics Committee for Health Research (Comité National d’Ethique pour la Recherche en Santé (CNERS)) must approve the clinical trial protocol before the drug import license application is submitted to the National Directorate of Pharmacy and Medicine (Direction Nationale de la Pharmacie et du Médicament (DNPM)). Therefore, the CNERS and DNPM reviews may not be conducted in parallel.

Regulatory Authority Approval

According to GIN-1, the DNPM’s approval of a drug import license application typically takes two (2) weeks.

Ethics Committee Approval

Per the Guinea-PHC, CNERS must give its opinion on any research protocol submitted within a period not exceeding 60 days from the project’s filing date. GIN-5 and GIN-12 indicate that the sponsor or principal investigator (PI) who submitted the protocol will be notified of the opinion of CNERS within 10 days of the committee meeting via email.

GIN-5 specifies that the PI is required to submit a research protocol to CNERS at least 15 days prior to the committee meeting for the application to be reviewed during the current month. However, this period may be expedited for health emergency reasons. GIN-6 similarly indicates that a minimum of three (3) weeks is required between the submission and its review by CNERS. GIN-6 further states that applications submitted during the first week of each month will be discussed at the regular monthly meeting which occurs on the last Thursday of each month. GIN-5 explains that the file must include all required documents for it to be admissible and evaluated by the committee (See the Submission Content section for the list of required documents.)

Per GIN-6, the CNERS Administrative Assistant will provide the applicant an acknowledgement of receipt and keep all files in the CNERS archives. GIN-12 states that committee members should have a copy of the protocol for review at least six (6) working days before the committee session. Per the Guinea-PHC, CNERS must give its opinion on any research protocol submitted within a period not exceeding 60 days from the project’s filing date. GIN-5 and GIN-12 indicate that the sponsor or PI who submitted the protocol will be notified of the opinion of CNERS within 10 days of the committee meeting via email and that CNERS approval is valid for one (1) year and is renewable upon request by the PI/sponsor.

Special Circumstances

Guinea-PHC states that when research is related to an epidemic or calamity, the proposal must be submitted within 30 days from the project’s filing date. GIN-5 further states that in emergencies (e.g., epidemics or disasters), an accelerated procedure is adopted without prejudice for the protocol submission requirements and includes the following:

• Reduction of the minimum and maximum periods of review and decision to 48 hours and one (1) week respectively
• Reduction of the required quorum of CNERS members to five (5)
• Possibility of calling on other national and international experts
• Acceptance of online submissions and evaluations
• Sending the response letter within 48 hours after evaluation

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.

Regarding the new notification scheme, the G-CTApp states that this pathway enables a more streamlined and risk-proportionate approach to processing clinical trial authorization for “initial” applications for Phase 4 and certain Phase 3 clinical trials deemed to be of lower risk. Applications submitted under this scheme will be processed by the MHRA within 14 calendar days from the application received effective date, provided the sponsor can demonstrate the trial meets the inclusion criteria. Authorization by the MHRA will be granted unless any criterion is not suitably met. If the MHRA determines the application does not meet the criteria, an objection decision will be communicated within 14 calendar days from the application received effective date, and the application will continue under the full authorization assessment with a decision communicated within the 30-day statutory timeframe.

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 (CHM) before approval for the trial can be given. See the G-CTApp for detailed requirements.

Overview

In accordance with DecreeNoD218, Guinea-PHC, and GIN-5, the principal investigator (PI) must obtain approval to conduct health research involving human participants from the National Ethics Committee for Health Research (Comité National d'Ethique pour la Recherche en Santé (CNERS)) before a clinical trial can commence. In addition, per GIN-1, the sponsor or the representative (typically the PI) is responsible for obtaining a license to import study drugs from the National Directorate of Pharmacy and Medicine (Direction Nationale de la Pharmacie et du Médicament (DNPM)) prior to initiating a study. No waiting period is required following the sponsor’s receipt of these approvals.

Per GIN-17, the research should comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7).

Clinical Trial Agreement

Furthermore, per GIN-7, the sponsor should obtain the investigator’s/institution’s agreement to:

• Conduct the trial in compliance with Good Clinical Practice (GCP), the applicable regulatory requirement(s), and the approved protocol
• Comply with procedures for data recording/reporting
• Permit monitoring, auditing, and inspection
• Retain the trial-related essential documents until the sponsor informs the investigator/institution these documents are no longer needed

The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

Clinical Trial Registration

According to GIN-1, the Ministry of Health and Public Hygiene (Ministère de la Santé et de l'Hygiène Publique (MSHP)) does not currently require the clinical trial to be registered with either a domestic or international clinical trial registry.

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. GBR-18 indicates that once all the relevant approvals are in place, all documentation has been finalized, and all participating sites have the information they need, the trial can begin. This process is often achieved by holding a start-up meeting at each site so that the CI ensures all technical aspects of a trial and protocol requirements are fully understood by relevant site staff. Trial-specific training (protocol and procedures) and review of trial conduct (e.g., safety reporting) is often undertaken at this stage. For clinical trials of an investigational product (IP), this communication should also include pharmacy staff, if applicable, so that they can confirm all requirements are in place before dispensing IPs to participants.

See GBR-40 for information about DigiTrials, which supports clinical trials in England to provide safe, authorized access to patient data to help set up trials. DigiTrials includes recruitment and feasibility services to identify whether there are enough suitable participants, as well as participant communication and outcomes services.

Per the MHCTR and GBR-18, specific documentation, including MHRA licensing, must be in place before an 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 the CTIMP-Condtns, MHRA assumes that the trial will commence within 12 months of the date of the favorable ethical opinion. The EC must be notified of the trial start date with evidence of the authorization. Further, the trial should not commence at any site until management permission has been obtained from the organization responsible for the care of the participants at the site. If the trial does not commence within 12 months of the favorable opinion being issued, the sponsor should send the EC a written explanation for the delay. A further written explanation should be sent after 24 months if the research has still not commenced. If the trial does not commence within 24 months of the favorable opinion being issued, the EC may recommend to the MHRA that the clinical trial authorization should be suspended or terminated. See CTIMP-Condtns for additional information on standard conditions for clinical trials.

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.

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.

The UKwide-Rsrch reiterates that national model contracts are available and, as such, contracting expectations and arrangements across the four (4) UK nations are broadly similar. For all four (4) nations:

• In commercially sponsored research, it is mandatory to use the unmodified contract templates appropriate to the study type
• In non-commercially sponsored research, it is expected that the unmodified contract appropriate to the study type is used; use of bespoke or modified agreements, where an appropriate template exists, is likely to result in significant delay and costly review; any modifications must be highlighted in the application

The UKwide-Rsrch also highlights national differences relating to the way contractual agreements are reviewed and agreed. In England and Wales, sponsors must obtain a waiver from HRA and HCRW to use a modified or bespoke agreement (an agreement that differs from a published UK-wide model agreement template). This waiver allows NHS sites to freely negotiate all the contractual terms of the agreement; in Wales, this negotiation is carried out with a central team. In Northern Ireland, to modify the UK-wide model agreement template, a waiver is needed from the Health and Social Care R&D Approvals Service, which allows sites to freely negotiate all the contractual terms of the agreement. In Scotland, sponsors can expect to carry out a single contract negotiation for all Scottish sites, which will be negotiated with a nominated lead site or central team. If the study is single center, it will be negotiated at the relevant site.

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-18, each clinical trial must have a unique trial number. Clinical trials with sites in the European Union (EU), the European Economic Area (EEA), or Northern Ireland should also apply for a European number. Per GBR-87, as of January 31, 2023, all new clinical trials with sites in Europe should register on the new Clinical Trials Information System (CTIS) (GBR-39). GBR-39 specifies that by January 31, 2025, any ongoing trials must be transitioned from EudraCT (GBR-87) to GBR-39. For more information, see the EudraCT transition fact sheet (GBR-16). CTIMP-Condtns indicates that for clinical trials involving sites in both the UK and the EU, a record in EU’s GBR-39 does not satisfy the public registry condition because the UK component of the trial will not be visible in CTIS (GBR-39). Failure to register is a breach of the clinical trial conditions unless a deferral has been agreed to.

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 clinicaltrials.gov (GBR-49). For any submissions prior to December 31, 2021, the applicant should have registered their clinical trial on an established international register.

Safety Reporting Definitions

Per G-PV-GIN, the following definitions provide a basis for a common understanding of Guinea’s safety reporting requirements:

• Adverse Event (AE) – Any harmful and unintended manifestation occurring in a subject during treatment. The term "adverse event", unlike "adverse effect", does not prejudge a causal link with exposure, particularly to a drug.
• Adverse Reaction (AR) – A harmful and unintended reaction to a drug or other health product, occurring at dosages normally used in humans for the prophylaxis, diagnosis, or treatment of disease or for the recovery, rectification, or modification of a physiological function, or resulting from misuse of the drug or product
• Adverse Drug Effect (ADR) – A harmful and unwanted reaction, occurring at dosages normally used in humans for the prophylaxis, diagnosis, or treatment of a disease or the modification of a physiological function or resulting from a misused drug, constituting a withdrawal syndrome when stopping the product or a dependency syndrome, as well as any reaction resulting from misuse. It also includes any harmful reactions that may arise from poor quality of the drug
• Serious Adverse Event (SAE) – An adverse effect that is lethal, or likely to be life-threatening, resulting in disability or incapacity, or causing or prolonging hospitalization, or resulting in a congenital anomaly
• Unexpected Adverse Drug Reaction – An adverse reaction whose nature, severity, or outcome does not correspond with the known authorized information for this medicinal product

As delineated in G-PV-GIN, Guinea’s pharmacovigilance system is coordinated by the National Directorate of Pharmacy and Medicine (Direction Nationale de la Pharmacie et du Médicament (DNPM)) according to the provisions in PharmLaw-GIN. G-PV-GIN is based on the GIN-7 guidelines, and may also contain additional requirements in accordance with the legislation in force. The National Pharmacovigilance System includes the National Pharmacovigilance Commission, the National Pharmacovigilance Technical Committee, the Pharmacovigilance Section of the National Directorate of Pharmacy and Medicine, the pharmacovigilance focal points at each level of the health pyramid, health programs, pharmaceutical companies, and the public. See G-PV-GIN for additional details).

Safety Reporting Requirements

As delineated in G-PV-GIN, pharmaceutical companies are required to notify the DNPM of SAEs/serious adverse drug reactions (SADRs) occurring during a clinical trial within seven (7) days. Additionally, the DNPM should be notified of any new fact likely to harm the safety of the participants participating in the trial 15 days following first knowledge of the sponsor. Non-serious AEs will be transmitted to the DNPM in the clinical study final report.

Per G-PV-GIN, clinical trial applicants are required to notify the DNPM of the following:

• Any AE (including symptoms and clinical signs)
• Changes in biological values (e.g., hypoglycaemia, etc.) or medication errors
• Therapeutic failures
• Drug interactions
• Any observation of overdose, abuse, or misuse
• Any problem related to exposure during pregnancy or breastfeeding
• Any observation of loss of efficacy, in particular with vaccines, contraceptives, or other pharmaceutical products intended for the treatment of diseases involving life-threatening conditions
• Any other effect deemed relevant to declare

G-PV-GIN specifies that all serious and unexpected AEs/ADRs that are fatal or life-threatening, as well as those occurring during a clinical trial, must be notified to the DNPM expeditiously, i.e., as soon as the notifier becomes aware of them or within a period not exceeding 48 hours. Update notes may be provided within an additional period not exceeding 7-15 days. All other serious or unexpected AEs/ADRs must be reported immediately, but within a period not exceeding seven (7) days. The count of days starts from the moment when the notifier becomes aware of the suspected AE/ADR and the minimum conditions for notification are met.

Per G-PV-GIN, the pharmaceutical industry must also report serious or unexpected AEs/ADRs within 24-48 hours, deaths within 24 hours, and non-serious AEs/ADRs monthly. Health professionals are required to report serious or unexpected AEs/ADRs within 24-48 hours, deaths are to be reported immediately, and non-serious AEs/ADRs should be reported as soon as possible, not to exceed seven (7) days.

Investigator Responsibilities

According to GIN-5, the principal investigator (PI) must report serious and unexpected AEs to the National Ethics Committee for Health Research (Comité National d’Ethique pour la Recherche en Santé (CNERS)) for review.

According to GIN-17, CNERS does have an AE/ADR database, however, an electronic link is not available nor is any other information regarding the database at this time.

Ethics Committee Responsibilities

As indicated in GIN-5, the ethics committee should assess the AEs that have occurred, the measures taken for the participant’s safety, and the information from CNERS (pharmacovigilance file).

Form Completion & Delivery Requirements

Per GIN-17, since CNERS has not yet developed a specific AE/ADR form, researchers should complete their own AE/ADR notification form and submit it to CNERS for review. Researchers submit completed AE/ADR notification forms to CNERS for review. No further information is available regarding delivery requirements.

G-PV-GIN notes all AE/ADR notifications are made on the national notification form designed by the DNPM. Refer to G-PV-GIN for form details.

In addition, per G-PV-GIN, Guinea also submits ADR notifications via the VigiFlow database (GIN-16). Per GIN-15, GIN-16 is a web-based platform developed by the World Health Organization (WHO)’s Uppsala Monitoring Centre to help countries manage AEs/ADRs. See GIN-15 for detailed information on VigiFlow, and see GIN-18 for submission instructions.

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 submitted via the combined review service, one USM notification is made via the combined review part of the Integrated Research Application System (IRAS) (GBR-125) and received by the MHRA. No additional notification is required directly to the EC. GBR-32 reaffirms this stating that SUSARs and safety reports for CTIMPs that were approved by combined review should be submitted to the MHRA only. If the safety report requires action, the MHRA will instruct the study team to submit a substantial amendment. Any other SUSARs or annual safety report submitted UK wide will be acknowledged by email by the EC. The submitted cover report for the SUSAR or annual safety report will not be signed and returned, and the email will act as the formal acknowledgement.

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.

See GBR-18 for a safety reporting flowchart that gives an overview of the investigator’s expedited safety reporting requirements to the sponsor for a clinical trial in the UK.

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

Per GBR-18, sponsors should develop formal, written processes for the management of adverse events and safety reports, including the handling of both expedited reports and annual safety reporting.

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 European number. GBR-87 indicates that as of January 31, 2023, all new clinical trials with sites in Europe should use the Clinical Trials Information System (CTIS) (GBR-39)
• 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)

As stated in the G-CTAuth-GBR, 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-18, 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.

See the Regulatory Fees section for information on fees for annual safety reporting and DSURs. See the G-CTAuth-GBR and GBR-99 for more details on submittal and delivery requirements.

Interim and Annual Progress Reports

According to GIN-5, the principal investigator (PI) is responsible for submitting a progress report on the status of a clinical trial to be evaluated by the National Ethics Committee for Health Research (Comité National d’Ethique pour la Recherche en Santé (CNERS)). In addition, per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7), which states the investigator should promptly provide written reports to the sponsor and the institutional ethics committee, and where applicable, the institution, on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.

Final Report

Per GIN-5, the PI is responsible for submitting a final study report upon the trial’s completion to be evaluated by CNERS.

Interim and Annual Progress Reports

As indicated in the G-CTAuth-GBR and GBR-9, the investigator and the sponsor share responsibility for submitting progress reports to the ethics committee (EC), as required, 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-32 and GBR-65, it is no longer a requirement to submit annual progress reports to the EC. However, GBR-65 states that depending on the type of approval, a progress report may be requested to track progress.

In addition, GBR-65 states that if the study was reviewed by an EC in Scotland or Northern Ireland, an annual progress report should be submitted 12 months after the date on which the favorable ethics opinion was given, except in the following instances:

• If the study is expected to run for less than two (2) years in duration
• If the study received a proportionate review
• If the study received a favorable ethics opinion from an EC in England or Wales

Furthermore, GBR-65, states that if a study was given a favorable ethics opinion by an EC in Scotland or Northern Ireland, there are separate forms for submitting progress reports, depending on the type of research. The form for clinical trials of investigational medicinal products (GBR-27) should be completed in typescript and authorized by the Chief Investigator (CI) or the sponsor/sponsor representative. An electronic copy should be emailed to the EC within 30 days of the end of the reporting period.

See the Regulatory Fees section for information on fees for annual progress reports.

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, the 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.

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.

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7), which defines a sponsor as an individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial.

In accordance with GIN-7, Guinea 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.

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, 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. 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 trial conclusion
• Communications relating to urgent safety measures
• Pharmacovigilance reporting

Overview

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7), which provides guidance to sponsors on investigator and site selection. According to GIN-7:

• The sponsor is responsible for selecting the investigator(s)/institution(s). Each investigator should be qualified by training and experience and should have adequate resources to properly conduct the trial for which the investigator is selected. If the organization of a coordinating committee and/or selection of coordinating investigator(s) are to be utilized in multicenter trials, their organization and/or selection are the sponsor’s responsibility.
• Before entering an agreement with an investigator/institution to conduct a trial, the sponsor should provide the investigator(s)/institution(s) with the protocol and an up-to-date Investigator’s Brochure, and the investigator/institution should be provided with sufficient time to review the materials.

Foreign Sponsor Responsibilities

No information is available regarding foreign sponsor regulatory requirements.

Data and Safety Monitoring Board

Per GIN-7, a Data and Safety Monitoring Board (DSMB) may be established 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 GIN-7, 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, and given ethics committee approval
• 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 among investigators is facilitated

In addition, the sponsor is responsible for the organization of a coordinating committee and/or selection of coordinating investigator(s), if they are to be utilized.

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) for CTIMPs, and made clear in a cover letter when submitting the amendment to the lead nation.

UK Local Information Pack

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 (LIP), which provides one (1) consistent package to support study setup and delivery across the UK.

The UKwide-Rsrch explains the LIP ensures that consistent information is given to all UK research sites and indicates that there are national differences in the LIP. In England and Wales, the LIP should include the Initial Assessment Letter, which may be shared with sites. Additionally, the sponsor should send the LIP directly to the site’s Research and Development (R&D) department, delivery team, and local clinical research network (if a National Institute for Health and Care Research Clinical Research Network (NIHR CRN) Portfolio) using the England and Wales non-commercial email template or commercial email template, as appropriate. For Welsh sites, it is expected that the sponsor has a process to translate patient-facing documents into the Welsh language if requested by sites or participants. In Northern Ireland, the sponsor may send the LIP to each participating site’s R&D department and delivery team once the application has been validated and once instructed to do so by the Health and Social Care R&D Approvals Service. The LIP should be shared using the Northern Ireland non-commercial email template or commercial email template, as appropriate. In Scotland, the NHS Research Scotland Permissions Coordinating Centre makes the LIP available to participating R&D departments and the appropriate Network or Portfolio Manager. The sponsor is responsible for making the information available to the research teams using the Scotland email template, which covers both non-commercial and commercial studies.

For help with LIP packages, email templates and other requirements, 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

Per GBR-18, for multicenter trials, the careful selection and evaluation of investigator sites is critical for the successful completion of a trial within budget, timelines, and to ensure the generation of high-quality data. When undertaking site selection, the preparation of ‘reserve’ investigator sites (so that the trial may be extended to these sites if recruitment issues arise) should be considered as part of proactive trial planning. Factors that should influence investigator site selection include:

• Interest in the research question
• Experience and qualifications of the investigator
• Sufficient staff to conduct the study and their experience and qualifications
• Availability of a suitable patient population
• Adequate time to conduct and oversee the trial
• Adequate facilities
• Previous track record with similar trials
• Geographic location
• Contractual and budgetary negotiations and arrangements

Per GBR-18, for multicenter trials, the CI must ensure that each PI is provided with all relevant, version-controlled documents before commencing recruitment. Further, it is good practice to ensure the PI signs a protocol signature page to confirm receipt and their agreement to comply with the current version of the protocol. The trial master file should be held at the coordinating site and copies of relevant documents should be kept at each participating site in an investigator site file.

Further, 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

Insurance

According to GIN-17, sponsors must submit proof of insurance as part of the clinical trial application submission to the National Ethics Committee for Health Research (Comité National d’Ethique pour la Recherche en Santé (CNERS)).

Compensation

Injury or Death

According to the Guinea-PHC, in the event of any temporary or permanent trial-related injury or disability, the participant should be compensated. In the case of the participant’s death, the legal heirs are entitled to financial compensation.

In addition, per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7), which 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.

Trial Participation

Per GIN-7, the participant should be provided with information regarding any anticipated prorated payment, if any, for participating in the trial.

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.

Quality Assurance/Quality Control

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (GIN-7), which provides guidance to sponsors on quality, data, and records management.

GIN-7 indicates that the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

• During protocol development, identifying processes and data that are critical to ensure participant protection and the reliability of trial results
• Identifying risks to critical trial processes and data
• Evaluating the identified risks against existing risk controls
• Deciding which risks to reduce and/or which risks to accept
• Documenting quality management activities and communicating to those involved in or affected by these activities
• Periodically reviewing risk control measures to ascertain whether the implemented quality management activities are effective and relevant
• Describing in the clinical study report, the quality management approach implemented in the trial and summarizing important deviations from the predefined quality tolerance limits and remedial actions taken

Monitoring Requirements

Per GIN-7, the sponsor should develop 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).

Premature Study Termination/Suspension

According to GIN-7, 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 ethics committee (EC) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor.

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 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 because 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.

See GBR-10 for best practices in improving clinical trial setup to reduce timelines and increase citizens’ access to research. Also see GBR-34 for investigator training and guidance on implementing people-centered research.

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 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. See GBR-92 for pre-inspection checklists and other resources. 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 upon arrangements, the sponsor should consider whether an amendment is required before submitting the end of study notification. GBR-65 also states that if research is terminated early or is temporarily suspended, then all relevant review bodies should be notified within 15 days.

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.

Electronic Data Processing System

According to GIN-17, Guinea is required to comply with the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (GIN-7). As per GIN-7, when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. The sponsor should base their approach to validate such systems on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. In addition, the sponsor should maintain standard operating procedures (SOPs) for the systems that cover system setup, installation, and use. The responsibilities of the sponsor, investigator, and other parties should be clear, and the system users should be provided with training. Refer to GIN-7 for additional information.

Records Management

As set forth in GIN-7, 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.

In addition, GIN-7 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.

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.

Responsible Parties

For the purposes of data protection requirements, the PDPLaw delineates the responsibilities of the “data controller.” The data controller, as defined by the PDPLaw, refers to the natural or legal person, public or private, or any other body or association which, alone or jointly with others, makes the decision to collect and process personal data, and determines the purposes thereof.

Data Protection

Per the PDPLaw, the data controller must be guided by the following principles:

• The collection, recording, processing, storage, transmission, and interconnection of personal data files must be done in a lawful and fair manner
• Personal data must be collected for specified, explicit, and legitimate purposes, and not be further processed in a manner incompatible with these purposes; be adequate, relevant, and not excessive regarding the purposes for which the data are collected and processed; be kept for a period that does not exceed the period necessary for the stated collection or processing purposes; data may only be kept beyond this required period to respond specifically to the process of said data for historical, statistical, or research purposes under the provisions of this law or any other laws or regulations in force regarding personal data protection
• The data collected must be accurate, and if necessary, updated
• The principle of transparency implies mandatory and clear information from the person responsible for processing personal data
• Personal data must be treated confidentially and protected, in particular when the process of this data involves data transmissions in a network
• When personal data processing is implemented on behalf of the data controller, the data controller must choose a subcontractor who is able to provide guarantees for the protection and confidentiality of the data
• The person responsible for processing personal data may only be authorized to transfer said data to a third country if it ensures a higher or equivalent level of protection of the privacy, freedoms, and fundamental rights of persons regarding the processing to which these data are or may be subject; before any actual transfer of personal data to this third country, the data controller must obtain prior authorization from the Personal Data Protection Authority; any transfer of personal data to a third country is subject to strict and regular control by the Personal Data Protection Authority, regarding their purpose

As set forth in PDPLaw, prior authorization from the competent authority (i.e., the Ministry of Health and Public Hygiene (Ministère de la Santé et de l’Hygiène Publique (MSHP)) is required before any implementation of personal data processing relating to:

• Genetic and medical data and scientific research in these fields
• Personal data including biometric data
• Personal data processing for public interest reasons, in particular for historical, statistical, or scientific purposes
• Planned transfer of personal data to a third country

See the PDPLaw for detailed information on data protection requirements in Guinea.

Consent for Processing Personal Data

As set forth in the PDPLaw, personal data processing is considered legitimate if the data subject expressly gives prior consent. However, this prior consent requirement may be waived when the controller is duly authorized and the processing is necessary for: compliance with a legal obligation to which the controller is subject; the performance of a task in the public interest or in the exercise of public authority, vested in the controller or the third party to whom the data is communicated; the execution of a contract to which the data subject is a party or for the execution of pre-contractual measures taken at the subject’s request; or to safeguard the interest or the fundamental rights and freedoms of the data subject.

Per PDPLaw, at the time of the data collection or before, the person responsible for processing personal data is required to provide the data subject the following information:

• The specific purpose(s) of the processing for which the data is intended
• The categories of data concerned
• The recipient(s) to whom the data is likely to be communicated
• The option of refusing to appear on the file in question
• The existence of a right of access to data concerning the person, and a right to rectify this data
• The data retention period
• The possibility of any transfer of data to a third country

In addition, per PDPLaw, the data subject may ask questions and obtain from the data processor the following:

• Information allowing the person to know about and contest the processing
• Confirmation that personal data concerning the data subject is or is not the subject of this processing
• Information relating to the purposes of the processing, the categories of personal data processed and the recipients or categories of recipients to whom the data is communicated

Refer to the PDPLaw for detailed personal data protection consent requirements.

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.

The UKwide-Rsrch describes the following differences among the UK nations regarding accessing identifiable data without consent, including for potential participants:

• England and Wales – If the project involves access to identifiable patient data relating to people living or receiving care and treatment in England and Wales without consent, the sponsor may need to apply to the HRA via the Confidentiality Advisory Group (CAG) (GBR-38). The CAG provides advice to the HRA on the use of confidential patient information for research uses. See GBR-41 for details and resources on the CAG.
• Northern Ireland – There is currently no legal basis for those outside of the direct care team to process identifiable data without consent. The Health and Social Care Privacy Advisory Committee can provide advice on any options available in Northern Ireland. The Health and Social Care Honest Broker Service does not provide identifiable data for consented studies or trials but may be able to offer advice on options to access anonymized data to support research
• Scotland – If a project is multi-center, a sponsor will need to obtain permissions through the Public Benefit and Privacy Panel for Health and Social Care. For single center studies, applicants should contact the Caldicott Guardian at the research site to discuss the requirements for accessing the data

UK-US Data Bridge

As explained in GBR-22, under the “UK Extension to the EU-US Data Privacy Framework” (GBR-23), businesses in the UK can transfer personal data to certified U.S. organizations without further safeguards as defined in the GBR-23. US organizations that have been certified can opt in to receive data from the UK through the UK-US data bridge. Per GBR-19, before transferring personal data, UK organizations must verify that the receiving US organization is certified pursuant to GBR-23. Sensitive personal data must be appropriately identified as sensitive when transferred under the UK-US data bridge to ensure it receives appropriate protections under the framework. Under the UK extension, sensitive personal information includes genetic data, biometric data for the purpose of uniquely identifying a natural person, and data concerning sexual orientation. See GBR-22, GBR-23, and GBR-19 for additional information about the UK Extension to the Data Privacy Framework.

Obtaining Consent

In all Guinean clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the Guinea-PHC. According to GIN-5 and GIN-6, the informed consent form (ICF) must be reviewed and approved by the National Ethics Committee for Health Research (Comité National d’Ethique pour la Recherche en Santé (CNERS)) with the clinical trial application. Per GIN-5, CNERS should also review modifications/amendments to the ICF and the assent form. (See the Required Elements section for details on what should be included in the form.)

Per the Guinea-PHC, investigator(s) must provide detailed research study information to the participant or legal representative/guardian. The ICF content should be presented in a manner that is easy to understand and without coercion or unduly influencing a potential participant to enroll in the clinical trial.

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7). As per the Guinea-PHC and GIN-7, a participant should not be coerced or pressured in any way during the consent process. Per GIN-7, none of the oral and written information concerning the trial, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or 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

No information is currently available regarding re-consent requirements.

Language Requirements

According to GIN-6, the clinical trial application and accompanying materials, including the ICF, must be provided in French.

Documenting Consent

As indicated in the Guinea-PHC, the participant or legal representative/guardian must sign and date the ICF before an independent witness.

Per GIN-7, when the participant is illiterate or the legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:

• The written ICF and any other written information to be provided to the participant is read and explained to the participant or legal representative/ guardian
• The participant or legal representative/guardian have orally consented to the participant’s involvement in the trial, and has signed and dated the ICF, if capable of doing so

Before participating in the study, the participant or legal representative/guardian should receive a copy of the signed and dated ICF.

Waiver of Consent

No information is available on waiver of consent requirements.

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 or legal representative/guardian. 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/guardian, 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.) For more guidance on the PIS, see the PrtInfoQty-Stds, the PrtInfo-DesignPrin, and GBR-14, which include FAQs, information principles, and standards.

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 or legal representative/guardian 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 or legal representative/guardian 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 or legal representative/guardian, and the investigator(s) must sign and date the ICF. Where the participant is illiterate, or the legal representative/guardian 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.

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7), which provides guidance on the elements to include in the informed consent form (ICF). As described in GIN-7, both the informed consent discussion and the written ICF and any other written information to be provided to participants should include explanations of the following:

• The trial involves research
• The purpose of the trial
• The trial treatment(s) and the probability for random assignment to each treatment
• The trial procedures to be followed, including all invasive procedures
• The participant’s responsibilities
• Those aspects of the trial that are experimental
• The reasonably foreseeable risks or inconveniences to the participant and, when applicable, to an embryo, fetus, or nursing infant
• The reasonably expected benefits. When there is no intended clinical benefit to the participant, the participant should be made aware of this.
• The alternative procedure(s) or course(s) of treatment that may be available to the participant, and their important potential benefits and risks
• The compensation and/or treatment available to the participant in the event of a trial-related injury
• The anticipated prorated payment, if any, to the participant for participating in the trial
• The anticipated expenses, if any, to the participant for participating in the trial
• The participant’s participation in the trial is voluntary and the participant may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the participant is otherwise entitled
• The monitor(s), the auditor(s), the ethics committee, and the regulatory authority(ies) will be granted direct access to the participant's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the participant, to the extent permitted by the applicable laws and regulations and that, by signing a written ICF, the participant or legal representative/guardian is authorizing such access
• The records identifying the participant will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. If the results of the trial are published, then the participant’s identity will remain confidential
• The participant or legal representative/guardian will be informed in a timely manner if information becomes available that may be relevant to the participant’s willingness to continue participation in the trial
• The person(s) to contact for further information regarding the trial and the rights of trial participants, and whom to contact in the event of trial-related injury
• The foreseeable circumstances and/or reasons under which the participant’s participation in the trial may be terminated
• The expected duration of the participant’s participation in the trial
• The approximate number of participants involved in the trial

Based on the MHCTR, the G-ConsentPIS, and the 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: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• 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 or legal representative/guardian 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.

Overview

In accordance with the Guinea-PHC, Guinea’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The Guinea-PHC states that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. GIN-6 requires the principal investigator to respect the fundamental ethical principles of research involving human beings.

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7).

The Right to Participate, Abstain, or Withdraw

As set forth in the Guinea-PHC and GIN-7, a potential research participant or legal representative/guardian should be informed that participation is voluntary and that the participant may refuse to participate or withdraw from the research study at any time.

The Right to Information

As delineated in the Guinea-PHC and GIN-7, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, study procedures, obligations associated with the participant’s participation, any potential benefits or risks, and any compensation for participation or injury/treatment.

The Right to Privacy and Confidentiality

As per the Guinea-PHC and GIN-7, all participants must be afforded the right to privacy and confidentiality.

The Right of Inquiry/Appeal

No information is currently available regarding the right of inquiry/appeal.

The Right to Safety and Welfare

The Guinea-PHC and GIN-7 state that a research participant’s right to safety and the protection of the participant’s health and welfare must always take precedence over the interests of science and society.

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 legal representative/guardian should be informed that participation is voluntary, that they 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 or legal representative/guardian 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 or legal representative/guardian 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.

The Guinea-PHC makes provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by an emergency. As delineated in the Guinea-PHC, in an emergency, when the participant is unable to give informed consent, the consent of a family member should be obtained.

According to GIN-17, Guinea is also required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7). Per GIN-7, in an emergency, if the signed informed consent form (ICF) has not been obtained from the research participant or legal representative/guardian, or if an effective treatment is lacking but the investigational product could address the participant’s emergency needs, the clinical trial may be conducted. However, the method used on the participant must be explained clearly in the trial protocol, and the ethics committee must approve the protocol in advance. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

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/guardian should be obtained. If the prior consent of the participant or legal representative/guardian 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 legal representative/guardian 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

Overview

As per the Guinea-PHC, in all Guinean clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. Vulnerable populations include persons who cannot give a fully free and informed consent because of the person’s situation or mental state, and may include, but are not limited to, children/minors, prisoners, physically or mentally handicapped, persons whose condition requires emergency treatment or life support, and pregnant or lactating women.

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7). GIN-7 includes the following as vulnerable populations: members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable populations include persons in nursing homes, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

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.

Guinea’s definition of a child/minor and the age of consent for children/minors are not specified in the currently available regulatory resources.

In accordance with the Guinea-PHC, when the research participant is a child, the informed consent form (ICF) must be signed by the child’s parent/legal guardian. In the case of disagreement between the wishes of the child and the parent/legal guardian, the child’s wishes should prevail. The child’s personal consent must be requested when the child’s age allows the child to understand the purpose of the research, the risk, and disadvantages of this research, and what is expected of the child’s participation. Research may only be conducted in children if it cannot be conducted in less vulnerable participants, such as for the purpose of researching childhood diseases or pathologies to which children are particularly susceptible.

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7). GIN-7 states that when a clinical trial includes minors, the minor should be informed about the trial to the extent compatible with their understanding and, if capable, should sign and personally date the written informed consent.

Assent Requirements

No information is currently available regarding assent requirements.

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 a parent/legal guardian. As per GBR-4, the researcher needs only to obtain consent from one (1) person with parental responsibility. GBR-130 further indicates that the parent/legal guardian 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 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, 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/legal guardian:

• 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 parent/guardian 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 parent/guardian 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.

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.

As per the Guinea-PHC, any research studies involving women who are pregnant or nursing require additional safeguards to ensure the research conforms to appropriate ethical standards. The informed consent of the pregnant woman or nursing mother is required for all proposed research studies. Studies to be conducted with this population should meet one (1) or more of the following conditions:

• The research should improve the health of the mother without harming the fetus or infant
• The research should increase the viability of the fetus
• The research should promote the proper development of the infant or the mother’s ability to nurse the infant

The Guinea-PHC further states that any research promoting abortion is prohibited by the Penal Code.

Per GIN-17, Guinea is also required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7). GIN-7 explains that 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.

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 their legal guardian) 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

According to the Guinea-PHC, prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. The Guinea-PHC states that prisoners may not participate in any research study while they are detained in prison and deprived of their freedom. Additionally, if an ill person is placed under the responsibility of the judicial authority, the agreement of the latter is required in addition to the informed consent of the participant.

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.

Per the UKwide-Rsrch, a prisoner or young offender is defined as any inmate of the prison systems of England and Wales, Scotland, or Northern Ireland. It does not include patients detained under the MHAct at special hospitals or other psychiatric secure units, or juvenile offenders detained in local authority secure accommodation or secure training centers. Health research involving prisoners or young offenders should relate directly to their health care and be of such a nature that it could only be conducted in this population. See the UKwide-Rsrch for details on differences between the four (4) United Kingdom nations with regard to research on prisoners.

As stated in the Guinea-PHC, participants with a mental impairment are at risk in research studies as they are unable to fully comprehend the nature of the research and the informed consent process. Per the Guinea-PHC, mentally impaired participants should be fully informed about the study in which they have been asked to participate. Informed consent must be obtained from the legal representative/guardian who have been informed about the trial. The refusal of a mentally impaired participant should always be respected. Research may only be conducted in mentally impaired participants if it cannot be conducted in healthy participants.

Per GIN-17, Guinea is also required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7). GIN-7 states that when a clinical trial includes participants with mental impairment (e.g., those with severe dementia), the participant should be informed about the trial to the extent compatible with their understanding and, if capable, should sign and personally date the written informed consent.

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/guardian. This consent should only be provided once the legal representative/guardian 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 the participant’s capacity of understanding regarding the trial, its risks, and its benefits
• No incentives or financial inducements are given to the participant or legal representative/guardian 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.

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7). GIN-7 defines an investigational product as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use.

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.

Manufacturing

According to GIN-4 and GIN-8, the National Directorate of Pharmacy and Medicine (Direction Nationale de la Pharmacie et du Médicament (DNPM)) is responsible for authorizing the manufacture of drug products in Guinea. Specific information concerning the DNPM’s role in reviewing and approving the manufacture of investigational products (IPs) is not currently available.

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7), which requires IPs to be manufactured, handled, and stored in accordance with applicable Good Manufacturing Practice (GMP) and used in accordance with the approved protocol.

Import

According to GIN-1, once the principal investigator (PI) obtains ethics committee approval from the National Ethics Committee for Health Research (Comité National d'Ethique pour la Recherche en Santé (CNERS)), the sponsor or the representative (typically the PI) must submit a written request along with additional documentation to the DNPM director to obtain approval to import IPs. (See the Submission Content section for detailed documentation requirements.) According to GIN-1, the DNPM’s approval of a drug import license application typically takes two (2) weeks.

Additional information on the DNPM review and approval process is not available at this time.

Please note: Guinea is party to the Nagoya Protocol on Access and Benefit-sharing (GIN-3), 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 GIN-10.

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.

Per G-ATMP, a manufacturer’s license from MHRA is needed to manufacture unlicensed advanced therapy medicinal products (ATMPs) in the UK. See G-ATMP for guidance on the two (2) ATMP manufacturer license pathways: the hospital exemption or the “specials” scheme.

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 their 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.

Investigator’s Brochure

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7).

As specified in GIN-7, the Investigator’s Brochure (IB) must include the following sections:

• Table of Contents
• Summary
• Introduction
• Physical, Chemical, and Pharmaceutical Properties and Formulation
• Nonclinical Studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
• Effects in Humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and post-marketing experiences)
• Summary of Data and Guidance for the Investigator(s)

The sponsor should also update the IB as significant new information becomes available. See GIN-7 for detailed content guidelines.

Quality Management

Per GIN-7, 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.

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 Management

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.

Per GIN-17, Guinea is required to comply with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (GIN-7), which states that the investigational product (IP) must be coded and labeled in a manner that protects the blinding, if applicable. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

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.

Supply, Storage, and Handling Requirements

According to GIN-7, the sponsor must supply the investigator(s)/institution(s) with the investigational products (IPs), including the comparator(s) and placebo, if applicable. The sponsor or the representative (typically the principal investigator (PI)) should not supply either party with the IP(s) until regulatory and ethics approval is obtained.

In addition, GIN-7 specifies that the sponsor must ensure the following:

• Timely delivery of the IP(s)
• Records maintained for IP document shipment, receipt, disposition, return, and destruction
• Written procedures including instructions for handling and storage of the IP(s), adequate and safe receipt of the IP(s), dispensing of the IP(s), retrieval of unused IP(s), return of unused IP(s) to the sponsor, and disposal of unused IP(s) by the sponsor
• IP product quality and stability over the period of use
• Maintain sufficient quantities of the IP(s) to reconfirm specifications, should this become necessary
• IP manufactured according to any applicable Good Manufacturing Practice (GMP)
• Proper coding, packaging, and labeling of the IP(s)
• Acceptable IP handling and storage conditions and shelf-life

Record Requirements

As per GIN-7, 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 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.

All sponsor-specific essential documents should be retained for at least two (2) years after formal discontinuation of the trial or in conformance with applicable regulatory requirements.

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: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• 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.

The Guinea-PHC and GIN-5 refer to specimens as biological materials.

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.

Import

No information is available regarding specimen imports.

Export

GIN-5 states that the applicant must provide the National Ethics Committee for Health Research (Comité National d'Ethique pour la Recherche en Santé (CNERS)) with information on the methods used to export biological materials from Guinea. CNERS must evaluate the proposed methods of conservation and transfer to determine whether they are well described and appropriate.

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.

Human Tissues, Cells, and Blood as Starting Material

Per G-ATMP, if tissues and cells are being used as starting materials in a medicinal product, the donation, procurement, and testing of the cells are covered by the HTRegs under the authority of the Human Fertilisation and Embryology Authority (HFEA) for the use of gametes and embryos, which may be used in the derivation (development) of cells in the manufacture of advanced therapy medicinal products (ATMPs), and under HTA for the licensing and inspection for all other tissues and cells. Once the starting materials have been made available, medicines legislation applies to and is regulated by the MHRA.

Per G-ATMP, the HTA and the MHRA have agreed that the collection of blood as a starting material for an ATMP can be carried out under either a tissues and cells license or a blood establishment license.

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.

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.

The Guinea-PHC states that the requirement for consent for research done on biological samples may be waived if it is impossible to locate the donor. However, approval must be granted by the National Ethics Committee for Health Research (Comité National d'Ethique pour la Recherche en Santé (CNERS)).

In accordance with the UK-HTA, Code-A, GBR-59, and GBR-9, prior to collecting, storing, or using a research participant’s specimens (known as relevant material/human tissue in the United Kingdom (UK)), consent from the participant or legal representative and ethics committee (EC) approval must be obtained. The scope of the UK-HTA provisions specifically cover England, Northern Ireland, and Wales. The UK-HTA licensing requirements do not apply in Scotland, with the exception of those provisions relating to the use of DNA. Scotland complies with the Scotland-AnatAct and the Scotland-HTA for the removal, retention, use, licensing, and import of human organs, tissue, and tissue samples specifically removed post mortem, and subsequently used for research.

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. As delineated in the UK-GDPR and UK-DPAct, personal data includes genetic data and biological samples. G-GDPR indicates that 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 UK-GDPR relating to consent do not apply to health and care research, and therefore, do not change the consent requirements to participate in a clinical trial and remove human tissue samples. For more information about the sponsor and investigator’s responsibilities to comply with the data protection requirements (e.g., transparency, safeguards, and data rights), see the Sponsorship topic.

Human Genetic Research Consent Requirements

As set forth in the UK-HTA and GBR-9, the UK-HTA considers it a UK-wide offense to have relevant material/human tissue with the intention of conducting a DNA analysis or using the results of this analysis without “qualifying consent” from a participant or legal representative, unless the information is being used for an “excepted purpose.” The UK-HTA states that “qualifying consent” is consent required in relation to the analysis of DNA manufactured by the human body. An “excepted purpose” is defined as the following:

• Medical diagnosis/treatment
• Coroner purposes
• Crime prevention/detection
• Prosecution
• National security
• Court/tribunal order
• An existing holding to be used for research

In addition to participant consent, EC approval is required for the analysis of DNA in material from the living, where the research is not within the terms of consent for research from the person whose body manufactured the DNA. Please refer to the UK-HTA, GBR-9, and GBR-75 for detailed DNA analysis consent requirements.

Donor Consent Requirements

In accordance with the UK-HTA, Code-A, and GBR-9, prior to removing, storing, or using any living or deceased person’s organs, tissues, or cells for the purpose of research in connection with disorders in, or the functioning of the human body, investigators must obtain “appropriate consent” from the trial participants or their legal representative as well as EC approval. The UK-HTA and Code-A define “appropriate consent” in terms of the person who may give consent. This person may be either the trial participant, the legal representative (referred to as “nominated representative” in the UK-HTA), or, in the absence of either of these, the consent of a person in a “qualifying relationship” with the participant immediately prior to death.

As indicated in the UK-HTA and Code-A, in the case of a living child donor, “appropriate consent” must be obtained from the child’s parent/legal guardian. If the child has died, the written consent must have been obtained from the child’s parent/legal guardian prior to the child’s death in the presence of at least one (1) witness, or it must be signed at the direction of the child concerned by the parent/legal guardian, in the child’s presence, and in the presence of at least one (1) witness.

As indicated in the UK-HTA and Code-A, in the case of an adult donor 18 years or older, consent must be obtained prior to removing any bodily materials. If the adult has died, the written consent is only valid when it is signed by the person prior to death in the presence of at least one (1) witness at their direction, or it is contained in the person’s will. An adult donor may also appoint one (1) or more people (“nominated representative(s)”) to consent on their behalf in the event of death. This consent may be obtained orally or in writing. If the deceased donor has neither provided consent nor an appointed or nominated representative, appropriate consent may be given by someone in a “qualifying relationship” with the donor immediately prior to death. Refer to the UK-HTA and Code-A to obtain a complete list of relatives in hierarchical order who may qualify to provide this consent.

In the case of obtaining materials from an adult donor who lacks the capacity to consent, and neither a decision to consent or not consent is in force, the UK-HTA, the MCA2005, and GBR-9, state that approval by an EC is required. In addition, a living person’s organs, tissues, or cells may be stored and used without consent if the investigator is unable to identify the individual and it is being used for an EC-approved research project. Please refer to the UK-HTA and Code-A for detailed consent requirements.

Per GBR-59, the legal exemptions to consent for research with relevant material are as follows:

• The relevant material is an existing holding held prior to September 1, 2006
• The relevant material is imported
• The relevant material is from a living person when the sample was taken, is non-identifiable, and will be used in research with/pending project-specific EC approval
• The relevant material is from a person who died more than 100 years ago

See the Required Elements and Participant Rights sections for additional information on informed consent.