Comparison: Peru and United Kingdom
Regulatory Authority
Regulatory Authority
Scope of Assessment
Regulatory Fees
Ethics Committee
Ethics Committee
Scope of Review
Ethics Committee Fees
Authorizing Body
Clinical Trial Lifecycle
Submission Process
Submission Content
Timeline of Review
Trial Initiation
Safety Reporting
Progress Reporting
Sponsorship
Definition of Sponsor
Trial Authorization
Insurance
Compensation
Quality, Data & Records Management
Site/Investigator Selection
Informed Consent
Documentation Requirements
Required Elements
Compensation Disclosure
Participant Rights
Special Circumstances/Emergencies
Vulnerable Populations
Children/Minors
Pregnant Women, Fetuses & Neonates
Prisoners
Mentally Impaired
Investigational Products
Definition of Investigational Product
Manufacturing & Import
IMP/IND Quality Requirements
Labeling & Packaging
Product Management
Specimens
Definition of Specimen
Specimen Import & Export
Consent for Specimen
Sources
Requirements
Additional Resources
Forms
To see the single-country view, click on the drop-down menu for the country you do not want to see.
X
Peru
United Kingdom
QUICK FACTS
Spanish Clinical trial application language English
No Regulatory authority & ethics committee review may be conducted at the same time Yes
Yes Clinical trial registration required Yes
Yes In-country sponsor presence/representation required Yes
Under 18 Age of minors Under 16
Unspecified Specimens export allowed Yes
Regulatory Authority > Regulatory Authority
Last content review/update: November 19, 2020

Overview

As per DecreeNo021-2017, the G-CTApplicProc, the G-ClinTrialInspection, and PER-62, Peru’s National Institute of Health (Instituto Nacional de Salud (INS)) is the regulatory authority responsible for clinical trial approvals, oversight, and inspections. The INS, through the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)), grants permission for clinical trials to be conducted in Peru in accordance with DecreeNo021-2017, the G-CTApplicProc, the INS-CTManual, and PER-74.

As indicated in LawNo27657, DecreeNo001-2003, PER-64, PER-75, and PER-65, the INS is a decentralized public executive agency within the Ministry of Health of Peru (Ministerio de Salud del Perú (MINSA)), and was granted authority to approve clinical trials by the MINSA in 2003. The INS’s OGITT carries out the INS’s mandate to review, record, and authorize clinical trials, to regulate research in Peru, and to ensure the implementation of international ethical guidelines and good clinical practice (GCP) in the conduct of clinical trials. In addition, the OGITT implements the INS’s objectives to promote, develop, and disseminate scientific and technological research, propose policies and standards, and provide health services to the Peruvian population. For information on OGITT’s role in clinical trial oversight, see Articles 119 through 128 of DecreeNo021-2017 and the G-ClinTrialInspection.

According to PER-65, the OGITT is also responsible for organizing and maintaining the Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)), the registration system for clinical trials, institutional ethics committees (ECs) (El Comité Institucional de Ética en Investigacións (CIEIs)), research sites, and contract research organizations (CROs) on the national level. (See PER-58 for detailed information on REPEC.)

Please note: Peru is party to the Nagoya Protocol on Access and Benefit-sharing (PER-11), 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 PER-57.

INS Contact Information
Instituto Nacional de Salud
Cápac Yupanqui 1400 - Jesus María
Lima 11
Perú
Phone: (511) 748 1111

or

Av. Defensores del Morro 2268 (Former Huaylas) Chorrillos
Lima 9
Peru
Phone: (511) 748 0000
Email: comunicaciones@ins.gob.pe

OGITT Contact Information
Instituto Nacional de Salud
Oficina General de Investigación y Transferencia Tecnológica
Capac Yupanqui 1400 - Jesus María
Lima 11
Perú
Phone: (511) 748 1111 Annex: 2616
Email: jparillo@ins.gob.pe
Clinical Trial Phone: 511 748 1111 (Ext. 2191)
Clinical Trial Email: consultaensayos@ins.gob.pe

Articles 6 and 32
Preamble, Introduction, Title I (Articles 4, 5, and 6) and Title II (Chapters I and III)
Articles 6, 7, 70, and 119-128
Preamble, Introduction, 4, 6.2-8, and Annex 1
2
Chapter VII (7.5 and 7.12) and Flow Chart No. 04
Last content review/update: April 22, 2021

Overview

As per the MHCTR and the MHCTR2006, the Medicines and Healthcare Products Regulatory Agency (MHRA) is the regulatory authority responsible for clinical trial approvals, oversight, and inspections in the United Kingdom (UK). The MHRA grants permission for clinical trials to be conducted in the UK in accordance with the MHCTR and the MHCTR2006.

According to GBR-57, the MHRA is an executive agency within the Department of Health and Social Care (DHSC), which grants the MHRA authority to regulate and license all medicines and medical devices within the UK. Per the G-CTAuth, the agency’s Clinical Trials Unit (CTU) focuses specifically on reviewing applications to conduct clinical trials of medicinal products.

Pursuant to 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: United Kingdom 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

MHRA
10 South Colonnade
Canary Wharf
LONDON
E14 4PU
UK

Phone: +44 020-3080-6000
Fax: +44 0203-118-9803
General Email:
info@mhra.gov.uk

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

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

Part 2 (Chapter 1)
Amendment of Schedule 1 to the Principal Regulations (27 - Part 2, Conditions Based on Article 3 of the Directive)
Part 1(4) and Part 3 (12, 17, and 18)
Clinical Trials Named Contact and Urgent Safety Measures
Regulatory Authority > Scope of Assessment
Last content review/update: November 19, 2020

Overview

In accordance with DecreeNo021-2017, the INS-CTManual, the G-CTApplicProc, the G-CTSubmissionProcs, and PER-71, Peru’s National Institute of Health (Instituto Nacional de Salud (INS)) is responsible for reviewing and approving clinical trial applications for drugs to be registered in Peru. As per DecreeNo021-2017 and DecreeNo016-2011, the scope of the INS’s assessment includes Phases I through IV clinical trials for pharmaceuticals including medicines, herbal medicines and other complementary products, dietetic products and sweeteners, biological products, and compounded (galenic) products. In addition, per ResolutionNo233-2020, the INS must ensure the governance of all health research involving human beings (e.g., clinical trials, epidemiological, behavioral, and observational research, etc.) is conducted ethically.

ResolutionNo686-2020, an INS technical health standard for preclinical and clinical research with vaccines in Peru, further states that clinical studies of vaccines in humans must be conducted in accordance with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (PER-53) and current national clinical trial regulations (DecreeNo021-2017). Per ResolutionNo686-2020, clinical trials in vaccines are recommended to demonstrate the efficacy and safety of new vaccines as long as they are not licensed for their use by regulatory agencies. Prospective observational studies could also be carried out later to estimate the effectiveness of the new vaccine. Refer to ResolutionNo686-2020 for detailed information and requirements associated with the clinical studies of vaccines.

As specified in DecreeNo021-2017, the INS-CTManual, the G-CTApplicProc, and PER-61, the INS’s review and approval of a clinical trial application is dependent upon obtaining proof of approval from an accredited institutional ethics committee (EC) (El Comité Institucional de Ética en Investigación (CIEI)). Therefore, the INS and EC reviews may not be conducted in parallel. Per the INS-CTManual and the G-CTApplicProc, EC approval of the research protocol and informed consent form must be submitted as part of the clinical trial application dossier in order for the INS to conduct its review. Refer to the INS-CTManual and the G-CTApplicProc for additional submission information. Per ResolutionNo0423-2019, the application for clinical trial authorization and corresponding instructions are in PER-24 and PER-10, respectively.

Per the INS-CTManual, the G-CTApplicProc, PER-60, and PER-59, the sponsor and his/her contract research organization (CRO) must also register with the Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) prior to submitting an application for clinical trial authorization. Refer to the INS-CTManual, the G-CTApplicProc, PER-60, and PER-59 for detailed registration instructions, and PER-37 and PER-36 for the sponsor and CRO registration forms. See also the Sponsorship topic, Trial Authorization subtopic for more detailed sponsor/CRO registration information. In addition, per DecreeNo021-2017 and the G-CTApplicProc, the sponsor must also ensure authorization by the research institution where the clinical trial will be carried out.

DecreeNo021-2017 states that the investigational product (IP) must meet at least one (1) of the following conditions to be authorized for use in clinical trials in Peru:

  • Must be approved for use in humans by drug regulatory authorities of countries with high health surveillance
  • Will serve to establish pharmaceutical therapeutic equivalence
  • Is considered a priority for the country’s public health or is within the scope of MINSA policies and/or research priorities
  • At the request of the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)), requires a clinical trial to support its efficacy and safety for the health registry

Clinical Trial Review Process

As per the INS-CTManual, the G-CTApplicProc, the G-CTSubmissionProcs, and PER-71, the sponsor or his/her CRO must submit the application electronically using the REPEC, at which time a registration code is assigned to the application. According to DecreeNo021-2017, DecreeNo016-2011, the INS-CTManual, the G-CTApplicProc, and the G-CTSubmissionProcs, the sponsor or his/her CRO must also obtain approval from the ANM to manufacture or import IPs in Peru. (Note: The ANM is also referred to as the General Directorate of Medicines, Supplies and Drugs (La Dirección General de Medicamentos Insumos y Drogas (DIGEMID)). As per DecreeNo021-2017, Peru’s INS must approve the clinical trial application prior to ANM’s approval of an IP. However, the INS does request that ANM assess the safety and quality profile of the IP to be used in a clinical trial as part of its application review and approval process.

As per LawNo27444, and DecreeNo004-2019 which modifies LawNo27444, the INS is required to complete its review and approval of a clinical trial application in a maximum of 30 working days (including the 30 days for the ANM per DecreeNo021-2017). In addition, per DecreeNo021-2017 and the INS-CTManual, if the clinical trial is related to an IP for the prevention, diagnosis, or treatment of tuberculosis or HIV/AIDS infection, the specific technical opinion of the General Directorate of Strategic Public Health Interventions will be requested to ensure the study does not interfere with its strategic interventions regarding these diseases.

DecreeNo021-2017 also notes that the INS will be able to convene a technical commission of experts when controversial situations arise during the authorization process. In addition, the sponsor has the right to appeal when the INS does not grant authorization.

DecreeNo021-2017 and the INS-CTManual state that the INS’s General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)) grants clinical trial authorization for the total period of time scheduled for its completion as indicated in the REPEC registration form submission.

Further, per DecreeNo021-2017, once the INS has completed the authorization process, the agency will post the following information regarding an authorized and unauthorized clinical trial on its website: study title, sponsor and investigators, IP, condition under study, study design, and number of participants included that have been considered within the World Health Organization test data set. (See the Clinical Trial Lifecycle topic, Submission Process, Submission Content, and Timeline of Review subtopics for detailed submission and review requirements.)

In addition, as indicated in DecreeNo021-2017, the clinical trial authorization will be valid for a maximum of 12 months from the date of its issuance. This period of validity is valid for all research centers, regardless of the authorization date of its operation. The clinical trial authorization is granted by the total period of time scheduled for execution, which was registered in the authorization request.

DecreeNo021-2017, ResolutionNo655-2019 which modifies DecreeNo021-2017, PER-67, and PER-27 provide information on how the sponsor or his/her CRO should request a trial extension. The following documents must be submitted within 30 calendar days prior to the trial’s expiration:

  • Application for extension of time (using the REPEC e-form (PER-27) (amended version per ResolutionNo0423-2019))
  • Report justifying the reasons for submitting the request
  • Approval of the extension granted by the legal representative of the research institution(s) where trial will be conducted
  • Approval of the extension by an INS-accredited EC
  • Proof of payment of processing fees
  • Current insurance policy

The authorized trial extension will be valid for a maximum of 12 months from the date of issue.

Article 35
Introduction
5.2
Preamble, Article 1, and Annexes (3 and 5)
Annexes A and B
Article 39
Title I (Article 2) and Title II (Chapters I and V)
Articles 2, 6, 7, 8, 10, 40, 74, 76, 52, 59, 63, 67-74, 80, 94, 119-121, Complementary Provisions - Final (Eighth), and Annexes 1-5
1, 2, 4, and 5
2, 4, and 6
Chapter VII (7.1, 7.2, 7.3, and 7.5), Flow Chart No. 01, 02, and 04, and Annexes 1 and 3
Bodies of the Vice Ministerial Office of Public Health - General Directorate of Strategic Public Health Interventions
Extension of Clinical Trial Time
Last content review/update: June 29, 2021

Overview

In accordance with the MHCTR and the MHCTR2006, the Medicines and Healthcare Products Regulatory Agency (MHRA) is responsible for reviewing, evaluating, and approving applications for clinical trials using registered or unregistered investigational products (IPs). (Note: IPs are known as investigational medicinal products (IMPs) in the United Kingdom (UK)). The MPHFR and the G-CTApp specify that the scope of the MHRA’s assessment includes all clinical trials (Phases I-IV). The G-CTApp permits MHRA’s review process to be conducted in parallel with the ethics committee (EC) review, stating that an EC opinion may be obtained before, during, or after the MHRA application submittal. However, pursuant to the MHCTR and the MHCTR2006, the clinical trial must be authorized by the MHRA, and an EC established and recognized by the United Kingdom Ethics Committee Authority (UKECA) must provide a favorable opinion in relation to the trial prior to the trial’s commencement. (See the Ethics Committee topic for detailed information on the EC review and approval process.)

Brexit

Per the G-MHRASubmiss, Brexit, the EUCouncil-Brexit, the WithdrlAgrmt, and the G-AfterTransition, the UK withdrew from the European Union (EU) on January 31, 2020. The MHRA has updated and published clinical trials guidance that became effective on January 1, 2021; these guidance documents are referenced and described throughout this profile. G-AfterTransition summarizes the guidance to sponsors and researchers from January 1, 2021. Furthermore, the G-MHRASubmiss describes how to make regulatory submissions to the MHRA starting on January 1, 2021, including all clinical trial submissions (initial applications, 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 GBR-114 explains that as a result of the Northern Ireland Protocol, different rules will apply in Northern Ireland than in Great Britain (which covers England, Wales, and Scotland). Broadly, Northern Ireland will continue to follow the EU regulatory regime (e.g., GBR-21), but its national competent authority will remain the MHRA. 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 investigational products for clinical trials from January 1, 2021, 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.”

Per GBR-54, the EU Clinical Trials Regulation (GBR-21) is expected to come into application on January 31, 2022. Per the GBR-115, the UK is committed to being as aligned as possible with GBR-21. The MMDAct grants authority for regulations to be made that correspond or are similar to GBR-21. Per GBR-71 and GBR-86, GBR-21 will harmonize the rules for conducting clinical trials throughout the EU.

Clinical Trial Review Process

Application Submission

Per the G-MHRASubmiss, as of January 1, 2021, MHRA started new processes to submit regulatory and notification information to the UK. For clinical trial applications to the UK, including initial applications, substantial amendments, end-of-trial notifications, and DSURs, applicants must submit information through the UK’s national portals. Per the G-CTApp, the applicant must complete the clinical trial application form on the Integrated Research Application System (IRAS) (GBR-78) and submit the form via MHRA Submissions (GBR-13) with the rest of the required documents. Note, per GBR-18 and GBR-17, every clinical trial must include a unique European Clinical Trials Database (EudraCT) number (GBR-87). This number must be included on all clinical trial applications and as needed on other documents relating to the trial (e.g., safety reports). To obtain a EudraCT number, follow the instructions at GBR-17 and GBR-87. The steps for gaining access to MHRA Submissions (GBR-13) are contained in the G-MHRASubmiss and GBR-11. (See Clinical Trial Lifecycle topic, Submission Process subtopic for additional details.)

The MHCTR, the G-CTApp, and GBR-23 specify that the MHRA coordinates the clinical trial application process. Per GBR-23, upon receipt of a clinical trial application, the MHRA’s Clinical Trials Unit (CTU) validates it and sends the sponsor or his/her designated legal representative an acknowledgement. The G-CTApp states that MHRA has moved from paper to 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. If the application is valid, the CTU assessment period begins from the date of receipt (Day 0). If the application is not valid, the sponsor or his/her designated representative will be informed of the deficiencies, and he/she must provide a completely new application. According to the MHCTR, if the sponsor or his/her designated representative does not receive a request for additional information from the MHRA within 30 days, the application is considered as authorized. (See the Clinical Trial Lifecycle topic, Timeline of Review subtopic for additional details.)

In addition, as stated in the G-CTApp, certain first-in-human (Phase I) trials with specific risk factors may require the MHRA’s CTU to seek advice from an Expert Advisory Group/the Commission on Human Medicines before giving approval. See the G-CTApp for examples of which trials require expert advice and for detailed requirements.

Notification Scheme Submission

As set forth in the G-CTApp and GBR-23, in lieu of a standard application, a sponsor or his/her designated representative may submit a notification of a clinical trial to the MHRA under the Notification Scheme when conducting “Type A” trials. Type A trials are those in which the potential risk associated with an IP is determined to be no higher than that of standard medical care, and involve medicinal products licensed in any EU Member State that meet the following criteria:

  • They relate to the licensed range of indications, dosage and form, or,
  • They involve off-label use established by practice and supported by published evidence and/or guidelines

See the G-CTApp and GBR-23, for detailed Notification Scheme requirements.

Upon receipt of a valid notification, the MHRA will send an acknowledgement to the sponsor or his/her designated representative stating that the trial may proceed if it does not raise an objection within 14 days. If the MHRA does not send a Notification Objection letter, the acknowledgement serves as the authorization. The G-CTApp states that MHRA has moved from paper to 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.

If the MHRA raises objections, the submission is assessed as a standard request for authorization (refer to information under the Application Submission heading above), and the CTU initial assessment is performed within 30 days of receipt of a valid application.

Governance Approval

Per GBR-78, all project-based research must also apply for governance and legal compliance approvals from the appropriate lead UK Health Department. The Integrated Research Application System (IRAS) (GBR-78) facilitates this process. As described in GBR-96 and GBR-67, approval from the Health Research Authority (HRA) is required for all project-based research in the National Health Service (NHS) 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 R&D 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.

(See the Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics for detailed submission requirements.)

Part 2 (Chapter 1)
Introduction and Article 1
Schedule 2 (Part 1(1))
Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 1 (2), Part 2 (5, 6, and 7), Part 3 (12, 14, 15, 17, and 18), and Schedule 2
When a Clinical Trial Authorization (CTA) is Needed, Trial Sponsor and Legal Representative, Registration of Your Clinical Trial, Ethics Committee, Clinical Trial Authorization Application Form, Documents to Send with Your Application, Assessment of Your Submission, and Notification Scheme
Part 4 (Article 126)
6
3
Help (Preparing and Submitting Applications)
Regulatory Authority > Regulatory Fees
Last content review/update: November 19, 2020

Overview

According to PER-77, new regulatory fees are going to be approved. Currently, the National Institute of Health (Instituto Nacional de Salud (INS)) is not receiving payments. An email may also be sent to consultaensayos@ins.gob.pe for any additional fee-related questions.

While the INS is not currently receiving payments, per DecreeNo021-2017, the G-CTSubmissionProcs, and PER-77, the sponsor or his/her contract research organization (CRO) is typically responsible for paying a fee, as applicable, to the INS to submit a clinical trial application for authorization. Additionally, per DecreeNo021-2017, INS payment is required to modify the trial as follows: to increase the number of research centers participating in a study; to change the sponsor or CRO under contract; to change the principal investigator; to request a time extension for the trial; to request authorization to change the trial name; or to request authorization to amend a report. Per ResolutionNo0423-2019, the forms required to modify the trial may be obtained from PER-26, PER-27, PER-28, PER-43, and PER-31. The G-CTSubmissionProcs also indicates that the INS reimburses processing fees when an application is cancelled.

Pursuant to ResolutionNo655-2019, which modifies DecreeNo021-2017 and the G-CTApplicProc, in the case of multicenter clinical trials, the sponsor or his/her CRO must submit a clinical trial application along with proof of payment information for the processing fee rather than requiring each of the participating research sites in Peru to submit their payment separately, as originally required.

Preamble, Article 1, and Annexes (4-6, 8, and 10)
Annexes A and B
Articles 67, 76, 78-80, 87, and 88
5
6
Clinical Trial Authorization Renewal, Extension for a Clinical Trial, Addition of New Research Sites
Last content review/update: April 22, 2021

Overview

As per the MHCTR, the MHCTR2006, the G-CTApp, and the G-MHRAFees, the sponsor or his/her designated representative is responsible for paying a fee to the Medicines and Healthcare Products Regulatory Agency (MHRA) to submit a clinical trial application for authorization. According to the G-MHRAPaymt, applicants do not need to attach proof of payment to applications. Applicants will receive an invoice to make a payment for the correct amount after validation of the application. Applicants must pay invoices upon receipt or they will incur penalty fees.

As delineated in the G-MHRAFees, the MHRA levies the following clinical trial processing fees, which will remain in effect through 2022:

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

The G-CTApp further indicates that no fees are required for applications submitted and authorized under the Notification Scheme. However, if the MHRA raises an objection to the notification, the submission is treated as a standard request for authorization and an assessment of the submission is carried out with associated fees.

Instructions for Payment of Clinical Trial Application Fees

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

Account Name: MHRA
Account Number: 10004386
Sort code: 60-70-80
Swift code: NWBKGB2L
IBAN: GB68NWBK60708010004386
Bank: National Westminster Bank

Bank address:
National Westminster Bank
RBS, London Corporate Service Centre, 2nd Floor
280 Bishopsgate
London
EC2M 4RB
UK

Credit or debit card payments may be made using MHRA’s online payments service (GBR-26).

Remittance advice notices can be sent to sales.invoices@mhra.gov.uk and should include the relevant invoice number on the remittance advice. MHRA cannot accept any documentation sent by postal mail service. Further information can be obtained by emailing sales.invoices@mhra.gov.uk or calling +44 (0)20 3080 6533 or +44 (0)30 3080 6533. G-MHRAPaymt further provides that invoice disputes/queries should be emailed to Clinical Trial Applications (CTA invoices) at ctdhelpline@mhra.gov.uk and cc: sales.invoices@mhra.gov.uk.

11, 13, and Explanatory Note
Part 3 (17)
Notification Scheme and Fees
8 (Clinical trials: application fees)
Ethics Committee > Ethics Committee
Last content review/update: March 10, 2021

Overview

As set forth in DecreeNo021-2017, the INS-CTManual, the G-CTApplicProc, PER-71, and PER-61, Peru requires clinical trial approval from an institutional ethics committee (EC) (El Comité Institucional de Ética en Investigación (CIEI)) that is accredited by the National Institute of Health (Instituto Nacional de Salud (INS))’s National Registry of Accredited Institutional Ethics Committees (PER-61). There are no stated requirements regarding which EC the sponsor should choose to conduct the clinical protocol review. As noted in DecreeNo021-2017, those research institutions that do not have an accredited EC may select another INS-accredited EC, preferably located in the same region. Per ResolutionNo655-2019, which amends DecreeNo021-2017, the application for accreditation/renewal of accreditation has been modified to be only an application for accreditation. Refer to PER-61, PER-20, and PER-21 for additional EC accreditation requirements and standards.

In addition, ResolutionNo233-2020, which now requires all ECs that conduct human health research be registered with the INS, explains that if the entities or institutions do not have an EC, they may select another INS-registered EC to evaluate their investigations. This arrangement may occur following a written agreement between the authorities of the entities or institutions involved and the respective EC. According to PER-77, INS-registered ECs are only required to obtain accreditation if they are conducting a review of a clinical trial protocol.

ResolutionNo233-2020 further states that ECs should have the goal of carrying out scientific research as one (1) of their main objectives. An EC may be constituted within a public, private, or mixed health institution that provides health services and is registered with the National Registry of Institutions that Provide Health Services (Registro Nacional de Instituciones Prestadoras de Servicios de Salud (RENIPRESS)). Refer to PER-80 for instructions on how to register a health service provider institution in RENIPRESS. An EC may also be an entity within the Ministry of Health of Peru (Ministerio de Salud del Perú (MINSA)), one (1) of the Peruvian universities, or a non-profit legal organization. Per ResolutionNo233-2020, ECs are constituted by statute, resolution, or other document that establishes, as a minimum, among others, the committee’s mission, its members, and their respective positions. The health institutions or entities may constitute more than one (1) EC in order to fulfill their requirements in the field of health research with human beings. DecreeNo021-2017, PER-21, and ResolutionNo233-2020 note that infrastructure requirements for the operation of institutional ECs must include ensuring work environments that guarantee confidentiality and computer equipment with sufficient capacity, providing administrative staff, and ensuring the availability other resources necessary for its operation.

Peru’s Institutional Research Ethics Committee of the National Institute of Health (El Comité Institucional de Ética en Investigación del Instituto Nacional de Salud (CIEI-INS)) does not approve clinical trials.

Institutional EC Composition

As delineated in DecreeNo021-2017 and ResolutionNo233-2020, institutional ECs should consist of at least five (5) members represented by a multidisciplinary group of professionals and community members, including (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

  • Persons with knowledge in research methodology and with scientific expertise in the health field, including those with expertise in behavioral or social sciences
  • Persons with expertise in ethical matters
  • Persons with expertise in legal matters
  • Community representatives, whose primary function is to share their views on the communities where the research participants are likely to come from
  • At least one (1) titular member that must be from the community and not belong to the field of health or to the research institution

In addition, all members must have at least one (1) certificate of basic training in research ethics and one (1) of its members must have training in bioethics. The EC should seek the assistance of expert consultants on different topics when it lacks the knowledge and experience necessary to evaluate the protocol. Furthermore, the authorities, managers, or the main persons in charge of the entities and institutions that constitute the ECs cannot be members or preside over the members; the list of all members must be publicly accessible.

Terms of Reference, Review Procedures, and Meeting Schedule for Institutional ECs

Pursuant to DecreeNo021-2017 and ResolutionNo233-2020, ECs must have stated rules and prepare a procedures manual that is approved by the research institution. The rules should establish composition, procedures, and internal requirements, and other acts for the EC’s operation. Per DecreeNo021-2017 and ResolutionNo233-2020, the manual must provide rules and procedures for the following (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

  • Conditions and terms of member appointments
  • EC structure
  • Member responsibilities
  • Meeting frequency
  • Specific quorum requirements
  • Filing dossier administrative requirements
  • Monitoring authorized research protocols
  • Preparing and approving meeting minutes
  • Filing related documentation
  • Submitting research projects for review
  • Assessing the types of review (i.e., whether a project requires ethical review or should be exempt)
  • Classifying decisions adopted and processes to communicate these decisions
  • Developing the mechanism for reconsidering decisions adopted by the EC
  • The follow-up and monitoring of research investigations, from the moment approved until terminated early or terminated (including presenting amendments, deviations, adverse events, etc.)
  • Seeking specialist(s) advice on diseases or methodologies outside the EC’s expertise
  • Ensuring alternate committee members have been selected
  • Replacing a member with a conflict of interest
  • Documenting EC activities in meeting minutes
  • Promoting collaboration with other ECs and other stakeholders involved in health research with human beings

See Title IV, Chapter 7 of DecreeNo021-2017 and ResolutionNo233-2020 for detailed EC requirements.

VII (7.2) and VIII (8.2 and 8.3)
Annex B
Articles 40, 59, 61-66, 71, 102, and Complementary Provisions - Final (Eighth)
4 and 6
Annexes 1 and 3
Last content review/update: June 29, 2021

Overview

As set forth in GAfREC and GBR-9, the United Kingdom (UK) has a centralized recognition process for ethics committees (ECs), (known as research ethics committees (RECs) in the UK). Per GAfREC and GBR-9, the UK Health Departments have authorized the Research Ethics Service (RES) (GBR-62) in England, within the Health Research Authority (HRA), to serve as the lead administrative body to coordinate the development of operational systems for ECs. See GAfREC for more detail about HRA functions related to the RES in the United Kingdom. ECs are recognized or established by the United Kingdom Ethics Committee Authority (UKECA), the HRA, or the Ministers of Health Departments of the four (4) UK nations (England, Northern Ireland, Scotland, and Wales).

As stated in GAfREC, the RES encompasses England’s Department of Health and Social Care (DHSC), Northern Ireland’s Department of Health, the Scottish Government Health and Social Care Directorates, 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 England’s HRA to perform some functions on behalf of the other head offices. A list of recognized ECs within the RES is available through GBR-95.

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. In accordance with the MHCTR and the MHCTR2006, ECs recognized to conduct reviews of clinical trials for investigational medicinal products (CTIMPs) are authorized by the statutory body, the UKECA, and are of central importance in this topic. Please refer to the Ethics Committee topic, Authorizing Body subtopic for additional details on the RES and the UKECA.

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. For detailed EC procedures and information on other administrative processes, see GAfREC, GBR-113, and GBR-9.

Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 2, Part 3 (11, 12, 14, 15, 17, and 18), and Schedule 2
1 - 6, Glossary, Annex C, Annex E, and Annex F
Introduction (Purpose and Scope, and Implementation), Terminology (Glossary), and Sections 1, 2, and 3
Foreword, Introduction, 1.24, 1.27, 2.6, 3, and 5.11
Ethics Committee > Scope of Review
Last content review/update: November 19, 2020

Overview

According to DecreeNo021-2017, ResolutionNo233-2020, and the G-EC-CTReview, the primary scope of information assessed by institutional ethics committees (ECs) (El Comité Institucional de Ética en Investigacións (CIEIs)) relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial. The EC scope also aligns with the principles delineated in the PeruConstitution and DecreeNo011-2011-JUS, which assert that the defense of the human person and respect for his/her dignity are the supreme goal of society and the state.

As per DecreeNo021-2017, DecreeNo011-2011-JUS, and the G-EC-CTReview, ECs must also pay special attention to reviewing informed consent and to protecting the welfare of certain classes of participants deemed to be vulnerable. Per DecreeNo021-2017, when a clinical trial is proposed for subordinate groups (e.g., students, health workers, employees, military members, police, prisoners, etc.), one or more members of the population under study, or another person within this community capable of guarding the conditions and human rights that correspond to the group in question, should participate in the EC review. (See Informed Consent topic, and the subtopics of Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired for additional information about these populations).

DecreeNo021-2017, the G-EC-CTReview, and ResolutionNo233-2020 also state that the National Institute of Health (Instituto Nacional de Salud (INS))-registered and accredited institutional 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.

ResolutionNo233-2020 further explains that the research studies should also consider the scientific validity and social value of the research; the equitable selection of research participants; the adequacy of the informed consent process; respect for the participants; and the participation and commitment of the communities. The Council for International Organizations of Medical Sciences’ (CIOMS) International Guidelines for Health-Related Research Involving Humans (PER-78) is referenced for further information on the previously listed ethical criteria. On a related note, ResolutionNo686-2020, an INS technical health standard for preclinical and clinical research with vaccines in Peru, states that in the ethical review of clinical studies of vaccines in humans, ECs must comply with the ethical criteria delineated in ResolutionNo233-2020, which are, in turn, based on the previously discussed CIOMS ethical guidelines (PER-78). As indicated in ResolutionNo686-2020, in all deliberations, ECs must ensure the following ethical criteria are present: social value and scientific validity of the research; favorable benefit/risk balance and risk minimization; fair selection of research subjects; informed consent process; respect for people; and community participation and commitment. Therefore, per ResolutionNo686-2020, an EC decision regarding the approval or disapproval of a vaccine clinical study protocol must have a solid and justified ethical basis in the aforementioned CIOMS criteria (PER-78).

In addition, per ResolutionNo233-2020, research entities or institutions must have policies of scientific integrity, in accordance with international standards on the matter and the National Code of Scientific Integrity (PER-79), which includes appropriate investigation and sanction procedures. Per DecreeNo021-2017, ECs must also conduct regular monitoring, with a frequency based on the degree of risk to participants, but no less than once a year, and suspend or cancel the trial when participants are exposed to uncontrolled risk. ResolutionNo233-2020 also states that the EC should monitor the progress of an approved research project until it has concluded. See DecreeNo021-2017, the G-EC-CTReview, and ResolutionNo233-2020 for detailed ethical review guidelines. Refer to PER-43 and PER-31 to submit an application for research center closure or to cancel a clinical trial using recently amended forms per ResolutionNo0423-2019.

Role in Clinical Trial Approval Process

As per DecreeNo021-2017, the INS-CTManual, the G-CTApplicProc, and the G-EC-CTReview, an INS-accredited EC must approve the clinical trial protocol and informed consent form prior to the sponsor or his/her contract research organization (CRO) submitting the clinical trial application to the INS. Therefore, the INS and EC reviews may not be conducted in parallel.

According to PER-77, each institutional EC determines its own review and approval timeline and continuing review requirements based on its internal regulations and standard operating procedures.

(See the Clinical Trial Lifecycle topic, Submission Process and Timeline of Review subtopics for detailed submission process and timeline details.)

Chapter 1 (Articles 1 and 2) and Chapter 2 (Article 7)
I, VII (7.2-7.4), and VIII (8.2 and 8.3)
5.2
Preamble, Article 1, and Annexes (8 and 10)
Preamble, Introduction, II (1 and 3), and V (1)
Articles 9, 24, 58-60, 67, and 70
Preamble, VII, Ethical Criterion 1, Ethical Criterion 5, and Annex 3
4, 6, and Annexes 1 and 3
Annexes 1 and 3
Last content review/update: June 29, 2021

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) recognized by 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).

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 Informed Consent topic and the subtopics of Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired for additional information about these populations).

As indicated in GAfREC, the MHCTR, the MHCTR2006, 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.

Role in Clinical Trial Approval Process

As described in GBR-9, GBR-66, GBR-111, 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. As discussed in the preceding subtopic, ECs recognized to conduct reviews of clinical trials for investigational medicinal products (CTIMPs) must be authorized by the United Kingdom Ethics Committee Authority (UKECA). Per GAfREC, 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 CTIMPs.

As indicated in the MHCTR, the MHCTR2006, and GAfREC, CTIMP applications require the favorable opinion of a UKECA-recognized EC, and approval by the Medicines and Healthcare Products Regulatory Agency (MHRA) prior to the sponsor or his/her designated legal representative initiating the trial. The G-CTApp permits MHRA’s review process to be conducted in parallel with the EC review, stating that an EC opinion may be obtained before, during, or after the MHRA application has been electronically submitted to the Integrated Research Application System (IRAS) (GBR-78). Therefore, to prepare an EC application, an IRAS account must be created. 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, the chief investigator (CI) must submit the electronic application to IRAS on the same day that a booking is made to schedule an EC review through the NHS Research Ethics Committee (REC)’s Online Booking Service (GBR-95). (See the Clinical Trial Lifecycle topic, Trial Initiation subtopic for additional information.)

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

Per GBR-68, unless an application is being processed under the proportionate review service (see GBR-31), 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, and will make one (1) of the following decisions:

  • Favorable opinion
  • Favorable opinion with additional conditions
  • Provisional opinion
  • Unfavorable opinion

GAfREC, the MHCTR, and GBR-9 also 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 Clinical Trial Lifecycle topic, Submission Process subtopic and Timeline of Review subtopic for detailed submission process requirements.)

Per GBR-116, a new fast-track research ethics review pilot opened in January 2021. The pilot is testing a rapid research ethics review for global clinical trials and phase I trials for any disease area (excluding trials that require review by the Gene Therapy Advisory Committee). The pilot—which runs until at least June 2021—tests whether the Health Research Authority (HRA), on behalf of the UK, can establish a sustainable model for providing rapid research ethics review. The pilot aims to provide a final opinion on applications within 15 calendar days, excluding the time for applicants to respond to any requests for further information after initial review. Clinical trials interested in joining the pilot should email fasttrack.rec@hra.nhs.uk for more information, and applications should be prepared using GBR-78.

While there is no stated expiration date for an EC approval in the MHCTR, GAfREC, or the Additional Resources, IRAS (GBR-78) requires identification of 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. See GBR-98 for guidance on what changes qualify as a substantial amendment, which requires notification to the EC and MHRA.

Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Amendment of the Clinical Trials Regulations; Amendment of the Adults with Incapacity (Scotland) Act 2000
Part 1 (2 and 3), Part 3 (11, 12, 14, 15, 17, and 18), Schedule 2, and Schedule 3 (Part 1)
Ethics Committee
2.3, 3, 4.3, and 5.4
1 and 2
Introduction (Purpose and Scope), Terminology (Glossary), and Sections 1, 3, and 5
Foreword, 1.27, 2, and 3
Definitions of Authorised REC and Recognized REC
Using IRAS, Preparing and Submitting Applications, Maintaining Your Approvals, End of Research, FAQs, and Documentation
Ethics Committee > Ethics Committee Fees
Last content review/update: November 19, 2020

Although specific ethics committees (EC) fees are not provided in Peru’s regulatory sources, per ResolutionNo233-2020, the entities and institutions that constitute an EC must provide the committee with all the economic, human, logistical, infrastructure, or other resources necessary for its operation.

Please refer to PER-70 for an example of 2020 fees that an accredited institutional EC is currently charging to conduct research reviews.

VII (7.2)
Last content review/update: December 08, 2020

Overview

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, per GAfREC, EC members receive no payment for contributing to the application review process at scheduled meetings or for attending these meetings.

4.3
Ethics Committee > Authorizing Body
Last content review/update: November 19, 2020

Overview

As set forth in DecreeNo001-2003, Peru’s National Institute of Health (Instituto Nacional de Salud (INS)) is the central body responsible for the oversight, promotion, and coordination of research. The INS is a decentralized public agency of the Ministry of Health of Peru (Ministerio de Salud del Perú (MINSA)).

Registration, Auditing, and Accreditation

As delineated in DecreeNo021-2017, the INS-CTManual, the G-CTApplicProc, the G-EC-CTReview, and PER-61, the INS’s General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)) is responsible for registering and accrediting institutional ethics committees (ECs) (El Comité Institucional de Ética en Investigacións (CIEIs)) listed in the INS’s Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) to review and approve clinical trials. The OGITT must evaluate and verify the EC‘s compliance with the registration and accreditation standards established in the INS-CTManual. DecreeNo021-2017 created the National Registry of Accredited Institutional Ethics Committees (PER-61) under this regulation in 2017.

ResolutionNo233-2020 further notes that the INS is responsible for managing and maintaining the public database of nationally registered ECs; providing advice, guidance and technical assistance to ECs and their entities or institutions; organizing training and education activities for EC members and researchers; promoting integration and cooperation networks among participating ECs; promoting relations between the ECs and different entities linked to the research ethics field; providing access to international resources to strengthen research ethics; establishing flexible review procedures and mechanisms appropriate for an expedited and rigorous ethical review of human health research in disaster situations and disease outbreaks; and assigning the INS’s OGITT to disseminate information and supervising ECs at the national level per the ethical research guidelines delineated in ResolutionNo233-2020.

Per ResolutionNo655-2019, which amends DecreeNo021-2017, the electronic accreditation application form (FOR-OGITT-025) should only be submitted for the initial accreditation approval and not for accreditation renewal (see PER-20 for the form). In addition to completing form FOR-OGITT-025, the applicant should electronically submit form FOR-OGITT-026 (PER-21) to demonstrate compliance with the accreditation standards delineated in the INS-CTManual. As part of this submission process, the applicant should complete and electronically submit the EC registration application form located on the National Registry of Accredited Institutional Ethics Committees website (PER-61). Once the form is submitted, the user will receive a temporary EC registration number. The completed form should be printed, signed, and attached along with the other accreditation documents required to be sent to the OGITT via the Documentary Procedure Office located in the INS headquarters (refer to PER-61 for detailed information).

DecreeNo021-2017 and the INS-CTManual, state that accreditation is temporary and must be renewed every three (3) years. Per DecreeNo021-2017, ResolutionNo655-2019 (which amends DecreeNo021-2017), and the INS-CTManual, The following accreditation requirements must be completed:

  • Copy of the resolution/decision issued by the highest authority of the research institution authorizing EC operation
  • Copy of institutionally approved EC regulations and its Manual of Procedures submitted in electronic form (editable PDF)
  • Affidavit of compliance with INS-CTManual accreditation standards (PER-21) per ResolutionNo0423-2019
  • Curriculum vitaes signed by each EC member submitted in electronic form (editable PDF)

The INS-CTManual further recommends that applications for EC accreditation renewals be submitted 30 calendar days before the end of term. DecreeNo021-2017 further grants a grace period of one (1) year following the approval of the updated INS-CTManual for ECs to comply with the accreditation requirements listed above.

Refer to the INS-CTManual and PER-61 for detailed submission instructions, and PER-20, PER-21, and PER-35 for the recently amended EC accreditation application and EC affidavit of compliance forms per ResolutionNo0423-2019.

Additionally, the INS-CTManual provides detailed information on the inspections that the INS-accredited ECs may be subject to before, during, and after the registration of an EC.

(Please note that Peru is in the process of finalizing new guidelines as well as the associated forms and instructions to support the ResolutionNo655-2019 and ResolutionNo0423-2019 amendments to DecreeNo021-2017; ClinRegs is monitoring these developments.)

VII (7.4) and VIII (8.1 and 8.2)
Preamble, Article 1, and Annexes (2-3)
Annex B
Title I, Title II (Chapters I and III)
Article 63 and Complementary Provisions - Final (Eighth)
Preamble and VII
4 and 6
Chapter VII (7.3, 7.4 and 7.9) and Flow Charts No. 02, 03, and 17
Last content review/update: June 29, 2021

Overview

Research Ethics Service

As stated in GAfREC, the United Kingdom (UK) Health Departments’ Research Ethics Service (RES) (GBR-62) encompasses England’s Department of Health and Social Care (DHSC), Northern Ireland’s Department of Health, the Scottish Government Health and Social Care Directorates, the Welsh Government’s Department of Health and Social Care, as well as authorized ethics committees (ECs) (known as research ethics committees (RECs) in the UK). The UK Health Departments have authorized the Health Research Authority (HRA), which is sponsored by England’s DHSC, to serve as the lead administrative body to coordinate the development of RES operational systems for ECs recognized or established by the United Kingdom Ethics Committee Authority (UKECA), the HRA, or the Ministers of Health Departments of the four (4) UK nations (England, Northern Ireland, Scotland, and Wales), including their respective head offices.

A head office represents each of the health departments within the four (4) UK nations and serves as the appointing authority for the recognized ECs. Per GAfREC and GBR-62, within England’s DHSC, the HRA is the head office with appointing authority for the RES. The official RES head offices (i.e., appointing authorities) for the other nations are represented by the Health and Social Care Research and Development (HSC R&D) Division (GBR-90) within Northern Ireland’s HSC Public Health Agency; the Chief Scientist Office (CSO) (GBR-91) within the Scottish Government Health and Social Care Directorates; and the Ethics Service within the Health and Care Research Wales (HCRW) (GBR-93). The head offices work together to maintain a consistent approach in operating the RES ECs.

UK Ethics Committee Authority 

As set forth in the MHCTR, the MHCTR2006, and GAfREC, the UKECA is responsible for establishing, recognizing, and monitoring ECs that review applications for clinical trials of investigational medicinal products (CTIMPs). As indicated in the MHCTR and GBR-9, the UKECA recognizes two (2) types of ECs for new CTIMPs applications:

  • Type 1: Reviews Phase I clinical trials in healthy volunteers taking place anywhere in the UK
  • Type 3: Reviews clinical trials in patients taking place anywhere in the UK

New applications are no longer allocated for review by ECs with Type 2 recognition.

Per GAfREC and GBR-9, the HRA is responsible for providing advice, assistance, and operational support to all UK ECs recognized by the UKECA.

As indicated in GBR-97, the Four Nations Policy Leads Group is tasked with acting as the UKECA, among other duties. This group works together across the four (4) nations of the UK, and provides a coordinated research approvals system and consistent policy and good practice standards. The Four Nations Policy Leads Group meetings are held every two (2) months. See GBR-97 for upcoming meeting dates.

Health Research Authority 

In accordance with the CareAct2014 and GBR-61, the HRA is a non-departmental public body established in 2015 and sponsored by England’s DHSC to standardize regulatory practices relating to health and social care research, and to encourage safe and ethical research conducted across the UK. According to GAfREC and GBR-9, the UK Health Departments have authorized the HRA in England to serve as the lead administrative body to coordinate the development of RES operational systems for ECs recognized or established by the UKECA, the HRA, or the Ministers or Health Departments of the four (4) UK nations (including their respective head offices). The RES is a core function of the HRA.

As indicated in GAfREC and GBR-64, the HRA, in support of the RES and UKECA, supports two (2) main types of ECs in the UK:

  • Authorized ECs – those authorized by the RES to review all applications except those relating to CTIMPs
  • Recognized ECs – those recognized by the UKECA, a statutory body established under the MHCTR, to review applications relating to CTIMPs. Recognized ECs may also review non-CTIMP research.

Registration, Auditing, and Accreditation

As delineated in GAfREC and GBR-9, the RES is responsible for ensuring the quality of the ECs, including the UKECA ECs, through regular monitoring, auditing, and accrediting their operations and performance.

Part 3 (Chapter 2, Section 109) and Part 4 (Sections 109-115)
Part 2 (Conditions Based on Article 3 of the Directive)
Part 2, Part 3 (12), and Schedule 2
1.3, 2.1, 2.3, 3.3, 5.4, Glossary, Annex C, Annex D, Annex E, and Annex F
Introduction (Purpose and Scope), Implementation, Terminology (Glossary), and Sections 1, 2, and 3
Definitions of Authorised REC and Recognized REC
Clinical Trial Lifecycle > Submission Process
Last content review/update: November 19, 2020

Overview

In accordance with DecreeNo021-2017, the INS-CTManual, the G-CTApplicProc, Peru requires the sponsor or his/her contract research organization (CRO) to obtain clinical trial authorization from the National Institute of Health (Instituto Nacional de Salud (INS)) and ensure that ethics committee (EC) approval is obtained from an INS-accredited EC.

DecreeNo021-2017 and the G-CTApplicProc also state that if the sponsor is not based in Peru, he/she is required to appoint a legal representative in the country who channels all communication with the INS’s General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)) for the trial’s duration, unless such responsibility is delegated to a CRO.

Please refer to PER-71 and PER-61 for detailed information on clinical trial authorization and EC accreditation. See also the INS-CTManual, the G-CTApplicProc, PER-60, and PER-59, for sponsor and contract research organization (CRO) registration instructions, and PER-36 and PER-37 for sponsor and CRO registration forms. According to DecreeNo021-2017, the INS-CTManual, and the G-CTApplicProc, the INS and EC reviews may not be conducted in parallel. The INS-accredited EC must first approve the research protocol and informed consent form (ICF), and the sponsor or his/her CRO must submit this information as part of the application dossier in order for the INS to conduct its review.

(See the Submission Content subtopic for detailed submission requirements).

OGITT Contact Information
Instituto Nacional de Salud
Oficina General de Investigación Y Transferencia Tecnológica
Cápac Yupanqui 1400
Jesus María
Lima 11
Perú

Phone: 511 748 1111
Fax: Not Available
Email:
webmaster@ins.gob.pe

Clinical Trial Phone: 511 748 1111 (Ext. 2191)
Fax: Not Available
Clinical Trial Email:
consultaensayos@ins.gob.pe

Assembly and Number of Copies

Based on information provided in DecreeNo021-2017, the INS-CTManual, the G-CTApplicProc, and the G-CTSubmissionProcs, and PER-71, the sponsor or his/her CRO must submit a request for clinical trial authorization electronically using the Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)), at which time a registration code is assigned to the application. Per the INS-CTManual, the electronic form should also be printed and signed by the sponsor or his/her CRO and delivered to the INS’s Documentary Processing Area within 20 working days.

As described in the G-CTApplicProc, the clinical trial application must be presented in both print and electronic format. One (1) printed copy of the application must be submitted to the INS as indicated in the requirements listed in DecreeNo021-2017. Per the G-CTApplicProc, the application should be completed using the OGITT approved forms that are available on the REPEC website.

Per the G-CTSubmissionProcs, if submitting procedures or communications for which there are no available forms, information should be provided by letter to the OGITT. Documentation must be clear and legible, with all the fields completed in the respective forms for each procedure as this information is subject to evaluation. All documents must be presented on A4 size bond paper, in a folder of A4 size with a wide spine to allow for unrestricted opening between the sections. The documents must also be organized using separators and foliated in the upper right hand corner according to the order established in the DecreeNo021-2017 requirements. The foliation is arranged from the front to the end, and the numbering assigned to each folio must be consecutive. In addition, the number assigned to each folio must be written legibly without amendments, on a blank page, and without altering texts, letterhead, stamps, originals, etc. The application must also include the address where INS application related notifications should be mailed.

As indicated in the G-CTApplicProc, two (2) CDs should be provided for the electronic submission of the application and include the following documentation:

  • Research protocol
  • Updated Investigator’s Brochure (IB)
  • List of clinical trial supplies (PER-42)
  • Information related to the quality of the investigational product (IP) according to Annex 5 of DecreeNo021-2017 (inside a folder referred to as Annex 05)

One (1) of the CDs should be sent to the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) for the evaluation of the safety profile and the quality of the product under investigation. (Note: The ANM is also referred to as the General Directorate of Medicines, Supplies and Drugs (La Dirección General de Medicamentos Insumos y Drogas (DIGEMID)).

In addition, per the G-CTSubmissionProcs, a printed page listing all of the attached digital media included in the application should accompany the electronic version. The attachment should contain the respective folio number, the clinical trial code, and a brief description of the content included in the digital medium. The applicant should ensure that the application submission complies with all of the requirements delineated in DecreeNo021-2017. If the OGITT’s Office of Documentary Processing requires any corrections, the applicant will have two (2) business days to amend the application, and this time will not be counted towards the period allotted for the OGITT’s review. If the two (2)-day timeframe is exceeded, the application will be discarded, and another application must be submitted to initiate the process again.

Refer to the INS-CTManual, the G-CTApplicProc, the G-CTSubmissionProcs, and PER-71 for additional submission information, PER-24 for the recently amended clinical trial application form per ResolutionNo0423-2019, and PER-10 for detailed instructions on completing the form.

Clinical Trial Application Language Requirements

As delineated in DecreeNo021-2017, the clinical trial application and accompanying material must be provided in Spanish. Any document not in Spanish must be submitted with a corresponding translation. The INS-CTManual specifically states that the sponsor registration application (PER-36) must be submitted in Spanish, or accompanied by a proper translation if issued in a language other than Spanish. Notification reports for IPs should contain a translated summary in English and Spanish.

Further, per ResolutionNo655-2019 (which amends DecreeNo021-2017) and the G-CTApplicProc, the research protocol and the ICF must be in Spanish and in the original language, if different from Spanish, and include a copy of the approval by an INS-accredited EC. All of the documents should be submitted in electronic form as an editable PDF. For amended protocols or ICF submissions, ResolutionNo655-2019 states that any changes should be submitted in tracked change format. The final protocol and ICF should include all of the incorporated amendments and comply with all of the previously discussed protocol submission requirements.

ResolutionNo655-2019 further explains that the updated IB must be written in Spanish, and in the original language, if different from Spanish. These documents are to be submitted in electronic form as an editable PDF. Refer to ResolutionNo655-2019 and the G-AmdAuthRept for detailed protocol amendment requirements. The application for approval of clinical trial amendments is in PER-33.

(Please note that Peru is in the process of finalizing new guidelines as well as the associated forms and instructions to support the ResolutionNo655-2019 amendments to DecreeNo021-2017; ClinRegs is monitoring these developments.)

DecreeNo021-2017 also states that if the protocol title is written in English, a single title in Spanish must be assigned for all purposes. The ICF must also be written in Spanish, and in the language the research participant identifies as his/her own. This requirement is also applicable to the protocol and ICF amendments. In addition, research and complementary IPs media labeling must be printed in indelible ink in Spanish or English.

Preamble, Article 1, and Annexes (2-3 and 11)
Annexes A and B
Articles 34, 40, 59, 61, 63, 67, 70, 71, 85-86, 88, 91, Annex 1, and Complementary Provisions Final
1, 2, 4, 5, and Key Points
4-6
Chapter VI (6.4), VII (7.1, 7.5, 7.8.2, and 7.8.3), Flow Chart No. 04, No. 13, and No. 14, and Annexes 1 and 3
Last content review/update: June 29, 2021

Overview

In accordance with the MHCTR, the MHCTR2006, the G-CTApp, and GBR-9, the United Kingdom (UK) requires the sponsor or his/her designated legal representative to obtain clinical trial authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA) prior to initiating the trial. Per G-CTApprovedCountries, MHCTR-EUExit lists 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. According to the G-CTApp, the clinical trial sponsor takes responsibility for the initiation, management, and financing (or arranging the financing) of that trial. Clinical trials can also be sponsored by two (2) or more persons or organizations, which is referred to as joint or co-sponsorship. GBR-103 provides that if a sponsor(s) is not established in the UK or on an approved country list (which initially includes EU/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. Details of the legal representative should be entered in the ‘legal representative’ section of the Integrated Research Application System (IRAS) (GBR-78). In all cases, evidence should be provided with the application that the legal representative is willing to take on that role and is established at an address in the UK or a country on the approved country list. For example, a copy of correspondence between the sponsor and legal representative on appropriately headed paper could be supplied, or a copy of a contract. Where the legal representative is also a co-sponsor, this should be separately recorded on the application form and details given of the allocation of sponsorship responsibilities. Evidence of insurance or indemnity cover should be provided.

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 MHRA and the ethics committee (EC). From January 1, 2021, 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. 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.

The G-CTApp permits the MHRA’s review process to be conducted in parallel with the EC review, stating that an EC opinion may be obtained before, during, or after the MHRA application submittal. Note that per GBR-9, 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 the G-MHRASubmiss, as of January 1, 2021, the MHRA started new processes to submit regulatory and notification information to the UK. For clinical trial applications to the UK, including initial applications, substantial amendments, end-of-trial notifications, and developmental safety update reports (DSURs), applicants must submit information through UK’s national portals. The steps for gaining access to MHRA Submissions (GBR-13) are contained in the G-MHRASubmiss and GBR-11. Per the G-CTApp, the applicant must complete the clinical trial application form on the Integrated Research Application System (IRAS) (GBR-78) and form via GBR-13. Note, per GBR-18 and GBR-17, every clinical trial must include a unique trial number, a European Clinical Trials Database (EudraCT) number (GBR-87). This number must be included on all clinical trial applications and as needed on other documents relating to the trial (e.g., safety reports). To obtain a EudraCT number, follow the instructions at GBR-17 and GBR-87.

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

(See Clinical Trial Lifecycle topic, Submission Content subtopic for detailed submission content requirements).

Submitting the Clinical Trial Application

According to the G-CTApp, applicants must complete the clinical trial authorization application form on IRAS (GBR-78) and submit it via MHRA Submissions (GBR-13) with the rest of the required documents. GBR-17 indicates that, until further notice, the MHRA will still expect a EudraCT number to be in place to provide a unique reference for clinical trials. The steps for gaining access to MHRA Submissions (GBR-13) are in G-MHRASubmiss and GBR-11.

Per the GBR-17, the clinical trial application will be validated on receipt and an acknowledgement letter will be sent to the person submitting the application. If the application is valid, then the assessment period will begin. This starts from the date of receipt of a valid application. If the application is not valid, then the applicant will be told of the deficiencies. Nothing will happen to the application until the missing components are provided.

GBR-9 states that the chief investigator (CI) must submit the electronic application to IRAS on the same day that a booking is made to schedule an EC review through the NHS Research Ethics Committee (REC)’s Online Booking Service (GBR-95). Detailed instructions about submitting EC applications through IRAS are available at GBR-78 and GBR-94.

GBR-72 contains information for participants who would like to submit a clinical trial application via the Combined Ways of Working (CWoW). As of January 2021, the Health Research Authority (HRA) started accepting applications from new sponsor organizations. To express an interest, email cwow@hra.nhs.uk. Applications to the CWoW must be submitted using the appropriate section of IRAS. CWoW aims to have the National Health Service (NHS)/HRA work closely with MHRA and across the devolved administrations to develop a single application route and a coordinated ethics and regulatory review leading to a single UK decision on a clinical trial. For detailed guidance and participating ECs, see GBR-72.

Assembly and Number of Copies

According to the G-CTApp, applicants must complete the clinical trial authorization application form on IRAS (GBR-78), create XML and PDF versions of the MHRA application form, save and sign them electronically, and submit them via MHRA Submissions with the rest of the required documents. The steps for gaining access to MHRA Submissions are in G-MHRASubmiss and GBR-11. All documents must have copy and paste functionality. MHRA does not currently accept password-protected documents. The information in the submission package will be used to validate the application and incomplete applications will be rejected. In addition, the naming of files is important and clearly naming files will reduce validation issues. Refer GBR-78 for detailed IRAS guidance. (See Clinical Trial Lifecycle topic, Submission Content subtopic for documentation to be included in the application package.)

Clinical Trial Application Language Requirements

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

2
Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 1 (3) and Part 3 (12, 14, 17, and 18)
Trial Sponsor and Representative, Ethics Committee, Clinical Trial Authorization Application Form, and Documents to Send with Your Application
Changes to the trial sponsor/legal representative
2
3
Terminology (Glossary) and Section 14
CI Checklist Before Seeking Approval, CTA Submission, Unique Trial Number, EudraCT Number
Help (Preparing and Submitting Applications)
Sponsor’s Legal Representative
Clinical Trial Lifecycle > Submission Content
Last content review/update: November 19, 2020

Overview

As set forth in DecreeNo021-2017, the INS-CTManual, and the G-CTApplicProc, Peru’s National Institute of Health (Instituto Nacional de Salud (INS)) requires the sponsor or his/her contract research organization (CRO) to apply for clinical trial authorization, and the principal investigator (PI) to apply for approval from an INS-accredited ethics committee (EC) to conduct a clinical trial. Please refer to PER-71 and PER-61 for detailed information on clinical trial authorization and EC accreditation. See also the INS-CTManual, the G-CTApplicProc, PER-60, and PER-59 for sponsor and CRO registration instructions, and PER-36 and PER-37 for sponsor and CRO registration forms.

INS Requirements

As specified in DecreeNo021-2017, ResolutionNo655-2019 (which modifies DecreeNo021-2017), the INS-CTManual, the G-CTApplicProc, and PER-71, a clinical trial application submission must include the following documents:

  • Application for clinical trial authorization and proof of payment (PER-24)
  • Approval(s) issued by legal representative of institution(s) where research will be conducted
  • EC approval of the research protocol and informed consent form (ICF)
  • Research protocol in Spanish, and in the original language if different from Spanish, submitted in electronic form as an editable PDF (see Annex 1 in DecreeNo021-2017)
  • ICF in electronic form as an editable PDF (see Annex 4 in DecreeNo021-2017)
  • Updated Investigator’s Brochure (IB) in Spanish, and in the original language if different from Spanish, submitted in electronic form as an editable PDF (See Annex 2 in DecreeNo021-2017)
  • Affidavit stating no conflict of financial interest signed by the sponsor or his/her CRO and the PI (see PER-34)
  • Affidavit signed by the PI and sponsor on preparation of research institution for trial (see PER-35)
  • In the case of foreign sponsor: copy of proof of delegation of functions to the sponsor representative, duly authenticated by Peru’s Ministry of Foreign Affairs
  • Affidavit on compensation for participants signed by the sponsor or his/her CRO and PI (covers budget and expenses for any trial-related injuries) (PER-51)
  • Copy of current insurance policy purchased by the sponsor
  • List of clinical trial supplies
  • Information related to the investigational product (IP) quality (electronic form) (see Annex 5 in DecreeNo021-2017)
  • Updated curriculum vitaes (CVs) of all research team members with attached copies
  • Copy of documents demonstrating training in Good Clinical Practices and Research Ethics in human beings for the entire research team within the past three (3) years (PER-50)
  • Detailed national budget total for trial
  • Copy of current record of authorized research institution(s) for clinical trials
  • Payment receipt for research site registration; in the case of multicenter trials, receipts must be provided to demonstrate each research site has made separate payments

Refer to DecreeNo021-2017, the INS-CTManual, the G-CTApplicProc, and PER-71 for detailed submission information; PER-24 for the recently amended clinical trial application form per ResolutionNo0423-2019; and PER-10 for detailed instructions on completing the form. (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.)

See also the Submission Process subtopic for additional submission requirements.

Institutional EC Requirements

According to ResolutionNo233-2020 and PER-77, institutional EC requirements for protocol evaluation are based on their internal regulations and standard operating procedures. However, PER-77 further notes that ECs generally require PIs to submit the following documentation for ethics approval:

  • Letter from the PI to the EC Chairman
  • Basic Format Application
  • Research protocol
  • ICF
  • PI and co-investigator(s) CV(s)
  • Declaration of the PI and research center director/research institution head
  • Declaration of financial details and potential conflicts of interest of the PI
  • Sponsor’s insurance policy
  • PI’s training in good clinical research ethics

Clinical Protocol

As delineated in DecreeNo021-2017, the clinical protocol should contain the following elements:

  • General information
  • Protocol summary
  • Background and justification (including IP description) (See Investigational Products topic for detailed coverage of this subject)
  • Objectives, valuation criteria or specific results and hypotheses
  • Test design
  • Participant selection/withdrawal
  • Participant treatment
  • Study evaluation and procedures
  • Adverse events (See Clinical Trial Lifecycle topic, Safety Reporting subtopic for additional information)
  • Statistical considerations
  • Data collection and monitoring
  • Data management and record maintenance
  • Ethical aspects
  • Publications results
  • Bibliography
  • Appendices

For complete protocol requirements, refer to Annex 1 of DecreeNo021-2017.

VIII (8.4)
Preamble, Article 1, and Annexes (2-3)
Annexes A and B
Articles 40, 59, 63, 67, 71, Complementary Provisions Final, and Annexes 1-5
4 and 6
Chapter VII (7.1, 7.2, and 7.5), Flow Charts No. 01 and 04, and Annexes 1 and 3
Last content review/update: June 29, 2021

Overview

As set forth in the MHCTR, the MHCTR2006, the G-CTApp, and GBR-9, the Medicines and Healthcare Products Regulatory Agency (MHRA) requires the sponsor or his/her designated legal representative to apply for clinical trial authorization, and the chief investigator (CI) to apply for a favorable opinion from a recognized ethics committee (EC). (See the Ethics Committee topic for detailed coverage of EC operations and responsibilities.)

MHRA Requirements

As specified in the G-CTApp, a clinical trial submission package to the MHRA should contain the following documents:

  • A cover letter (when applicable, the subject line should state that the submission is for a Phase I 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 MHRA invoice and allocate payments promptly and efficiently
  • A clinical trial application form in PDF and XML versions
  • A protocol document
  • An investigator’s brochure (IB)
  • An investigational medical product dossier (IMPD) or a simplified IMPD
  • A 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 Investigational Products topic, Manufacturing & Import subtopic for more information)
  • A 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
  • The content of the labelling of the investigational medicinal product (IMP) (or justification for its absence)

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 details and submittal details are in the G-PIPs and the G-PIPsProcess.

EC Requirements

As per the MHCTR, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), and GBR-77, ECs require the CI to submit the following documentation for ethics approval:

  • Application for an EC opinion (Note, per GBR-18, every clinical trial must include a unique trial number, a European Clinical Trials Database (EudraCT) number (GBR-87))
  • A summary of the trial, including justification, relevance, and methodology to be used
  • Research hypothesis
  • Statistical analysis and justification for the numbers of participants to be recruited
  • Protocol
  • IB
  • Peer review process details
  • Sponsor name and contact information
  • Financial arrangements for the trial (e.g., funding sources, participant reimbursement, compensation provisions in the event of trial-related injury or death, and insurance or indemnity coverage for sponsor and investigator(s)) (see Sponsorship topic, Compensation subtopic for additional information)
  • Terms of agreement between sponsor and participating institution(s)
  • Material to be used (including advertisements) to recruit potential research participants
  • ICF and copies of materials to be provided to participants (See Informed Consent topic, Required Elements subtopic for additional information)
  • Participant treatment plans
  • Benefit/risk assessment for participants
  • Investigator(s) Curriculum Vitaes (CVs)
  • Trial design and suitability of facilities

Additionally, according to GBR-95, the CI must submit the electronic application to the Integrated Research Application System (IRAS) (GBR-78) on the same day that a booking is made to schedule an EC review through the National Health Service (NHS) Research Ethics Committee’s Online Booking Service (GBR-95). EC reviews are booked through the Online Booking Services and will be booked in the first available slot for an EC that is suitable for the type of study. ECs are geographically located across the UK. Applicants are strongly encouraged to attend meetings in person. Some studies must be reviewed by an EC that is flagged for the type of research to take place. Refer to GBR-95 for detailed submission and booking instructions.

Clinical Protocol

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
  • Investigational Product description (See Investigational Products topic for detailed coverage of this subject)
  • Form, dosage, route, method, and frequency of administration; treatment period
  • Trial objectives and purpose
  • Trial design, random selection method, and blinding level
  • Participant selection/withdrawal
  • Participant treatment
  • Summary of potential risks and known benefits to research participants
  • Safety and efficacy assessments
  • Adverse event reporting requirements (See Clinical Trial Lifecycle topic, Safety Reporting subtopic for additional information)
  • Statistics and methods to track trial data
  • Sponsor specifications for direct access to source data/documents
  • Quality control/quality assurance procedures and practices
  • Ethical considerations
  • Data management and recordkeeping
  • Financing and insurance details
  • Publication policy

For complete protocol requirements, refer to GBR-113.

Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 3 (12, 14, 15, 17, and 18) and Schedule 3 (Parts 1 and 2)
Documents to Send with Your Application
Legal Background and Scope
Terminology (Glossary) and Section 14
3.1 and 6
Chief Investigator Checklist
Clinical Trial Lifecycle > Timeline of Review
Last content review/update: November 19, 2020

Overview

Based on DecreeNo021-2017, the INS-CTManual, and the G-CTApplicProc, the National Institute of Health (Instituto Nacional de Salud (INS))’s review and approval of an application to conduct a clinical trial is dependent upon obtaining ethics committee (EC) approval from an INS-accredited EC. Therefore, the INS and EC reviews may not be conducted in parallel.

INS Approval

Clinical Trial Application Submission

As per LawNo27444, and DecreeNo004-2019 which modifies LawNo27444, the INS is required to complete its review and approval of a clinical trial application in a maximum of 30 working days (including the 30 days for the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) review). (Note: The ANM is also referred to as the General Directorate of Medicines, Supplies and Drugs (La Dirección General de Medicamentos Insumos y Drogas (DIGEMID))).

In addition, per DecreeNo021-2017 and the INS-CTManual, if the clinical trial is related to an IP for the prevention, diagnosis, or treatment of tuberculosis or HIV/AIDS infection, the specific technical opinion of General Directorate of Strategic Public Health Interventions will be requested to ensure the study does not interfere with its strategic interventions regarding these diseases.

For specific information on pre-submission registration requirements, see Clinical Trial Lifecycle topic, Submission Process subtopic.

DecreeNo021-2017 and the INS-CTManual state that the INS, through the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)), grants clinical trial authorization for the total period of time scheduled for its completion, which is recorded as “Total duration of the trial” as indicated in the recently amended Application for Clinical Trial Authorization (PER-24) per ResolutionNo0423-2019.

In addition, per the G-CTSubmissionProcs, if any corrections to a clinical trial application submission are required by the OGITT’s Office of Documentary Processing, the applicant will have two (2) business days to amend the application, and this time will not be counted towards the period allotted for the OGITT’s review. If the two (2) day timeframe is exceeded, the application will be discarded, and another application must be submitted to initiate the process again.

In addition, as indicated in DecreeNo021-2017, the clinical trial authorization will be valid for a maximum of 12 months from the date of its issuance. This period of validity is valid for all research centers, regardless of the authorization date of its operation. The clinical trial authorization is granted by the total period of time scheduled for execution, which was registered in the authorization request.

DecreeNo021-2017, ResolutionNo655-2019 (which modifies DecreeNo021-2017), PER-72, and PER-27 also provide information on how the sponsor or his/her CRO should request a trial extension. The following documents must be submitted within 30 calendar days prior to the trial’s expiration:

  • Application for extension of time to conduct the clinical trial, explaining the reasons for such request and stating the number and date of the proof of payment of processing fees (using the REPEC e-form (PER-27)) per PER-72
  • Copy of the document approving the time extension granted by the legal representative of the research institution(s) where the trial will be conducted
  • Copy of the document containing the time extension approval by an INS-accredited EC

The authorized trial extension will be valid for a maximum of 12 months from the date of issue.

As indicated in DecreeNo021-2017 and the G-CTApplicProc, the Investigator’s Brochure (IB) and the protocol are also simultaneously forwarded to the ANM in order to obtain a safety evaluation of the IP. DecreeNo021-2017 states that the ANM must provide a technical opinion within 30 days.

Ethics Committee Approval

The EC review and approval process timeline will vary by institution.

Article 35
Preamble, Article 1, and Annexes (3, 5, 8, and 11-12)
Annexes A and B
Article 39
Articles 8, 40, 59, 63, 69, 70, 71, 80, and Complementary Provisions Final
5
5 and 6
Chapter VI (6.4), VII (7.1, 7.2, and 7.5), Flow Charts No. 01 and 04, and Annexes 1 and 3
Bodies of the Vice Ministerial Office of Public Health - General Directorate of Strategic Public Health Interventions
Clinical Trial Authorization and Extension for a Clinical Trial (English website); Clinical Trial Time Extension (Spanish website)
Last content review/update: June 29, 2021

Overview

Based on the MHCTR, the MHCTR2006, GAfREC, and GBR-9, the sponsor or his/her designated representative must submit an application for clinical trial authorization to the Medicines and Healthcare Products Regulatory Agency (MHRA)'s, and the chief investigator (CI) must submit an application to a recognized ethics committee (EC) to obtain a favorable opinion prior to the trial’s commencement. The G-CTApp permits MHRA’s review process to be conducted in parallel with the EC review, stating that an EC opinion may be obtained before, during, or after the MHRA application submittal to the Integrated Research Application System (IRAS) (GBR-78).

MHRA Approval

Clinical Trial Application Submission

As per the MHCTR and the G-CTApp, the MHRA review and approval process for a clinical trial application takes 30 days. For Phase I trials, the average is 14 days. According to the G-CTApp, if the sponsor or his/her designated representative is required to submit an amended application, the MHRA provides a response to the amendment within 60 days of receipt of the original application. Additionally, responses for Phase I healthy volunteer studies will be reviewed within an average of 14 days, and studies using gene therapy, somatic cell therapy (including xenogenic cell therapy) products or products containing genetically modified organisms will be reviewed within 90 days or receipt of the original application.

The MHCTR and the G-CTApp specify that the MHRA coordinates the clinical trial application process. The G-CTApp states that MHRA has moved from paper to 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 his/her designated representative does not receive a request for additional information from the MHRA within 30 days, the clinical trial application is treated as authorized.

In addition, as stated in the G-CTApp and GBR-35, certain first-in-human (Phase I) 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 (CTBVEAG) of the Commission on Human Medicines before approval for the trial can be given. See the G-CTApp and GBR-35 for detailed requirements.

Notification Scheme Submission

The G-CTApp indicates that in place of a standard application, a notification of a clinical trial may be submitted for “Type A” trials. This includes trials involving medicinal products licensed in any European Union (EU) Member State that meet the following criteria:

  • they relate to the licensed range of indications, dosage and form, or,
  • they involve off-label use established by practice and supported by published evidence and/or guidelines

Type A trials include studies in which the potential risk associated with an investigational medicinal product is determined to be no higher than that of standard medical care. See the G-CTApp for detailed Notification Scheme requirements.

Upon receipt of the notification, the MHRA sends an acknowledgement to the sponsor or his/her designated representative stating that the trial may proceed if an objection is not raised within 14 days. If the MHRA does not send a Notification Objection letter, the acknowledgement serves as the authorization. If the MHRA raises objections, the submission is treated as a standard request for authorization.

Ethics Committee Approval

As specified in the MHCTR, GAfREC, GBR-9, and GBR-68, an EC must give its opinion within 60 calendar days of receipt of a valid application. When an EC requires further information before confirming its opinion, it may give a provisional opinion, and it is permitted to make one (1) written request for further information, clarification, or changes to documentation. The time it takes for the EC to receive a complete response to the request does not count against the 60-day timeline. Studies using gene therapy, somatic cell therapy (including xenogenic cell therapy) products or products containing genetically modified organisms will take 90 days, or 180 days if a specialist group or committee is consulted. For other exceptions, see GAfREC and the MHCTR.

As delineated in GBR-9, the CI is responsible for submitting an application to an EC via IRAS. GBR-95 indicates that the CI must submit the electronic application to IRAS on the same day that a booking is made to schedule an EC review through the National Health Service (NHS) Research Ethics Committee’s Online Booking Service (GBR-95).

Per GBR-9, the ethical review includes an assessment of the suitability of each site or sites at which the research is to be conducted in the United Kingdom (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. See the Ethics Committee topic, Scope of Review subtopic for additional information on the “main EC.”

Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 2 (5 and 7), Part 3 (12, 14, 15, 17, and 18)
Ethics Committee, Assessment of Your Submission, Notification Scheme, and Applications that Need Expert Advice
3
3.1
Terminology (Glossary) and Sections 1, 3, 5, and 14
Clinical Trial Lifecycle > Trial Initiation
Last content review/update: November 19, 2020

Overview

In accordance with DecreeNo021-2017, the INS-CTManual, and the G-CTApplicProc, a clinical trial can only commence after the sponsor or his/her contract research organization (CRO) receives authorization from Peru’s National Institute of Health (Instituto Nacional de Salud (INS)), which is dependent on ethics committee (EC) approval from an INS-accredited EC. Therefore, the INS and EC reviews may not be conducted in parallel. No waiting period is required following the applicant’s receipt of these approvals.

According to DecreeNo021-2017 and DecreeNo016-2011, the INS-CTManual, and the G-CTApplicProc, the sponsor or his/her CRO must obtain approval from the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) to manufacture or import investigational products (IPs) and to obtain an import license for the shipment of IPs to be used in the trial. (Note: The ANM is also referred to as the General Directorate of Medicines, Supplies and Drugs (La Dirección General de Medicamentos Insumos y Drogas (DIGEMID))). (See the Investigational Products topic, Manufacturing & Import subtopic for additional information).

As stated in the DecreeNo021-2017, all investigators must possess appropriate qualifications, training, and experience, and per ResolutionNo233-2020, must also have basic training in ethical research with human beings. Furthermore, per the INS-CTManual, the trials should be conducted in compliance with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (PER-53).

Clinical Trial Agreement

According to DecreeNo021-2017, the INS-CTManual, the G-CTApplicProc, and PER-71, the sponsor and principal investigator (PI) must sign an affidavit of compliance with the minimum requirements of the research center where the clinical trial will be executed (see PER-35). Further, per the G-CTApplicProc and PER-71, both the sponsor and the PI must sign an affidavit establishing that there is no conflict of financial interest in executing the trial (PER-34).

EC Confirmation of Review and Approval

DecreeNo021-2017, the INS-CTManual, and the G-CTApplicProc, mandate that the sponsor or his/her CRO obtain written confirmation of review and approval from an INS-accredited EC prior to submitting a clinical trial application for INS approval and before the trial commences. (See Ethics Committee topic, Scope of Review subtopic and Clinical Trial Lifecycle topic, Submission Content subtopic for additional details on the EC review process).

Peruvian Clinical Trials Registry

As per DecreeNo021-2017, the INS-CTManual, the G-CTApplicProc, the G-CTSubmissionProcs, and PER-71, the sponsor or his/her CRO must register the clinical trial application electronically using the INS’s Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)), at which time, a registration code is assigned to the application.

For details on submitting protocol amendments and the related forms, refer to ResolutionNo655-2019 (which amends DecreeNo021-2017), the G-AmdAuthRept, and PER-33.

Per the INS-CTManual, the G-CTApplicProc, PER-60, and PER-59, the sponsor and his/her contract research organization (CRO) must also register with REPEC prior to submitting an application for clinical trial authorization.

Refer to the INS-CTManual, the G-CTApplicProc, and PER-71 for detailed submission instructions, PER-24 and PER-10 for the clinical trial application form and detailed instructions on completing the form. See also PER-60 and PER-59 for sponsor and CRO registration instructions, and PER-36 and PER-37 for the sponsor and CRO registration forms.

Data Safety Monitoring Board

DecreeNo021-2017 requires the sponsor to provide information on the Data Safety Monitoring Board (DSMB) including its composition, a summary of its role and notification procedure, a statement of independence from the sponsor and any conflicts of interest. Additionally, the sponsor should specify where to find other details about the by-laws not included in the protocol, or, explain why a DSMB is not necessary.

VIII (8.4)
Annexes A and B
Title II (Chapter I and II) and Title III (Chapter I)
Articles 2, 8, 40, 51, 52, 59, 63, 67, 70, 71, 94, Complementary Provisions Final, and Annexes 1-5
1, 2, 4, and 5
4 and 6
Chapter VI (6.4), VII (7.1, 7.2, 7.3, and 7.5), Flow Charts No. 01, 02, and 04, and Annexes 1 and 3
4
Last content review/update: June 29, 2021

Overview

In accordance with the MHCTR, the MHCTR2006, GAfREC, and GBR-9, a clinical trial can only commence after the sponsor or his/her designated representative receives authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA) and the chief investigator (CI) receives an approval from a recognized ethics committee (EC). No waiting period is required following the applicant’s receipt of these approvals.

GBR-103 provides that if a sponsor(s) is not established in the United Kingdom (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 G-CTApprovedCountries, MHCTR-EUExit will refer to a list of countries where a sponsor of a clinical trial, or their legal representative, may be established; these countries are initially EU and EEA countries.

The G-CTApp permits MHRA’s review process to be conducted in parallel with the EC review, stating that an EC opinion may be obtained before, during, or after the MHRA application submittal. Furthermore, GBR-9 states that the CI should be based in the UK. In rare cases when this is not required, adequate arrangements must be in place for supervision of the study in the UK.

In addition, per the MHCTR and the G-CTApp, a Manufacturer’s Authorization for Investigational Medicinal Products (MIA(IMP)) must be obtained by the person responsible for the manufacture or importation of any investigational product (IP) (known as investigational medicinal product (IMP) in the UK) to be used in the trial. The sponsor or his/her designated representative must include a copy of the MIA(IMP) in the clinical trial application submission to the MHRA. (See Clinical Trial Lifecycle topic, Submission Content subtopic, and the Investigational Products topic, Manufacturing & Import subtopic for detailed submission and IMP requirements respectively).

As stated in the MHCTR, all investigators must possess appropriate qualifications, training, and experience. The 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 investigational products must comply with the UK-GLPs.

Governance Approval

Per GBR-78, all project-based research must also apply for governance and legal compliance approvals from the appropriate lead UK Health Department. The Integrated Research Application System (IRAS) (GBR-78) facilitates this process. As described in GBR-96 and GBR-67, approval from the Health Research Authority (HRA) is required for all project-based research in the National Health Service (NHS) 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. These 2021 model agreements replace the 2020 versions. See GBR-107 for the notes that provide further background, an overview of the changes from the 2020 versions, and more information on how and under which circumstances the templates should be used. While the 2020 versions of these templates will still be accepted in IRAS (GBR-78), applicants are encouraged to adopt the 2021 versions at their earliest opportunity. Versions older than March 2020 are no longer accepted with new IRAS submissions. Applicants are advised to use the templates without modification. Any proposed modifications will not be accepted unless first agreed to by the UK Contracting Leads. Proposing modifications to the templates is likely to result in significant delay. Feedback on the content of the templates and their use by sponsors should be provided to mCTA@hra.nhs.uk.

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

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

Ethics Committee Confirmation of Review and Approval

The MHCTR and the MHCTR2006 mandate that the sponsor or his/her designated representative is responsible for ensuring that the CI has obtained confirmation of the EC’s approval. Per the G-CTApp, an EC opinion may be obtained before, during, or after the MHRA application has been electronically submitted to IRAS (GBR-78). Per GBR-9, the EC’s final opinion will be in a letter from the Chair of the Committee (or chair of the sub-committee in the case of proportionate review). It is also acceptable for the letter to be signed by a vice-chair or a member of the staff supporting the EC acting under delegated authority from the Chair. The letter is emailed to the applicant within the relevant time limit for review of the application. The final favorable opinion letter can be obtained from IRAS (GBR-78). The MHRA is notified automatically through its access to the HRA Assessment Review Portal (HARP), which is a database for authorized users (e.g., EC members and regulators) who manage or review studies submitted to the HRA.

As per the MHCTR and GBR-9, the sponsor or his/her designated representative should also notify the EC of any substantial amendments to the protocol, and submit all relevant documents in support of such amendments. These amendments may not be implemented without a favorable opinion from the EC. (See Ethics Committee topic, Scope of Review subtopic and Clinical Trial Lifecycle topic, Submission Content subtopic for additional details on the EC review and approval process).

Clinical Trial Registration

As per the G-CTReg and GBR-102, 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. Per GBR-102, HRA recognizes any register covered by the World Health Organization (WHO) list or the International Committee of Medical Journal Editors (ICMJE). The G-CTApp indicates that any favorable opinion given by a UK EC is subject to the clinical trial being registered on a publicly accessible database. In the long term, the HRA has made a commitment to register clinical trials on behalf of sponsors and researchers in its Make It Public research transparency strategy. Until this system is in place, the clinical trial should be registered on an established international registry such as the International Standardized Randomized Controlled Trial Number (ISRCTN) Registry (GBR-47) or ClinicalTrials.gov (GBR-49), to ensure the public is aware. If trial registration is deferred (for example if it is an adult phase I trial), then contact the HRA at study.registration@hra.nhs.uk.

The registry number(s), if available, should continue to be used in section A.5. of the application form in IRAS (GBR-78) when preparing the application. If this number is not available at the time of application, email the MHRA at clintrialhelpline@mhra.gov.uk with subject line “Clinical Trial Registration” within six (6) weeks of recruiting the first research participant. The applicant should also let the EC know the registration number as soon as possible.

7
2
Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 1 (3), Part 3 (12, 13, 14, 17, 18, 22, and 24) and Part 6 (36 and 38)
Registration of Your Clinical Trial, Ethics Committee, Clinical Trial Authorization Application Form, Documents to Send with Your Application, and Assessment of Your Submission
2
3.2
6
Terminology (Glossary) and Sections 1, 3, and 14
1.17, 5.1.2, and 8.2.6
Help (Preparing and Submitting Applications)
Clinical Trial Lifecycle > Safety Reporting
Last content review/update: November 19, 2020

Overview

According to DecreeNo021-2017, DecreeNo021-2017-Corrections, and the G-SafetyRpting, the following definitions provide a basis for a common understanding of Peru’s safety reporting requirements:

  • Adverse Event (or Adverse Experience) (AE) – Any untoward medical occurrence in a participant to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product
  • Adverse Drug Reaction (ADR) – Any noxious 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) or Serious Adverse Drug Reaction (SADR) – Any AE/ADR that results in death, is life threatening, requires or extends hospitalization, results in persistent or significant disability/incapacity, or causes a congenital anomaly/birth defect
  • Unexpected Adverse Drug Reaction – An adverse reaction where the nature or severity is inconsistent with the applicable product information
  • Suspected Unexpected and Serious Adverse Reaction (SUSAR) – Any serious AE/ADR in which there is at least a reasonable possibility of a causal relationship with the investigational product (IP) and the nature and severity of the event/reaction is not described in the investigator’s brochure and/or the fact sheet technique

Reporting Requirements for AEs/ADRs

Investigator Responsibilities

According to DecreeNo021-2017, the INS-CTManual, and the G-SafetyRpting, the principal investigator (PI) and the sponsor or his/her contract research organization (CRO) are responsible for monitoring the safety of the IP. As specified in DecreeNo021-2017 and the G-SafetyRpting, the PI is also responsible for notifying the sponsor or his/her CRO or the ethics committee (EC) of any SAEs/SADRs and SUSARs within a period not exceeding one (1) calendar day from the date the event occurs, or, the PI becomes aware of the incident.

ResolutionNo233-2020 also indicates that investigators should report immediately to the EC and the corresponding authorities any AE or unanticipated risk to research participants related to the research. Furthermore, in cases where protocol or informed consent process changes are necessary to prevent harm to the participants, the investigators must submit report deviations within 24 hours.

DecreeNo021-2017 notes that the PI must also follow up with a detailed written report. Per the G-SafetyRpting, the PI must record the SAEs/SADRs and notify the sponsor according to the procedure described in the study protocol.

Furthermore, per DecreeNo021-2017, the PI must inform the sponsor or his/her CRO and the EC of the following:

  • Any SAE/SADR that has occurred to a participant following the trial’s completion
  • Any non-serious AEs/ADRs identified as determinants of safety assessments in the protocol within the periods specified

In addition, the G-SafetyRpting states that if the PI becomes aware of SAEs/SADRs occurring after the end of the trial, he/she should notify the sponsor or his/her CRO and the EC.

Lastly, per DecreeNo021-2017, the PI must provide the sponsor or his/her CRO, the EC, and the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)) within Peru’s National Institute of Health (Instituto Nacional de Salud (INS)) with any additional safety information requested.

Sponsor Responsibilities

According to DecreeNo021-2017, the INS-CTManual, the G-SafetyRpting, and PER-72, the sponsor or his/her CRO should report IP-related AEs/ADRs, SAEs/SADRs, and SUSARs and provide these reports to the INS’s OGITT.

Per DecreeNo021-2017, DecreeNo021-2017-Corrections, the INS-CTManual, PER-72, PER-66, and PER-38, the sponsor or his/her CRO and the PI are required to submit all expected and unexpected SAEs/SADRs (related or not per PER-72) and SUSAR reports electronically through the Serious Adverse Events Virtual Reporting System (Sistema de Reporte de Eventos Adversos Serios (REAS-NET)) (PER-69) to the OGITT within seven (7) calendar days from the occurrence of the incident, or, as soon as the sponsor is aware of the incident. The G-SafetyRpting specifies that the sponsor or his/her CRO is responsible for evaluating, categorizing, and reporting all SAEs/SADRs and SUSARs that occur within the country through REAS-NET. The notification should be completed using the online form, FOR-OGITT-046 (PER-38).

Per the INS-CTManual, the electronic form (PER-38) submitted via REAS-NET should be printed and signed by the sponsor or his/her CRO. The INS-CTManual and the G-SafetyRpting state that the submitted information above must be updated with any additional relevant information in a follow-up tracking report within eight (8) calendar days. The G-SafetyRpting also notes that if the causality assessment of the SAE conducted by the investigator differs from the causality assessment made by the sponsor, the investigator’s assessment cannot be modified. The INS-CTManual further states that both the follow-up report and the final report completed in REAS-NET should be submitted electronically and in print formats to the OGITT.

In addition, per DecreeNo021-2017, DecreeNo021-2017-Corrections, and PER-72, the sponsor or his/her CRO must notify the OGITT, the ECs, and the PIs within a maximum period of seven (7) calendar days of any findings that could adversely affect the safety of research participants, have an impact on the conduct of the study, or alter the benefit/risk balance. This report should be prepared independently and separately from other required AE/ADR submission deadlines outlined in this subtopic.

The G-SafetyRpting further explains that if the sponsor or his/her CRO is aware of safety findings that are not covered within the scope of an SAE/SADR or SUSAR, these findings require another measure or action such as a security emergency measure, an amendment to the protocol or informed consent, or the suspension or cancellation of the clinical trial. The sponsor should communicate this information to the OGITT through a detailed report that includes the measures and actions taken at the local and international levels, if already established. The ECs and PI should also be notified within seven (7) calendar days. The information must be written in Spanish and English, be contained in an electronic medium (CD), and be presented in the document processing area of the OGITT. The sponsor is subsequently required to initiate administrative procedures that correspond to the measure or action taken, and in accordance with the requirements established by the clinical trial regulations. Refer to the G-SafetyRpting for examples of administrative procedures.

As delineated in DecreeNo021-2017, the G-SafetyRpting, and PER-72, the sponsor is also required to submit, electronically on a quarterly or semi-annual basis, SAE/SADR and SUSAR reports occurring internationally, to the OGITT and the Council for International Organizations of Medical Sciences (CIOMS) whether they have occurred in the authorized trial, in other trials with the same IP, or in a context of different use. The G-SafetyRpting specifies that the information should be presented on magnetic media. Refer to Annex 1 in the G-SafetyRpting for data requirements. PER-72 further indicates that the sponsor should send the SUSAR reports for events that have occurred abroad as soon as possible to the investigator using CIOMS Form I (PER-18). The investigator, in turn, will send the reports to the EC. The INS-CTManual also notes that the sponsor or his/her CRO should submit a printed copy of the CIOMS report in Spanish or English. (See the Investigational Products topic for additional information on IPs.)

Further, per DecreeNo021-2017, the OGITT must notify the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) of any SAEs/SADRs and SUSARs caused by an IP being used in an authorized trial in Peru within a maximum period of 15 working days after receiving notification about the incident. The INS-CTManual also indicates authorized ANM personnel will have access to SAEs/SADRs and SUSARs that have occurred in Peru via REAS-NET. (Note: The ANM is also referred to as the General Directorate of Medicines, Supplies and Drugs (La Dirección General de Medicamentos Insumos y Drogas (DIGEMID))).

According to the INS-CTManual and the G-SafetyRpting, in cases of prenatal exposure due to a pregnant woman’s participation in a clinical trial, the PI, the sponsor or his/her CRO is required to submit an electronic form available in REAS-NET to notify the OGITT of the SAE/SADR or SUSAR. (Refer to PER-39 for the form (FOR-OGITT-047)). Per the G-SafetyRpting, the sponsor submits the form and the procedures for monitoring and controlling the pregnancy and newborn on magnetic media. The notification of a pregnancy must be made within seven (7) calendar days. The INS-CTManual also indicates prenatal monitoring reports must also be prepared during pregnancy, childbirth, and for six (6) months postpartum following the occurrence. See the Informed Consent topic, Pregnant Women, Fetuses & Neonates subtopic for additional information on this vulnerable population.

As delineated in the INS-CTManual and the G-SafetyRpting, the sponsor or his/her CRO must also submit an annual IP safety report (DSUR) to the OGITT. Per the INS-CTManual, the translation of the annual report summary must be presented in English and Spanish. The G-SafetyRpting explains that the DSUR should be prepared after the first authorization of the clinical trial in any country. This is referred to as the Development International Birth Day (DIBD). The report should comply with the ICH Harmonised Tripartite Guideline: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A) (PER-52). The sponsor must complete the online form (FOR-OGITT-048) (see PER-45) in Spanish as well as submit a copy of the DSUR to the OGITT on CD.

In addition, per the G-SafetyRpting, the sponsor or his/her CRO must describe in the protocol the SAEs that will not be reported promptly because they are expected to occur in the study population with a frequency independent from their exposure to the IP. The sponsor or his/her CRO is also required to describe in the protocol the procedures for monitoring SAEs produced by the IP. Moreover, depending on the trial design, the pathology, and the IP, the sponsor or his/her CRO will describe in the protocol the notification procedures for non-serious AEs.

Pursuant to the G-SafetyRpting, to report post-study AEs, the sponsor or his/her CRO should send an email to consultaensayos@ins.gob.be to coordinate with the person in charge of computer systems and grant him/her access to REAS-NET to complete and submit the online form (FOR-OGITT-046) (PER-38). SAEs/SADR notifications following a trial’s completion should remain in the research center archives.

See DecreeNo021-2017, the INS-CTManual, the G-SafetyRpting, PER-66, and PER-38 for detailed sponsor/CRO reporting requirements.

Form Completion & Delivery Requirements

As per DecreeNo021-2017, the INS-CTManual, the G-SafetyRpting, and PER-72, all AEs/ADRs, SAEs/SADRs, and SUSARs must be reported electronically by the sponsor or his/her CRO using REAS-NET. Refer to PER-38 for the OGITT SAE/SADR form, FOR-OGITT-046. All SAEs/SADRs and SUSARs must also be reported on the CIOMS Form I (PER-18).

Data Safety Monitoring Board

DecreeNo021-2017 requires the sponsor to provide information on the Data Safety Monitoring Board (DSMB) including its composition, a summary of its role and notification procedure, a statement of independence from the sponsor and any conflicts of interest. Additionally, the sponsor should specify where to find other details about the by-laws not included in the protocol, or, explain why a DSMB is not necessary.

VIII (8.4)
Article 2, 40, 52, and 108-111
V-VII
Chapter VI (6.4), VII (7.8.1-7.8.3), and Flow Charts No. 12, 13, and 14
Serious Adverse Events Report
Last content review/update: April 22, 2021

Overview

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 Serious ADR – Any AE, ADR, or unexpected ADR that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or a congenital anomaly/birth defect
  • Unexpected Adverse Drug Reaction (ADR) – An adverse reaction where the nature or severity is inconsistent with the applicable product information
  • Suspected Unexpected Serious Adverse Reaction (SUSAR) – A suspected serious adverse reaction, which is also “unexpected,” meaning that its nature and severity are not consistent with the information about the medicinal product in question.

Per the G-CTAuth, 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 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.

Reporting Requirements for AEs/ADRs

Investigator Responsibilities

As specified in the MHCTR, GBR-1, and GBR-30, the investigator is responsible for reporting all SAEs/SADRs immediately to the sponsor. The report may be made orally or in writing, and followed by a detailed report no later than 24 hours after the event. When the reported event results in a participant’s death, the investigator must provide the sponsor with any requested information. According to the MHCTR, in cases where reporting is not immediately required according to the protocol or the Investigator’s Brochure (IB), the investigator should report an SAE/SADR within the appropriate timeframe based on the trial requirements, the seriousness of the SAE/SADR, and protocol or IB guidelines. Per GBR-1, the investigator and the sponsor share responsibility for the assessment and evaluation of adverse events with regard to seriousness, causality, and expectedness.

Sponsor Responsibilities

According to the MHCTR, the G-CTAuth, the MHCTR-EUExit, GBR-115, and GBR-99, 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 ethics committee (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, 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 the G-CTAuth and the G-SftyRpts, sponsors must submit Development Safety Update Reports (DSURs) to the MHRA. G-CTAuth specifies that the DSUR should take into account 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 must include a unique European Clinical Trials Database (EudraCT) number (GBR-87))
  • An analysis of the participant’s safety in the concerned clinical trial(s) with an appraisal of its ongoing risk/benefit
  • A listing of all suspected serious adverse reactions (including all SUSARs) that occurred in the trial(s)
  • An aggregate summary tabulation of SUSARs that occurred in the concerned trial(s)

At the end of the DSUR reporting period, the sponsor may assess the new safety information that has been generated and submit any proposed safety changes to the Investigator’s Brochure 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.

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 EC, and the MHRA for clinical trials for investigational medicinal products (CTIMPs), must be notified immediately (no later than within three (3) days) in the form of a substantial amendment that such measures have been taken and the reasons why. The G-CTAuth 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 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. Submissions should be made using MHRA Submissions (GBR-13) via the Human Medicines Tile then selecting ‘Clinical Trial’ as the Regulatory Activity and ‘CT - Amendment’ from the Regulatory sub activity dropdown list.

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

Form Completion & Delivery Requirements

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

  • MHRA’s eSUSAR website (GBR-50) - Before using the eSUSAR website, users should complete the eSUSAR registration form (download from GBR-50) and email it to esusar@mhra.gov.uk with the subject line ‘eSUSAR registration’.
  • MHRA Gateway (which replaces the EudraVigilance Gateway) - To gain access to the MHRA Gateway, which is used to submit bulk reports, users must first register via MHRA Submissions (GBR-13). The steps for gaining access to MHRA Submissions are contained within the G-MHRASubmiss and GBR-11.

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

G-SftyRpts states that with respect to the DSUR, sponsors should use MHRA Submissions (GBR-13) via the Human Medicines Tile, and select ‘Development Safety Update Report’ as the Regulatory Activity and ‘Original Submission’ from the Regulatory sub activity dropdown list. Acknowledgements of receipt for DSUR submissions are generated by MHRA Submissions where a confirmation of submission is emailed to the reporter.

 See the G-CTAuth, G-SftyRpts, GBR-50, and GBR-99 for more details on submittal and delivery requirements.

Data Monitoring Committee (DMC)

The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (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.

14
Part 5
Reference Safety Information - updated guidance, Suspected Unexpected Serious Adverse Reactions (SUSARs), Development Safety Update Reports (DSURs), and Urgent Safety Measures
Reporting SUSARs using the new reporting routes, Registering for MHRA Gateway, Reporting SUSARs using the eSUSAR website, Transition between reporting to EU and UK systems, and Submitting DSURs to the MHRA
4 and 5
1, 4.11, 5.16, 5.17, and 5.5
Chief Investigator Checklist, Safety Reporting, and Urgent Safety Measures
SUSAR
Clinical Trial Lifecycle > Progress Reporting
Last content review/update: November 19, 2020

Overview

In accordance with DecreeNo021-2017, the INS-CTManual, and PER-72, the sponsor or his/her contract research organization (CRO) is responsible for submitting progress and final reports to the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)) within Peru’s National Institute of Health (Instituto Nacional de Salud (INS)). As per DecreeNo021-2017, the principal investigator (PI) is responsible for submitting clinical trial progress and final reports to the research institution and the institutional ethics committee (EC) (El Comité Institucional de Ética en Investigación (CIEI)). ResolutionNo233-2020 further indicates that researchers should submit progress reports, final reports, suspension reports, and early termination reports, among others, per the terms established by the EC.

Interim/Progress Reports

As delineated in DecreeNo021-2017, the INS-CTManual, PER-72, PER-47, and PER-8, the sponsor or his/her CRO must submit a progress report for each institution in which a trial is conducted from the date of the study’s authorization to the INS’s OGITT. The report should be submitted quarterly or biannually to the INS’s Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) for each of the approved research centers. Per the INS-CTManual, this report should be submitted regardless of the enrollment status in each center. The INS-CTManual further specifies that the submission deadline is up to seven (7) calendar days after completing the quarterly or half-yearly period. The sponsor or his/her CRO should print and sign the electronic form and deliver it to the INS’s Office of Documentary Procedure within 20 working days. Refer to the INS-CTManual for additional information, and PER-47 and PER-8 for the progress report form and detailed submission instructions.

In addition, DecreeNo021-2017 and PER-72 state that the progress report must be sent in print and electronic media, and include the following information:

  • Number of patients enrolled in the study and status (e.g., in treatment, retired from study, completed study, or who are not ready to enroll) (DecreeNo021-2017)
  • Summary of serious adverse events/adverse drug reactions (SAEs/SADRs) and non-serious AEs/ADRs related to the investigational product (IP), and deviations occurring in the corresponding period (DecreeNo021-2017)
  • Number of patients who failed the screening (PER-72)
  • Number of patients with clinical failure (PER-72)
  • SAEs
  • Non-SAEs

According to PER-72, the following documentation should also be attached to the progress report:

  • Quarterly or half-yearly report of deviations/breaches to the protocol for every research site that occurred during the stated timeframe
  • Quarterly or half-yearly report of the serious and unexpected adverse reactions (SUSARs) related to the IP that have occurred abroad

Final Report

As delineated in DecreeNo021-2017, the INS-CTManual, PER-72, PER-48, and PER-16, the sponsor or his/her CRO must submit a research site final report to the REPEC for each of the participating centers for a specific clinical trial within 30 calendar days following the closing visit made by the monitor. Per the INS-CTManual, this information should be provided regardless of the enrollment status of each center. The INS-CTManual also notes that the electronic form should also be printed and signed by the sponsor or his/her CRO and delivered to the INS’s Office of Documentary Procedure within 20 working days. Refer to the INS-CTManual for additional information, and PER-48 and PER-16 for the final report form and detailed submission instructions.

DecreeNo021-2017 also states that the final report should include the following information:

  • Number of screened, enrolled, and retired patients who completed the trial
  • Summary of serious SAEs/SADRs and non-serious AEs/ADRs related to the IP, and deviations occurring since the date of the last progress report

Further, according to DecreeNo021-2017, the INS, in coordination with the sponsor, must submit a Results Publication after the final national or international report is completed to provide the results of authorized and performed clinical trials through REPEC using the form FOR-OGITT-058 (PER-23). The sponsor is also obligated to submit an article to a national or international scientific journal that strictly reflects the final report submitted to the OGITT using the form FOR-OGITT-059 (PER-41). The published article must also be sent to the INS and the research institution in print and electronic media.

National Final Report

Per DecreeNo021-2017, DecreeNo021-2017-Corrections, the INS-CTManual, and PER-72, national final reports should be submitted to REPEC for the INS’s OGITT review within 60 calendar days following the date of the final report submission of the last research center. Per the INS-CTManual and PER-72, the national final reports should be electronically submitted (refer to PER-49 and PER-17 for the submission form and instructions).

For clinical trials performed only in Peru, the report must be submitted within a maximum period of six (6) months following the trial’s conclusion as indicated in DecreeNo021-2017, DecreeNo021-2017-Corrections, the INS-CTManual, and PER-72. The OGITT will send a copy of the final national report of clinical trials to the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) within 30 business days following receipt of the report.

Per the INS-CTManual, the electronic form should also be printed and signed by the sponsor or his/her CRO and delivered to the INS’s Office of Documentary Procedure within seven (7) working days. If applicable, a report of the study results and conclusions must be attached as established in the INS-CTManual. Refer to the INS-CTManual for additional information, and PER-49 and PER-17 for the national final report form and detailed submission instructions.

DecreeNo021-2017 further explains that the national final report should include the following information:

  • Number of screened, enrolled, retired patients who completed the trial
  • Summary of serious SAEs/SADRs and non-serious AEs/ADRs related to the IP, and deviations that occurred
  • For trials performed only in Peru, the report should also include the final results and conclusions of the trial

International Final Report

As delineated in DecreeNo021-2017, the INS-CTManual, and PER-72, international final reports should be submitted to REPEC within 12 months following the completion of the last clinical trial in all international research centers. Per the INS-CTManual, the sponsor or his/her CRO should also print and sign the electronic form and deliver it to the INS’s Office of Documentary Procedure within 20 working days. In addition, a report of the study results and conclusions should be attached as established in the INS-CTManual. PER-72 also notes that the report should include the results and the study conclusions before publication. Refer to the INS-CTManual for additional information, and PER-46 and PER-9 for the international final report form and detailed submission instructions.

VIII (8.4)
Articles 2, 40, 52, and 104-107
Chapter VII (7.13.3-7.13.5) and Flow Charts No. 25, 30, 31, and 32
Clinical Trial Progress Report and Final Reports
Last content review/update: June 29, 2021

Overview

As indicated in the G-CTAuth, GBR-65, and GBR-9, the investigator and the sponsor share responsibility for submitting progress reports on the status of a clinical trial and for submitting a final study report upon the trial’s completion. These requirements comply with the progress and final reporting requirements delineated in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113).

Interim and Annual Progress Reports

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

Health Research Authority (HRA)-approved research projects that have also been reviewed by an EC should submit regular progress reports to the HRA using the guidance outlined for ECs above.

Final Report

As per the MHCTR and the G-CTAuth, 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. The G-CTAuth 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 (contained in G-CTAuth and GBR-24) and a cover letter. Note that only the global end-of-trial notification is required to be submitted. However, a facility may inform 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, we would still expect to receive relevant safety updates and substantial amendments for the ongoing trial until the global end of trial notification is received. T. 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 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. Sponsors must submit end-of-trial declarations using MHRA Submissions (GBR-13). G-MHRASubmiss and GBR-11 outline the steps for gaining access to MHRA Submissions.

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

As per GBR-9, the investigator is also required to submit a summary of the final study report to the main EC within one (1) year of the trial’s conclusion. There is no standard format for final reports. However, the minimum information to be provided to the EC should include whether the trial achieved its objectives, the main findings, and arrangements for publication or dissemination of research.

Part 3 (Section 27)
End of Trial and Clinical Trial Summary Results
Terminology (Glossary), and Sections 1 and 14
4.10 and 4.13
Progress Reporting
Sponsorship > Definition of Sponsor
Last content review/update: November 19, 2020

Overview

DecreeNo021-2017 defines a sponsor as an individual, group of individuals, company, institution, or organization with legal representation in the country, and duly registered in the corresponding public registries. The sponsor takes ultimate responsibility for trial initiation, maintenance, conclusion, and financing. When an independent researcher initiates and takes full responsibility for a clinical trial, then he/she assumes the role of sponsor.

DecreeNo021-2017 and the G-CTApplicProc also state that sponsors not based in Peru are required to appoint a legal representative who channels all the communication with the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)) within Peru’s National Institute of Health (Instituto Nacional de Salud (INS)) for the trial’s duration.

DecreeNo021-2017 also explains that a sponsor can authorize a contract research organization (CRO) with legal status and an office in Peru to carry out certain work and obligations regarding the trial. However, the sponsor is ultimately responsible for the execution of the research protocol and the results of the trial.

For the purposes of data protection requirements, LawNo29733 provides that the “person in charge of the personal data bank” is any natural person, private legal entity, or public entity that, alone or acting in conjunction with another, performs the processing of personal data on behalf of the owner of the personal data bank. DecreeNo1353 and DecreeNo003-2013 modify the definition provided by LawNo29733 by stating that the entity “responsible for processing personal data” is any natural person, private legal entity, or public entity that, alone or acting jointly with another, performs the processing of personal data on behalf of the owner of the personal data bank by virtue of a legal relationship that binds him to it and defines the scope of its performance.

Article 2
Article 2
Article 2
Articles 41 - 45
6
Last content review/update: June 29, 2021

Overview

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 and the GBR-103, a clinical trial sponsor 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. If this is not the case, then the sponsor must have a legal representative who is so established. The GBR-103 specifies that details of the legal representative should be entered in the ‘legal representative’ section of Integrated Research Application System (IRAS) (GBR-78). The legal representative:

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

The MHCTR also permits two (2) or more parties to take responsibility for the sponsor’s functions. When this applies, the MHCTR requires one (1) of the parties to submit the clinical trial application for authorization to the Medicines and Healthcare Products Regulatory Agency (MHRA), and to specify who is responsible for carrying out the following functions:

  • Communications relating to substantial amendments, modified amendments, and the conclusion of the trial
  • Communications relating to urgent safety measures
  • Pharmacovigilance reporting

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

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 UK, as well as controller responsibilities.

Part 1 and Part 2 (Chapter 2)
Amendment of Regulation 3 of the Principal Regulations; Amendment of Regulation 12 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 1 (3)
Trial Sponsor and Legal Representative
What the Law Says - Controllers and personal data in health and care research
Changes to the trial sponsor/legal representative
Basic Principles and Table 1
Terminology (Statutory Definitions Relating to CTIMPS)
5.1 and 5.2
Responsibilities
Sponsorship > Trial Authorization
Last content review/update: November 19, 2020

Overview

In accordance with DecreeNo021-2017, and the INS-CTManual, the sponsor or his/her contract research organization (CRO) is responsible for ensuring his/her principal investigators (PIs) obtain approval from a National Institute of Health (Instituto Nacional de Salud (INS))-accredited ethics committee (EC). The sponsor or his/her CRO must then submit the clinical trial application to the INS to obtain authorization to conduct a clinical trial. Per the INS-CTManual, the G-CTApplicProc, PER-60, and PER-59, the sponsor and his/her CRO must also register with the INS’s Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) prior to submitting an application for clinical trial authorization. See also PER-36 and PER-37 for the sponsor and CRO registration forms.

As delineated in the INS-CTManual, the G-CTApplicProc, the G-CTSubmissionProcs, and PER-71, to complete the clinical trial application package, the sponsor or his/her CRO must submit a request for clinical trial authorization electronically using REPEC, at which time, a registration code is assigned to the application. In addition, per the INS-CTManual and the G-CTApplicProc, the application should be submitted both electronically via REPEC and in print format. The INS-CTManual states that the sponsor or his/her CRO should print and sign the electronic application form and deliver it to the INS’s Office of Documentary Procedure within 20 working days. The G-CTSubmissionProcs further specify that all documents contained in the printed copy must be on A4 size bond paper, in a folder of A4 size with a wide spine to allow for unrestricted opening between the sections, organized using separators, and foliated in the upper right hand corner per the requirements delineated in DecreeNo021-2017. In addition to sending a printed copy of the completed application, the sponsor or his/her CRO must also provide the EC approval letter, clinical protocol, the Investigator’s Brochure (IB), the informed consent form (ICF), and other documentation covered in the Clinical Trial Lifecycle topic, Submission Content subtopic.

Additionally, DecreeNo021-2017 states that the sponsor must inform the INS’s General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)) when the first research participant is enrolled in Peru as well as the enrollment termination date in the country.

Articles 40 and 67
1, 2, 4, 5, and Key Points
6
Chapter VII (7.1, 7.2, 7.3, and 7.5), Flow Charts No. 01, 02, and 04, and Annexes 1 and 3
Last content review/update: June 29, 2021

Overview

In accordance with the MHCTR, the MHCTR2006, the G-CTApp, GBR-2, and GBR-9, the sponsor or his/her designated representative is responsible for submitting a clinical trial application to the Medicines and Healthcare Products Regulatory Agency (MHRA) to obtain authorization to conduct a clinical trial. GBR-103 provides that if a sponsor(s) is not established in the United Kingdom (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 MHCTR-EUExit will refer to a list of countries where a sponsor of a clinical trial, or their legal representative, may be established; these countries are initially EU and EEA countries. 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 MHRA and the ethics committee (EC). From January 1, 2021, 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.

Per the G-MHRASubmiss, as of January 1, 2021, MHRA implemented new processes to submit regulatory and notification information to the UK. For clinical trial applications to the UK, including initial applications, substantial amendments, end-of-trial notifications, and developmental safety update reports (DSURs), applicants must submit information through UK’s national portals. The G-MHRASubmiss and GBR-11 provide steps for gaining access to MHRA Submissions (GBR-13).

According to the G-CTApp, applicants must complete the clinical trial authorization application form on the Integrated Research Application System (IRAS) (GBR-78). IRAS enables researchers to enter the information required by all UK review bodies only once, rather than having to complete several separate application forms to obtain these permissions and approvals. (See the Clinical Trial Lifecycle topic, Submission Content subtopic for documentation to be included in the application package.)

In addition to the completed application, per the MHCTR and the G-CTApp, the sponsor or his/her designated representative must provide the MHRA with a copy of the EC opinion (if available), the clinical protocol, the investigator’s brochure, a signed declaration by the investigators, a certificate of good manufacturing practice for the manufacture of the trial medicine, and other documentation covered in the Clinical Trial Lifecycle topic, Submission Content subtopic.

2
Part 2 (Conditions Based on Article 3 of the Directive)
Part 1 (3), Part 3 (12, 17, and 18), and Schedule 3 (Part 2)
Registration of Your Clinical Trial, Ethics Committee, Clinical Trial Authorization Application Form, Documents to Send with Your Application, and Assessment of Your Submission
Changes to the trial sponsor/legal representative
2
Introduction and Table 1
Section 14
Sponsorship > Insurance
Last content review/update: November 19, 2020

Overview

As set forth in DecreeNo021-2017, the G-CTApplicProc, and PER-71, it is a legal requirement for the sponsor or his/her contract research organization (CRO) to carry a valid insurance policy for the expected duration of the study for any unforeseen injury to research participants. Per ResolutionNo0423-2019 the sponsor or his/her CRO should sign an affidavit (PER-51) guaranteeing an active insurance policy is in place according to requirements in the INS-CTManual.

DecreeNo021-2017 also specifies that the sponsor or his/her CRO must obtain insurance coverage in Peru, or have a legal representative in Peru who will represent the sponsor or his/her CRO if the policy is from a foreign company. The insurance policy must be in force until the date of submission of the National Final Report. At the end of this period, it should be renewed whenever there is still a possibility of late damages arising from the adjudication of injuries resulting from the clinical trial.

See the Sponsorship topic, Compensation subtopic and Informed Consent topic, Compensation Disclosure subtopic for specific details related to sponsorship compensation obligations.

(Please note that Peru is in the process of finalizing new guidelines as well as the associated forms and instructions to support the ResolutionNo0423-2019 amendments to DecreeNo021-2017; ClinRegs is monitoring these developments.)

Annex (1)
Articles 2 and 28
6
Chapter VII (7.14)
Last content review/update: April 22, 2021

Overview

As set forth in the MHCTR and the MHCTR2006, it is a legal requirement for an insurance and indemnity provision to be made to cover the liability of the investigator and sponsor for trial related injuries. The MHCTR does not ascribe responsibility to the sponsor or his/her designated representative to obtain insurance and indemnity. However, GBR-2, GBR-103, and GBR-101, state that the sponsor or his/her designated representative is responsible for ensuring adequate insurance and indemnity arrangements are in place to cover the sponsor’s and the investigator’s potential liability, and for providing a copy of this coverage in the clinical trial application submission.

In addition, according to GBR-2, the sponsor or his/her 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 his/her designated representative’s requirement to insure or indemnify the investigator participating in industry-sponsored Phase I clinical trials.

The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113) also guides sponsors on providing insurance. See the Sponsorship topic, Compensation subtopic and Informed Consent topic, Compensation Disclosure subtopic for specific details related to sponsorship compensation obligations.

Part 2 (Conditions Based on Article 3 of the Directive)
Part 3 (15) and Schedule 1 (Part 1 (16))
6
Introduction, Basic Principles, and Table 1
5.8
Responsibilities
Sponsorship > Compensation
Last content review/update: November 19, 2020

Overview

As specified in DecreeNo021-2017 and the G-CTApplicProc, the sponsor or his/her contract research organization (CRO) is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death.

DecreeNo021-2017 also specifies that the sponsor or his/her CRO must obtain insurance coverage in Peru or have a legal representative in Peru who will represent the sponsor or his/her CRO if the policy is from another country. DecreeNo021-2017, the G-CTApplicProc, and PER-71 further state that the sponsor or his/her CRO must also submit an affidavit (PER-51) guaranteeing a financial fund is immediately and conveniently available. The fund ensures free medical treatment to participants who suffer any trial-related injuries, as long as the insurance policy is activated, and the sponsor or his/her CRO signs a statement to that effect. The G-CTApplicProc also explains that the amount designated for the financial fund is different from the amount indicated for the insurance policy coverage. The sponsor determines the financial fund amount based upon the number of participants to be included in the study and the possible adverse event risks. DecreeNo021-2017 also notes that participants must be ensured free access to the investigational product (IP) following the trial’s conclusion. Before the study commences, post-study access should be anticipated, and this information must be provided during the informed consent process.

In addition, as described in DecreeNo021-2017, compensation will be awarded in the following circumstances:

  • Any damage to the research participant as a result of his/her participation in the clinical trial
  • Any damage that occurred during pregnancy or that would have occurred to the newborn in the case of pregnancy in a female research participant or in the couple of the male research participant, as long as it is a result of their participation in the trial
  • Economic damages derived directly from earlier stated damages, provided that the damage is not inherent to the pathology under study, or to the individual evolution of the research participant

The sponsor’s obligation to award compensation is independent of the validity or available coverage of the contracted insurance.

(See Informed Consent topic, Compensation Disclosure subtopic for more information on participant compensation rights).

Articles 27-29, 40, 115 - 118, and Annex 4
6
Last content review/update: December 08, 2020

Overview

As specified in the MHCTR, the sponsor or his/her designated representative is responsible for providing compensation to research participants and/or their legal heirs in the event of Phase I trial-related injuries or death. According to GBR-33, the sponsor or his/her designated representative may be required to follow the principles set forth in the Association of the British Pharmaceutical Industry (ABPI)’s guidelines to comply with the United Kingdom (UK)’s participant compensation and treatment requirements due to Phase I trial-related injuries. The guidelines state that the sponsor should furnish written assurance to the investigator that the sponsor will agree to pay compensation to participants and/or his/her legal heirs in the event of trial-related injuries or death whenever a causal relationship with participation is demonstrated. The investigator, in turn, communicates this information to the relevant ethics committees (ECs).

The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (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. See the Informed Consent topic, Compensation Disclosure subtopic for additional information.

Part 3 (15), Part 4 (8), and Schedule 1 (Part 1 (1))
3 and 4
4.8 and 5.8
Sponsorship > Quality, Data & Records Management
Last content review/update: November 19, 2020

Overview

As stated in DecreeNo021-2017, the sponsor or his/her contract research organization (CRO) is responsible for ensuring that all information on the investigational product and additional documentation corresponds to the research protocol and complies with good clinical practices (GCPs), as well as the requirements established in DecreeNo021-2017.

DecreeNo021-2017 also specifies that the sponsor or his/her CRO is responsible for obtaining agreement from the investigators to ensure that they will allow monitoring, audits, ethics committee (EC) monitoring, and trial inspections by the National Institute of Health (Instituto Nacional de Salud (INS))'s General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)).

Data Protection

As delineated in LawNo29733, the person in charge of the personal data bank in data protection legislation, is required to protect the confidentiality of the owner of the personal data and his/her background. This obligation continues even after the conclusion of the relationship between the owner of the personal data and the person in charge. However, the person in charge of the personal data may be relieved of his/her obligation to uphold the owner’s confidentiality when there is prior, informed, explicit, and unequivocal consent by the owner, or, when there are justifiable reasons related to national defense, public safety, or public health.

According to LawNo29733, the person in charge of the personal data bank has the following obligations:

  • To carry out the processing of personal data, only with prior informed, explicit, and unequivocal consent of the owner of the personal data
  • To not collect personal data by fraudulent, unfair, or illegal means
  • To collect personal data that is updated, necessary, relevant, and adequate, in relation to specific, explicit, and lawful purposes for which the data was obtained
  • To not use the personal data processed for purposes other than those that motivated its collection, unless there is an anonymization or dissociation procedure
  • To store personal data in a way that allows the exercise of the owner’s rights
  • To delete and replace, or, where appropriate, correct the personal data subject to processing when he/she becomes aware of its inaccurate or incomplete nature, without prejudice to the rights of the owner in this regard
  • To delete personal data subject to processing when it is no longer necessary or relevant to the purpose for which it had been collected, or, the deadline for its treatment has expired, unless there is an anonymization or dissociation procedure
  • To provide the National Authority for the Protection of Personal Data with information related to the processing of personal data that it requires, and allow access to the personal data banks that it manages, for the exercise of its functions, within the framework of an administrative procedure in case it is requested by the affected party

DecreeNo1353 restates the obligations included in LawNo29733 above, however, the “person in charge of the personal data bank” is referred to as the “person in charge of processing personal data.”

DecreeNo003-2013 similarly states that the owner of the personal data bank or the person in charge of processing personal data must obtain the consent of the data holder to process his/her data in accordance with the provisions of LawNo29733 and this regulation. In cases involving sensitive data, consent must be granted in writing, through the personal data holder’s signature, digital signature, or any other authentication mechanism that guarantees the unequivocal will of the holder. Per DecreeNo003-2013, sensitive data is information related to personal data referring to physical, moral, or emotional characteristics, facts, or circumstances of an individual’s emotional or family life, personal habits that correspond to the most intimate sphere, or information related to physical health or mental or other analogs that affect an individual’s privacy.

Electronic Data Processing System

No relevant regulatory provisions

Record Management

As set forth in DecreeNo021-2017, the sponsor or his/her CRO is required to possess a documented monitoring record, including the provision of specially selected and specialized personnel (monitors). Additionally, the sponsor or his/her CRO is responsible for filing in the country all documentation and data obtained for at least 10 years after the conclusion of the study. After two (2) years, the documentation/data may be filed electronically, after communication with the INS.

Audit Requirements

As part of the clinical protocol requirements, DecreeNo021-2017 notes that the following data collection and monitoring activities should be implemented:

  • Develop plans to evaluate and collect baseline, outcome, and other study data, including a process to improve data quality and a description of instruments used in the study along with their reliability and validity, if known
  • Prepare plans to promote participant retention and complete follow up, including a list of data to be collected from participants who leave the trial or deviate from it
  • Document (or provide) data monitoring committee details including its composition, a summary of its role and notification procedure, a statement of its independence from the sponsor, and its conflicts of interest. Details about by-laws not included in the protocol should be specified, or an explanation about why this committee is not needed
  • Describe trial monitoring arrangements/audits and sponsor’s statement to ensure that investigators will allow monitoring, audits, EC monitoring, and INS’s OGITT trial inspections, including direct access to clinical trial documentation
  • Provide plans to enter, encode, protect and save data, including any process to improve its quality
  • Specify where data management procedure details not included in the protocol can be found

No specific timeframe is provided for the audit process.

The G-ClinTrialInspection explains that the INS’s OGITT inspection team carries out GCP inspections in accordance with DecreeNo021-2017. Trial inspection findings are based on the severity of the clinical trial conditions, practices, or processes and their potential to affect adversely the rights, safety, or well-being of the research participants and/or data quality and integrity. Inspections are carried out through ordinary and extraordinary inspections, with qualified personnel (multidisciplinary, if applicable) and may be conducted at the beginning, the middle, or the end of the trial. Ordinary inspections are conducted according to the OGITT’s Annual Schedule of Ordinary Inspections. Extraordinary inspections are performed in response to a complaint received by phone, written communication, formal document submitted through the INS reception desk, or from any relevant information received through safety reports, progress reports, and/or a justified request by a clinical trial evaluation team that has obtained OGITT approval. If required, the OGITT coordinates with the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) for the agency’s assistance in verifying compliance with good manufacturing practices standards, good storage practices, and other investigational product (IP) related standards. (Note: The ANM is also known as the General Directorate of Medicines, Supplies and Drugs (La Dirección General de Medicamentos Insumos y Drogas (DIGEMID))).

In addition, during an inspection, the evaluation of biological samples is conducted in accordance with the provisions in DecreeNo021-2017. Please refer to the G-ClinTrialInspection for detailed clinical trial inspection procedures.

The INS-CTManual and the G-ClinTrialInspection indicate that when a regulatory medicines agency of high health surveillance notifies a research center to carry out an inspection visit in Peru, the sponsor or his/her contract research organization (CRO) is required to inform the INS’s OGITT of the date and time of this visit within five (5) business days of receiving the notification. The OGITT will then coordinate with the regulatory medicines agency of high health surveillance to arrange for their participation in the inspection visit as an observer.

Per the INS-CTManual, for regular clinical trial inspections scheduled by the INS’s OGITT, when inspection findings are critical, the sponsor or his/her CRO is required to submit a defense within a period of no more than seven (7) working days following receipt of the inspection report. If the inspection observations are minor or major, the sponsor or his/her CRO should submit his/her defense within a period of no more than 15 working days, after receiving the inspection report. The inspector will issue an official notice of compliance within a period of no more than 15 business days if the sponsor or his/her CRO addresses the issues identified in the report in a timely way. Please refer to section 7.9 of the INS-CTManual for detailed information on preparing for the INS’s OGITT scheduled clinical trial inspections and responding to the inspection reports received.

Premature Study Termination/Suspension

DecreeNo021-2017 states that the sponsor or his/her CRO is responsible for submitting the required documentation to Peru's INS to request a trial’s suspension. Per DecreeNo021-2017 and ResolutionNo655-2019 (which modifies DecreeNo021-2017), an application must be submitted that substantiates the reasons for the suspension and describes the data obtained until the time of the suspension.

Multicenter Studies

Per DecreeNo021-2017, multicenter clinical trials require an appointed coordinator responsible for processing all of the data and analyzing the results.

Article 17, Title IV (Article 28)
Article 28
Annexes A and B
Article 2, 11, and 14
Articles 2, 40, 83, and Annex 1
6.2 and 7.5
Chapter VII (7.9)
Last content review/update: April 22, 2021

Overview

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 effect 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.

Data Protection

Per the UK-GDPR, the UK-DPAct, and the G-GDPR, the sponsor (known as the “controller” in data protection legislation) must comply with the 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 activity of processing data 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 type of organization that is the data controller for the processing:

  • 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. For additional information about consent and individual rights, see the Informed Consent topic, Documentation Requirements and Required Elements subtopics.

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 United Kingdom’s (UK) transition out of the European Union (EU), see GBR-16 and GBR-7.

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.

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 subject protection and reliability of trial results. In addition, the sponsor must maintain 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 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.

Audit Requirements

As part of its QA system, GBR-113 notes that the sponsor should ensure the trial is monitored. If or when the sponsor performs an audit, the purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, GBR-113, and other applicable regulatory requirements. The sponsor should appoint auditors to review the clinical trial. The sponsor should ensure that the auditors are qualified by training and experience, and auditor’s qualifications should be documented. The sponsor must also ensure that the audit is conducted in accordance with his/her own SOPs and the auditor observations are documented. 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

The G-CTAuth 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. The notification should be made as a substantial amendment using the notification of amendment form (GBR-25), clearly explaining what has been stopped and the reasons for the suspension. Substantial amendments relating to temporary suspension must be submitted using MHRA Submissions (GBR-13) via the Human Medicines Tile and selecting ‘Clinical Trial’ as the Regulatory Activity and ‘CT – Amendment’ from the Regulatory sub activity dropdown list. The G-MHRASubmiss and GBR-11 provide the steps for gaining access to MHRA Submissions (GBR-13). To restart a trial that has been temporarily suspended, the sponsor 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 and GBR-18, to terminate a trial, the sponsor must complete the end of trial declaration form (GBR-24) and include a brief explanation of the reasons for ending the trial, particularly when the trial has been terminated early. This form must be submitted using MHRA Submissions (GBR-13) via the Human Medicines Tile and selecting ‘Clinical Trial’ as the Regulatory Activity and ‘CT –EOT’ from the Regulatory sub activity dropdown list. GBR-18 specifies that the sponsor must make the end of trial notification to regulatory authorities (MHRA in the UK) and ECs of all countries with sites within 90 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.

Multicenter Studies

As delineated in GBR-113, in the event of a multicenter clinical trial, the sponsor must ensure that:

  • All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor
  • The case report forms (CRFs) are designed to capture the required data at all multicenter trial sites
  • Investigator responsibilities are documented prior to the start of the trial
  • All investigators are given instructions on following the protocol, complying with a uniform set of standards to assess clinical and laboratory findings, and completing the CRFs
  • Communication between investigators is facilitated

Data Monitoring Committee (DMC)

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.

Part 1, Part 2 (Chapter 2), and Schedules 2-4
Amendment of Regulation 31 of the Principal Regulations and Part 2 (Principles Based on Articles 2 to 5 of the GCP Directive)
Part 3 (15), Part 4 (28), Part 6 (36 and 38), and Schedule 7 (Parts 2 and 3)
Chapter II (Articles 5 and 6) and Chapter IV (Articles 24-43)
Suspend or Terminate a Trial and End of Trial
What the Law Says, What You Need to do
1.65, 5.0, 5.1, 5.2, 5.5, 5.18, 5.19, 5.21, 5.23, 6.10, and 8
Ongoing Management and Monitoring, MHRA Inspection, Temporary Halt or Termination, End of Trial Declaration, and Trial does not Recommence
Principles, Lawful Basis for Processing, Individual Rights, Accountability and Governance
Sponsorship > Site/Investigator Selection
Last content review/update: March 10, 2021

Overview

As set forth in DecreeNo021-2017, the sponsor or his/her contract research organization (CRO) 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 sponsor or his/her CRO must also ensure that the investigator(s) are qualified based on training and experience.

As delineated in DecreeNo021-2017, prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor or his/her CRO should provide the investigator(s) with the protocol and an investigator’s brochure (IB), and ensure that they agree to comply with good clinical practices and ethical standards.

Further, per DecreeNo021-2017 and ResolutionNo655-2019, which modifies DecreeNo021-2017, research centers must register with the Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)), but are no longer required to provide proof of this registration in the clinical trial authorization application. As delineated in ResolutionNo655-2019, the research institution’s legal representative must submit an application for registration that includes the following:

  • A code from the National Registry of Institutions that Provide Health Services (Registro Nacional de Instituciones Prestadoras de Servicios de Salud (RENIPRESS)) (Refer to PER-80 for instructions on how to register a health service provider institution in RENIPRESS.)
  • Details of the categorization level assigned to the health institution interested in obtaining registration as a research site to conduct clinical trials; (per ResolutionNo546-2011, categorization is based on the institution’s levels of complexity and functional characteristics)
  • Number and date of proof of payment of processing fees

According to PER-73, research centers should apply using the recently updated application form provided in PER-19 per ResolutionNo0423-2019, and complete the affidavit form in PER-44. Research center registration is valid for three (3) years. Refer to PER-73 for detailed registration instructions. Per DecreeNo021-2017, multicenter clinical trials require an appointed coordinator responsible for processing all of the data and analyzing the results.

Foreign Sponsor Responsibilities

DecreeNo021-2017 and the G-CTApplicProc state that if the sponsor is not based in Peru, he/she is required to appoint a legal representative in the country for the trial’s duration. As specified in DecreeNo021-2017, the sponsor may transfer any or all of his/her study related duties and functions to a CRO. However, he/she is ultimately responsible for the execution of the research protocol and results of the clinical trial.

Data Safety Monitoring Board (DSMB)

DecreeNo021-2017 requires the sponsor to provide data on the Data Safety Monitoring Board (DSMB) including its composition, a summary of its role and notification procedure, a statement of independence from the sponsor, and any conflicts of interest. Additionally, the sponsor should specify where to find other details about the by-laws not included in the protocol, or, explain why a DSMB is not necessary.

Preamble, Article 1, and Annexes (1)
Annexes A and B
Articles 2, 40-42, 53-57, 108, and Annexes 3 and 4
6
Last content review/update: April 22, 2021

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.

As delineated in the MHCTR, the MHCTR2006, GBR-113, and GBR-35, 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.

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, on June 5, 2019, the United Kingdom (UK) launched the UK Local Information Pack. Researchers working with National Health Service (NHS)/ Health and Social Care in Northern Ireland (HSC) organizations will use one (1) consistent package to support study setup and delivery across the UK. The Statement of Activities (used in England and Wales) and the Site Specific Information form (used in Northern Ireland and Scotland) are being replaced with a UK-wide Organizational Information document. The Organizational Information document will be a component of the Integrated Research Application System (IRAS) (GBR-78) form submission and will be required as part of the UK Local Information Pack for both commercial and non-commercial research. GBR-106 provides guidance, background information, and templates of the commercial and non-commercial versions of the Organizational Information document.

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 MHRA and the ethics committee (EC), pursuant to the guidelines in the G-CTAuth. 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.

Insertion of Regulation 3A of the Principal Regulations, Insertion of Regulation 29A of the Principal Regulations, and Part 2 (Principles based on Articles 2 to 5 of the GCP Directive)
Part 1 (3) and Part 3 (15)
Apply to Change Your Trial’s Protocol or Documentation
Changes to the trial sponsor/legal representative
2
5 and 9
5.5, 5.6, 6, and 7
Addition of New Sites and Investigators
Preparing and Submitting Application (Site-specific information)
Informed Consent > Documentation Requirements
Last content review/update: November 19, 2020

Overview

In all Peruvian clinical trials, a freely given informed consent must be obtained from each participant in accordance with the principles set forth in LawNo26842, DecreeNo021-2017, the G-EC-CTReview, and the Declaration of Helsinki (PER-76). DecreeNo011-2011-JUS further states that all scientific and technological research and applications will be developed with respect for the prior, free, express, and informed consent of the person concerned, based on adequate information. Consent in such terms implies the recognition of the patient's right to be treated as a free person and capable of making their own decisions.

Per DecreeNo021-2017 and the G-EC-CTReview, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an institutional ethics committee (EC) and provided to Peru’s National Institute of Health (Instituto Nacional de Salud (INS)) with the clinical trial application. (See the Informed Consent topic, Required Elements subtopic for details on what should be included in the form.) Per ResolutionNo233-2020, investigators must also submit any modifications or amendments to the initially approved research project and informed consent processes in a report to the EC in a timely manner, except in cases where these changes are necessary to prevent harm to the research participants when ECs must be informed within 24 hours. ResolutionNo233-2020 further indicates that participants must be kept constantly informed about the changes, progress, and results of the research according to the applicable regulations.

As delineated in DecreeNo021-2017, RegLawNo29414, the G-EC-CTReview, and ResolutionNo233-2020, investigator(s) must provide detailed research study information to the participant and/or his/her legal representative(s) or guardian(s). The ICF content should be presented briefly and clearly in writing, in a manner that is easy to understand, commensurate with the comprehension level of the research participants, and without coercion or unduly influencing a potential participant to enroll in the clinical trial. The participant and his/her legal representative(s) or guardian(s) should also be given adequate time to consider whether to participate. Per DecreeNo021-2017, when drafting and presenting the ICF, special consideration must be taken with regard to the participant’s culture, traditional values, intelligence, and education.

Re-Consent

As indicated in DecreeNo021-2017, the participant and/or his/her legal representative(s) or guardian(s) is required to sign a revised ICF if any changes occur in the protocol or in the treatment methods or procedures.

Language Requirements

Per DecreeNo021-2017, the ICF must be written in Spanish and in the language of the research participant.

Documentation Copies

DecreeNo021-2017 and the G-EC-CTReview state that the participant and/or the participant’s legal representative(s) or guardian(s), and the investigator(s) must sign and date the ICF. Where the participant is illiterate and/or his/her legal representative(s) or guardian(s) is illiterate, his/her fingerprint will serve as a signature, and should be obtained in the presence of and countersigned by an impartial witness who does not belong to the research team. Before participating in the study, the participant should receive a copy of the signed and dated ICF.

Consent for Processing Personal Data

Per LawNo29733, DecreeNo1353 (which modifies LawNo29733), and DecreeNo003-2013, consent to participate in research is not the same as consent as the legal basis for processing personal data under the data protection legislation.

However, LawNo29733 and DecreeNo003-2013 do provide definitions to address health related data. Per LawNo29733 and DecreeNo1353, sensitive data is defined as personal data constituted by biometric data that by themselves can identify the holder; data referring to racial and ethnic origin; economic income, opinions or political, religious, philosophical or moral convictions; union affiliation; and information related to health or sexual life. DecreeNo003-2013, in turn, provides the following definitions:

  • Personal data related to health – information concerning the past, present, or forecasted, physical or mental health of a person, including the degree of disability and their genetic information
  • Sensitive data – information related to personal data referring to physical, moral, or emotional characteristics, facts or circumstances of an individual’s emotional or family life, personal habits that correspond to the most intimate sphere, or information related to physical health or mental or other analogs that affect an individual’s privacy

The entity responsible for processing personal data must obtain the data holder’s consent per the provisions of DecreeNo003-2013, LawNo29733, and DecreeNo1353. However, in cases involving sensitive data, DecreeNo003-2013 specifies that consent must be granted in writing, through the data holder’s handwritten signature, digital signature, or any other authentication mechanism that guarantees the unequivocal will of the holder.

LawNo29733 and DecreeNo1353 also indicate that sensitive data is subject to special protection, and consent for the purposes of its treatment must also be made in writing. Even if the owner does not consent, the processing of sensitive data can be carried out when authorized by law, provided that it addresses important reasons of public interest.

In addition, LawNo29733 and DecreeNo1353 further explain that prior to the collection of his/her data, the holder of the personal data has the right to be informed of the following information in a detailed, simple, express, and unambiguous manner:

  • The purpose for which the personal data will be processed
  • Who the recipients are or may be
  • The existence of the databank in which his/her data will be stored, as well as the identity and address of the owner, and, if applicable, the person in charge of the processing of his/her personal data
  • The obligatory or optional nature of his/her answers to the questionnaire that is presented, especially regarding sensitive data
  • The transfer of personal data
  • The consequences of providing his/her personal data and his/her refusal to do so
  • The time during which his/her personal data is kept, and
  • The possibility of exercising the rights granted by law and the means provided for it
Title I (Articles 4-5) and Title II (Articles 25, and 27-28)
Articles 3, 13, 18, and Title IV (Article 28)
Articles 2 and 18
VIII (8.4)
Article 24
Article 2 and 18
II (3)
Articles 2, 11, 32, 33, 34, and Annex 4
Ethical Criterion 4, and Annexes 2 and 3
Last content review/update: June 29, 2021

Overview

In all United Kingdom (UK) clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the MHCTR, 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). The ICF must be provided to the EC with the clinical trial application. (See the Informed Consent topic, Required Elements subtopic for details on what should be included in the form.)

The MHCTR and G-ConsentPIS, state that the investigator(s) must provide detailed research study information to the participant and/or his/her legal representative(s) or guardian(s). The MHCTR and 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 his/her legal representative(s) or guardian(s), should also be given adequate time to consider whether to participate. Per G-ConsentPIS, the Participant Information Sheet (PIS) supports the consent process to help ensure participants have been adequately informed. In addition, the PIS forms part of the transparency information that must be provided to participants under the data protection legislation for the use and processing of personal data. 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. For more information about the sponsor’s and investigator’s responsibilities to comply with the data protection requirements (e.g., transparency, safeguards, and data rights), see the Sponsorship topic.

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.

Re-Consent

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

Language Requirements

As stated in the MHCTR, applications to the EC and the Medicines and Healthcare Products Regulatory Agency (MHRA) and any accompanying material, such as the ICF content, should be presented in English.

Documentation Copies

The MHCTR states that the participant and/or the participant’s legal representative(s) or guardian(s), and the investigator(s) must sign and date the ICF. Where the participant is illiterate, and/or his/her legal representative(s) or guardian(s) is illiterate, verbal consent should be obtained in the presence of and countersigned by an impartial witness.

Part 1(1), Part 2(2)
Amendment of Regulation 3 of the Principal Regulations; Amendment of Regulation 12 of the Principal Regulations; Amendment of Regulation 15 of the Principal Regulations; Amendment of Schedule 1 to the Principal Regulations; Amendment of Schedule 3 to the Principal Regulations; and Part 2 (Principles Based on Articles 2 to 5 of the GCP Directive and Conditions Based on Article 3 of the Directive)
Part 1 (3), Part 3 (12, 15, 17, and 18), Schedule 1 (Part 1 (3) and Part 2), and Schedule 3 (Parts 1 and 3)
Chapter I (Article 4), Chapter II (Article 6)
Principles, Content, and Examples and Templates
What the Law Says – Consent, What You Need to Do – Consent
Introduction (Purpose and Scope), Terminology (Glossary), and Section 1: New Applications for Ethical Review (Validations of Applications and Special Allocations to Flagged RECs (Allocation of CTIMPs to Recognised Ethics Committees))
2, 4.4, 4.8, 8.2, and 8.3
Informed Consent
Informed Consent > Required Elements
Last content review/update: November 19, 2020

Overview

As delineated in DecreeNo021-2017 and the G-EC-CTReview, prior to beginning a clinical trial, the sponsor or his/her contract research organization (CRO) is required to obtain ethics committee (EC) approval from an accredited institutional EC for the written informed consent form (ICF) and any other information being provided to the research participant and/or his/her legal representative(s) or guardian(s).

No Coercion

DecreeNo021-2017, RegLawNo29414, and the G-EC-CTReview state that none of the information concerning the research study, including the written ICF, should contain any language that causes the participant and/or his/her legal representative(s) or guardian(s) to waive or to appear to waive his/her legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

ICF Required Elements

Per DecreeNo021-2017 and the G-EC-CTReview, the ICF should include the following statements or descriptions, as applicable (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

  • Trial title (include version and date)
  • Sponsor(s), research institution, principal investigator (PI), EC, and the INS's General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)) contact information
  • Explicit invitation to participate in an experimental research study and the voluntary nature of participation
  • Trial rationale, objectives, and purpose
  • Trial treatments or interventions
  • Randomization and blinding procedures
  • Trial procedures and purpose
  • Expected duration of research participant’s involvement in trial­
  • The approximate number of participants in the study
  • Expected or unforeseeable risks and discomforts arising from the trial
  • Free treatment and procedures used as part of the trial design
  • The expected benefits that can be obtained from the study
  • If there are alternative procedures that could be advantageous to the participant
  • The commitments assumed by the participant if he/she agrees to participate in the study
  • The guarantee of receiving answer to any question and clarification to any doubt about the procedures, risks, benefits, and other trial related matters and the treatment of the participant
  • In the event of trial-related injuries, contact information for the PI, the EC president, and the OGITT
  • Participant’s right to withdraw his/her consent at any time and to stop participating in the study without creating any detriment to continue his/her care and treatment
  • The extent to which confidentiality of records identifying the participant will be maintained and the possibility of record access by National who may have access to these records
  • The participant and/or his/her legal representative agrees to authorize access to his/her personal data to verify procedures and/or trial data without violating the participant’s confidentiality
  • The extent to which confidentiality of records identifying the participant will be maintained, and the possibility of record access by the National Institute of Health (Instituto Nacional de Salud (INS)) and the EC
  • The commitment to provide up-to-date information about the investigational product (IP) or procedure, or when the participant requests this information, although this may affect the participant’s willingness to continue participating
  • Foreseeable circumstances and/or reasons under which the investigator(s) may remove the participant without his/her consent
  • Medical treatment and compensation available to the participant in the case of trial-related injuries and proof of the sponsor’s insurance contract
  • Economic compensation for additional expenses (e.g., transportation, accommodation, communication, and food)
  • Specify when final trial results will be provided to participant
  • Inform the participant of post-study access to IP after trial completion
  • Provide a trial description in the INS’s Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC))

The G-EC-CTReview states that the participant should be provided with detailed information on the biological samples to be collected and stored. Per DecreeNo021-2017, if biological sample storage and collection is being considered for future use, then this point should be made explicit in an additional ICF. Refer to the Specimens topic, Consent for Specimens subtopic for further information on participant consent requirements for use of biological samples.

See the Informed Consent topic, Compensation Disclosure and Vulnerable Populations subtopics for further information.

Article 24
Articles 32, 34, 40, 67, 115-118, and Annex 4
Preamble, VII, Ethical Criterion 4, Ethical Criterion 5, and Annex 2
Last content review/update: April 22, 2021

Overview

As delineated in the MHCTR, the MHCTR2006, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), prior to beginning a clinical trial, the chief investigator (CI) is required to obtain a favorable opinion from a recognized ethics committee (EC) for the written informed consent form (ICF) and any other information being provided to the research participant and/or his/her legal representative(s) or guardian(s).

No Coercion

As per the G-ConsentPIS and GBR-113, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant and/or his/her legal representative(s) and/or guardian(s) to waive or to appear to waive his/her legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

Participant Information Sheet

Per the 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 indicated in the G-GDPR and GBR-100, the Health Research Authority (HRA) has developed a series of templates 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 (i.e., before or after May 25, 2018).

Per the UK-GDPR and the UK-DPAct, consent to participate in research is not the same as consent as the legal basis for processing under the data protection legislation. For more information about the sponsor’s and investigator’s responsibilities to comply with the data protection requirements (e.g., the lawful basis to hold and use personal data, transparency, safeguards, and data rights), see the Sponsorship topic.

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

Informed Consent Form Required Elements

Based on the MHCTR, the G-ConsentPIS, and GBR-113, the ICF should include the following statements or descriptions, as applicable. (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

  • The study purpose, procedures, and duration
  • Study title and the study 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 ECs, the auditor(s), and the monitor(s)
  • That the participant and/or his/her legal representative(s) or guardian(s) will be notified if significant new findings developed during the study may affect the participant's willingness to continue
  • Individuals to contact for further information regarding the trial, the rights of trial participants, and whom to contact in the event of trial-related injury
  • Foreseeable circumstances under which the investigator(s) may remove the participant without his/her consent

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

(See the Informed Consent topic, Compensation Disclosure and Vulnerable Populations subtopics and the Specimens topic, Consent for Specimen subtopic for further information.)

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

Part 1 (1), Part 2 (2)
Amendment of Regulation 3 of the Principal Regulations; Amendment of Regulation 12 of the Principal Regulations; and Amendment of Schedule 3 to the Principal Regulations
Part 1 (3), Part 3 (12 and 15), and Schedule 3 (Parts 1 and 3)
Chapter I (Article 4), Chapter II (Article 6)
Principles of consent: General principles and Role of Participant Information Sheets; Content: Participant Information Sheet and Consent Form
What the Law Says – Consent, What You Need to do – Consent
1 and 2
4.4 and 4.8
Informed Consent > Compensation Disclosure
Last content review/update: November 19, 2020

Overview

In accordance with DecreeNo021-2017 and the G-EC-CTReview, the informed consent form (ICF) should contain a statement describing the compensation and medical treatment a participant can receive for participating in a clinical trial.

Compensation for Participation in Research

As delineated in Annex 4 of the DecreeNo021-2017 and Annex 2 of the G-EC-CTReview, the ICF should contain a statement describing the financial compensation participants can receive for additional expenses (travel, accommodations, communication, and food) incurred while participating in the trial. The ICF must also explicitly list the specific amount to be provided for each additional expense.

DecreeNo021-2017 also states that participants must be ensured free access to the investigational product (IP) following the trial’s conclusion. Before the study commences, post-study access should be anticipated, and this information must be provided during the informed consent process. The G-EC-CTReview further specifies that the ICF should explain if the IP will be made available to participant(s) for whom the product has proven to be beneficial. A trial clinician will indicate when and how the participant may obtain the product once the trial has concluded.

Compensation for Injury

Per DecreeNo021-2017 and the G-EC-CTReview, the ICF should include a statement advising the participant that compensation and free medical treatment are available in the event of any trial-related injury. In addition, the G-EC-CTReview states that the ICF should also state that compensation for the participant’s and/or his/her legal representative(s) or guardian(s) should also be provided in the event of the participant’s death or disability resulting from the trial.

The G-EC-CTReview further notes that insurance coverage should also be provided to the participants.

(See the Informed Consent topic, Required Elements subtopic for additional details on what should be included in the ICF.)

Articles 34, 35, 40, 115-118, and Annex 4
Ethical Criterion 5 and Annex 2
Last content review/update: December 08, 2020

Overview

In accordance with the MHCTR, the G-ConsentPIS, and GBR-35, the informed consent form (ICF) should contain a statement describing the compensation or medical treatment a participant can receive for participating in a clinical trial.

Compensation for Participation in Research

As stated in the MHCTR and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), ethics committees should consider, in particular, the provision of indemnity or compensation in the event of injury or death attributable to the trial.

Compensation for Injury

As per the MHCTR and GBR-113, the ICF should contain a statement advising the participant of available compensation and medical treatment in the event of any trial-related injury in a clinical trial.

(See the Informed Consent topic, Required Elements subtopic for additional details on what should be included in the ICF, and the Sponsorship topic, Compensation subtopic for information on sponsor requirements.)

Schedule 1 (Parts 4 and 5)
Principles of consent: General principles and role of Participant Information Sheets
19
3.1, 4.8, and 5.8
Informed Consent > Participant Rights
Last content review/update: November 19, 2020

Overview

In accordance with LawNo26842, DecreeNo021-2017, the G-EC-CTReview, ResolutionNo233-2020, the PeruConstitution, DecreeNo011-2011-JUS, and the Declaration of Helsinki (PER-76), Peru’s ethical standards promote respect for all human beings and safeguard the rights of research participants. Per DecreeNo021-2017, the G-EC-CTReview, and ResolutionNo233-2020, 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

DecreeNo021-2017, RegLawNo29414, and the G-EC-CTReview state that the participant or his/her legal representative(s) or guardian(s) should be informed that participation is voluntary, that he/she may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As explained in DecreeNo021-2017, RegLawNo29414, and the G-EC-CTReview, a potential research participant and/or his/her legal representative(s) or guardian(s) has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

Pursuant to DecreeNo021-2017 and the G-EC-CTReview, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. The ICF must also incorporate the following items related to privacy:

  • Data the participant will have access to and what information will be collected
  • How collected data will be used, stored and protected, and who will have access
  • That representatives of the sponsor, ethics committee (EC) and the National Institute of Health (Instituto Nacional de Salud (INS)) will have access to the data
  • How biological data and samples are handled if consent is withdrawn
  • That participants’ data will be de-identified in the case of publications and presentations of the clinical trial results

Per LawNo29733, DecreeNo1353 (which modifies LawNo29733), and DecreeNo003-2013, participants have the right to be informed about the collection and use of their personal data. LawNo29733 further states that the owner of the personal data bank, the person in charge, and others involved in any way with processing an individual’s personal data are obligated to protect the confidentiality of his/her background and data. This obligation continues even after the conclusion of the relationship between the personal data holder and the entity responsible for the data. However, the person in charge of the personal data may be relieved of his/her obligation to uphold the owner’s confidentiality when there is prior, informed, explicit, and unequivocal consent by the owner, or, when there are justifiable reasons related to national defense, public safety or public health.

The Right of Inquiry/Appeal

Per DecreeNo021-2017 and the G-EC-CTReview, the research participant and/or his/her legal representative(s) or guardian(s) should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries and/or to appeal against a violation of his/her rights.

The ICF must guarantee that the participant will receive answers to any questions and clarification to any doubt about the procedures, risks, benefits and other matters related to the clinical trial and the treatment of the participant. There must also be a commitment to provide up-to-date information about the product or procedure under investigation when the participant requests it.

The Right to Safety and Welfare

DecreeNo021-2017, the G-EC-CTReview, and DecreeNo001-2011-JUS indicate that the research participant’s dignity, safety, and welfare must be guaranteed while ensuring the quality of the research process in developing new products. The G-EC-CTReview further states that the interests of science cannot take precedence over the interests of the research participants.

Title I (Articles 4 and 5) and Title II (Articles 25, 27, and 28)
Articles 5, 9, 13, 17-18, and Title IV (Article 28)
Chapter 1 (Articles 1 and 2) and Chapter 2 (Article 7)
Article 18
I and VIII (8.4)
Articles 18 and 24
Articles 11 and 14
Preamble, Article 2, II (1-3), and V (1 and 6)
Articles 4, 9, 34, and 40, and Annex 4
VII, Ethical Criterion 4, Ethical Criterion 5, Annex 2
Last content review/update: April 22, 2021

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 his/her legal representative(s) or guardian(s) should be informed that participation is voluntary, that he/she may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As delineated in the MHCTR, the G-ConsentPIS, and GBR-113, a potential research participant and/or his/her legal representative(s) or guardian(s) has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

As per the MHCTR 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.

Per 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. For more information about the sponsor’s (called the “controller” in the UK-GDPR) data protection requirements, see the Sponsorship topic, Quality, Data & Records Management subtopic.

The Right of Inquiry/Appeal

The MHCTR and GBR-113 state that the research participant and/or his/her legal representative(s) or guardian(s) should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries.

The Right to Safety and Welfare

The MHCTR, 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.

Part 1, Part 2 (Chapter 2), Schedules 2-4
Amendment of Regulation 3 of the Principal Regulations; Amendment of Schedule 1 to the Principal Regulations; and Part 2 (Principles Based on Articles 2 to 5 of the GCP Directive and Conditions Based on Article 3 of the Directive)
Part 1 (3 and 15), Schedule 1 (Parts 1, 2, and 5)
Chapter II (Articles 5 and 6), Chapter III (Articles 12-23)
Principles and Content
What the Law Says – Consent, What You Need to do – Consent
4.8
Principles and Individual Rights
Informed Consent > Special Circumstances/Emergencies
Last content review/update: November 19, 2020

Overview

The G-EC-CTReview and LawNo1384, which amends LawNo295, make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by special circumstances. Special circumstances include when a participant is mentally incapacitated.

Research Involving Persons in a Coma

As delineated in the G-EC-CTReview, persons in a comatose state may be involved in a clinical study as long as the appropriate legal representative(s) or guardian(s) are in place that comply with LawNo1384, which amends LawNo295. According to LawNo1384, any legal representative(s) or guardian(s) designated prior to a person becoming comatose will be upheld. However, for those persons who have not designated a legal representative(s) or guardian(s), a judge shall designate the necessary supports and safeguards. This measure will only be taken after efforts have been made to obtain the person’s consent and when the designation of legal representative(s) or guardian(s) is necessary for the exercise and protection of his/her rights.

Article 2
Title V (Articles 44-45)
Ethical Criterion 4
Last content review/update: December 08, 2020

Overview

The MHCTR, the MHCTR2006-No2, the MHCTR-BSQ, GBR-3, 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 is complicated by special circumstances. Special circumstances include medical emergencies and when a participant is mentally incapacitated.

Medical Emergencies

As delineated in the G-ConsentPIS, GBR-3, and GBR-4, in an emergency, if the signed informed consent form (ICF) cannot be obtained from the research participant, the consent of his/her legal representative(s) or guardian(s) should be obtained. If the prior consent of the participant or his/her legal representative(s) or guardian(s) cannot be obtained, the participant’s enrollment should follow measures specified in the protocol, and the ethics committee (EC) must provide documented approval in order to protect the participant’s rights, safety, and well-being. The participant or his/her legal representative(s) or guardian(s) should provide consent as soon as possible.

The MHCTR-BSQ amends the MHCTR and creates an exception for minors participating in a trial where urgent treatment is required and prior consent cannot be obtained. This situation also requires the EC to issue its approval beforehand.

Mentally Incapacitated Persons

The 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 UK 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 (IMP) 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
Section 51
2 and Explanatory Note
4 and Explanatory Note
Schedule 1 (Parts 4 and 5)
Principles of Consent: Emergency Research
4.3
5.5.4
4.8.15
Informed Consent > Vulnerable Populations
Last content review/update: November 19, 2020

Overview

As per DecreeNo021-2017, in all Peruvian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. Additionally, the G-EC-CTReview specifies that the ethics committee (EC) should identify the vulnerabilities of the research participants to determine the additional protections required and to protect their welfare and rights.

DecreeNo021-2017 defines vulnerable populations are those who are relatively (or absolutely) incapable of protecting their own interests due to a lack of autonomy, intelligence, education, resources, strength, or other necessary attributes. This may include those in subordinate groups, indigenous or native peoples, and those who cannot give their consent. In addition, per DecreeNo011-2011-JUS, in the case of individuals who do not have the capacity to exercise their autonomy, measures will be taken to safeguard their rights, always ensuring what is most favorable to them. The protection of human life considers the protection of health, as well as taking into account vulnerability and personal integrity. DecreeNo011-2011-JUS further explains that the cultural and plural diversities of Peru cannot represent a justification for transgressing legitimate limits established by the recognition of the principle of respect for human dignity.

See the Informed Consent topic, and the subtopics of Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired for additional information about these vulnerable populations. Information on the other vulnerable populations specified in DecreeNo021-2017 is provided below.

Persons in Subordinate or Dependent Groups

Clinical trials involving participants who are involved in subordinate or dependent relationships must meet the following requirements:

  • One or more of the ethics committee (EC)’s members must represent the population under study or work with someone who has expertise in addressing social, cultural, and other issues related to the group in question
  • A participant’s refusal or withdrawal of consent during the trial should not affect his/her performance review or result in any negative consequences to the participant

These relationships include participants who are in junior or subordinate positions in hierarchically structured groups, such as students and teachers, employees and their supervisors, and soldiers and their superiors in military settings.

Research Involving Indigenous Communities

As explained in DecreeNo021-2017, clinical trials involving participants from indigenous communities may only be conducted under the following conditions:

  • When the expected benefit is reasonably assured; that is, when the product or knowledge generated by research is available or applied for the benefit of the community
  • The principal investigator (PI) has the approval to conduct the trial from the regional health authority and other authorities in the community, in addition to obtaining informed consent from trial participants
  • Sponsors and investigators develop culturally appropriate ways through working with anthropologists, sociologists, and translators to communicate the necessary information, and to meet the standards required in the informed consent process. In addition, the research protocol must describe and justify the methods the investigators plan to use to communicate information to research participants
  • Investigators agree to discontinue using individual participants when the community does not have the capacity to understand the implications of the participants’ involvement in the trial, despite the use of a translator or interpreter
  • In the case of including biological storage samples, it must have the authorization of the corresponding regional and local government, and of the respective community authorities, who must consider the interest of the community involved

The G-EC-CTReview further notes that the EC should ensure it has adopted all the appropriate measures when running a clinical trial in a community to minimize the potentially negative effects on the group and to ensure the community’s active involvement in the trial. The G-EC-CTReview also references DecreeNo021-2017’s provision pertaining to indigenous communities, which requires approval by the community’s authorities to conduct the study prior to obtaining individual informed consent. However, approval by the community authorities may not replace the consent of each individual research participant within the group.

Research Involving Participants with Physical Disabilities

Per DecreeNo021-2017 and DecreeNo021-2017-Corrections, in clinical trials involving participants with physical disabilities that prevent them from signing the informed consent form (ICF), but with the mental capacity to provide their consent, their legal representative(s) may grant his/her written consent by printing his/her fingerprint. This consent must be provided in the presence of at least one (1) witness designated by the participant and does not belong to the research team, and who in turn will sign the ICF. If the participant is unable to sign or provide a fingerprint, another means may be used that the participant approves. In this case, his/her legal representative(s) are required to sign the ICF with a witness present who is not a member of the research team. The participant and/or his/her legal representative(s) may withdraw his/her consent at any time without negative consequences as long as the withdrawal does not jeopardize the participant’s health.

Additionally, in the case of participants who, due to disabilities, are unable to give their informed consent and have not given consent prior to the onset of their disability, the following provisions must be met:

  • The informed consent must comply with the requirements delineated in the Informed Consent topic, Required Elements subtopic
  • The protocol must be approved by an EC that has experts in the disease under study, or, has consulted on the clinical, ethical and psycho-social aspects in the area of the disease and the group of patients affected

The G-EC-CTReview also notes that, per LawNo1384 which amends LawNo295, persons with disabilities have an equal capacity to exercise their rights in all aspects of life, including the right to choose to be a participant in a research study with the support of a legal representative(s), if applicable. In addition, LawNo1384 states that any person with a disability that requires reasonable adjustments or support to exercise his/her legal rights may request or designate a legal representative(s) of his/her choice for assistance. Persons with disabilities who cannot communicate their own wishes will receive support and safeguards from judicially designated entities.

Articles 1 and 2
Title II (Article 3) and Title V (Articles 42-44, and 46-47)
II (1-3)
Articles 2, 19, 24, 25, 33 and 38
Ethical Criterion 4, Ethical Criterion 5, and Ethical Criterion 6
Last content review/update: December 08, 2020

Overview

As per the MHCTR, GBR-3, GBR-4, 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. GBR-3, GBR-4, and GBR-35 characterize vulnerable populations as those who are dependent on others and are unable to express their opinion freely or make their own decisions. These participants may include children, persons with mental or physical incapacities, persons with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, prisoners, detainees, refugees, members of a group with a hierarchical structure, such as students, subordinate hospital and laboratory personnel, pharmaceutical industry employees, members of the armed forces, and persons kept in detention.

See the Informed Consent topic, and the subtopics of Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired for additional information about these vulnerable populations.

Schedule 1 (Parts 1, 4, and 5)
10.3
4.3
1.3
1.61, 3.1, and 4.8
Informed Consent > Children/Minors
Last content review/update: November 19, 2020

Overview

Pursuant to LawNo27337, LawNo295, LawNo1384, and the G-EC-CTReview, the age of majority is 18 years of age. Per LawNo295 and the G-EC-CTReview, children under 16 are considered to be absolutely incapable of providing consent, except for those acts determined by law. Individuals who are over 16 and under 18 are considered to be relatively incapable of providing consent. However, individuals older than 16, who are married or have obtained an official title authorizing them to practice a profession or trade, are exempt from this regulation. Per LawNo295 and LawNo1384, females over 14 who are married are also exempt from this regulation. If a marriage is terminated, individuals who acquire this capacity by marriage do not lose this right. LawNo1384 further clarifies that individuals over 14 and under 18 who marry, or who become parents are considered fully capable of providing consent.

Per DecreeNo021-2017 and the G-EC-CTReview, assent should also be obtained from a child or adolescent under 18 years of age. DecreeNo021-2017 and the G-EC-CTReview note that children aged eight (8) to adolescents under 18 years of age are generally considered to be capable of understanding the explanation of the research as a research participant and can give their assent.

In addition to a minor providing his/her assent, DecreeNo021-2017 and the G-EC-CTReview state that the consent of both parents or his/her legal representative(s) or guardian(s) is required. Per DecreeNo021-2017, the consent of the legal representative(s) or guardian(s) may only be dismissed in the case of death, loss of rights according to Decree requirements, or, proven impossibility to obtain consent has been documented appropriately. In the event that one parent is a minor, the consent of the direct ascendant relative is also required unless the parent is a minor of 16 years of age or more, the participant has gotten married, or, has obtained an official professional or trade title as earlier noted per LawNo295. The assent of a pediatric participant from the age of 8 and under 18 years of age must be obtained to participate in an investigation.

DecreeNo021-2017 further explains that all pediatric participants should be fully informed about the trial and its risks and benefits in language and terms that they are easily able to understand. The investigator(s) must also accept the withdrawal of informed consent at the request of the child’s legal representative(s) or guardian(s) at any time, provided that the child’s health will not be jeopardized. A minor who is a teenager must also be excluded from a trial when a conflict of views exists between the legal representative(s) or guardian(s) and the teenager. A minor who reaches the age of majority during a trial must provide consent before he/she can continue to participate in the study.

In addition, an ethics committee (EC) that has a specialist in pediatrics, or has obtained advice on the clinical, ethical, and psycho-social aspects of the trial from a pediatric expert, if applicable, must approve the protocol.

Preliminary Title (Article 1)
Article 1
Title V (Articles 42-46)
Articles 2, 18, 33, and 36
Ethical Criterion 4
Last content review/update: June 29, 2021

Overview

According to the MHCTR, a minor is an individual under 16 years of age. However, per GBR-4, in situations where the MHCTR does not apply, a minor is an individual under 18 years of age.

As set forth in the MHCTR, the MHCTR2006, 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 his/her legal representative(s) and/or guardian(s). As per GBR-4, legally, the researcher needs only to obtain consent from one (1) person with parental responsibility; however, consent from all legal representative(s) and/or guardians is encouraged.

Additionally, precautions against possible physical and mental harms should be exercised. All pediatric participants should be informed to the fullest extent possible about the study in language and terms that they are easily able to understand. The rights of the minors should also be respected for their voluntary decision to participate in a clinical study.

The MHCTR, the MHCTR2006, GBR-4, GBR-9, and GBR-35 state that a study may only be conducted on minors if several conditions are fulfilled including:

  • An ethics committee (EC), following consultation with pediatric experts, has endorsed the protocol
  • The legal representative(s) and/or guardian(s) has had an interview with the investigator(s) to understand the trial objectives and risks, been provided with a point of contact for further information, and been informed of the right to withdraw the minor from the trial at any time
  • No incentives or financial inducements are given to the minor or his/her legal representative(s) and/or guardian(s) except in the event of trial-related injury or loss
  • The trial relates directly to a condition from which the minor suffers, or, is of such a nature that it can only be carried out on minors
  • The participant(s) will derive some direct benefit from their participation in the trial
  • The trial is necessary to validate data obtained in other trials involving persons able to give informed consent, or, by other research methods
  • The trial has been designed to minimize pain, discomfort, fear, and any other foreseeable risk in relation to the disease and the minor’s stage of development

See the MHCTR, the MHCTR2006, 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 delineated in GBR-4, if a minor is deemed competent to give assent to decisions about participation in research, the investigator(s) must obtain that assent in addition to the consent of his/her legal representative(s) and/or guardian(s). If the child does not assent, this should be respected.

Furthermore, GBR-4 states that a minor’s ability to assent or consent is based on his/her ability to understand and assess options, rather than on his/her age. For a minor to be able to have the capacity to make a particular decision, he/she must be able to:

  • Comprehend and retain information material to the decision, especially the consequences of having or not having any intervention
  • Use and weigh this information in a decision-making process
  • Reach and communicate a decision

In addition, GBR-4 specifies that if the competent minor specifically asks for the family not to be involved, and they cannot be persuaded otherwise, his/her privacy should be respected.

Amendment of Schedule 1 to the Principal Regulations; Amendment of Regulation 15 of the Principal Regulations; and Part 2 (Conditions Based on Article 3 of the Directive)
Part 1 (2) and Schedule 1 (Part 4)
10.3
5
2.51-2.58
4.8.12
Informed Consent > Pregnant Women, Fetuses & Neonates
Last content review/update: November 19, 2020

Overview

As per DecreeNo021-2017, studies involving women of childbearing age or who are pregnant require additional safeguards to ensure that the research assesses the risks and benefits as well as any potential impact on fertility, pregnancy, the embryo or fetus, labor, lactation, and the newborn.

Clinical trials may only be conducted under the following conditions:

  • The informed consent of the woman and her spouse or partner is obtained, and they are given information about any potential risks to the embryo, fetus, or newborn prior to the trial
  • The spouse’s or partner’s consent may only be dismissed in the case of death; their inability to provide reliable consent; loss of rights; or, when there is imminent risk to the health or life of the woman or the embryo, fetus, or newborn
  • Informed consent may be withdrawn by the woman or spouse’s or partner’s request at any time, without detriment to them, provided the woman or fetus is not endangered
  • The research must be preceded by trials in non-pregnant women to demonstrate their safety, except for specific tests that require pregnant participants
  • The research must be aimed at improving the health of pregnant women and represent only a minimal risk to the embryo or fetus and the participant
  • During the study, investigators will not have the authority to decide on the timing, method, or procedure used to terminate the pregnancy, or to participate in decisions about the viability of the fetus
  • Informed consent for pregnant teenagers complies with the requirements stated in the Informed Consent topic, Children/Minors subtopic

Clinical trials may only be carried out in women in labor, postpartum, or breastfeeding when the following conditions are met:

  • Consent must be obtained before labor starts
  • Research will be authorized in postpartum women and breastfeeding only when there is minimal risk to the infant
  • Informed consent may be withdrawn at the participant’s or spouse’s or partner’s request at any time, without detriment to them, provided they do not affect or endanger the mother or the fetus or infant
  • The clinical trial has the potential to generate direct benefits greater than the risks to the nursing woman or child after birth

See Title III, Chapter II (Article 23) of DecreeNo021-2017, for additional details on embryos, fetuses, and newborns.

Research Involving Men and Women with Reproductive Capacity

Clinical trials involving men and women with reproductive capacity are only permitted under the following conditions:

  • For women, the principal investigator (PI) must conduct a pregnancy test to rule out any pregnancies, and to secure commitment from the women to use effective contraceptive methods. The sponsor will provide free access and a list of contraceptive methods to the participant(s) to be selected by the participant(s) and consistent with the trial
  • In the event of pregnancy during the study, the protocol should establish the exclusion of the mother; the application of procedures to monitor and control the pregnancy as well as monitoring and control of the newborn until at least six (6) months of age to identify any effects related to the investigational product
  • For men, the PI must secure a commitment from the men to prevent conception, and to use effective contraceptive methods to be provided free of charge to the participant(s) by the PI/sponsor, as specified in the protocol and the informed consent form
Articles 20-23 and Annex 4
Last content review/update: December 08, 2020

Overview

The G-ConsentPIS states that in studies where there could be harm to an unborn child and/or risk to an infant 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.

For women, researchers must give a clear warning to potential participants when there is a risk of harm to an unborn child or risk when breastfeeding. The information should include 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. Information concerning the importance of careful contraception and what to do if their partner becomes pregnant is essential. 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 his/her legal representative(s) and/or guardian(s)) during the consent process and with young potential participants as part of the assent process
  • Consider local social beliefs
  • Involve pediatricians and the ethics committee in preliminary discussions if this is a concern
  • Consult young people when designing consent and writing information
  • Respect the young person's autonomy but encourage involvement of the parents
  • Be aware that in CTIMPs, it is the parents of children under 16 who legally provide consent, and this will include consent to pregnancy testing and discussion of contraception
  • Information needs to go beyond "We will do a pregnancy test…" to include, what in broad terms, will happen

As set forth in GBR-35, any research studies involving women capable of becoming pregnant and breastfeeding women require additional safeguards to ensure the research conforms to appropriate ethical standards and upholds societal values. According to GBR-35, the following conditions are required for research to be conducted with this population:

  • Reproductive toxicology studies have been completed and the results support conducting a trial, or, there is a good reason not to conduct the reproductive toxicology studies and/or the risk of pregnancy is minimized (e.g., because she agrees to adhere to a highly effective method of contraception); Women using a hormonal contraceptive, such as “the pill,” should use an alternative method of contraception until the possibility of an interaction with the investigational product has been excluded
  • The female participant is not pregnant according to her menstrual history and a pregnancy test, and is not at risk of becoming pregnant during, and for a specified interval, after the trial
  • The female participant is warned about the potential risks to the developing child should she become pregnant, and she is tested for pregnancy during the trial, as appropriate
  • The female is tested for pregnancy before dosing starts and possibly during the trial, as appropriate
Content – Participant Information Sheet
10.3
Informed Consent > Prisoners
Last content review/update: November 19, 2020
No relevant provisions
Last content review/update: December 08, 2020

Overview

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

1.61
Informed Consent > Mentally Impaired
Last content review/update: November 19, 2020

Overview

The Peruvian government recently passed LawNo30947 to establish a legal framework that guarantees access to services, promotion, prevention, treatment and rehabilitation in mental health as conditions for the full exercise of the right to health and well-being of the person, the family, and the community. The law states that mental health care takes into account the model of community care as well as respect for human rights and the dignity of the individual, without discrimination and using the intercultural approach, which eliminates the stigmatization of people with mental health problems. Some of the principles addressed in LawNo30947 specifically applicable to ensuring consent in this vulnerable population include:

  • Confidentiality – Mental health care guarantees the confidentiality of information obtained in the clinical context. The disclosure, examination, or release of medical records without the express consent of the individuals involved, or, if applicable, the consent of their legal representative(s), is prohibited
  • Dignity – Care and treatment of an individual with mental health issues is based on protecting and promoting the dignity of an individual through the recognition of his/her fundamental rights
  • Human rights – The therapeutic, prophylactic, and promotional strategies, actions, and interventions in mental health matters must comply with the Convention on the Rights of Persons with Disabilities (CRPD) (PER-54) and other international and regional human rights instruments to which Peru is a party

LawNo30947 defines a representative as a person who, according to law, gives consent for the treatment of the mental health problems of children and adolescents. In the treatment of psychiatric disorders, mental health services also consider the special needs of the population in vulnerable situations, and prioritizes mental health care in vulnerable populations including early childhood, adolescence, women, and older adults.

Per LawNo30947, some, but not all of the rights, of users of mental health services related to consent are listed below:

  • To receive complete, timely, and ongoing information about their mental health status, in understandable terms, including diagnosis, prognosis, and treatment alternatives; as well as the risks, contraindications, precautions, and warnings of the interventions, treatments, and medications that are prescribed and administered
  • To be informed of their right to refuse to receive or to continue treatment, and to explain the consequences of that refusal
  • To authorize or not the presence of people who are not directly related to medical care, at the time of the evaluations
  • To allow their consent to be in writing when they are the subject of investigation for the application of medications or treatments
  • To choose not to receive contraception method without prior informed consent, and to be obtained by the individual when he/she is not in a crisis situation due to the diagnosed mental health problem
  • To not be discriminated against or be stigmatized for having or for suffering from, permanently or temporarily, a mental health problem
  • To be treated with respect to their dignity, autonomy and needs, in accordance with the provisions of the CRPD

In addition, LawNo295 further states that individuals who, for any reason, are deprived of discernment are considered to be absolutely incapable of giving consent. Individuals who suffer from mental deterioration that prevents them from expressing their free will are considered to be relatively incapable of giving consent.

The G-EC-CTReview specifies that persons who are temporarily mentally incapacitated may participate in a research study if their designated legal representative(s) or guardian(s) decides on their behalf to allow them to participate per the requirements specified in LawNo1384, which amends LawNo295. The legal representative(s) or guardian(s) should be over 18 years of age. When no support has been designated and there is no representation for a mentally incapacitated person, the decision regarding his/her participation in a clinical trial will be made by his/her legal representative(s) or guardian(s) in accordance with the consanguinity or affinity ties delineated in RegLawNo29414. See LawNo1384 and RegLawNo29414 for requirements related to the roles and responsibilities of legal representative(s) or guardian(s).

DecreeNo021-2017, in turn, indicates that the following conditions must be met for clinical trials involving participants who are mentally incapable of giving consent:

  • Informed consent must be obtained from the legal representative(s) or guardian(s) who have been informed of the possible risks, discomforts, and benefits of the trial
  • Informed consent may be obtained from the participant when he/she has been fully informed about the trial in easily understandable language
  • Consent may be withdrawn at any time without harm to the participant and/or his/her legal representative(s) or guardian(s)
Articles 1, 3-4, 6, 9, and 32
Article 3
Title V (Articles 43-44 and 46-47)
Article 5
Article 37
Ethical Criterion 4
Last content review/update: June 29, 2021

Overview

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 patient population.

The MHCTR and the G-ConsentPIS, specify that when a study involves adult participants with mental incapacities, informed consent should be obtained from his/her legal representative (s) and/or guardian(s). This consent should only be provided once the legal representative(s) or guardian(s) has had an interview with the investigator(s) to understand the trial objectives and risks, been provided with a point of contact for further information, and been informed of the right to withdraw the participant from the trial at any time. The G-ConsentPIS provides additional country-specific information on legal representative requirements.

As delineated in the MHCTR, a clinical trial of an investigational product may involve participants with mental incapacities under the following conditions:

  • The participant has received information according to his/her capacity of understanding regarding the trial, its risks, and its benefits
  • No incentives or financial inducements are given to the participant or his/her legal representative(s) and/or guardian(s) except in the event of trial-related injury or loss
  • The trial relates directly to a condition from which the participant suffers, or, is of such a nature that it can only be carried out on participants with mental incapacities
  • The participant(s) will derive some direct benefit from their participation in the trial, or produce no risk at all
  • The trial is necessary to validate data obtained in other trials involving persons able to give informed consent, or, by other research methods
  • The trial has been designed to minimize pain, discomfort, fear, and any other foreseeable risk in relation to the disease and the participant’s stage of development

See the MHCTR, G-ConsentPIS, and GBR-9 for detailed requirements.

Part 1 (15), Schedule 1 (Parts 1 and 5)
Principles of Consent - Adults Who Are Not Able to Consent for Themselves
2.51-2.58
Investigational Products > Definition of Investigational Product
Last content review/update: November 19, 2020

Overview

As delineated in DecreeNo021-2017, the G-CTApplicProc, and the G-SafetyRpting, an investigational product (IP) is defined as a pharmaceutical form of an active substance or placebo, being tested or used as an active comparator 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.

DecreeNo021-2017 also defines a placebo as a product with a pharmaceutical form, with no active ingredient, and therefore devoid of specific pharmacological action, which may be used as a control in the clinical trial or for maintaining blinding.

Article 2
V
2
Last content review/update: June 29, 2021

Overview

As delineated in the MHCTR, the Guideline for Good Clinical Practice E6(R2) (GBR-113), GBR-9, and GBR-35, an investigational product (IP), referred to as an investigational medicinal product (IMP) in the United Kingdom (UK), is defined as a pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial. This includes a product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form; when used for an unapproved indication; or when used to gain further information about an approved use.

Part 1 (2)
Appendix 4
Terminology (Statutory Definitions Relating to CTIMPs)
1.3
Investigational Products > Manufacturing & Import
Last content review/update: November 19, 2020

Overview

According to DecreeNo021-2017, DecreeNo016-2011, the INS-CTManual, and the G-CTApplicProc, the sponsor or his/her contract research organization (CRO) must obtain approval from the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) to manufacture or import investigational products (IPs) in Peru. (Note: The ANM is also referred to as the General Directorate of Medicines, Supplies and Drugs (La Dirección General de Medicamentos Insumos y Drogas (DIGEMID))). As per DecreeNo021-2017, Peru’s National Institute of Health (Instituto Nacional de Salud (INS)) must approve the clinical trial application prior to ANM’s approval of an IP. However, as specified in DecreeNo021-2017 and the G-CTApplicProc, the INS does request ANM to assess the safety profile of the IP to be used in a clinical trial as part of its application review and approval process.

DecreeNo021-2017 and DecreeNo016-2011 specify that ANM will authorize the import of IPs exclusively for research involving humans when the applicant can provide information to support the product’s safety and quality according to the stage and type of research being conducted. Documentation requirements for ANM’s approval are as follows:

  • Application for authorization to import the product(s) under investigation and complementary products
  • Copy of INS clinical trial authorization approval
  • List of INS-approved research products, complementary products and supplies to be used in the trial
  • Proof of payment for processing fee

The ANM will grant this authorization within three (3) business days of filing the application.

Per the INS-CTManual, to obtain INS approval for an amended supplies list, the sponsor or his/her CRO must submit the following documents:

  • Form FOR-OGITT-033 (PER-42)
  • Analysis certificate
  • IP labeling
  • Certificate of Good Manufacturing Practices

The ANM is also responsible for authorizing post-study access to the IP by study participants when it is demonstrated to be beneficial.

See Clinical Trial Lifecycle topic, Timeline of Review subtopic for additional information on ANM’s role in the clinical trial application approval process.

Please note: Peru is party to the Nagoya Protocol on Access and Benefit-sharing (PER-11), 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 PER-57.

Title II (Chapter I and V) and Title III (Chapter I)
Articles 8, 69, 70, 90, 94, 97, and 115-118
4-5
Chapters VI (6.4) and VII (7.5), and Flow Charts No. 04
Last content review/update: April 22, 2021

Overview

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 and import of investigational products (IPs) (known as investigational medicinal products (IMPs) in the United Kingdom (UK)) to be used in a trial. A Manufacturer’s Authorization for Investigational Medicinal Products (MIA(IMP)) must be obtained by the person responsible for the manufacture or importation of any IP to be used in the trial. The sponsor or his/her designated representative must include a copy of the MIA(IMP) in the clinical trial application submission to the MHRA. The applicant must complete the form listed in GBR-28 to obtain an MIA(IMP) from the MHRA. The MHCTR defines “manufacturing authorization” to include importing and assembly authorizations, as applicable. The G-CTApp states that if an IP is manufactured outside the European Union (EU), the clinical trial application should include an MIA(IMP), importer authorization, and qualified person (QP) declaration on good manufacturing practice (GMP) for each site. The MHRA will approve the manufacture or import of an IP after the clinical trial application has been approved.

As per the MHCTR, the MHCTR2006, the G-GMP-GDP, and GBR-15, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), the MIA(IMP) holder must also comply with the GMP guidelines and provide an IMP Certificate of Analysis. In addition, the MHCTR, the MHCTR2006, and the G-GMP-GDP, specify that the holder of an MIA(IMP) must always have the services of at least one (1) Qualified Person (QP) at his/her disposal. The QP must satisfy the qualification and experience requirements delineated in the aforementioned sources. The QP’s primary legal responsibility is to certify batches of IPs prior to using in a clinical trial, or prior to releasing for sale and placing on the market. See Part 6 and Schedule 6 of the MHCTR for detailed applicant requirements.

In accordance with the G-ImportIMPs, the sponsor of a UK clinical trial using IPs imported from countries on the list of approved countries (G-CTApprovedCountries), 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). There will be a one-year transition period from January 1, 2021 to implement this guidance. IPs coming to Great Britain from Northern Ireland do not require this additional oversight. IPs coming directly to the UK from third 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. 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.

Amendment of Regulation 13 of the Principal Regulations; Amendment of Regulation 42 of the Principal Regulations; Amendment of Regulation 44 of the Principal Regulations; and Part 2 (Principles based on Articles 2 to 5 of the GCP Directive, Conditions Based on Article 3 of the Directive and Amendment of Schedule 6 to the Principal Regulations)
Part 1 (2), Part 3 (13), Part 6, Schedule 1 (Part 2), Schedule 3 (Part 2), Schedule 6, and Schedule 7
Documents to Send with Your Application
Application for New Manufacturer’s Authorization for Investigational Medicinal Products MIA (IMP) (Human Use)
Annex 2
Investigational Products > IMP/IND Quality Requirements
Last content review/update: November 19, 2020

Overview

In accordance with DecreeNo021-2017 and the G-CTApplicProc, the sponsor or his/her contract research organization (CRO) is responsible for providing the investigators with an Investigator’s Brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse events data. As noted in DecreeNo021-2017, the IB must be validated and updated on a regular basis by the sponsor and at least once a year by the responsible team member (if not the sponsor), when new information on the IP—not yet included in the manual—becomes available. DecreeNo021-2017 and the INS-CTManual indicate that the updated IB should be sent to the National Institute of Health (Instituto Nacional de Salud (INS))’s General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)), the EC(s), and the PIs. The INS-CTManual further specifies that the sponsor or his/her CRO is required to submit a signed notification form to inform the INS’s OGITT of any IB updates (see PER-41). The form must be accompanied by an update report of the applicable IP(s).

IB Content Requirements

As specified in DecreeNo021-2017, 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)
  • Clinical studies (pharmacokinetics, metabolism, pharmacodynamics, dose response safety, efficacy, and other pharmacological activities; safety and efficiency
  • Post-marketing experience (e.g., countries where the IP has been marketed or approved or did not receive approval/registration, was withdrawn, or registration was suspended; any significant information arising from marketed use; potential risks and adverse reactions)
  • Publication and report references

See Annex 2 of DecreeNo021-2017 for detailed content guidelines.

In addition, per the G-SafetyRpting, the sponsor or his/her CRO must ensure that the IB specifies and lists the adverse events (AEs) observed with the IP and for which there is a confirmed or suspected causal relationship. Refer to the G-SafetyRpting for detailed information to include in the IB.

As specified in DecreeNo021-2017, the INS-CTManual, and the G-CTApplicProc, Peru’s INS requires the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM) to assess the safety and quality of the IP to be used in a clinical trial as part of its application review and approval process. Per DecreeNo021-2017, the ANM’s assessment must be completed within 30 days. (Note: The ANM is also referred to as the General Directorate of Medicines, Supplies and Drugs (La Dirección General de Medicamentos Insumos y Drogas (DIGEMID))).

DecreeNo021-2017 states that the IP must also meet at least one (1) of the following conditions to be authorized for use in clinical trials in Peru:

  • Must be approved for use in humans by drug regulatory authorities of countries with high health surveillance
  • Is produced in Peru, is used in preclinical research, and complies with Ministry of Health of Peru (Ministerio de Salud del Perú (MINSA))’s political and/or research priorities
  • Will serve to establish pharmaceutical therapeutic equivalence
  • Is considered a priority for the country’s public health or is within the scope of MINSA policies and/or research priorities
  • At the request of the ANM require a clinical trial to support its efficacy and safety for the health registry

Additionally, per DecreeNo021-2017, to obtain trial authorization, the following documents relating to the IP must be submitted:

  • Labeling info
  • Certificate of batch release analysis or documents that include technical specifications of the batch/series result of the finished product
  • Accelerated or long-term stability studies as appropriate
  • Current certificate of the good manufacturing practices of the IP manufacturer, issued by the competent authority of the country of origin or document that guarantees its compliance

For detailed information on submission requirements for comparator IPs and complementary products, refer to Annex 5 of DecreeNo021-2017.

Drug Manufacturing Certificate Requirements

As stated in DecreeNo021-2017 and the G-CTApplicProc, ANM must approve the manufacture of IPs for their use in a clinical trial. DecreeNo021-2017 also specifies that the sponsor or his/her CRO must ensure the products are manufactured in accordance with the current codes of Good Manufacturing Practice (GMP).

According to PER-42, the sponsor or his/her CRO must also supply the investigator(s)/institution(s) with the IP(s), including the comparator(s) and placebo, if applicable.

Per the INS-CTManual, the sponsor or his/her CRO must complete the List of Products and Supplies to be Used in the Clinical Trial (refer to PER-42). As indicated in PER-42, the form requires the sponsor or his/her CRO to provide the following data:

  • Name of product
  • Active ingredient(s)
  • Route of administration
  • Pharmaceutical form and concentration
  • Manufacturer name
  • Country of origin
  • Quantity
  • Lot number or coding system

In addition, per DecreeNo021-2017 and the INS-CTManual, if the sponsor or his/her CRO plans to modify or expand the IP list to be imported, he/she must apply to the INS within 30 calendar days prior to the trial’s expiration. According to the INS-CTManual, the following documents must be submitted:

  • Request for expansion or modification of the list of supplies
  • Report justifying the reasons for the expansion or modification of the list of supplies
  • Additional or modified detailed list of supplies necessary for the trial’s execution

See PER-42 for the form and the INS-CTManual for additional instructions on completing this form. Per the INS-CTManual, the INS approval process will be completed within a maximum of 10 days.

(See Investigational Products topic, Product Management subtopic for additional information on sponsor requirements).

Articles 8, 40, 68, 69, 70, 108, and Annexes 2 and 5
VII
4-6
Chapter VI (6.4), VII (7.5, 7.6.3, 7.7.2, and 7.8.4), Chapter IX, and Flow Charts No. 04, No. 08, No. 11, and No. 15
Last content review/update: April 22, 2021

Overview

In accordance with the MHCTR, the MHCTR2006, and GBR-92, the sponsor or his/her designated representative is responsible for complying with the principles of good clinical practice (GCP) as specified in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), and for providing investigators with an Investigator’s Brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs) (known as investigational medicinal products (IMPs) in the United Kingdom (UK)) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse events data. The sponsor or his/her designated representative should also update the IB as significant new information becomes available.

Investigator's Brochure Content Requirements

As specified in 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 IMPs in humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; regulatory and post marketing experiences)
  • Summary of data and guidance for the investigator(s)
  • Bibliography

See Section 7 of GBR-113 for detailed content guidelines.

As defined in GBR-113, the sponsor is also accountable for supplying the IMP, including the comparator(s) and placebo, if applicable. The MHCTR, the MHCTR2006, the G-GMP-GDP, GBR-15, and GBR-35 also specify that the sponsor or his/her designated representative must ensure that the products are manufactured in accordance with current Good Manufacturing Practice (GMP) guidelines. (See Investigational Products topic, Product Management subtopic for additional information on IP supply, storage, and handling requirements).

Certificate of Analysis

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.

Insertion of Regulation 3A of the Principal Regulations; Amendment of Regulation 13 of the Principal Regulations; Amendment of Regulation 15 of the Principal Regulations; Amendment of Regulation 42 of the Principal Regulations, Amendment of Regulation 44 of the Principal Regulations; and Part 2 Principles based on Articles 2 to 5 of the GCP Directive
Part 1 (2), Part 3 (13), Part 6, Schedule 6, and Schedule 7
8, 9, 12, 13, 16, and 25
5.12-5.15, 5.5, and 7
Investigational Products > Labeling & Packaging
Last content review/update: November 19, 2020

Overview

Investigational product (IP) labeling in Peru must comply with the requirements set forth in DecreeNo021-2017. Labels for IPs used in a clinical trial must written in Spanish or English language and printed in indelible ink.

In addition, the following information must be included as a minimum on the product label:

  • Name, address and telephone number of the sponsor or contract research organization (CRO)
  • Trial number and/or trial title
  • IP name or unique code
  • Date of IP’s expiration or reanalysis
  • Manufacturing lot number
  • Number of units and pharmaceutical form
  • Route of administration
  • Special storage and conservation requirements
  • “For research use only”, “no sale”, or similar wording indicating the IP is clinical trial material

The inner labeling of the IP should contain:

  • IP name
  • Active ingredient concentration
  • Route of administration
  • Manufacturer's name or logo
  • Batch number and expiration date

In double-blind trials where the IP character, lot number, and manufacturer’s name are not included on the label, the package must include a document that links to information that identifies possible blinded treatments. Furthermore, the labeling must indicate the most restrictive storage requirements on both products.

(See Investigational Products topic, Product Management subtopic for additional information on investigational medicinal product (IMP) supply, storage, and handling requirements).

Article 91
Last content review/update: April 22, 2021

Overview

Labeling for investigational products (IPs) (known as investigational medicinal products (IMPs) in the United Kingdom (UK)) must comply with the requirements set forth in the MHCTR, the MHCTR2006, GBR-15, the EU Good Manufacturing Practice Directive (GBR-12), and the European Medicines Agency’s implementation of the 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 Clinical Trial Lifecycle topic, Submission Content subtopic 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.

Amendment of Regulation 46 of the Principal Regulations
Part 1 (2) and Part 7, and Schedule 3, Part 2 (12)
Article 15
Annex 13 – Investigational Medicinal Products – Packaging, Labelling, and Table 1
5.13
Investigational Products > Product Management
Last content review/update: November 19, 2020

Overview

In accordance with DecreeNo021-2017, the INS-CTManual, and the G-CTApplicProc, the sponsor or his/her contract research organization (CRO) is responsible for providing the investigators with an Investigator’s Brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse events data. The sponsor should also update the IB as significant new information becomes available.

Investigational Product Supply, Storage, and Handling Requirements

According to PER-42, the sponsor or his/her CRO must supply the investigator(s)/institution(s) with the IP(s), including the comparator(s) and placebo, if applicable. In addition, if the sponsor or his/her CRO plans to modify or expand the IP list to be imported, he/she must apply to the National Institute of Health (Instituto Nacional de Salud (INS))’s General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)) and attach a report justifying the reasons for the application submission. See the INS-CTManual for detailed instructions on completing this form. The duration of the approval process for the extended or modified list is 10 days. In addition, according to DecreeNo021-2017, DecreeNo016-2011, and the G-CTApplicProc, the sponsor or his/her CRO must obtain approval from the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) to manufacture or import IPs in Peru. (Note: The ANM is also referred to as the General Directorate of Medicines, Supplies and Drugs (La Dirección General de Medicamentos Insumos y Drogas (DIGEMID))).

In addition, per the INS-CTManual, the sponsor or his/her CRO must complete the List of Products and Supplies to be Used in the Clinical Trial (refer to PER-42). This form requires the sponsor or his/her CRO to provide the following data:

  • Name of product
  • Active ingredient(s)
  • Route of administration
  • Pharmaceutical form and concentration
  • Manufacturer name
  • Country of origin
  • Quantity
  • Lot number or coding system

Per DecreeNo021-2017, IPs will be dispensed through a Dispensation Unit for Clinical Trials under the Service or Pharmacy Department of the research institution where the trial will be conducted. The dispensation process must comply with the Ministry of Health of Peru (Ministerio de Salud del Perú (MINSA))’s Good Practices of Storage and Good Dispensation Practices and study specifications agreed to by the sponsor. The Clinical Trial Dispensing unit is responsible for:

  • Maintaining a record of dates in which IP quantities are received/dispensed
  • Inventorying IPs
  • Controlling overused, used, and unused IPs for final disposal as established in the protocol

Additionally, per DecreeNo021-2017, the sponsor must fund IPs for use in trials and provide them free of charge to research participants.

As per DecreeNo021-2017, the IP must also meet at least one (1) of the following conditions to be authorized for use in clinical trials in Peru:

  • Must be approved for use in humans by drug regulatory authorities of countries with high health surveillance
  • Is produced in Peru, is used in preclinical research, and complies with MINSA’s political and/or research priorities
  • Will serve to establish pharmaceutical therapeutic equivalence
  • Is considered a priority for the country’s public health or is within the scope of MINSA policies and/or research priorities
  • At the ANM’s request, require a clinical trial to support its efficacy and safety for the health registry

DecreeNo021-2017 further notes that the sponsor or his/her CRO is responsible for the following IP surveillance activities:

  • Continuously evaluate IP safety and implement an IP security monitoring system
  • Notify the OGITT of all serious adverse events (SAEs), serious adverse drug reactions (SADRs), suspected and unexpected serious adverse reactions (SUSARs)
  • Submit SAE/SADR and SUSAR reports on international incidents to the OGITT using the Council for International Organizations of Medical Sciences (CIOMS) form
  • Submit IB updates to the OGITT, ethics committees (ECs) and principal investigators (PIs)
  • Submit annual IP safety reports to the OGITT and ANM
  • Notify the OGITT, EC, and PIs of any findings that could adversely affect the research participant safety, affect the conduct of the study, or alter the benefit/risk balance. A report must be prepared for the INS and corresponding EC within a maximum period of seven (7) calendar days
  • Maintain detailed records of all adverse events communicated by the PIs

As delineated in DecreeNo021-2017, the ANM is also responsible for authorizing post-study access to the IP by study participants when it is demonstrated to be beneficial. ANM authorization is granted on a case by case basis through the following procedures:

  • Authorization of a clinical trial corresponding to an OGITT approved extension study
  • ANM authorization for an IP which must have proved to be beneficial to a participant, at the PI’s discretion, and its use will be maintained as soon as there is benefit
  • The PI should communicate to the sponsor the IP’s benefit to the participant, and the sponsor must, in turn, request ANM authorization (See Title X of DecreeNo021-2017 for documentation submission requirements)
Title II (Chapter I and II) and Title III (Chapter I)
Articles 8, 89, 90, 92-94, 97, 108, 115-118, and Annex 2
4 and 6
Chapter VI (6.4), VII (7.5, 7.6.3, and 7.8.4), Chapter IX, and Flow Charts No. 04, No. 08, and No. 15
Last content review/update: April 22, 2021

Overview

In accordance with the MHCTR, the MHCTR2006, and GBR-92, the sponsor or his/her designated representative is responsible for complying with the principles of good clinical practice (GCP) as specified in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (GBR-113), and for providing investigators with an Investigator’s Brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs) (known as investigational medicinal products (IMPs) in the United Kingdom (UK)) obtained through the earlier research phases, including preclinical, toxicological, safety, efficacy, and adverse event data. The sponsor should also update the IB as significant new information becomes available.

Investigational Product Supply, Storage, and Handling Requirements

As defined in the MHCTR, GBR-113, and GBR-35, the sponsor must supply the investigator(s)/institution(s) with the IP(s), 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).

The sponsor must ensure the following:

  • 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 IMP(s)
  • IP use record including information on the quantity, loading, shipment, receipt, dispensing, handling, reclamation and destruction of the unused IP
  • Acceptable storage temperatures, conditions, and times for the 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, GBR-113, and GBR-35 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-35 and 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.

Insertion of Regulation 3A of the Principal Regulations; Amendment of Regulation 15 of the Principal Regulations; and Amendment of Regulation 31 of the Principal Regulations
Part 3 (13 and 15), Part 4 (28), Part 6 (36 and 38), and Schedule 7 (Parts 2 and 3)
8, 12, 13, 22, and 23
Annex 13 – Investigational Medicinal Products – Packaging, Labelling
5.12, 5.13, 5.14, 5.15, 5.5, and 7
Specimens > Definition of Specimen
Last content review/update: November 19, 2020

No relevant provisions are currently available that define specimens.

However, as noted in DecreeNo021-2017, standards relating to biological samples to be used in clinical trials will be approved in a forthcoming National Institute of Health (Instituto Nacional de Salud (INS)) resolution.

Complementary Provisions Final
Last content review/update: April 22, 2021

Overview

The term “specimen” is not referenced within the United Kingdom (UK). However, the following terms are used relating to specimens:

  • Relevant material: As per the UK-HTA, Code-E, 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: 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.
Part 3 (53)
Glossary
Bodily Material and Tissues
Definition of Relevant Material
Specimens > Specimen Import & Export
Last content review/update: November 19, 2020

No relevant provisions are currently available regarding the import or export of specimens.

However, as noted in DecreeNo021-2017, standards relating to biological samples to be used in clinical trials will be approved in a forthcoming National Institute of Health (Instituto Nacional de Salud (INS)) resolution.

Complementary Provisions Final
Last content review/update: June 29, 2021

Overview

As set forth in the UK-HTA, the HTRegs, and GBR-9, the Human Tissue Authority (HTA) regulates the storage and use of specimens (known as “relevant materials” or “human tissue” in the United Kingdom (UK)) from the living, and the removal, storage, use, and licensing of relevant materials/human tissue from the deceased for specified health-related purposes in the UK. The UK-HTA refers to specified purposes as “scheduled purposes.” Per 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 storage of specimens for certain research projects that have been approved by an ethics committee (EC). 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.

Relevant Materials/Human Tissue

As specified in the UK-HTA, the HTA has jurisdiction regarding the import and export of relevant materials/human tissue, and complies with the Code of Practice on import and export set forth in Code-E. According to the UK-HTA, Code-E, and 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 if it is deemed to be for a specified or scheduled purpose.

If relevant material/human tissue is being imported or exported for an application, the HTRegs specify that this must be carried out under the authority of a license or third party agreement with an establishment licensed by the HTA to store material for human application. Per G-Tissues-Brexit, because the UK has left the European Union (EU) single market and customs union, there may be regulatory changes to an import/export license to continue to receive tissues and cells for human application from the EU, or send tissues and cells intended for human application to the EU. For detail and forthcoming updates, see the G-Tissues-Brexit. For more information about Brexit, see the Regulatory Authority topic, Scope of Assessment subtopic.

Code-E requires imported material to be procured, used, handled, stored, transported, and disposed of in accordance with the donor’s consent. In addition, due regard should be given to safety considerations, and with the dignity and respect accorded to human bodies, body parts, and tissue as delineated in Code-E. Any individual or organization wishing to import human bodies, body parts, and tissue into England, Wales or Northern Ireland must comply with the guidelines set forth in Code-E.

Exported material should also be procured, used, handled, stored, transported and disposed of, in accordance with the donor’s consent, with due regard for safety considerations, and with the dignity and respect accorded to human bodies, body parts, and tissue as stated in Code-E. This includes providing donors with adequate information upon taking consent, that their samples may be transported as exported samples for use abroad. It is the responsibility of the recipient country to ensure that, prior to export, the material is handled appropriately and that the required country standards have been met.

In addition, the G-QualityBlood lists the quality and safety standards when importing or exporting blood into or from the European Union (EU)/European Economic Area (EEA). In addition, after the Brexit transition period from January 1, 2021, this guidance states that there is no change to blood quality and safety practices. The UK is maintaining 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.

Section 3: Licenses and Section 7: Licenses: general provisions
Part 5 (53 (6))
Part 2 (13, 14, 16, 26, and 41)
Part 1 (6), and Part 2 (7), and Part 3
Introduction to the Human Tissue Authority Codes of Practice, Licensing – Import and Export, Licensing – HTA Licensing Standards, and Annex A
Glossary/Definitions, Import and Export
Section 12 and Annex H
1 and 3
Import and Export of Tissue
Specimens > Consent for Specimen
Last content review/update: November 19, 2020

Overview

In accordance with DecreeNo021-2017, if a clinical trial team is considering the collection and storage of biological samples for future use, this point should be delineated explicitly in a separate informed consent form (ICF).

Annex 4 of DecreeNo021-2017 and the G-EC-CTReview also state that the ICF must list the following biological sample study procedures:

  • Sample collection details: type, quantity and number of times to be extracted; explaining how many times and how much is needed, in measures that the research participant understands
  • Final destination of remaining samples: stating explicitly that the samples obtained will be used only for ongoing research, and will be destroyed when the trial is completed, unless storage is contemplated for future use
  • Sample storage or their remainders for future studies: if stock samples are to be stored beyond the end of the trial and/or biological samples are to be taken for storage and future studies, it should be incorporated into a specific ICF for that end

Per the G-EC-CTReview, donors of biological samples and related data must give their consent (either specific or broad) to authorize the future use of their samples. The ethics committee (EC) responsible for reviewing the associated research protocol must verify that the proposed uses of the donor samples are within the scope of authorization that the donor agreed to in the informed consent form.

In addition, Annex 4 of DecreeNo021-2017 and the G-EC-CTReview specify that in the event a research participant withdraws his/her informed consent, the ICF must explain how the participant’s rights to privacy and confidentiality in the handling of his/her biological data and samples will be upheld.

Further, as set forth in DecreeNo021-2017, when a clinical trial is to be conducted in indigenous peoples in Peru and the storage of biological samples is being considered, authorization must be obtained from the corresponding regional and local government, and of the respective community authorities, who must consider the interest of the community involved.

Per LawNo27337, children and adolescents are also guaranteed protection from experiments or genetic manipulations contrary to their integrity and their physical or mental development.

As noted in DecreeNo021-2017, standards relating to biological samples to be used in clinical trials will be approved in a forthcoming National Institute of Health (Instituto Nacional de Salud (INS)) resolution.

Civil Rights (Articles 1 and 4)
Articles 25, 34, Annex 4, and Complementary Provisions Final
Ethical Criterion 4 and Annex 2
Last content review/update: June 29, 2021

Overview

In accordance with the UK-HTA, Code-A, GBR-35, GBR-34, 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 and/or his/her legal representative(s) and ethics committee (EC) approval must be obtained. The scope of the UK-HTA provisions specifically cover England, Northern Ireland, and Wales. The UK-HTA licensing requirements do not apply in Scotland, with the exception of those provisions relating to the use of DNA. Scotland complies with the Scotland-AnatAct and the Scotland-HTA for the removal, retention, use, licensing, and import of human organs, tissue, and tissue samples specifically removed post mortem, and subsequently used for research.

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, GBR-9, and GBR-37, the UK-HTA considers it a UK-wide offense to have relevant material/human tissue with the intention of conducting a DNA analysis or using the results of this analysis without “qualifying consent” from a participant and/or his/her legal representative(s), unless the information is being used for an “excepted purpose.” The UK-HTA 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, GBR-37, and GBR-75 for detailed DNA analysis consent requirements.

Human Tissue/Relevant Material Consent Requirements

In accordance with the UK-HTA, Code-A, GBR-35, GBR-34, 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 and/or their legal representative(s) 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, his/her legal representative (referred to as “nominated representative” in the UK-HTA), or, in the absence of either of these, the consent of a person in a “qualifying relationship” with the participant immediately before he/she dies.

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

As indicated in the UK-HTA and Code-A, in the case of an adult donor, 18 years or older, his/her consent must be obtained prior to removing any materials from his/her body. If the adult has died, his/her written consent is only valid when it is signed by the person prior to his/her death in the presence of at least one (1) witness at his/her direction, or it is contained in the person’s will. An adult donor may also appoint one (1) or more people (“nominated representative(s)”) to consent on his/her behalf in the event of his/her death. This consent may be obtained orally or in writing. If the deceased donor has neither provided consent nor an appointed or nominated representative, appropriate consent may be given by someone in a “qualifying relationship” with the donor immediately prior to his/her death. Refer to the UK-HTA and 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, GBR-9, and GBR-37 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.

See the Informed Consent topic, Required Elements and Participant Rights subtopics for additional information on informed consent.

Introductory (3) and Miscellaneous (7)
Part 1 and Part 2 (Chapter 2)
Part 5 (53 (6))
Part 1 (1, 2, 3, 4, 6, and 7), Part 3 (45 and 54), and Schedules 1 and 4
Research
Chapter I (Article 4), and Chapter 2 (Article 6)
Section One – Guiding Principles, Section Two – The Fundamental Guiding Principle of Consent, Section Three – Consent Requirements
Principles, Content, and Examples and Templates
What the Law Says - Controllers and personal data in health and care research
1, 2, 3, 4, and Appendices A, B and C
Areas Requiring Special Consideration (Research Involving Human Tissue)
18.4
Section 12 and Annex H
Sources > Requirements
(Legislation) Law No. 26842 – General Health Law (LawNo26842 - Spanish) (Effective January 5, 1998)
Congress of the Republic
(Legislation) Law No. 27337 – Law that Approves the New Code of Children and Adolescents (LawNo27337 - Spanish) (Effective August 2, 2000)
Ministry of Women and Vulnerable Populations
(Legislation) Law No. 27444 – Law of the General Administrative Procedure (LawNo27444 - Spanish) (Effective April 10, 2001)
Congress of the Republic
(Legislation) Law No. 27657 – Law of the Ministry of Health (LawNo27657 - Spanish) (Effective January 28, 2002)
Congress of the Republic
(Legislation) Law No. 29733 - Protection of Personal Data (LawNo29733 - Spanish) (Effective July 3, 2011)
Congress of the Republic
(Legislation) Law No. 30947 – Mental Health Law (LawNo30947 - Spanish) (Effective May 23, 2019)
Congress of the Republic
(Legislation) Legislative Decree No. 1384 - Recognizing and Regulating the Legal Capacity of Persons with Disabilities in Equal Conditions (LawNo1384 - Spanish) (September 3, 2018)
Congress of the Republic
(Legislation) Legislative Decree No. 295 – Civil Code (LawNo295 - Spanish) (Effective November 14, 1984)
Congress of the Republic
(Legislation) Political Constitution of Peru of 1993 (PeruConstitution - Spanish) (Amended through March 2019)
Congress of the Republic
(Legislation) Legislative Decree No. 1353 – Creates the National Authority for Transparency and Access to Public Information, Strengthens the Personal Data Protection Regime and the Regulation of Interest Management (DecreeNo1353 - Spanish) (January 07, 2017) (Updated September 28, 2018)
Congress of the Republic
(Regulation) Ministerial Resolution No. 233-2020 – Ethical Considerations for Health Research with Human Beings (ResolutionNo233-2020 - Spanish) (April 28, 2020)
Ministry of Health
(Regulation) Ministerial Resolution No. 686-2020/MINSA - Approves the Technical Health Standard for the Research and Development of Vaccines against Infectious Diseases (ResolutionNo686-2020 - Spanish) (September 1, 2020)
Ministry of Health
(Regulation) Corrections - Supreme Decree No. 021-2017-SA – Clinical Trials Regulation (DecreeNo021-2017-Corrections - Spanish) (Effective July 12, 2017)
National Institute of Health, Ministry of Health
(Regulation) Directoral Resolution 0423-2019/OGITT/INS – Provides for the Amendment of Administrative Procedure Requirements Specified in the Supreme Decree No. 021-2017-SA by the National Institute of Health (INS) for the Authorization of Clinical Trials (ResolutionNo0423-2019 - Spanish) (September 24, 2019)
National Institute of Health, Ministry of Health
(Regulation) Ministerial Resolution No. 655-2019/MINSA – Provides for the Elimination of Administrative Procedure Requirements Specified in the Supreme Decree No. 021-2017-SA by the National Institute of Health (INS) (ResolutionNo655-2019 - Spanish) (July 27, 2019)
Ministry of Health
(Regulation) Regulation of Law No. 29414 – Law that Establishes the Rights of the Users of Health Services – (Issued by Supreme Decree No. 027-2015-SA) (RegLawNo29414 - Spanish) (August 13, 2015)
Ministry of Health, Ministry of Labor and Employment Promotion, Ministry of Defense, and Ministry of Interior
(Regulation) Supreme Decree 004-2019-JUS – Approving the Single Text Ordered of Law No. 27444 - Law of General Administrative Procedure (DecreeNo004-2019 - Spanish) (Effective July 24, 2019)
Ministry of Labor and Employment Promotion
(Regulation) Supreme Decree No. 001-2003-SA: Approves the Regulation of Organization and Functions of the National Institute of Health (DecreeNo001-2003 - Spanish) (January 9, 2003)
Ministry of Health
(Regulation) Supreme Decree No. 016-2011-SA: Regulatory Approval for the Registration, Control and Sanitary Surveillance of Pharmaceutical Products, Medical Devices and Health Products (DecreeNo016-2011 - Spanish) (July 27, 2011)
Ministry of Health
(Regulation) Ministerial Resolution No. 546/2011 – Technical Health Standard Categories of Health Sector Establishments (ResolutionNo546-2011 - Spanish) (July 13, 2011)
Ministry of Health
(Regulation) Supreme Decree No. 003-2013-JUS of March 21, 2013, Whereby the Regulation of Law No. 29733, Law on Protection of Personal Data is Approved (DecreeNo003-2013 - Spanish) (March 22, 2013)
Ministry of Justice and Human Rights
(Regulation) Supreme Decree No. 011-2011-JUS: Guidelines to Guarantee the Implementation of Bioethics to Ensure the Protection of the Human Rights (DecreeNo011-2011-JUS - Spanish) (July 27, 2011)
Ministry of Justice and Human Rights
(Regulation) Supreme Decree No. 021-2017-SA: Approved Clinical Trials Regulation (DecreeNo021-2017 - Spanish) (GoogleTranslate-DecreeNo021-2017) (June 30, 2017)
National Institute of Health, Ministry of Health
(Guidance) External User’s Guide for Safety Reporting in Clinical Trials (G-SafetyRpting - Spanish) (Edition No. 01) (March 22, 2019)
General Office of Research and of Health Technology Transfer, National Institute of Health, Ministry of Health
(Guidance) Guidance for the Procedure for the Request for Authorization of the Amendment Report (G-AmdAuthRept - Spanish) (Edition No. 01) (April 29, 2019)
National Institute of Health, Ministry of Health
(Guidance) Guide for Inspections of Clinical Trials (G-ClinTrialInspection - Spanish) (April 30, 2019)
General Office of Research and of Health Technology Transfer, National Institute of Health, Ministry of Health
(Guidance) Guide for the Ethical Review of Clinical Trials by Institutional Research Ethics Committees (G-EC-CTReview - Spanish) (Edition No. 1) (January 8, 2020)
Executive Office of Research, General Office for Research and Technology Transfer, National Institute of Health, Ministry of Health
(Guidance) Guide of General Guidelines for the Submission of Procedures Related to the Regulation of Clinical Trials (G-CTSubmissionProcs - Spanish) (Edition No. 01) (November 28, 2017)
National Institute of Health, Ministry of Health
(Guidance) Guideline for the Procedure for Requesting Authorization of the Clinical Trial (G-CTApplicProc - Spanish) (Edition No. 02) (November 15, 2019)
National Institute of Health, Ministry of Health
(Guidance) Procedures Manual of Clinical Trials (MAN-INS-001) (INS-CTManual - Spanish) (3rd Edition) (November 17, 2017)
National Institute of Health, Ministry of Health
(Legislation) Adults with Incapacity (Scotland) Act 2000 (AIA2000) (May 9, 2000)
Scottish Parliament, Scotland
(Legislation) Anatomy Act 1984 (Scotland-AnatAct) (May 24, 1984)
UK Parliament
(Legislation) Care Act 2014 (Chapter 23) (CareAct2014) (May 14, 2014)
Parliament, UK Government
(Legislation) Data Protection Act 2018 (UK-DPAct) (May 23, 2018)
UK Parliament
(Legislation) European Union (Withdrawal Agreement) Act of 2020 (c. 1) (Brexit) (January 23, 2020)
UK Parliament
(Legislation) Human Tissue (Scotland) Act 2006 (Scotland-HTA) (2006)
Scottish Parliament
(Legislation) Human Tissue Act 2004 (UK-HTA) (November 15, 2004)
UK Parliament
(Legislation) Medicines and Medical Devices Act 2021 (MMDAct) (February 11, 2021)
UK Parliament
(Legislation) Mental Capacity Act 2005 (Chapter 9) (MCA2005) (April 7, 2005)
UK Parliament
(Legislation) On the Conclusion of the Agreement on the Withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community (Council Decision (EU) 2020/135) (EUCouncil-Brexit) (January 30, 2020)
EU Council
(Regulation) The Good Laboratory Practice Regulations 1999 (S.I. 1999/3106) (UK-GLPs) (December 14, 1999)
UK Parliament
(Regulation) The Human Tissue (Quality and Safety for Human Application) Regulations 2007 (S.I. 2007/1523) (HTRegs) (May 25, 2007)
UK Parliament
(Regulation) The Medicines (Products for Human Use) (Fees) Regulations 2013 (MPHFR) (Effective March 11, 2013)
Department of Health and Social Care
(Regulation) The Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations 2019 (No. 744) (MHCTR-EUExit) (Effective January 1, 2021)
Department of Health and Social Care
(Regulation) The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (S.I. 2006/1928) (MHCTR2006) (August 29, 2006)
Department of Health and Social Care, Implements EU Good Clinical Practice Directive 2005/28/EC
(Regulation) The Medicines for Human Use (Clinical Trials) Amendment (No.2) Regulations 2006 (S.I. 2006/2984) (MHCTR2006-No2) (December 12, 2006)
Department of Health and Social Care
(Regulation) The Medicines for Human Use (Clinical Trials) and Blood Safety and Quality (Amendment) Regulations 2008 (S.I. 2008/941) (MHCTR-BSQ) (May 1, 2008)
Department of Health and Social Care
(Regulation) The Medicines for Human Use (Clinical Trials) Regulations 2004 (S.I. 2004/1031) (MHCTR) (May 1, 2004)
Department of Health and Social Care, Implements EU Clinical Trials Directive 2001/20/EC
(Regulation) UK General Data Protection Regulation – Keeling Schedule (UK-GDPR) (October 14, 2020)
UK Parliament
(Guidance) Clinical Trials for Medicines: Apply for Authorisation in the UK (G-CTApp) (Last Updated March 18, 2021)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Clinical Trials for Medicines: Manage Your Authorisation, Report Safety Issues (G-CTAuth) (Last Updated March 18, 2021)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Code A: Guiding Principles and the Fundamental Principle of Consent (Code-A) (May 20, 2020)
Human Tissue Authority
(Guidance) Code E: Research - Code of Practice and Standards (Code-E) (April 2017)
Human Tissue Authority
(Guidance) Completed Pediatric Studies - Submission, Processing, and Assessment (G-PIPs) (December 31, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Consent and Participant Information Guidance (G-ConsentPIS) (Version 9) (September 2020)
Medical Research Council, Health Research Authority
(Guidance) GDPR Guidance for Researchers and Study Coordinators (G-GDPR) (Current as of April 21, 2021)
Health Research Authority
(Guidance) Good Manufacturing Practice and Good Distribution Practice (G-GMP-GDP) (Last Updated December 27, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Guidance for Health and Social Care Researchers at the End of the Transition Period (G-AfterTransition) (Last Updated January 5, 2021)
Health Research Authority
(Guidance) Guidance for the Notification of Serious Breaches of GCP or the Trial Protocol (G-MHRA-SeriousBreaches) (Version 6) (July 8, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Guidance on Submitting Clinical Trial Safety Reports (G-SftyRpts) (December 31, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Guidance on Substantial Amendments to a Clinical Trial (G-SubtlAmndmt) (December 31, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) HTA Guide to Quality and Safety Assurance for Human Tissues and Cells for Patient Treatment (G-QAHumTissue) (January 2021)
Human Tissue Authority
(Guidance) Importing Investigational Medicinal Products into Great Britain from Approved Countries (G-ImportIMPs) (December 31, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) List of Approved Countries for Clinical Trials and Investigational Medicinal Products (G-CTApprovedCountries) (December 31, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Make a Payment to MHRA (G-MHRAPaymt) (Last Updated March 24, 2021)
Medicines and Healthcare Products Regulatory Agency
(Guidance) On-Site Access to Electronic Health Records by Sponsor Representatives in Clinical Trials (G-EHRAccess) (November 26, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Procedures for UK Paediatric Investigation Plan (PIPs) (G-PIPsProcess) (December 31, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Quality and Safety of Human Blood and Blood Products (G-QualityBlood) (Last Updated December 31, 2020)
Department of Health and Social Care
(Guidance) Register to Make Submissions to the MHRA (G-MHRASubmiss) (Last Updated May 4, 2021)
Medicines and Healthcare Products Regulatory Agency, Department of Health and Social Care
(Guidance) Registration of Clinical Trials for Investigational Medicinal Products and Publication of Summary Results (G-CTReg) (December 31, 2020)
Medicines and Healthcare Products Regulatory Agency
(Guidance) Statutory Guidance: Current MHRA Fees (G-MHRAFees) (Last Updated April 1, 2021)
Medicines and Healthcare Products Regulatory Agency
(Guidance) UK Transition Guidance (G-Tissues-Brexit) (Last Updated June 10, 2021)
Human Tissue Authority
(Guidance) Governance Arrangements for Research Ethics Committees: 2020 Edition (GAfREC) (Last Updated March 26, 2020)
UK Health Departments
(Correspondence) Letter to Medicines and Medical Product Suppliers: 17 November 2020 (BrexitLtr-IPs) (Last Updated December 28, 2020)
Department of Health and Social Care
(International Agreement) Agreement on the Withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community (WithdrlAgrmt) (January 31, 2020)
European Union, European Atomic Energy Community, and the United Kingdom of Great Britain and Northern Ireland
Sources > Additional Resources
(Article) Changes in the Law on Protection of Personal Data (DL 1353) (PER-2 - Spanish) (January 16, 2017)
GTDI
(Article) Regulation of Law 29733 Approved: Law on Protection of Personal Data (PER-1 - Spanish) (March 22, 2013)
RPP News
(Article) The Protection of Personal Data (Law No. 29733) (PER-3 - Spanish) (May 28, 2019)
Belling, Miguel Ampudia; Peruweek
(Document) Communique No. 001-2018-OGITT/INS Notification of the Deviations to the Protocol of the Critical or Very Serious and Major or Serious Clinical Trial (PER-12 - Spanish) (March 13, 2018)
General Office of Research and of Health Technology Transfer, National Institute of Health, Ministry of Health
(Document) Communique No. 001-2019-OGITT/INS – Legal Representative/Foreign Sponsor Representative Responsibilities (PER-7 - Spanish) (March 6, 2019)
General Office of Research and of Health Technology Transfer, National Institute of Health, Ministry of Health
(Document) Communique No. 002-2018-OGITT/INS - List of Products and Supplies to be Used in the Clinical Trial (PER-13 - Spanish) (March 18, 2018)
General Office of Research and of Health Technology Transfer, National Institute of Health, Ministry of Health
(Document) Communique No. 002-2019-OGITT/INS – Research Products Requirements for Clinical Trial Authorization (PER-5 - Spanish) (May 08, 2019)
General Office of Research and of Health Technology Transfer, National Institute of Health, Ministry of Health
(Document) Communique No. 003-2018-OGITT/INS - Forms for Reporting Progress and Final Reports (PER-14 - Spanish) (May 7, 2018)
General Office of Research and of Health Technology Transfer, National Institute of Health, Ministry of Health
(Document) Communique No. 003-2019-OGITT/INS – Publication of Documents Related to Adverse Events and Inspections of Clinical Trials (PER-6 - Spanish) (May 24, 2019)
General Office of Research and of Health Technology Transfer, National Institute of Health, Ministry of Health
(Document) Communique No. 005-2018-OGITT/INS - Application of Article 35 of the Approved Clinical Trials Regulation: Compensation to Research Subjects (PER-15 - Spanish) (July 3, 2018)
General Office of Research and of Health Technology Transfer, National Institute of Health, Ministry of Health
(Document) Instructions for Filling Out Form FOR-OGITT-028 Edition No. 03 – Request for Clinical Trial Authorization (PER-10 - Spanish) (Edition No. 03) (May 8, 2019)
National Institute of Health, Ministry of Health
(Document) Instructions for Filling Out Form FOR-OGITT-054 Edition No. 01 – Clinical Trial Progress Report (PER-8 - Spanish) (Edition No. 01) (Date Unavailable)
National Institute of Health, Ministry of Health
(Document) Instructions for Filling Out Form FOR-OGITT-055 Edition No. 01 - Final Report of the Research Center (PER-16 - Spanish) (Edition No. 01) (Date Unavailable)
National Institute of Health, Ministry of Health
(Document) Instructions for Filling Out Form FOR-OGITT-056 Edition No. 01 - Final National Report (PER-17 - Spanish) (Edition No. 01) (Date Unavailable)
National Institute of Health, Ministry of Health
(Document) Instructions for Filling Out Form FOR-OGITT-057 Edition No. 01 – International Final Report (PER-9 - Spanish) (Edition No. 01) (Date Unavailable)
National Institute of Health, Ministry of Health
(Document) Nagoya Protocol on Access and Benefit-sharing (PER-11) (2011)
Convention on Biological Diversity, United Nations
(Document) National Code of Scientific Integrity (PER-79 - Spanish) (October 30, 2019)
National Council of Science, Technology and Technological Innovation (CONCYTEC)
(Document) Communique No. 001-2017-OGITT/INS - Notification of Deviations to the INS OGITT (PER-4 - Spanish) (July 19, 2017)
General Office of Research and of Health Technology Transfer, National Institute of Health, Ministry of Health
(International Guidance) Convention on the Rights of Persons with Disabilities (CRPD) (PER-54) (Spanish) (Effective May 3, 2008)
UN General Assembly
(International Guidance) Declaration of Helsinki (PER-76) (October 19, 2013)
World Medical Association
(International Guidance) ICH Harmonised Tripartite Guideline: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A) (PER-52) (Step 4) (October 27, 1994)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (PER-53) (Step 4 Version) (November 9, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(International Guidance) International Guidelines for Health-Related Research Involving Humans (PER-78) (2016)
Council for International Organizations of Medical Sciences (CIOMS) and World Health Organization (WHO)
(Not Available Online) NIAID Communication with Peru’s National Institute of Health (January 2020) (PER-77)
(Webpage) Government Enacts Mental Health Law (PER-68 - Spanish) (May 23, 2019)
Ministry of Health
(Webpage) Organization of the Ministry of Health (PER-67 - Spanish) (Last Updated December 20, 2019)
Ministry of Health
(Webpage) Register Your Health Service Provider Institution in Renipress (PER-80) (Last Updated July 31, 2020)
National Institute of Health, Ministry of Health
(Webpage) About OGITT - Introduction (PER-65 - Spanish) (Current as of November 19, 2020)
National Institute of Health, Ministry of Health
(Webpage) About the Executive Research Office (OGITT) (PER-75 - Spanish) (Current as of November 19, 2020)
National Institute of Health, Ministry of Health
(Webpage) About the Regulatory Authority (PER-74 - Spanish) (Current as of November 19, 2020)
REPEC, National Institute of Health, Ministry of Health
(Webpage) Country Profile: Peru (PER-57) (Current as of November 19, 2020)
Access and Benefit-sharing Clearing-house, Convention on Biological Diversity, United Nations
(Webpage) General Directorate of Medicines, Supplies and Drugs (DIGEMID) (PER-56 - Spanish) (Current as of November 19, 2020)
Ministry of Health
(Webpage) History of the Processes Involved in the Legislation of Clinical Trials in Peru (PER-62 - Spanish) (Current as of November 19, 2020)
REPEC, National Institute of Health, Ministry of Health
(Webpage) INS - About Us (PER-64 - Spanish) (Current as of November 19, 2020)
National Institute of Health, Ministry of Health
(Webpage) INS - Contact Us (PER-63 - Spanish) (Current as of November 19, 2020)
National Institute of Health, Ministry of Health
(Webpage) List of Procedures (PER-72) (Spanish) (Current as of November 19, 2020)
REPEC, National Institute of Health, Ministry of Health
(Webpage) National Registry of Accredited Institutional Ethics Committees (PER-61 - Spanish) (Current as of November 19, 2020)
REPEC, National Institute of Health, Ministry of Health
(Webpage) Peruvian Clinical Trials Registry (REPEC) (PER-58 - Spanish) (English) (Current as of November 19, 2020)
REPEC, National Institute of Health, Ministry of Health
(Webpage) Registration of a Clinical Trial - Authorization (PER-71 - Spanish) (Current as of November 19, 2020)
REPEC, National Institute of Health, Ministry of Health
(Webpage) Registration of a Sponsor (PER-60 - Spanish) (Current as of November 19, 2020)
REPEC, National Institute of Health, Ministry of Health
(Webpage) Registration of Contract Research Organization (CRO) (PER-59 - Spanish) (Current as of November 19, 2020)
REPEC, National Institute of Health, Ministry of Health
(Webpage) Registration of Research Centers (PER-73 - Spanish) (Current as of November 19, 2020)
REPEC, National Institute of Health, Ministry of Health
(Webpage) Serious Adverse Event Reporting - REAS NET (PER-66 - Spanish) (Current as of November 19, 2020)
National Institute of Health, Ministry of Health
(Webpage) Serious Adverse Events Virtual Reporting System (REAS-NET) (PER-69 - Spanish) (Current as of November 19, 2020)
National Institute of Health, Ministry of Health
(Webpage) Vialibre – Institutional Bioethics Committees - 2020 Rates (PER-70 - Spanish) (Current as of November 19, 2020)
Vialibre
(Article) Agency Joining Government Hub (GBR-36) (June 15, 2018)
Medicines and Healthcare Products Regulatory Agency
(Document) Applying a Proportionate Approach to the Process of Seeking Consent (GBR-31) (Version 1.02) (May 3, 2018)
Health Research Authority
(Document) Clinical Trial Authorisation (CTA) Application Flowchart (GBR-23) (Current as of November 30, 2020)
Medicines and Healthcare Products Regulatory Agency
(Document) Consent and Confidentiality in Clinical Genetic Practice: Guidance on Genetic Testing and Sharing Genetic Information: A Report of the Joint Committee on Medical Genetics (GBR-37) (Second Edition) (September 2011)
Royal College of Physicians, Royal College of Pathologists, and The British Society for Human Genetics
(Document) Explanatory Memorandum to the Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations 2019 (No. 744) (GBR-115) (2019)
Department of Health and Social Care
(Document) Good Practice in Research and Consent to Research: Supplementary Guidance (GBR-34) (Updated March 2013)
General Medical Council, UK
(Document) Guidelines for Phase I Clinical Trials (2018 Edition) (GBR-35) (May 29, 2018)
Association for the British Pharmaceutical Industry, UK
(Document) HRA Approval: Assessment Criteria and Standards Document (GBR-29) (Version 4.0) (March 30, 2016)
Health Research Authority
(Document) Insurance and Compensation in the Event of Injury in Phase I Clinical Trials (GBR-33) (June 27, 2012)
Association for the British Pharmaceutical Industry, BioIndustry Association, Clinical Contract Research Association
(Document) Joint Statement on Seeking Consent by Electronic Methods (GBR-6) (Version 1.2) (September 2018)
Medicines and Healthcare Products Regulatory Agency (MHRA), Health Research Authority
(Document) MRC Ethics Guide 2007 – Medical Research Involving Adults Who Cannot Consent (GBR-3) (2007)
Medical Research Council, UK
(Document) MRC Ethics Guide – Medical Research Involving Children (GBR-4) (2004)
Medical Research Council, UK
(Document) MRC/DH Joint Project to Codify Good Practice in Publicly-Funded UK Clinical Trials with Medicines - Workstream 6: Pharmacovigilance (GBR-1) (July 2012)
Health Research Authority
(Document) Nagoya Protocol on Access and Benefit-sharing (GBR-5) (2011)
Convention on Biological Diversity, United Nations
(Document) RES SOPs (Version 7.5) Summary of Changes (GBR-8) (March 2021)
UK Health Departments’ Research Ethics Service, Health Research Authority
(Document) SOP – Submitting a CTA Application to the MHRA (GBR-17) (Version 12.0) (Effective March 25, 2021)
Imperial College London, National Health Service
(Document) Sponsorship Principles (GBR-2) (Version 5) (Last Updated June 2016)
Research and Development Forum, National Health Service
(Document) Standard Operating Procedures for Research Ethics Committees (GBR-9) (Version 7.5) (March 2021)
UK Health Departments’ Research Ethics Service, Health Research Authority
(Document) User Reference Guide – Gaining Access to MHRA Submissions (GBR-11) (Date Unavailable)
Medicines and Healthcare Products Regulatory Agency
(Document) Clinical Trials Facilitation Group (CTFG) Q&A document – Reference Safety Information (GBR-30) (November 2017)
Heads of Medicines Agencies (in cooperation with the European Medicines Agency and the European Commission)
(International Guidance) Commission Directive 2003/94/EC of 8 October 2003 Laying Down the Principles and Guidelines of Good Manufacturing Practice in Respect of Medicinal Products for Human Use and Investigational Medicinal Products for Human Use (GBR-12) (EU Good Manufacturing Practice Directive) (October 8, 2003)
European Commission, European Parliament and European Council
(International Guidance) EudraLex - Volume 4 - Good Manufacturing Practice (GMP) Guidelines (GBR-15) (Date Varies by Guidance)
European Commission
(International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (Step 4 Version) (GBR-113) (November 9, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(International Guidance) Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on Clinical Trials on Medicinal Products for Human Use, and Repealing Directive 2001/20/EC (GBR-21) (EU Clinical Trials Regulation) (April 16, 2014)
European Parliament and Council
(Webpage) Applying to a Research Ethics Committee (GBR-68) (Last Updated February 26, 2021)
Health Research Authority
(Webpage) Brexit: New Rules Are Here (GBR-60) (Current as of June 28, 2021)
Government of United Kingdom
(Webpage) Clinical Trial Regulation (GBR-54) (Current as of June 28, 2021)
European Medicines Agency
(Webpage) Clinical Trials in the Post Brexit Europe (GBR-114) (October 30, 2020)
Pharmiweb.com
(Webpage) Clinical Trials of Investigational Medicinal Products (CTIMPs) (GBR-71) (Last Updated February 5, 2020)
Health Research Authority, Department of Health and Social Care
(Webpage) Clinical Trials Toolkit – Routemap (GBR-18) (Current as of April 9, 2021)
Medicines and Healthcare Products Regulatory Agency, Department of Health and Social Care
(Webpage) Combined Ways of Working (GBR-72) (Last Updated April 21, 2021)
Health Research Authority
(Webpage) Contact MHRA (GBR-58) (Last Updated April 9, 2020)
Medicines and Healthcare Products Regulatory Agency
(Webpage) eSUSAR (GBR-50) (Current as of April 21, 2021)
Medicines and Healthcare Products Regulatory Agency
(Webpage) EU Clinical Trials Register (GBR-53) (Current as of March 18, 2020)
European Medicines Agency
(Webpage) EudraCT – European Union Drug Regulating Authorities Clinical Trials Database (GBR-87) (Version 10.5.0.0) (Last Updated February 16, 2021)
European Medicines Agency
(Webpage) Examples of Substantial and Non-Substantial Amendments (GBR-98) (Last Updated March 25, 2021)
Health Research Authority
(Webpage) Fast-track Research Ethics Review (GBR-116) (Last Updated April 21, 2021)
Health Research Authority
(Webpage) Four Nations Policy Leads Group (GBR-97) (Last Updated December 2, 2020)
Health Research Authority
(Webpage) Glossary (GBR-64) (Current as of December 1, 2020)
Health Research Authority
(Webpage) Good Clinical Practice for Clinical Trials (GBR-92) (Last Updated March 25, 2021)
Medicines and Healthcare Products Regulatory Agency
(Webpage) Guide to the UK General Data Protection Regulation (UK GDPR) (GBR-89) (Current as of June 28, 2021)
Information Commissioner’s Office
(Webpage) Health and Social Care Research and Development (HSC R&D) Division Northern Ireland (GBR-90) (Current as of December 1, 2020)
HSC R&D Division, Public Health Agency, Northern Ireland Government
(Webpage) Health Research Authority – About Us (GBR-61) (Current as of December 1, 2020)
Health Research Authority
(Webpage) Help - Using IRAS - New Users (GBR-106) (Current as of December 1, 2020)
Health Research Authority
(Webpage) HRA Approval Implementation 31 March 2016 (GBR-96) (Last Updated March 16, 2016)
Health Research Authority
(Webpage) HRA Approval (GBR-67) (Last Updated December 16, 2020)
Health Research Authority
(Webpage) Human Tissue Act 2004 (GBR-75) (Last Updated November 20, 2020)
Human Tissue Authority
(Webpage) Information Rights After the End of the Transition Period – FAQs (GBR-16) (Current as of April 9, 2021)
Information Commissioner’s Office
(Webpage) Informing Participants and Seeking Consent (GBR-69) (Last Updated September 4, 2019)
Health Research Authority
(Webpage) Integrated Research Application System (IRAS): Collated Question-Specific Guidance for NHS REC Form (GBR-77) (Version 14) (Last Updated July 27, 2017)
Health Research Authority
(Webpage) Integrated Research Application System (IRAS) (GBR-78) (Version 5.19) (Last Updated March 9, 2021)
Health Research Authority
(Webpage) Integrated Research Application System (GBR-94) (Last Updated January 16, 2018)
Health Research Authority
(Webpage) International Clinical Trials Registry Platform (ICTRP) (GBR-108) (Current as of December 1, 2020)
World Health Organization
(Webpage) IRAS - Templates for Supporting Documents (GBR-107) (Last Updated March 29, 2021)
Health Research Authority, Department of Health and Social Care
(Webpage) Keep Data Flowing at the End of the UK’s Transition out of the EU (GBR-7) (December 3, 2020)
Information Commissioner’s Office
(Webpage) Launch of the UK Local Information Pack: Supporting the Set-up of NHS/HSC Research in the UK (GBR-63) (Last Updated June 4, 2019)
Health Research Authority
(Webpage) MHRA - About Us (GBR-57) (Current as of December 1, 2020)
Medicines and Healthcare Products Regulatory Agency
(Webpage) MHRA Account Request – MHRA Submissions (GBR-13) (Current as of March 3, 2021)
Medicines and Healthcare Products Regulatory Agency
(Webpage) Model Agreements (GBR-70) (Last Updated July 31, 2019)
Health Research Authority
(Webpage) Online Booking Service (GBR-95) (Last Updated January 4, 2021)
Health Research Authority
(Webpage) Progress Reports (GBR-65) (Last Updated March 24, 2021)
Health Research Authority
(Webpage) Relevant Material Under the Human Tissue Act 2004 (GBR-76) (Last Updated June 24, 2021)
Health Tissue Authority
(Webpage) Research Ethics Committees Overview (GBR-111) (Last Updated February 4, 2020)
Health Research Authority
(Webpage) Research Ethics Service (GBR-62) (Last Updated April 26, 2019)
Health Research Authority
(Webpage) Research FAQs (GBR-105) (Last Updated April 20, 2021)
Human Tissue Authority
(Webpage) Research Registration and Research Project Identifiers (GBR-102) (Last Updated February 3, 2021)
Health Research Authority, Department of Health and Social Care
(Webpage) Roles and Responsibilities (GBR-103) (Last Updated February 3, 2021)
Health Research Authority
(Webpage) Safety Reporting (GBR-99) (Last Updated July 15, 2020)
Health Research Authority
(Webpage) Scottish Government Health Directorates – Chief Scientist Office (GBR-91) (Current as of December 1, 2020)
Chief Scientist Office, National Health Service Scotland
(Webpage) Summary of Legal Requirements for Research with Human Tissues in Scotland (GBR-52) (V2) (June 2016) (Research and Human Tissue Legislation Series)
Medical Research Council
(Webpage) Templates: Recommended Wording to Help You Comply with GDPR (GBR-100) (Current as of April 21, 2021)
Health Research Authority
(Webpage) UK Policy Framework for Health and Social Care Research (GBR-101) (Last Updated March 10, 2021)
Health Research Authority (England), the Department of Health and Social Care (Northern Ireland), the Scottish Government Health and Social Care Directorates, and the Department for Health and Social Services (Wales)
(Webpage) Use of Human Tissue in Research (GBR-73) (Last Updated July 11, 2019)
Health Research Authority
(Webpage) What Approvals and Decisions Do I Need? (GBR-66) (Current as of December 1, 2020)
Health Research Authority
(Webpage) Clinical Trials - Regulation EU No 536/2014 (GBR-86) (Current as of December 1, 2020)
European Commission
(Webpage) ClinicalTrials.gov (GBR-49) (Current as of December 1, 2020)
U.S. National Library of Medicine
(Webpage) Country Profile: United Kingdom (GBR-48) (Current as of December 1, 2020)
Access and Benefit-sharing Clearing-house, Convention on Biological Diversity, United Nations
(Webpage) International Standardized Randomized Controlled Trial Number (ISRCTN) Registry (GBR-47) (Current as of December 1, 2020)
BioMed Central
(Webpage) Obtaining Approval (GBR-93) (Current as of March 18, 2020)
Health and Care Research Wales, National Health Service Wales, Department of Welsh Government
Sources > Forms
(Form) Affidavit of Absence of Financial Interest Conflict (FOR-OGITT-063) (PER-34 - Spanish) (Edition No. 01) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Affidavit of Compliance with Minimum Research Center Requirements (FOR-OGITT-023) (PER-44 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) Affidavit of Compliance with the Responsibilities and Obligations Set Out in the REC and Availability of a Financial Fund – Sponsor (FOR-OGITT-029) (PER-51 - Spanish) (Edition No. 03) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Affidavit of Research Center Preparedness for Clinical Trial (FOR-OGITT-064) (PER-35 - Spanish) (Edition No. 01) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Accreditation/Renewal of the Accreditation of the Institutional Ethics Committees (CIEI) (FOR-OGITT-025) (PER-20 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Approval of Clinical Trial Amendments (FOR-OGITT-044) (PER-33 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Clinical Trial Authorization (FOR-OGITT-028 (PER-24 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Clinical Trial Cancellation (FOR-OGITT-042) (PER-31 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Clinical Trial Suspension (FOR-OGITT-041) (PER-30 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Clinical Trial Title Change (FOR-OGITT-043) (PER-32 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Contract Research Organization Registration (FOR-OGITT-021) (PER-37 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) Application for Extension of the Clinical Trial (FOR-OGITT-037) (PER-27 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Principal Investigator Change (FOR-OGITT-038) (PER-28 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Registration of the Research Center (FOR-OGITT-022) (PER-19 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Research Center Closure for a Clinical Trial (FOR-OGITT-040) (PER-43 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Sponsor or CRO Change (FOR-OGITT-039) (PER-29 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Application for Sponsor Registration (FOR-OGITT-020) (PER-36 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) Application for the Extension of the Number of Research Centers (FOR-OGITT-036) (PER-26 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) CIOMS Form I (PER-18) (Date Unavailable)
Council for International Organizations of Medical Sciences
(Form) Clinical Trial Progress Report (FOR-OGITT-054) (PER-47 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) Curriculum Vitae of the Research Team (FOR-OGITT-031) (PER-50 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Detailed Total National Budget of the Clinical Trial (FOR-OGITT-032) (PER-25 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Final National Report (FOR-OGITT-056) (PER-49 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) Final Report of the Research Center (FOR-OGITT-055) (PER-48 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) International Final Report (FOR-OGITT-057) (PER-46 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) List of Products and Supplies to be Used in the Clinical Trial (FOR-OGITT-033) (PER-42 - Spanish) (Edition No. 02) (April 9, 2018)
National Institute of Health, Ministry of Health
(Form) Notification of Deviations to the Protocol (FOR-OGITT-053) (PER-40 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) Notification of Pregnant Woman and Newborn in Clinical Trials (FOR-OGITT-047) (PER-39 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) Other Relevant Notifications (FOR-OGITT-059) (PER-41 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) Report of Clinical Trial Results to be Published in REPEC (FOR-OGITT-058) (PER-23 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) Serious Adverse Event Report (FOR-OGITT-046) (PER-38 - Spanish) (Edition No. 02) (June 4, 2018)
National Institute of Health, Ministry of Health
(Form) Summary of the Annual Security Report of the Research Product (FOR-OGITT-048) (PER-45 - Spanish) (Edition No. 01) (October 4, 2017)
National Institute of Health, Ministry of Health
(Form) Affidavit of Compliance with the Accreditation Standards of the Institutional Ethics Committees (CIEI) (FOR-OGITT-026) (PER-21 - Spanish) (Edition No. 02) (September 24, 2019)
National Institute of Health, Ministry of Health
(Form) Verification of Compliance with the Accreditation Standards of the Institutional Ethics Committees (CIEI) (FOR-OGITT-027) (PER-22 - Spanish) (Edition No. 1) (January 29, 2020)
National Institute of Health, Ministry of Health
(Form) Clinical Trial of an Investigational Medicinal Product (CTIMP), Annual Progress Report to Research Ethics Committee (GBR-27) (Version 4.5) (Last Updated January 2021)
Health Research Authority
(Form) Declaration of the End of Trial Form (GBR-24) (Revision 3, June 2010) (EudraLex, Volume 10, Clinical Trials Guidelines)
European Commission
(Form) Medicines: Application Forms for a Manufacturer License (GBR-28) (May 14, 2020)
Medicines and Healthcare Products Regulatory Agency
(Form) Pay MHRA Invoices (GBR-26) (Current as of April 21, 2021)
Medicines and Healthcare Products Regulatory Agency
(Form) Substantial Amendment Notification Form (GBR-25) (Revision 3, June 2010) (EudraLex, Volume 10, Clinical Trials Guidelines)
European Commission
Sections
Use the symbols below to refine your search
SymbolExplanation
No symbol At least one of the keywords must be present
Search example: serious adverse event
Result: Will contain serious and/or adverse and/or event
+ Leading plus sign indicates that the word must be present
Search example: serious +adverse event
Result: Will contain adverse and may contain serious and/or event
- Leading minus sign indicates that the word must not be present
Search example: serious adverse -event
Result: Will contain serious and/or adverse but won’t contain event
“ ” Exact phrase must be present
Search example: “serious adverse event”
Result: Will contain the phrase serious adverse event
Call for online focus group participants!
x

ClinRegs content is published in English. ClinRegs offers translations of the content through Google Translate, which is an external translation service. ClinRegs does not control the quality or accuracy of translated content and may result in unexpected and unpredictable degradation of portions of text, images and the general appearance on translated pages.