Clinical Research Regulation For Canada and Peru

Last content review/update: July 26, 2024

Overview

In accordance with the CanadaFDA, Health Canada (HC) reviews, evaluates, and approves applications for clinical trials using authorized therapeutic products. HC also approves the sale or importation of drugs for use in clinical trials. (See the Manufacturing & Import section for additional information on importation.) As delineated in the CanadaFDR and the G-CanadaCTApps, institutional ethics committee (EC) review is required for each clinical trial site and may occur in parallel with HC’s clinical trial application (CTA) review and approval. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100. See CAN-23 and CAN-19 for background information on HC’s scope of assessment.

Per the CanadaFDA, a “therapeutic product” is defined as a drug or device, or any combination of drugs and devices, but does not include natural health products; and “therapeutic product authorization” refers to a license that is approved for the import, sale, advertisement, manufacture, preparation, preservation, packaging, labeling, storage, or testing of a therapeutic product. As per the G-CanadaCTApps, a drug is defined as a pharmaceutical, biologic, gene therapy, blood product, vaccine, and radiopharmaceutical for human use that is to be tested in a clinical trial. HC’s scope of assessment includes clinical trials (Phases I - III) using:

Drugs not authorized for sale in Canada in development and in comparative bioavailability studies
Marketed drugs where the proposed use of the drug for one (1) of the following is different: indication(s) and clinical use; target patient populations(s); route(s) of administration; or dosage regimen(s)

Clinical Trial Review Process

As set forth in the G-CanadaCTApps and CAN-23, HC’s Health Products and Food Branch (HPFB) coordinates the CTA approval process. The G-CanadaCTApps and CAN-23 state that prior to initiating the trial, the sponsor must file a CTA to the appropriate HPFB Directorate. CTAs involving pharmaceutical drugs should be sent to the Pharmaceutical Drugs Directorate (PDD), and CTAs involving biologics and/or radiopharmaceuticals should be sent to the Biologic and Radiopharmaceutical Drugs Directorate (BRDD).

The G-CanadaCTApps and CAN-23 indicate that upon receipt of a CTA, the HPFB Directorate (PDD/BRDD) screens the application package for completeness. If deficiencies are found, the Directorate sends the sponsor a Request for Clarification or a Screening Rejection Letter. If the Directorate finds the application complete, an acknowledgement letter is issued to indicate the 30-day default review period commenced on the date of receipt.

Per the G-CanadaCTApps, once a clinical trial is authorized, the sponsor is allowed to sell or import a drug for use in a trial, if a CTA has been filed with HC and has not received an objection within 30 days. As delineated in the G-CanadaCTApps and CAN-23, if the clinical trial is authorized, a No Objection Letter (NOL) is issued. If the CTA is rejected, a Not Satisfactory Notice (NSN) is issued. As specified in the G-CanadaCTApps and CAN-23, during the review period, the Directorate may request additional information from the sponsor, who has two (2) calendar days to provide such information. Please see the G-CanadaCTApps for special requirements regarding reviews of comparative bioavailability studies and joint reviews of clinical trials covering a combination of devices, biologics, and pharmaceuticals. See the Submission Process section for detailed application submission requirements.

Per the G-CanadaCTApps, soon after HC issues an NOL, it will publish the following information about the clinical trial in HC’s publicly accessible database:

Protocol number
Protocol title
Drug name
Medical condition
Study population
Authorization date
Sponsor name
HC control number
Trial start and end dates, if known

The CanadaFDR and the G-CanadaCTApps also delineate that a clinical trial application-amendment (CTA-A) is required for proposed changes to a previously authorized study when the changes to clinical trial drug supplies affect the quality or safety of the drug, or when the changes to an authorized protocol alter the risk to clinical trial participants, or both. CTA-As must be authorized by HC prior to implementation of the changes. However, if the sponsor is required to immediately implement changes because the clinical trial or the use of the clinical trial drug endangers the health of participants or other persons, the sponsor may immediately make the amendment without prior review by HC. Sponsors must notify HC of this change, provide the relevant rationale in support of the immediate implementation, and file a CTA-A that clearly identifies the change and rationale for immediate implementation of the change within 15 days after the amendment implementation date. In addition, sponsors may make the following changes immediately if it notifies HC in writing within 15 days after the date of the change: a change to the chemistry and manufacturing information that does not affect the quality or safety of the drug; or a change to the protocol that does not alter the risk to the health of a participant.

Per the CanadaFDR, HC will suspend the authorization to sell or import a drug for clinical trial purposes if it has reasonable grounds to believe that:

The sponsor has contravened any relevant laws or regulations
Any information submitted in respect of the drug or clinical trial is false or misleading
The sponsor has failed to comply with good clinical practices
The sponsor has failed to provide information or samples as required by the regulation

See the CanadaFDR for additional details on HC’s suspension and cancellation responsibilities.

What is the Health Products and Food Branch?

Clinical Trial Site Information form

1.2, 2.1, 2.3-2.7, and Appendix 1

5.1, 5.2, 5.5, and 5.6

2 and Part II (Section 30 (1.2))

Part C (Division 5 (C.05.001, C.05.002, C.05.005-.008, and C.05.016-.017))

Last content review/update: April 24, 2024

Overview

In accordance with the provisions delineated in Decree021-2017, the INS-CTManual, and Res252-2022 (which amends the INS-CTManual), Peru’s National Institute of Health (Instituto Nacional de Salud (INS)) is responsible for reviewing and approving clinical trial applications using registered or unregistered investigational drug products. As per Decree021-2017, 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. As specified in Decree021-2017, Res655-2019 (which amends Decree021-2017), the INS-CTManual, Res252-2022, and PER-61, the INS’s review and approval of a clinical trial application is dependent upon obtaining proof of approval from an accredited ethics committee (EC). Therefore, the INS and EC reviews may not be conducted in parallel.

Per the INS-CTManual and Res252-2022, EC approval of the research protocol and the informed consent form (ICF) must be submitted as part of the clinical trial application dossier in order for the INS to conduct its review. PER-83 further specifies that the sponsor or the contract research organization (CRO) must provide a copy of the research protocol and ICF that is stamped and signed by the EC in its entirety as evidence that the approved version is being presented. Refer to the INS-CTManual and Res252-2022 for additional submission information. Per Res0423-2019, the application for clinical trial authorization and corresponding instructions are in PER-24 and PER-10, respectively.

In addition, per Decree021-2017, the sponsor must also ensure authorization by the research institution where the clinical trial will be carried out.

Decree021-2017 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

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 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

Per Decree016-2011, the following are considered to be countries with high health surveillance: France, Holland, United Kingdom, United States, Canada, Japan, Switzerland, Germany, Spain, Australia, Denmark, Italy, Norway, Belgium, and Sweden.

Clinical Trial Review Process

In accordance with Decree021-2017, Res184-2023, Decree028-2023 (which amends Decree021-2017), the INS-CTManual, and Res252-2022, the INS’s Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT))), is responsible for conducting the review and approval of clinical trial applications. As per Decree021-2017 and Res252-2022, the INS also requests that the ANM assess the safety and quality of the IP to be used in a clinical trial and issue a binding technical opinion as part of the INS’s application review and approval process. Following a review of the research protocol, the ANM technical opinion, and other required documentation included in the application package, the INS will approve the clinical 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)) (PER-109)).

Decree021-2017, the INS-CTManual, and Res252-2022 also note that the Clinical Trials Subdirectorate will be able to convene a technical commission of experts when controversial situations arise during the authorization process.

In addition, per Decree021-2017, the INS-CTManual, and Res252-2022, 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 MINSA’s General Directorate of Strategic Interventions in Public Health (Dirección General de Intervenciones Estratégicas en Salud Pública (DGIESP)) will be requested to ensure the study does not interfere with its strategic interventions regarding these diseases.

Decree021-2017 and the INS-CTManual state that the INS’s DIIS grants clinical trial authorization for the total period of time scheduled for its completion as indicated in the PER-89 registration form submission. Further, per Decree021-2017, once the INS has completed the authorization process, the agency will post the approval status of a clinical trial via PER-89. The following application requirements, which align with the World Health Organization’s Trial Registration Data Set (PER-86), will also be provided in the approval status record: study title, sponsor and investigators, IP, condition under study, study design, and number of participants. See PER-111 for additional information on REPEC’s trial data record requirements. Refer to the INS-CTManual and Res252-2022 for details on the DIIS application review process, and PER-6 for a flowchart delineating the clinical trial authorization process.

See the Submission Process, Submission Content, and Timeline of Review sections for detailed submission and review requirements.

Per Decree021-2017, any modifications of the conditions under which a clinical trial was authorized, and amendments to the research protocol and/or informed consent, require prior authorization from the INS’s DIIS. The following are grounds for modification of clinical trial authorization conditions:

Expansion of the number of research sites
Expansion or modification of the list of supplies to be imported
Change of sponsor or CRO
Change of principal investigator (PI)
Extension of time for conducting the clinical trial
Closure of a research site for a clinical trial
Suspension of clinical trial
Cancellation of clinical trial

Decree028-2023 and Res184-2023 further modify Decree021-2017 to distinguish between amendments and minor changes to the protocol and/or ICF. The updated definition of amendment specifies that an amendment refers to a substantial change(s) that modifies the original version of the protocol and/or ICF and requires INS and EC reauthorization. A minor change(s) is defined as one proposed by the sponsor that complies with Decree028-2023 and the DIIS issued standards delineated in Res184-2023, and the responsibility for executing the protocol remains with the sponsor. Per Decree028-2023, a minor change(s) only requires the approval of the INS registered and accredited EC that originally approved the current version, and the sponsor must communicate the change(s) in writing to the INS’s DIIS prior to its implementation.

Res184-2023 states that changes or modifications must meet certain criteria to be considered minor changes. For changes that are not considered minor, it is necessary to initiate the corresponding amendment procedure delineated in Decree021-2017. Moreover, any new safety information derived from the Investigator’s Brochure is not considered a minor change. See the Scope of Review section and Res184-2023 for detailed descriptions of minor changes to the protocol and/or ICF that do not require DIIS approval.

See also the Submission Process section for additional information on trial extension documentation and review requirements.

Chapter VII (7.1) and Annex 4 (Flowcharts No. 01-04)

Preface, Articles 1-2, and Annex 1

Annex B

Preface, Article 1 (Articles 2 (10) and 40), Article 2 (Articles 2 (48), 6, and 85-A), and Article 3 (Final Complementary Provision)

Preamble, Article 3, and Annex 3

Preamble, Requirements for Initiating the Procedure (3, 10, and 13), and Annexes 1-3 and 9

Title II (Articles 10 and 21)

Title I (Articles 2 and 6-8), Title II (Article 10), Title IV (Articles 40, 52, 59, and 63), Title V (Chapter I and Articles 70 and 75), Title VI (Article 94), Title X (Articles 119-121), Supplementary Provisions - Final (Fourth and Eighth), and Annexes 1-5

Regulatory Fees

Last content review/update: July 26, 2024

According to CAN-33, there are no fees to submit a clinical trial application in Canada.

Question 5

Last content review/update: April 24, 2024

National Institute of Health (INS)

Per Decree021-2017, the sponsor or the contract research organization (CRO) is responsible for paying a fee, as applicable, to the National Institute of Health (Instituto Nacional de Salud (INS)) to submit a clinical trial application for authorization. Additionally, per Decree021-2017, INS payment is required to modify the trial as follows: to increase the number of research sites participating in a study; to change the sponsor or the 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 Res0423-2019, the forms required to modify the trial may be obtained from PER-26, PER-27, PER-28, PER-43, and PER-31.

According to PER-77, the INS is revising the clinical trial application fees but in the meantime is charging the fees outlined in PER-97 and PER-112, which state that the processing fee for a clinical trial authorization is 1,775.00 Peruvian Soles. An email may be sent to consultaensayos@ins.gob.pe for any additional fee-related questions.

Pursuant to Res655-2019, which amends Decree021-2017, in the case of multicenter clinical trials, the sponsor or the 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.

Payment Instructions

As indicated in PER-112, the clinical trial application fee can be paid as follows:

Via transfer to the beneficiary account number (Código de Cuenta Interbancario (CCI)): INS 018-00000000028241304 Banco de la Nación
CURRENT ACCOUNT. 0000-282413 in the name of the INS of the Banco de la Nación
In person in the form of cash or by cashier's check

For any additional questions, send an email to Ms. Ana Rojas of the Economics Office of the National Institute of Health at arojas@ins.gob.pe.

See PER-71 for payment receipt requirements to request authorization of a clinical trial via the Virtual Submission Platform (Mesa de Partes Virtual (MPV)) (PER-106). See PER-72 for a list of trial procedures and associated payment receipt requirements, if applicable. Refer to the Submission Process section for additional information on application submission requirements.

Clinical Trial Authorization Renewal, Extension for a Clinical Trial, Addition of New Research Sites

Annex B

Preamble, Articles 1 and 3, and Annexes (4-6, 8, and 10)

Title V

Ethics Committee

Last content review/update: October 1, 2024

Overview

As indicated in the CanadaFDR and the G-CanadaCTApps, Canada has a decentralized process for the ethical review of clinical trial applications, and requires the sponsor to obtain institutional ethics committee (EC) approval for each participating trial site. (Note: institutional ECs are referred to as Research Ethics Boards (REBs) in Canada.) Canadian provinces may have varying requirements, and, therefore, the sponsor should consult with the applicable province(s) for more information.

Per CAN-35 and CAN-13, all proposed or ongoing research involving human participants carried out by, funded by, or otherwise under the auspices of Health Canada (HC) or the Public Health Agency of Canada (PHAC) must obtain approval from a joint EC representing those two (2) agencies—as well as complying with the CanadaFDR and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50. This joint EC is known as the HC-PHAC REB. Further, if an institution is conducting an HC- or PHAC-funded project, the HC-PHAC REB must review and approve the research even if it has been previously reviewed and approved by another EC. See CAN-35 for details on the HC-PHAC REB’s development, responsibilities, and composition. HC’s operational policy (CAN-13) outlines policies and procedures that the joint HC-PHAC REB must follow when reviewing clinical trials.

Institutional ECs are required to comply with the provisions delineated in the CanadaFDR, the G-CanadaCTApps, and CAN-52. Note that per CAN-50, HC-implemented ICH guidance takes precedence over other HC guidance when they are not consistent. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100. In addition, institutional ECs are guided by the G-TCPS2. Jointly developed by Canada’s three (3) federal research agencies: the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), and the Social Sciences and Humanities Research Council (SSHRC), the G-TCPS2 is a policy that sets the ethical benchmark for all Canadian institutional ECs. However, only CIHR-, NSERC-, and SSHRC-funded institutions are required to comply with this guideline as a condition of funding. According to CAN-14, the CIHR, the NSERC, and the SSHRC created the Panel on Research Ethics (PRE) to promote the ethical conduct of research involving human participants. The PRE develops, interprets, and implements the G-TCPS2.

Ethics Committee Composition

As delineated in the CanadaFDR, the G-CanadaCTApps, and CAN-52, institutional ECs must have at least five (5) members representing a mixed gender composition, the majority of which are Canadian citizens or permanent residents, and must include:

Two (2) members from a scientific discipline, with broad experience in the relevant research methods and areas, one (1) of whom is from a medical or dental discipline
One (1) member knowledgeable in ethics
One (1) member knowledgeable in relevant Canadian biomedical research laws
One (1) member from a nonscientific discipline
One (1) community representative

The G-TCPS2 mirrors these EC composition requirements. As mentioned earlier, only CIHR-, NSERC-, and SSHRC-funded institutions are required to comply with this guidance as a condition of funding.

Terms of Reference, Review Procedures, and Meeting Schedule

According to CAN-52, institutional ECs must establish written standard operating procedures (SOPs) to cover the entire review process. The SOPs should include EC composition, meeting schedules, notifications, frequency of reviews, protocol deviations, reporting to the EC, and recordkeeping. Further, ECs should make decisions at announced meetings where a quorum is present. Only those members who participate in the EC review and discussion should vote, provide their opinion, or advise. For detailed EC procedures and information on other administrative processes, see CAN-52. For examples of EC SOPs, see CAN-13 for the HC-PHAC REB operational policy.

2 and 3

Introduction, 1.24, 1.27, and 2.6, 3

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

About the REB and Policies, Guidelines, and Resources

1.2, 1.4, 2.1, and 2.7

5.1, 5.2, 5.5, 5.6, and 5.10

Introduction and Chapter 6 (Articles 6.4 and 6.10)

Part C (Division 5 (C.05.001, C.05.002, C.05.005, C.05.006, and C.05.010))

Last content review/update: April 24, 2024

Overview

As set forth in Decree021-2017, Res655-2019 (which amends Decree021-2017), the INS-CTManual, and Res252-2022 (which amends the INS-CTManual), and PER-71, 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. In addition, as noted in Decree021-2017, those research institutions that do not have their own EC may select an INS-accredited EC, preferably located in the same region.

Ethics Committees for Human Subjects Health Research Other than Clinical Trials

Res233-2020, which regulates human subjects research other than clinical trials of drugs or devices, states that health institutions or entities may establish one (1) or more ECs in order to fulfill their requirements to conduct health research with human beings. Per Res233-2020, ECs that conduct health research with humans are established by statute, resolution, or other document that establishes, as a minimum, among others, the committee’s mission, its members, and their respective positions. 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)). 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. 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. See the Oversight of Ethics Committees section for information on registering a health service provider institution in RENIPRESS.

Institutional Research Ethics Committee of the National Institute of Health (CIEI-INS)

As described in PER-94, 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)) is an advisory committee that aims to protect the rights, life, health, privacy, dignity, and well-being of research participant(s) while adhering to the ethical principles accepted by national and international regulations, and the agreements signed by Peru on research ethics. According to PER-77, the CIEI-INS is not accredited to approve clinical trials. It approves research with human participants conducted with the involvement of the INS except for clinical trials with drugs or devices. (See PER-102 for a list of accredited ECs.)

Ethics Committee Composition

As delineated in Decree021-2017, institutional ECs must be multidisciplinary, with the participation of civil society, and be composed of at least five (5) regular members, who must ensure independence in their decision-making process.

Decree021-2017 lists the following membership requirements:

Persons 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 research participants are likely to come
At least one (1) full member must be from the community and not belong to the health field, or to the research institution

In addition, Decree021-2017 specifies that 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. Per Decree021-2017, the EC may consider the assistance of expert consultants on different topics, and the committee must also make the list of all members publicly accessible.

Ethics Committees for Human Subjects Health Research Other than Clinical Trials

As indicated in Res233-2020, ECs are multidisciplinary, reflecting the country’s social and cultural diversity, and must be comprised of at least five (5) members.

Res233-2020 lists the following membership requirements:

Persons with knowledge in research methodology and knowledge in the health field as well as in behavioral or social sciences
Persons with knowledge of legal and ethical matters
Community representatives; people outside the entities and institutions that comprise the ECs should also be included

In addition, Res233-2020 states that researchers must possess the relevant qualifications to carry out the investigation proposal, including basic training in ethics of research with human beings with the corresponding diplomas, certifications, titles, among others. Res233-2020 further indicates that 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

Pursuant to Decree021-2017, for their operations, ECs must have stated rules and prepare a procedures manual that is approved by the research institution. Per Decree021-2017, the manual must provide rules and procedures for the following:

Composition and requirements that must be met by its members
Minimum EC infrastructure requirements (e.g., specific areas that allow for work performance under conditions that guarantee confidentiality; adequate computer equipment; and administrative personnel to allow an EC to function properly)
Meeting frequency
Specific quorum requirements
Administrative requirements for the presentation of files
Monitoring authorized research protocols
Preparing and approving meeting minutes
Filing related documentation
Obtaining 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
Renewal procedures

See Title IV, Chapter 7 of Decree021-2017 for detailed EC requirements.

Decree021-2017 and PER-21 further note that minimum infrastructure requirements for the operation of institutional ECs must include ensuring specific work environments that permit their work to be conducted under conditions that guarantee confidentiality, and computer equipment with sufficient capacity to handle all the information generated by the EC.

Ethics Committees Human Subjects Health Research Other than Clinical Trials

As delineated in Res233-2020, ECs must have regulations and a procedures manual approved by the entity or institution that created them, specifying procedures, internal regulations, and other operational requirements.

Res233-2020 specifies that the procedures manual must include the following:

Conditions and terms for the appointment of members
Committee structure
Member responsibilities
Submitting research projects for review
Assessing the types of review
Classifying adopted decisions and processes to communicate these decisions
Developing the mechanism for determining whether a research project requires ethical review or should be exempt
Procedures for monitoring and surveillance of investigations, from the moment approved until terminated (including presenting amendments, deviations, adverse events, etc.)
Specifying required procedures and criteria for submitting expedited reviews
Reviewing projects based on ethical criteria (i.e., scientific validity and social value of the research, favorable benefit/risk balance ratio, equitable research participant selection, adequate informed consent process, respect for people, community participation and commitment)
Independent deliberation by members (i.e., EC members, researchers, sponsors, or other agents related to the research project under review should not be present)
Adopting research projects by consensus or by vote, and always with the participation of at least one (1) community representative and/or a member external to the entity or institution that constituted the EC
Requesting external assistance from independent consultants when necessary, taking into account the specialty or complexity of research under review

See Chapter 7 of Res233-2020 for detailed EC requirements.

Res233-2020 further notes that the entities and institutions that constitute the ECs must provide all of the economic, human, logistical, infrastructure, or the availability of other resources necessary for its operation.

7.4 and Annexes 1 and 4 (Flowchart 03)

I, VII (7.1 and 7.2), and VIII (8.2 and 8.3)

Annex B

Requirements for Initiating the Procedure (3) and Annex 3

Title IV (Article 40 and Chapter VII), Title V (Article 67), and Supplementary Provisions—Final (Eighth)

Scope of Review

Last content review/update: December 23, 2024

Overview

According to the CanadaFDR, the G-CanadaCTApps, the G-TCPS2, and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), the primary scope of information assessed by institutional ethics committees (ECs) (called Research Ethics Boards (REBs) in Canada) relates to maintaining and protecting the dignity and rights of human research participants and ensuring their safety throughout their participation in a clinical trial. ECs must also pay special attention to reviewing informed consent and protecting the welfare of certain classes of participants deemed vulnerable. (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations.) Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.

CAN-52, which Canada has implemented per CAN-50, also states that ECs must ensure an independent, timely, and competent review of all ethical aspects of the clinical trial protocol. They must act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants, and they must verify the adequacy of confidentiality and privacy safeguards. See CAN-52 for detailed ethical review guidelines.

Role in Clinical Trial Approval Process

As per the CanadaFDR and CAN-52, HC must approve a clinical trial application (CTA) and an institutional EC(s) must give ethical clearance prior to a sponsor initiating a clinical trial. In addition, as delineated in the CanadaFDR and the G-CanadaCTApps, institutional EC review for each clinical trial site may occur in parallel with HC’s CTA review and approval. Once HC completes its review, the department issues a No Objection Letter (NOL) if the CTA is approved. However, per the CanadaFDR, the G-CanadaCTApps, CAN-6, and CAN-30, HC will not authorize the sponsor to begin the clinical trial until an institutional EC approval for each participating trial site is submitted. The sponsor should use the Clinical Trial Site Information Form (CAN-6) to submit the required information. The CanadaFDR also states that the EC must review and approve any protocol amendments prior to those changes being implemented. For HC’s interpretation of the relevant provisions of CanadaFDR, see the G-FDR-0100.

The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ECs, requires EC review and approval of research involving living human participants and human biological materials. Further, ECs must have procedures in place to receive and respond to reports of new information, including, but not limited to, safety data, unanticipated issues, and newly discovered risks.

See TCPS2-InterpReview for the Panel on Research Ethics (PRE)’s interpretations of the G-TCPS2, including on the EC’s review of secondary use of non-identifiable information, delegated review of minimal risk studies, and ongoing review.

The G-TCPS2 lays out options, procedures, and considerations for the ethics review of multi-jurisdictional research either entirely within Canada, or in Canada and other countries. An institutional EC may approve alternative review models for research with multiple ECs and/or institutions but remains responsible for the ethics and conduct of research in its jurisdiction or under its auspices regardless of where the research is conducted. The SingleECRev provides guidance on the G-TCPS2’s single EC review model for multi-jurisdictional minimal risk, which seeks to streamline the research ethics review process where additional ethics reviews are not expected to add greater participant protections. In line with a proportionate approach to research ethics review, if research is of minimal risk and spans multiple jurisdictions, institutions that have approved the use of the single EC review model authorize the review of the research by one (1) EC. See the G-TCPS2 for more information about the various review models for multi-jurisdictional research.

Per CAN-8, an attestation must be completed by the EC that reviewed and approved the clinical trial. The completed attestation must be retained by the clinical trial sponsor for a period of 15 years. The attestation should not be submitted to HC unless requested. (See the Submission Process section for detailed submission requirements.)

The G-TCPS2 directs the researcher to submit an annual report to enable the EC to evaluate the continued ethical acceptability of the research. Per the G-CanadaCTApps, in the event that an EC terminates or suspends any prior approval or favorable opinion, it must document its views in writing, clearly identifying the trial, the documents reviewed, and the date for the termination or suspension.

1.2, 1.4, 2.1, 2.5, and 2.7

5.1, 5.2, 5.5, 5.6, and 5.10

Introduction, and Chapters 1-2, 6, 8, and 11

Part C (Division 5 (C.05.001, C.05.005, C.05.006, and C.05.010))

1.27, 2, 3, and 5.11

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Last content review/update: April 24, 2024

Overview

According to Decree021-2017 and the G-EC-CTRev, the primary scope of information assessed by institutional ethics committees (ECs) (Comités Institucional de Ética en Investigación (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 Decree011-2011, which assert that the defense of the human person and respect for their dignity are the supreme goal of society and the state.

As per Decree021-2017, Decree011-2011, and the G-EC-CTRev, 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 Decree021-2017, when a clinical trial is proposed for subordinate groups (e.g., students, health workers, employees, military members, police, prisoners, etc.), one (1) 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 the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these populations).

Decree021-2017 and the G-EC-CTRev also state that the National Institute of Health (Instituto Nacional de Salud (INS))-registered and accredited 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.

Res686-2020, in turn, states that in the ethical review of clinical studies of vaccines in humans, ECs must comply with the ethical criteria delineated in Res233-2020. Additionally, 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 Res686-2020, an EC decision regarding the approval or disapproval of a vaccine clinical study protocol must have a solid and justified ethical basis in the Council for International Organizations of Medical Sciences (CIOMS) criteria (PER-78).

Ethics Committees for Human Subjects Health Research Other than Clinical Trials

Res233-2020, which regulates human subjects research other than clinical trials of drugs or devices, similarly states that the focus of ECs that conduct human health research is to ensure the protection of the rights, safety, and well-being of the research participants. In addition, the INS must ensure the governance of all health research involving human beings is conducted ethically; the scientific validity and social value of the research is considered by the research studies; 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. Res233-2020 further specifies that human studies include, but are not limited to, epidemiological research, genetic research, social science research, research on medical records, and research on stored samples, among others.

Per Res233-2020, the ECs are also responsible for conducting rigorous, timely, and competent ethical reviews of research projects based on the CIOMS' International Guidelines for Health-Related Research Involving Humans (PER-78). Furthermore, the ECs should monitor the progress of an approved research project until it has concluded.

Additionally, per Res233-2020, the research entities or institutions that constitute ECs conducting human health research 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.

Role in Clinical Trial Approval Process

As per Decree021-2017, Res655-2019 (which amends Decree021-2017), the INS-CTManual, Res252-2022 (which amends the INS-CTManual), and the G-EC-CTRev, an INS-accredited EC must provide written confirmation of review and approval of the clinical trial protocol and the informed consent form (ICF) prior to the sponsor or the 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 Decree021-2017, each institutional EC determines its own review and approval timeline and continuing review requirements based on its internal regulations and standard operating procedures.

Per Decree028-2023 (which amends Decree021-2017), a minor change(s) to the protocol and/or ICF only requires the approval of the INS registered and accredited EC that originally approved the current version, and the sponsor must communicate the change(s) in writing to the INS’s DIIS prior to its implementation. Decree028-2023 and Res184-2023 (which amends Decree021-2017) also note that a minor change does not generate a new version of the protocol or ICF; however, if a subsequent amendment is made to the protocol, it must also contain the minor change(s) made. (See Timeline of Review section for timeline information on submitting minor changes to the INS’s DIIS.)

Res184-2023 specifically lists the following as minor changes to the protocol and/or ICF:

Typographical error corrections - A material unintentional error in a word, term, or expression that results from the writing, transcription, or translation of a specific expression that does not alter the meaning, objective, or intent of the word, term, or expression.
Modification of the conditions of clinical trial authorization or amendments - Updates made to the approved protocol and/or ICF, as a result of procedures for clinical trial modifications or amendments, linked to the change of protocol title, and/or name of the principal investigator, sponsor, and/or CRO; and/or study completion date, provided that the change is previously authorized by Director's Resolution or Official Letter issued by the INS's DIIS, as a result of the corresponding administrative procedure.
Clarifications and/or modifications of an administrative or operational aspect - Changes made to the approved protocol and/or ICF for strictly administrative or operational reasons. In addition, a clarification refers to a clarification of the protocol and/or ICF information or content which does not alter the meaning, objective, or intention of the document.

See Res184-2023 for detailed descriptions of minor changes to the protocol and/or ICF.

Per Decree021-2017, ECs must also conduct regular monitoring, with a frequency based on the degree of risk to participants, but no less than once a year. Further, they must suspend or cancel the trial when participants are exposed to uncontrolled risk and inform the research institution, the sponsor and/or the CRO, and the INS’s Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT))) of the suspension or cancellation.

(See the Submission Process and Timeline of Review sections for detailed submission process and timeline details.)

Preamble, VII, Ethical Criterion 1, Ethical Criterion 5, and Annex 3

Annexes 1 and 3

Chapter 1 (Articles 1 and 2) and Chapter 2 (Article 7)

Preface, Articles 1-2, and Annex 1

I, VII (7.1-7.3), and VIII (8.2 and 8.3)

Annex B

4 and 5.2

Preface, Article 1 (Articles 2 (10) and 40), and Article 2 (Articles 2 (48), 6, and 85-A)

Requirements for Initiating the Procedure (3) and Annex 3

Preamble, Introduction, II (1 and 3), and V (1)

Title I (Article 4), Title II (Article 9), Title III (Article 24), Title IV (Articles 58-60 and 64-67), and Title V (Article 70)

Ethics Committee Fees

Last content review/update: July 26, 2024

Institutional ethics committees (ECs) may independently decide whether to charge fees to conduct protocol reviews. For example, an institutional EC may require industry sponsors or other for-profit organizations to pay a fee. See specific examples of institutional fee requirements in CAN-3 and CAN-1.

REB Review Fees

Last content review/update: April 24, 2024

Fees are determined by each accredited institutional ethics committee.

Oversight of Ethics Committees

Last content review/update: July 26, 2024

There are no applicable regulations or guidance regarding the registration, auditing, and accreditation of institutional ethics committees (ECs).

Last content review/update: April 24, 2024

Overview

As set forth in Decree021-2017, the INS-CTManual, and PER-61, the National Institute of Health (Instituto Nacional de Salud (INS))’s Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the 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) (Comités Institucional de Ética en Investigación (CIEIs)) listed in the INS’s Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) (PER-89) (also referred to as REPECv2) to review and approve clinical trials. The DIIS must evaluate and verify EC compliance with the registration and accreditation standards established in the INS-CTManual. Per Decree021-2017, the INS-CTManual, PER-71, and PER-61, Peru requires clinical trial approval from an EC that is accredited by the INS’s National Registry of Accredited Institutional Ethics Committees (PER-61). (See PER-102 for a list of accredited ECs.)

Ethics Committees for Human Subjects Health Research Other than Clinical Trials

As delineated in Res233-2020, the INS is also responsible for providing advice, guidance, and technical assistance to all ECs and their entities or institutions that review health research with human beings; 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 DIIS to disseminate information and supervising ECs at the national level per the ethical research guidelines delineated in Res233-2020.

Registration, Auditing, and Accreditation

Per Decree021-2017, each research institution may establish an EC and register it with the INS via PER-89. (Refer to PER-102 for instructions on registering in the REPEC system.)

Per Decree021-2017, Res233-2020, the INS-CTManual, and the G-ECRegProcs, INS-registered ECs are only required to obtain accreditation if they are conducting a review of a clinical trial protocol involving pharmaceutical products. In addition to completing the accreditation/renewal application form (see PER-85 for FOR-OGITT-025), the applicant should complete the affidavit form (see PER-21 for FOR-OGITT-026) to demonstrate compliance with the accreditation standards delineated in the INS-CTManual. Both forms must be electronically submitted via PER-89. See PER-81 for instructional videos on registering on the REPEC platform.

PER-61 explains that once the registration form is electronically submitted, the user will receive a temporary EC registration number. Both the affidavit form and the registration forms should be printed and signed, and then attached along with the other accreditation documents required to be sent to the DIIS via the Document Processing Office located in the INS headquarters (refer to PER-61 and PER-98 for detailed requirements and instructions).

Decree021-2017 and the INS-CTManual state that accreditation is temporary and must be renewed every three (3) years. Per Decree021-2017, Res655-2019 (which amends Decree021-2017), and the INS-CTManual, the following accreditation requirements must be completed:

EC accreditation application sent to INS (PER-85), per Res0423-2019
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 Res0423-2019
Curriculum vitaes signed by each EC member submitted in electronic form (editable PDF)

Per the INS-CTManual, it is recommended that applications for EC accreditation renewals be submitted 30 calendar days before the end of term. Additionally, the INS-CTManual provides detailed information on the inspections that the INS-accredited ECs may be subject to before, during, and after EC registration.

Refer to the INS-CTManual and PER-61 for detailed submission instructions, and PER-85, PER-21, PER-22, and PER-35 for the EC accreditation application and EC affidavit of compliance forms.

Ethics Committees for Human Subjects Health Research Other than Clinical Trials

Res233-2020, which regulates human subjects research other than clinical trials of drugs or devices, requires ECs to be registered with the INS via the National Registry of Research Ethics Committees (Registro Nacional de Comités de Ética en Investigación), per the G-ECRegProcs. The G-ECRegProcs establishes standardized procedures for the INS’s DIIS to conduct EC registration evaluation in compliance with Res233-2020. As specified in the G-ECRegProcs, the DIIS’s Clinical Trials Subdirectorate (Subdirección de Ensayos Clínicos) (formerly known as the Executive Office of Investigation (Oficina Ejecutiva de Investigación (OEI)) is responsible for receiving, evaluating, and responding to EC registration requests. Depending on the implementation period, registration can be immediate, in which registration occurs at the time of the request, or progressive, in which implementation is carried out over a maximum period of two (2) years after initial EC registration. During the implementation of progressive requirements, the DIIS can provide advice and guidance to the EC upon request.

Per the G-ECRegProcs, in the case of immediate registration approval, once the registration application file is initially reviewed for completeness, it is forwarded to the application evaluator who verifies whether the file minimally complies with all the immediate requirements within 30 days. If the registration file meets the immediate requirements and the information provided complies with the INS-CTManual and the G-ECRegProcs provisions, the evaluator prepares a favorable response report and a draft record of registration, addressed to the Clinical Trials Subdirectorate. Once the favorable response report has been received, the Clinical Trials Subdirectorate evaluates and endorses it, sending the report and draft record of registration to the DIIS. The DIIS issues the EC certificate of registration and incorporates registration into the National Registry of Research Ethics Committees (Registro Nacional de Comités de Ética en Investigación) database. In addition, per the G-ECRegProcs, an EC registration may be suspended if the EC has not completed implementation of the progressive registration requirements within the two-year term. Refer to G-ECRegProcs for additional information on the DIIS’s registration review and approval process.

Chapter VII (7.3-7.4 and 7.9) and Annex 4 (Flowcharts No. 02-03 and 17)

I, VII (7.4) and VIII (8.1 and 8.2)

Annex B

Preamble, Article 1, and Annexes (2-3)

Title IV (Articles 54, 58, and 63), Title V (Article 67), Title VII (Article 102), and Supplementary Provisions—Final (Eighth)

Submission Process

Last content review/update: July 26, 2024

Overview

In accordance with the CanadaFDR and the G-CanadaCTApps, Canada requires the sponsor to obtain clinical trial authorization from Health Canada (HC) prior to initiating the trial. The sponsor must file a clinical trial application (CTA) to the appropriate Directorate within HC’s Health Products and Food Branch (HPFB). In addition, as delineated in the CanadaFDR and the G-CanadaCTApps, the sponsor may submit a CTA for clinical trial authorization to the HC in parallel with its submission to an institutional ethics committee (EC) (known as a Research Ethics Board (REB) in Canada) for a favorable ethical opinion. However, per the CanadaFDR, the G-CanadaCTApps, CAN-6, and CAN-30, HC will not authorize the sponsor to begin the clinical trial until an institutional EC approval (provided in the required Clinical Trial Site Information (CTSI) form (CAN-6)) for each participating trial site is submitted. The HCNotice-CTSIForm indicates that the CTSI form improves efficiencies and supports the submission of CTAs using the electronic Common Technical Document (eCTD) format. See CAN-30 for instructions on filling out and submitting CAN-6.

CAN-19 provides a full list of HC’s forms for drug-related applications and submissions. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

Regulatory Submission

Per the G-CanadaCTApps, CTAs (CAN-4) should be sent directly to the appropriate HPFB Directorate for review—the Pharmaceutical Drugs Directorate (PDD) for pharmaceutical drugs or the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) for biological drugs and radiopharmaceuticals. The outer label should be clearly identified with "Clinical Trial Application." Per CAN-44, applicants must submit CTAs electronically in either eCTD format or non-eCTD format. According to the G-MDSA, HC does not accept paper copies of CTAs, CTA amendments, and CTA notifications.

The G-MDSA and the G-CanadaCTApps indicate that sponsors may request a pre-submission/application meeting with the appropriate Directorate within the HPFB if they have any questions or concerns prior to filing a CTA. Additional details on requesting a meeting and meeting procedures are available in the aforementioned guidance documents. According to CAN-4, the submission can be in French or English. For CTAs that use pharmacometric approaches, sponsors should consider the policy statements in G-Pharmacometrics. Pharmacometrics is the science of using quantitative analysis and modelling and simulation approaches to inform and enhance drug development and regulatory review. In addition, see the G-CTACell for guidance on preparing CTAs for use of cell therapy products in humans.

Per the CanadaFDR, an application by a sponsor for authorization to sell or import a drug for the purposes of a clinical trial must be submitted to HC, signed and dated by the sponsor’s senior medical or scientific officer in Canada and senior executive officer. The sponsor’s clinical trial attestation must be submitted with the application (CAN-4). For guidance on completing CAN-4, see the G-DrugApp.

eCTD Electronic Submission

As indicated in the G-eCTD, clinical trial applications in eCTD format are recommended, not mandatory. However, once a sponsor files a regulatory activity in eCTD format, all additional information and subsequent regulatory activities for the same dossier must be filed in eCTD format. CAN-36 explains that prior to filing the first regulatory transaction for a dossier in eCTD format, the sponsor must request a dossier ID using the online dossier ID request. Per the ElecSubms, CAN-20 is the request form for biological clinical trial dossiers and CAN-21 is for pharmaceutical clinical trial dossiers. A request for a dossier ID should be sent a maximum of eight (8) weeks prior to submitting the CTA. In addition, applicants should review the Rules-eCTD for validation rules before submission. (Note: As per ElecSubms, G-eCTD and CAN-36 are only available upon request at no-reply.ereview.non-reponse@hc-sc.gc.ca. Please ensure the text 'Request for eCTD Guidance Document' is in the subject line of the email.)

Per the G-eCTD and CAN-28, all regulatory transactions in eCTD format must be sent via the Common Electronic Submissions Gateway (CESG) (CAN-25), except for those exceeding 10 gigabytes (GB) in size. The CESG allows users to submit secure regulatory transactions electronically to HC, including CTAs. The G-eCTD and CAN-36 describe how to file CTAs and other clinical trial regulatory transactions (e.g., CTA amendments, responses to requests for information, and other in-scope activities) in eCTD format to CESG. The G-eCTD clarifies that prior to using the CESG for sending transactions, sponsors must register as a trading partner. To access and use CESG, CAN-34 instructs sponsors to follow these steps:

Register as a trading partner with the US Food & Drug Administration (FDA) by completing the FDA Electronic Submissions Gateway (ESG) (CAN-51) registration for an account (CAN-47).
Send regulatory transactions to HC by selecting “HC” as the center on the FDA ESG system; CTAs intended for HC will be automatically redirected.

For detailed information on how to become a trading partner and send regulatory transactions, refer to CAN-25 and the FDA User Guide (CAN-47).

As indicated in the G-eCTD, the following media formats are acceptable for eCTD transactions greater than 10 GB: Universal Serial Bus (USB) 2.0 or 3.0 drive; or portable external hard drive with USB 2.0 or 3.0 interfaces. (Contact HC at hc.ereview.sc@canada.ca for other media formats that may be acceptable at the time of filing.) A paper copy of the cover letter must accompany the media (unless otherwise indicated), and a pre-paid envelope must be provided if the media is to be returned. The complete regulatory transaction must be provided on a single drive, and the label on the drive should contain the following information:

Stakeholder Name
Brand Name
Dossier ID, which is based on the protocol number
Sequence (regulatory transaction) number

Media must be mailed to HC at the address below:

Health Canada
Finance Building
101 Tunney’s Pasture Driveway
Address Locator: 0201A1
Ottawa, Ontario
K1A 0K9

See the G-CESG, the G-eCTD, CAN-47, CAN-34, CAN-36, CAN-25, and CAN-28 for details on registering as a trading partner for CESG transactions, how to use CESG, and submitting CTAs in eCTD format. (Note: As per ElecSubms, G-CESG is only available upon request at no-reply.ereview.non-reponse@hc-sc.gc.ca. Please ensure the text 'Request for eCTD Guidance Document' is in the subject line of the email.)

Non-eCTD Electronic Submission

For non-eCTD electronic submissions, G-Non-eCTD indicates that HC requires both PDF and MS-Word formats for the CTA (CAN-4). The PDF documents must be generated from electronic sources (not scanned material), except when access to an electronic source document is unavailable or where a signature is required. It is important that PDF files be properly bookmarked and hyperlinked. Documents that legally require signatures may be signed with an electronic signature, or the signature page can be printed, signed, scanned, and saved as a PDF file. The cover letter does not require a signature, but should include a printed name, phone number, and email address. All regulatory submissions should be validated prior to transmitting to HC. For validation rules, see the Rules-Non-eCTD. The ElecSubms contains a zip file of the folder structure for clinical trial non-eCTD submissions. (Note: As per ElecSubms, G-Non-eCTD is only available upon request at no-reply.ereview.non-reponse@hc-sc.gc.ca. Please ensure the text 'non eCTD Guidance Document' is in the subject line of the email.)

Per the G-Non-eCTD, CTA submissions to the appropriate Directorate within HC’s HPFB must be in one (1) of these accepted media formats:

Compact Disc-Recordable (CD-R) conforming to the Joliet specification
USB 2.0 or 3.0 drive
Digital Versatile Disc (DVD-RAM and DVD+R/-R) in Universal Disk Format (UDF) standard

All media should be labelled and contain the following information:

Stakeholder Name
Brand Name
Dossier ID (if known)

Subsequent to burning the CD/DVD or transferring data to a drive, applicants should ensure that all files can be opened, files are not corrupted, and that "Thumb.db" files are removed.

As per the G-Non-eCTD, CAN-18, and CAN-17, non-eCTD CTAs involving pharmaceutical drugs should be sent to PDD, and CTAs involving biologics and/or radiopharmaceuticals should be sent to BRDD at the addresses listed below.

Office of Clinical Trials
Pharmaceutical Drugs Directorate
Health Canada
5th Floor, Holland Cross, Tower B
1600 Scott Street
Address Locator: 3105A
Ottawa, Ontario, Canada
K1A 0K9
General Inquiries E-mail: oct.enquiries-requetes.bec@hc-sc.gc.ca

Office of Regulatory Affairs
Biologic and Radiopharmaceutical Drugs Directorate
Ground Floor, Health Canada Building 6
100 Eglantine Driveway
Address Locator: 0601C
Ottawa, Ontario, Canada
K1A 0K9
General Enquiries E-mail: brdd.ora@hc-sc.gc.ca

Per the HCNotice-CTSIForm, questions related to pharmaceutical CTSI forms should be sent to: oct.enquiries-requetes.bec@hc-sc.gc.ca and questions related to biologic CTSI forms should be sent to brdd.ora@hc-sc.gc.ca.

Per the G-Non-eCTD, if an applicant submits a non-eCTD CTA via email, they should meet the following requirements:

The maximum email size accepted by the corporate mail server is 20 megabytes. If the clinical trial submission is larger than 20 megabytes, the submission may be split and sent as separate emails (e.g., an email for Module 1, and another email for Module 2/3). The subject line of the emails should clearly link to each other (e.g., "Email 1 of 2" in the relevant subject line)
A duplicate copy must not be provided by mail
The submission should be organized in folders and the body of the email should only contain the zipped regulatory submission
Zipped files and documents contained in the email should not be password protected

The G-Non-eCTD provides additional information on emailing other clinical trial submissions, including responses to a clarification request, responses to a no objection letter, notifications, and development safety update reports.

Ethics Review Submission

As indicated in the CanadaFDR and the G-CanadaCTApps, all research involving human participants in Canada must be reviewed by an institutional ethics committee (EC). (Note: institutional ECs are referred to as Research Ethics Boards (REBs) in Canada.) Because the submission process at individual institutional ECs will vary, applicants should review and follow their institution’s specific requirements. Further, Canadian provinces may have varying requirements, and, therefore, the sponsor should consult with the applicable province(s) for more information. See CAN-35 for submission requirements to the joint HC-Public Health Agency of Canada (PHAC)’s REB. This joint EC reviews all research involving human subjects that is carried out by HC or PHAC researchers, on the premises, or in collaboration with external researchers.

1.2, 2.2, 2.3, and 2.7

5.2, 5.4, and 5.5

3.1-3.4 and Appendix B

Guidance documents, notices, and supporting documents

7.1, 8.1, and 8.2

1.3 (Table 1), 3.2, and 5

Part C (Division 5 (C.05.002, C.05.004, C.05.005))

Last content review/update: April 24, 2024

Overview

In accordance with Decree021-2017, Res655-2019 (which amends Decree021-2017), the INS-CTManual, and Res252-2022 (which amends the INS-CTManual), the sponsor or the contract research organization (CRO) is responsible for submitting a clinical trial application to the National Institute of Health (Instituto Nacional de Salud (INS)) to obtain approval to conduct a clinical trial in Peru. Per Decree021-2017, Res655-2019, the INS-CTManual, Res252-2022, and the G-EC-CTRev, the INS-accredited ethics committee (EC) must first approve the research protocol and informed consent form (ICF), and the sponsor or the CRO must submit this information as part of the application dossier in order for the INS to conduct its review. Therefore, the INS and EC reviews may not be conducted in parallel. Decree021-2017 also states that sponsors not based in Peru are required to appoint a legal representative in the country who coordinates all communication with the INS’s Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the 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.

Regulatory Submission

REPEC Pre-Submission Registrations

As delineated in Decree021-2017, Res655-2019, Res252-2022, the INS-CTManual, PER-60, and PER-59, prior to submitting an application for clinical trial authorization, the sponsor and the CRO must register with the Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) (PER-89) (also referred to as REPECv2). The INS-CTManual also notes 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. See the INS-CTManual, PER-60, and PER-59 for detailed sponsor and CRO registration instructions and PER-36 and PER-37 for the sponsor and the CRO registration forms. Refer to Res393-2021 for additional information on the updated sponsor registration form (PER-36). See also PER-81 for instructional videos on registering with PER-89.

Additionally, as specified in PER-89, the REPECv2 platform should be used to obtain information or request feedback on procedures and operations related to a newly submitted clinical trial, to track the status of the authorization process, to identify critical events that require immediate attention via an alert system (e.g., expiring or expired authorizations and necessary notifications per Decree021-2017), and to obtain updated information on clinical trials being conducted in Peru. Also, as explained in PER-114, DIIS has initiated the process of migrating information from the older platform (REPECv1) (PER-91) to PER-89 to receive and manage clinical trial information on a single platform, therefore all new requests for clinical trial procedures should be entered through PER-89. However, per PER-88, any requests for procedures related to an already active clinical trial must still be requested using the older REPEC platform via PER-91. PER-114 further notes that requests for clinical trials that are in progress and have been entered through REPECv1 will not be migrated to REPECv2 until the procedure is concluded.

Submissions

Pursuant to Res252-2022, all application related documents must be electronically submitted through the Virtual Submission Platform (Mesa de Partes Virtual (MPV)) (PER-106). According to PER-103, all notifications relating to procedures submitted via PER-106 will only be responded to in the PER-106 notification mailbox; notifications will not be communicated via email or other forms of communication.

Per PER-104, users must also be registered on PER-106 prior to submitting any application related documents. Registration is done through PER-106 or via the MPV link on the INS webpage. Although, as indicated in PER-106, non-citizens cannot register directly with PER-106, and require an in-country representative to provide proof of citizenship to register using either a national identity document or an immigration card. Refer to the G-MPVManual and the G-VirtSubPlatfrm for detailed user instructions and procedures, and PER-107, PER-110, and PER-105 for additional information on the MPV system.

As explained in Decree021-2017, the INS-CTManual, Res252-2022, and PER-71, once the sponsor or the CRO is registered in the REPEC and MPV systems, a request for clinical trial authorization must be submitted electronically via PER-89. (See PER-24 for the clinical trial application form and PER-10 for instructions on completing the form.) Per Res252-2022, the completed electronic request form should then be submitted via PER-106 along with the required documentation as set forth in Decree021-2017 and Res655-2019.

Decree021-2017 and Res655-2019 further indicate that the clinical trial application and accompanying material (including the updated Investigator’s Brochure (IB)) must be provided in Spanish. Any document not in Spanish must be submitted with a corresponding translation. Decree021-2017 also states that if the protocol title is written in English, a single title in Spanish must be assigned for all purposes. In addition, the research protocol and the ICF must also be in Spanish and in the original language, if different from Spanish, and include a copy of the approval by an INS-accredited EC. Per Decree021-2017, research and complementary investigational product (IP) media labeling must also be printed in indelible ink in Spanish or English. The INS-CTManual also notes that notification reports for IPs should contain a translated summary in English and Spanish.

For amended protocols or ICF submissions, Res655-2019 states that any changes should be electronically submitted (editable PDF) with track changes in Spanish and in the original language. The final protocol and ICF should include all of the incorporated amendments in an editable PDF file and comply with all of the previously discussed protocol submission requirements. See also Res655-2019, PER-32, PER-33, PER-34, and PER-35, for additional details on submitting protocol amendments and the related forms. See PER-105 and G-MPVManual for information on submitting documents electronically via PER-106 or via the MPV link on the INS webpage.

PER-92 indicates that for questions or problems with PER-89, contact:

Jenny Parillo, Engineer
Phone: (511) 748 0000 Extension: 2616 or 984108368 (Cell)
Email: jparillo@ins.gob.pe

(Note: Application submission instructions in earlier sources including Res655-2019, the INS-CTManual, and PER-71, do not reflect this new electronic submission option.)

For reference, the following are applications and forms that may be used to submit various procedures via PER-106:

PER-24 for the clinical trial application for authorization
PER-26 for the application to extend the number of research sites
PER-28 for the application to change the principal investigator (PI)
PER-29 for the application to change the sponsor/CRO
PER-31 for the application to cancel a clinical trial
PER-35 for the affidavit to be signed by the principal investigator (PI) and sponsor on the research site’s preparedness for the clinical trial
PER-43 for the application to close a clinical trial research site
PER-44 for the affidavit of compliance with minimum research site requirements
PER-50 for the research team curriculum vitae form
PER-85 for the EC accreditation/accreditation renewal form
PER-87 for the form and requirements to request INS approval to supervise a clinical trial virtually

Refer to the INS-CTManual, Res252-2022, and PER-71 for additional submission information. See PER-6 for a flowchart delineating the clinical trial authorization process. See also the Submission Content section for detailed documentation requirements.

Ethics Review Submission

Because the submission process at individual institutional ECs will vary, applicants should review and follow their institution’s specific requirements.

Annex 3

Chapter VII (7.1-7.2 and 7.8.2-7.8.3) and Annexes 1, 3, and 4 (Flowcharts No. 04, No. 13, and No. 14)

Annexes A and B

Requirements for Initiating the Procedure (3), 1.1-1.4, 2.3, 4.1-4.4, 7.1-7.2, and Annexes 1-3

Title I (Articles 6-7), Title III (Article 34), Title IV (Articles 39-40, 59, and 63), Title V (Articles 67, 75, 80, and 88), Title VI (Article 91), Supplementary Provisions—Final (Eighth), and Annex 1

Submission Content

Last content review/update: October 1, 2024

Regulatory Authority Requirements

As set forth in the CanadaFDR, the G-CanadaCTApps, and CAN-31, Health Canada (HC) requires the sponsor to apply for clinical trial authorization by submitting a clinical trial application (CTA) to HC. As specified in the G-CanadaCTApps and the G-QCM-PharmCTAs, the CTA should be organized into three (3) modules in Common Technical Document (CTD) format:

Module 1 - Administrative and clinical information about the proposed trial
Module 2 - Quality (Chemistry and Manufacturing) summaries about the drug product(s) to be used in the proposed trial
Module 3 - Additional supporting quality information

Per the CanadaFDR, the clinical trial application form (CAN-4) and the following information and documents must be submitted:

Protocol
Summary of potential risks/benefits
Clinical trial attestation that includes drug information (chemistry, names, classifications, dosage, therapeutic purpose, human-sourced excipient, drug identification number or notice of compliance, manufacturing information); sponsor’s contact information; if the drug is to be imported, contact information for the sponsor’s representative in Canada who is responsible for the sale of the drug; and contact information for the qualified investigator at each site, if known at the time of submittal
Contact information for each institutional ethics committee (EC) (known as Research Ethics Board (REB) in Canada) that approved the protocol, if known at the time of submitting the application
Contact information of any institutional EC that previously refused to approve the protocol, its reasons, and refusal date
Investigator’s Brochure (IB)
Informed consent form (ICF)
Information about use of a human-sourced excipient
Chemistry and manufacturing information
Proposed date for trial commencement at each site, if known

Refer to the CanadaFDR, the G-CanadaCTApps, the G-DrugApp, the G-QltyBioCTs, and the G-QCM-PharmCTAs for detailed submission information.

Ethics Committee Requirements

Each institutional EC has its own application form and clearance requirements, which can differ significantly regarding the number of copies to be supplied and application format requirements. However, the following requirements comply with the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, and are basically consistent across all Canadian ECs:

Clinical protocol
ICFs and participant information
Participant recruitment procedures
IB
Safety information
Participant payments and compensation
Investigator(s) current curriculum vitaes (CVs)
Additional required institutional EC documentation

See section 3.1.2 of CAN-52 for additional submission content requirements.

The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ECs, requires clinical trial researchers to include a plan for monitoring safety, efficacy/effectiveness (where feasible), and validity in their proposal for EC review. See the G-TCPS2 for additional details on the plan’s required contents.

See CAN-35 for submission requirements to the joint HC-Public Health Agency of Canada (PHAC)'s REB. This joint EC reviews all research involving human subjects that is carried out by HC or PHAC researchers, on the premises, or in collaboration with external researchers.

Clinical Protocol

As delineated in CAN-52, the clinical protocol should include the following elements:

General information
Background information
Trial objectives and purpose
Trial design
Participation selection/withdrawal
Participant treatment
Efficacy assessment
Safety assessment
Statistics
Direct access to source data/documents
Quality control/quality assurance procedures
Ethical considerations
Data handling and record keeping
Financing and insurance
Publication policy
Supplements

For complete protocol requirements, see section 6 of CAN-52.

3.1.2, 6, and 7

Efficacy guidelines

Apply for Ethics Review

2.3 and 2.7

I, S Drug Substance, and P Drug Product

Chapter 11 (Article 11.6)

Part C (Division 5 (C.05.001, C.05.004, and C.05.005))

Last content review/update: April 24, 2024

Regulatory Authority Requirements

As specified in Decree021-2017, Res655-2019 (which amends Decree021-2017), the INS-CTManual, Res252-2022 (which amends the INS-CTManual), PER-71, and PER-83, a clinical trial application submission must include the following documents (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Application for clinical trial authorization and proof of payment (PER-24) (per Annex B in Res655-2019)
Approval(s) issued by legal representative of institution(s) where research will be conducted (per Annex 1 in INS-CTManual and Annex 2 in Res252-2022)
Copy of the approved research protocol and informed consent form (ICF) stamped and signed by the ethics committee (EC) in its entirety (per Annex 3 in INS-CTManual and Annex 3 in Res252-2022)
Research protocol in Spanish, and in the original language if different from Spanish, submitted in electronic form as an editable PDF (per Annex B in Res655-2019)
ICF in electronic form as an editable PDF (per Annex B in Res655-2019)
Updated Investigator’s Brochure (IB) in Spanish, and in the original language if different from Spanish, submitted in electronic form as an editable PDF (per Annex B in Res655-2019)
Affidavit stating no conflict of financial interest signed by the sponsor or the contract research organization (CRO) and the principal investigator (PI) (PER-34)
Affidavit signed by the PI and sponsor on preparation of research institution for trial (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 the 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 (PER-42)
Information related to the investigational product (IP) quality (electronic form) (per Annex B in Res655-2019)
Updated curriculum vitaes (CVs) of all research team members with attached copies (PER-50) (per Annex B in Res655-2019)
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) (per Annex B in Res655-2019)
Detailed national budget total for trial form (PER-25)
Copy of current record of authorized research institution(s) for clinical trials
Payment receipt for research site registration; in the case of multicenter trials, proof of payment for processing fee (per Annex B in Res655-2019)

Refer to Decree021-2017, Res655-2019, the INS-CTManual, Res252-2022, and PER-71 for detailed submission information; PER-24 for the recently amended clinical trial application form per Res0423-2019; and PER-10 for detailed instructions on completing the form.

See also the Submission Process section for additional submission requirements, and PER-6 for a flowchart delineating the clinical trial authorization process.

Trial Extensions

Decree021-2017, Res655-2019, PER-72, PER-27, and PER-93 indicate that the sponsor or the CRO must submit the following documents for clinical trial application extensions: (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

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 FOR-OGITT-037 (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 National Institute of Health (Instituto Nacional de Salud (INS))-accredited EC

Report justifying the reasons for submitting the request
Current insurance policy

Ethics Committee Requirements

Specific institutional EC requirements are not provided in Peru’s regulatory sources. However, according to PER-77, 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 site 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 practices and human research ethics

Clinical Protocol

As delineated in Decree021-2017, 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 Safety Reporting section 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 Decree021-2017.

Clinical Trial Authorization and Extension for a Clinical Trial (English website); Clinical Trial Time Extension (Spanish website)

Chapter IX (Forms), Chapter X (Annex 1, Annex 3, and Annex 4 (Flowchart No. 04))

Annexes A and B

Preamble, Article 1, and Annex 3

Requirements for Initiating the Procedure and Annexes 1-9

Title V (Article 67) and Annexes 1-2 and 4-5

Timeline of Review

Last content review/update: October 1, 2024

Overview

As delineated in the CanadaFDR and the G-CanadaCTApps, the review and approval of a clinical trial application (CTA) by Health Canada (HC) and an institutional ethics committee (EC) (known as Research Ethics Board (REB) in Canada) may be conducted in parallel. However, per the CanadaFDR, the G-CanadaCTApps, CAN-6, and CAN-30, HC will not authorize the sponsor to begin the clinical trial until an institutional EC approval (provided in the required Clinical Trial Site Information (CTSI) form) for each participating trial site is submitted. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

Regulatory Authority Approval

According to the CanadaFDR and the G-CanadaCTApps, an authorized clinical trial is one that has been filed with HC and has not received an objection within 30 days. All CTAs are subject to the 30-day default period from the date of receipt of the completed application at the appropriate Directorate within HC’s Health Products and Food Branch (HPFB). While the Directorates can establish shorter administrative targets of seven (7) days for the review of bioequivalence trials, the 30-day default system remains the regulatory requirement. Applications to conduct Phase I clinical trials using somatic cell therapies, xenografts, gene therapies, prophylactic vaccines, or reproductive and genetic technologies are not included in the seven-day target system. Please see the G-CanadaCTApps for special requirements regarding reviews of comparative bioavailability studies and joint reviews of clinical trials covering a combination of devices, biologics, and pharmaceuticals.

As specified in the G-CanadaCTApps and the G-MDSA, during the review period, the Directorate may request additional information from the sponsor, who has two (2) calendar days to provide such information. The G-MDSA clarifies that, where warranted, HC can adjust the timelines to be longer or shorter based on the complexity of the request, dialogue with the sponsor, and/or circumstances of the review, including pausing the clock during the scientific review. According to the G-CanadaCTApps and the G-MDSA, if HC authorizes the CTA, then it issues a No Objection Letter (NOL). If HC rejects the CTA, it sends a Not Satisfactory Notice (NSN). HC will issue an NSN if it identifies significant deficiencies, or, if a timely response to requested information has not been provided. The sponsor may resubmit the information and material at a future time, and it will be processed as a new CTA.

Ethics Committee Approval

The EC review and approval process timeline varies by institution. However, according to the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, the institutional EC should review a proposed clinical trial within a reasonable time. The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ECs, recommends a proportionate approach to ethics review—the lower the level of risk, the lower the level of scrutiny (delegated review); the higher the level of risk, the higher the level of scrutiny (full board review). In either case, pursuant to the G-TCPS2, the institutional EC should make its decisions in an efficient and timely manner. See CAN-35 for ethics review timelines with the joint HC-Public Health Agency of Canada (PHAC)'s REB. This joint EC reviews all research involving human subjects that is carried out by HC or PHAC researchers, on the premises, or in collaboration with external researchers.

3.1.2

Efficacy guidelines

Apply for Ethics Review

2.1, 2.3.3, 2.5, and 2.7

5.5 and 5.6

Chapter 2 (Articles 2.8 and 2.9) and Chapter 6 (Article 6.13)

11.1, 12.1, and 13.3-13.4

Part C (Division 5 (C.05.005 and C.05.006))

Last content review/update: April 24, 2024

Overview

Based on Decree021-2017, Res655-2019 (which amends Decree021-2017), the INS-CTManual, and Res252-2022 (which amends the INS-CTManual), 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.

Regulatory Authority Approval

As per Law27444 and Decree004-2019 (which amends Law27444), the INS is required to complete its review and approval of a clinical trial application in a maximum of 30 working days. Per Decree021-2017, this timeline includes the 30-day requirement for the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) to issue a binding technical opinion on the safety and quality of the investigational product (IP). (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)) (PER-109)).

As explained in the INS-CTManual and Res252-2022, the person in charge of the Documentary Processing Area (Área de Trámite Documentario (ATO)) receives the application file and reviews the file with a health professional assigned from the DIIS’s Clinical Trials Subdirectorate (Subdirección de Ensayos Clínicos) (formerly known as the Executive Office of Investigation (Oficina Ejecutiva de Investigación (OEI))) to ensure completeness. The applicant has a maximum of two (2) business days to make any corrections that have been identified. If the corrections have not been made in the required timeline, the file is returned to the applicant, who is reimbursed for any processing fees. If the file is deemed complete and any required corrections have been addressed, the file is assigned a registration number in SIGNANET, the INS’s integrated administrative management system. Res252-2022 further explains that the authorization request procedure is formally initiated when the sponsor is provided with the file registration number. At this stage, an identification number is also assigned to the clinical trial in the Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) (PER-89) (also referred to as REPECv2).

Per Res252-2022, the file is then forwarded to the Clinical Trial Processing Area (Área de evaluación de Ensayos Clínicos (AEC)). Upon receipt of the application file, the AEC reviewer receives the file and sends the list of clinical trial supplies (PER-42) along with the required documentation in Annex 5 of Decree021-2017 to the Research Product Safety Surveillance Area (Área de Vigilancia de la Seguridad del Producto en Investigación (AVISPI)). AVISPI, in turn, sends this documentation to the ANM to request a binding technical opinion on the IP safety and quality. Concurrent with the request for the ANM’s review, the AEC reviewer evaluates the file, including the ANM binding technical opinion once received, and prepares a draft evaluation report which is reviewed by the Functional Clinical Trials Team (Equipo Funcional de Ensayos Clínicos (EFEC)) coordinator. If agreed to, the EFEC coordinator forwards the file to the Clinical Trials Subdirectorate’s Legal Advice Functional Team (Equipo Funcional de Asesoría Jurídica (EFAJ)) who prepares a report for the Clinical Trials Subdirectorate Executive Director’s review.

The Clinical Trials Subdirectorate Executive Director reviews the evaluation documents and legal report generated by the EFEC and the EFAJ. If the evaluation is agreed to, then the Executive Director signs the report, approves the project, and sends it to the INS’s DIIS, who also reviews and approves the file and signs off on the project. Otherwise, the file is returned to the EFEC to be handled as a non-compliant project. The process is finalized when the sponsor or the CRO is notified of the approval. The DIIS secretary registers the decision in SIGANET and all documentation is registered in PER-89. Per Decree021-2017, the sponsor has the right to appeal when the INS does not grant authorization.

Per Decree021-2017, any modifications of the conditions under which a clinical trial was authorized, and amendments to the research protocol and/or informed consent, require prior authorization from the INS’s DIIS.

Decree028-2023 (which amends Decree021-2017) further specifies that a minor change(s) to the protocol and/or informed consent form (ICF), only requires the approval of the INS registered and accredited EC that originally approved the current version, and the sponsor must communicate the change(s) in writing to the INS’s Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT))) within 10 business days prior to its implementation. Per Decree028-2023 and Res184-2023 (which amends Decree021-2017), a minor change does not generate a new version of the protocol or ICF; however, if a subsequent amendment is made to the protocol, it must also contain the minor change(s) made. (See Scope of Assessment and Scope of Review sections for additional information on submitting minor changes to the INS’s DIIS.)

Per Decree021-2017, Res655-2019, PER-72, and PER-93, the sponsor or the CRO should also request a trial extension within 30 calendar days prior to the trial’s expiration. The authorized trial extension will be valid for a maximum of 12 months from the date of issue.

Ethics Committee Approval

The EC review and approval process timeline varies by institution.

Chapter VII (7.1-7.2) and Annexes 1, 3, and 4 (Flowcharts No. 01 and 04)

Article 35

Annex 1

Annexes A and B

Article 2 (Article 85-A)

Preamble, Requirements for Initiating the Procedure (3, 10, and 13), 2.1-2.3, 3.1-3.4, 4.1-4.4, 5.1-5.7, 6.1-6.2, 7.1-7.6, and Annexes 1-3 and 9

Article 39

Title I (Articles 6 and 8), Title IV (Articles 40, 59, and 63), Title V (Articles 67, 69-71, 75, and 80), Supplementary Provisions—Final (Eighth), and Annex 5

Initiation, Agreements & Registration

Last content review/update: October 1, 2024

Overview

In accordance with the CanadaFDR and the G-CanadaCTApps, a clinical trial can only commence after the sponsor receives authorization from both Health Canada (HC) and an institutional ethics committee (EC) (known as Research Ethics Board (REB) in Canada). No waiting period is required following the applicant’s receipt of these approvals. CAN-30 specifies that for purposes of the Clinical Trial Site Information (CTSI) Form (CAN-6), the trial commencement date is the date when the clinical trial site is ready to enroll participants. The commencement date is a date after which the sponsor has both the HC authorization from the appropriate Directorate (date on the No Objection Letter (NOL)) and approval from the relevant EC. Further, the commencement date would be the date when the sponsor implements the protocol, which includes the screening period that occurs prior to the check-in date. See the Scope of Review section for detailed institutional EC requirements, and the Submission Content section for additional HC approval information. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

In addition, per the G-CanadaCTApps, if a sponsor (Canadian or foreign) wants to import a drug into Canada to conduct a clinical trial, a copy of HC’s clinical trial authorization (i.e., the NOL) must be included with the drug shipment. According to the G-CanadaCTApps and CAN-32, if a sponsor plans to import investigational drugs directly to each trial site, then the sponsor must also authorize the importer (i.e., the clinical trial site) when submitting the clinical trial application using Appendix I of HC’s Drug Submission Application Form (CAN-4). See the Manufacturing & Import section for detailed import requirements.

Clinical Trial Agreement

Prior to initiating the trial, as delineated in the G-FDR-0100 and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, the sponsor must sign an agreement between all involved parties, including ECs, Qualified Investigators (QIs), contract research organizations, and others, to ensure full compliance with the regulatory requirements. Further, the sponsor should obtain the investigator’s/institution's agreement:

To conduct the trial in compliance with good clinical practice, with the applicable regulatory requirement(s), and with the protocol agreed to by the sponsor and given approval/favorable opinion by the EC
To comply with procedures for data recording and reporting
To permit monitoring, auditing, and inspection
To retain the trial-related essential documents until the sponsor informs the investigator/institution these documents are no longer needed

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

In accordance with the G-CanadaCTApps, prior to initiating a clinical trial, the sponsor must ensure that a Qualified Investigator Undertaking (QIU) form (CAN-37 or similar documentation that meets the CanadaFDR requirements) has been completed and is kept on file by the sponsor. Per the CanadaFDR, the form certifies that the QI will conduct the clinical trial in accordance with good clinical practice and will immediately inform trial participants and the institutional EC of trial discontinuance and the reason for this discontinuance. If there is a change in the QI at a site, a new CTSI Form must be submitted to HC, and a new QIU form must be maintained by the sponsor.

See CAN-6, CAN-8, and CAN-19 for additional clinical trial forms.

Clinical Trial Registration

As per the G-CanadaCTApps, sponsors should register their clinical trials on one (1) of two (2) publicly accessible registries accepting international clinical trial information and recognized by the World Health Organization (WHO), ClinicalTrials.gov (CAN-45), and the International Standardized Randomized Controlled Trial Number (ISRCTN) Registry (CAN-46). According to HCNotice-CTRegDisc, clinical trial registration is not a mandatory requirement at this time. However, per the G-TCPS2, which sets the ethical benchmark for all Canadian institutional ECs, clinical trials must be registered before recruitment of the first trial participant in a publicly accessible registry that is acceptable to the WHO or the International Committee of Medical Journal Editors (ICMJE). In addition, following registration, researchers are responsible for ensuring that the registry is updated in a timely manner with: new information; safety and, where feasible, efficacy reports; reasons for stopping a trial early; and the location of findings.

1.17, 5.1.2, 5.6.3, and 8.2.6

Efficacy guidelines

1.2 and 2.7

5.6

Chapter 11 (Articles 11.10-11.11)

Part C (Division 5 (C.05.006))

Last content review/update: April 24, 2024

Overview

In accordance with Decree021-2017, Res655-2019 (which amends Decree021-2017), the INS-CTManual, and Res252-2022 (which amends the INS-CTManual), a clinical trial can only commence after the sponsor or the contract research organization (CRO) receives authorization from Peru’s National Institute of Health (Instituto Nacional de Salud (INS)) and approval from an INS-accredited institutional ethics committee (EC) (El Comité Institucional de Ética en Investigación (CIEI)). No waiting period is required following the applicant’s receipt of these approvals.

According to Decree021-2017, Decree016-2011, the INS-CTManual, and Res252-2022, the sponsor or the CRO must also 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)) (PER-109)). (See the Manufacturing & Import section for additional information).

Additionally, per Decree021-2017 and Res252-2022, the sponsor must ensure authorization by the research institution where the clinical trial will be carried out. Decree021-2017 further states that the sponsor must inform the INS’s Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the 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.

The INS-CTManual further specifies that the trials should be conducted in compliance with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (PER-53).

Res686-2020, in turn, 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 (Decree021-2017). Refer to Res686-2020 for detailed information and requirements associated with clinical vaccine studies.

Clinical Trial Agreement

According to Decree021-2017, the INS-CTManual, Res252-2022, and PER-71, the sponsor and principal investigator (PI) must sign an affidavit of compliance with the minimum requirements of the research site where the clinical trial will be executed (see PER-35). Further, per Res252-2022 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).

In addition, per Decree021-2017, the INS’s DIIS refers to the requirements laid down in PER-53 for topics not addressed in Decree021-2017. Accordingly, PER-53 states that prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor or the 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. The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

Clinical Trial Registration

As per Decree021-2017, the INS-CTManual, Res252-2022, and PER-71, the sponsor or the CRO must register the clinical trial application electronically using the INS’s Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) (PER-89) (also referred to as REPECv2), at which time, a registration code is assigned to the application.

As specified in PER-89, the REPEC platform should be used to register all requests for procedures related to newly submitted clinical trials, to track the status of the authorization process, to identify critical events that require immediate attention via an alert system (e.g., expiring or expired authorizations and necessary notifications per Decree021-2017, and to obtain updated information on clinical trials being conducted in Peru). However, per PER-88, any requests for procedures related to already active clinical trials must still be submitted using the older REPEC platform via PER-91. See PER-81 for instructional videos on registering with the new REPEC platform. Refer to the Oversight of Ethics Committees section for instructions on EC registration/accreditation and the Submission Process section for instructions on sponsor/CRO registration.

4.5 and 5.6.2-5.6.3

Chapter VII (7.1-7.3), and Annexes 1, 3, and 4 (Flowcharts No. 01, 02, and 04)

Annex B

4 and 5.2

Requirements for Initiating the Procedure (2-3, 5-6, 10, and 13), 1.1-1.4, 4.1-4.4, and Annexes 3, 5, and 9

Title II (Chapters I and V)

Title I (Articles 6-8), Title IV (Articles 39-40, 45, 54, 59, and 63), Title V (Articles 67 and 70-71), Title VI (Article 94), Supplementary Provisions—Final (First and Eighth), and Annexes 1-5

Safety Reporting

Last content review/update: October 1, 2024

Safety Reporting Definitions

According to the CanadaFDR and G-CanadaCTApps, and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), the following definitions provide a basis for a common understanding of Canada’s safety reporting requirements:

Adverse Event (AE) – Any adverse occurrence in the health of a clinical trial subject who is administered a drug that may or may not be caused by the administration of the drug, and includes an adverse drug reaction.
Adverse Drug Reaction (ADR) – Any noxious and unintended response to a drug that is caused by the administration of any dose of the drug.
Serious Adverse Drug Reaction (SADR) or Serious Adverse Event (SAE) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or causes a congenital anomaly/birth defect.
Serious, Unexpected ADR – A serious ADR that is not identified in nature, severity, or frequency in the risk information set out in the investigator’s brochure or on the label of the drug.

The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ethics committees (ECs), requires researchers to promptly report new information revealed during the conduct of the trial that might affect the welfare or consent of participants to the EC, to a publicly accessible registry, and to other appropriate regulatory or advisory bodies. In addition, when new information is relevant to participants’ welfare, researchers must promptly inform all participants to whom the information applies (including former participants). Researchers must work with their ECs to determine which participants must be informed, and how the information should be conveyed.

For Health Canada (HC)’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

Safety Reporting Requirements

Investigator Responsibilities

Per CAN-52, which Canada has implemented per CAN-50, all SAEs should be reported immediately to the sponsor except for those SAEs that the protocol or other document (e.g., Investigator's Brochure) identifies as not needing immediate reporting. The immediate reports should be followed promptly by detailed, written reports. The immediate and follow-up reports should identify participants by unique code numbers assigned to the trial subjects rather than by their names, personal identification numbers, and/or addresses. The investigator should also comply with the applicable regulatory requirement(s) related to the reporting of unexpected serious ADRs to the regulatory authority(ies) and the EC. AEs and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the sponsor according to the reporting requirements and within the time periods specified by the sponsor in the protocol. For reported deaths, the investigator should supply the sponsor and the EC with any additional requested information (e.g., autopsy reports and terminal medical reports).

Sponsor Responsibilities

As delineated in the CanadaFDR, the G-CanadaCTApps, and CAN-22, the sponsor is required to expedite reports of ADRs to HC that meet these three (3) criteria: serious, unexpected, and having a suspected causal relationship. ADR reports that are expected or unexpected, but not serious, should not be reported to HC, but rather monitored and tracked by the sponsor. Further detail and clarifications on AE/ADR reporting criteria can be found in CAN-22. As specified in the G-CanadaCTApps, when evaluating whether an AE is serious and unexpected, the Qualified Investigator’s (QI) and sponsor’s determination of causality is important. Only serious and unexpected ADRs found to have a reasonable suspected causal relationship to the drug should be reported by the sponsor to HC.

Per the CanadaFDR and the G-CanadaCTApps, during a clinical trial, the sponsor is required to inform HC of any serious, unexpected ADR that has occurred inside or outside Canada. An ADR report must be filed in the following specified timelines:

When the ADR is neither fatal nor life-threatening, within 15 days after becoming aware of the information
When it is fatal or life-threatening, immediately when possible and, in any event, within seven (7) days after becoming aware of the information
Within eight (8) days after having informed HC of the ADR, submit a report that includes an assessment of the importance and implication of any findings

Other Safety Reports

The G-DSUR delineates that the development safety update report (DSUR) and the DSUR Checklist (CAN-38) should be provided when requested by HC. A DSUR may be submitted voluntarily to HC when important new safety information on a drug needs to be conveyed by a clinical trial sponsor. In these cases, a rationale/justification for the filing of the DSUR should be included in the cover letter. For additional details, see the G-DSUR.

The G-DSUR-CanUK describes the region-specific requirements for DSURs submitted to the regulatory authorities of Canada and the United Kingdom. This guidance applies to both marketed and non-marketed drugs that are used in clinical trials and applies to DSURs prepared by the manufacturer and/or marketing authorization holder of the investigational drug.

Form Completion & Delivery Requirements

As per the G-CanadaCTApps and CAN-22, all serious and unexpected ADRs should be reported individually to HC. According to CAN-48 (which Canada adopted pursuant to CAN-50), at a minimum, the report should include an identifiable patient, the name of a suspect medicinal product, an identifiable reporting source, and an event or outcome that can be identified as serious and unexpected and for which, in clinical investigation cases, there is a reasonable suspected causal relationship. The G-CanadaCTApps requires the sponsor to complete the expedited reporting form (CAN-5) and the CIOMS Form I (CAN-7) and fax them to the appropriate HC Directorate: BRDD Fax: 613-957-0364; PDD Fax: 613-941-2121.

Additionally, the G-DSUR indicates that HC recommends that DSURs in electronic Common Technical Document (eCTD) format be submitted via the Common Electronic Submission Gateway (CESG). For information on eCTD format, refer to the ElecSubms. For technical questions on eCTD filings, contact ereview@hc-sc.gc.ca as instructed in the G-DSUR.

1.1, 1.2, 1.50, 1.60, and 4.11

Efficacy guidelines

Notice, 1.2, and 2.4

2.1 and 2.8

5.14

Chapter 11 (Article 11.8)

Part C (Division 5 (C.05.001 and C.05.014))

Last content review/update: April 24, 2024

Safety Reporting Definitions

According to Decree021-2017, Decree021-2017-Correct, the G-SafeRpt, and the G-CTSafety, the following definitions provide a basis for a common understanding of Peru’s safety reporting requirements (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Adverse Event (or Adverse Experience) (AE) – Any event or situation harmful to the health of the research participant to whom an investigational product (IP) has been administered, which does not necessarily have a causal relationship with its administration
Adverse Reaction (AR) – Any AE in which there is a clearly defined causal relationship with an IP or there is at least a reasonable possibility of causation, which occurs regardless of any dose administered to that participant
Serious Adverse Event (SAE) or Serious Adverse Reaction (SAR) – Any AE/AR 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 Reaction – An AR where the nature or severity is inconsistent with the applicable IP information, i.e., it is not described in the investigator’s brochure (IB) and/or the technical data sheet
Suspected Unexpected and Serious Adverse Reaction (SUSAR) – Any serious AE/AR in which there is at least a reasonable possibility of a causal relationship with the IP and the nature and severity of the event/reaction is not described in the IB and/or technical data sheet

Safety Reporting Requirements

Investigator Responsibilities

According to Decree021-2017, the INS-CTManual, and the G-SafeRpt, the principal investigator (PI) and the sponsor or the contract research organization (CRO) are responsible for monitoring the safety of the IP. As specified in Decree021-2017 and the G-SafeRpt, the PI is also responsible for notifying the sponsor or the CRO or the ethics committee (EC) of any SAEs/SARs 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.

Decree021-2017 notes that the PI must also follow up with a detailed written report. Per the G-SafeRpt, the PI must record the SAEs/SARs and notify the sponsor according to the procedure described in the study protocol.

Furthermore, per Decree021-2017, the PI must inform the sponsor or the CRO and the EC of the following:

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

In addition, the G-SafeRpt states that if the PI becomes aware of SAEs/SARs occurring after the end of the trial, they should notify the sponsor or the CRO and the EC.

Lastly, per Decree021-2017, the PI must provide the sponsor or the CRO, the EC, and the Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as 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.

Res233-2020, which regulates human subjects research other than clinical trials of drugs or devices, indicates that investigators should immediately report 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.

Sponsor Responsibilities

According to Decree021-2017, the INS-CTManual, the G-SafeRpt, and PER-72, the sponsor or the CRO should report IP-related AEs/ARs, SAEs/SARs, and SUSARs and provide these reports to the INS’s DIIS. Decree021-2017 also notes that the sponsor or the CRO should also maintain detailed records of all AEs/ARs communicated by the PIs.

Per Decree021-2017, Decree021-2017-Correct, the INS-CTManual, PER-72, and PER-38, the sponsor or the CRO and the PI are required to submit all expected and unexpected SAEs/SARs (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 DIIS within seven (7) calendar days from the occurrence of the incident, or as soon as the sponsor is aware of the incident. The G-SafeRpt specifies that the sponsor or the CRO is responsible for evaluating, categorizing, and reporting all SAEs/SARs and SUSARs that occur within the country through REAS-NET (PER-69). 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 (PER-69) should be printed and signed by the sponsor or the CRO. The INS-CTManual and the G-SafeRpt 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-SafeRpt 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 (PER-69) should be submitted electronically and in print formats to the DIIS.

In addition, per Decree021-2017, Decree021-2017-Correct, and PER-72, the sponsor or the CRO must notify the DIIS, 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/AR submission deadlines outlined in this section. Decree021-2017, Decree021-2017-Correct, PER-4, and PER-12 further state that the sponsor or the CRO is also required to notify the DIIS of critical or very serious and major or serious deviations to the clinical trial protocol within a maximum period of seven (7) calendar days from the time of becoming aware of the incident.

The G-SafeRpt further explains that if the sponsor or the CRO is aware of safety findings that are not covered within the scope of an SAE/SAR 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 DIIS 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 DIIS’s Document Processing Office. 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-SafeRpt for examples of administrative procedures.

As delineated in Decree021-2017, the G-SafeRpt, and PER-72, the sponsor is also required to submit, electronically on a quarterly or semi-annual basis, SAE/SAR and SUSAR reports occurring internationally, to the DIIS 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-SafeRpt specifies that the information should be presented on magnetic media. Refer to Annex 1 in the G-SafeRpt 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. Further, per Decree021-2017, the DIIS 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 (PER-69). (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)) (PER-109)). See also the G-CTSafety for information on actions taken by the INS’s DIIS in response to SAEs/SARs, SUSARs, and safety reports.

Other Safety Reports

As delineated in the INS-CTManual and the G-SafeRpt, the sponsor or the CRO must also submit an annual IP safety report (DSUR) to the DIIS. Decree021-2017 further specifies that the DSUR should be sent to the DIIS and the ANM. Per the INS-CTManual, the translation of the annual report summary must be presented in English and Spanish. The G-SafeRpt 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 form FOR-OGITT-048 (PER-45) online in Spanish as well as submit a copy of the DSUR to the DIIS on CD.

In addition, per the G-SafeRpt, the sponsor or the 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 the 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 the CRO will describe in the protocol the notification procedures for non-serious AEs. Decree021-2017 also notes that the sponsor or the CRO should continuously evaluate IP safety and implement an IP security monitoring system.

According to the INS-CTManual and the G-SafeRpt, in cases of prenatal exposure due to a pregnant woman’s participation in a clinical trial, the PI, the sponsor or the CRO is required to submit form FOR-OGITT-047 (PER-39) to notify the DIIS of the SAE/SAR or SUSAR. Per the G-SafeRpt, 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 Pregnant Women, Fetuses & Neonates section for additional information on this population.

See Decree021-2017, the INS-CTManual, the G-SafeRpt, and PER-38 for detailed sponsor/CRO reporting requirements.

Form Completion & Delivery Requirements

As per Decree021-2017, the INS-CTManual, the G-SafeRpt, and PER-72, all AEs/ARs, SAEs/SARs, and SUSARs must be reported electronically by the sponsor or the CRO using REAS-NET (PER-69). PER-12 specifies that notifications of very serious and major or serious protocol deviations should be submitted using FOR-OGITT-053 (PER-40) via the INS’s Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) (PER-89) (also referred to as REPECv2). PER-114 further notes that reports of SAEs (REAs) and deviations can be submitted via PER-89, regardless of the year of trial authorization. However, REAs and deviations that have been submitted via the older REPECv1 platform (PER-91) will remain on this platform for consultation, if required.

(Refer to PER-38 for the DIIS SAE/SAR form, FOR-OGITT-046. All SAEs/SARs and SUSARs must also be reported on the CIOMS Form I (PER-18). The INS-CTManual further notes that the sponsor or the CRO should also submit a printed copy of the CIOMS report in Spanish or English to the INS’s DIIS.

Pursuant to the G-SafeRpt, to report post-study AEs, the sponsor or the CRO should send an email to consultaensayos@ins.gob.be to coordinate with the person in charge of computer systems and grant the person access to REAS-NET (PER-69) to complete and submit the online form FOR-OGITT-046 (PER-38). SAEs/SAR notifications following a trial’s completion should remain in the research site archives.

Serious Adverse Events Report

V-VII and Annex 1

Chapter VI (6.4), VII (7.8.1-7.8.3), and Annex 4 (Flowcharts No. 12-14)

I, VII (7.1), and VIII (8.4)

Title I (Article 2), Title IV (Articles 40 and 52), and Title IX (Articles 108-111)

Progress Reporting

Last content review/update: October 1, 2024

Interim and Annual Progress Reports

Pursuant to the CanadaFDR, the G-CanadaCTApps, CAN-22, and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), investigators and sponsors share responsibility for submitting interim and annual reports on the status of a clinical trial. The investigator is required to provide annual progress reports to the institutional ethics committee (EC) and submit interim progress reports to the EC and Health Canada (HC) if there are any significant changes affecting the trial or risk to participants. The sponsor is required to submit annual reports (in the form of an updated Investigator’s Brochure (IB)) to HC. Note that per CAN-50, HC-implemented ICH guidance takes precedence over other HC guidance when they are not consistent. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

As per CAN-52, which Canada has implemented per CAN-50, the investigator should promptly provide written reports to the sponsor and the institutional EC on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.

According to the G-TCPS2, investigators must report new information that may affect the welfare or consent of participants to the institutional EC, HC, and other appropriate regulatory or advisory entities. When new information is relevant to participants’ welfare, researchers must promptly inform all participants to whom the information applies (including former participants). Researchers should work with their ECs to determine which participants must be informed, and how the information should be conveyed. New information may comprise a range of issues, including, but not limited to:

Changes to the research design
Evidence of any new risks
Unanticipated issues that have possible health or safety consequences for participants
New information that decisively proves the benefits of one (1) intervention over another
New research findings, including relevant non-trial findings
Unanticipated problems
Closure of trials at other sites for reasons that may be relevant to the welfare or consent of participants in the ongoing trial

Pursuant to CAN-52, the investigator should submit written summaries of the trial status to the institutional EC annually, or more frequently, if requested.

Final Report

Upon completion of the trial, as delineated in CAN-52, the investigator is required to submit a final report to the institutional EC summarizing the trial’s outcome. The CanadaFDR does not require submission of a final study report to HC.

Per the G-CanadaCTApps, the sponsor should notify the HC Directorate when a clinical trial is completed or a clinical trial site is closed. A study is considered to be completed after the last participant globally completes the "end of study" visit as defined in the protocol. The "end of study visit" is the final visit for study-related tests and procedures, including the capture of any final potential study-related adverse events, and usually occurs after the participant has completed/discontinued study drug administration. The "end of study visit" is normally an in-person visit, but for some studies it can also be carried out over the telephone. There may be certain scenarios (e.g., gene therapies, drugs with very long half-lives) where a study may be considered to be ongoing well beyond the period of study treatment, i.e., where long-term safety monitoring and reporting would be required. The reporting requirements with regards to such long-term follow-up of safety are normally specified in the study protocol and agreed to between the sponsor and HC prior to the authorization of the clinical trial in Canada.

4.10 and 4.13

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

2.8

5.12 and 5.13

Chapter 11 (Article 11.8)

Part C (Division 5 (C.05.012 and C.05.013))

Last content review/update: April 24, 2024

Interim and Annual Progress Reports

National Institute of Health (INS)

As delineated in Decree021-2017, the INS-CTManual, PER-72, PER-47, PER-8, and PER-14, the sponsor or the contract research organization (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 Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as 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)). The report should be submitted quarterly or biannually to the INS’s Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) (PER-89) (also referred to as REPECv2) for each of the approved research sites. Per the INS-CTManual, this report should be submitted regardless of the enrollment status in each site. The INS-CTManual and PER-14 further specify that the submission deadline is up to seven (7) calendar days after completing the quarterly or half-yearly period. The sponsor or the CRO should print and sign the electronic form and deliver it to the INS’s Document Processing Office 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.

PER-92 further notes that while the older REPECv1 platform (PER-91) is closed for the entry of progress reports, research center final reports, national final reports, and international final reports, the reports will remain in the system for consultation.

In addition, Decree021-2017 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) (Decree021-2017)
Summary of serious adverse events/adverse reactions (SAEs/SARs) and non-serious adverse events (AEs)/adverse reactions (ARs) related to the investigational product (IP), and deviations occurring in the corresponding period (Decree021-2017)
Number of patients who failed the screening (PER-72)
Number of patients with clinical failure (PER-72)

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

Ethics Committees

As per Decree021-2017, the principal investigator (PI) is also 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)).

Res233-2020, which regulates human subjects research other than clinical trials of drugs or devices, indicates that researchers should submit progress reports, final reports, suspension reports, and early termination reports, among others, to the EC per the terms established by the committee.

Final Report

As delineated in Decree021-2017, the INS-CTManual, PER-72, PER-48, PER-16, and PER-14, the sponsor or the CRO must submit a research site final report via PER-89 for each of the participating sites 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 site. The INS-CTManual notes that the electronic form should also be printed and signed by the sponsor or the CRO and delivered to the INS’s Document Processing Office 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.

Decree021-2017 also states that the final report should include the following information:

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

National Final Reports

Per Decree021-2017, Decree021-2017-Correct, the INS-CTManual, PER-72, and PER-14, national final reports should be submitted via PER-89 for the INS’s DIIS review within 60 calendar days following the date of the final report submission of the last research site. 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 Decree021-2017, Decree021-2017-Correct, the INS-CTManual, and PER-72. The DIIS 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. (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)) (PER-109)).

Per the INS-CTManual, the electronic form should also be printed and signed by the sponsor or the CRO and delivered to the INS’s Document Processing Office 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.

Decree021-2017 further explains that the national final report should include the following information:

Number of screened, enrolled, retired patients who completed the trial
Summary of SAEs/SARs and non-serious AEs/ARs 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 Reports

As delineated in Decree021-2017, the INS-CTManual, and PER-72, international final reports should be submitted to PER-89 within 12 months following the completion of the last clinical trial in all international research sites. Per the INS-CTManual, the sponsor or the CRO should also print and sign the electronic form and deliver it to the INS’s Document Processing Office 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 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.

Results Publication

Further, according to Decree021-2017, 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 PER-89 using 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 DIIS and notify DIIS of this submission using 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.

Clinical Trial Progress Report and Final Reports

Chapter VII (7.13.3-7.13.5) and Annex 4 (Flowcharts No. 25 and 30-32)

I, VII (7.1), and VIII (8.4)

Title I (Article 2), Title IV (Articles 40 and 52), and Title VIII (Articles 104-107)

Definition of Sponsor

Last content review/update: October 1, 2024

As per the CanadaFDR and the G-CanadaCTApps, a sponsor is defined as an individual, corporate body, institution, or organization that conducts a clinical trial. The International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, expands on this definition to include individuals, companies, institutions, or organizations that take responsibility for the initiation, management, and/or financing of a clinical trial.

In accordance with CAN-52, Canada 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. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.

According to the CanadaFDR and G-CanadaCTApps, a sponsor may be domestic or foreign. A foreign sponsor is required to have a senior medical or scientific officer who is residing in Canada who will represent the sponsor, and sign and date the application and the clinical trial attestation form.

For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

1.53, 5.1, and 5.2

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

2.1

5.1 and 5.5

Part C (Division 5 (C.05.001, C.05.005, C.05.015))

Last content review/update: April 24, 2024

Decree021-2017 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 the role of sponsor is assumed.

Decree021-2017 also states that sponsors not based in Peru are required to appoint a legal representative who channels all the communication with the Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as 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.

Decree021-2017 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.

Title IV (Articles 41-45)

Site/Investigator Selection

Last content review/update: October 1, 2024

Overview

As set forth in the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, the sponsor should select 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 must also ensure that the investigator(s) are qualified by training and experience. Furthermore, the sponsor must sign an agreement or contract with the participating institution(s). Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.

In accordance with the G-CanadaCTApps, prior to initiating a clinical trial, the sponsor must ensure that a Qualified Investigator Undertaking (QIU) form (CAN-37) (or similar documentation that meets the CanadaFDR requirements) has been completed and kept on file by the sponsor; it should be retained by the sponsor for 15 years. Per the CanadaFDR, the form certifies that the qualified investigator will conduct the clinical trial in accordance with good clinical practice, and will immediately inform trial participants and the institutional ethics committee (EC) (known as Research Ethics Boards in Canada) of trial discontinuance, and the reason for this discontinuance. (See the Submission Content section for additional information on clinical trial application requirements). For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

Per CAN-11, the Canadian Clinical Trials Asset Map (CCTAM) (CAN-26) is a pan-Canadian research inventory of investigators, clinical research sites, and other resources across the country. Sponsors can use CCTAM to identify potential sites and investigators, which may expedite study feasibility and start-up timelines. To view the CCTAM, the user must register and create an account.

Foreign Sponsor Responsibilities

According to the CanadaFDR and the G-CanadaCTApps, a sponsor may be domestic or foreign. A foreign sponsor is required to have a senior medical or scientific officer residing in Canada to represent the sponsor, and sign and date the application and the clinical trial attestation form.

Data and Safety Monitoring Board

Although not specified as a sponsor requirement, CAN-52 states that a Data and Safety Monitoring Board (DSMB) (known as an Independent Data-Monitoring Committee in Canada) may be established to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial.

The G-TCPS2 provides the following considerations to help researchers and ECs determine whether a DSMB is needed:

The magnitude of foreseeable research-attributable harms to participants
Whether the circumstances of the participants make them vulnerable in the context of research
The feasibility of interim data analysis
The complexity of the study
Conflicts of interest

Multicenter Studies

Per CAN-52, if a multicenter trial will be conducted, the sponsor must organize a coordinating committee or select coordinating investigators. In addition, the sponsor must ensure that:

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

The CanadaFDR and the G-CanadaCTApps, require the sponsor to complete and retain the Research Ethics Board (REB) Attestation (CAN-8) and Qualified Investigator Undertaking (QIU) (CAN-37) forms at each trial site, while submitting in electronic format the Clinical Trial Site Information Form (CAN-6) to the appropriate HC Directorate for each trial site.

The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ECs, provides that in multi-site clinical trials, a lead principal investigator (PI) is a designated PI who is responsible for the ethical conduct of the study for all sites. The lead PI is responsible for communicating any changes to the study, new information, and/or unanticipated events to the EC, to the sponsor, and to local site PIs.

Per CAN-50, Canada has implemented the ICH Guidance E17: Multi-Regional Clinical Trials (CAN-40), which describes general principles for the planning and design of multi-regional clinical trials with the aim of increasing the acceptability of these trials in global regulatory submissions. HC recognizes that the scope and subject matter of current HC guidance may not be entirely consistent with ICH guidance. In such circumstances, HC-implemented ICH guidance takes precedence.

1.25, 5.5, 5.6, and 5.23

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Canadian Clinical Trials Asset Map

2.1 and 2.7.2

5.5

Chapter 11 (Article 11.7)

Part C (Division 5 (C.05.005))

Last content review/update: October 31, 2024

Overview

Per Decree021-2017, the National Institute of Health (Instituto Nacional de Salud (INS))’s Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT))), follows the requirements provided in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (PER-53) for topics not addressed in Decree021-2017. Accordingly, PER-53 states that the sponsor or the 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. Investigators should also be qualified by education, training, and experience to assume responsibility for the proper conduct of the trial. Decree021-2017 further specifies that, in addition to professional competence, the sponsor or the CRO should also ensure that investigators have enough time to conduct the trial and agree to comply with good clinical practices (GCP) and ethical standards. Res233-2020 also requires investigators to have basic training in ethical research with human beings. PER-53 may also be referred to for additional information on investigator requirements.

Per Decree021-2017 and Res655-2019 (which amends Decree021-2017), research institutions must also register with the INS’s Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) (PER-89) (also referred to as REPECv2), but are no longer required to provide proof of this registration in the clinical trial authorization application. As delineated in Res655-2019, 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 center to conduct clinical trials (per Res546-2011, categorization is based on the institution’s levels of complexity and functional characteristics)
Number and date of proof of payment of processing fees

Decree021-2017 also requires research centers to register with REPEC (PER-89) to carry out clinical trials at the research institution’s request. According to PER-73, research centers should apply electronically via REPEC (PER-89), submit the printed application form, FOR-OGITT-022 (PER-19) per Res0423-2019, and complete the printed affidavit form, FOR-OGITT-023 (PER-44). Research center registration is valid for three (3) years. Refer to PER-73 for detailed registration instructions and PER-90 for a research center registration checklist. According to PER-73, public and private sector research centers must also be registered in (REPEC) (PER-89), at the request of the research institution, to carry out clinical trials.

Per PER-113, the INS’s DIIS has established the Validity of the Record of Registration of Research Center in compliance with Law1452 (which amends Law27444). In accordance with Law1452, any Research Center Registration Certificate (Constancia de Registro de Centros de Investigación (RCI)) that is valid as of September 16, 2018, and all those certificates subsequently issued, are valid for an indefinite period, and are therefore exempt from the registry renewal process delineated in Decree021-2017. However, the DIIS may continue to carry out subsequent scheduled or unscheduled audits in accordance with its authority, and may revoke the certificate, if it verifies changes in the conditions essential to obtaining the registration.

PER-131 further states that the RCIs are no longer valid for research centers that do not have active clinical trials and whose RCI was issued prior to September 16, 2015. Research institutions that intend to continue carrying out clinical trials may request an update of the RCI validity by completing and signing the printed application form, FOR-OGITT-022 (PER-19), and affidavit form, FOR-OGITT-023 (PER-44), and submitting via REPEC (PER-89). Research institutions must also notify the Virtual Submission Platform (Mesa de Partes Virtual (MPV)) (PER-106) of the submitted procedures, and attach PER-19 and PER-44. Additionally, as indicated in PER-130, sponsors or CROs are obligated to verify that the research center where a clinical trial will be conducted is authorized in the specialty related to the proposed trial. If the research center did not provide the related specialty information in its REPEC registration, the research institution’s legal representative, as research center administrator, must submit a request to the INS’s DIIS to modify the registration to include the required specialty. The new RCI must also include the required specialty. All of these procedures must be carried out prior to the request for authorization of a clinical trial.

Foreign Sponsor Responsibilities

Decree021-2017 states that the sponsor is required to appoint a legal representative in the country for the trial’s duration when based outside of Peru. Per Decree021-2017, the in-country legal representative channels all communication with the INS’s DIIS during the study’s execution, unless this responsibility is delegated to a CRO. As specified in Decree021-2017, the sponsor may transfer any or all of the study related duties and functions to a CRO. However, the sponsor is ultimately responsible for the execution of the research protocol and results of the clinical trial.

See PER-7 for detailed documentation submission requirements for a foreign sponsor to delegate an in-country legal representative or for a local sponsor to appoint a legal representative. Decree021-2017 further explains that the in-country representative must also be registered in REPEC (PER-89) for the trial’s duration. Refer to the Submission Process section for additional REPEC registration instructions.

Data and Safety Monitoring Board

Decree021-2017 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.

Multicenter Studies

Per Decree021-2017, multicenter clinical trials are carried out by more than one (1) investigator and require an appointed coordinator responsible for processing all of the data and analyzing the results.

In addition, according to PER-53, in the event of a multicenter clinical trial, the sponsor must ensure that:

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

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

4.1, 5.6, and 5.23

Article 36-B

Article 35

VII (7.1) and VIII (8.4)

Annexes A and B

Preamble and Annex 1

Title I (Article 2), Title IV (Articles 40-42 and 53-54), Title VIII (Article 108), Supplementary Provisions—Final (First), and Annex 1

Insurance & Compensation

Last content review/update: October 1, 2024

Insurance

The CanadaFDR does not require the sponsor to provide insurance coverage to investigators, institutions, or trial participants. However, the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, guides sponsors on providing insurance. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.

Compensation

Injury or Death

The Canadian regulations do not require compensation for trial participants in the event of trial-related injuries or death. However, CAN-52 indicates that the sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries.

Trial Participation

The Canadian regulations do not require compensation for trial participation. However, as per the G-TCPS2 and CAN-52, the informed consent form (ICF) should contain a statement with a description of the anticipated prorated payment to the participant(s) that is reasonably expected for participation in the trial. Any compensation or incentive to participants must not be so excessive that it may unfairly influence participants or cause them to overlook important facts and risks. CAN-35 further states that the ICF should describe any compensation, incentives, or reimbursements to be paid or given to participants and how participant withdrawal will affect the offered compensation (e.g., prorated remuneration). If no compensation will be provided, this should be stated.

4.8 and 5.8

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Policies, Guidelines, and Resources, Consent Process (Consent Form Template)

Chapter 3 (Article 3.2)

Last content review/update: April 24, 2024

Insurance

As set forth in Decree021-2017, the G-EC-CTRev, and PER-71, it is a legal requirement for the sponsor or the 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 Res0423-2019, the sponsor or the CRO should sign an affidavit (PER-51) guaranteeing an active insurance policy is in place according to requirements in the INS-CTManual.

Decree021-2017 also specifies that the sponsor or the CRO must obtain insurance coverage in Peru or have a legal representative in Peru who will represent the sponsor or the 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.

Compensation

Injury or Death

According to Decree021-2017 and PER-71, in addition to guaranteeing an active insurance policy is in place, the affidavit (PER-51) submitted by the sponsor or the CRO also certifies 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.

In addition, as described in Decree021-2017, compensation will be awarded in the following circumstances:

Any damage to the research participant as a result of 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.

Trial Participation

Per Decree021-2017, research participants may receive reasonable compensation from the sponsor for extraordinary expenses incurred and loss of productivity arising from their participation, which will be specified in the informed consent. The institutional ethics committee (EC) (El Comité Institucional de Ética en Investigación (CIEI)) will evaluate this form of compensation on a case-by-case basis and determine whether it unduly influences the consent of the research participant.

PER-15 further states the following:

Research participants may receive compensation in order to reimburse them for expenses (e.g., transportation, accommodation, communication, food expenses) and/or compensate the loss of productivity, time, among others, derived from their participation. Any compensation to the participants of the investigation must be reasonable and proportionate and, in no case, may it constitute undue influence.
In order to safeguard the rights of research participants, researchers and sponsors should take into account the personal and specific considerations of each research participant for the calculation of compensation for expenses incurred arising from their participation and,
ECs must evaluate the compensation amount, paying special attention to the information that appears in the informed consent forms, in order to ensure that the established compensations consider the possible conditions of each research participant

Post-Trial Access to the Investigational Product

As delineated in Decree021-2017, the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) is also responsible for authorizing post-study access to the investigational product (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 a Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (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 Decree021-2017 for documentation submission requirements) (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)).

Decree021-2017 also notes that participants must be ensured free access to the 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.

Ethical Criterion 5 and Annex 2

Chapters VII (7.14) and IX

Annex 1

Title I (Articles 2 and 8), Title III (Articles 27-29), Title III (34-35), Title IV (Article 40), Title X, and Annex 4

Risk & Quality Management

Last content review/update: October 1, 2024

Quality Assurance/Quality Control

Per the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. Per CAN-50, Canada implements the ICH Guidance E8(R1): General Considerations for Clinical Studies (CAN-49), which provides guidance on conduct during the clinical trial. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.

As indicated in CAN-52, the quality management system should use a risk-based approach that includes:

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

As stated in the CanadaFDR and CAN-52, the sponsor is responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data generated, recorded, and reported in compliance with the protocol, CAN-52, and the applicable regulatory requirements. The sponsor is responsible for obtaining 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. A written agreement must be signed by both the sponsor and the investigator or any other parties involved with the clinical trial, verifying that both parties agree to the trial protocol, the monitoring and auditing practices, the SOPs, and their respective duties.

Per CAN-50, HC adopted and implements the ICH guidance on statistical principles for clinical trials (CAN-53), as well as the ICH addendum on estimands and sensitivity analysis (CAN-39), which presents a framework for defining an appropriate estimand for a clinical trial and conducting sensitivity analyses.

Monitoring Requirements

As part of its QA system, CAN-52 notes that the sponsor should ensure the trial is monitored and audited. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, CAN-52, and other applicable regulatory requirements. The sponsor should appoint auditors to review the clinical trial. The sponsor should ensure that the auditors are qualified by training and experience, and the auditors’ qualifications should be documented. The sponsor must also ensure that the audit is conducted in accordance with their 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).

Per the HCNotice-ICH-E19, HC adopted and implements ICH guidance on selective safety data collection in specific late stage pre-approval or post-approval clinical trials (CAN-15). Selective safety data collection refers to the recording of certain data by investigators in case report forms. It does not affect the monitoring and clinical care of individual trial participants or documentation of their adverse events in medical records. See the HCNotice-ICH-E19 and the CAN-15 for more information.

Premature Study Termination/Suspension

The CanadaFDR and the G-CanadaCTApps state that if a trial is prematurely terminated or suspended, the sponsor should inform HC no later than 15 days after the termination or suspension. In addition, the sponsor should provide HC with the reason(s) for the termination or suspension and its impact on the proposed or ongoing clinical trials related to the drug in Canada by the sponsor. The sponsor should also promptly notify the qualified investigators of the termination or suspension and advise them in writing of any potential risks to the participants’ health. Further, the G-CanadaCTApps states that the sponsor’s notification to HC should include confirmation that the sale or importation of the drug to the discontinued sites has been stopped and that reasonable measures to ensure the return of all unused quantities of the drug will be taken. This notification must also be submitted for premature discontinuation of a clinical trial or clinical trial site outside Canada where there are ongoing trials with the drug in Canada.

According to CAN-52, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the ethics committee (EC) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor.

Purpose and Scope, and Glossary

5.0-5.2, 5.18, 5.19, 5.21, and 6.10

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

2.8.1

Part C (Division 5 (C.05.007-008, C.05.010, and C.05.015))

Last content review/update: April 24, 2024

Quality Assurance/Quality Control

As stated in Decree021-2017, the sponsor or the contract research organization (CRO) is responsible for ensuring that all information on the investigational product (IP) and additional documentation corresponds to the research protocol and complies with good clinical practices (GCPs) as provided in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (PER-53), as well as the requirements established in Decree021-2017. PER-53 further explains that the sponsor or the CRO is responsible for implementing and 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, documented (recorded), and reported in compliance with the protocol, PER-53, Decree021-2017, and other applicable regulatory requirements.

Declaration of the sponsor guaranteeing that the researchers will allow the monitoring, audits, supervision of the institutional ethics committee (EC) (El Comité Institucional de Ética en Investigación (CIEI)) and inspections of the clinical trial by the National Institute of Health (Instituto Nacional de Salud (INS))'s Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT))), including direct access to the documentation of the clinical trial. Per Decree021-2017, the sponsor or the 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 DIIS, including direct access to the clinical trial documentation. PER-53 further states the sponsor is responsible for securing agreements from all involved parties to ensure direct access to all trial related sites, source data/documents, and reports for the purpose of monitoring and auditing by the sponsor and inspection by domestic and foreign regulatory authorities.

In addition, PER-53 states that the sponsor or the CRO should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

During protocol development, identification of processes and data that are critical to ensure participant protection and the reliability of trial results
Identification of risks to critical trial processes and data
Evaluation of the identified risks against existing risk controls
Decisions on which risks to reduce and/or which risks to accept
Documentation of quality management activities and communication to those involved in or affected by these activities
Periodic review of risk control measures to ascertain whether the implemented quality management activities are effective and relevant
In the clinical study report, a description of the quality management approach implemented in the trial and a summary of important deviations from the predefined quality tolerance limits and remedial actions taken

Monitoring Requirements

As part of the clinical protocol requirements, Decree021-2017 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 DIIS 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-CTInspec explains that the INS’s DIIS inspection team carries out GCP inspections in accordance with Decree021-2017. 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 DIIS’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 DIIS approval. If required, the DIIS 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 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)) (PER-109)).

In addition, during an inspection, the evaluation of biological samples is conducted in accordance with the provisions in Decree021-2017. Please refer to the G-CTInspec for detailed clinical trial inspection procedures. See also PER-100 for the clinical trial inspection sheet form (FOR-OGITT-049). The INS-CTManual and the G-CTInspec indicate that when a regulatory medicines agency of high health surveillance notifies a research site to carry out an inspection visit in Peru, the sponsor or the contract research organization (CRO) is required to inform the INS’s DIIS of the date and time of this visit within five (5) business days of receiving the notification. The DIIS 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 DIIS, when inspection findings are critical, the sponsor or the 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 the CRO should submit their 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 the 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 DIIS scheduled clinical trial inspections and responding to the inspection reports received.

Per Decree021-2017, Res064-2021, and the G-CTSanction, in the event of a DIIS inspection during which violations in the implementation of a clinical trial are identified, the sponsor or the CRO will be subject to the following sanctions: a warning(s) and a fine for the infraction(s). In addition to the warning(s) and fine, the sponsor will also be required to cancel the trial. See also G-CTFines for additional information on how fines are assessed and graded.

As explained in Res064-2021 and the G-CTSanction, once an investigation is initiated, the DIIS’s Clinical Trials Subdirectorate (Subdirección de Ensayos Clínicos) (formerly known as the Executive Office of Investigation (Oficina Ejecutiva de Investigación (OEI)) notifies the participant(s) responsible for conducting the trial of the possible sanction(s) and the charges being made. The participant(s) then has five (5) business days from the date of notification to dispute the charges. The Clinical Trials Subdirectorate may subsequently carry out an examination to determine the existence of the liability(ies) subject to sanction within a maximum period of 30 business days. A final instructional report by the Clinical Trials Subdirectorate is prepared within no more than 15 business days and submitted to the DIIS. Once the report is received, within a maximum term of 15 business days, the DIIS decides on the application of the sanction and may order the performance of complementary actions if considered essential to resolving the procedure. Within a term not exceeding 15 business days, the DIIS then issues a resolution that applies the sanction or the decision to archive the procedure and the participant will be notified. The participant has 15 business days to file an appeal to the DIIS which will then be resolved within 30 business days.

Premature Study Termination/Suspension

Decree021-2017 states that the sponsor or the CRO is responsible for submitting the required documentation to Peru's INS to request a trial’s suspension. Per Decree021-2017 and Res655-2019 (which amends Decree021-2017), an application must be submitted that substantiates the reasons for the suspension and describes the data obtained until the time of the suspension. Refer to PER-43 for the clinical trial research site closure application form, PER-30 for the clinical trial suspension application form, and PER-31 for the clinical trial cancellation request form.

1.46-1.47 and 5.0-5.1

2 and 4.3-4.4

6.2 and 7.5

Chapter VII (7.9)

2 and 4.3-4.4

Annexes A and B

Title I (Article 2), Title IV (Article 40), Title V (Article 83), Supplementary Provisions—Final (First), and Annex 1

Data & Records Management

Last content review/update: October 1, 2024

Electronic Data Processing System

Per the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, 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 standard operation procedures (SOPs) that cover system setup, installation, and use. The SOPs should describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. With respect to the use of these computerized systems, the responsibilities of the sponsor, investigator, and other parties should be clear, and the users should receive relevant training. Note per CAN-50, HC-implemented ICH guidelines take precedence over other HC guidance when they are not consistent. Refer to CAN-52 for additional information.

The G-FDR-0100 provides that if electronic records are generated during a clinical trial, then the electronic system must be validated to confirm that the system’s specifications meet the goals and requirements for the clinical trial. This evidence of validation should be kept for the required record retention period and available for inspection by Health Canada (HC) inspectors. See the G-FDR-0100 for additional details.

Records Management

As set forth in the CanadaFDR and the CanadaFDR1024, the sponsor must record, handle, and store all trial-related information to allow complete and accurate reporting, interpretation, and verification. The CanadaFDR requires the sponsor to maintain all trial-related records for a period of 15 years. Per the G-FDR-0100, sponsors may also be required to maintain records under provincial law, institutional policies, and contractual agreements with investigators, ethics committees (ECs), or others. Where it is not possible to comply with both sets of requirements, the CanadaFDR would govern and the records must be maintained for 15 years.

Pursuant to CanadaFDR1024, the sponsor must submit requested records to HC within 48 hours if safety concerns arise. Additionally, to facilitate inspection of a site, the sponsor must submit information to HC within seven (7) days of a request. Per CAN-8, an attestation must be completed by the EC that reviewed and approved the clinical trial. The completed attestation must be retained by the clinical trial sponsor for a period of 15 years. The attestation should not be submitted to HC unless requested.

In addition, CAN-52 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

1.65, 5.5, 6.10, and 8

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

5.12

Regulatory Impact Analysis Statement

Part C (Division 5 (C.05.012))

Last content review/update: April 24, 2024

Electronic Data Processing System

No information is currently available.

Records Management

As set forth in Decree021-2017, the sponsor or the contract research organization (CRO) is required to possess a documented monitoring record, including the provision of specially selected and specialized personnel (monitors). Additionally, the sponsor or the 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 National Institute of Health (Instituto Nacional de Salud (INS)).

Per Decree021-2017, Peru also complies with the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (PER-53), which provides guidance to sponsors on records management. PER-53 further specifies that sponsor-specific essential documents should be retained until at least two (2) years after the last approval of a marketing application, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of the investigational product’s clinical development. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.

In addition, PER-53 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.

5.5 and 8.1

Title I (Article 2), Title IV (Article 40), and Supplementary Provisions—Final (First)

Personal Data Protection

Last content review/update: July 26, 2024

Responsible Parties

The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ethics committees (ECs), states that where researchers seek to collect, use, share, and access different types of information or data about participants, they should determine whether the information or data proposed in research may reasonably be expected to identify an individual. Researchers and ECs must consider whether information is identifiable or non-identifiable.

Data Protection

Per CAN-42, the Office of the Privacy Commissioner of Canada provides advice and information for individuals about protecting personal information, and enforces the two (2) federal privacy laws that set out the rules for how federal government institutions and certain businesses must handle personal information, including health data. The PrivAct covers the personal information-handling practices of federal government departments and agencies in Canada, and the PIPEDA regulates private businesses’ data protection practices. In addition, some provinces and territories have laws that deal specifically with protection of personal health information. See CAN-43 for a list of provincial and territorial privacy laws and webpages.

Per the G-TCPS2, in the research context, the most simplified method to protect participants is through the collection and use of anonymous or anonymized data. When anonymized data is not possible or desirable, a next best alternative is to use de-identified data, which is provided to the researcher in de-identified form and the existing key code is accessible only to a custodian or trusted third party who is independent of the researcher. Where it is not feasible to use anonymous or anonymized data for research, the ethical duty of confidentiality and the use of appropriate measures to safeguard information become paramount. Researchers should consult their ECs if they are uncertain about whether information proposed for use in research is identifiable (e.g., when proposing to link anonymized or coded data sets).

Consent for Processing Personal Data

Both PIPEDA and the PrivAct require consent for the use of personal data, including health data, except under prescribed conditions, such as for research or during emergencies. Also see CAN-43 for provincial and territorial privacy laws.

Chapter 2 (Article 2.1) and Chapter 5 (A. Key Concepts)

Part I (2, 6.1, and 7)

3, 7, and 8

Last content review/update: April 24, 2024

Responsible Parties

Law29733 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. Law1353 and Decree003-2013 modify the definition provided by Law29733 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.

RegDir294-2020 (approved by Res688-2020), similarly defines the “holder of the personal data bank” as the natural person, private legal person or public entity, responsible for determining the purpose and content of the personal data bank, its treatment and the security measures. As described in RegDir294-2020, personal data bank holders specifically refer to public, private, or mixed entities in the health sector that are overseen by the Ministry of Health of Peru (Ministerio de Salud del Perú (MINSA)).

Data Protection

As delineated in Law29733, the person in charge of the personal data bank, is required to protect the confidentiality and background of the owner of the personal data. 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 the 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 Law29733, the person in charge of the personal data bank (also referred to as the person in charge of processing personal data, as per Law1353) 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 once 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

RegLaw1353, which regulates the application of Law1353 and strengthens the personal data protection requirements delineated in Law29733, further establishes the terms of personal data protection violations provided in Law29733. Please refer to RegLaw1353 for information on sanctions imposed on personal data violations that include, but are not limited to, failing to treat personal data without the free, express, unequivocal, prior, and informed consent of the personal data holder and conducting sensitive personal data processing in breach of established security measures.

RegDir294-2020 (as approved by Res686-2020), in turn, establishes administrative criteria for the adequate treatment of personal data related to health or personal data in health in accordance with Law26842, Law29733, and Law27806. Pursuant to RegDir294-2020, MINSA classifies information relating to the problems, situation, or health conditions of the population in the health sector into two (2) categories: Personal Health Data (DPS) or Personal Data related to Health, and Health Information (IS). DPS are those related to the health or disease situation of a person that identifies or makes the person individually identifiable, corresponding to the past, present, or predicted health and disease, physical or mental, of a person, including the degree of disability and their genetic information.

RegDir294-2020 further explains that DPS are generated in any medical or health act, or any health care received in a health facility or outside of it, including the DPS generated in health-related research. DPS also includes information related to the medical act or health information that may affect personal and family privacy or self-image, national security, and foreign relations. When subjected to the proper anonymization and dissociation procedures, DPS become IS, where it is not possible to know the identity of the owners of the original DPS. In this case, health establishments may transmit health information related to the health of its users. Additionally, information generated from the care of patients in health emergency or pandemic situations, insofar as it corresponds to DPS, must receive the same treatment that DPS receive under normal conditions per the requirements specified in RegDir294-2020. See RegDir294-2020 for more information on the treatment of DPS.

Consent for Processing Personal Data

Prior to the collection of personal data, the entity responsible for processing this data must obtain the data holder’s consent for the collection and use of personal data per the provisions of Law29733, Law1353 (which amends Law29733), and Decree003-2013.

Law29733 and Decree003-2013 provide definitions to address health related data. Per Law29733 and Law1353, 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. Decree003-2013, 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

Law29733 and Law1353 further explain that prior to the data collection, 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
Recipient identity
The existence of the databank in which the holder’s data will be stored, as well as the identity and address of the owner, and, if applicable, the person in charge of processing the personal data
The obligatory or optional nature of the holder’s answers to the questionnaire that is presented, especially regarding sensitive data
The transfer of personal data
The consequences of the holder providing personal data and the refusal to do so
The time during which the holder’s personal data is kept, and
The possibility of exercising the rights granted by law and the means provided for it

Decree003-2013 states that 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.

Law29733 and Law1353 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.

Law29733 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 the individual’s 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 the 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.

In addition, per RegDir294-2020, the DPS owner’s written consent is required to process their personal data. Further, even when the owner’s consent is not obtained, sensitive data processing can be carried out when authorized by law, provided that it meets important reasons of public health interest. These reasons refer to the exceptional access to the DPS of a person(s), without their consent, when that information is necessary to protect the population. In no case does this exception extend to the entire population or groups of populations, as this would require the written and express consent of each person per Law29733.

RegDir294-2020 further explains that all DPS have an owner to whom they belong and can exercise their rights of access, rectification, cancellation, opposition, right to guardianship, objective, treatment, among others as indicated in Law29733. As long as the DPS owner gives prior and explicit written consent, the public, private, and mixed health sector entities may share the DPS owner’s information. The health sector entities must also designate an area to respond to DPS holder requests to exercise their rights regarding their information. The DPS owners must be provided the appropriate conditions to grant their consent through handwritten or digital signature, or any other authentication instrument that guarantees the owner’s unequivocal will. The DPS owner may revoke consent to the treatment of their DPS at any time, and the health professional or person who treats them must respect their will.

Refer to PER-3 for additional information on Law29733, and PER-99 and PER-101 for information on RegDir294-2020.

Title I (Articles 4-5) and Title II (Articles 25 and 27-28)

Articles 2-3, 5, 9, 13, 17-18, and 28

Supplementary Provisions ((Third Modification, Articles 2-3, and 18) and (Fourth Modification, Article 28))

Article 17 (5)

5.2

Preamble and Article 1

Introduction, 5.1, 5.3-5.5, 6.7, 6.10, and Annexes No. 02 and 05

Preamble and Article 1, Chapter I (Article 1), Supplementary Amending Provisions (Title VI, Article 132)

Article 2, 11, 14, and 18

Documentation Requirements

Last content review/update: October 1, 2024

Obtaining Consent

In all Canadian clinical trials, a freely given informed consent is required from each participant in accordance with the requirements set forth in the CanadaFDR, the G-TCPS2, CAN-35, and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

As per the CanadaFDR, the G-TCPS2, and CAN-52, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an institutional ethics committee (EC) (known as a Research Ethics Board (REB) in Canada) and provided to HC with the clinical trial application (CTA). (See the Required Elements section for details on what should be included in the form.)

The G-TCPS2 and CAN-52 state that the qualified investigator (QI) must provide detailed research study information to the participant or legal representative/guardian. As delineated in the G-TCPS2, CAN-35, and CAN-52, the ICF content should be in plain language (i.e., non-technical and easy to understand) and provided in a format that facilitates understanding. For example, written documentation may be supplemented with audio and/or visual aids. The participant and legal representative/guardian should also be given adequate time to consider whether to participate. CAN-35 notes that the person obtaining consent may also need to explain the consent form verbally to ensure that the participant fully understands the information. See CAN-35 for informed consent and assent templates and sample forms.

Re-Consent

According to CAN-52, any change in the ICF that is relevant to the participant’s consent should be approved by the institutional EC prior to implementing any changes. The participant or legal representative/guardian should also be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented.

Per the G-TCPS2, consent must be maintained throughout the research project. Researchers have a continuous duty to provide participants with all information relevant to their ongoing consent to participate in the research. Consent begins with the initial contact (e.g., recruitment) and carries through to the end of participation in the study. Throughout the clinical trial, researchers have a continuous responsibility to provide participants and ECs with all information relevant to participants’ ongoing consent to participate in the research. The researcher also must notify participants of any changes to the research project that may affect them. These changes may have ethical implications, may be relevant to their decision to continue in the study, or may be unique to the particular circumstances of individual participants. Specifically, researchers must disclose changes to the risks or potential benefits of the research. Change in participant capacity is an important element of ongoing consent. Rather than an age-based approach to consent, researchers should use an approach based on decision-making capacity in compliance with any laws governing research participation. This includes those whose decision-making capacity is in the process of development, those whose decision-making capacity is diminishing or fluctuating, and those whose decision-making capacity remains only partially developed. Mechanisms should be in place from the outset to identify and address any changes that could affect consent. Further, within the limits of consent provided by the participant, researchers should disclose to the participant any material incidental findings discovered in the course of research. Incidental findings are considered to be material incidental findings if they are reasonably determined to have significant welfare implications for the participant or prospective participant. Where material incidental findings are foreseeable, researchers should inform participants during the initial consent process. In addition, researchers should develop a management plan for review by the EC. For more information on how to address material incidental findings, see G-ConsentMatIncFindings.

Language Requirements

CAN-35 further specifies that consent forms should be provided in the language that participants are most comfortable with. The G-TCPS2 and CAN-52 require the ICF to be presented in plain language that the participant is able to understand. Per CAN-35, ICFs should be translated where it is relevant to particular communities. If there is a language barrier, the G-TCPS2 indicates that the qualified investigator should select an intermediary who has the necessary language skills to ensure effective communication. Further, per CAN-35, the level of language used should be appropriate to the age and comprehension/reading level of the participant population, generally at approximately a grade 6-8 reading level.

Documenting Consent

As per the G-TCPS2, CAN-52, and CAN-35, the participant or legal representative/guardian, as well as the qualified investigator, must sign and date the ICF. CAN-52 and the G-FDR-0100 state that the QI should retain the signed ICF. CAN-35 indicates that information letters and ICFs must be presented on institutional/department letterhead.

According to CAN-52, where the participant is illiterate and/or the legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:

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

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

As per the G-TCPS2 and CAN-52, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or appear to waive the participant’s legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representative(s) from their liabilities for any negligence.

Per CAN-35, in some situations, written consent is not be feasible or desirable, for example due to logistical issues or because of the preferences of the participants. In addition, some individuals may perceive written consent as an attempt to legalize the consent process, thereby creating mistrust. It is also important to recognize that in some cultures written consent is not consistent with community traditions. In these cases, it may be more appropriate to use a handshake, a verbal agreement, or oral consent. Article 10.2 of the G-TCPS2 further indicates that researchers can use a range of procedures to seek and document consent, including oral consent documented in field notes, and other forms of recording (e.g., a consent log, audio or video recordings, or other electronic means). Evidence of consent may also be documented via completed questionnaires (in person, by mail, or by email or other electronic means). ECs should consider the power relationship that might exist between researchers and participants, and whether a waiver of the requirement for signed written consent may affect the welfare of the participants. If researchers plan to obtain non-written consent, they must explain their strategy to the EC.

Waiver of Consent

As explained in the G-TCPS2, there are research situations that call for alterations of consent. The EC may approve research that involves an alteration to the consent requirements if the EC is satisfied, and documents, that all of the following apply:

The research involves no more than minimal risk to the participants
The change to consent requirements is unlikely to adversely affect the welfare of participants
It is impossible or impracticable to carry out the research and to address the research question properly, given the research design, if the prior consent of participants is required
In the case of a proposed alteration, the exact nature and extent of any proposed alteration is defined
There is a plan to brief participants and offer the option of refusing consent and/or withdrawing data and/or human biological materials

4.8, 8.2, and 8.3

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Policies, Guidelines, and Resources; Consent Process (Key Considerations)

5.5, 5.6, 5.8, and 5.10

Chapters 3 and 10

Part C (Division 5 (C.05.005, C.05.006, C.05.008, and C.05.010))

Last content review/update: April 24, 2024

Obtaining Consent

In all Peruvian clinical trials, a freely given informed consent must be obtained from each participant in accordance with the principles set forth in Law26842, Decree021-2017, the G-EC-CTRev, and the Declaration of Helsinki (PER-76). Decree011-2011 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 Decree021-2017 and the G-EC-CTRev, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an National Institute of Health (Instituto Nacional de Salud (INS))-registered institutional ethics committee (EC) (El Comité Institucional de Ética en Investigación (CIEI)) and provided to the INS with the clinical trial application. PER-83 further specifies that the sponsor or the contract research organization (CRO) must provide copies of the research protocol and ICF that are stamped and signed by the EC in its entirety as evidence that the approved version is being presented. (See the Required Elements section for details on what should be included in the form.)

As delineated in Decree021-2017, RegLaw29414, the G-EC-CTRev, and Res233-2020, investigator(s) must provide detailed research study information to the participant or legal representative/guardian. 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 the legal representative/guardian should also be given adequate time to consider whether to participate. Per Decree021-2017, when drafting and presenting the ICF, special consideration must be taken with regard to the participant’s culture, traditional values, intelligence, and education.

Res233-2020, which regulates human subjects research other than clinical trials of drugs or devices, states that 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. Furthermore, participants must be kept constantly informed about the changes, progress, and results of the research according to the applicable regulations.

Re-Consent

As indicated in Decree021-2017, the participant or legal representative/guardian is required to sign a revised ICF if any changes occur in the protocol or in the treatment methods or procedures.

Language Requirements

Per Decree021-2017, the ICF must be written in Spanish and in the language of the research participant.

Documenting Consent

Decree021-2017 and the G-EC-CTRev state that the participant or legal representative/guardian, and the investigator(s) must sign and date the ICF. Where the participant is illiterate or the legal representative/guardian is illiterate, a 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.

Waiver of Consent

No information is available regarding waiver of consent.

Ethical Criterion 4 and Annexes 2-3

Title I (Articles 4-5) and Title II (Articles 25 and 27-28)

I, VII (7.1), and VIII (8.4)

Article 24

II (3)

Title I (Article 2), Title II (Article 11), Title III (Articles 32-34), and Annex 4

Required Elements

Last content review/update: October 1, 2024

Based on the G-TCPS2, the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), and CAN-35, the informed consent form (ICF) should include the following statements or descriptions in plain language, as applicable (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

The study involves research and an explanation of its purpose and duration
The trial treatment(s) and the probability for random assignment to each treatment
The procedures to be followed, including all invasive procedures
The participant’s responsibilities
Those aspects of the trial that are experimental
Any reasonably foreseeable risks or inconveniences to the participant and, when applicable, to an embryo, fetus, or nursing infant
Any reasonably expected benefits; if no benefit is expected, the participant should be made aware of this
The disclosure of specific alternative procedure(s) or therapies available to the participant, and their important potential benefits and risks
Compensation and/or treatment available to the participant in the event of a trial-related injury
The anticipated prorated payment, if any, to the participant for participating in the trial
Any expenses the participant needs to pay to participate in the trial
That participation is voluntary, and that the participant can refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the participant is otherwise entitled
Information concerning the possibility of commercialization of research findings, and the presence of any real, potential, or perceived conflicts of interest on the part of the researchers, their institutions, or the research sponsors
Confidentiality of records identifying the participant will be maintained, and permission given to monitors, the auditors, the ethics committee (EC), and Health Canada (HC) to access the participant’s medical records to verify the procedures and/or data, without violating the confidentiality of the participant, insofar as the applicable laws and regulations permit, and that, by signing a written ICF, the participant or legal representative/guardian is authorizing such access
That records identifying the participant will not be made publicly available, insofar as the applicable laws and/or regulations permit; if the results of the trial are published, the participant’s identity will remain confidential
The participant or legal representative/guardian will be notified in a timely manner if information becomes available that may affect the participant’s willingness to continue
The qualified investigator’s contact information for further information regarding the trial and the rights of participants, and whom to contact in the event of a trial-related injury
The identity and contact information of a qualified designated representative who can explain scientific or scholarly aspects of the research to participants
Information on stopping rules, foreseeable circumstances, and/or reasons under which the participant’s involvement in the trial may be terminated
The approximate number of participants in the trial

Per CAN-50, Canada has implemented CAN-52.

Per CAN-35, if blood is taken, indicate total volume (e.g., teaspoons and milliliter equivalent) and note the possibility of bruising or swelling while giving blood, or other possible discomforts at the site where blood is drawn. Further, state that there may be minimal chance of infection and that discomforts experienced will be brief and transient.

CAN-35 also indicates that participants should not be told if an EC has approved the study, since this may appear to offer a guarantee of safety. Further, no clause or language should be used to excuse or appear to excuse investigators or other persons or institutions involved from liability for their negligence or other faults. Sample consent forms can be found in CAN-35.

See the Vulnerable Populations and Consent for Specimen sections for further information.

4.8

Efficacy guidelines

Policies, Guidelines, and Resources, and Consent Process (Sample consent forms)

Chapter 3

Last content review/update: April 24, 2024

As delineated in Decree021-2017 and the G-EC-CTRev, the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Trial title (include version and date)
Sponsor(s), research institution, principal investigator (PI), ethics committee (EC), and the National Institute of Health (Instituto Nacional de Salud (INS)) 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 the 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 when agreeing to participate in the study
The guarantee of receiving answers to any questions and clarification for any doubts 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 Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)))
Participant’s right to withdraw consent at any time and to stop participating in the study without creating any detriment to continue care and treatment
The participant and/or the legal representative agrees to authorize access to 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 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 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 the participant
Inform the participant of post-study access to the IP after trial completion
Provide a trial description in the INS’s Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) (PER-89) (also referred to as REPECv2)

Additionally, the G-EC-CTRev states that the participant should be provided with detailed information on the biological samples to be collected and stored. Per Decree021-2017, 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 Consent for Specimen section for further information on participant consent requirements for use of biological samples.

See also the Vulnerable Populations section for further information.

Annex 2

Title III (Article 34) and Annex 4

Participant Rights

Last content review/update: October 1, 2024

Overview

In accordance with the CanadaFDR, the G-TCPS2, and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), Canada’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The G-TCPS2 and CAN-52, which Canada has implemented per CAN-50, state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

The informed consent template in CAN-35 provides that if a participant has any questions about their rights, they should contact:

Health Canada-PHAC Research Ethics Board Secretariat
70 Colombine Driveway, Room 941C, PL: 0909C
Brooke Claxton Building, Tunney's Pasture
Ottawa, ON K1A 0K9
Telephone: 613-941-5199
Fax: 613-941-9093
reb-cer@hc-sc.gc.ca

The Right to Participate, Abstain, or Withdraw

As stated in the G-TCPS2 and CAN-52, the participant or legal representative/guardian should be informed that participation is voluntary, that they may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

Per CAN-35, participants should be assured that their participation is completely voluntary, they are under no obligation to participate, and they are free to withdraw at any time without consequence. It should be made clear that their decision to withdraw will not influence their relationship with the researcher in any way. The researcher should explain what will happen to participant samples or data if they choose to withdraw. If applicable, clearly state the point in the study at which removal of samples or data becomes difficult or impossible.

The Right to Information

As per the G-TCPS2 and CAN-52, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation or treatment in the case of injury, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

According to the G-TCPS2 and CAN-52, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.

Per CAN-35, the ICF should explain what information will be collected about participants and for what purpose, including the type of information that will be collected (e.g., will it be coded or de-identified?) and how it will be stored. Further, the ICF should state who will have access to the collected information and describe the efforts that will be made to prevent the risk of participant re-identification. Limits to confidentiality and additional requirements for projects led by HC or the Public Health Agency of Canada (PHAC) are provided in CAN-35.

The Right of Inquiry/Appeal

The G-TCPS2 and CAN-52 state that the research participant or legal representative/guardian should be provided with contact information for the individual responsible for addressing trial-related inquiries and/or the participant’s rights.

The Right to Safety and Welfare

CAN-52, which upholds the Declaration of Helsinki, clearly state that a research participant’s right to safety and the protection of their health and welfare must take precedence over the interests of science and society.

See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.

1.27, 3.1, and 4.8

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Consent Process (Consent Form Template)

5.1 and 5.5

Chapter 1 (Article 1.1), Chapter 2, and Chapter 3 (Articles 3.1 and 3.2)

Part C (Division 5 (C.05.001 and C.05.005))

Last content review/update: April 24, 2024

Overview

In accordance with Law26842, Decree021-2017, the G-EC-CTRev, Res233-2020, the PeruConstitution, Decree011-2011, 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 Decree021-2017, the G-EC-CTRev, and Res233-2020, 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

Decree021-2017, RegLaw29414, and the G-EC-CTRev state that the participant or the legal representative/guardian should be informed that participation is voluntary, that study withdrawal may occur 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 Decree021-2017, RegLaw29414, and the G-EC-CTRev, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

Pursuant to Decree021-2017 and the G-EC-CTRev, 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

The Right of Inquiry/Appeal

Per Decree021-2017 and the G-EC-CTRev, the research participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries and/or to appeal against a violation of the participant's rights.

The ICF must guarantee that the participant will receive answers to any questions and clarification to any doubts 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

Decree021-2017, the G-EC-CTRev, and Decree011-2011 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-CTRev further states that the interests of science cannot take precedence over the interests of the research participants.

VII, Ethical Criterion 4, Ethical Criterion 5, and Annex 2

Title I (Articles 4 and 5) and Title II (Articles 25, 27, and 28)

Chapter 1 (Articles 1 and 2) and Chapter 2 (Article 7)

I and VIII (8.4)

Articles 18 and 24

Preamble, Article 2, II (1-3), and V (1 and 6)

Title I (Article 4), Title II (Article 9), Title III (Article 34), Title IV (Article 40), and Annex 4

Emergencies

Last content review/update: October 1, 2024

The G-TCPS2 and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent. As per CAN-52, in an emergency, if the signed informed consent form (ICF) has not been obtained from the research participant or legal representative/guardian, or, if an effective treatment is lacking but the investigational product could address the participant’s emergency needs, the clinical trial may be conducted. However, the method used on the participant must be explained clearly in the trial protocol, and the ethics committee (EC) (known as Research Ethics Board (REB) in Canada) must approve the protocol in advance. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

Per G-TCPS2, research involving medical emergencies must be conducted only if it addresses the emergency needs of the individuals involved, and then only in accordance with criteria established in advance of such research by the EC. The EC may allow research that involves medical emergencies to be carried out without the consent of participants, or legal representatives/guardians, if all of the following apply:

A serious threat to the prospective participant requires immediate intervention
Either no standard efficacious care exists, or the research offers a realistic possibility of direct benefit to the participant in comparison with standard care
Either the risk is not greater than that involved in standard efficacious care, or it is clearly justified by the prospect for direct benefits to the participant
The prospective participant is unconscious or lacks capacity to understand the risks, methods, and purposes of the research project
Authorization from the legal representative/guardian cannot be secured in sufficient time, despite diligent and documented efforts to do so
No relevant prior directive by the participant is known to exist

4.8

Information on ICH guidelines implemented by Health Canada and Efficacy Guidelines

Chapter 3 (Articles 3.7-3.9)

Last content review/update: April 24, 2024

No information is currently available.

Vulnerable Populations

Last content review/update: October 1, 2024

Overview

As per the G-TCPS2, in all Canadian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. The International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52) characterizes vulnerable populations as those who may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from not participating. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students; subordinate hospital and laboratory personnel; employees of the pharmaceutical industry; members of the armed forces; and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

CAN-52, which Canada has implemented per CAN-50, specifies that ethics committees (ECs) (known as Research Ethics Boards in Canada) must pay special attention to protecting participants who are from vulnerable populations. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.

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

1.61, 3.1, and 4.8

Information on ICH guidelines implemented by Health Canada and Efficacy Guidelines

Chapter 3 (Article 3.9) and Chapter 4 (Article 4.7)

Last content review/update: April 24, 2024

Overview

As per Decree021-2017, 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-CTRev 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.

Decree021-2017 defines vulnerable populations as 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 Decree011-2011, 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. Decree011-2011 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 Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these vulnerable populations. Information on the other vulnerable populations specified in Decree021-2017 is provided below.

Indigenous Peoples

As explained in Decree021-2017, 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-CTRev 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-CTRev also references Decree021-2017’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.

Persons in Dependent Groups

Per Decree021-2017, clinical trials involving participants in subordinate or dependent relationships must meet the following requirements:

One (1) or more of the 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
Refusal or withdrawal of consent during the trial should not affect a participant’s 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.

Persons with Physical Disabilities

Per Decree021-2017 and Decree021-2017-Correct, 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 their written consent by printing their 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, the 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 the legal representative(s) may withdraw 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 Required Elements section
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-CTRev also notes that, per Law1384 which amends Law295, 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, Law1384 states that any person with a disability that requires reasonable adjustments or support to exercise their legal rights may request or designate a legal representative(s) of their choosing for assistance. Persons with disabilities who cannot communicate their own wishes will receive support and safeguards from judicially designated entities.

Ethical Criterion 4, Ethical Criterion 5, and Ethical Criterion 6

Articles 1-2

Title II (Article 3) and Title V (Articles 42-44 and 46-47)

II (1-3)

Title I (Article 2) and Title III (Articles 19, 24-25, 33, and 38)

Children/Minors

Last content review/update: October 1, 2024

Per CAN-35, because the G-TCPS2 does not specify an age of consent for children, the decision on whether to seek consent from children is based on whether they have the capacity to understand the research and the risks and benefits of their participation. Youth who have not reached the age of majority (either 18 or 19 depending on the province or territory) may still be old enough to provide their own consent. For children who are not sufficiently mature to provide consent but are able to understand the nature of study participation, researchers must obtain the child’s assent in addition to the consent of an authorized third party. The decision of a child not to assent must be respected regardless of whether third-party consent was obtained.

CAN-35 provides the following criteria for determining whether participants can provide their own consent, or whether an authorized third party should be involved:

The risk level associated with the research project
The legal requirements for age of consent in that jurisdiction
The characteristics of the research participant (e.g., maturity level)
In certain cases, the topic of the research itself

CAN-35 states that it is generally accepted that youth can consent to minimal risk studies at 16 years of age, and that assent should be sought from children beginning at approximately seven (7) years of age. However, it is ultimately up to the researcher to determine whether to obtain assent or consent from children, and to provide the rationale for this decision to the ethics committee (EC) (known as a Research Ethics Board in Canada). Researchers should also consider that within a single research project, some minors may be capable of consenting while others may not. See CAN-35 for additional details regarding obtaining consent from minors.

As per the G-TCPS2 and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), when the research participant is a child, the informed consent form (ICF) must be signed by the child’s parent/legal guardian. All pediatric participants, however, should be informed to the extent compatible with the child’s understanding, and if capable, the pediatric participant should sign and personally date the ICF. Per CAN-50, Canada has implemented CAN-52. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.

As stated in G-TCPS2, children should only participate in clinical studies when the research objective cannot be achieved with adult participants only. When considering the inclusion of children in research, the investigators and ECs must consider a child’s stage of physical, physiological, psychological, and social development to ensure adequate protections for the child’s welfare.

Assent Requirements

Per G-TCPS2 and TCPS2-InterpCnsnt, where a child has some ability to understand the significance of the research, the researcher must ascertain the wishes of that individual with respect to participation. Children—whose decision-making capacity is in the process of development—may be capable of verbally or physically assenting to, or dissenting from, participation in research. While their assent would not be sufficient to permit them to participate in the absence of consent by the child’s parent/legal guardian, their expression of dissent must be respected.

Further, according to CAN-12, which offers best practices and guidance to researchers and ECs in pediatric research and complements the G-TCPS2, provincial laws in Canada vary as to when a child is presumed to be legally competent to provide informed consent. Some provinces use age while others use a competence-based evaluation.

As per CAN-12, if the pediatric participant has the capacity for assent, then affirmative assent is required to participate in a study according to the participant’s level of development and capacities. When the child develops the legal capacity to provide informed consent or attains the legal age of majority (which depends on the province), researchers should obtain an informed consent. Regarding dissent, CAN-12 states that the researchers must respect the dissent of a child who is capable of understanding.

CAN-35 provides sample assent forms and templates. For more detail and guidance about best practices for research involving pediatric participants, see CAN-12.

Guidelines III and IV

4.8

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Consent Process (Key Considerations)

Chapter 3 (Article 3.10) and Chapter 4 (Article 4.4)

1

Last content review/update: April 24, 2024

Pursuant to Law27337, Law295, Law1384, and the G-EC-CTRev, the age of majority is 18 years of age. Per Law295 and the G-EC-CTRev, 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 Law295 and Law1384, 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. Law1384 further clarifies that individuals over 14 and under 18 who marry, or who become parents are considered fully capable of providing consent.

Per Decree021-2017, for studies involving minors, 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.

Assent Requirements

Per Decree021-2017 and the G-EC-CTRev, the assent of a pediatric participant from the age of eight (8) and under 18 years of age must be obtained to participate in an investigation.

In addition to a minor providing assent, Decree021-2017 and the G-EC-CTRev state that the consent of both parents or the minor’s legal guardian is required. Per Decree021-2017, the consent of the legal guardian 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 (1) 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 Law295.

Decree021-2017 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 guardian 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 guardian and the teenager. A minor who reaches the age of majority during a trial must provide consent before continuing to participate in the study.

Ethical Criterion 4

Article 1

Preliminary Title (Article 1)

Title V (Articles 42-46)

Title I (Article 2) and Title III (Articles 18, 33, and 36)

Pregnant Women, Fetuses & Neonates

Last content review/update: October 1, 2024

As per the G-TCPS2, studies involving women of childbearing age, or who are pregnant, require additional safeguards to ensure that the research assesses the risks to the women and the fetuses. The following guidance applies to research involving materials related to human reproduction:

Research using materials related to human reproduction in the context of an anticipated or ongoing pregnancy must not be undertaken if the information can reasonably be obtained by alternative methods
Materials related to human reproduction for research use must not be obtained through commercial transaction, including exchange for services

Per the G-TCPS2, research on in vitro embryos already created and intended for implantation to achieve pregnancy is acceptable if:

The research is intended to benefit the embryo
Research interventions will not compromise the care of the woman, or the subsequent fetus
Researchers closely monitor the safety and comfort of the woman and the safety of the embryo
Consent was provided by the gamete donors

According to the G-TCPS2, research involving embryos that have been created for reproductive or other purposes permitted by law, but are no longer required for these purposes, may be ethically acceptable if:

The ova and sperm from which they are formed were obtained in accordance with the G-TCPS2
Consent was provided by the gamete donors
Embryos exposed to manipulations not directed specifically to their ongoing normal development will not be transferred for continuing pregnancy
Research involving embryos will take place only during the first 14 days after their formation by combination of the gametes, excluding any time during which embryonic development has been suspended

Per the G-TCPS2, research involving a fetus or fetal tissue:

Requires the consent of the woman
Must not compromise the woman’s ability to make decisions regarding continuation of her pregnancy

In accordance with the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, informed consent requirements for conducting clinical trials with pregnant or nursing women or fetuses follow the general requirements listed in the Required Elements section. Specifically, the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.

4.8

Information on ICH guidelines implemented by Health Canada and Efficacy Guidelines

Chapter 4 (Article 4.3) and Chapter 12 (Articles 12.6-12.9)

Last content review/update: April 24, 2024

As per Decree021-2017, 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 Children/Minors section

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 request of the participant, spouse, or partner 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 (Article 23) of Decree021-2017, 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

Title III (Articles 20-23) and Annex 4

Prisoners

Last content review/update: October 1, 2024

According to the G-TCPS2 and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, 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. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.

1.61

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Chapter 3 (Article 3.1) and Chapter 4 (Article 4.7)

Last content review/update: April 24, 2024

No information is currently available.

Mentally Impaired

Last content review/update: October 1, 2024

According to the G-TCPS2 and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), the ethics committee (EC) (known as Research Ethics Board in Canada) must approve the participation of research participants who are mentally or physically incapable of giving consent. Per CAN-50, Canada has implemented CAN-52.

Per CAN-35, adults with diminished decision-making capacity include:

Individuals whose decision-making capacity remains only partially developed, such as those living with permanent cognitive impairment, and
Individuals who once were capable of making an autonomous decision regarding consent but whose decision-making capacity is diminishing or fluctuating (e.g., due to cognitive impairment resulting from an injury or disease).

Per CAN-35, as is the case for any vulnerable population, care must be taken to ensure that adults with diminished decision-making capacity are not inappropriately included in research because of their situation, and neither should they be excluded from participating in research that may benefit them.

The G-TCPS2 indicates that for research involving individuals who lack the capacity, either permanently or temporarily, to decide for themselves whether to participate, the EC must ensure that, at a minimum, the following conditions are met:

The researcher involves participants who lack the capacity to decide on their own behalf to the greatest extent possible in the decision-making process
The researcher seeks and maintains consent from the participant’s legal representative/guardian in accordance with the best interests of the persons concerned
The legal representative/guardian is not the researcher or any other member of the research team
The researcher demonstrates that the research is being carried out for the participant’s direct benefit, or for the benefit of other persons in the same category; if the research does not have the potential for direct benefit to the participant but only for the benefit of the other persons in the same category, the researcher shall demonstrate that the research will expose the participant to only a minimal risk and minimal burden, and demonstrate how the participant’s welfare will be protected throughout the participation in research
When authorization for participation was granted by a legal representative/guardian, and a participant acquires or regains decision-making capacity during the course of the research, the researcher must promptly seek the participant’s consent as a condition of continuing participation

Per CAN-35 and the G-TCPS2, the participant’s legal representative/guardian can provide consent for adults who lack the capacity to decide on their own behalf in accordance with the best interests of the persons concerned. In such cases, participants should still be involved to the greatest extent possible in the decision-making process, and their assent to participate must be obtained if they are capable of expressing their wishes in a meaningful way (whether verbally or physically). Importantly, when authorization for participation was granted by the participant’s legal representative/guardian and a participant acquires or regains decision-making capacity during the course of the research, the researcher must promptly seek the participant’s consent as a condition of continuing participation.

Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.

1.61 and 3.1

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

Consent Process (Key Considerations)

Chapter 3 (Article 3.7-3.10)

Last content review/update: April 24, 2024

Law30947 establishes 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 Law30947 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 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

Law30947 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 Law30947, 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 a contraception method without prior informed consent, and to be obtained by the individual when not in a crisis 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 in regard to their dignity, autonomy, and needs, in accordance with the provisions of the CRPD

In addition, Law295 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-CTRev specifies that persons who are temporarily mentally incapacitated may participate in a research study if their designated legal representative/guardian decides on their behalf to allow them to participate per the requirements specified in Law1384, which amends Law295. The legal representative/guardian 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 participation in a clinical trial will be made by the person’s legal representative/guardian in accordance with the consanguinity or affinity ties delineated in RegLaw29414. See Law1384 and RegLaw29414 for requirements related to the roles and responsibilities of legal representative/guardian.

Decree021-2017, 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/guardian who have been informed of the possible risks, discomforts, and benefits of the trial
Informed consent may be obtained after the participant has been fully informed about the trial in easily understandable language
Consent may be withdrawn at any time without harm to the participant or legal representative/guardian

As delineated in the G-EC-CTRev, persons in a comatose state may be involved in a clinical study as long as the appropriate legal representative/guardian are in place that comply with Law1384, which amends Law295. According to Law1384, any legal representative/guardian designated prior to a person becoming comatose will be upheld. However, for those persons who have not designated a legal representative/guardian, 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/guardian is necessary for the exercise and protection of the participant's rights.

Ethical Criterion 4

Articles 2-3

Articles 1, 3-4, 6, 9, and 32

Title V (Articles 43-47)

Article 5

Title IV (Article 37)

Definition of Investigational Product

Last content review/update: October 1, 2024

As delineated in the CanadaFDR, the G-GMP-Annex13, and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), an investigational product is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form. Per CAN-50, Canada has implemented CAN-52. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.

For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

1.33

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

3.0

5.1

Part C (Division 5 (C.05.001))

Last content review/update: April 24, 2024

As delineated in Decree021-2017 and the G-SafeRpt, 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.

Decree021-2017 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.

V

Title I (Article 2)

Manufacturing & Import

Last content review/update: October 1, 2024

Manufacturing

As specified in the CanadaFDR, the G-CanadaCTApps, and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), Health Canada (HC) authorizes the manufacture of investigational products (IPs) in Canada. HC approves the manufacture of IPs as part of the clinical trial application (CTA) approval. Per CAN-50, Canada has implemented CAN-52. Note that per CAN-50, HC-implemented ICH guidance takes precedence over other HC guidance when they are not consistent. The G-QCM-PharmCTAs provides guidance and templates to assist sponsors in completing the quality portion of the CTA, which in turn, enables HC to assess IP characteristics adequately. The G-GMP-Annex13 requires the sponsor to ensure that IPs for clinical trials are manufactured and imported in accordance with its provisions and with CanadaFDR requirements. Per the G-CanadaCTApps, sponsors must file amendments or notifications to a previously authorized CTA when manufacturing changes are proposed that may affect the quality or safety of the clinical trial drug or biologic supplies.

Import

Per the CanadaFDR and the G-FDR-0100, HC authorizes the sponsor to import an IP. A sponsor who is not based in Canada must have a Canadian representative who is responsible for the import of the IP and demonstrates compliance with the applicable regulatory requirements. This representative should be the sponsor’s senior medical or scientific officer residing in Canada and is responsible for providing an attestation with respect to the CTA at the time of filing. Per the G-CanadaCTApps, the G-DrugApp, and CAN-4, if clinical trial drugs are to be imported into Canada, the authorization template (Appendix 1) in CAN-4 should be completed and submitted for each importer in Canada. The G-DrugApp states that Canadian importer(s) must be located within Canada. As additional importers are identified, additional copies of the authorization template in CAN-4 should be provided to HC. The G-FDR-0100, provides additional guidance on requirements if a sponsor plans to send the clinical trial IP(s) directly to each trial site:

Each party, including individual Canadian clinical trial sites, importing drugs directly (i.e., receiving drug shipment directly from outside of Canada) is identified on Appendix 1 of the Drug Submission Application Form (HC/SC 3011 form) (CAN-4) for Phase I-III trials (submitted with the application if known at the time or prior to importation at the site). Appendix 1 may be replicated as many times as necessary to capture all importing parties.
Clinical Trial Site Information (CTSI) forms (CAN-6) for each Canadian site conducting the clinical trial are submitted to HC for Phase I-III trials, prior to the start of the study.
Systems are in place, when appropriate, to monitor the transportation and storage conditions from the foreign source to the various clinical trial sites across Canada.
There is documented accountability of the imported drugs used in clinical trials and distributed to various clinical trial sites located in Canada, including the disposition of drugs returned from the clinical trial sites.
A written agreement is in place between the sponsor and the qualified investigator describing their specific responsibilities, and this agreement is available at the clinical trial site.
There is evidence that the drugs used in clinical trials conducted in Canada meet Good Manufacturing Practice (GMP) requirements (e.g., certificates of manufacture, certificates of analysis, and/or evidence of approved lot release by a qualified individual).

The G-CanadaCTApps, the G-HlthProdImprtExptReqs, the G-FDR-0100, and CAN-32 state that if a sponsor wants to import a drug into Canada for a clinical trial, a copy of HC’s authorization (i.e., the No Objection Letter (NOL)) issued by either the Pharmaceutical Drugs Directorate (PDD) or the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) must be included for the applicable trial with the shipment. A copy of this authorization must be provided at the port of entry. The G-HlthProdImprtExptReqs states that drugs without a Drug Identification Number may be imported where authorized for a Canadian clinical trial and a NOL was issued. The G-FDR-0100 further states that if 30 days have passed and the NOL was not issued, specific requests to import IPs should be directed to the Health Product Border Compliance Program at the following email account: hc.hpbcp-pcpsf.sc@canada.ca. Note that a sponsor does not have to submit a CTA for authorization to import an IP used in a Phase IV clinical trial.

Per CanadaFDR, the sponsor can make the following changes to the authorized use or importation of drugs if the sponsor notifies HC in writing within 15 days after the date of the change:

A change to the chemistry and manufacturing information that does not affect the quality or safety of the drug
A change to the protocol that does not alter the risk to the health of a clinical trial subject

Other changes must follow the amendment requirements delineated in the CanadaFDR. See the G-FDR-0100 for additional HC interpretations of the relevant provisions of the CanadaFDR.

Appendix 1

2.12 and 5.13

Drug Importation

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

1.0

2.3 and 2.7

5.2-5.3 and 5.6

I, S Drug Substance, and P Drug Product

Section # Block D and Appendix 1 Guidance

Importer’s Role, Table 1, and Human Drugs

Part C (Divisions 2-5)

Last content review/update: April 24, 2024

Manufacturing

According to Decree021-2017, Decree016-2011, the INS-CTManual, and Res252-2022 (which amends the INS-CTManual), the sponsor or the 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 investigational products (IPs) exclusively for research purposes in Peru. Decree021-2017 states that the manufacture of IPs in the country will be subject to Good Manufacturing Practices (GMPs) and other regulations issued by the Ministry of Health of Peru (Ministerio de Salud del Perú (MINSA)). Decree016-2011 further specifies that the national manufacture of pharmaceutical products for research purposes involving human beings must be carried out in pharmaceutical establishments that have a sanitary authorization and a GMP certificate, as appropriate. Refer to Decree016-2011 for detailed ANM pharmaceutical manufacturing requirements. (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)) (PER-109)).

Import

As delineated in Decree021-2017, the INS-CTManual, and Res252-2022, to obtain clinical trial authorization, the National Institute of Health (Instituto Nacional de Salud (INS))’s Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT))) requires the sponsor or the CRO to provide a list of products and supplies necessary for the development of the clinical trial using form FOR-OGITT-033 (PER-42). This form requires the sponsor or the 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

Decree021-2017 and Decree016-2011 also specifies that the 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 approval
List of INS-approved research products, complementary products, and supplies to be used in the trial (see Form FOR-OGITT-033 (PER-42))
Proof of payment for processing fee

Decree021-2017 specifies that the ANM will grant this authorization within three (3) business days of filing the application.

See Scope of Assessment section for additional information on the ANM’s role in the clinical trial application approval process, and PER-6 for a flowchart delineating the clinical trial authorization process.

In addition, per Decree021-2017, the INS-CTManual, and Res252-2022, the sponsor or the CRO must apply to the INS’s DIIS using PER-42 to modify or expand the list of supplies to be imported. Per the INS-CTManual, the INS approval process will be completed within a maximum of 10 business days.

According to Decree021-2017, 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

The INS-CTManual further explains that in addition to submitting PER-42 and a report justifying the reasons for the amended supply list request, the following should be provided:

To modify by the batch number: Certificate of analysis and IP labeling
To modify by the manufacturer or country: Certificate of Good Manufacturing Practices, Certificate of analysis, and IP labeling

See PER-42 for the form and the INS-CTManual for detailed instructions on completing this form.

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.

Chapter VII (7.6), Chapter IX, and Annex 4 (Flowcharts No. 04 and 08)

Requirements for Initiating the Procedure (10 and 13), 4.1-4.4, and Annexes 1 and 9

Title II (Chapters I and V)

Title I (Article 8), Title V (Article 75), Title VI (Articles 90 and 94), and Annex 5

Quality Requirements

Last content review/update: October 1, 2024

Investigator’s Brochure

In accordance with the CanadaFDR and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, the sponsor is responsible for providing the investigators with an Investigator’s Brochure (IB). The CanadaFDR and CAN-52 specify that the IB must contain all of the relevant information on the investigational product(s) (IPs), including significant physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information. The sponsor must ensure that an up-to-date IB is made available to the investigator(s), and the investigator(s) must provide an up-to-date IB to the ethics committee. Note that per CAN-50, Health Canada (HC)-implemented ICH guidance takes precedence over other HC guidance when they are not consistent. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

The CanadaFDR and CAN-52 require the IB to 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 IP in humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and post-marketing experiences)
Summary of data and guidance for the investigator(s)

See Section 7.3 of CAN-52 for detailed content guidelines.

In accordance with the G-CanadaCTApps and CAN-22, the sponsor must submit annually to HC an updated IB, which serves as the annual report, including all safety information and global status. Revisions that are more frequent may be appropriate depending on the stage of development and the generation of relevant new information.

Quality Management

Pursuant to CAN-52, 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. As specified in CAN-52, G-GMP-CAN, and G-GMP-Annex13, the sponsor must ensure that the products are manufactured in accordance with Good Manufacturing Practice (GMP). The G-GMP-CAN requires a quality management system, incorporating GMP, to ensure that IPs are of the quality required for their intended use. Per the G-GMP-Annex13, the manufacturer’s quality system should be described in written procedures and available to the sponsor, taking into account GMP principles and guidelines.

2.12, 5.13, 7.3, and 8.2

Information on ICH guidelines implemented by Health Canada and Efficacy guidelines

4

2.8

5.1, 5.5, and 5.12

Part C (Division 5 (C.05.001, C.05.005, and C.05.012))

Last content review/update: April 24, 2024

Investigator’s Brochure

In accordance with Decree021-2017, Res655-2019 (which amends Decree021-2017), and Res252-2022 (which amends the INS-CTManual), the sponsor or the 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 Decree021-2017, 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 IB—becomes available. Decree021-2017 and the INS-CTManual indicate that the updated IB should be sent to the National Institute of Health (Instituto Nacional de Salud (INS))’s Directorate of Health Research and Innovation (Dirección de Investigación e Innovación en Salud (DIIS)) (formerly known as the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT))), the ethics committees (ECs), and the principal investigators (PIs). The INS-CTManual further specifies that the sponsor or the CRO is required to submit a signed notification form (FOR-OGITT-059) to inform the DIIS of any IB updates (PER-41). The form must be accompanied by an update report of the applicable IP(s).

As specified in Decree021-2017, 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 Decree021-2017 for detailed content guidelines.

In addition, per the G-SafeRpt, the sponsor or the 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-SafeRpt for detailed safety information to include in the IB.

Quality Management

As specified in Decree021-2017, Res655-2019, and the INS-CTManual, the 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. The ANM's evaluation is based on its review of the IB, the research protocol, and the information related to the IP quality per Annex 2 of Decree021-2017. (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)) (PER-109)). Additionally, to obtain trial authorization, per Decree021-2017, the INS-CTManual, and Res252-2022, the sponsor or the CRO is required to provide quality information regarding the IP in compliance with the requirements in Annex 5 of Decree021-2017. As specified in Annex 5, the following documents relating to the IP must be submitted:

Labeling information
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 Decree021-2017.

VII

Chapter VII (7.8.4), Chapter IX, and Annex 4 (Flowcharts No. 04 and No. 15)

Annex B

Requirements for Initiating the Procedure (9-10 and 13), 4.1-4.4, and Annex 9

Title I (Articles 2 and 8), Title IV (Article 40), Title V (Articles 67-70), Title IX (Article 108), and Annexes 2 and 5

Labeling

Last content review/update: October 1, 2024

Investigational product (IP) labeling in Canada must comply with the requirements set forth in the CanadaFDR, the G-CanadaCTApps, the G-GMP-Annex13, and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52). The CanadaFDR and the G-CanadaCTApps state that for an IP to be used in a clinical trial, it must be properly labeled in both official languages: English and French. The CanadaFDR requires that IPs be packaged and labelled under the supervision of personnel who have had satisfactory technical, academic, and other training. The packager and/or labeler must have written procedures and ensure that the IP is packaged, labelled, and tested in compliance with those procedures. For Health Canada (HC)’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100. Per CAN-50, Canada has CAN-52.

As delineated in the CanadaFDR and the G-GMP-Annex13, the following information must be included on the IP label:

A statement indicating that the drug is an investigational drug to be used only by a qualified investigator
Name, number, or identifying mark
Expiration date
Recommended storage conditions
Lot number
Sponsor’s name and address
Protocol code or identification
Radiopharmaceutical information, if applicable

With regard to the expiration date, the G-GMP-Annex13 further states that if it becomes necessary to change the expiration date, an additional label should be affixed to the IP. This additional label should state the new expiration date and repeat the batch number. It may be superimposed on the previous expiration date, but for quality control reasons, not on the original batch number. This operation should be performed at an appropriately authorized manufacturing site. However, when justified, it may be performed at the investigational site by or under the supervision of the clinical trial site pharmacist, or other health care professional in accordance with national regulations and with the sponsor’s requirements. Where this is not possible, it may be performed by the clinical trial monitor(s) who should be appropriately trained. The operation should be performed in accordance with good manufacturing practice (GMP) principles, specific and standard operating procedures and under contract, if applicable, and should be checked by a second person. This additional labelling should be properly documented in both the trial documentation and in the packaging records.

In addition, CAN-52 state that the IP must be coded and labeled in a manner that protects the blinding, if applicable.

5.13

Efficacy guidelines

8.7

2.8.7

5.11

Part C (Divisions 2 (C.02.006, C.02.011, C.02.015-016) and 5 (C.05.011))

Last content review/update: April 24, 2024

Investigational product (IP) labeling in Peru must comply with the requirements set forth in Decree021-2017. Labels for IPs used in a clinical trial must be 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 the Product Management section for additional information on IP supply, storage, and handling requirements).

Title VI (Article 91)

Product Management

Last content review/update: October 1, 2024

Supply, Storage, and Handling Requirements

Per CanadaFDR, drugs must be manufactured, handled, and stored in accordance with good manufacturing practice (GMP). As defined in the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CAN-52), which Canada has implemented per CAN-50, the sponsor must supply the investigator(s) with the investigational products (IP(s)), including the comparator and placebo, if applicable. The sponsor should not supply the IP(s) until approvals from Health Canada (HC) and the institutional ethics committee (EC) are obtained. CAN-52 specifies that the sponsor must ensure the following:

Timely delivery of the IP(s)
Records maintained for IP document shipment, receipt, disposition, return, and destruction
Written procedures including instructions for IP handling and storage, adequate and safe receipt of the IP(s), dispensing of the IP(s), retrieval of unused IP(s), return of unused IP(s) to the sponsor, and disposal of unused IP(s) by the sponsor
IP product quality and stability over the period of use
IP manufactured according to any application of GMP
Proper coding, packaging, and labeling of the IP(s)
Acceptable IP handling and storage conditions and shelf-life

For IP packaging, the G-GMP-Annex13 provides the following guidance:

The risk of product mix up must be minimized by using appropriate procedures, specialized equipment, and relevant staff training.
To prevent errors, particularly when IPs are blinded, use heightened precautions, such as label reconciliation, line clearance, and in-process control checks by appropriately trained staff.
The packaging must ensure that the IP remains in good condition during transport and storage at intermediate destinations; any opening or tampering of the outer packaging during transport should be readily discernible.

The G-Storage provides principles and interpretations on the environmental control of clinical trial drugs during storage and transportation, including packaging. See G-Storage for information regarding compliance with the CanadaFDA and the CanadaFDR, as it relates to packaging clinical trial drugs for human use, such as the role of environmental controls, quality risk management, and special considerations for active pharmaceutical ingredients. In addition, CAN-52 state that the IP must be packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage. Refer to CAN-52 for detailed sponsor-related IP requirements.

Record Requirements

As set forth in the CanadaFDR, the G-FDR-0100, and the CanadaFDR1024, the sponsor must record, handle, and store all trial-related information to allow complete and accurate reporting, interpretation, and verification. The CanadaFDR states that the sponsor should maintain all trial-related records for a period of 15 years. Pursuant to CanadaFDR1024, the sponsor must submit requested records to HC within 48 hours if safety concerns arise. Additionally, to facilitate inspection of a site, the sponsor must submit information to HC within seven (7) days of a request.

The G-Storage provides that when contracted parties, such as warehouses or commercial carriers, store or transport drugs, there should be a written agreement that outlines all relevant conditions.

5.5, 5.12, 5.13, 5.14, and 7

Efficacy guidelines

8.6

5.1, 5.5, 5.10, and 5.12

Regulatory Impact Analysis Statement

Part C (Division 5 (C.05.001, C.05.005, C.05.010, and C.05.012))

Last content review/update: April 24, 2024

Supply, Storage, and Handling Requirements

Per PER-53, the sponsor or the contract research organization (CRO) should supply the investigator(s)/institution(s) with the investigational products (IPs). Decree021-2017 indicates that the IPs will be dispensed through a Dispensation Unit for Clinical Trials under the Pharmacy Service or Department of the research institution where the trial will be conducted. The dispensation process must comply with the G-GSPs and G-GDPs, and study specifications agreed to by the sponsor. The Clinical Trial Dispensing unit is responsible for:

Inventorying IPs
Controlling overused, used, and unused IPs for final disposal as established in the protocol

Decree021-2017 further indicates that the sponsor or the CRO is responsible for the destruction of the unused and/or returned IP. The IP must not be destroyed without the sponsor’s or the CRO’s prior written authorization, and any discrepancy in their final accounting has been investigated, explained, and resolved. Refer to Decree021-2017 for additional IP and complementary product destruction requirements. See also PER-41 for the notification form (FOR-OGITT-059) to dispose of IPs.

Additionally, per Decree021-2017, the sponsor must fund IPs for use in trials and provide them free of charge to research participants. See the Insurance & Compensation section for additional information on participant post-trial access to IPs.

Record Requirements

Per Decree021-2017, the sponsor must also keep samples of the IPs, its manufacturing and control protocols, as well as IP records. In addition, all IP destruction procedures must be documented. The records must detail the quantities destroyed and allow the traceability of the IP.

Decree021-2017 further states that the Clinical Trials Dispensing Unit or the Pharmacy Service or Department of the research institution where the trial will be conducted is also responsible for maintaining a record of dates in which IP quantities are received/dispensed.

5.14

Title IV (Article 40), Title V (Articles 67 and 75), Title VI (Articles 92-93 and 96-98)

Definition of Specimen

Last content review/update: July 26, 2024

In Canada, a specimen is referred to as “human biological material” or “biological material.” According to the G-TCPS2, human biological materials include tissues, organs, blood, plasma, skin, serum, DNA, RNA, proteins, cells, hair, nail clippings, urine, saliva, and other body fluids. The term also comprises materials related to human reproduction, including embryos, fetuses, fetal tissues, and human reproductive materials. The G-TCPS2 breaks down human biological material further into the following categories: anonymized, anonymous, coded, and identified human biological materials. Refer to the G-TCPS2 for more detailed information on these categories.

In addition, CAN-2 defines biological material as pathogenic and non-pathogenic microorganisms, proteins, and nucleic acids, as well as any biological matter that may contain microorganisms, proteins, nucleic acids, or parts thereof. Examples include, but are not limited to, bacteria, viruses, fungi, prions, toxins, genetically modified organisms, nucleic acids, tissue samples, diagnostic specimens, live vaccines, and isolates of a pathogen (e.g., pure culture, suspension, purified spores).

Glossary

Chapter 12 and Glossary

Last content review/update: April 24, 2024

No relevant provisions are currently available that define specimens.

However, as noted in Decree021-2017, 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.

Supplementary Provisions—Final (Sixth)

Specimen Import & Export

Last content review/update: July 26, 2024

Import/Export

According to the G-HlthProdImprtExptReqs, Health Canada (HC) does not have jurisdiction over human biological materials to be imported for testing or research purposes. The G-HlthProdImprtExptReqs further states that all blood samples as well as cultures, diagnostic specimens, or research tissue are considered to be potential carriers of human or animal pathogens, and are regulated by the Public Health Agency of Canada (PHAC) and the Canadian Food Inspection Agency (CFIA). Per CAN-24, CAN-2, and CAN-9, the PHAC’s Centre for Biosecurity oversees the licensing process under the authority of the HPTA and the HPTR. The HPTA states that a license must be issued by the Minister that authorizes the import or export of human pathogens or toxins.

As specified in the HPTA, the HPTR, and CAN-2, individuals planning to conduct controlled activities (including producing, possessing, handling, using, storing, providing access to, transferring, disposing of, releasing, abandoning, or importing/exporting) with a human pathogen or toxin, whether imported or domestically acquired, must obtain a license. Per CAN-2, because all human biological materials are potential carriers of human pathogens, the PHAC has categorized these materials by risk group based on risk to the individual/animal and risk to the community. Risk Group 1 consists of microorganisms, nucleic acids, or proteins that are unable or unlikely to cause human or animal disease so they are generally not considered to be pathogens, and are therefore exempt from the HPTA and the HPTR licensing requirements. Risk groups 2 through 4 are considered to be pathogens or toxins with moderate to high individual risk and low to high community risk, and are subject to the HPTA and the HPTR licensing requirements. See CAN-2 and CAN-9 for detailed information and instructions on how to obtain a license for activities associated with Risk Groups 2 through 4.

Chapter 21

Chapters 1 and 2

Blood and blood components for transfusion

Purpose of the Act, Interpretation and Application, Obligation, Prohibitions, and Licenses

Licenses

Last content review/update: April 24, 2024

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

However, as noted in Decree021-2017, 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.

Supplementary Provisions—Final (Sixth)

Consent for Specimen