National Institute of Health (INS)

As per Decree021-2017 and the G-CTInspec, Peru’s National Institute of Health (Instituto Nacional de Salud (INS)) is the regulatory authority responsible for clinical trial approvals, oversight, and inspections. The INS, through the General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)), grants permission for clinical trials to be conducted in Peru in accordance with Decree021-2017, the INS-CTManual, and Res252-2022 (which amends the INS-CTManual).

As indicated in Law27657, Decree001-2003, PER-64, and PER-75, the INS is a decentralized public executive agency within the Ministry of Health of Peru (Ministerio de Salud del Perú (MINSA)), and was granted authority to approve clinical trials by the MINSA in 2003. PER-75 further explains that the OGITT and the Executive Office of Investigation (Oficina Ejecutiva de Investigación (OEI)) are jointly responsible for carrying out the INS’s mission. As the INS’s public executing agency, the OEI establishes the administrative and technical procedures for the evaluation, approval, and financing for the development of observational biomedical research.

Decree021-2017, the INS-CTManual, and PER-74 explain that the INS’s OGITT carries out the INS’s mandate to authorize and supervise the conduct of clinical trials to ensure the quality and integrity of the data or other elements related to the trial; to protect the rights and well-being of research subjects; to ensure the safety of the investigational products used in the trials; and to establish procedures within the framework of Decree021-2017, the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (PER-53), and other applicable national and international standards and regulations. In addition, according to Decree001-2003, PER-75, and PER-65, the OGITT, through the OEI, implements the INS’s objectives to promote, develop, disseminate and manage scientific and technological research; establish administrative and technical procedures related to biomedical research; propose health research and technology transfer policies and guidelines, and provide health services to the Peruvian population. For information on OGITT’s role in clinical trial inspections, see Title XI of Decree021-2017 and the G-CTInspec. According to PER-74 and PER-75, the OGITT is also responsible for organizing and maintaining the Peruvian Clinical Trials Registry (Registro Peruano de Ensayos Clínicos (REPEC)) (PER-89) (also referred to as REPECv2), the national registration system for clinical trials, institutional ethics committees (ECs) (los Comités Institucional de Ética en Investigación (CIEIs)), research sites, and contract research organizations (CROs). Refer to the Scope of Assessment, Submission Process, and Initiation, Agreements & Registration sections for additional information on PER-89.

National Authority for Pharmaceutical Products, Medical Devices and Medical Products (ANM)

As described in Decree016-2011, as a decentralized body of MINSA, the National Authority for Pharmaceutical Products, Medical Devices and Medical Products la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM))’s fundamental objective is to ensure the Peruvian population has access to safe, effective, and quality medicines that are used rationally. Pursuant to Decree021-2017 and Decree016-2011, the ANM is responsible for issuing binding technical opinions on the safety and quality of investigational products (IPs) according to the stage and type of research; evaluating research protocols for bioequivalence studies to demonstrate interchangeability as part of the requirement for health registration in the country; authorizing, exclusively for research purposes, the import or manufacture of IPs and complementary products; and authorizing the use of an IP under post-study access conditions. Per Decree016-2011, the ANM also authorizes the importation, manufacture, and use of pharmaceutical products or medical devices without granting a sanitary registration for use in emergency or declared emergency situations. The ANM’s other responsibilities center on regulating, developing, promoting, monitoring, supervising, and evaluating the Peruvian System of Pharmacovigilance and Technovigilance (Sistema Peruano de Fármacovigilancia y Tecnovigilancia). (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)).

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.

Contact Information

National Institute of Health (INS)

According to PER-63, the INS contact information is as follows:

Instituto Nacional de Salud
Cápac Yupanqui 1400 - Jesus María
Lima 11
Peru
Phone: (511) 748 1111

or

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

General Office for Research and Technology Transfer (OGITT)

According to PER-13, PER-58, and PER-63, the INS’ OGITT contact information is as follows:

Instituto Nacional de Salud
Oficina General de Investigación Y Transferencia Tecnológica
Sede Chorrillos
Av. Defensores del Morro 2268 (Ex Huaylas) - Chorrillos
Lima 9
Perú

Clinical Trial Phone: 511 748 1111 (Ext. 2191)
Clinical Trial Email: consultaensayos@ins.gob.pe

General Phone: (511) 748 1111
Email: webmaster@ins.gob.pe

Phone: (511) 748 1111 Extension: 2616
Email: jparillo@ins.gob.pe

National Authority for Pharmaceutical Products, Medical Devices and Medical Products (ANM)

PER-109 indicates the ANM’s contact information is as follows:

DIGEMID
Av. Parque de las Leyendas 240
San Miguel
Perú

Phone: (511) 631-4300 Extension: 6700 and 6705
Email: atenciontramite@minsa.gob.pe

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 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, the INS-CTManual, and Res252-2022, the INS’s 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 as part of its application review and approval process. However, the INS must still approve the clinical trial application prior to the ANM’s approval of an 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 OGITT’s 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 technical report 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 OEI’s Legal Advice Functional Team (Equipo Funcional de Asesoría Jurídica (EFAJ)) who prepares a report for the OEI Executive Director’s review.

The OEI 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 OGITT General Directorate, 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 OGITT 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.

Decree021-2017, the INS-CTManual, and Res252-2022 also note that the INS’s OEI 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 OGITT 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 OGITT 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. 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
• 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

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

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, 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

No information is currently available regarding clinical trial application fee payment instructions.

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.

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)

According to PER-77, 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 not accredited to approve clinical trials (See PER-102 for a list of accredited ECs). As described in PER-94, the CIEI-INS 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. See PER-94 for additional information on the CIEI-INS.

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.

Other Ethics Committees Conducting Human Health Research

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.

Other Ethics Committees Conducting Human Health Research

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 decisions adopted 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.

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 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 General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)) of the suspension or cancellation.

PER-96 also states that when these documents (research protocol, protocol amendments, and ICF) are evaluated in person, the EC’s stamp should be used on each page, and when the documents are evaluated virtually, the EC’s scanned or electronic stamp should be used on each page.

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

Fees are determined by each accredited institutional ethics committee.

Overview

As set forth in Decree021-2017, the INS-CTManual, and PER-61, the National Institute of Health (Instituto Nacional de Salud (INS))’s General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)) 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 OGITT 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 OGITT 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. (See PER-85 for accreditation/renewal application form FOR-OGITT-025.) In addition to completing PER-85, 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 OGITT 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 OGITT to conduct EC registration evaluation in compliance with Res233-2020. As specified in the G-ECRegProcs, the OGITT’s 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 OGITT 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 OEI. Once the favorable response report has been received, the OEI evaluates and endorses it, sending the report and draft record of registration to the OGITT. The OGITT General Directorate 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 implementing the progressive registration requirements within the two-year term.

Refer to G-ECRegProcs for additional information on the OGITT’s registration review and approval process.

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 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 REPEC.

Additionally, as specified in PER-89, the REPEC platform should then 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. 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. See the Submission Content section for detailed documentation requirements.

Electronic (MPV) 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. (Note: As per PER-77, PER-106 may not be accessible to users residing outside of Peru. Users can contact Jenny Parillo at jparillo@ins.gob.pe for assistance with accessing the platform.) 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.

Per the INS-CTManual and Res252-2022, for all submission files deemed complete, a unique file registration number corresponding to the specific procedure or communication is assigned in SIGANET, the INS’s integrated administrative management system. Res252-2022 notes that the authorization request procedure is formally initiated when the sponsor is provided with the file registration number. An identification number is also assigned to the clinical trial in PER-89 at this time.

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.

(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 also PER-6 for a flowchart delineating the clinical trial authorization process.

Ethics Review Submission

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

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: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

• 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: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• 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.

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)).

In addition, per Res252-2022, if any corrections to a clinical trial application submission are required by the OGITT’s Document Processing Office, the applicant will have two (2) business days to amend the application, and this time will not be counted towards the period allotted for the OGITT’s review. If the two (2)-day timeframe is exceeded, the application will be discarded, and another application must be submitted to initiate the process again.

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.

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 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 OGITT 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.

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: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• 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 to 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 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 OGITT. 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, PER-66, 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 OGITT within seven (7) calendar days from the occurrence of the incident, or as soon as the sponsor is aware of the incident. The G-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 OGITT.

In addition, per Decree021-2017, Decree021-2017-Correct, and PER-72, the sponsor or the CRO must notify the OGITT, the ECs, and the PIs within a maximum period of seven (7) calendar days of any findings that could adversely affect the safety of research participants, have an impact on the conduct of the study, or alter the benefit/risk balance. This report should be prepared independently and separately from other required AE/AR submission deadlines outlined in this subtopic. Decree021-2017, Decree021-2017-Correct, PER-4, and PER-12 further state that the sponsor or the CRO is also required to notify the OGITT 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. PER-12 further specifies that this notification should be submitted using the online form, 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). See also PER-31 to submit an application for research site closure or to cancel a clinical trial via REPEC.

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 OGITT through a detailed report that includes the measures and actions taken at the local and international levels, if already established. The ECs and PI should also be notified within seven (7) calendar days. The information must be written in Spanish and English, be contained in an electronic medium (CD), and be presented in the OGITT’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 OGITT and the Council for International Organizations of Medical Sciences (CIOMS) whether they have occurred in the authorized trial, in other trials with the same IP, or in a context of different use. The G-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 OGITT must notify the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) of any SAEs/SADRs and SUSARs caused by an IP being used in an authorized trial in Peru within a maximum period of 15 working days after receiving notification about the incident. The INS-CTManual also indicates authorized ANM personnel will have access to SAEs/SADRs and SUSARs that have occurred in Peru via REAS-NET (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 OGITT 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 OGITT. Decree021-2017 further specifies that the DSUR should be sent to the OGITT 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 the online form (FOR-OGITT-048) (PER-45) in Spanish as well as submit a copy of the DSUR to the OGITT 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 OGITT 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, PER-66, 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). Refer to PER-38 for the OGITT 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 OGITT.

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 him/her 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.

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 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.

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

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 OGITT 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 OGITT will send a copy of the final national report of clinical trials to the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) within 30 business days following receipt of the report. (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 OGITT and notify OGITT 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.

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 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.

Overview

Per Decree021-2017, the National Institute of Health (Instituto Nacional de Salud (INS))’s General Office for Research and Technology Transfer (Oficina General de Investigación y Transferencia Tecnológica (OGITT)), 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 (GCPs) 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 site 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 sites to register with REPEC (PER-89) to carry out clinical trials at the research institution’s request. According to PER-73, research sites should also 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 site registration is valid for three (3) years. Refer to PER-73 for detailed registration instructions and PER-90 for a research site registration checklist.

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 OGITT 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.

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 (FOR-OGITT-029) (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 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.

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 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 OGITT, 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 OGITT trial inspections, including direct access to clinical trial documentation
• Provide plans to enter, encode, protect, and save data, including any process to improve its quality
• Specify where data management procedure details not included in the protocol can be found

No specific timeframe is provided for the audit process.

The G-CTInspec explains that the INS’s OGITT 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 OGITT’s Annual Schedule of Ordinary Inspections. Extraordinary inspections are performed in response to a complaint received by phone, written communication, formal document submitted through the INS reception desk, or from any relevant information received through safety reports, progress reports, and/or a justified request by a clinical trial evaluation team that has obtained OGITT approval. If required, the OGITT coordinates with the National Authority for Pharmaceutical Products, Medical Devices and Medical Products (la Autoridad Nacional de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios (ANM)) for the agency’s assistance in verifying compliance with good manufacturing practices standards, good storage practices, and other 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 OGITT of the date and time of this visit within five (5) business days of receiving the notification. The OGITT will then coordinate with the regulatory medicines agency of high health surveillance to arrange for their participation in the inspection visit as an observer.

Per the INS-CTManual, for regular clinical trial inspections scheduled by the INS’s OGITT, when inspection findings are critical, the sponsor or 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 OGITT scheduled clinical trial inspections and responding to the inspection reports received.

Per Decree021-2017, Res064-2021, and the G-CTSanction, in the event of an OGITT 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 this 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 OGITT’s 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 OEI 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 OEI is prepared within no more than 15 business days and submitted to the OGITT. Once the report is received, within a maximum term of 15 business days, the OGITT 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 OGITT 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 OGITT 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, FOR-OGITT-040, and PER-30 for the clinical trial suspension application form, FOR-OGITT-041.

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.

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-2 and PER-3 for additional information on Law29733, and PER-99 and PER-101 for information on RegDir294-2020.

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-96 and PER-83 further specify that the sponsor or the contract research organization (CRO) must provide a 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 and/or the legal representative(s) or guardian(s). The ICF content should be presented briefly and clearly in writing, in a manner that is easy to understand, commensurate with the comprehension level of the research participants, and without coercion or unduly influencing a potential participant to enroll in the clinical trial. The participant and the legal representative(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s) is required to sign a revised ICF if any changes occur in the protocol or in the treatment methods or procedures.

Language Requirements

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

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: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

• Trial title (include version and date)
• Sponsor(s), research institution, principal investigator (PI), 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 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.

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(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s) has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study.

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 and/or the legal representative(s) or guardian(s) should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries 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.

No information is currently available.

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

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.

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 representative(s) or guardian(s) is required. Per Decree021-2017, the consent of the legal representative(s) or guardian(s) may only be dismissed in the case of death, loss of rights according to Decree requirements, or proven impossibility to obtain consent has been documented appropriately. In the event that one (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 representative(s) or guardian(s) at any time, provided that the child’s health will not be jeopardized. A minor who is a teenager must also be excluded from a trial when a conflict of views exists between the legal representative(s) or guardian(s) and the teenager. A minor who reaches the age of majority during a trial must provide consent before continuing to participate in the study.

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 participant’s or spouse’s or partner’s request at any time, without detriment to them, provided they do not affect or endanger the mother or the fetus or infant
• The clinical trial has the potential to generate direct benefits greater than the risks to the nursing woman or child after birth

See Title III (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

No information is currently available.

The Peruvian government recently passed Law30947 to establish a legal framework that guarantees access to services, promotion, prevention, treatment and rehabilitation in mental health as conditions for the full exercise of the right to health and well-being of the person, the family, and the community. The law states that mental health care takes into account the model of community care as well as respect for human rights and the dignity of the individual, without discrimination and using the intercultural approach, which eliminates the stigmatization of people with mental health problems. Some of the principles addressed in 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(s) or guardian(s) decides on their behalf to allow them to participate per the requirements specified in Law1384, which amends Law295. The legal representative(s) or guardian(s) should be over 18 years of age. When no support has been designated and there is no representation for a mentally incapacitated person, the decision regarding participation in a clinical trial will be made by the person’s legal representative(s) or guardian(s) 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(s) or guardian(s).

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(s) or guardian(s) 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 and/or the legal representative(s) or guardian(s)

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(s) or guardian(s) are in place that comply with Law1384, which amends Law295. According to Law1384, any legal representative(s) or guardian(s) designated prior to a person becoming comatose will be upheld. However, for those persons who have not designated a legal representative(s) or guardian(s), a judge shall designate the necessary supports and safeguards. This measure will only be taken after efforts have been made to obtain the person’s consent and when the designation of legal representative(s) or guardian(s) is necessary for the exercise and protection of the participant's rights.

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.

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 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 OGITT 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.

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 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 OGITT 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 Documentation

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.

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).

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 Ministry of Health of Peru (Ministerio de Salud del Perú (MINSA))’s 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.

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.

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.

In accordance with Decree021-2017, if a clinical trial team is considering the collection and storage of biological samples for future use, this point should be delineated explicitly in a separate informed consent form (ICF).

Annex 4 of Decree021-2017 and the G-EC-CTRev also state that the ICF must list the following biological sample study procedures:

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

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

In addition, Annex 4 of Decree021-2017 and the G-EC-CTRev specify that in the event a research participant withdraws their informed consent, the ICF must explain how the participant’s rights to privacy and confidentiality in the handling of their biological data and samples will be upheld.

Further, as set forth in Decree021-2017, when a clinical trial is to be conducted in indigenous peoples in Peru and the storage of biological samples is being considered, authorization must be obtained from the corresponding regional and local government, and of the respective community authorities, who must consider the interest of the community involved.

Per Law27337, children and adolescents are also guaranteed protection from experiments or genetic manipulations contrary to their integrity and their physical or mental development.

As noted in 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.