Clinical Research Regulation For Kenya and Mexico

Last content review/update: July 2, 2024

Overview

In accordance with the PPA, the CTRules, the G-KenyaCT, and KEN-21, Kenya’s Pharmacy and Poisons Board (PPB), together with its Expert Committee on Clinical Trials (ECCT), is responsible for reviewing, evaluating, and approving applications for clinical trials using registered or unregistered investigational products (IPs). The G-KenyaCT specifies that the scope of the PPB’s assessment includes all clinical trials (Phases I-IV). As delineated in the CTRules, the G-KenyaCT, and KEN-21, the PPB review and approval process may not be conducted in parallel with the ethics committee (EC) review. Rather, EC approval must be obtained prior to applying for PPB approval. As delineated in the STI-Act and G-ECBiomedRes, the principal investigator or the head of a research institution must obtain a favorable opinion from an EC accredited by the National Commission for Science, Technology and Innovation (NACOSTI) and a NACOSTI research license prior to initiating a study.

Clinical Trial Review Process

Pharmacy and Poisons Board

Per the CTRules and the G-KenyaCT, the PPB, through the ECCT, communicates the decision to approve, request additional information, or reject the application to the sponsor or the representative in writing within 30 working days of receiving a valid application. The G-KenyaCT indicates that in the case of rejection, the applicant may appeal and provide additional information to satisfy PPB requirements. In specific cases, the PPB may decide to refer the matter to external experts for recommendation.

As specified in the G-KenyaCT, each ECCT member, prior to reviewing the application, will declare any conflict of interest in the study and should have no financial or personal interests, which could affect their impartiality. During the protocol review, the reviewers must use the standard criteria (including available clinical and non-clinical data etc.) defined by the PPB. Confidentiality must be maintained during the review. Per the CTRules and the G-KenyaCT, the PPB/ECCT’s review must consider:

The reliability and robustness of the data generated in the clinical trial, taking into account statistical approaches, design of the clinical trial, and methodology, including sample size and randomization, comparator, and endpoints
Compliance with the requirements concerning the manufacturing and import of IPs and auxiliary medicinal products
Compliance with the labelling requirements
The completeness and adequateness of the investigator's brochure

Regarding protocol amendments, the CTRules and the G-KenyaCT stipulate that any new information affecting the conduct/management of the trial, safety of the participants, and manufacture of the IP necessitating changes to the protocol, consent form, and trial sites require immediate submission of the amended documents to PPB for review and approval. Arrangements must be in place to take appropriate urgent safety measures to protect participants against any immediate hazard where new events relating to the conduct of the trial, or the development of the IP are likely to affect the safety of the participants. A copy of a favorable opinion letter from the EC on record must be submitted with the request for approval of a proposed amendment to the PPB. PPB approval must be obtained for all substantial amendments. Minor amendments or administrative changes may be implemented after getting the EC’s approval, but a record of these amendments must be kept for possible inspection by the PPB. See Submission Process and Submission Content sections for additional details on amendment submissions. Also, see the G-KenyaCT for examples of substantial amendments.

In addition, per the G-KenyaCT, the sponsor or the representative is required to request approval annually from the PPB at least six (6) weeks prior to the expiration of the previous approval.

Per the CTRules and the G-KenyaCT, the PPB may withdraw the authorization to conduct a clinical trial if it finds that the safety of the participants in the trial is compromised or that the scientific reasons for conducting the trial have changed. Additionally, per the CTRules, the PPB may revoke the approval if it determines that the IP has expired or is not usable.

As delineated in the G-KenyaCT, the PPB may inspect clinical trial sites to ensure that the generally accepted principles of good clinical practice (GCP) are met. The objectives of the inspection are to:

Ensure that participants are not subjected to undue risks and that their rights, safety, and wellbeing are protected
Validate the quality of the data generated
Investigate complaints
Verify the accuracy and reliability of clinical trial data submitted to the PPB in support of research or marketing applications
Assess compliance with PPB guidelines and regulations governing the conduct of clinical trials
Provide real-time assessment of ongoing trials

Per CRO-Inspect, the PPB is responsible for inspecting clinical trial and bioequivalence study sites that generate data for registration of medicines. The PPB requires that these sponsor and contract research organization sites comply with applicable good practices, including GCP, good laboratory practice (GLP), and good documentation practices. Based on risk assessments, the PPB will determine compliance with generally accepted good practice through inspections and, where appropriate, document reviews. In addition, see Cert-Emrgcy for information about GCP and good manufacturing practice certifications during emergencies.

Special Circumstances and Public Health Emergencies

The CTRules delineates that the PPB may, in special circumstances, authorize the conduct of a clinical trial under fast-track procedures or non-routine procedures. PPB may recognize and use clinical trial decisions, reports, or information from other competent authorities authorizing fast-track clinical trials. The special circumstances may include:

A public health emergency
The rapid spread of an epidemic disease
Any other circumstance as may be determined by the PPB

The G-KenyaCT outlines PPB’s scope of assessment of a clinical trial application during a public health emergency. The PPB will conduct an expedited review and liaise with relevant stakeholders (including relevant ECs and other oversight bodies) to facilitate a holistic review of an application in a fast-track manner. The following prioritization criteria must be applied in the selection of applications for expedited review:

Epidemiology of the emergency
Morbidity and mortality associated with the emergency and/or condition under study
Supporting scientific data/information available for the IP at the time of submission
Feasibility of the implementation of the trial design within the context of the emergency
Benefit impact of the intervention and/or trial design

In addition, PPB’s assessment will consider the following:

The research does not compromise the response to an outbreak or appropriate care
Studies are designed to yield scientifically valid results under the challenging and often rapidly evolving conditions of disasters and disease outbreak
The research is responsive to the health needs or priorities of the disaster victims and affected communities and cannot be conducted outside a disaster situation
The participants are selected fairly and adequate justification is given when particular populations are targeted or excluded, for example, health workers
The potential burdens and benefits of research participation and the possible benefits of the research are equitably distributed
The risks and potential individual benefits of experimental interventions are assessed realistically, especially when they are in the early phases of development
Communities are actively engaged in study planning to ensure cultural sensitivity, while recognizing and addressing the associated practical challenges
The individual informed consent of participants is obtained from individuals capable of giving informed consent
Research results are disseminated, data are shared, and any effective interventions developed or knowledge generated are made available to the affected communities

National Commission for Science, Technology and Innovation

STI-Act stipulates that NACOSTI issues research licenses if it finds that the conduct of the research is beneficial to the country and will not adversely affect any aspect of the nature, environment, or security of the country. The license issued will have NACOSTI’s seal and will indicate the commencement and expiration of the research. In addition, NACOSTI maintains a register of all persons granted a license, which is available for public inspection during normal working hours free of charge.

KEN-31 states that if a research license application does not meet the conditions required under the STI-Act, NACOSTI must reject the application and communicate the reasons to the applicant. Any person may appeal NACOSTI’s decision to the Cabinet Secretary within 30 days of being notified of the decision. For approved research, NACOSTI may conduct an evaluation to assess compliance with the conditions of the license. If the research project has not been completed within the stipulated period, the researcher may apply for renewal of the license and pay the requisite fee. The researcher is expected to apply for renewal by attaching a progress report instead of a proposal. KEN-31 indicates that the duration of the research license is one (1) year.

Forward and 1

Glossary of Terms, Introduction, 1.1, 1.7-1.25, 1.189, 1.492-1.506, 1.519-1.534, 1.557-1.574, and Annex 7

3A, 3B, and 25A

Part IV

Part II (Sections 4 and 5), Part IV (Sections 11 and 18), and Part V (Sections 19 and 23)

Last content review/update: November 8, 2024

Overview

In accordance with GenHlthLaw, Reg-COFEPRIS, HlthResRegs, NOM-012-SSA3-2012, and COFEPRIS-GCP, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is the regulatory authority responsible for reviewing, evaluating, and approving all requests for research protocol authorization in human beings and/or their biological samples using registered or unregistered investigational products (IPs). Per NOM-257-SSA1-2014, COFEPRIS requires biotechnological drugs used in clinical research studies to follow the same protocol authorization procedure as is required for all IPs. COFEPRIS-GCP and HlthResRegs specify that the scope of COFEPRIS’s assessment includes all clinical trials (Phases I-IV).

As indicated in HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, COFEPRIS’s review and approval of a protocol authorization request is dependent upon obtaining a favorable decision from the health institution’s Research Ethics Committee (REC) and Research Committee where the study is being conducted, and when applicable, the Biosafety Committee. Therefore, the COFEPRIS and EC reviews may not be conducted in parallel. In addition, per NOM-012-SSA3-2012, the REC’s favorable decision is only later submitted to COFEPRIS with the protocol authorization request. Refer to the Ethics Committee section for detailed information on the REC, and the Initiation, Agreements & Registration section for additional information on the Research Committee and Biosafety Committee.

Clinical Trial Review Process

As delineated in Reg-COFEPRIS and MEX-53, COFEPRIS’s Sanitary Authorization Commission (Comisión de Autorización Sanitaria (CAS)) is responsible for recording, evaluating, and issuing opinions on requests for human research protocol authorizations. According to MEX-104, CAS’s work is performed by its protocols area. Per MEX-15, CAS’s technical/protocols area conducts its work via COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37), a public service system established by the Mexican government to facilitate the processing of the agency’s standardized procedures and services.

As indicated in G-HumResProt and G-ResProtocolAmd, the applicant must submit an application to the CIS (MEX-37) to request protocol authorization or modification/amendment of a protocol authorization, and the application is then forwarded to CAS’s technical/protocols area for evaluation. (Note: COFEPRIS refers to applications as requests or procedures). Per G-HumResProt, the designated evaluator reviews and evaluates the information, comparing the information presented to assess whether it complies with current Mexican legislation on the matter. The information is also evaluated for completeness and accuracy and is reviewed to detect deficiencies or anomalies in the documentation or in the study process. Once the evaluator issues a resolution of authorization or a prevention letter, it is forwarded to the head of CAS for signature.

Following its review of the application documentation, per G-HumResProt and G-ResProtocolAmd, CAS’s technical/protocols area issues an official resolution of authorization or a prevention letter (in which additional or missing information is requested). If authorized, the clinical study may begin. However, if a prevention letter is received, the applicant must respond to what is stated in the letter and resubmit a request for continued processing after addressing all of the issues raised. CAS’s technical/protocols area will issue a final resolution following resubmission of the application for protocol authorization or modification/amendment. G-HumResProt also indicates that for in-person submissions, applicants can go to the CIS (MEX-37) to obtain the resolution.

G-ResProtocolAmd specifies that protocol modifications may be submitted to amend the research protocol, amend the informed consent/assent form, update the clinical and/or preclinical sections of the investigator’s brochure (also known as investigator’s manual in Mexico), remove or add research center(s)/research institution(s), or provide updated clinical and/or preclinical security/safety IP information. Refer to G-ObsrvStdies information on submitting applications to conduct risk-free research (observational studies), and G-BioequivStud for information on submitting applications to conduct bioequivalence studies.

Additionally, as indicated in G-DIGIPRiS-ResProts, once an official authorization from COFEPRIS is obtained, some of the data provided by the applicant via COFEPRIS’s digital procedures and services platform, DIGIPRiS: Online Regulation (MEX-86), will be migrated to the CIS (MEX-37) and to the National Registry of Clinical Trials (Registro Nacional de Ensayos Clínicos (RNEC)) database (MEX-68). According to MEX-109, the G-RNECManual is useful for information on registering with RNEC for clinical trial applications submitted in person at the CIS (MEX-37). See also G-DIGIPRiS-DocComp for instructions on validating and comparing resolutions issued through DIGIPRiS (MEX-86) for research protocols). See Submission Process section for detailed DIGIPRiS (MEX-86) submission requirements.

Reg-HlthProd further explains that applicants must submit a request to COFEPRIS to obtain a sanitary registration for biosimilar biotechnological drug products. The specific requirements for the approval of each biosimilar biotechnological drug (e.g., in vitro studies, preclinical study reports, and comparative pharmacokinetic study reports) will be determined by the Ministry of Health, who will take into consideration the opinion of the Committee of New Molecules. When there is no relevant information in the Pharmacopoeia of the United Mexican States (Farmacopea de los Estados Unidos Mexicanos (FEUM)) and its supplements, nor in national guides or monographs, the Ministry may evaluate biosimilar tests using clinical data obtained from biosimilar biotechnological drug studies conducted in other countries. However, clinical trials are required to be conducted in Mexico when an applicant requests the renewal of an approval for a biosimilar biotechnological drug product. According to MEX-91, COFEPRIS’s acceptance of data produced abroad will accelerate the introduction of biosimilar drug products into Mexico. Additionally, per MEX-120, COFEPRIS has implemented modifications to NOM-177-SSA1-2013, the standard which establishes the tests and procedures to demonstrate that generic drugs or biosimilar biotechnological drugs comply with established interchangeability tests and delineates requirements for the authorized third parties that perform these tests. Pursuant to NOM-177-SSA1-2013-Mod, the modification expands the standard to include studies that are carried out in Mexico as well as in other countries to demonstrate interchangeability and biocomparability. MEX-120 also notes the modifications in NOM-177-SSA1-2013-Mod are designed to expedite the registration of generic and biosimilar biotechnological drugs. See NOM-177-SSA1-2013 and NOM-177-SSA1-2013-Mod for details.(Note: In Mexico, biosimilar is also referred to as biocomparable.)

UHAP Evaluations

Per HlthResRegs, prior to submitting an authorization request, applicants may also obtain a pre-assessment evaluation by an authorized third party that helps to facilitate COFEPRIS’s review. MEX-21 and MEX-10 explain that rather than submitting the application directly to the CIS, the applicant has the option of first choosing to obtain a pre-assessment (third party) evaluation of the application through an Enabled Pre-Assessment Support Unit (Unidad Habilitada de Apoyo al Predictamen (UHAP)) (MEX-69) within the Coordinating Commission of National Institutes of Health and High Speciality Hospitals (Comisión Coordinadora de Institutos Nacionales de Salud y Hospitales de Alta Especialidad (CCINSHAE)) (referred to as the UHAP-CCINSHAE) or a UHAP within the Mexican Social Security Institute (Instituto Mexicano del Seguro Social (IMSS)). MEX-9 states that the CCINSHAE oversees (12) UHAPs. According to MEX-90, the Faculty of Medicine of the Autonomous University of Nuevo León (Facultad de Medicina de Universidad Autónoma de Nuevo León (UANL)) UHAP is another third-party unit authorized by COFEPRIS to assist in the evaluation and assessment of human research protocols. Refer to MEX-19, MEX-69, and MEX-70 for detailed information on the CCINSHAE, the IMSS, and the UANL UHAP application submission requirements and evaluation process. See also HlthResRegs for information on the third party authorization process by the Secretariat, and MEX-10 and MEX-121 for additional information on authorized third parties. See Timeline of Review section for timeline information on submitting UHAP applications.

According to MEX-10, the UHAP has a maximum of 30 calendar days to respond to an evaluation request. See the Scope of Assessment and Submission Process sections for detailed UHAP information.

1-2

In More Detail

9.2

What is a Comprehensive Service Center?

“Process for handling procedures 04-010 and 09-012 in DIGIPRiS”

XIII. Specific Sections of the Procedure on the Platform (IX and XI-XIII)

Requirements and Steps

Requirements (13-15, 26, and 40), Validity, and Steps

Preamble, 1.3, 1.7, and 2

Title II (Chapter II, Article 17 Bis), Title III (Chapter III, Article 41 Bis), Title V (Chapter I, Articles 98 and 102), and Title XVI (Chapter III, Article 391 Bis)

Chapter I (Articles 1-3) and Chapter IV (Article 14)

Article 177

Title II (Chapter I, Article 14), Title III (Chapter I, Article 62) and (Chapter II, Articles 65-66, and 69), and Title V (Chapter I, Articles 99, 102, and 109-111)

2.1-2.2

7

4.2, 5.2, 6.3, 9.2, and 10.3

Regulatory Fees

Last content review/update: July 2, 2024

Pharmacy and Poisons Board

Per the PPA and the G-KenyaCT, the sponsor or the representative is responsible for paying a fee to the Pharmacy and Poisons Board (PPB) to submit a clinical trial application for authorization. The PPB currently requires a non-refundable application fee of $1,000 USD, or the equivalent in Kenya Shillings at the prevailing bank rates.

Payment Instructions

As stated in Annex 2 of the G-KenyaCT, payment is to be made by a bank check payable to the “Pharmacy and Poisons Board” and presented to the PPB’s accounts office upon submitting the application.

Payment can also be made by electronic fund transfer (EFT) to the PPB Bank account, if required. The sponsor or the representative is responsible for all bank charges associated with the EFT. Details of the EFT payment should be obtained from the PPB prior to initiating such a transaction.

National Commission for Science, Technology and Innovation

As delineated in KEN-31, the National Commission for Science, Technology and Innovation (NACOSTI) charges a fee that varies depending on the applicant’s status as Kenyan or non-Kenyan, and standing as a researcher (i.e., student, public/private institution, private company). The fees are non-refundable and also apply to research license renewals. Details on additional requirements are provided in the Submission Content section.

Student, Undergraduate/Diploma: East African Community (EAC) Countries – 100 Kenya Shillings; Kenyan Citizens – 100 Kenya Shillings; Rest of Africa – 200 Kenya Shillings; Non-Africans - $150 USD
Research (Masters): EAC Countries – 1,000 Kenya Shillings; Kenyan Citizens – 1,000 Kenya Shillings; Rest of Africa – 2,000 Kenya Shillings; Non-Africans - $350 USD
Research (PhD): EAC Countries – 2,000 Kenya Shillings; Kenyan Citizens – 2,000 Kenya Shillings; Rest of Africa – 4,000 Kenya Shillings; Non-Africans - $400 USD
Post-Doctoral: EAC Countries – 5,000 Kenya Shillings; Kenyan Citizens – 5,000 Kenya Shillings; Rest of Africa – 10,000 Kenya Shillings; Non-Africans - $500 USD
Public Institutions: Kenyan Citizens – 10,000 Kenya Shillings
Private Institutions, Commercial/Market Research, Companies: Kenyan Citizens – 20,000 Kenya Shillings

See KEN-31 for information on service charges.

Payment Instructions

Per KEN-31, NACOSTI has migrated payment services for research licensing to the eCitizen platform (KEN-12). East African citizens have the following payment options on KEN-12 with a Kenya Shillings account: mobile money via Mpesa Express or Paybill Number 222222; or these other available payments via KEN-12:

Airtel Money
Kenya Commercial Bank
Co-operative Bank
Pesaflow Direct
National Bank
RTGS

KEN-31 indicates that non-Kenyans should use the US Dollar account on KEN-12 with these payment options:

Kenya Commercial Bank (USD)
Co-operative Bank (USD)
NBK (USD)
Equity Cash
Debit/credit/prepaid card

1.7-1.12 and Annex 2

3A and 25A

Last content review/update: November 8, 2024

Federal Commission for the Protection Against Sanitary Risks (COFEPRIS)

As indicated in G-HumResProt, G-BioequivStud, G-ObsrvStdies, G-ResProtocolAmd, MEX-84, G-DIGIPRiS-ResProts, the applicant is responsible for paying a non-refundable fee (also referred to as “Proof of Payment of Rights”) to submit a request for protocol authorization to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)).

According to MEX-37 and MEX-15, applicants may obtain the fee information for a specific procedure or service using COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37). Per MEX-15, CIS is a public service system established by the Mexican government to facilitate the processing of the agency’s standardized procedures and services. MEX-15 and MEX-37 indicate that applicants may call CIS (MEX-37) or schedule an appointment for assistance with determining the COFEPRIS procedure code to obtain the correct processing instructions and fees and for help with submitting the payment. See MEX-37 and MEX-15 for information on scheduling an appointment with CIS.

G-HumResProt, G-BioequivStud, G-ObsrvStdies, G-ResProtocolAmd, and MEX-11 provide requirements and corresponding costs to submit requests to COFEPRIS for protocol authorizations or amendments/modifications. The costs linked to these procedures are as follows:

Request for authorization of research protocol in humans for medicines, biological, and biotechnological: 7,553.00 Mexican Pesos (G-HumResProt and MEX-11)
Authorization of research protocol in humans (bioequivalence studies): 7,553 Mexican Pesos (G-BioequivStud)

Authorization of research protocol without risk (observational) in humans: 7,553.00 Mexican Pesos (G-ObsrvStdies)
Amendment or modification to the research protocol or inclusions to the protocol: 5,665 Mexican Pesos (G-ResProtocolAmd and MEX-11)

In addition, per G-UnregDrugImprts, the fee to request a health permit to import investigational products for research purposes is 6,727.65 Mexican Pesos.

As indicated in MEX-10, the fee for requesting a pre-assessment application evaluation through an Enabled Pre-Assessment Support Unit (Unidad Habilitada de Apoyo al Predictamen (UHAP)) (MEX-69) within the Coordinating Commission of National Institutes of Health and High Speciality Hospitals (Comisión Coordinadora de Institutos Nacionales de Salud y Hospitales de Alta Especialidad (CCINSHAE)) (referred to as the UHAP-CCINSHAE) is 60,000 Mexican Pesos. The cost is the same for obtaining a review from any of the UHAPs within CCINSHAE. In addition, if the applicant selects a scientific committee within an institution that has a UHAP, the cost is 40,000 Mexican Pesos. The cost for each amendment is 3,500 Mexican Pesos, and corrections to the pre-assessment document are free.

Payment Instructions

As explained in MEX-50, G-HumResProt, G-BioequivStud, G-ObsrvStdies, and G-ResProtocolAmd, applicants should make payments for these procedures and services through an authorized credit institution using E5cinco (MEX-52). (See also MEX-52 for a link to participating financial institutions). Per MEX-50 and MEX-52, E5cinco is an electronic scheme created to enable users to submit the Payment of Rights, Products and Benefits (Derechos, Productos y Aprovechamientos (DPAs)) to a participating credit institution through its Internet portal or banking window. See also MEX-51 and MEX-6 for detailed DPA payment instructions via E5cinco (MEX-52).

In addition, G-HumResProt, G-BioequivStud, G-ObsrvStdies, G-ResProtocolAmd, and MEX-84 provide a website link, Help Sheet for the Generation of the Fee Payment Format, for users to generate a payment form for fees based on their procedure in order to make a payment at the banking institution of their choice. Refer to G-HumResProt, G-BioequivStud, G-ObsrvStdies, G-ResProtocolAmd, MEX-84, and G-DIGIPRiS-ResProts for additional information on this process.

Requirements (32) and Cost

2. General Requirements (2.2 Proof of Payment of Fees)

Other Permits or Authorizations - Supplies for Health (p.10)

Where can I go to submit my paperwork to COFEPRIS? and What is a Comprehensive Service Center?

XIII. Specific Sections of the Procedure on the Platform (III)

Requirements (2) and Cost

Cost

Requirements (2) and Cost

Ethics Committee

Last content review/update: July 2, 2024

Overview

As per the G-KenyaCT, the G-ECBiomedRes, and KEN-30, Kenya requires an independent review of research through a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC) in one (1) of the local institutions charged with the responsibility of conducting research in human participants. KEN-25 provides a list of the accredited institutional ECs.

Ethics Committee Composition

As delineated in the G-ECAccred, institutional ECs should consist of at least seven (7) members, or an odd number above seven (7). The G-ECBiomedRes states that these members should be multidisciplinary and multisectoral in composition, collectively encompass relevant scientific expertise, balanced age and gender distribution, and include laypersons representing community interests and concerns. Per the G-ECAccred, the composition should meet the following requirements:

At least one (1) member with knowledge and understanding of Kenyan law
At least one-third of the members must be female, and one-third must be male
At least one (1) member who is unaffiliated with the institution
At least two (2) members must have research expertise and experience, one (1) of whom must be in the health field
At least one (1) member must be a lay member
For ECs reviewing clinical research, at least two (2) members must be clinicians, one (1) of whom is currently in active practice or clinical research
Reflect the regional and ethnic diversity of the people of Kenya

The chairperson must also have some basic training and/or experience in bioethics and leadership. All EC appointments are the responsibility of the institution’s administrative head. See the G-ECAccred and the G-ECBiomedRes for detailed institutional EC requirements.

Terms of Reference, Review Procedures, and Meeting Schedule

Per G-ECBiomedRes, ECs need to have independence from political, institutional, professional, and market influences. As delineated in the G-ECAccred, the G-ECBiomedRes, and the STI-Regs, institutional ECs must operate within written standard operating procedures (SOPs) which delineate the EC’s process for conducting reviews. Per the G-ECAccred, SOPs should include but are not limited to information on EC scope, responsibility, and objectives, institutions served, committee functions, terms and conditions of member appointment, business procedures including meeting schedules and types of reviews, documentation, recordkeeping, and archiving procedures, quorum requirements, communication procedures, and complaint process and dispute resolution procedures. Per the G-ECAccred and the STI-Regs, these documents must be provided to NACOSTI.

Per the G-ECAccred, the quorum for NACOSTI-accredited EC meetings must be:

At least 50 percent of the membership must form the quorum
A lay person must be present in all meetings
For ECs reviewing clinical research, at least two (2) members must be clinicians, one (1) of whom is currently in active practice or clinical research.

The G-ECBiomedRes also defines quorum requirements:

The minimum number of members required to compose a quorum (e.g., more than half the members)
The professional qualifications requirements (e.g., physician, lawyer, statistician, paramedical, or layperson) and the distribution of those requirements over the quorum; no quorum should consist entirely of members of one (1) profession or one (1) gender; a quorum should include at least one (1) member whose primary area of expertise is in a non-scientific area, and at least one (1) member who is independent of the institution/research site

Per G-ECBiomedRes, EC member terms of appointment should be established that include the duration of an appointment, the policy for the renewal of an appointment, the disqualification procedure, the resignation procedure, and the replacement procedure. A statement of the conditions of appointment should be drawn up that includes the following:

A member should be willing to publicize their full name, profession, and affiliation
All reimbursement for work and expenses, if any, within or related to an EC should be recorded and made available to the public upon request
A member should sign a confidentiality agreement regarding meeting deliberations, applications, information on research participants, and related matters

Regarding training, EC members should have initial and continued education regarding the ethics and science of biomedical research. The conditions of appointment should indicate the availability and requirements of introductory training, as well as on-going continuing education. This education may be linked to cooperative arrangements with other ECs in the area, country, and region.

For detailed institutional EC requirements and information on other administrative processes, see the G-ECAccred and the G-ECBiomedRes. See KEN-17 and KEN-26 for examples of accredited EC submission and review guidelines.

Review Process, Submission Forms, Electronic Submission, SERU Applicant SOPs, and Contact Us

Definition of Terms, 1.0, 2.0, 3.0, 4.0, and Annexes I-III

1 and 7.1

1.188-1.212 and 1.492-1.496

The Science, Technology and Innovation (Registration and Accreditation of Research Institutions) Regulations, 2014 (Third Schedule); and The Science, Technology and Innovation (Relevance and Quality Assurance in Research) Regulations, 2014 (Part II)

Last content review/update: November 8, 2024

Overview

As delineated in GenHlthLaw, HlthResRegs, REC-Op, REC-Op-Ref, G-RECs-Op-2018, and NOM-012-SSA3-2012, Mexico has a decentralized process for the ethics review and approval of clinical trial research. Accordingly, every health care institution which carries out research activities in human beings is required to have a Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) that is responsible for evaluating and ruling on research protocols in human beings. RECs are subject to current legislation and the criteria established by the National Bioethics Commission (Comisión Nacional de Bioética (CONBIOÉTICA)).

RECs must also comply with guidelines for the ethical evaluation of research involving human beings as delineated in GenHlthLaw, G-RECs-Op-2018, HlthResRegs and NOM-012-SSA3-2012. Pursuant to G-RECs-Op-2018, RECs must adhere to international guidelines relevant to research with human beings including the Declaration of Helsinki (MEX-76) and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MEX-22)).

In addition, per GenHlthLaw, HlthResRegs, and NOM-012-SSA3-2012, every health institution where research is conducted is required to establish a Research Committee and a Biosafety Committee. Per HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, REC and Research Committee approval is required for each trial site where a study is being conducted, and when applicable, Biosafety Committee approval is required as well.

GenHlthLaw further notes that in addition to establishing an REC, public, social, or private sector health care establishments of the National Health System must have a Hospital Bioethics Committee for the resolution of problems arising from medical care along with engaging in other bioethical and ethical related activities.

As per HlthResRegs, REC-Op, REC-Op-Ref, G-RECs-Op-2018, and NOM-012-SSA3-2012, Hospital Bioethics Committees also operate through CONBIOÉTICA. MEX-47 specifies that CONBIOÉTICA is responsible for registering RECs and Hospital Bioethics Committees. See the Oversight of Ethics Committees section for details on ethics committee registration.

Ethics Committee Composition

Research Ethics Committee Composition

As indicated in GenHlthLaw, RECs must be interdisciplinary gender-balanced groups composed of medical personnel from different specialties; professionals from psychology, nursing, social work, sociology, anthropology, philosophy, or law fields who have bioethics training; and community representatives affected by the health condition under study or other health services users who may or may not be attached to the health unit or institution. In addition to the previously stated criteria, G-RECs-Op-2018 indicates that these professionals should have a professional license and accredited training and experience in research ethics, good clinical practice, bioethics, and have experience related to the research area they will be evaluating. HlthResRegs further notes that the REC must consist of at least three (3) scientists including both genders and recommends that at least one (1) of them be based outside the health institution. The medical professionals should also represent the moral, cultural, and social values of the research groups. By comparison, NOM-012-SSA3-2012 states that REC health professionals should have expertise in the subjects investigated at the institution, regardless of whether the professionals have experience in the scientific methodology applied to the research. Further, the community representatives should embody the moral, cultural, and social values of the research participants.

Per REC-Op and REC-Op-Ref, the REC members must also be recognized and able to document their professional excellence in research/research bioethics, have personal records that prove ethical suitability and conduct, and advanced knowledge in qualitative and quantitative methodology. Additionally, GenHlthLaw, G-RECs-Op-2018, and NOM-012-SSA3-2012 state that REC members may or may not be based at the associated institution where the study is being conducted.

Additionally, NOM-012-SSA3-2012 specifies that the REC should be composed of a minimum of three (3) scientists, plus community representatives, as deemed necessary, with a total of at least six (6) members and a maximum of 20. G-RECs-Op-2018, REC-Op, and REC-Op-Ref note that the REC should comprise a president, at least four (4) members, one (1) of whom will serve as secretary, a representative from the affected study group or other health services users, with at least one (1) member who has expertise in bioethics and research ethics, and internal or external specialists to be included on an as needed basis. G-RECs-Op-2018 also notes that the member acting as a representative is not required to have a professional license in research or medical care and may include individuals with basic education or technical training.

Hospital Bioethics Committee Composition

Per GenHlthLaw and G-CHBs-Op, Hospital Bioethics Committees must be multidisciplinary, diverse, gender-balanced groups composed of medical personnel from different specialties and the health team; professionals from psychology, nursing, social work, sociology, anthropology, and philosophy fields; lawyers with knowledge in health matters, and community representatives affected by the health condition under study or other health services users who may or may not be attached to the health unit or institution. G-CHBs-Op notes that the members must have previous bioethics training or receive the training within the six (6) months after joining the Committee. Administrative personnel, directors of institutions, or people who occupy managerial positions in the institution should not be included, in order to promote an environment of equity.

In addition, per G-CHBs-Op, the Hospital Bioethics Committee should be composed of a president and a minimum of four (4) members with assistance from a secretary, to be appointed from among the members by the president. At least one (1) member not assigned to the health establishment must be included.

Terms of Reference, Review Procedures, and Meeting Schedule

Research Ethics Committees

Per NOM-012-SSA3-2012, the constitution and operation of the REC will be subject to the provisions of current legislation and, where appropriate, to the criteria referred to in article 41 Bis of the GenHlthLaw. REC-Op, G-RECs-Op-2018, NOM-012-SSA3-2012, and COFEPRIS-GCP specify that RECs should operate within written standard operating procedures (SOPs) to conduct their reviews. REC-Op and G-RECs-Op-2018 indicate that the health institution owner must approve the SOPs and issue a certificate of appointment to each of the REC members. HlthResRegs, G-RECs-Op-2018, and NOM-012-SSA3-2012 note that members must hold office for three (3) years and may be approved for an equal period.

Per REC-Op, G-RECs-Op-2018, NOM-012-SSA3-2012, and COFEPRIS-GCP, the following minimum requirements must be met (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

RECs must meet at least six (6) times a year, and at least once every two (2) months
The minimum number of members required to complete a quorum must be greater than 50% of the members, and the president and/or secretary must be present to form a quorum
In the evaluation of multicenter studies and when otherwise warranted, the REC may meet jointly with other RECs that belong to other establishments in the country, for the assessment and opinion for these protocols
Minutes must be prepared for legal and administrative purposes in meetings
An annual report of activities should be presented to the institutional head in the first 30 calendar days of the year
Avoid conflicts of interest in protocol evaluations or be declared disqualified for that particular review
Participation is required in initial training and bioethics continuing education
Liaisons with other RECs within and outside the country to better carry out its functions
A general policy on the confidentiality of information for protocols reviewed must be established and implemented
A code of conduct for REC members must be established and implemented
Members must refrain from participating in the evaluation and opinion of their own research
Members will remain in office for the time established in each committee’s installation act and may be ratified at the end of each period, if applicable. Members may be replaced in a staggered manner, for which documentary evidence must be kept
The committee will designate the person who will occupy the position of president and who will be responsible to the head of the institution or establishment and for the committee’s activities
In the committee sessions, members of external committees may participate or have the support of external advisors, who will have a voice but no vote. In these cases, researchers from the institution or establishment itself may also participate as long as they work in areas related to the subject of the project or research protocol in the opinion phase
It is the responsibility of the committee to issue the technical opinion on ethics, according to the nature of the proposed investigations

For detailed REC procedures and information on other administrative processes, see REC-Op, G-RECs-Op-2018, NOM-012-SSA3-2012, and COFEPRIS-GCP. See also MEX-72 for information on CONBIOÉTICA’s REC follow-up monitoring reports.

As per G-RECs-Op-2018, the REC should also keep documentation related to its integration, operation, and registration activities for up to three (3) years after the conclusion of the committee’s activities. The committee should also define the procedure for transferring the files and appoint the responsible person at the institution where the REC registration was granted. In addition, the REC will keep all the essential documents reviewed and related to each evaluated investigation, up to five (5) years following the end of the investigation or during the period established in the applicable provisions.

See G-RECs-Op-2018 for additional REC recordkeeping requirements.

Hospital Bioethics Committees

As indicated in G-CHBs-Op, Hospital Bioethics Committees must establish operating rules, which specify member functions as well as the internal mechanisms and procedures for operations during the sessions. In newly created Committees and during the first six (6) months, the members must be trained in bioethics on an ongoing basis. Per G-CHBs-Op and GenHlthLaw, the Committee will also promote, with the head of the hospital, the dissemination, elaboration and implementation of institutional bioethical guidelines and guides for medical care and teaching. It will also promote the ongoing the bioethical education of its members and hospital staff. GenHlthLaw also notes the Hospital Bioethics Committees must comply with current legislation and CONBIOÉTICA guidelines.

G-CHBs-Op further explains that Hospital Bioethics Committees must meet in an ordinary manner, at least six (6) times a year, and in an extraordinary way, at any time, at the President’s request, or when requested by the majority of its members. Quorum requirements to review and decide on a request must include attendance of at least half the number of committee members and the president. Minutes will also be prepared for each of the Committee sessions. The resolutions issued by the Committee are the result of the analysis and deliberation of the members present at the session and must be communicated through a letter addressed to the applicant who presented the case. The recommendations issued by the Committee must not be incorporated into the clinical file. The Committee President is responsible for safeguarding the files. For detailed Hospital Bioethics Committee procedures and information on other administrative processes, see G-CHBs-Op.

9.2

XIII. Specific Sections of the Procedure on the Platform (XI-XIII)

Requirements (11)

2

1.2-1.3, 2-3, 3.1, 3.3, 4.1, 4.3, 5.1-5.2, 6.1-6.2, 8.1, 9, 11, and Annexes 1 and 2

Integration, Operation, Sessions, Minutes, Quorum, Issuance of Recommendations, and Information and Files

Title III (Chapter III, Article 41 Bis) and Title V (Chapter I, Articles 98 and 100)

Preamble, Fourth, Sixth-Tenth, and Twelfth

Preamble, Article One (Twelfth, Twelfth Bis 1, Twelfth Bis 2, and Sixteenth)

Title II (Chapter I, Articles 13-14), Title V (Chapter I, Articles 99-102, 104, and 108-109)

0-1 and 9

Scope of Review

Last content review/update: July 2, 2024

Overview

According to G-ECBiomedRes, the primary scope of information assessed by the institutional ethics committees (ECs) relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial. The G-ECAccred further states that the National Commission for Science, Technology and Innovation (NACOSTI) accredits ECs in order to uphold the standard of ethics review in the country; develop public confidence and trust in the national research system; facilitate equitable access to research and human health records in health facilities; and facilitate coordination and collaboration among ECs. See the G-ECAccred and the G-ECBiomedRes for detailed ethical review guidelines.

Role in Clinical Trial Approval Process

As per the G-KenyaCT and KEN-21, the Pharmacy and Poisons Board (PPB)’s review and approval of a clinical trial application is dependent upon obtaining approval by an accredited institutional EC. Consequently, the PPB and EC reviews may not be conducted in parallel.

As set forth in the G-ECBiomedRes, ECs must be constituted to ensure an independent and competent review and evaluation of all ethical aspects of clinical trials. ECs must review research involving human participants to ensure they meet these ethical principles:

Respect for persons, including respect of autonomy, protection of vulnerable groups, and protection of privacy and confidentiality
Beneficence
Justice, which in research means equitable distribution of the benefits and the burdens

For additional details on the principles and benchmarks for ethical review, see G-ECBiomedRes.

Per the G-ECBiomedRes, expedited review may be permitted for protocols involving no more than minimal risk to research participants.

The G-ECBiomedRes indicates that all ECs should carry out regular monitoring of approved protocols involving human participants. In case of any adverse events, the EC should report this immediately to Kenya’s National Bioethics Committee (NBC).

Per the G-ECBiomedRes, with collaborative research projects, the collaborating investigators, institutions, and countries must function as equal partners with safeguards to avoid exploitation of local researchers and participants. An external sponsoring agency should submit the research protocol to their country’s EC, as well as the Kenyan EC where the research is to be conducted. Further, this research must be responsive to the health needs of Kenya and reasonably accessible to the community in which the research was conducted. Consideration should be given to the sponsoring agency agreeing to maintain health services and faculties established for the purposes of the study in Kenya after the research has been completed. Such collaborative research must have a local/Kenyan co-principal investigator.

1.0-1.2

3.0, 3.1, 4.1, 4.2, 6.0, and 7.1

Glossary of Terms and 1.188- 1.212 and 1.492-1.496

Last content review/update: November 8, 2024

Overview

According to HlthResRegs, REC-Op, and G-RECs-Op-2018, the primary scope of information assessed by the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) relates to maintaining and protecting the dignity and rights of human research participants and ensuring their safety throughout their participation in a clinical trial. Per HlthResRegs and G-RECs-Op-2018, RECs must also pay special attention to reviewing informed consent and protecting the welfare of certain classes of participants deemed vulnerable. (See Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations.)

HlthResRegs and G-RECs-Op-2018 also state that RECs must ensure an independent, timely, and competent review of all ethical aspects of the clinical trial protocol. They must act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants, and they must verify the adequacy of confidentiality and privacy safeguards. See HlthResRegs and G-RECs-Op-2018 for detailed ethical review guidelines.

Role in Clinical Trial Approval Process

Per HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, the applicant must obtain a favorable decision from the REC and the Research Committee at the health institution where the study is being conducted, and when applicable, a favorable decision from the Biosafety Committee. As per COFEPRIS-GCP, HlthResRegs, and NOM-012-SSA3-2012, the REC must provide a favorable decision for the research protocol and informed consent form prior to the applicant submitting a request for protocol authorization to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)). Consequently, the REC and COFEPRIS reviews may not be conducted in parallel.

HlthResRegs, GenHlthLaw, and G-HumResProt explain that the REC provides ethics recommendations on protocols for research in human beings, including a review of the research risks and benefits, and per G-HumResProt, assesses the technical quality and scientific merit of the protocol. HlthResRegs further notes that RECs also prepare ethics guidelines for conducting research in humans.

As delineated in G-RECs-Op-2018, the REC agenda and documents corresponding to each session should be delivered at least seven (7) days prior to the meeting. It is then recommended that the REC’s decision be sent within a period not exceeding five (5) working days after the committee has met, or if applicable, not to exceed 30 calendar days from the review request date. G-RECs-Op-2018 and G-DIGIPRiS-ResProts also state that the approval of a new application is valid for one (1) year.

After obtaining a favorable opinion from the REC that validated the initial project or protocol, per NOM-012-SSA3-2012, the principal investigator (PI) must submit an amended protocol to the Ministry of Health (Secretaría de Salud) to request a new authorization for any amendments to be made to the methodological design of the initial research project. In those cases where the lives of research participants are endangered, amendments can be applied immediately, prior to approval by the REC and authorization by the Ministry of Health. However, in these situations, it will be necessary for the PI to provide documentary evidence following the event to the REC and the Ministry.

In addition, G-RECs-Op-2018 indicates that the REC should establish procedures for monitoring approved studies, from the point at which the decision was made until the completion of the investigation and reporting of results. Per NOM-012-SSA3-2012 and G-RECs-Op-2018, the REC must assess and approve the research protocol at the beginning of the project, and periodically throughout the project’s duration to ensure conformance with ethical principles and applicable regulations. NOM-012-SSA3-2012 further specifies that the REC must propose to the head of the institution or establishment where health research is carried out that the research be suspended or cancelled in the presence of any adverse effect that is an impediment from an ethical or technical point of view to continue with the study.

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

9.2

XIII. Specific Sections of the Procedure on the Platform (XI-XIII)

Requirements (11)

2

3.1-3.3, 4.3-4.4, 7.2, 8.1-8.2, 11, and Annexes 5 and 6

Title V (Chapter I, Article 100)

Preamble and Fifth

Preamble, Title II (Chapter I, Article 13 and Chapter II, Article 29), Title III (Chapter I, Article 61-62), and Title V (Chapter I, Articles 99-102, 104, and 108-109)

0, 6.3, 8.4, 9.2, and 10.3

Ethics Committee Fees

Last content review/update: July 2, 2024

As per the G-KenyaCT, G-ECBiomedRes, and KEN-30, Kenya requires an independent review of research through a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC) in one (1) of the local institutions charged with the responsibility of conducting research in human participants. The EC fee to review a clinical trial application will vary depending on the institution. See KEN-25 and KEN-38 for lists of NACOSTI-accredited institutional ECs. For an example of institutional fee requirements charged by the Scientific and Ethics Review Unit (SERU) at the Kenya Medical Research Institute (KEMRI), see KEN-27.

Where do I get a letter of ethical approval before applying for a research license?

1, 4.1, and 7.1

Glossary of Terms

Last content review/update: November 8, 2024

As set forth in G-RECs-Op-2018, COFEPRIS-GCP, and REC-Op, Research Ethics Committees (RECs) (Comités de Ética en Investigación (CEIs)) do not charge sponsors/investigators for their review. Rather, the health institution must finance REC operating expenses, without this causing any conflict of interest in the committee’s functions.

G-RECs-Op-2018 further states that the institution may also receive support from external sources for evaluating protocols. However, this funding should not be given directly to any of the REC members, and the contributions should not lead to a conflict of interest between the funding source and the REC’s functions. Similarly, the committee’s evaluations should not result in financial gains as a result of these contributions.

Per G-RECs-Op-2018, REC financial support should not be used for purposes other than for its operation, and all activities should be handled with full transparency. Support is provided for the following activities:

Time for participation in committee meetings
Work recognition for their performance in the REC
Support for training in bioethics and research ethics inside and outside the institution
Physical space for the REC headquarters, both for meetings and receipt of documents, and safeguarding of documentation protocols, opinions, and minutes
Administrative assistance for REC activities

No information is available on Hospital Bioethics Committee fees.

2.7

4.2

Seventh, Ninth, and Eleventh

Oversight of Ethics Committees

Last content review/update: July 2, 2024

Overview

As set forth in the STI-Act and KEN-32, the National Commission for Science, Technology and Innovation (NACOSTI) is the central body responsible for the oversight, promotion, and coordination of research. NACOSTI’s role is to regulate and ensure quality in the science, technology, and innovation sector, and to advise the Kenyan government on related matters. As per the G-ECAccred, NACOSTI has delegated the task of reviewing research proposals for ethical clearance to accredited institutional ethics committees (ECs) to ensure that research conducted in the country observes high research ethics standards.

Per the G-ECBiomedRes, Kenya's National Bioethics Committee (NBC) advises NACOSTI on research ethics. In addition, NBC offers dispute resolution if an applicant is dissatisfied with the decision of an EC. Finally, the NBC must terminate research at any stage if it is found to be harmful to the participants.

Registration, Auditing, and Accreditation

As per the STI-Regs and the G-ECAccred, NACOSTI is responsible for accrediting institutional ECs. Per the G-ECAccred, the application requirements for accreditation are:

A completed application form (KEN-10 or Annex III of the G-ECAccred)
Copy of the standard operating procedures (SOPs)
Copies of abridged curriculum vitaes (CVs) (no more than four (4) pages) for each member of the proposed EC (including the training attended)
Profile of the organization/institution detailing the areas of competence (no more than four (4) pages)

Upon creating an account in NACOSTI’s Kenya National Research Information System (KENRIS) (KEN-23), users can perform the following functions:

Researchers: Apply for researcher registration, register and track applications, and maintain research profile
Research Institutions: Apply for new research institution registration, maintain/update data, and submit annual reports
Institutional ECs: Apply for accreditation, preview and track accreditation proposals, submit annual reports, and maintain/update data

Per the G-ECAccred, NACOSTI issues a certificate of accreditation to accredited institutional ECs, which is valid for three (3) years from the date of NACOSTI’s notification. All accredited ECs must submit annual reports to NACOSTI by July 31st for review and monitoring. Applications for renewal of accreditation should be made six (6) months before expiry of the accreditation period. Failure to renew accreditation or failure to maintain the appropriate standards for continuity of accreditation will mean that the accredited status of the EC will lapse at the end of the current accreditation period. Accreditation must be terminated if the accredited committee fails to maintain the required standards. For re-accreditation review purposes, ECs must provide the SOPs under which they will operate. The SOPs are not required as part of the annual reporting process, unless they have been amended, but are required to be stated/included for the re-accreditation review process (every three (3) years). See the G-ECAccred for additional details on the accreditation process.

See the Site/Investigator Selection section for more information on the sponsor and site’s registration and application requirements.

1.0, 2.0, 4.0, and Annex III

4.1 and 7.1

Part II

The Science, Technology and Innovation (Relevance and Quality Assurance in Research) Regulations, 2014 (Part II)

Last content review/update: November 8, 2024

Overview

The National Bioethics Commission (Comisión Nacional de Bioética (CONBIOÉTICA)) was established as a decentralized entity of the Ministry of Health (Secretaría de Salud) in 2005, as specified in D-CONBIOETICA. According to D-CONBIOETICA and MEX-55, the agency has technical and operational autonomy in defining and establishing national bioethics policies in medical care and health research. Per D-CONBIOETICA, GenHlthLaw, G-RECs-Op-2018, and MEX-57, CONBIOÉTICA is also responsible for promoting the organization and operation of Research Ethics Committees (RECs) (Comités de Ética en Investigación (CEIs)) and Hospital Bioethics Committees in public and private health institutions, for establishing and disseminating criteria to support development of REC activities, and for providing committee member training support.

In addition, per D-CONBIOETICA, CONBIOÉTICA’s other roles include:

Exercising the Commission’s legal authority and head Commission operations
Presiding over the Commission’s Advisory Council
Issuing positions on bioethical issues relevant to society
Establishing links with federal entities to promote the creation and operation of state bioethics commissions
Signing and implementing collaborative agreements with organizations and opportunities that favor the development and consolidation of bioethical culture
Carrying out activities assigned by the Secretary of Health
Providing information and technical cooperation required by the Ministry of Health’s administrative units and other dependencies/entities within the Federal Public Administration

Registration, Auditing, and Accreditation

Research Ethics Committees

As delineated in HlthResRegs, REC-Op, REC-Op-Ref, REC-Op-Amd, G-RECs-Op-2018, G-RECReg, and MEX-57, all RECs are required to register with CONBIOÉTICA in order to conduct health research in humans.

G-RECs-Op-2018, and G-RECReg further state that CONBIOÉTICA has 10 working days from the business day following application receipt to accept the application, or require the applicant to correct omissions in the application within 15 working days from the business day following the date when the applicant is notified. If the applicant fails to respond within this timeframe, the application must be deemed not filed. Once the application has been admitted for processing, the Commission has 30 working days to notify the applicant of receipt, and if appropriate, to issue the corresponding registration certificate, which will be valid for three (3) years. The registration record must also be visibly displayed in the institution where REC operations occur and on its website, if applicable. Additionally, the registration number must be included in all official committee communications.

Per REC-Op-Amd, MEX-58, and G-RECReg, the REC registration form (MEX-29) is available for completion or download via MEX-58 or G-RECReg, and should be submitted in person according to the requirements outlined in REC-Op-Amd, MEX-58, and G-RECReg. The application must include the REC’s health institution identification data, an email address in order to receive Commission notifications, and the name and signature of the responsible person heading the REC. G-RECReg specifies that the applicant may request an appointment by phone or email to deliver all the documentation in printed form to CONBIOÉTICA, or send the application documentation via certified mail.

Refer to REC-Op-Amd, G-RECs-Op-2018, MEX-58, and G-RECReg for detailed registration application instructions and documentation requirements. See also MEX-57 for a list of registered RECs.

As delineated in REC-Op-Amd, G-RECs-Op-2018, and G-RECRegRenew, a registration renewal application must be submitted by the principal or owner of the health establishment or by the legal representative to CONBIOÉTICA within 45 working days prior to the expiration of the validation period covered by the registration certificate. From this point, the timing requirements are the same as for the initial application. See REC-Op-Amd, G-RECs-Op-2018, and G-RECRegRenew for detailed registration renewal application requirements and the application form.

In addition to CONBIOÉTICA’s REC registration requirement, per GenHlthLaw, G-RECs-Op-2018, REC-Op, and REC-Op-Ref, RECs must be installed under the responsibility of the head of the health institution where the study is taking place. They are required to sign a REC Installation Certificate (MEX-27), which stipulates its characteristics and functions. Refer to G-RECs-Op-2018 for detailed certificate requirements. See also MEX-72 for information on CONBIOÉTICA’s REC follow-up monitoring reports.

According to NOM-012-SSA3-2012, the research institution owner must also register the REC with the Ministry of Health (Secretaría de Salud), and report on the modification, designation, or substitution of any of its members. Additionally, an annual report documenting the integration and activities of these committees must be submitted to the Ministry during the first 10 business days of June each year.

Hospital Bioethics Committees

G-CHBs-Op and G-CHBReg indicate that Hospital Bioethics Committees must also register with CONBIOÉTICA, who is, in turn, required to issue a registration record within a maximum of 15 business days. CONBIOÉTICA’s registration is valid for three (3) years. Per G-CHBs-Op, the Hospital Bioethics Committee registration form must be submitted electronically through CONBIOÉTICA’s website. The application for registration renewal can be submitted one (1) month prior to the registration’s expiration date. Refer to G-CHBs-Op, MEX-56, MEX-59, and G-CHBReg for additional Hospital Bioethics Committee registration information.

Registration Process of Research Ethics Committees (CEI) and List of Registered CEI

Preamble, Articles One-Three, and Seven

Requirements, Who Can Apply?, Legal Basis, Steps, Response Time, Validity, and Additional Information

5.3, 11, and Annex 4

Registry of the Hospital Bioethics Committees, Proof of Registration, Validity of the Registration, Renewal of the Registration, and Appendix 1

Title III (Chapter III, Article 41 Bis) and Title V (Chapter I, Article 98)

Preamble, Article One (Twelfth and Twelfth Bis 1), and Transients (Third)

Preamble, Fourth, Sixth-Tenth, Twelfth, and Annex 1

Article One (Seventh, Twelfth, Twelfth Bis 2, and Sixteenth), and Annex 1

Title V (Chapter I, Articles 99-102, 104, and 108-109)

4.8 and 9.1.4

Submission Process

Last content review/update: July 2, 2024

Overview

In accordance with the PPA, the STI-Act, the CTRules, the G-KenyaCT, the G-ECBiomedRes, KEN-21, and KEN-16, Kenya requires the sponsor or the representative to obtain clinical trial authorization from the Pharmacy and Poisons Board (PPB)’s Expert Committee on Clinical Trials (ECCT) and an independent ethics review through a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC) in a local institution. In addition, the STI-Act and KEN-31 specify that applicants must obtain a research license from NACOSTI prior to initiating a study. The G-KenyaCT also states that the PPB review and approval process may not be conducted in parallel with the EC review. EC approval must be obtained prior to applying for PPB approval.

Regulatory Submission

Pharmacy and Poisons Board

As described in the G-KenyaCT and KEN-16, the sponsor or the representative is expected to submit the clinical trial application electronically via the PPB online system (KEN-16). The clinical trial application form is available in KEN-16. Per the G-KenyaCT, in the event of a multicenter clinical trial, the sponsor should only file one (1) application to the PPB. According to KEN-34, all application documents should be signed, dated, and version referenced, if applicable, and should be in English. See Annex 7 of the G-KenyaCT to view a flowchart of the submission and approval process.

Per the G-KenyaCT, upon receipt of a clinical trial application, the PPB’s Clinical Trial Division of the Product Safety Department screens the application package for completeness. When an application for a clinical trial is accepted, an acknowledgement of receipt will be issued with a reference number for each application. This PPB/ECCT reference number must be quoted in all correspondence concerning the application in the future. This will be communicated through email to the applicant or through KEN-16.

Per the G-KenyaCT, sponsors (applicants) can request pre-submission meetings with the PPB to discuss pertinent issues prior to making a formal submissions. The request must be made via KEN-16 or in an official letter and include the following information:

Background information on the disease to be treated
Background information on the product
Quality development
Non-clinical development
Clinical development
Regulatory status
Rationale for seeking advice
Proposed questions and applicant’s positions

In addition, per the G-KenyaCT, the letter must be addressed to the Chief Executive Officer of the PPB and sent to admin@pharmacyboardkenya.org and copied to cta@pharmacyboardkenya.org. The request for a meeting should propose two (2) different dates for the meeting at least three (3) weeks away.

Per G-KenyaCT, any new information that affects the conduct/management of the trial; safety of the participants; and manufacture of the product necessitating changes to the protocol, consent form, and trial sites, etc. will require immediate submission of the amended documents to the PPB for review and approval. Minor amendments or administrative changes may be implemented after getting the EC’s approval, but a record of these amendments must be kept for possible inspection by the PPB.

National Commission for Science, Technology and Innovation

Per KEN-31, an application for a NACOSTI research license should be submitted online via the Research Information Management System (RIMS) (KEN-24).

Ethics Review Submission

Each institutional EC has its own required submission procedures, which can differ significantly regarding the application format and number of copies. See KEN-17 for an example of a NACOSTI-accredited EC’s guidelines.

1.0 and 4.1

Glossary of Terms, Introduction, 1.1-1.29, 1.182-1.185, 1.492-1.496, and Annexes 1-7

25A

Parts II, IV, V, and X and Fourth Schedule

Part II (Section 4)

Last content review/update: November 8, 2024

Overview

In accordance with GenHlthLaw, Reg-COFEPRIS, HlthResRegs, and NOM-012-SSA3-2012, Mexico requires the applicant to obtain research protocol authorization from the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)). Per HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, the applicant must also obtain a favorable decision from the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and the Research Committee at the health institution where the study is being conducted, and when applicable, a favorable decision from the Biosafety Committee. Because COFEPRIS’s review and approval of a protocol authorization request is dependent upon obtaining a favorable decision from the REC and Research Committee, the COFEPRIS and ethics committee (REC and Research Committee) reviews may not be conducted in parallel.

Regulatory Submission

MEX-15 states that applicants may submit research authorization requests or protocol modification/amendment requests in person or by mail to COFEPRIS at the Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37), a public service system established by the Mexican government to facilitate the processing of the agency’s standardized procedures and services. According to G-HumResProt, G-ResProtocolAmd, MEX-109, and MEX-37, however, requests should be submitted to the CIS (MEX-37) in person or electronically via COFEPRIS’s digital procedures and services platform, DIGIPRiS: Online Regulation (MEX-86). (Note: COFEPRIS refers to applications as requests or procedures).

Pre-submission Registrations

As delineated in G-DIGIPRiS-Regis and G-DIGIPRiS-SystAccess, prior to submitting a request for research protocol authorization via DIGIPRiS (MEX-86), an applicant must first register in (MEX-86) using an e.signature (also known as e.firma) digital certificate. MEX-49 explains that the signature is a secure, encrypted digital file that identifies an applicant, and can be used to carry out procedures electronically with various government agencies. An e.signature can be obtained from the Tax Administration Service (Servicio de administración tributaria (SAT)) as described in MEX-105. G-DIGIPRiS-Regis and G-DIGIPRiS-SystAccess further explain that an e.signature is used to validate the natural person or legal entity registering in MEX-86. DIGIPRiS’s Terms of Use, which is accessible via MEX-86, also notes that the applicant is required to be registered with the Federal Taxpayer Registry (Registro Federal de Contribuyentes (RFC)). See G-DIGIPRiS-Regis, G-DIGIPRiS-SystAccess, and DIGIPRiS’s Terms of Use for details on registering in MEX-86. See also MEX-106 for an instructional tutorial on registering in MEX-86, and see G-DIGIPRiS-FAQs for frequently asked questions on using MEX-86.

DIGIPRiS Submissions

DIGIPRiS’s Terms of Use further explains that the application process is carried out entirely electronically via DIGIPRiS (MEX-86), unless the user is required to present printed documents with a handwritten signature or a physical inspection is required. The application request will be considered active when the documentation is signed and submitted, otherwise it will only remain in the system for 90 calendar days. When the request is active, the user receives a “Procedure Entry Receipt” through which COFEPRIS assigns a procedure number and the entry date and time is recorded. Once the procedure has begun, the user will be notified in MEX-86 of all request related administrative acts (e.g., requirements, actions, preventions or missing information, and resolutions). Authorizations issued via MEX-86 will take effect on the date and time indicated in the corresponding document. The email address the user provides during registration will be used to send notices of notification availability related to submitted applications. Refer to DIGIPRiS’s Terms of Use for detailed information on the administrative act notification process via MEX-86. See also G-DIGIPRiS-SystAccess for instructions on registering and updating emails in MEX-86.

Pursuant to G-DIGIPRiS-SystAccess and G-DIGIPRiS-ResProts, users can view the flow and status of the entire application process (application, evaluation, verification, signature and resolution) in DIGIPRiS (MEX-86), as well as view previously authorized applications. Additionally, multiple requests and procedures can be in process simultaneously in MEX-86. See also G-DIGIPRiS-DocComp for instructions on validating and comparing documents issued through MEX-86 for research protocols. Refer to MEX-96, MEX-97, and MEX-108 for additional background information on MEX-86. Per G-HumResProt, electronic submissions via MEX-86 are tracked via the applicant’s e.signature (MEX-105). See also G-DIGIPRiS-Reqs&Amdts for instructions on submitting requests for protocol amendment/modification via MEX-86.

CIS Submissions

As indicated in MEX-37 and MEX-15, applications submitted in person at the CIS (MEX-37) can be tracked via a CIS assigned reference number in the COFEPRIS Electronic Procedures Portal (MEX-103). MEX-109 specifies that the Electronic Procedures Portal (MEX-103) is only to be used for procedures submitted in person at the CIS (MEX-37) while procedures submitted via DIGIPRiS (MEX-86) should be tracked through the DIGIPRiS platform.

As per MEX-15, and MEX-71, applications as well as technical inquiries, or those inquiries requiring an official response, should be submitted to the CIS (MEX-37) at:

COFEPRIS
Centro Integral de Servicios
Oklahoma No. 14
Colonia Nápoles
Del. Benito Juárez
CP 03810, Ciudad de México

COFEPRIS Call Center Phone: 01-800-033-5050 (toll free within Mexico) or 55 53 40 09 96 (international calls) (per MEX-37)
Foreign Processing Area Phone (for entry and/or tracking number of procedure): 01-800-420-4224 (toll free within Mexico) (per MEX-25)
Email: contactociudadano@cofepris.gob.mx (per MEX-71 and MEX-37)

Per G-DIGIPRiS-ResProts, all documents uploaded to DIGIPRiS (MEX-86) must be in “.pdf” format (unrestricted text file), unless another format is specified.

Per G-HumResProt, G-ResProtocolAmd, and MEX-18, the Authorizations, Certificates and Visits form (MEX-25) should also be included in the application submission, as well as the original proof of payment of rights with two (2) copies of the receipt for protocol authorization and protocol modification/amendment requests. See the Submission Content section for detailed submission documentation requirements.

G-HumResProt and G-ResProtocolAmd state that all documentation related to submitting applications for research protocol authorization and protocol modification/amendment is required to be in Spanish. MEX-84 also specifies that the protocol, investigator’s brochure (known as the researcher’s manual in Mexico), and the informed consent forms should be in Spanish.

Enabled Pre-Assessment Support Unit (UHAP) Evaluation Submissions

Per MEX-21 and MEX-10, rather than submitting the application directly to the CIS, the applicant has the option of first choosing to obtain a pre-assessment evaluation of the application through an Enabled Pre-Assessment Support Unit (Unidad Habilitada de Apoyo al Predictamen (UHAP)) (MEX-69) within the Coordinating Commission of National Institutes of Health and High Speciality Hospitals (Comisión Coordinadora de Institutos Nacionales de Salud y Hospitales de Alta Especialidad (CCINSHAE)) (referred to as the UHAP-CCINSHAE) or a UHAP within the Mexican Social Security Institute (Instituto Mexicano del Seguro Social (IMSS)). See Scope of Assessment section for detailed information on UHAPs.

Ethics Review Submission

As earlier stated, per HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, all requests for research protocol authorization in human beings and/or their biological samples in Mexico require the applicant to obtain a favorable decision from the REC and the Research Committee, and when applicable, a favorable decision from the Biosafety Committee. Because the submission process at individual institutional RECs will vary, applicants should review and follow their institution’s specific requirements.

9.2

1. Homoclave, name and modality of procedure (Homoclaves COFEPRIS-04-010-A, COFEPRIS-04-010-B, and COFEPRIS-04-010-D)

Access with Electronic Signature of the SAT and Terms of Use

Introduction, Access to the system creation of the profile, Register an email to receive notifications from the platform, and Abbreviations

Introduction, XIII. Specific Sections of the Procedure on the Platform (IX and XI-XIII)

Requirements (31-32 and 11) and Additional Information

Requirements (1-2) and Additional Information

Title II (Chapter II, Article 17 Bis) and Title III (Chapter III, Article 41 Bis), and Title V (Chapter I, Article 98)

Chapter I (Articles 1 and 3) and Chapter IV (Article 14)

Title III (Chapter II, Article 65) and Title V (Chapter I, Articles 99, and 109-111)

5.2, 6.3, and 9.2

Submission Content

Last content review/update: July 2, 2024

Regulatory Authority Requirements

Pharmacy and Poisons Board

As per the CTRules, the G-KenyaCT, and KEN-34, the following documentation must be submitted (signed, dated, and version referenced) to the Pharmacy and Poisons Board (PPB) (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Cover letter
Study protocol
Proof of study registration in the Pan African Clinical Trials Registry (KEN-19)
Patient information leaflet and informed consent form (ICF)
Investigators brochure (IB) and package inserts
Investigational Medicinal Product Dossier (IMPD), including stability data for the investigational product (IP)
Adequate data and information on previous studies and phases to support the current study
Good manufacturing practice (GMP) certificate of the IP from the site of manufacture issued by a competent health authority in the manufacturer’s jurisdiction of origin
Certificate of analysis of the IP
Pictorial sample of the IPs, including the labeling text
Signed investigator(s) curriculum vitae(s) (CV(s)), including that of the study pharmacist (the CV should include the current workload of the principal investigator (PI))
Evidence of contractual agreement between the relevant parties
Evidence of recent good clinical practice (GCP) training of the core study staff
Data and Safety Monitoring Board (DSMB) information, including the charter, composition, and meeting schedule
Detailed study budget
Financial declaration by the sponsor and PI (KEN-2 and Annex 5 of the G-KenyaCT)
No conflict of interest declaration by the sponsor and PI
Signed declarations by the sponsor, PI, and the monitor that the study will be carried out according to the protocol and applicable laws, regulations, and GCP requirements (KEN-1 and Annex 4 of the G-KenyaCT)
Indemnity cover for PI, investigators, and study pharmacist
Clinical trials insurance cover for the study participants
Copy of favorable opinion letter from local ethics committee (EC)
Copy of current practice licenses for the investigators and study pharmacist
Copy of approval letter(s) from collaborating institutions or other regulatory authorities, if applicable
For multicenter/multi-site studies, an addendum for each of the proposed sites including, among other things, the sites’ capacity to carry out the study (e.g., personnel, equipment, laboratory)
A signed statement by the applicant indicating that all information contained in, or referenced by, the application is complete and accurate, and is not false or misleading (Annex 4 of the G-KenyaCT)
Payment of fees
Statistical analysis plan
A signed checklist (KEN-34 and Annex 2 of the G-KenyaCT)

Per the G-KenyaCT, a request for approval of an amendment must include a summary of the proposed amendments; the reason for the amendment; the impact of the amendment on the original study objectives; the impact of the amendments on the study endpoints and data generated; and the impact of the proposed amendments on the safety and wellbeing of study participants.

KEN-35 describes the submission content for requesting annual approval from the PPB.

National Commission for Science, Technology and Innovation

Per the STI-Regs and KEN-31, non-Kenyan applicants must be affiliated with a Kenyan institution. Per KEN-31, applicants must apply online through National Commission for Science, Technology and Innovation (NACOSTI)’s Research Information Management System (RIMS) website (KEN-24) and upload the following:

Passport size color photo in JPG or PNG format
Scanned ID/passport in PDF format
Introductory letter from relevant institution signed by an authorized officer
Affiliation letter from relevant local institution for foreigners signed by an authorized officer and valid for one (1) year
Grant letter from the funding agency to support the amount indicated to fund the research
PPB clinical trial approval
Prior Informed Consent (PIC), Mutually Agreed Terms (MAT), or Material Transfer Agreement (MTA) where applicable, for applications to conduct research on genetic resources and derivatives
Approved research proposal in PDF format
Certificate of ethical clearance of the research (see list of accredited ECs in KEN-25)
Evidence of payment as the last page of the uploaded proposal

Per KEN-31, the following conditions apply to the research license:

The research license is valid for the proposed research, site, and specified period
Both the research license and any rights thereunder are non-transferable
NACOSTI may monitor and evaluate the research
The licensee must inform the relevant County Director of Education, County Commissioner, and County Governor before research commencement
Excavation, filming, and collection of specimens are subject to further permissions from relevant government agencies
The research license does not give authority to transfer research materials
The licensee shall submit one (1) hard copy and upload a soft copy of their final report within one (1) year of completion of the research
NACOSTI reserves the right to modify the conditions of the research license including its cancellation without prior notice

KEN-31 states that if the research is not completed within the stipulated period, the applicant may apply for renewal of the research license and pay the requisite fee. A progress report should be submitted with the request for renewal instead of a proposal. The progress report must indicate the objectives and activities that have been accomplished, as well as the research work that has yet to be undertaken. KEN-31 further indicates that submissions requesting renewal should be made at least 30 days prior to the expiration of the approval period.

Ethics Committee Requirements

EC requirements vary depending on the specific EC. See KEN-17 and KEN-26 for examples of accredited EC submission and review guidelines.

As set forth in the G-ECBiomedRes, a foreign sponsoring agency must also submit its research protocol for ethics review according to its own country’s standards. This research must be responsive to the health needs of Kenya and reasonably accessible to the community in which the research was conducted.

Clinical Protocol

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). The CTRules the G-KenyaCT, the G-ECBiomedRes, and KEN-14 outline the key elements of a research protocol in Kenya (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

A project title that adequately captures the essence of the study
The names, addresses, signatures, and updated abridged curriculum vitae of the investigators
Evidence that the PI has prior training in GCP
Contact information for the EC and collaborating institutions
A summary of the project
Introduction, background, and literature review, including nonclinical data
Study objectives, rationale, questions, and hypothesis/es
Study site, design, and methodology
Ethical considerations
Role of investigators
Schedule
References
Budget
Publication policy
Consent explanation - elements of consent explanations
ICF with signature provisions for participants and the PIs
Risks and benefits
Mode of assessment of the safety and efficacy of the IP
Mode of collecting, analyzing, and reporting the statistics of the clinical trial
Source data documents of the clinical trial
Quality control and quality assurance
Confidentiality
Recruitment, selection, treatment, and withdrawal of participants
Compensation and post-trial access program
Undue inducement and coercion
Voluntariness
Alternative treatment(s) if available
Storage of specimens
MTA, where applicable
Data management and statistical analysis

In addition, per the G-KenyaCT, the protocol should have a clear description of study stoppage rules indicating reasons, who makes the decision, and how the decision will be communicated to the PPB and the EC.

6

Guidelines for Proposal Development

Submission Forms

1.0, 4.2, and 6.0

1.48, 1.63, 1.89-1.130, 1.495, 1.533, and Annexes 1-2 and 4-5

The Science, Technology and Innovation (Research Licensing) Regulations, 2014 (Part II)

Part II (Section 4) and Part IV (Section 9)

Last content review/update: November 8, 2024

Regulatory Authority Requirements

As specified in GenHlthLaw, HlthResRegs, NOM-012-SSA3-2012, COFEPRIS-GCP, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, the following documentation must be submitted to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) as part of the approval process (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Authorizations, Certificates and Visits form (original and two (2) copies) (MEX-25)
Proof of payment of rights (original and two (2) copies)
Request letter (in editable format (.docx) containing study data (title, investigator’s name, etc.), description of study risk level and duration (including estimated start and end dates (DD/MM/YYYY), and documents submitted for research protocol authorization (original)
Response to COFEPRIS prevention letter requesting missing or additional information should be submitted in a new request letter
Research protocol (original and one (1) copy)
Acceptance letter from research institution head and responsible principal investigator (PI)
Sponsor letter of acceptance of position and delegation of responsibilities (must include at least sponsor contact information, description of obligations and protocol rights, sponsor legal representative/authorized person signature, protocol number, when applicable, a certified copy of the apostilled, notarized, and translated power of attorney) (one (1) copy)
Letter of No Conflict of Interest from the sponsor (one (1) copy)
Document proving applicant’s legal identity (e.g., health license, operating notice or, where appropriate, the Federal Taxpayer Registry (Registro Federal de Contribuyentes (RFC)) (one (1) copy)
Follow-up letter from sponsor providing monitoring/auditing plan
Model letter of informed consent in Spanish
Informed consent of the research participant or, where appropriate, the legal representative (original and one (1) copy)
Study schedule (original and one (1) copy)
Health warehouse license for operation of storage and distribution warehouse for biological products for human use, with handling of medications: narcotics, psychotropics, vaccines, toxoids, serums and antitoxins of animal origin and/or blood derivatives (one (1) copy)
Letter of acceptance of responsibility from the importer (signed by legal representative of the importer)
Importer name, license number, and address
Sanitary license of the warehouse for storage and distribution of the research product (only narcotics, psychotropics, biologicals, radiopharmaceuticals, and vaccines)
Letter of import supplies providing approximate total quantity and description of investigational products (IPs) requiring importation at each stage of the study; letter serves as acknowledgement of information, not authorization (original and one (1) copy)
IP route of administration
Insurance policy or current document from the financial fund that covers all study participants at the local level (one (1) copy)
Current Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and Research Committee registration and Biosafety Committee registration, where applicable (one (1) copy)
Favorable opinion of REC, Research Committee, and where appropriate, Biosafety Committee (original and one (1) copy)
REC member list
REC member letters recusing themselves if on research team (one (1) copy)
REC letter describing study follow-up monitoring process (one (1) copy)
Letter of No Conflict of Interest and Confidentiality signed by REC members (one (1) copy)
Institution’s or establishment’s sanitary license or notice of operation (one (1) copy)
Letter of authorization to carry out the research, signed by institutional head or health institution owner (must include protocol title/number, PI name, institution/establishment head signature and position, research center name/address) (original and one (1) copy)
Where applicable, copy of agreement between research centers that have agreements for emergency medical care with other institutions
Acceptance letter from the head of the institution or establishment describing resources available for emergency management (original and one (1) copy)
Health license of the establishment to carry out medical emergency care
Agreement or contract of the establishment for the care of medical emergencies of the research (must include at least title/protocol number; PI name; scope, clauses, and validity; signature of holders and legal representatives of both institutions; statement establishing the care of medical emergencies)
Agreement or contract with institution or establishment to provide care for research related medical emergencies (one (1) copy)
Letter of acceptance, confidentiality, and commitment to report suspected adverse reactions and events signed by the PI (original and one (1) copy)
Summary of PI’s professional record/official professional documentation issued and registered by competent educational authorities (original and one (1) copy)
Professional background of the PI (one (1) copy)
Summary of academic preparation and experience of medical personnel, paramedics, and other experts involved in study (include updated Curriculum Vitae (CV), dated and signed, for each member; include a copy of documentation issued and registered by competent educational authorities accrediting academic preparation) (original and one (1) copy)
Express letter of No Conflict of Interest to conduct the research, signed by the PI and research team
PI letter describing research team’s delegation of responsibilities (must including protocol title/number, detailed description of activities, PI name/signature, team member signatures) (one (1) copy)
Investigator’s Brochure (IB) (original and one (1) copy) (also known as investigator’s manual in Mexico)
Letter describing the sponsoring institution’s or establishment’s resources for the study’s development (include institution/establishment name, PI name, protocol title/number, type of support required (e.g., human, material, financial, advisory information, equipment, auxiliary laboratory services, cabinets, and other resources), and how support will be provided and distributed) (original and one (1) copy)
Document indicating drugs used in study comply with Good Manufacturing Practices (GMPs) and have the expected quality characteristics for IPs to be used in study, or letter documenting GMPs (one (1) copy)
Status of stability studies, or letter documenting IP stability studies comply with applicable regulations (one (1) copy)
Basic pharmacological and preclinical product information
Additional study information (countries where research will be conducted, health conditions/problems, public consultation contact, scientific consultations contact)
Optional pre-assessment evaluation opinion (See Scope of Assessment and Submission Process sections for details on pre-assessment evaluations)

See also Scope of Assessment and Timeline of Review sections for additional COFEPRIS review process and timeline information.

Refer to GenHlthLaw, HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, G-DIGIPRiS-ResProts, and MEX-18 for more detailed submission information. See also MEX-36 for information on obtaining a certificate of GMPs.

Ethics Committee Requirements

As indicated in MEX-84 and G-DIGIPRiS-ResProts, the following documentation should be submitted to obtain the favorable opinion of the REC, the Research Committee, and where appropriate, the Biosafety Committee:

Full title and number of the research protocol
Research protocol with the version and date in Spanish
IB with the version and date in Spanish
Full name of the IP corresponding to the research center
Research center company name and address
Informed consent forms with the version and date in Spanish
Protocol summary
Detailed description of the documents evaluated and approved in Spanish, citing version and date
Validity of the approval opinion (not greater than one (1) year)
Name, position, and signature of the person responsible who supports the opinion
Confirmation of the evaluation of aspects of a scientific nature, the risk/benefit of the protocol as well as the guarantee and well-being of the participants

Additionally, a signed opinion issued on letterhead should be submitted that includes:

Committee name and address (in accordance with its current registration)
Date the opinion was issued
PI name
Company name and address of the research center
Title of the study and protocol number
Status/result of the evaluation of the documents (must be approved)
Date of issue of the opinion (day, month, and year)
Name and position of the signatory who supports the opinion (must be the President or the Secretary Member)

G-DIGIPRiS-ResProts, also notes that only the opinions with the signature of the President of the REC (or, where appropriate, the Secretary-Vocal) will be accepted with a letter attached stating “NO VOTE” or a justification for the absence of the president. See MEX-84 and G-DIGIPRiS-ResProts for additional ethics committee requirements.

Clinical Protocol

As set forth in MEX-84 and G-DIGIPRiS-ResProts, which are in compliance with the Guideline for Good Clinical Practice E6 (R2) (MEX-22), and NOM-012-SSA3-2012, the research protocol should include the following elements (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Title, acronym, and protocol number (corresponds to the opinion of the committee(s) evaluators)
Document version and date, and amendments (if applicable) (corresponds to the opinion of the committee(s) evaluators)
Sponsor name/address and monitor, if different from sponsor
Theoretical framework (IP name/description, preclinical findings summary, etc.)
Definition of problem
Participant selection and withdrawal criteria
Statement that the clinical trial will be conducted in accordance with the protocol, good clinical practices, and local regulatory requirements
Background
Rationale
Hypotheses (if applicable, includes statistical hypotheses)
General objective (if applicable, includes specific, primary, secondary, or exploratory objectives)
specific objectives)
Materials and methods
Study design (e.g., inclusion/exclusion and elimination criteria; information input, processing, analysis, and interpretation)
Phase and type of study
Study duration
Sample size (global and local, as appropriate)
Countries where the research will be carried out
Health conditions or problems studied
Capture, processing, analysis, and interpretation of the information obtained
Route of administration, dose, dosing regimen, and treatment period(s) and justification
Accountability procedure for handling the IP and placebo (if applicable)
Mechanisms for maintaining randomization and blinding (if applicable), and codes for breaking them (e.g., criteria for premature unblinding, etc.)
Statistical considerations
Ethical considerations
Efficacy and safety assessments
Study schedule (document detailing activities to be carried out during the investigation)
Bibliographic references and relevant trial data
Names and signatures of PI and associate researchers (no more than five (5), classified according to their involvement in the research project)
Other documents related to the research project or protocol
Optional pre-assessment evaluation opinion (See Scope of Assessment and Submission Process sections for details on pre-assessment evaluations)

In addition to the protocol submission, per NOM-012-SSA3-2012, an additional letter should accompany the application. Please refer to NOM-012-SSA3-2012 for more specific letter instructions. See also MEX-84 and G-DIGIPRiS-ResProts for more detailed protocol requirements.

2-10

1. Homoclave, name and modality of procedure (Homoclaves COFEPRIS-04-010-A, COFEPRIS-04-010-B, and COFEPRIS-04-010-D)

6. Clinical Trial Protocol and Protocol Amendment(s)

Change Control, V, X. Sections that Make Up a Request for Protocols of Research in Human Beings, and XIII. Specific Sections of the Procedure on the Platform (I - XV)

Requirements

2 and 10.1

Title V (Chapter I, Article 102)

Title III (Chapter I, Article 62) and (Chapter II, Article 69)

6.1-6.3

Timeline of Review

Last content review/update: July 2, 2024

Overview

Based on the CTRules and the G-KenyaCT, the Pharmacy and Poisons Board (PPB)'s review and approval of an application to conduct a clinical trial is dependent upon obtaining ethics approval from a National Commission for Science, Technology and Innovation (NACOSTI)-accredited ethics committee (EC). Therefore, the PPB and EC reviews may not be conducted in parallel. In addition, the STI-Act and KEN-31 specify that all applicants must obtain a research license from NACOSTI prior to initiating a study.

Regulatory Authority Approval

Pharmacy and Poisons Board

Per the G-KenyaCT, sponsors (or applicants) can request pre-submission meetings to discuss pertinent issues prior to making a formal submission. The request must be made via the PPB online system (KEN-16) or in an official letter addressed to the Chief Executive Officer of the PPB and sent to admin@pharmacyboardkenya.org and copied to cta@pharmacyboardkenya.org. The request for a meeting should propose two (2) different dates for the meeting with the proposed dates being at least three (3) weeks away. (See Submission Process section for details on the content of request.)

Per the G-KenyaCT, upon receipt of a clinical trial application, the PPB’s Clinical Trial Division of the Product Safety Department screens the application package for completeness, which takes five (5) days. If accepted, an automatic system-generated reference number will be issued for each application. If additional information is needed, the sponsor will have 10 days to respond. The PPB aims to respond to applications within 30 working days. The sponsor or the representative must reference the PPB/Expert Committee on Clinical Trials (ECCT) number in all future application-related correspondence. The application is then evaluated by the ECCT and PPB staff according to their respective standard operating procedures. The PPB/ECCT’s decision to approve, request additional information, or reject the application is communicated to the sponsor or the representative in writing within 30 days of receiving a valid application. If additional information is requested, the sponsor has 90 days to respond after which the PPB has 15 days to issue a final decision. In certain cases, the PPB may refer the application to external experts for their recommendation.

Per the G-KenyaCT, the sponsor or the representative is also required to request approval annually from the PPB at least six (6) weeks prior to the expiration of the previous approval. Refer to the Checklist for Submitting a Request for Annual Approval (KEN-35) for relevant documentation requirements.

National Commission for Science, Technology and Innovation

Per KEN-5 and KEN-31, the timeline for NACOSTI’s license application process is 30 days.

KEN-31 states that if a research license application does not meet the conditions required under the STI-Act, NACOSTI must reject the application and communicate the reasons to the applicant. Any person may appeal NACOSTI’s decision to the Cabinet Secretary within 30 days of being notified of the decision.

Ethics Committee Approval

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

1.13-1.29, 1.182-1.185, and Annex 7

Part II (Section 4)

Last content review/update: November 8, 2024

Overview

As delineated in HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS))’s review and approval of a protocol authorization request is dependent upon obtaining a favorable decision from the health institution’s Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and the Research Committee, and where applicable, the Biosafety Committee. Therefore, COFEPRIS and ethics committee (REC, Research Committee, and Biosafety Committee) reviews may not be conducted in parallel. However, per HlthResRegs, the REC, the Research Committee, and the Biosafety Committee may meet together to decide whether to authorize a protocol to conduct research on humans, as appropriate.

Regulatory Authority Approval

Pursuant to HlthResRegs, COFEPRIS must approve a request for research protocol authorization within 30 working days from the day following an application’s filing. However, according to G-HumResProt, COFEPRIS is required to complete its review of a research protocol authorization request and notify the applicant within three (3) months.

According to Reg-COFEPRIS and MEX-53, COFEPRIS’s Sanitary Authorization Commission (Comisión de Autorización Sanitaria (CAS)) is responsible for recording, evaluating, and issuing opinions on requests for human research protocol authorizations. Per G-HumResProt, the evaluator in CAS issues a resolution of authorization or a prevention letter, and it is forwarded to the head of the area (CAS) for signature. If a prevention letter is issued in which additional or missing information is requested, the applicant is required to address the issues within 30 calendar days. See Submission Process section for details on tracking submitted procedures via the Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37) or COFEPRIS’s digital procedures and services platform, DIGIPRiS: Online Regulation (MEX-86).

Per G-ResProtocolAmd, G-ObsrvStdies, and G-BioequivStud, COFEPRIS’s review deadlines (three (3) months or 90 calendar days) to notify applicants are also applicable to requests for authorization of protocol amendments or modifications and requests for authorization to conduct risk-free research (observational studies) and bioequivalence studies. Refer to G-ResProtocolAmd, G-ObsrvStdies, and G-BioequivStud for details. See Submission Process section for detailed submission requirements.

Additionally, per Reg-HlthProd and G-UnregDrugImprts, COFEPRIS has 10 days to approve import requests for investigational drug products. If COFEPRIS does not respond within this timeframe, the request is deemed approved. G-UnregDrugImprts also notes that COFEPRIS has four (4) business days to send the applicant a prevention notification regarding missing or additional information required. The applicant, in turn, has five (5) business days to respond.

Per HlthResRegs and G-RNECManual, once the applicant obtains an official authorization from COFEPRIS, the applicant has a maximum of five (5) working days to enter this information into the National Registry of Clinical Trials (Registro Nacional de Ensayos Clínicos (RNEC)) database (MEX-68). The RNEC is in charge of the CAS’s Clinical Trials technical area and serves as the interface through which applicants are required to submit their application documentation in order to maintain an updated national inventory of clinical studies involving humans and/or their biological samples.

Enabled Pre-Assessment Support Unit (UHAP) Evaluations

Per HlthResRegs, prior to submitting an authorization request, applicants may also obtain a pre-assessment evaluation by an authorized third party that helps to facilitate COFEPRIS’s review. MEX-21 and MEX-10 explain that rather than submitting an application directly to the CIS, the applicant has the option of first choosing to obtain a pre-assessment (third party) evaluation of the application through an Enabled Pre-Assessment Support Unit (Unidad Habilitada de Apoyo al Predictamen (UHAP)) (MEX-69) within the Coordinating Commission of National Institutes of Health and High Specialty Hospitals (Comisión Coordinadora de Institutos Nacionales de Salud y Hospitales de Alta Especialidad (CCINSHAE)) (referred to as the UHAP-CCINSHAE) or a UHAP within the Mexican Social Security Institute (Instituto Mexicano del Seguro Social (IMSS)). According to MEX-10, the UHAP has a maximum of 30 calendar days to respond to an evaluation request. See MEX-10 and MEX-121 for additional information on authorized third parties. See the Scope of Assessment and Submission Process sections for detailed UHAP information.

Ethics Committee Approval

As delineated in G-RECs-Op-2018, the REC agenda and documents corresponding to each session should be delivered at least seven (7) days prior to the meeting. It is then recommended that the REC’s decision be sent within a period not exceeding five (5) working days after the committee has met, or if applicable, not to exceed 30 calendar days from the date of request for its review. G-RECs-Op-2018 and G-DIGIPRiS-ResProts also state that the approval of a new application is valid for one (1) year.

In addition, G-RECs-Op-2018 indicates that the REC should establish procedures for monitoring approved studies, from the point at which the decision was made until the completion of the investigation and reporting of results. RECs should conduct at least one (1) review a year.

9.2

10

XIII. Specific Sections of the Procedure on the Platform (XI-XIII)

Requirements (11), Response Time, and Steps

Response Time and Steps

Validity of the Resolution

3.3, 6.2, 8.1, and 8.2

Response Time and Steps

Chapter IV (Article 14)

Title VI (Chapter IV, Article 196)

Title III (Chapter I, Articles 62 and 74a) and (Chapter II, Articles 65 and 69) and Title III bis

5.2, 6.3, 9.2, and 10.3

Initiation, Agreements & Registration

Last content review/update: July 2, 2024

Overview

In accordance with the PPA, the STI-Act, the G-KenyaCT, the G-ECBiomedRes, KEN-21, and KEN-16, a clinical trial can only commence after the sponsor or the representative receives authorization from Kenya’s Pharmacy and Poisons Board (PPB), and ethics committee (EC) approval from an institutional EC that has been accredited by the National Commission for Science, Technology and Innovation (NACOSTI) prior to initiating a study. ECs are accredited pursuant to the requirements delineated in the G-ECAccred. The G-KenyaCT specifies that the PPB review and approval process may not be conducted in parallel with the EC review. In addition, the STI-Act and KEN-31 state that all applicants must obtain a research license from NACOSTI prior to initiating a study. No waiting period is required following the applicant’s receipt of these approvals. Regarding notifications, KEN-31 requires the licensee to inform the relevant County Director of Education, County Commissioner, and County Governor before commencement of the research. Further, the licensee must disclose to NACOSTI, the institutional ECs, and the relevant national agencies any findings that are of national strategic importance.

As per the PPA and the G-KenyaCT, the sponsor or the representative is required to obtain an import license for the shipment of an investigational product to be used in the trial. (See the Manufacturing & Import section for additional information).

As stated in the G-KenyaCT, Kenyan clinical trials should be conducted in compliance with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14).

Clinical Trial Agreement

Prior to initiating the trial, the G-KenyaCT requires that the sponsor agree with investigator(s) on the definition, establishment, and assignment of responsibilities specified in the protocol. These responsibilities include conduct of the trial in compliance with KEN-14 and the approved protocol; data management; unblinding of treatment codes; statistical considerations; and preparation of the final clinical report. The sponsor, in a written document, may agree to transfer all related activities of the clinical trial to designated research institutions. However, all responsibility for the trial lies with the sponsor. Prior to the initiation of the clinical trial, the agreement between the sponsor and investigators should be in writing as part of the protocol submitted for PPB approval or in a separate agreement. The sponsor and investigators must sign and date the protocol of the trial to confirm the agreement.

Clinical Trial Registration

As per the G-KenyaCT, all clinical trials taking place in Kenya must be registered in the PPB’s Online Clinical Trials Registry System (KEN-16). The principal investigator is required to log in and set up an account to register a study.

In addition, as required by KEN-34, all clinical trials taking place in Kenya must be registered in the Pan African Clinical Trials Registry (KEN-19).

1.25, 4, and 5.5

Introduction

1.0, 4.1, and 5.1

Introduction, 1.1, 1.48, 1.63-1.88, 1.346-1.354, and 1.542-1.555

Part III (25A) and Part IV (44)

Parts II, IV, V, and X, and Fourth Schedule

Last content review/update: November 8, 2024

Overview

In accordance with GenHlthLaw, Reg-COFEPRIS, HlthResRegs, NOM-012-SSA3-2012, COFEPRIS-GCP, G-HumResProt, and MEX-84, a clinical trial can only commence after an applicant receives authorization from Mexico’s Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)). Per HlthResRegs, G-HumResProt, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, the applicant must also obtain a favorable decision from the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and the Research Committee at the health institution where the study is being conducted, and when applicable, a favorable decision from the Biosafety Committee. No waiting period is required following the applicant’s receipt of these approvals.

As per GenHlthLaw, an applicant must be a resident of Mexico and is required to obtain an import license from COFEPRIS for the shipment of an investigational product to be used in the trial. The applicant must be a resident of Mexico or have a legal representative submit the application on their behalf. (See the Manufacturing & Import section for additional information).

As set forth in NOM-220-SSA1-2016, the health record holder, principal investigator (PI), sponsor, or person responsible for a study authorized by COFEPRIS must also issue a notice of a study’s commencement (e.g., first visit of the first patient) and a notice of its completion (e.g., last visit of the last patient).

Clinical Trial Agreement

Prior to initiating the trial, as set forth in NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, if applicable, the sponsor must sign a letter of acceptance that serves as an agreement to assume the project obligations and rights stated in the letter. G-DIGIPRiS-ResProts also notes that the letter must include the sponsor’s delegation of activities to other institutions and/or companies duly authorized to accept the obligations, responsibilities, and rights imposed by the development and conduct of the study. Per G-DIGIPRiS-ResProts and NOM-012-SSA3-2012, in the case of corporate entities, this position must be accepted by an individual authorized to do so or by a corporation’s legal representative, according to its organizational structure or incorporation regime.

Additionally, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts state that the sponsor must sign a letter to ensure there are no conflicts of interest that could lead to the interruption of treatment for the research participant. NOM-012-SSA3-2012, further specifies that when the research is sponsored by a public or private organization, that it must be guaranteed that this will not generate conflicts of interest that could cause the interruption of treatment for the research participant. A detailed explanation of the resources available and the way in which they will be provided and distributed must also be attached in the research protocol.

According to COFEPRIS-GCP, COFEPRIS requires the sponsor or the contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32) for conducting clinical trials. COFEPRIS-GCP indicates that the sponsor must establish in writing each of the research team member functions and responsibilities, and the financial agreement with the PI. The sponsor or the CRO must also establish a declaration of financing, sponsorship, affiliations, contracts of agreements with other institutions involved, and procedures for handling any conflict(s) of interest, and a system for providing incentives and quantity/payments to research participants. MEX-32 specifies that the financial aspects of the trial should be documented in an agreement between the sponsor and the investigator and the institution.

Further, per MEX-32, prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an investigator’s brochure and should provide sufficient time for the investigator and institution to review the protocol and the information provided.

COFEPRIS-GCP further states that in the case of delegating investigation-related activities to a CRO, the sponsor must also establish in writing each of the activities that are delegated. However, the ultimate responsibility for all CRO activities remains with the sponsor. Additionally, COFEPRIS-GCP indicates that the sponsor or the CRO must establish a declaration of financing, sponsorship, affiliations, contracts, or agreements with other institutions involved, handling of any conflict of interest, incentives, and quantity and payments to the research participants.

According to MEX-32, the sponsor or the CRO must also obtain the investigator(s)’s and the institution(s)’s agreement to:

Conduct the trial in compliance with MEX-32 and the protocol agreed to by the sponsor and approved by the ethics committee
Comply with data recording and reporting procedures
Permit monitoring, auditing, and inspection
Retain essential documents until the sponsor informs them that they are no longer needed

Per MEX-32, the sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

Clinical Trial Registration

Per G-DIGIPRiS-ResProts, once an official authorization from COFEPRIS is obtained, some of the data provided by the applicant in COFEPRIS’s digital procedures and services platform, DIGIPRiS: Online Regulation (MEX-86), will be migrated to COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37) and to the National Registry of Clinical Trials (Registro Nacional de Ensayos Clínicos (RNEC)) database (MEX-68). According to MEX-109, the G-RNECManual is useful for information on registering with RNEC for clinical trial applications submitted in person at the CIS (MEX-37).

Governance

Per GenHlthLaw, HlthResRegs, and NOM-012-SSA3-2012, every health institution where research is conducted is required to establish a Research Committee and a Biosafety Committee. Per HlthResRegs, NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, REC and Research Committee approval is also required for each trial site where a study is being conducted, and when applicable, Biosafety Committee approval is required as well.

HlthResRegs explains that the Research Committee evaluates the technical quality and scientific merit of the proposed research, and its opinion must contain the REC opinion and, where applicable, the Biosafety Committee opinion. The Biosafety Committee, in turn, is responsible for determining and regulating the use of ionizing radiation or genetic engineering techniques within the health institution as indicated in HlthResRegs, GenHlthLaw, and NOM-012-SSA3-2012. Pursuant to HlthResRegs, NOM-012-SSA3-2012, and G-HumResProt, the Biosafety Committee issues a technical opinion on the biosafety aspects of the proposed research and ensures that research study staff, research participants, the community, and the environment are protected against radiological risks.

Additionally, per MEX-47, COFEPRIS is responsible for registering Research Committees and Biosafety Committees. Refer to MEX-47, G-BiosafetyReg, and G-ResCommReg for detailed Research Committee and Biosafety Committee registration requirements. See MEX-26 for COFEPRIS’s Research Committee and Biosafety Committee registration form.

2, 4.1, 4.5, and 9.2

4.9, 5.6, and 5.9

XIII. Specific Sections of the Procedure on the Platform (IX and XI-XIII)

Requirements (2-3 and 11)

Preamble, 2, 4.1, 4.9-4.11, 4.13, and 5.7

Title V (Chapter I, Article 98), Title XII (Chapter I, Articles 194 and 194 bis) and (Chapter XIII, Articles 238-239 and 283-285), and Title XVI (Chapter I, Articles 368-369 and 371-372)

Chapter I (Articles 1 and 3) and Chapter IV (Article 14)

Title I (Chapter I, Articles 9 and 10), Title III (Chapter I, Article 62) and (Chapter II, Articles 65 and 69), Title V (Chapter I, Articles 99-102 and 110-111), and Title VI (Chapter I, Articles 113 and 117)

7.4

5.2, 6.3, 7.4, and 9.1-9.2

Safety Reporting

Last content review/update: July 2, 2024

Safety Reporting Definitions

According to the CTRules and the G-KenyaCT, the following definitions provide a basis for a common understanding of Kenya’s safety reporting requirements:

Adverse Event (or Adverse Experience) (AE) – Any untoward medical occurrence in a participant in a clinical investigation study or intervention product, and which does not necessarily have a causal relationship with the treatment
Adverse Drug Reaction (ADR) – All noxious and unintended responses to a clinical trial study or interventional product related to any dose or all unintended noxious responses to a registered medicinal product which occurs at doses normally used in humans for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function
Serious Adverse Event (SAE) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect
Suspected Unexpected Serious Adverse Reaction (SUSAR) – A serious adverse reaction that is not identified in practice, severity, or frequency by the referenced safety information

Safety Reporting Requirements

Investigator Responsibilities

Per G-KenyaCT, the investigator must ensure that all SAEs are reported promptly to Kenya’s Pharmacy and Poisons Board (PPB) within the mandated timelines, as described below. Proper protection procedures or treatments should be administered to trial participants with SAEs.

Sponsor Responsibilities

As indicated in the CTRules and the G-KenyaCT, the sponsor should report to the PPB and all relevant institutions, all SAEs and SUSARs occurring during the course of the trial. The G-KenyaCT specifies that the sponsor should expedite reporting all SAEs to the PPB and the ethics committee (EC), and the sponsor and investigators should immediately undertake appropriate and necessary measures and treatment to protect the trial participants. The CTRules delineates that where a sponsor conducts a clinical trial on the same health product or active pharmaceutical substance in another country, the sponsor must submit a report of any SUSAR or SAE that occurs in the other clinical trial to the PPB. Per the CTRules and the G-KenyaCT, a sponsor must submit an initial report of an fatal or life-threatening SUSAR or SAE as soon as it occurs but, in any case, not later than seven (7) days after the occurrence of the event. The G-KenyaCT indicates that if the initial report is incomplete, the sponsor must submit a completed report based on the initial information within an additional eight (8) days. As required in the CTRules and the G-KenyaCT, a report of the occurrence of a SUSAR or SAE must specify whether the SUSAR or SAE is related to the clinical trial.

As indicated in the CTRules and the G-KenyaCT, other important considerations and timelines include the following (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

The sponsor must notify all the investigators involved in ongoing clinical trials of the investigational product (IP) of all SAEs and SUSARs within 15 calendar days
Any IP-related SAE must receive immediate medical attention and be reported to the PPB
The SAE report form must be completed (including lab results) and submitted to enable causality assessment
All fatal cases must be accompanied by a formal autopsy report, and a verbal autopsy report should be submitted in those exceptional cases where a formal autopsy is not possible
Any frequent IP related AE/ADR must receive immediate medical attention and be reported to the PPB within seven (7) days
The sponsor must submit a report on a SUSAR that is not fatal or life-threatening within 15 days after the occurrence of the event
The principal investigator (PI) is required to submit follow-up information as soon as it becomes available
All additional information should be clearly marked as updated and must include the Protocol Number and Participant Number
Foreign regulatory decisions that affect the safety or use of the product under study must be reported to the PPB within seven (7) days through a detailed report
Literature reports that have implications for the safety of the IP must be submitted within 15 days with a detailed report and a copy of the publication
New information or notification of change in nature, severity, or frequency of risk factors for the product under study or conduct of trial must be submitted within 15 days

Other Safety Reports

The G-ECBiomedRes indicate that ECs should monitor research, and will report to the National Bioethics Committee upon notification of an AE.

The CTRules and the G-KenyaCT state that the sponsor must also submit a safety report to the PPB once a year throughout the clinical trial, or upon request. The purpose of the annual safety report is to briefly describe all new safety information relevant to one (1) or more clinical trial(s), and to assess the safety conditions of the participants enrolled in these trial(s). The safety report must include a log of SAE and SUSAR events. The SAE and SUSAR log should include the following:

Patient Identification
Age
Date of recruitment into the study
Type of SAE or SUSAR
SAE or SUSAR start and end dates
Reason for reporting the event as an SAE or SUSAR
Relation to IP
SAE or SUSAR outcome

Note that the PPB may require more frequent reporting of the safety reports depending on the nature of the clinical trial being implemented. When this is the case, the PPB must communicate the required frequency to the PI and sponsor in writing.

Form Completion & Delivery Requirements

As per the G-KenyaCT and KEN-16, all SAEs and SUSARs must be reported to the PPB via the Pharmacovigilance Electronic Reporting System (PvERS) (KEN-6).

4.1 and 5.1

Glossary of Terms, 1.59, 1.63-1.88, and 1.318-1.339

Part I (2) and Part IV (12)

Last content review/update: November 8, 2024

Safety Reporting Definitions

In accordance with NOM-220-SSA1-2016, NOM-012-SSA3-2012, G-ClinResPV, and G-PharmPerSafRpt, the following definitions provide a basis for a common understanding of Mexico’s safety reporting requirements (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Adverse Event/Experience (AE) – Any undesirable medical event that may occur in a research participant during the clinical investigation stage of a drug/vaccine, but does not necessarily have a causal relationship to it
Adverse Drug Reaction or Adverse Reaction (ADR) – An unwanted response to a drug, in which the causal relationship with it is, at least, reasonably attributable
Unexpected Adverse Drug Reaction – One whose nature or severity is inconsistent with the applicable product information, or in the documentation presented for its sanitary registration
Suspected Adverse Drug Reaction (SRAM) – Any clinical or laboratory manifestation that occurs after administration of one (1) or more drugs

Safety Reporting Requirements

As specified in NOM-220-SSA1-2016-Mod, for clinical study related incidents involving health professionals (public and private) or institutions conducting health research, notifications to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS))’s National Pharmacovigilance Center (CNFV) must be submitted according to the following timelines:

Serious SRAMs or serious AEs/ADRs must be reported within a maximum of seven (7) calendar days, if fatal, and within a maximum of 15 days, if not fatal (severe cases from abroad should only be included in the final study safety report, if the study has a research center in Mexico)
Not serious SRAMs or AEs/ADRs must be reported at the end of the study
Two (2) or more serious cases, in the same place with the same drug and the same batch, must be reported immediately, and no later than 48 hours
When a review of scientific literature shows a safety issue, it should be reported within a maximum of 30 calendar days from first knowledge of the AE/ADR

HlthResRegs and NOM-012-SSA3-2012 state that the institution must notify and provide a report to the Ministry of Health (Secretaría de Salud) within a period of 15 days after the suspension or cancellation of the research has been agreed upon. The report should specify the effect(s) detected, all medical care steps adopted, and the consequences produced. A detailed report on the research participant(s) physical condition should also be included. NOM-012-SSA3-2012 indicates that all serious or deadly adverse reactions or effects must be immediately reported to the Ministry. Per NOM-012-SSA3-2012, the principal investigator (PI), the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)), the institutional head(s), or the Ministry of Health must also suspend or cancel the research as soon as any AE representing an ethical impediment to research is identified.

Additionally, per NOM-220-SSA1-2016, institutions must notify the CNFV of a study’s suspension or cancellation within a maximum of 15 days. If the study is resumed, the CNFV must also be notified within a maximum of 15 working days following the study’s recommencement.

Per MEX-2, COFEPRIS has also implemented the following International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines:

Guideline E2B (R3) on Electronic Transmission of Individual Case Safety Reports (ICSRs) – Data Elements and Message Specification – Implementation Guide (MEX-79)
ICH Harmonised Tripartite Guideline: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A) (MEX-80)
ICH Harmonised Tripartite Guideline: Pharmacovigilance Planning (E2E) (MEX-82)

Investigator Responsibilities

As specified in HlthResRegs, NOM-012-SSA3-2012, and COFEPRIS-GCP, the PI must report to the REC all probable AEs or any AEs directly related to the research study. Per NOM-012-SSA3-2012, the investigator is also responsible for submitting safety reports to the CNFV.

Other Safety Reports

As indicated in NOM-220-SSA1-2016, a pharmacovigilance study protocol should be prepared and submitted to the Executive Director of Pharmacopeia and Pharmacovigilance through COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37).

Per NOM-220-SSA1-2016, a clinical safety report is also required to be submitted to the CNFV for all trials, sponsored or not, that have at least one (1) site or research center in Mexico. In addition, G-ClinResPV explains that a final safety report must be submitted to the CNFV in the following circumstances:

A study is completed that has included at least one (1) research center in Mexico
A study has been cancelled, discontinued, or definitively suspended
A bioequivalence, bioavailability, and pharmacokinetics study is concluded

Refer to G-ClinResPV and G-PharmPerSafRpt for additional report writing instructions and criteria that align with the safety reporting requirements delineated in NOM-220-SSA1-2016 and NOM-220-SSA1-2016-Mod. See also G-PharmRptReq for detailed pharmacovigilance reporting guidelines and to extend sanitary registrations for drug products.

Form Completion & Delivery Requirements

G-ClinResPV specifies that clinical safety reports must be written in Spanish and submitted electronically (in PDF format) to the CNFV. In addition, reports should be submitted by either the health record holder or the sponsor or the legal representative to avoid sending duplicate information to the CNFV. G-PharmPerSafRpt states, in turn, that the safety report must be written in Spanish in the sections delineated in Annex 1 of G-PharmPerSafRpt and submitted electronically via CD or USB in editable PDF format. As indicated in G-ClinResPV and G-PharmPerSafRpt, the annual safety report submission date is determined by the date of the study’s first national authorization by COFEPRIS.

As per MEX-117, the E-Reporting Industry platform, which is linked to VigiFlow (MEX-43), was developed by the World Health Organization (WHO)’s Uppsala Monitoring Centre for the pharmaceutical industry to manage individual case safety reports at the national level. Reports are submitted by pharmaceutical industry professionals including health registration holders or their legal representatives and institutions/establishments where research is conducted as well as contract research organizations, distributors, and marketers. MEX-117 also specifies the CNFV is responsible for granting access to the E-Reporting Industry tool, and requests can be made via email: xmlvigiflow@cofepris.gob.mx. Refer to MEX-117 for details. Additionally, per MEX-77, state centers, institutional coordinating centers, institutional centers, and pharmacovigilance units of the National Health System should also report AE/ADRs, SRAMs, ESAVIs, and other safety issues via MEX-43.

MEX-78, in turn, provides patients, consumers, and health professionals instructions on reporting ADRs via VIGIRAM (MEX-118). See MEX-12 for instructions on using MEX-118, see MEX-30 for the form to be completed via MEX-118, and see MEX-119 for additional information on MEX-118. See also G-ADR-PatientRpt for information on how patients, consumers, and/or family members report suspected ADRs.

Refer to NOM-220-SSA1-2016 for detailed reporting requirements, and the G-AENotif, MEX-44, and MEX-117 for submitting safety reports via VigiFlow (MEX-43). See also MEX-54 for additional CNFV issued pharmacovigilance guidelines and requirements.

1. Generalities, 3. Content Development (3.1), and 5. Annex A

XIII. Specific Sections of the Procedure on the Platform (IX)

3.6

2-6

1-5

1, 4, 6, Table 1, and Annex 1

Title III (Chapter I (Article 64))

4.21, 4.44-4.45, 4.53, 4.55-4.56, 4.59, 4.72, 7.5, 7.7, and 8.1-8.3

8.1.2, 8.1.11, and 8.2.1-8.2.10

4.5, 8.7-8.10, and 10.9

Progress Reporting

Last content review/update: July 2, 2024

Interim and Annual Progress Reports

As stated in the G-KenyaCT, the sponsor and/or the principal investigator (PI) is required to send progress reports to the Pharmacy and Poisons Board (PPB) on an annual basis, or as may be required, from the date of the trial’s initiation. The progress report should contain the following:

Current status of the study
Summary of the participants screened (e.g., failed screenings, participants enrolled, withdrawn, or lost to follow-up, and other challenges)
Summary of protocol deviations and violations
Updated investigational product Investigator’s Brochure
Drug Safety Update Report
Copy of the latest Data Safety Management Board report
Copy of favorable opinion from the ethics committee (EC) on record
Copy of annual practice license for the investigators and pharmacists
Suspected, Unexpected, Serious Adverse Event (SUSAR) and Serious Adverse Event (SAE) Log

For multisite trials, per the G-KenyaCT, the sponsor or the representative must submit a summarized report for all of the sites and include the information listed above.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As per KEN-14, the investigator should promptly provide written reports to the sponsor and the institutional EC on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.

According to the G-KenyaCT, for annual renewal of the study, the sponsor or the representative must submit a copy of the progress report including the documents listed above. The request must also be accompanied by copies of annual practice licenses for the investigators and pharmacists, and a copy of valid insurance coverage for the participants. All documents must be submitted using the PPB’s Online Clinical Trials Registry System (KEN-16). The sponsor or the representative must receive an acknowledgement of this submission before proceeding with the study. These documents must be submitted to the PPB at least six (6) weeks prior to the expiration of the previous approval.

Pursuant to KEN-14, the investigator should submit written summaries of the trial status to the institutional EC annually, or more frequently, if requested.

Final Report

Per the G-KenyaCT, the sponsor must notify the PPB of the end of a clinical trial taking place at a Kenyan site within 15 days. After the trial has been conducted and closed, the applicant must submit an executive summary report of the study within 30 days. This should be followed by a clinical study report within 180 days of the study closure unless otherwise justified. The report must comply with the International Council for Harmonisation's ICH E3 format (KEN-13). The report must include a short but comprehensive summary of the trial’s essential findings and methodology and should also contain a layman’s summary. Additionally, the sponsor must inform the PPB of any results that will be publicly released at least 14 days before release. In addition, upon completion of the trial, as delineated in KEN-14, the investigator is required to submit a final report to the institutional EC summarizing the trial’s outcome.

For multi-site research, the G-ECBiomedRes requires all parties to decide on procedures for drafting a common final report and publication at the onset of the research. Individual sites or institutions must not publish any data until the appropriate authorities accept the combined report.

KEN-31 further indicates that the research license applicant must submit one (1) hard copy and upload a soft copy of the final research report to the National Commission for Science, Technology and Innovation (NACOSTI) within one (1) year of the research’s completion.

4.10 and 4.13

5.1

1.48, 1.63, 1.497-1.506, 1.515-1.518, and 1.533-1.536

Last content review/update: November 8, 2024

Interim and Annual Progress Reports

Per HlthResRegs, NOM-012-SSA3-2012, and MEX-28, the principal investigator (PI) must prepare and submit a progress report (also referred to as a partial technical or technical-descriptive report) (MEX-31) to the Ministry of Health (Secretaría de Salud) at any time, but at least once a year, to communicate progress and partial research study results. In addition, per NOM-012-SSA3-2012, information related to any investigation that the PI submits to the Ministry of Health must be classified as confidential. NOM-012-SSA3-2012 further states that the PI must also provide a copy of every report to the head of the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and the Research Committee, and if applicable, the Biosafety Committee of the institution where the research takes place.

NOM-012-SSA3-2012 specifies that the progress reports should describe the results obtained and at a minimum should include the following elements:

Identification data
Materials and methods
Results
Conclusions
Bibliographic references
Any relevant exhibits

In accordance with NOM-012-SSA3-2012, a report should be submitted annually to the Ministry of Health on the integration and activities of the REC, the Research Committee, and, if applicable, the Biosafety Committee, during the first 10 business days of June.

Final Report

As set forth in HlthResRegs, NOM-012-SSA3-2012, and MEX-28, the PI is also required to submit a final report to the Ministry of Health in order to communicate the final results of a research protocol or project as well as the major findings obtained throughout the course of the study. Additionally, per NOM-012-SSA3-2012, the PI must deliver a copy of this report to the research team members, the REC, the Research Committee, and the Biosafety Committee, as applicable, where the study was conducted.

As per NOM-012-SSA3-2012, the final reports should describe the results obtained and at a minimum should include the following elements:

Identification data
Summary
Introduction
Materials and methods
Results
Discussion
Conclusions
Bibliographic references
Any relevant exhibits/Annexes

See section 7.4 of NOM-012-SSA3-2012 for additional required report information.

HlthResRegs further states that the PI is also required to submit a final report to the Research Committee at the institution where the study was conducted. Refer to MEX-31 for the reporting form.

Title VI (Chapter I (Articles 116 and 119-120))

4.8-4.10, 7.1, 7.4, 10.10, and 12.1

Definition of Sponsor

Last content review/update: July 2, 2024

As per the G-KenyaCT, a sponsor is defined as an individual, a company, an institution, or an organization who takes legal responsibility for the initiation, management, and financing of a trial. According to the G-KenyaCT, a sponsor, in a written document, may agree to transfer all related activities of the clinical trial to designated research institutions. However, all responsibility for the trial lies with the sponsor. The G-ECBiomedRes indicates that sponsors may be foreign, but must comply with certain conditions including affiliating themselves to institutions recognized in Kenya.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). In accordance with KEN-14, Kenya permits a sponsor to transfer any or all of its trial-related duties and functions to a contract research organization (CRO) and/or institutional site(s). However, the ultimate responsibility for the trial data’s quality and integrity always resides with the sponsor. Any trial-related responsibilities transferred to a CRO should be specified in a written agreement. The CRO should implement quality assurance and quality control.

5.1 and 5.2

4.1 and 6.0

Glossary of Terms, 1.48, 1.63, and 1.68

Last content review/update: November 8, 2024

As set forth in NOM-012-SSA3-2012, COFEPRIS-GCP, and MEX-84, a sponsor is defined as an individual or corporation willing to undertake responsibilities to participate and finance a research project or protocol, in full or in part.

According to COFEPRIS-GCP, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires the sponsor or the contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32) for conducting clinical trials. Per COFEPRIS-GCP and MEX-32, a sponsor is an individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial. A sponsor may also hire a CRO to conduct one (1) or more of the activities related to health research that are sponsored in the country. The sponsor must specify in writing any trial-related duty and function that is transferred to and assumed by a CRO. However, the ultimate responsibility for all CRO activities remains with the sponsor. Additionally, MEX-32 notes the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor, and any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor. COFEPRIS-GCP also indicates that CROs of foreign origin must also have a registered address in Mexico, and an authorization to carry out clinical research activities in the country.

4.1

1.53 and 5.2

1.5-1.6, 4.1-4.2, and 4.15

4.18

Site/Investigator Selection

Last content review/update: July 2, 2024

Overview

The G-KenyaCT, which requires sponsors to follow the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), states that the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial and for ensuring that the investigator(s) are qualified by education, training, and experience.

Per the CTRules and the G-KenyaCT, investigators must also meet the following requirements (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Provide evidence of their qualifications and experience through an up-to-date curriculum vitae (CV)
Have a current practice license from the relevant regulatory authority
Be familiar with the characteristics and appropriate use of the investigational product (IP) as described in the protocol, current investigator’s brochure (IB), in the product information, and in other information sources
Have a clear understanding and willingness to obey the ethical, good clinical practice (GCP) and legal requirements in the conduct of the trial
Permit monitoring and auditing of the trial and inspection by the Pharmacy and Poisons Board (PPB) or appointed representatives
Keep a list of appropriately qualified persons to whom the investigator has delegated significant trial-related duties
The principal investigator (PI) must be an appropriately qualified and competent person having practical experience within the relevant professional area and who is responsible for the conduct of the clinical trial at a clinical site
The PI must have a degree in medicine, pharmacy, pharmacology, toxicology, biochemistry, dentistry, or a related discipline from a university recognized in Kenya
The PI must have a valid practice license from the relevant regulatory authority
The PI must have a valid professional indemnity cover
The PI must be a citizen of Kenya or a permanent resident in Kenya
A PI must have had previous experience as a co-investigator in at least two (2) trials in the relevant professional area
Have adequate time and resources to carry out the study (See Annex 6 of the G-KenyaCT for the PPB’s recommended format to document the investigator’s workload)

Further, the G-KenyaCT states that sponsors must ensure that investigators have had formal training in GCPs with proof that a GCP course was attended within the last two (2) years. If training has not been completed, it is the responsibility of the sponsor to organize this training prior to initiating the study. The investigators will need to provide evidence of having obtained this training. As delineated in KEN-14, prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an IB. Furthermore, the sponsor must sign an agreement or contract with the participating institution(s). Additionally, the sponsor must define and allocate all study related duties and responsibilities to the relevant parties participating in the study. (See the Submission Content section for additional information on clinical trial application requirements.)

Institutional Registration

The STI-Act and the STI-Regs require research institutions to register with the National Commission for Science, Technology and Innovation (NACOSTI) and obtain a Certificate of Registration. For detailed guidance on the vetting and approval process, see the STI-Regs and the G-InstitutionRegistration.

Upon creating an account in NACOSTI’s Kenya National Research Information System (KENRIS) (KEN-23), research institutions can apply for new research institution registration, maintain/update data, and submit annual reports. The application for registration of research institutions is also provided in KEN-11, and the reporting tool for registered research institutions is provided in KEN-36.

Foreign Sponsor Responsibilities

The G-ECBiomedRes requires that with collaborative research projects, the collaborating investigators, institutions, and countries must function as equal partners with safeguards to avoid exploitation of local researchers and participants. An external sponsoring agency should submit the research protocol to their country’s EC, as well as the Kenyan EC where the research is to be conducted. Further, this research must be responsive to the health needs of Kenya and reasonably accessible to the community in which the research was conducted. Consideration should be given to the sponsoring agency agreeing to maintain health services and faculties established for the purposes of the study in Kenya after the research has been completed. Such collaborative research must have a local/Kenyan co-principal investigator.

Data and Safety Monitoring Board

The G-KenyaCT indicates that the PPB recommends establishing a Data and Safety Monitoring Board (DSMB) to monitor trials in the following types of studies:

Where the endpoint is such that a highly favorable or unfavorable result, or even a finding of futility at an interim analysis, might ethically require the trial to be terminated early
When there are safety concerns due to the use of a particularly invasive treatment
Where there is prior information suggesting the possibility of serious toxicity with the study treatment
Where the participants involved represent a vulnerable population (e.g., children, pregnant women, elderly, terminally ill, or mentally incapacitated)
When the participants represent a population at higher risk of death or other serious outcomes
When the study is large, of long duration, and multi-center

KEN-14 states that a DSMB may be established to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial.

Per the G-KenyaCT, the DSMB must provide the following documentation to the PPB:

DSMB composition
Copy of DSMB charter
DSMB reports to be submitted to the PPB within two (2) weeks of its deliberations and in the request for annual approval

For multicenter trials, the G-ECBiomedRes requires that centralized data management and analysis should be planned as per G-WHO-DSMB.

Multicenter Studies

Per the G-KenyaCT, for multicenter studies in Kenya, the coordinating investigator should be a Kenyan resident and should assume full responsibility for the trial.

The G-ECBiomedRes requires that multicenter trials conducted simultaneously by several investigators at different sites follow the same protocol. Ideally, these trials should be initiated at the same time at all sites. The sponsor must provide the protocol to the investigators, who will accept the protocol in writing. If approved by the EC of the local host institution, the protocol may be modified to suit the local conditions. Meetings should be organized at the initial and intermediate stages of the trial to ensure uniform procedures at all sites. All sites and parties should also agree on procedures for publication of a final report. Research staff should receive training at every trial site on the uniform procedures. In addition, research staff at all sites should implement standard methods for recruitment and evaluation/monitoring of laboratory procedures and conduct of trial. There must be monitoring to ensure the sites are following the protocol, which must include measures to terminate the participation of some sites, if necessary. Finally, centralized data management and analysis should be planned as per G-WHO-DSMB.

Additional multicenter guidance is delineated in KEN-14:

All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor, and, if required, by the PPB, and given EC 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

1.25, 5.5, 5.6, and 5.23

4.1, 5.1, and 6

Glossary of Terms, 1.30-1.88, 1.340-1.345, and Annex 6

Part V

Science, Technology and Innovation (Registration and Accreditation of Research Institutions) Regulations, 2014 (Part II, First Schedule, and Second Schedule)

Part III (7)

Last content review/update: November 8, 2024

Overview

According to COFEPRIS-GCP, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires the sponsor or the contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32) for conducting clinical trials. COFEPRIS-GCP states the sponsor or the CRO is responsible for selecting each research center and ensuring that COFEPRIS has authorized its operation as well as the human and material resources needed to conduct research. MEX-32 indicates the sponsor should ensure the investigator(s) have adequate resources to properly conduct the trial for which they are selected. Additionally, MEX-32, explains the investigator should have available an adequate number of qualified staff and adequate facilities for the foreseen duration of the trial to conduct the trial properly and safely.

Per COFEPRIS-GCP, the sponsor must establish in writing each of the research team member functions and responsibilities, and the financial agreement with the principal investigator (PI). G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts also note the sponsor or the CRO must specify in a letter the human and material resources that will be allocated for the research and the way in which they will be provided and distributed to the research sites.

As stated in the HlthResRegs and NOM-012-SSA3-2012, all investigators must possess appropriate qualifications, training, and experience. Per COFEPRIS-GCP, the PI is also responsible for selecting a research team with knowledge, education, and training in MEX-32, and in the process of the investigation in which the investigator is involved. Per MEX-32, the sponsor must ensure each investigator is qualified by education, training, and experience to assume responsibility for the proper conduct of the trial; meets all the qualifications specified by the applicable regulatory requirement(s); and provides evidence of such qualifications through updated curriculum vitae (CV) and/or other relevant documentation requested by the sponsor, the ethics committee (EC), and/or COFEPRIS. G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts also indicate the PI should provide legally issued and registered documentation delineating appropriate academic training and experience appropriate to the research to be conducted, which includes academic preparation, representative scientific production, and clinical practice.

G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts also indicate that institutions in charge of providing medical care for study related medical emergencies are required to sign an agreement or contract to provide these services, and a provide letter stating the institution’s acceptance, authorization, and description of the available resources.

Foreign Sponsor Responsibilities

COFEPRIS-GCP indicates that foreign CROs must have a registered address in Mexico, and an authorization or notice specifying the activities to be carried out in the country.

Data Safety Monitoring Board

According to COFEPRIS-GCP, the sponsor or the CRO is responsible for the continuous monitoring of the study which should be established based on the nature of the study, and must ensure study monitoring is carried out in compliance with MEX-32. Per MEX-32, the sponsor or the CRO may consider establishing an independent data monitoring committee to assess the progress of a clinical trial, the safety data, the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial. The committee should have written operating procedures and maintain written records of its meetings.

Multicenter Studies

As delineated in MEX-32, in the event of a multicenter clinical trial, the sponsor or the CRO must ensure that:

All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor, and, if required, by COFEPRIS, 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 between investigators is facilitated

4.6, 7.2-7.3, and 8.2

1.25, 4.1-4.2., 5.5-5.7, and 5.23

XIII. Specific Sections of the Procedure on the Platform (IV, VIII, and IX)

Requirements (4, 19-20, and 24)

Preamble, 3.8, 4.14.7, 4.10-4.11, 4.13, and 4.15

Title III (Chapter I, Article 62) and Title VI (Chapter I, Articles 113 and 117)

10.1

0 and 1

Insurance & Compensation

Last content review/update: July 2, 2024

Insurance

As set forth in the G-KenyaCT and the G-ECBiomedRes, the sponsor must provide insurance cover for the study participants and ensure that the clinical trial institution, contract research organization (CRO), and researchers have sufficient insurance cover for the clinical trial. Per the G-KenyaCT, the sponsor’s policies and procedures should address the treatment costs for trial participants in the event of trial-related injuries, and the sponsor should submit this information as part of the clinical trial application (see KEN-34). In addition, a no-fault insurance cover must be obtained for all controlled human infection studies. The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14) guides sponsors on providing insurance. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

For all sponsor-initiated studies, insurance coverage must be provided by an insurer registered by Kenya’s Insurance Regulatory Authority (IRA), and a valid insurance certificate must be issued by the IRA prior to the trial’s initiation and cover the duration of the study. The insurance certificate must be submitted as evidence to the Pharmacy and Poisons Board (PPB). The certificate must be properly executed by an insurance company under a valid insurance policy which makes explicit reference to the proposed study. In addition, the policy must grant coverage for any participant injury that is causally linked to trial activities. The policy must also cover the investigator(s)’ and the sponsor(s)’ liability in the trial, without excluding any damage which may be attributed to negligence. Moreover, self-insurance of the participants by other entities, such as the National Health Insurance Fund, will not be sufficient.

Further, per the G-KenyaCT, the sponsor must ensure that the investigators and CROs have professional indemnity insurance coverage for the period of the trial. The host institution must also have in place sufficient insurance to meet the potential liability of its investigators, those acting on behalf of the investigators, and its research members.

Compensation

Injury or Death

As specified in the G-KenyaCT and the G-ECBiomedRes, the sponsor is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death. Per the G-ECBiomedRes, participants are entitled to such financial or other assistance as would compensate them equitably for any temporary or permanent impairment or disability. In the case of adverse events, there should be proper assessment, evaluation, and compensation. The G-ECBiomedRes also indicates that when investigational vaccines contain active or live-attenuated micro-organisms, should participants in the control group contract the disease for which a vaccine is being tested, free treatment must be provided.

In addition, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14) provides guidance for sponsors on providing compensation to research participants in the event of trial-related injuries or death. The sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries.

Trial Participation

The G-ECBiomedRes defines compensation to include offers to participants, monetary or otherwise, to offset the time and inconvenience for participating in research.

Post-Trial Access

Per the G-KenyaCT, the sponsor must put in place measures to ensure that the study participants have access to successful investigational products for their disease condition before the products have received a marketing authorization in Kenya, especially for the Phase III clinical trials. The G-ECBiomedRes indicates that when investigational vaccines contain active or live-attenuated micro-organisms, post-trial access to the vaccine should be available to the control group.

4.8 and 5.8

Definitions, 3.2, 4.2, and 5.3

1.48, 1.63-1.130, 1.173-1.181, and 1.437-1.490

Last content review/update: November 8, 2024

Insurance

As set forth in COFEPRIS-GCP, the sponsor or the contract research organization (CRO) must establish a financial fund or have insurance to cover serious adverse events that result from the medication or the research study.

Additionally, per COFEPRIS-GCP, which requires the sponsor or the CRO to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32), the sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator/institution against claims arising from the trial, except for those claims arising from malpractice and/or negligence. Per MEX-32, if required by the applicable regulatory requirement(s), the sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator and the institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence.

Compensation

As specified in COFEPRIS-GCP, the sponsor or the designated CRO must establish a statement of funding and describe the quantity and payments to be allocated for research participants.

Per MEX-32, the ethics committee (EC) should review both the amount and method of payment to participants to ensure that neither presents problems of coercion or undue influence on the trial participants. Payments to a participant should be prorated and not wholly contingent on the completion of the trial by the participant.

Injury or Death

Although NOM-012-SSA3-2012 does not specifically ascribe responsibility to the sponsor, it indicates that the research budget must include the availability of a financial fund as well as mechanisms to guarantee continuity of medical treatment and indemnity of the research participant, in the event of trial-related injuries. Additionally, the head of the institution or establishment, the, Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)), Research Committee, or Biosafety Committee, the PI, and, where applicable, the sponsor, must be responsible, in accordance with their area of competence, for the damage to health resulting from the development of the research as well as damage resulting from the interruption or early suspension of treatment for reasons not attributable to the research participant.

Per HlthResRegs and GenHlthLaw, the health care institution and the sponsor or the CRO must provide medical attention to injured participants, and where appropriate, legally required compensation, if the injuries are directly related to the study. Medical attention that is provided to such participants will not prejudice the compensation that may be legally due from the study.

In addition, per COFEPRIS-GCP, the sponsor or the CRO is also responsible for ensuring that research institutions provide urgent care resources, or where appropriate, have a written agreement with the health institution that will handle the emergencies. The agreement must comply with NOM-206-SSA1-2002, which establishes the criteria for the operation and attention in providing emergency services in health care institutions

MEX-32 explains the sponsor's policies and procedures should address the costs of treatment of trial subjects in the event of trial-related injuries in accordance with the applicable regulatory requirement(s). In addition, when study participants receive compensation, the method and manner of compensation should comply with applicable regulatory requirement(s).

In addition, per G-DIGIPRiS-ResProts and G-HumResProt, the sponsor should provide the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) with a copy of the financial fund or current insurance policy, which guarantees the continuity of the medical treatment and the compensation to which the participant will be legally entitled in the event of suffering damages directly related to the development of the research. MEX-84 specifies that the insurance policy or current document from the financial fund should cover all study participants at the local level. The document guarantees coverage to the participant in case of any injury or damage related to the research. The insurance policy and certificate must indicate the number of participants that will be covered, study title, protocol number, and must be on behalf of the license holder and the sponsor.

Trial Participation

Per COFEPRIS-GCP, the sponsor or the CRO must ensure that each and every treatment, clinical analysis procedure, and other study procedures are delivered in a timely manner, in good condition, and free of charge to the research participant.

4.3

3.1 and 5.8

XIII. Specific Sections of the Procedure on the Platform (IV)

Requirements (6)

Preamble, 4.1, 4.8, and 4.13-4.14

Title V (Chapter I, Article 100)

Title II (Chapter I, Article 14) (Chapter II, Article 21), and (Chapter V, Article 58)

5.14 and 7.2

Risk & Quality Management

Last content review/update: July 2, 2024

Quality Assurance/Quality Control

As stated in the CTRules and the G-KenyaCT, the sponsor is responsible for maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), the STI-Regs, and other applicable regulatory requirements. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed. In addition, per the STI-Regs, all persons and research institutions (i.e., sponsors) undertaking research in Kenya must ensure the highest standards and quality of research for the realization of institutional mandates and national priorities.

In addition to complying with KEN-14, the G-KenyaCT indicates QA processes should be developed to ensure:

Regular and continuous monitoring of the study and the implementation of monitoring reports’ recommendations
Submission of the study monitoring plan to the Pharmacy and Poisons Board (PPB) during the initial submission of the application
The clinical trials research site must have valid registrations and approvals
Patient safety and confidentiality are not compromised
Analysis or evaluation of samples is performed in accordance with the protocol and good clinical practice (GCP) principles and, where applicable, the contract/agreement, the work instruction, and associated methods
Adherence to the laboratories’ policies and SOPs
Trial data is recorded and reported accurately, legibly, completely, and in a timely manner
Trial data is archived
Preparation of a work instruction detailing the procedures that will be used to conduct the analysis or evaluation prior to the initiation of sample analysis or evaluation, as necessary
Be built or adapted for the purpose
Have automated equipment for routine hematology, biochemistry, and serology tests
Have procedures for analyzer calibration and quality control
Regular maintenance of all the equipment, including point-of-care equipment
Have a procedure for transporting samples safely and quickly from clinical areas to the laboratory
Have written procedures for all assays, and to validate the assays
Reagents and consumables are used within their expiry dates based on a stock control procedure
Records are kept, including source documents and final reports
Have a procedure for authorizing and releasing results
Have a procedure for ‘flagging’ and notifying medical staff of abnormal results
Have a laboratory information management system, and validate and back up the system
Protective clothing and safety equipment are provided for staff
Have a central alarm system for all fridges and freezers
Have an internal audit program

Per KEN-14, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

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

Per the G-KenyaCT protocol violations and protocol deviations must be reported to the PPB within seven (7) days of the principal investigator (PI) becoming aware of them. The details to be reported must include:

Date of the deviation/violation
Study participant(s) affected
Name of the treating physician
Detailed description of the deviation/violation
Indication whether the study participants were adversely affected by the deviation/violation
Explanation of why the deviation/violation occurred
Measures taken to address the deviation/violation
Measures taken to preclude future recurrence of the deviation/violation

In addition, see G-KenyaCT for information about medical care of trial participants during and following the clinical trial. Also see the Bft-Risk for a standardized approach for evaluating and reporting the balance between the benefits and risks of health products, which includes investigational products (IPs) undergoing clinical trial application.

The CT-Emrgcy provides guidance to sponsors, PIs, and institutions on the conduct of clinical trials during public health emergencies to maximize the safety of research participants, minimize risks to participants and the community, and ensure the integrity of the clinical trials. See CT-Emrgcy for details on a range of issues, including contingency planning, communications with participants, changes to studies, protocol deviations, reporting, and supply of IPs during a public health emergency.

Controlled Human Infection Studies

The G-KenyaCT also provides detailed information on controlled human infection studies (CHIS) requirements to ensure investigator/study personnel compliance with GCP and other QA/QC requirements, including the following:

The well characterized strain of an infectious agent should be administered at a controlled dose and by a specific route to carefully selected adult volunteers
The studies require safe and accurate microbiology, good clinical facilities, careful recruitment, and monitoring
Participants must be monitored for evidence of carriage or infection under medical supervision to anticipate or manage symptoms of disease and adverse events
The value of the information to be gained should clearly justify the risks and the study must have a risk mitigation plan
The investigators should be adequately qualified, trained, and experienced in the conduct of CHIS as well as treating patients with the infectious disease being investigated

For the complete list of requirements, see the G-KenyaCT.

The G-ECBiomedRes provides additional considerations when investigational vaccines contain active or live-attenuated micro-organisms:

The participant to be vaccinated should be given adequate information about the adverse effects.
Should participants in the control group contract the disease for which a vaccine is being tested, free treatment must be provided.
Because the risks associated with vaccines produced by recombinant DNA techniques are not completely known, PPB guidelines must be strictly followed.
Post-trial access to the vaccine should be available to the control group

Monitoring Requirements

As part of its QA system, the G-KenyaCT requires the sponsor to develop an internal audit program. The G-KenyaCT defines an audit as a systematic examination, carried out independently of those directly involved in the trial, to determine whether the conduct of a trial complies with the agreed study protocol and whether data reported are consistent with those on record at the site. Further, the sponsor is required to obtain agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities An investigator must, upon request from any properly authorized officer or employee of PPB, at reasonable times, permit such officer or employee to have access to, and copy and verify any records or reports made by the investigator.

Per KEN-14, the sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose onsite monitoring, a combination of onsite and centralized monitoring, or, where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan).

KEN-31 indicate that the National Commission for Science, Technology and Innovation (NACOSTI) may conduct an evaluation, or cause an evaluation to be conducted, of a research study to assess and evaluate compliance with the conditions of the applicable research license.

Premature Study Termination/Suspension

The G-KenyaCT states that if a trial is terminated by the PI or the sponsor, the PI or the sponsor must inform the PPB not later than 15 days following the termination date. The co-investigators must also be informed as soon as possible and should be advised in writing of potential risks to the research participants, and they must ensure that patients continue to receive medical care. The PPB must be provided with reason(s) for the termination and its impact on the proposed or ongoing trials with respect to the IP, including issues relating to IP accountability and disposal as well as record(s) maintenance. In addition, the PPB may withdraw the authorization to conduct a clinical trial if it finds that the safety of the participants is compromised or that the scientific reasons for conducting the trial have changed.

According to KEN-14, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the EC should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor.

5.0-5.2, 5.5, 5.18-5.19, 5.21, and 6.10

4.2 and 5.3

1.42A, 1.63-1.88, 1.125, 1.437-1.491, 1.497-1.506, 1.525, and 1.533-1.536

The Science, Technology and Innovation (Registration and Accreditation of Research Institutions) Regulations, 2014 (Part III); and The Science, Technology and Innovation (Relevance and Quality Assurance in Research) Regulations, 2014 (Parts I-III)

Part III (8)

Last content review/update: November 8, 2024

Quality Assurance/Quality Control

According to COFEPRIS-GCP, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires the sponsor or the contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32), and to ensure and control the quality of the research during a study. Per COFEPRIS-GCP and MEX-32, the sponsor or the CRO is also responsible for establishing written standard operating procedures (SOPs) for each stage of the investigation. In addition, the sponsor or the CRO must implement and maintain quality assurance (QA) and quality control (QC) systems to make certain the trial is conducted, and data are generated, recorded, and reported in compliance with the protocol.

MEX-32 further delineates the sponsor or the CRO is required to obtain agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. The sponsor and investigator(s) agreement should be confirmed in writing prior to the trial. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed.

Monitoring Requirements

According to COFEPRIS-GCP, the sponsor or the CRO must ensure and control the quality of the research through periodic monitoring visits and audits to ensure compliance with the protocol and the SOPs, and if necessary, compliance with reports derived from inspections or verifications by COFEPRIS. The principal investigator (PI) is responsible for reporting and guaranteeing the quality and validity of the data obtained during the investigation. MEX-32 indicates the sponsor should ensure that the trials are adequately monitored and determine the appropriate extent and nature of monitoring, which should be based on considerations such as the objective, purpose, design, complexity, blinding, size, and endpoints of the trial.

Additionally, per MEX-32, the sponsor should also appoint the monitors who should be appropriately trained, and have the scientific and/or clinical knowledge needed to monitor the trial adequately. A monitor’s qualifications should be documented. Monitors should also be thoroughly familiar with the investigational product(s), the protocol, written informed consent form, and any other written information to be provided to research participants, the sponsor’s SOPs, COFEPRIS-GCP, and the applicable regulatory requirement(s).

MEX-32 further indicates the sponsor should appoint individuals, who are independent of the clinical trials/systems, to conduct audits and ensure the auditors are qualified by training and experience to conduct audits properly. An auditor’s qualifications should be documented. The sponsor should also ensure the auditing of clinical trials/systems is conducted in accordance with the sponsor's written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports. The sponsor's audit plan and procedures for a trial audit should be guided by the importance of the trial to submissions to regulatory authorities, the number of study participants, the type and complexity of the trial, the level of risks to the study participants, and any identified problem(s). Auditor(s) observations and findings of the auditor should be documented.

Pursuant to MEX-32, noncompliance with the protocol, SOPs, good clinical practice, and/or applicable regulatory requirement(s) by an investigator/institution, or by member(s) of the sponsor's staff should lead to prompt action by the sponsor to secure compliance. If the monitoring and/or auditing identifies serious and/or persistent noncompliance on the part of an investigator/institution, the sponsor should terminate the investigator's/institution’s participation in the trial and notify promptly the regulatory authority(ies). Also, upon the request of the monitor, auditor, ethics committee (EC), or COFEPRIS, the investigator/institution should also make available for direct access all requested trial-related records. See MEX-32 for detailed monitoring and auditing requirements.

Per NOM-012-SSA3-2012, the institutional head, the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)), Research Committee, or Biosafety Committees, the PI, and, where applicable, the sponsor, must be responsible, in accordance with their area of competence, for monitoring the research. NOM-012-SSA3-2012, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts further require the sponsor or the CRO to provide a follow-up letter to COFEPRIS describing the monitoring and auditing plan to be carried out during the investigation. G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts specify the letter must contain the following (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Type of plan: audit or monitoring
Frequency of application
Responsibility for monitoring, and where appropriate, cite the third party to carry out the activity
Objective and scope of monitoring
Evaluation tools and methodology implemented
Methodology to carry out the scientific, technical, and ethical monitoring
Communication and notification strategies between investigator, sponsor, ECs, and COFEPRIS
Profile of the monitor or auditor
Classification of findings and decision-making
Decision-making derived based on severity classification
Notification mechanism to the PI, ECs, and COFEPRIS
Design of the Action Plan: Corrective, Improvement, or Preventive
Reporting results through the partial and annual technical report (See MEX-31 for the partial reporting form)

COFEPRIS-GCP also states that the PI is responsible for reporting and guaranteeing the quality and validity of the data obtained during the investigation.

Premature Study Termination/Suspension

Per HlthResRegs the PI, the REC, the institutional head or other authorized institutional officers, or the Ministry of Health (Secretaría de Salud) must order the immediate suspension or cancellation of a research study as soon as any adverse effect is identified that might become an ethical or technical impediment to continuing with the study. The health care institution will submit a report to the Secretariat within 15 business days following the day in which the suspension or cancellation of the study was agreed, specifying the effect noticed, the measures adopted, and consequences produced. NOM-012-SSA3-2012 similarly states the head of the institution or establishment, the REC, the Research Committee, the Biosafety Committee, or PI must order the immediate suspension or cancellation of research, in the presence of any severe adverse effects, which become an ethical or technical impediment to continue with the study and notify the Secretariat in detail. The institutional head must notify the Secretariat of any adverse effect resulting from the experimental research within a maximum period of 15 working days from the event occurrence, including the care measures adopted, the identified sequelae, as well as a detailed report on the physical condition of the patient, which mentions whether the patient is free of any risk at the time of notification. In such case, the resumption of the research will require a new authorization. The investigator is also responsible for suspending the investigation if there is a risk of serious injury, disability, or death of the research subject in accordance with GenHlthLaw. Additionally, per NOM-220-SSA1-2016, institutions must notify the National Pharmacovigilance Center (CNFV) of a study’s suspension or cancellation within a maximum of 15 days. If the study is resumed, the CNFV must also be notified within a maximum of 15 working days following the study’s recommencement. The investigator is responsible for submitting safety reports to the CNFV.

MEX-32 delineates if a trial is prematurely terminated or suspended, the sponsor should promptly inform the investigators/institutions and the regulatory authority(ies) of the termination or suspension and the reason(s) for the termination or suspension. The EC should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor or by the investigator/institution, as specified by the applicable regulatory requirement(s). The EC should also be provided with a detailed written explanation of the termination or suspension.

MEX-32 further indicates that if the trial is prematurely terminated or suspended for any reason, the investigator/institution should promptly inform the trial participants, ensure appropriate therapy and follow-up for the participants, and, where required by the applicable regulatory requirement(s), inform the regulatory authority(ies). If the investigator terminates or suspends a trial without prior agreement of the sponsor, the investigator should inform the institution where applicable, and the investigator/institution should promptly inform the sponsor and the EC and provide the sponsor and the EC with a detailed written explanation of the termination or suspension. If the EC terminates or suspends its approval/favorable opinion of a trial, the investigator should inform the institution where applicable, and the investigator/institution should promptly notify the sponsor and provide the sponsor with a detailed written explanation of the termination or suspension.

4.2

4.9, 4.12, 5.1, 5.12, and 5.18-5.21

XIII. Specific Sections of the Procedure on the Platform (IV)

Requirements (5)

Preamble, 3.5, 4.1, 4.6, 4.9, and 4.13

Title V (Chapter I, Article 100)

Title III (Chapter I, Article 64)

7.5

7.2, 8.7-8.8, 9.2, and 10.5

Data & Records Management

Last content review/update: July 2, 2024

Electronic Data Processing System

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As per KEN-14, when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. Per KEN-14, the sponsor should base their approach to validate such systems on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. In addition, the sponsor should maintain standard operating procedures (SOPs) for the systems that cover setup, installation, and use. The responsibilities of the sponsor, investigator, and other parties should be clear, and the system users should be provided with training. Refer to KEN-14 for additional information.

Records Management

According to the G-KenyaCT, it is the responsibility of the investigator and the sponsor to archive safely all trial-related documentation. All Kenyan trial site-related documentation must be archived within the country and not exported. Additionally, the sponsor/applicant must inform the Pharmacy and Poisons Board (PPB)’s Expert Committee on Clinical Trials (ECCT) in writing prior to destroying any trial documents. The notification must include the protocol number, start and end date, and the license number.

The G-KenyaCT states that study documents must be archived for a minimum of 10 years from the end of the study. Also, records must be made available to the PPB within three (3) days if there is a concern regarding the use of a clinical trial drug and/or a risk to the health of the clinical trial participant. In any other case, records must be provided within seven (7) days of request.

Per the STI-Regs, sponsors should store research findings and information regarding research systems in a designated location with clear labels of the subject area. Research findings must be documented in bound books or documents with the research title, author, year, and other relevant information clearly printed on the cover page. A report of research work by staff and the research institution must be submitted to the National Commission for Science, Technology and Innovation (NACOSTI) within two (2) months after publication or compilation of the research report.

In addition, KEN-14 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

1.65, 5.5, and 8

Glossary of Terms, 1.48, 1.63, and 1.537-1.541

The Science, Technology and Innovation (Registration and Accreditation of Research Institutions) Regulations, 2014 (Part IV)

Last content review/update: November 8, 2024

Electronic Data Processing System

According to COFEPRIS-GCP, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires the sponsor or the contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32) for conducting clinical trials. Per MEX-32, the sponsor should utilize appropriately qualified individuals to supervise the overall conduct of the trial, to handle the data, to verify the data, to conduct the statistical analyses, and to prepare the trial reports.

In addition, per MEX-32, when using electronic trial data processing or handling systems or remote electronic trial data systems, the sponsor should:

Ensure and document that the electronic data processing system(s) conform(s) to the sponsor's established requirements for completeness, accuracy, reliability, and consistent intended performance
Maintain standard operating procedures (SOPs) for using these systems
Ensure that the systems are designed to permit data changes in such a way that the data changes are documented and that there is no deletion of entered data
Maintain a security system that prevents unauthorized access to the data
Maintain a list of the individuals who are authorized to make data changes
Maintain adequate backup of the data
Safeguard the blinding, if any

See MEX-32 for additional data processing requirements.

Records Management

As indicated in MEX-32, the sponsor, or other owners of the data, should retain all of the sponsor-specific essential documents pertaining to the trial (see section 8 of MEX-32). The sponsor should retain all sponsor-specific essential documents in conformance with the applicable regulatory requirement(s) of the country(ies) where the investigational product (IP) is approved, and/or where the sponsor intends to apply for approval(s). If the sponsor discontinues the clinical development of an IP (i.e., for any or all indications, routes of administration, or dosage forms), the sponsor should maintain all sponsor-specific essential documents for at least two (2) years after formal discontinuation or in conformance with the applicable regulatory requirement(s).

MEX-32 also states the essential documents should be retained until at least two (2) years after the last marketing approval or at least two (2) years have elapsed since the formal discontinuation of clinical development of the IP. These documents should be retained for a longer period, however, if required by the applicable regulatory requirement(s) or if needed by the sponsor. The sponsor should inform the investigator(s)/institution(s) in writing of the need for record retention and should notify the investigator(s)/institution(s) when trial-related records are no longer needed.

In addition, as delineated in COFEPRIS-GCP, the principal investigator (PI) is responsible for preparing, integrating, using, filing, and ensuring the safekeeping of the research participant’s clinical file for a minimum of five (5) years in accordance with NOM-004-SSA3-2012, MEX-32, and Good Documentation Practices per NOM-164-SSA1-2015.

Per NOM-004-SSA3-2012, clinical records are the property of the institution or the medical services provider that generates them. However, the patient/participant has ultimate ownership rights over this information to protect their health and the confidentiality of their data. Consequently, because the documents are prepared in the interest and benefit of the patient/participant, they must be kept for a minimum period of five (5) years, which is calculated from the date of the last medical procedure/visit.

4.9, 5.5, and 8

3.7 and 4.1

4.1, 5.1, and 5.2

5.4

Personal Data Protection

Last content review/update: July 2, 2024

Responsible Parties

For the purposes of data protection requirements, DPA delineates that the sponsor acts as the “data controller” in relation to research data. This is because the sponsor determines the purpose and means of processing personal data. The "data processor" processes personal data on behalf of the data controller. Data controllers and processors must be registered with the Kenya Data Commissioner. Per the DataProtect, an application for registration of a data controller or data processor must be on Form DPR1 (found in the First Schedule of DataProtect) with supporting materials and the required registration fees as specified in the Second Schedule. See the DataProtect for additional details on registration requirements.

Data Protection

Per the DPA, the data controller (sponsor) must ensure that personal data is:

Processed in accordance with the right to privacy of the data subject
Processed lawfully, fairly, and in a transparent manner in relation to any data subject
Collected for explicit, specified, and legitimate purposes and not further processed in a manner incompatible with those purposes
Adequate, relevant, and limited to what is necessary in relation to the purposes for which it is processed
Collected only where a valid explanation is provided whenever information relating to family or private affairs is required
Accurate and, where necessary, kept up to date, with every reasonable step being taken to ensure that any inaccurate personal data is erased or rectified without delay
Kept in a form that identifies the data subjects for no longer than is necessary for the purposes for which it was collected
Not transferred outside Kenya, unless there is proof of adequate data protection safeguards or consent from the data subject

The DataProtect, which implements the DPA, requires data controllers and data processors to develop, publish, and regularly update a policy on their personal data handling practices. The policy should include the nature of personal data collected and held, how a data subject may access their personal data, complaints handling mechanisms, the lawful purpose for processing personal data, and requirements for when personal data is to be transferred outside Kenya. Regarding cross-border transfers of data, a data controller or data processor who is a transferring entity must (before transferring personal data out of Kenya) ascertain that the transfer is necessary. This necessity decision should be based on considerations such as data protection safeguards, an adequacy decision made by the Data Commissioner, and if there is consent of the data subject.

Per the DataProtect, data controllers and/or data processors must retain personal data processed for a lawful purpose and only as long as may be reasonably necessary for the purpose for which the personal data is processed. A data controller or data processor must establish a personal data retention schedule with appropriate time limits and periodic reviews. When the retention period has ended, the personal data must be erased, anonymized, or pseudonymized.

See DataProtect for additional details on data protection, including data subject rights, data protection design and principles, notification of breaches, impact assessments, and exemptions.

See Parts IV-VII of the DPA for detailed requirements on data processing, sensitive personal data, exemptions, and transfer of personal data outside of Kenya. The G-ECBiomedRes requires compliance with the DPA.

Consent for Processing Personal Data

Per the DPA, the data controller (sponsor) or data processor must bear the burden of proof for establishing a data subject’s consent to the processing of their personal data for a specified purpose. For the purposes of processing personal data, consent means any manifestation of express, unequivocal, free, specific, and informed indication of the data subject’s wishes by a statement or by a clear affirmative action, signifying agreement to the processing of personal data relating to the data subject. Unless otherwise provided under the DPA, a data subject has the right to withdraw consent at any time. The withdrawal of consent must not affect the lawfulness of processing based on prior consent before its withdrawal.

The DataProtect requires data controllers and data processors to ensure that a data subject has the capacity to consent and voluntarily gives consent. In seeking consent (prior to the processing), the data subject should be informed of:

The identity of the data controller or data processor
The purpose of each of the processing operations for which consent is sought
The type of personal data that is collected and used
Information about the use of the personal data for automated decision-making, where relevant
The possible risks of data transfers due to absence of an adequacy decision or appropriate safeguards
Whether the personal data processed will be shared with third parties
The right to withdraw consent
The implications of providing, withholding, or withdrawing consent

Per the DataProtect, this information may be presented to the data subject through a written notice, oral statement, audio or video message. The data controller or a data processor must ensure that the data subject has the capacity to voluntarily give consent that is specific to the purpose of processing.

Children

The DPA indicates that in cases where the data subject is a minor, a person who has parental authority or a guardian may exercise personal data protection rights conferred on the subject. With regard to data processing, the DPA requires that every data controller (sponsor) or data processor must not process personal data relating to a child unless consent is given by the child's parent or guardian and the processing is in a manner that protects and advances the rights and best interests of the child. A data controller or data processor must incorporate appropriate mechanisms for age verification and consent to process personal data of a child, including available technology, volume of personal data processed, proportion of such personal data likely to be that of a child, possibility of harm to a child arising out of processing of personal data, and other factors as may be specified by the Kenya Data Commissioner.

Mentally Impaired

The DPA indicates that in cases where the data subject has a mental or other disability, a person duly authorized to act as the participant’s guardian or administrator may exercise personal data protection rights conferred on the subject.

4.2.5

Part I (2), Part III (18) and (25), and Parts IV-VII

No. 263 (Parts I-X) and No. 265 (5, First Schedule, and Second Schedule)

Last content review/update: November 8, 2024

New Info (Not Yet in Profile)

Effective March 21, 2025, the new Federal Law on the Protection of Personal Data Held by Private Parties repeals PDP-PrivateLaw. The law provides some revisions to key definitions, data controllers’ obligations, and data subjects’ rights, amongst other things.

Responsible Parties

According to the PDP-PrivateLaw, the PDP-Reg, the PDP-Public, and MEX-4, a private entity that processes personal data is called the “responsible person or entity” or “controller.” Federal, state, or local authorities are referred to as “obliged subjects” and make decisions about the processing of personal data. The private and public entities must protect personal data in accordance with the above laws and regulations.

Data Protection

PDP-PrivateLaw, PDP-Reg, and PDP-Public provide the requirements, responsibilities, and restrictions for handling personal data in the public and private sectors. The PDP-Public regulates the processing of personal information in the public sector by “obliged subjects”. The PDP-PrivateLaw and the PDP-Reg regulate the processing of personal information in the private sector by an individual or legal entity of a private nature.

Per the PDP-PrivateLaw, the PDP-Reg, and the PDP-Public, the sponsor or the sponsor’s representative(s) must comply with the principles of data protection: legality, purpose, loyalty, consent, quality, proportionality, information, and responsibility in the processing of personal data.

According to the PDP-PrivateLaw, the PDP-Reg, and the PDP-Public, the sponsor is also required to protect the confidentiality of the owner of the personal data and their background. The PDP-PrivateLaw further notes that this obligation will remain in place even after the data processing activities have been completed and the relationship between the sponsor or the sponsor’s representative(s) and the data owner has concluded.

Additionally, the PDP-PrivateLaw and the PDP-Public provide definitions to address health related data. Sensitive personal data refers to the most intimate sphere of its owner, whose improper use may result in discrimination, or carries a serious risk of resulting in discriminatory activities. More specifically, data considered to be sensitive may reveal personal information such as racial or ethnic origin, present or future health status, genetic information, religious, philosophical, and moral beliefs, political opinions, and sexual preferences.

Per the PDP-PrivateLaw, the PDP-Reg, and the PDP-Public, data owners have the right to be informed about the collection and use of their personal data. Per the PDP-Reg, the person responsible must also inform the information owner regarding the existence and main characteristics of the treatment to which their personal data will be subjected through the consent document, known as the “privacy notice,” in accordance with the provisions of the PDP-PrivateLaw and the PDP-Reg.

Please refer to the PDP-PrivateLaw, the PDP-Reg, and the PDP-Public for detailed information on the principles guiding the protection and handling of personal data. See also MEX-3 and MEX-4 for additional information on data protection requirements.

Consent for Processing Personal Data

As explained in the PDP-PrivateLaw and the PDP-Public, the consent document or “privacy notice” is a physical document, electronic, or any format generated by the sponsor, that is made available to the data owner prior to processing the owner’s personal data. The PDP-Reg further explains that the privacy notice must be characterized as simple, with necessary information expressed in clear and understandable language, and with a structure and design that facilitates the owner’s understanding.

The PDP-PrivateLaw states that in the case of sensitive data, the sponsor is required to obtain the express and written consent of the data owner for the sponsor’s use, through a written or electronic signature, or any authentication mechanism established for that purpose. In cases where sensitive personal data is being processed, the sponsor must make reasonable efforts to limit processing to the minimum period necessary to complete the goal as delineated in the privacy notice. Moreover, databases containing sensitive personal data may not be created without justifying their creation for legitimate, concrete purposes, and if they are not in accordance with the specified activities delineated and pursued by the sponsor. The PDP-Reg also notes that sponsors may only create databases containing sensitive personal data when they obey a legal mandate; are justified pursuant to the territorial scope of the regulation; or are required by the sponsor for legitimate, concrete purposes, and in accordance with the activities or explicit purposes indicated in the privacy notice.

The PDP-Reg, whose focus is on regulating the process of personal data held in physical or electronic media, further indicates that the sponsor must obtain prior consent to process the data when acquired personally or directly from its owner. Whether tacit or express, the consent process must be:

Free: without error, bad faith, violence, or intent, which may affect the manifestation of the owner’s will
Specific: referring to one (1) or more specific purposes that justify the treatment, and
Informed: the owner has knowledge of the privacy notice prior to granting consent to the processing of their data

The sponsor must obtain the owner’s express consent when their data is deemed sensitive. The express consent must also be unequivocal; that is, there are elements that indisputably demonstrate its granting.

As delineated in the PDP-Public, the sponsor will not be required to obtain consent when processing sensitive data in the following cases:

When an applicable law authorizes such processing, and is consistent with and does not contravene the bases, principles, and provisions set forth in the PDP-Public
When sensitive personal data transfers are made between those responsible, the transfers are compatible with the original purpose that motivated the processing of personal data
When there is a judicial order, resolution, or well-founded and motivated mandate of the competent authority
For the recognition or defense of the owner's rights before the competent authority
When personal data is required to exercise a right or fulfill obligations derived from a legal relationship between the owner and the person in charge
When there is an emergency that could potentially harm an individual or the individual’s property
When personal data is necessary to carry out a treatment for the prevention, diagnosis, or provision of health care
When the personal data appear in publicly accessible sources
When personal data is subject to a prior dissociation procedure
When the owner of the personal data is a person reported missing under the terms of the law on the matter

Please refer to the PDP-PrivateLaw, the PDP-Reg, and the PDP-Public for detailed consent and privacy notice requirements.

Consent for Processing Personal Data of Minors

Per the PDP-Public, in processing the personal data of minors, the best interest of the children and adolescents must be prioritized in accordance with the applicable legal provisions. MEX-4 further states legal guardians must always give consent when processing children’s personal data. This applies to any individual younger than 18 years of age.

(See the Children/Minors section for additional information on consent requirements for children/minors.)

2.1, 6.1, and 8.2

Articles 1-3, 6, 8-9, 12-17, 21, and 23-25

Articles 1, 3, 7, 16, 22-23, 26, 31, and 59

Articles 1-4, 9-12, 15, 23-24, 36, and 56-57

Documentation Requirements

Last content review/update: July 2, 2024

Obtaining Consent

In all Kenyan clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14). (Per the G-KenyaCT, research must be conducted in accordance with the requirements set forth in KEN-14.) The informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by a National Commission for Science, Technology and Innovation (NACOSTI)-accredited institutional ethics committee (EC). The ICF must be provided to the Pharmacy and Poisons Board (PPB) with the clinical trial application. (See the Required Elements section for details on what should be included in the form.)

The CTRules, the G-KenyaCT, and the G-ECBiomedRes state that the investigator, or the designated representative, must provide detailed research study information to the participant or legal representative/guardian. Per G-ECBiomedRes, all individual consent must be written and, in no case, should collective community agreement or the consent of a community leader or other authority substitute for an individual informed consent. The G-KenyaCT and the G-ECBiomedRes also specify that the oral and written information concerning the trial, including the ICF, should be easy to understand and presented without coercion or unduly influencing a potential participant to enroll in the clinical trial. None of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or to appear to waive the legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or the representatives from their liabilities for any negligence. The participant or legal representative/guardian should also be given adequate time to consider whether to participate.

Re-Consent

According to the CTRules, the G-KenyaCT, and KEN-14, any change in the ICF due to a protocol modification should be approved by the EC before such changes are implemented. The participant or legal representative/guardian will also be required to re-sign the revised ICF and receive a copy of any amended documentation.

Language Requirements

As stated in the CTRules and the G-KenyaCT, the ICF content should be presented in either English or Kiswahili, and the local spoken language of the area, where applicable. Copies of the English ICF should be submitted to the PPB and to the EC.

Documenting Consent

The CTRules and the G-KenyaCT state that the participant or legal representative/guardian, and the person who conducted the informed consent discussion should sign and personally date the ICF. Where the participant is illiterate, and/or the legal representative/guardian is illiterate, verbal consent should be obtained in the presence of and countersigned by an impartial witness. Before participating in the study, the participant should receive a copy of the signed and dated ICF, and any other written information provided during the informed consent process. The participant or legal representative/guardian should also receive a copy of any updates to the signed and dated ICF.

According to KEN-14, where the participant is illiterate and/or the legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:

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

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

Waiver of Consent

No information is available.

2, 4.4, 4.8, 8.2, and 8.3

Definitions, 4.1, 4.2, and 4.13

1.48, 1.63, and 1.188-1.212

Part IV (11)

Last content review/update: November 8, 2024

Obtaining Consent

In all Mexican clinical trials, a freely given informed consent is required from each participant in accordance with the requirements set forth in HlthResRegs, GenHlthLaw, NOM-004-SSA3-2012, and COFEPRIS-GCP. Per COFEPRIS-GCP, the principal investigator (PI) is required to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32) in obtaining and documenting informed consent, and per G-RECs-Op-2018, the PI must also comply with consent requirements as delineated in the Declaration of Helsinki (MEX-76). (Note: Per MEX-2, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is in the process of implementing the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (MEX-22)).

As per HlthResRegs and G-RECs-Op-2018, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by a Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and provided to COEFPRIS with the request for research protocol authorization. (See the Required Elements section for details on what should be included in the form.)

HlthResRegs, COFEPRIS-GCP, and NOM-012-SSA3-2012 state that the PI must provide detailed research study information to the participant or legal representative/guardian. As delineated in HlthResRegs, G-RECs-Op-2018, NOM-012-SSA3-2012, MEX-32, and MEX-84, the ICF content should be presented with a clear explanation and provided in a format that facilitates understanding. Per NOM-012-SSA3-2012 and MEX-32, the participant or legal representative/guardian should also be given adequate time to consider whether to participate. GenHlthLaw and MEX-84 further note the ICF should be expressed in writing in an accessible, timely manner and in understandable language, using accurate and complete information, including the possible benefits and expected risks, and the treatment alternatives, to ensure that services are provided on the basis of free and informed consent. Once comprehension of the information is guaranteed through the necessary means and supports, individuals have the right to accept or reject consent. G-DIGIPRiS-ResProts, MEX-84, and G-HumResProt indicate the ICF and/or assent form, as applicable, is a document through which the research participant agrees to voluntarily participate in a research study and to undergo experimental procedures when the information is presented in a sufficient, timely, clear and truthful manner regarding the expected risk and benefits.

As per HlthResRegs, G-RECs-Op-2018, and MEX-32, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or appear to waive their legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

Re-Consent

According to G-RECs-Op-2018 and MEX-32, any change in the ICF that is relevant to the participant’s consent should be approved by the REC prior to implementing any changes. Per G-RECs-Op-2018 and MEX-32, the participant or legal representative/guardian should also be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participating in the trial. MEX-32 further states the communication of this information should be documented.

Language Requirements

G-HumResProt states that the applicant must submit the request for protocol authorization application and all associated documentation (including the protocol and the ICF) in Spanish.

Documenting Consent

As delineated in HlthResRegs, G-RECs-Op-2018, and MEX-32, the participant or legal representative/guardian, as well as two (2) witnesses, must sign the ICF. MEX-32 specifies that the ICF should be dated, and any updates must also be signed, and a copy of the amendments provided to the participant or legal representative/guardian. If the participant does not know how to sign, the participant will provide a fingerprint and will also need to designate someone to sign the participant’s name on their behalf. A copy of the signed ICF will be provided to the participant or legal representative/guardian. Per G-DIGIPRiS-ResProts, which complies with MEX-22, the ICF version and date must coincide with what is recorded as approved in the opinions of the ethics committees (ECs). G-HumResProt further specifies the ICF should be signed by the PI, the participant and the participant’s family, or a legal representative and two (2) witnesses. The names of the witnesses, the addresses, and the relationships the witnesses have with the research participant must be indicated. MEX-84 also notes a section in the ICF should be provided for the participant or the legal representative to sign the document to indicate express acceptance. The section must include general data (full name, address, relationship with the participant) and signatures of two (2) witnesses.

Waiver of Consent

No information is currently available regarding waiver requirements.

3.3

25-32

1.28, 2.9, and 4.8

Search for the Status of Implementation of ICH Guidelines by ICH Members

XIII. Specific Sections of the Procedure on the Platform (V)

Requirements (9) and Additional Information

3.1 and 3.9

1.2, 3.3, 10, Annexes 5 and 6, and Glossary

Title III (Chapter IV, Article 51 Bis 2) and Title V (Chapter I, Article 100)

Title II (Chapter I, Articles 20-22)

0 (Introduction)

4.3 and 10.6

Required Elements

Last content review/update: July 2, 2024

Based on the CTRules, the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14), the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Title of the project and that the study involves research and an explanation of its nature and purpose
The expected duration of the participant’s participation
The participant’s responsibilities in participating in the trial
Experimental aspects of the study
Approximate number of participants involved in the trial
Trial treatment schedule and the probability for random assignment to each treatment
Principal investigator(s), institution, and ethics committee (EC) contact information, the person(s) to contact for further information regarding the trial and the rights of trial participants, and whom to contact in the event of trial-related injury
Any foreseeable risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
Any expected benefits or prorated payment to the participant; if no benefit is expected, the participant should also be made aware of this
Alternative procedures or treatment that may be available to the participant, including a statement on disclosure of appropriate alternative procedures or courses of treatment that might be advantageous to participants when the research involves non-validated procedures, devices, or therapies
Compensation and/or medical treatment available to the participant or the family or dependents in the event of a trial-related injury
Any additional costs to the participant that may result from participation in the research
The extent to which confidentiality records identifying the participant will be maintained, and if the results of the trial are published, the participant’s identity will remain confidential
That the Pharmacy and Poisons Board (PPB) will be granted direct access to the participant’s original medical records to verify clinical trial procedures and/or data without violating the participant’s confidentiality
The details on storage and exportation of biological samples, if applicable
The details on storage and ownership of personal data
Information about unblinding, if applicable
The extent of the investigator’s responsibility, if any, to provide medical services to the participant
That therapy will be provided free of charge for specified types of research-related injury, including the investigators’ responsibilities in this regard
That participation is voluntary, the participant may withdraw at any time, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled
That the participant will be informed about the dissemination of findings and about any publication of the participant’s medical information, including photographs and pedigree charts
Foreseeable circumstances under which the investigator(s) may remove the participant without consent
That the participant or legal representative/guardian will be notified in a timely manner if significant new findings develop during the study which may affect the participant’s willingness to continue
Consent to incomplete disclosure, for example, if it is necessary to inform participants that some information is being withheld deliberately and the reasons for that decision; an offer to disclose the purpose at the conclusion of the study can be made

Note that per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

In addition, the CTRules delineates that if the potential participant is a child, the ICF must also contain these elements:

The pathophysiology of the disease or subject of the clinical trial
The methods of diagnosis
The currently available treatment or prevention strategy in the pediatric population
The incidence and prevalence of the disease or subject of the clinical trial in the overall population and in the pediatric population
The evidence and assumptions on key differences between the disease or subject of the clinical trial in the overall population and the pediatric population

4.4 and 4.8

Definitions, 4.1, and 4.2

1.48, 1.63, and 1.188-1.212

Part IV (10 and 11)

Last content review/update: November 8, 2024

As delineated in G-RECs-Op-2018 and MEX-84, the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Identification data (Title, protocol number, version, version date, research institution data, principal investigator (PI) name, medical emergency establishment data, and Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)), and this data must coincide with the opinions of the ethics committees)
The study rationale and objectives
Purpose and procedures, including all invasive procedures
Identification of experimental aspects of the study
Trial duration
Participant’s responsibilities
Investigator responsibilities
Approximate number of participants
Circumstances that may terminate the study
Duration of study
Any expected risks or discomforts to the participant
Any expected benefits to the participant; if no benefit is expected, the participant should be informed of this point (physical examination, laboratory tests and imaging should not be considered as benefits to the participant)
Alternative treatments that may be beneficial to the participant
Trial treatment(s) and the probability for random assignment to each treatment
Explains the blinding of the study (if applicable) and what it consists of
Allocation method
Compensation and/or treatment available for the participant by the health care institution in the case of trial-related injury
All drugs, products, and procedures are free
That participation is voluntary, and that the participant can withdraw from the study at any time without penalty or loss of benefits, including medical treatment, to which the participant is otherwise entitled
Assurance that the participant will not be identified and that their confidential information relating to their privacy will be maintained
Confidentiality of records identifying the participant will be maintained (including sensitive personal data and data derived from the study), and permission given to monitors, auditors, the REC, and the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) to access the participant’s medical records to verify the procedures or trial data, without violating the participant’s confidentiality, insofar as the applicable laws and regulations permit
Contact information for the sponsor and PI in the event of participant problems or trial-related injuries
Communication channels and data to request clarification and to guarantee a response to questions and clarification of concerns about procedures, risks, benefits, and other matters related to the investigation and treatment of the participant
Foreseeable circumstances under which the PI(s) may remove the participant without their consent
Commitment to provide updated information throughout the study although this may affect the participant’s willingness to continue
Notification that any additional research study expenses will be absorbed by the research budget

The Guideline for Good Clinical Practice E6 (R1) (MEX-32) also mentions the following required elements:

Any expected risks or discomforts, when applicable, to the embryo, fetus, or nursing infant
Any anticipated prorated payment to the participant for participating in the trial
Any expenses the participant needs to pay to participate in the trial

Additionally, per NOM-012-SSA3-2012, the investigator must ensure that the ICF explicitly states the compensation to which the research participant is entitled in the event of suffering damage to their health directly attributable to the research, and the availability of free medical treatment, even in the event the participant decides to withdraw from the study before it is concluded.

See HlthResRegs, NOM-012-SSA3-2012, G-RECs-Op-2018, and MEX-32 for additional details related to ICF requirements. (Note: Per MEX-2, COFEPRIS is in the process of implementing the International Council for Harmonisation's Guideline for Good Clinical Practice E6 (R2) (MEX-22)).

Also, see the Vulnerable Populations and Consent for Specimen sections for further information.

3.3

4.8

Search for the Status of Implementation of ICH Guidelines by ICH Members

Annex 5

Title II (Chapter I, Article 21)

4.3, 4.6, 9.29, 10.6-10.7, 11.2-11.3

Participant Rights

Last content review/update: July 2, 2024

Overview

In accordance with the Declaration of Helsinki (KEN-33) principles upheld in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), Kenya’s ethical standards promote respect for all human beings and safeguard the rights of research participants. A participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

The Right to Participate, Abstain, or Withdraw

As set forth in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and KEN-14, a participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As delineated in the CTRules, the G-KenyaCT, the G-ECBiomedRes, and KEN-14, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study.

The DPA further indicates that data subjects have a right to:

Be informed of how their personal data is to be used
Access their personal data in custody of the data controller (sponsor) or data processor
Object to the processing of all or part of their personal data
Correct false or misleading data
Delete false or misleading data about them

The Right to Privacy and Confidentiality

As per the G-KenyaCT, the G-ECBiomedRes, and KEN-14, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.

The Right of Inquiry/Appeal

The G-KenyaCT, KEN-14, and the G-ECBiomedRes state that the participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries. Further, the G-ECBiomedRes requires that the ethics committee contact information also be provided.

The Right to Safety and Welfare

The G-ECBiomedRes and KEN-14 state that a research participant’s right to safety and the protection of the participant’s health and welfare must take precedence over the interests of science and society. KEN-14 upholds the Declaration of Helsinki (KEN-33). (See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.)

3.1 and 4.8

3.1, 4.1, and 4.2

1.48, 1.63, and 1.188-1.212

Part IV (26) and Part V (46-47)

Part IV (11 and 17)

Last content review/update: November 8, 2024

Overview

In accordance with HlthResRegs, NOM-012-SSA3-2012, G-RECs-Op-2018, and the Guideline for Good Clinical Practice E6 (R1) (MEX-32), Mexico’s ethical standards promote respect for all human beings and safeguard the rights of research participants. (COFEPRIS-GCP requires the principal investigator (PI) to comply with MEX-32). HlthResRegs and MEX-32 state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. (Note: Per MEX-2, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is in the process of implementing the International Council for Harmonisation's Guideline for Good Clinical Practice E6 (R2) (MEX-22)).

The Right to Participate, Abstain, or Withdraw

As stated in HlthResRegs, NOM-012-SSA3-2012, G-RECs-Op-2018, MEX-32, and MEX-84, the participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As per HlthResRegs, NOM-012-SSA3-2012, G-RECs-Op-2018, MEX-32, and MEX-84, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation or treatment in the case of injury, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

According to G-RECs-Op-2018, MEX-32, and MEX-84, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. In addition, per NOM-004-SSA3-2012, although clinical records are the property of the institution or the medical services provider that generates them, the participant has ultimate ownership rights over this information to protect their health and the confidentiality of their data.

The Right of Inquiry/Appeal

MEX-32 states that the research participant or legal representative/guardian should be provided with contact information for the individual responsible for addressing trial-related inquiries and/or their rights. G-RECs-Op-2018 further specifies that the names and contact information of the PI and the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI))’s president, including a 24-hour telephone number in case of emergency, should be provided.

The Right to Safety and Welfare

HlthResRegs, NOM-012-SSA3-2012, G-RECs-Op-2018, COFEPRIS-GCP, and MEX-32 that upholds the Declaration of Helsinki (MEX-76), clearly state that a research participant’s right to safety and the protection of their health and welfare must take precedence over the interests of science and society.

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

3.3

Introduction and 4.8

Search for the Status of Implementation of ICH Guidelines by ICH Members

Preamble and 3.1

1.1, 1.2, 3.2, and Annex 5

Title II (Chapter I, Articles 13 and 21)

5.4

0, 5.3, and 11.3

Emergencies

Last content review/update: July 2, 2024

The G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by emergencies. Per the G-KenyaCT, research must be conducted in accordance with KEN-14. As delineated in the G-KenyaCT and the G-ECBiomedRes, in an emergency, if the signed informed consent form (ICF) cannot be obtained from the research participant, the consent of the legal representative/guardian should be obtained. If the prior consent of the participant or legal representative/guardian cannot be obtained, the participant’s enrollment should follow measures specified in the protocol, and/or elsewhere, to ensure compliance with ethics committee (EC) and the Pharmacy and Poisons Board (PPB) requirements. The G-ECBiomedRes requires that the principle of clinical equipoise be applied, which essentially means the participant is not any worse off by enrolling.

During a public health emergency, the G-KenyaCT stipulates that the informed consent of participants must be obtained in individuals capable of giving informed consent. The CT-Emrgcy includes safeguards to protect clinical trial participants during a public health emergency, including the recommendation to reconsent if there are amendments as a result of the emergency.

Per KEN-14, in an emergency, if the signed ICF has not been obtained from the participant or legal representative/guardian, or if an effective treatment is lacking but the investigational product could address the participant’s emergency needs, the clinical trial may be conducted. However, the method used on the participant must be explained clearly in the trial protocol, and the EC must approve the protocol in advance. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

4.8

4.1 and 4.2

Participants

1.48, 1.63, 1.188-1.212, and 1.557-1.574

Last content review/update: November 8, 2024

The HlthResRegs and the Guideline for Good Clinical Practice E6 (R1) (MEX-32) make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies (COFEPRIS-GCP requires the principal investigator (PI) to comply with MEX-32). (Note: Per MEX-2, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is in the process of implementing the International Council for Harmonisation’s Guideline for Good Clinical Practice E6 (R2) (MEX-22)).

According to HlthResRegs, in an emergency, when it is deemed necessary to use an investigational drug, or a known drug with indications, doses, or routes of administration other than the established uses, the treating physician must obtain the favorable opinion of the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) and the Research Committee, and an informed consent form (ICF) signed by the research participant or legal representative/guardian. The terms under which this documentation is obtained must meet the following requirements:

The REC and Research Committee will be informed of the use of the investigational drug in advance if the researcher can anticipate the need for use in emergency situations. If this is not possible, an opinion must be obtained after the situation occurs. In both cases, the committees will issue an opinion in favor or against approving the planned or recurring unintended use of the drug.
A signed ICF must be obtained from the participant or legal representative/guardian unless the participant’s condition prevents them from signing the form, the legal representative/guardian are not available to sign the form, or stopping use of the drug constitutes an almost absolute risk of death to the participant.

Per MEX-32, in emergency situations, when prior consent of the participant is not possible, the consent of the legal representative/guardian, if present, should be requested. When prior consent of the participant or legal representative/guardian cannot be obtained, the ethics committee must provide documented approval in order to protect the participant’s rights, safety, and well-being, pursuant to the applicable regulations. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

In addition, per GenHlthLaw, in cases of medical emergency, and when the terminally ill patient is unable to express their consent, and in the absence of family members, a legal representative, guardian or trusted person, the specialist doctor and/or the institution’s Bioethics Committee will make the decision to apply a necessary surgical medical procedure or treatment.

4.8

Search for the Status of Implementation of ICH Guidelines by ICH Members

3.1

Title V (Chapter I, Article 100) and Title VI (Chapter II, Article 166 Bis 8)

Title III (Chapter II, Article 71)

Vulnerable Populations

Last content review/update: July 2, 2024

Overview

As per the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), in all Kenyan clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. Vulnerable populations include those participants with diminished autonomy whose decision to participate in a clinical trial may be unduly influenced by the expectation of benefits associated with participation or by coercion. This may include, but is not limited to, children/minors, pregnant women, neonates, fetuses, medical students, members of the uniformed forces, prisoners, orphans, homeless populations, unemployed, internally displaced persons, economically or educationally disadvantaged persons, marginalized social groups, individuals with terminal illnesses, and the mentally challenged. KEN-14 also includes members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include persons in nursing homes, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

Elderly Persons

The G-ECBiomedRes defines an elderly/senior citizen as a person who has attained the age of 65 years. Their physical or mental state may affect their ability to make voluntary decisions regarding their participation in research projects. Such research involving elderly/senior citizens must comply with the following requirements:

Strict adherence to ethical principles
The risk-benefit ratio must be favorable to the research participant
The participants must be protected from gross violation of human rights

Persons in Dependent Groups

Per the G-ECBiomedRes, research involving data collection by superiors on their subordinates involves relationships such as employer-employee, teacher-students, supervisor-staff, sponsor-dependent, and parent-children. This relationship impairs independent consent by the participants leading to complacency. Therefore, research involving the superior/subordinate relationships must fulfill the following requirements:

The superior must strictly follow ethical principles to avoid undue pressure
Subordinates must be protected from gross violation of human rights
The trial design must be based on a need-to-know principle and improve the conditions of the participants

Persons in Low-Resource Communities

The G-ECBiomedRes provides the following requirements related to conducting research on participants in low-resource settings:

Persons in such settings should not be involved in research that could be carried out reasonably well in developed communities
The research should be responsive to the health needs and priorities of the community in which it is to be implemented
Undue inducement to participate in the research must be avoided at all costs

Armed Forces

The G-ECBiomedRes stipulates that research involving the members of the armed forces may be vulnerable because of the conditions of their service, which may affect their ability to make voluntary decisions regarding their participation in research. Such research must be conducted to ensure that:

Participants are protected from gross violations of human rights
There is strict adherence to ethical principles
There is at least one (1) member of the ethics committee approving such research who is an enlisted and authoritative member of the armed forces

Terminally Ill

Per the G-ECBiomedRes, research involving participants who are terminally ill with an incurable medical condition are vulnerable. Their state may affect their ability to make voluntary decisions regarding their participation in research. Such research can only be conducted when:

The objectives of the project(s) cannot be achieved using another non-vulnerable group
There is strict adherence to ethical principles
The risk-benefit ratio should be favorable to the research participant

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

1.61, 3.1, and 4.8

4.2

Glossary of Terms, 1.48, and 1.63

Last content review/update: November 8, 2024

Overview

As delineated in G-RECs-Op-2018, in all Mexican clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. G-RECs-Op-2018 characterizes vulnerable populations as individuals or groups experiencing diminished autonomy due to imposing social, political, and/or economic situations that prevent them from having control over their quality of life. Populations traditionally viewed as vulnerable include minors, women, persons with disabilities, the elderly, those suffering from mental illness, immigrants, those who are illiterate, those belonging to ethnic or racial minorities, the unemployed, the homeless, and reclusive individuals.

As per COFEPRIS-GCP, the principal investigator (PI) is required to comply with the Guideline for Good Clinical Practice E6 (R1) (MEX-32), which similarly characterizes vulnerable populations as those who may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from not participating. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students; subordinate hospital and laboratory personnel; employees of the pharmaceutical industry; members of the armed forces; and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent. (Note: Per MEX-2, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is in the process of implementing the International Council for Harmonisation’s Guideline for Good Clinical Practice E6 (R2) (MEX-22)).

G-RECs-Op-2018 specifies that Research Ethics Committees (RECs) (Comités de Ética en Investigación (CEIs)) should ensure that additional security mechanisms are implemented to minimize the specific risks for each group. MEX-32 similarly states that ethics committees must pay special attention to protecting participants who are from vulnerable populations.

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 HlthResRegs is provided below.

Persons in Dependent Groups

As indicated in HlthResRegs, for clinical trials involving participants who are involved in subordinate or dependent relationships, the REC must ensure the following:

Participation or refusal of individuals to participate or withdrawal of consent during the study, will not affect their school, work, military status, or that which is related to the judicial process and any conditions of compliance with a sentence, if applicable
Research results are not used to the detriment of the individuals involved
The health institution and sponsors take responsibility for dangers associated with medical treatment, and where appropriate, provide legally required compensation for the harmful consequences of the investigation

Per G-RECs-Op-2018, the following criteria must also be met to conduct a study with a subordinate population:

The PI must clearly define the reasons for planning to recruit a subordinate population
Protocol approval must also be obtained in which a written statement from the immediate boss or corresponding authority of the subordinate participant(s) verifying that no coercion has existed
If resident doctors or partners are recruited for the study, the program director must provide the REC with a letter of support issued by a person without ties to the study
Confidentiality of research data for the group of subordinate and student participants is important to consider to avoid negatively impacting the participants’ employment possibilities, professional development, study plans, or social relationships. The REC will also need to pay special attention to the PI’s plans to safeguard data security

The HlthResRegs and G-RECs-Op-2018 further specify that these relationships include participants who are in junior or subordinate positions in hierarchically structured groups, such as students, employees, workers in laboratories and hospitals, members of the armed forces, prisoners, social rehabilitation centers, and other members of special population groups in which informed consent can be influenced by some authority.

Persons in Local Communities

As per HlthResRegs, clinical trials involving participants in local communities must meet the following requirements:

Research will be permitted when the expected benefit is reasonably assured, and when previous studies carried out on a small scale have not produced conclusive results
The PI must obtain the approval of the health authorities and other civil authorities of the community to be studied, in addition to obtaining informed consent from individuals who are included in the trial
In the case of vulnerable communities due to their economic or social conditions, such as indigenous communities, the REC is also required to issue a favorable opinion
Experimental investigations in communities may only be carried out by establishments that have the Ministry of Health (Secretaría de Salud)’s prior authorization
The experimental design should offer practical measures of protection for research participants, and ensure that valid results will be obtained, involving the minimum number of participants
The most pertinent ethical considerations applicable to research on participants must be extrapolated to the communal context

Terminally Ill Persons

As stated in GenHlthLaw, if a terminally ill patient is a minor, or is incapable of expressing their consent, consent should be provided by the patient’s parent(s) or guardian(s), and in their absence, by their legal representative(s).

1.61

Search for the Status of Implementation of ICH Guidelines by ICH Members

3.1

Annex 5

Title VI Chapter II (Article 166 Bis 8)

Title II (Chapters II and V)

Children/Minors

Last content review/update: July 2, 2024

According to the G-KenyaCT, a minor is someone under 18 years of age. As set forth in the G-KenyaCT, the G-ECBiomedRes, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), when the research participant is a minor, informed consent should be obtained from the parent/guardian. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14. The informed consent forms, assent forms, and the patient information sheets should be in a language that the parent/guardian clearly understand. All pediatric participants should be fully informed about the trial and its risks and benefits in a language and terms that they are easily able to understand.

Per the G-KenyaCT, a minor should take part in the informed consent procedure in a way tailored to their age and mental maturity. If capable, the participant should sign and personally date the written informed consent. In addition, consent given by pediatric participants should not be considered valid without prior approval by the ethics committee (EC).

The CTRules, the G-ECBiomedRes, and the G-KenyaCT state that a study may only be conducted on minors if several conditions are fulfilled including (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Pediatric participants will not be involved in research that might be equally carried out in adults
The purpose of the research is to generate knowledge relevant to the health needs of children
The parent/guardian must provide proxy consent and ensure assent has been obtained to the extent of the child’s capabilities. However, if the minor refuses to participate after proxy consent is given, the minor’s refusal must be respected unless there is no other medical alternative from which the minor could benefit
The risk presented by interventions not intended to benefit the minor is low and commensurate with the importance of the knowledge to be gained
Interventions that are intended to provide therapeutic benefit are likely to be at least as advantageous to the individual child as any available alternative
No incentives or financial inducements are given to the participant or parent/guardian except to provide compensation for expenses and loss of earnings directly related to the participation in the trial

Additionally, per the G-KenyaCT, the trial should also address the following considerations:

Provide useful answers to the study population
The medicine satisfies a need for the population being studied
Children are adequately monitored and protected
If there is no direct benefit to the child, or there is no more than minimal risk to the participant(s)
Trial results will be published
End-of-trial treatment provisions will be made

Assent Requirements

As delineated in the G-KenyaCT, before undertaking research involving children, the investigator must ensure that the agreement (assent) of each child has been obtained to the extent of the child’s capabilities, and a child’s refusal to participate or continue in the research must be respected. Assent is defined as a child’s affirmative agreement to participate in research, where the child is below the age of the majority but old enough to understand the proposed research in general, its expected risks and possible benefits, and the activities expected of them as participants. The G-ECBiomedRes provides that in children above seven (7) years and below 18 years where the parent(s)/guardian(s) gives proxy consent, assent must be obtained from the child.

For an example of an accredited EC’s assent requirements, see the Kenyatta National Hospital-University of Nairobi (KNH-UoN) Ethics and Research Committee’s sample minor assent form (KEN-17).

4.8

Parental Consent for Children and Sample Minor Assent Form

4.2

Glossary of Terms, 1.48, 1.63, and 1.131-1.172

Part IV (10)

Last content review/update: November 8, 2024

Per ChildRts, a child is defined as under 12 years of age, and adolescents are those between 12 and 18 years of age. When there is doubt as to whether the person is over 18 years of age, it should be presumed that the person is an adolescent. When there is doubt as to whether the person is over or under 12 years of age, it should be presumed that the person is a child.

Additionally, per HlthResRegs, in all cases, a written informed consent must be obtained from those exercising parental authority, or the legal guardian(s) of the minor, except in the case of emancipated minors over 16 years of age. Moreover, when the mental capacity or psychological state of the minor or incapacitated person permits, their acceptance must also be obtained after the investigator(s) have explained what they intend to do in the study. However, the Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) may waive compliance with these requirements for justified reasons.

As set forth in G-RECs-Op-2018 and HlthResRegs, a research study involving minors must ensure that similar studies have been previously done in older people and in immature animals, except when it comes to studying conditions that are specific to the neonatal stage or specific conditions associated with certain ages.

Per G-RECs-Op-2018, research studies classified as risky and likely to benefit the minor directly, will be admissible when the following requirements are met:

The risk is justified by the importance of the benefit that the minor will receive
The benefit is equal to or greater than other alternatives already established for its diagnosis and treatment
When the mental capacity and psychological state of the minor allow, the informed assent must also be obtained, after explaining what is intended to be done. The REC may waive compliance with these requirements for justified reasons
The informed consent information provided is appropriate for the understanding of minors

Per G-RECs-Op-2018 and HlthResRegs, when two (2) persons exercise the parental authority of a minor, only the consent of one (1) of them must be permitted if there is irrefutable or manifest proof that the other is unable to provide it, proof of the parental authority’s negligence, or imminent risk to the minor’s health or life.

HlthResRegs indicates that investigations classified as risky, and with a probability of direct benefit for the minor, will be permitted in the following circumstances:

The risk is justified by the importance of the benefit that the minor will receive, and
The benefit is equal to or greater than other alternatives already established for diagnosis and treatment

Per HlthResRegs, investigations classified as risky and without direct benefit to the minor, will be allowed in the following circumstances:

When the risk is minimal: The intervention or procedure must represent a reasonable experience for minors, and comparable with those characteristics of their current or expected medical, psychological, social, or educational situation. Also, the intervention or procedure should have high probability of obtaining generalizable knowledge about the condition or illness of the minor to benefit others with this disorder as well
When the risk is greater than the minimum: The research should offer a good chance of understanding, preventing, or alleviating a serious problem affecting the health and well-being of children. Also, the head of the health institution should establish strict supervision to evaluate the magnitude of the risks anticipated or others that may arise, and immediately suspend the investigation when the risk could affect the biological, psychological, or social welfare of the minor

Assent Requirements

The applicable regulatory requirements do not specify the age of assent required for minors.

Per G-RECs-Op-2018, assent must also be obtained from a minor who is deemed capable of providing assent, and the minor must be informed about the study in a manner tailored to their emotional and intellectual maturity level, considering at all times the seriousness of the decision.

Article 5

Annex 5

Title II (Chapter III)

Pregnant Women, Fetuses & Neonates

Last content review/update: July 2, 2024

Per the G-KenyaCT, research must be conducted in accordance with the requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). In accordance with KEN-14, informed consent requirements for conducting clinical trials with pregnant or nursing women or fetuses follow the general requirements listed in the Required Elements section. Specifically, the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant.

As per the G-ECBiomedRes, research involving pregnant, lactating, and breastfeeding women may pose compromised long-term outcomes for the child. In addition, potential parent(s) can make decisions on behalf of the fetus(es), embryo(s), and zygote(s).

For fetal, embryo, and zygote(s) cases, research should be limited as follows:

Cases that present no harm or offer assistance to the life system of the participants
No procedures should be permitted that are likely to harm them
A fetus ex-utero and alive, embryo, and zygote must not be involved in research unless it is intended to enhance the life of that fetus, embryo, and zygote or unless the research involves no risk to them

Additionally, the following guidelines must be followed for research involving pregnant, lactating, and breastfeeding women:

The research carries no more than minimal risk to the fetuses or nursing infants
Pregnant or nursing women should generally not be clinical trial participants except where such trials are designed to protect or advance the health of the pregnant/nursing women or fetuses/nursing infants, and for which women who are not pregnant or nursing would not be suitable participants
The justification for such research should be that participants must not be arbitrarily deprived of the opportunity to benefit from investigational drugs, vaccines, or other agents that promise therapeutic or preventive benefits

4.8

4.2

1.48 and 1.63

Last content review/update: November 8, 2024

As per HlthResRegs, studies involving women of childbearing age; women who are in any stage of pregnancy or are postpartum; or studies involving treatments or procedures using embryos, fetuses, or newborns, are required to obtain an informed consent form (ICF) from the woman and her spouse or partner. In addition, HlthResRegs and G-RECs-Op-2018 note that consent from the spouse or partner may only be waived in the case of their incapacity (or irrefutable or manifest inability) to provide it, or when there is imminent risk to the health or life of the woman, embryo, fetus, or newborn. All studies must also comply with the general ethics requirements that must be fulfilled prior to research involving humans as delineated in HlthResRegs.

HlthResRegs and G-RECs-Op-2018 further state that research in pregnant women will only be permitted if it is for therapeutic benefit, and represents an opportunity to understand, prevent, or alleviate any serious pathology. HlthResRegs and G-RECs-Op-2018 indicate that these studies are allowed when they are aimed at improving a pregnant woman’s health with minimal risk to the embryo or fetus, or per HlthResRegs, seek to increase the fetus’s viability, with minimal risk to a pregnant woman. G-RECs-Op-2018 adds that the ICF should mention the possible risk to the fetus.

According to HlthResRegs, investigations to be carried out on pregnant women should be preceded by studies carried out on non-pregnant woman to demonstrate the study’s safety, with the exception of studies requiring the specific condition. Those investigations classified as higher than minimum risk and will be conducted using women of childbearing age should implement the following measures:

Certify the women are not pregnant prior to their acceptance as research participants, and
Decrease the chances of pregnancy as much as possible during the development of the investigation

Per HlthResRegs and G-RECs-Op-2018, during studies conducted with pregnant women, the following requirements must be met:

The investigators will not have the authority to decide on the time, method, or procedure used to terminate the pregnancy, nor will they participate in decisions regarding the viability of the fetus
The Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI))’s authorization is required prior to any modification of the method used to terminate the pregnancy. These modifications mean that there will be minimal risk to the mother’s health and do not represent any risk to the survival of the fetus, and
In any case, it is strictly forbidden to grant monetary or other incentives to interrupt the pregnancy, for the interest of the investigation or for other reasons

As set forth in HlthResRegs and G-RECs-Op-2018, investigators must comply with the following additional criteria when conducting studies with women who are in any stage of pregnancy or are postpartum:

Research without therapeutic benefit in pregnant women, whose objective is to obtain general knowledge about pregnancy, should not represent a risk greater than the minimum for the woman, the embryo, or the fetus
Investigations in pregnant women that imply an intervention or experimental procedure not related to pregnancy, but with therapeutic benefit for women (e.g., cases of toxemia gravidarum, diabetes, hypertension, and neoplasms, etc.) should not expose the embryo or the fetus to a greater than minimum risk, except when the use of the intervention or procedure is justified to save the life of the woman
For investigations during labor, the informed consent must be obtained prior to initiating the study and must expressly state that consent may be withdrawn at any time during labor
Investigations in women during the puerperium will be allowed when they do not interfere with the health of the mother and the newborn
Research on women during lactation will be authorized when there is no risk for the infant, or when the mother decides not to breastfeed, she ensures her feeding by another method and provides informed consent

Per HlthResRegs, studies involving treatments or procedures using embryos, fetuses, or newborns must meet the following requirements:

Fetuses will be permitted to be subjects of investigation only if the techniques and means used provide maximum security for them and the pregnant woman
Newborns will not be used as subjects of investigation until it has been established with certainty whether or not they are live births, except when the research is aimed at increasing their probability of survival until the viability phase, the study procedures do not cause the cessation of their vital functions or when, without adding any risk, they seek to obtain important generalizable knowledge that cannot be obtained in any other way
Live births may be used as subjects of investigation if the investigator(s) obtain consent from the woman and her spouse or partner

In addition, HlthResRegs indicates that investigations involving embryos, deaths, fetuses, still births, macerated fetal matter, cells, tissues and the use of biological materials extracted from them, must comply with GenHlthLaw. GenHlthLaw specifically prohibits the use, for any purpose, of embryonic or fetal tissues caused by induced abortions. G-RECs-Op-2018, by comparison, states that for investigators to use biological materials derived from abortions, the informed consent must be independent from the consent granted for an abortion, and will not include financial compensation.

Annex 5

Title XIV (Chapter I, Article 318 and Chapter III, Article 330)

Title II (Chapter IV, Articles 41-55)

Prisoners

Last content review/update: July 2, 2024

Per the G-ECBiomedRes and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14. A research study involving prisoners should ensure that these prospective participants are informed and given the opportunity to make their own decisions without any interference or reprisals from a higher authority. The ethics committee must also ensure that the study will be independently monitored to assure the dignity and rights of the prisoners involved in the research.

1.61

4.2

1.48 and 1.63

Last content review/update: November 8, 2024

No applicable requirements

Mentally Impaired

Last content review/update: July 2, 2024

As per the G-ECBiomedRes and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), an ethics committee (EC) within the relevant institution must approve the participation of adult research participants who are incapable by reason of physical and mental capacity to give consent. Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in KEN-14.

In addition, as delineated in the G-ECBiomedRes, a research study may involve participants with mental incapacities or behavioral disorders under the following conditions:

Such research could not be carried out equally well with individuals who are in possession of their full mental faculties
The knowledge gained would be relevant to the health needs of persons with mental or behavioral disorders
The participant’s consent has been obtained to the extent of the participant’s capabilities, and a prospective participant’s refusal to participate is always respected
In the case of incompetent individuals, informed consent shall be obtained from a legal guardian or other duly authorized person
The degree of risk attached to the intervention not intended to benefit the individual participant is low and commensurate with the importance of knowledge to be gained
Interventions that are intended to provide therapeutic benefit are likely to be at least as advantageous to the individual participant as any alternative

1.61 and 3.1

4.2

1.48 and 1.63

Last content review/update: November 8, 2024

The Mexican government has updated the GenHlthLaw to prioritize mental health with the development of health policies required to be in accordance with the provisions of the MexConstitution and international treaties on human rights. For the purposes of this law, mental health is understood as a state of physical, mental, emotional, and social well-being determined by the individual's interaction with society and linked to the full exercise of human rights. Refer to GenHlthLaw for details on consent requirements for the treatment of the mental health services user population.

Per HlthResRegs, when the mental capacity and psychological state of the participant permits, their acceptance must also be obtained after the investigator(s) explain what they intend to do during a clinical study. The Research Ethics Committee (REC) (Comité de Ética en Investigación (CEI)) may waive compliance with these requirements for justified reasons. All studies must also comply with the general ethics requirements that must be fulfilled prior to research involving humans as delineated in HlthResRegs.

As indicated in HlthResRegs, investigations classified as risky, but with a probability of direct benefit for the mentally incompetent participant, will be allowed when:

The risk is justified by the importance of the benefit that the incompetent participant will receive, and
The benefit is equal to or greater than other alternatives already established for diagnosis and treatment

In addition, per HlthResRegs, investigations classified as risky and without direct benefit to the mentally incompetent, will be allowed in the following circumstances:

When the risk is minimal: The intervention or procedure must represent a reasonable experience for the incompetent participant and be comparable with those characteristics of their current or expected medical, psychological, social, or educational situation. The intervention or procedure should also have a high probability of obtaining generalizable knowledge about the condition or illness of the mentally incompetent participant to benefit others with this disorder
When the risk is greater than the minimum: The research should offer a good chance of understanding, preventing, or alleviating a serious problem affecting the health and well-being of the mentally incapacitated. In addition, the head of the health institution should establish strict supervision to evaluate the magnitude of the risks anticipated or others that may arise, and immediately suspend the investigation when the risk could affect the biological, psychological, or social welfare of the mentally incompetent participant.

Title III (Chapter VII, Articles 72 and 75)

Title I (Chapter I, Article 1)

Title II (Chapter I, Article 14 and Chapter III, Articles 34, 36-39)

Definition of Investigational Product

Last content review/update: July 2, 2024

The G-KenyaCT defines an investigational product (IP) as any pharmaceutical product, including a new product or existing product for a new indication, in the form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, or when used for an unapproved indication, or when used to gain further information about an approved use.

Glossary of Terms, 1.48, and 1.63

Last content review/update: November 8, 2024

As delineated in COFEPRIS-GCP and the Guideline for Good Clinical Practice E6 (R1) (MEX-32), an investigational product (IP) is defined as any pharmaceutical form containing an active ingredient or placebo, or a product of biological or biotechnological origin that is used or tested in a clinical trial, including a registered product when used or packaged in a different way with for which it was authorized, or when it is tested for indications that have not been authorized, or when it is used to obtain more information about its authorized use. COFEPRIS-GCP also notes this definition also applies to new chemical and biological entities, generics, new formulations, combination products, and biosimilars, and medical devices with or without the release of some active ingredient.

NOM-012-SSA3-2012 similarly states that investigational medicines or devices are used or applied to humans for scientific research purposes, for which there is insufficient scientific evidence to demonstrate its preventative, therapeutic, or rehabilitative effectiveness, or is intended to modify the therapeutic indications of already known products.

NOM-059-SSA1-2015 further defines an IP as a drug or biological product for which there is no previous experience in the country, has not been registered by the Ministry of Health (Secretaría de Salud), and therefore, has not been distributed commercially. This definition also encompasses medicines registered and approved for sale, when they are being investigated for an unapproved indication, dose, or route of administration, including their use in combination with other products that are different from the approved use.

(Note: In Mexico, IPs are also referred to as “drugs/products in research”).

1.33

1.7

1 and 4.16

3.77

Manufacturing & Import

Last content review/update: July 2, 2024

Manufacturing

According to the PPA and the G-KenyaCT, the Pharmacy and Poisons Board (PPB) is responsible for authorizing the manufacture of all drug products, including investigational products (IPs) in Kenya. Per the CTRules and the G-KenyaCT, an IP must be manufactured in accordance with the requirements of good manufacturing practice (GMP). The CTRules requires a sponsor to immediately notify the PPB in writing when a pharmaceutical or chemical alteration may affect the quality, safety, or efficacy of the IP product during an ongoing clinical trial. The G-KenyaCT states that the sponsor must submit the IP dossier directly to the PPB or may submit it through the principal investigator. The IP dossier must be prepared as per the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14), which is required per G-KenyaCT. The manufacture of IPs may be subject to GMP inspection by the PPB in the same way as in the case of marketed drug products. See the G-KenyaCT for detailed chemistry and manufacturing information to be provided to the PPB if the IP has not been registered with the PPB.

KEN-14 also requires IPs to be manufactured, handled, and stored in accordance with applicable GMPs and used in accordance with the approved protocol.

Per the PPA, the PPB is authorized to regulate the manufacturing of medicine, including:

Ensure that all medicinal products manufactured in, imported into, or exported from the country conform to prescribed standards of quality, safety, and efficacy
Ensure that the personnel, premises, and practices employed in the manufacture, storage, marketing, distribution, and sale of medicinal substances comply with the defined codes of practice and other prescribed requirements
Grant or revoke licenses for the manufacture, importation, exportation, distribution, and sale of medicinal substances
Inspect and license all manufacturing premises, importing and exporting agents, wholesalers, distributors, pharmacies (including those in hospitals and clinics), and other retail outlets

See the KenyaGMP, for PPB’s compilation of recommended World Health Organization GMP guidelines to help comply with GMP requirements and prepare for an inspection, including for manufacture of IPs.

Import

Per the PPA and the ImpExp, the PPB is authorized to regulate the import and export of health products and technologies, including IPs. As per the ImpExp and the G-KenyaCT, to obtain an import permit for a clinical trial, the sponsor or investigator must submit an application online to the Kenya Trade Network Agency’s Kenya TradeNet Single Window System (KEN-28). The following documents must be submitted (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

The proforma invoice or invoice
The ethics committee favorable opinion letter
The Expert Committee on Clinical Trials approval letter from the PPB
Registration of the institution where the research is being undertaken

The G-KenyaCT states that the sponsor must submit to the PPB a copy of the endorsed clinical trial import permit and/or evidence of delivery to the approved investigator(s)/trial center(s) on importation and supply of each consignment of the product. The product must only be supplied to the investigator(s) at the trial site(s) named in the clinical trial import license application for the purpose and use as stated in the said application. Prior PPB notification and approval is required for changes in the investigator, trial site, or protocol. The sponsor must inform PPB of any change in information, or any information received that casts doubt on the continued validity of the data, which was submitted with, or in connection with the application for the import permit. The sponsor must also inform the PPB of any decision to discontinue the trial to which the permit relates and state the reason for the decision. See KEN-8 for additional details on the procedures for obtaining an import license.

Per the CTRules, the import of an IP must comply with the applicable regulatory requirements to ensure integrity and accountability of the products. The PPB may revoke or suspend an import permit if the IP was manufactured in conditions not consistent with GMP; if the clinical trial was discontinued; or if the sponsor provided false information.

Please note: Kenya is party to the Nagoya Protocol on Access and Benefit-sharing (KEN-3), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see KEN-15.

2.12 and 5.13

Glossary of Terms, 2.0, 5.1.7, and 6.0-6.3

Legal Framework, 1.24-1.26, 1.48, 1.63, 1.215-1.240, 1.346-1.354, and 1.542-1.551

Part 1 (3B), Part IIIA (35A and 35B), and Part IV (44)

Part IV (14)

Last content review/update: November 8, 2024

Manufacturing

According to GenHlthLaw, Reg-COFEPRIS, and Reg-HlthProd, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is responsible for authorizing the manufacture of all drug products for human use, including investigational products (IPs), in Mexico. Pursuant to GenHlthLaw, COFEPRIS, acting on behalf of the Ministry of Health (Secretaría de Salud), also issued NOM-059-SSA1-2015 and NOM-164-SSA1-2015 to provide standards delineating the minimum requirements necessary for the manufacture of drugs or active ingredients to be marketed in the country or used in clinical research. See NOM-059-SSA1-2015-Annexes to access the annexes to NOM-059-SSA1-2015.

As indicated in GenHlthLaw and Reg-HlthProd, drug manufacturers must submit a request to COFEPRIS to obtain a sanitary registration prior to initiating any drug manufacturing activities. Reg-HlthProd states that COFEPRIS must complete its review in 60 days, or the application will be deemed approved. Per GenHlthLaw, the sanitary registration is valid for five (5) years. The sanitary registration may be extended for an additional five (5) years if the extension is requested prior to the expiration of the current authorization, or the registration will be cancelled or revoked. See also GenHlthLaw and Reg-HlthProd, for detailed drug manufacturer registration submission requirements. In addition, per MEX-110, COFEPRIS is recognized as a National Regulatory Authority of Regional Reference of Medicines and Biological Products by the Pan American Health Organization (PAHO)/World Health Organization (WHO), and per MEX-111, is also a member of Pharmaceutical Inspection Co-operation Scheme (PIC/S). Per MEX-2, COFEPRIS has also implemented the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)’s Harmonised Tripartite Guideline: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (Q7) (MEX-81).

Import

As delineated in GenHlthLaw, Reg-COFEPRIS, Reg-HlthProd, and G-UnregDrugImprts, COFEPRIS is also responsible for authorizing the import of IPs. According to Reg-HlthProd, G-UnregDrugImprts, and G-UnregDrugImprts, an applicant or the legal representative may submit a request to import an IP after COFEPRIS has approved the sanitary authorization request for those drugs that are neither narcotic nor psychotropic, that do not have sanitary registrations, and that are intended to be used for human research. As per GenHlthLaw, the applicant must be a resident of Mexico or have a legal representative submit an import request on the applicant’s behalf. Additionally, per MEX-84 and G-DIGIPRiS-ResProts, the following documentation is required for submission to COFEPRIS:

Letter of delegation of responsibility to the importer signed by the sponsor
Letter of acceptance of responsibility from the importer signed by the importer’s legal representative

Per Reg-HlthProd, G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, foreign manufacturers must submit a license, a good manufacturing practices (GMP) certificate, or a document issued by the competent authority in the country of origin that proves the company has permission to manufacture drugs. See MEX-36 for additional information on obtaining a GMP certificate.

Reg-HlthProd further states that COFEPRIS may grant permission to import raw materials or finished products without sanitary registration only in the following cases:

When a contingency arises
When required by health policy
For purposes of scientific research, registration, or personal use, or
For laboratory tests

In addition, Reg-HlthProd indicates that three (3) types of sanitary import permits may be issued:

Definitive import – authorizes the entry of products to remain in the national territory for an unlimited time
Temporary import – authorizes the entry of products for a limited time and with a specific purpose, with the understanding that they must return to the country of origin in a period not exceeding one (1) year
Import in transit – authorizes the entry of products for their transfer from one (1) national office to another, for their departure to leave the country, within a period not exceeding 30 days, and for sale or temporary distribution. The sale or distribution is authorized exclusively for medicines to be used for strategic purposes

Reg-HlthProd, G-UnregDrugImprts, and G-UnregDrugImprts state that an import request may be submitted to COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37) once the agency has authorized the protocol for research to be conducted on human beings. The following documentation should be included (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Authorizations, Certificates and Visits Form (see MEX-25) (Original)
Proof of payment of fees (original and two (2) copies)
Health License
Notice of Operation (original and one (1) copy)
Approval from the research protocol office authorized by COFEPRIS and its amendments, (only in the case of research on human beings) (original and one (1) copy)
Technical and scientific information demonstrating the identity and purity of its components in accordance with Pharmacopoeia of the United Mexican States (Farmacopea de los Estados Unidos Mexicanos (FEUM)) and its supplements; the stability of the finished product in accordance with the corresponding standards, and; therapeutic efficacy and safety according to the corresponding scientific information
Prescribing information (broad and reduced versions)
Sample label
Free sale certificate issued by the health authority of the country of origin
Certificate that the company has permission to manufacture medicines and proof of good manufacturing practices issued by the corresponding authority of the country of origin
Letter of representation, when the laboratory that manufactures import product abroad is not a subsidiary or parent company of the laboratory requesting the registration

In addition, Reg-HlthProd requires documents originating from a foreign country to be presented in Spanish, or if in another language, with a Spanish translation made by an expert translator.

Per Reg-HlthProd and G-UnregDrugImprts, COFEPRIS has 10 days to approve the request. If COFEPRIS does not respond within this timeframe, the request is deemed approved. G-UnregDrugImprts also notes that COFEPRIS has four (4) business days to send the applicant a prevention notification regarding missing or additional information required. The applicant, in turn, has five (5) business days to respond. Reg-HlthProd and G-UnregDrugImprts further states that the maximum validity of import authorizations is 180 days, which may be extended for an equal period, provided the conditions in which they have been granted have not changed.

As set forth in Agrmnt_RegHlthSup, COFEPRIS published an agreement that recognizes the requirements, tests, and evaluation procedures carried out by an approved list of regulatory authorities specified in this agreement to be equivalent to those conducted in Mexico for the purposes of evaluating and approving allopathic drug products for sale, distribution, and use. Per Agrmnt_RegHlthSup, COFEPRIS will also permit the regulatory authorities referenced in this agreement to import raw materials or finished drug products, aimed at any disease or condition, whether the products are registered or unregistered in Mexico, and even if the products do not meet COFEPRIS’s quality, safety, efficacy, and GMP standards. The imported products or raw materials must be registered by the approved regulatory authorities, be prequalified by the WHO, or be registered with a regulatory agency that is a PIC/S member like COFEPRIS. See NOM-059-SSA1-2015-Annexes for additional information on COFEPRIS’s compliance with PIC quality risk management and master file preparation requirements that are included as annexes to NOM-059-SSA1-2015.

Per Agrmnt_RegHlthSup, the Ministry of Health may only grant permission for these unregistered drug products to be imported from regulatory authorities approved by COFEPRIS if the drugs are required by necessity in accordance with Reg-HlthProd, as described earlier in this section. Agrmnt_RegHlthSup requires the manufacturer to initiate the sanitary registration process with COFEPRIS within five (5) business days following the import of an unregistered drug product. COFEPRIS will then have a maximum of 60 business days to issue its decision.

As discussed in detail in Agrmnt_RegHlthSup, imported drugs must comply with the legal and technical provisions laid down in GenHlthLaw and Reg-HlthProd. MEX-13 further notes that COFEPRIS is allowed to purchase medicines anywhere in the world with the fundamental goal of avoiding a drug shortage in Mexico. The agreement also guarantees the quality of imported drugs through the regulatory measures COFEPRIS established mandating the analysis of all drug batches that enter the country to go through the Analytical Control and Coverage Expansion Commission, the laboratory that will then carry out a corresponding analysis. The imported drugs must also originate from countries with a regulatory standard equivalent to COFEPRIS and from those manufacturers that can provide health records from the country of origin demonstrating that the drugs have already been used in their population.

Refer to Agrmnt_RegHlthSup for detailed information and documentation requirements to register drugs and biological products. See also MEX-42 for additional background information on this agreement.

D-CargoTransprt bars exclusive cargo shipments to the Mexico City International Airport (AICM). See D-CargoTransprt and D-ModCargoTransprt for more details regarding the relocation of cargo shipments to other airports in Mexico.

Please note: Mexico is party to the Nagoya Protocol on Access and Benefit-sharing (MEX-5), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see MEX-35.

4.4, 5.1, and 10.1

Introduction (Box 1)

XIII. Specific Sections of the Procedure on the Platform (VI and XIV)

Requirements (29)

Requirements, Response time, Validity of the Resolution, and Steps

Title V (Chapter I, Article 102), Title XII ((Chapter I, Articles 194, 194 Bi., 195, 197, 198, and 200-204), (Chapter IV, Articles 221-222), (Chapter VII, Articles 257-258), and (Chapter XIII, Articles 285 and 295)), and Title XVI ((Chapter I, Articles 368-376, 376 Bis, and 378) and (Chapter III, Article 391 Bis))

Preamble, First-Third, Section II (Second, Third, Fourth, and Fifteenth), and Section IV

Chapter I (Article 3)

Title IV ((Chapter I, Articles 99-100) and (Chapter II, Article 113)), Title V (Chapter I, Article 132), Title VI ((Chapter I, Articles 160-161), (Chapter II, Articles 162-163), (Chapter III, 167-171, 185-186, 190-bis 1, 190-bis 2, 190-bis 5, 190-bis 6), and (Chapter IV, Articles 193-194 and 196)), and Title VII

1 and 16

1 and 10.9

Quality Requirements

Last content review/update: July 2, 2024

Investigator’s Brochure

In accordance with the CTRules and the G-KenyaCT, the sponsor must provide an up-to-date investigator’s brochure (IB). An updated IB and Drug Safety Update Report (DSUR) must be submitted whenever available but at least once year as a notification to the Pharmacy and Poisons Board (PPB) or when there are substantial changes to the previous version.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As specified in the G-KenyaCT and KEN-14, the IB must provide coverage of the following areas:

Physical, chemical, and pharmaceutical properties
The pharmacological aspects including its metabolites in all animal species tested
The pharmacokinetics and metabolism including its biological transformation in all animal species tested
Toxicological effects in any animal species tested under a single dose study, a repeated dose study, or a special study
Results of clinical pharmacokinetic studies
Information regarding safety, pharmacodynamics, efficacy, and dose responses that were obtained from previous clinical trials in humans

The G-KenyaCT indicates that the sponsor must also follow the guidance contained in KEN-14.

Quality Management

In accordance with the G-KenyaCT, a good manufacturing practice (GMP) certificate must be provided by a competent authority from the country of manufacture to the PPB in the clinical trial application. At a minimum, the GMP certificate should include the competent authority’s name and contact details, address of the manufacturing site, date of inspection, and validity period. Certificates of Analysis (CoAs) must also be provided to the PPB for all investigational products (IPs) and comparator products. Per KEN-14, the sponsor must maintain a CoA to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

See the G-KenyaCT for detailed chemistry and manufacturing information to be provided to the PPB if the IP has not been registered with the PPB. In addition, see Cert-Emrgcy for information about good clinical practice (GCP) and GMP certifications during emergencies.

(See Product Management section for additional information on sponsor requirements).

7

Glossary of Terms, 1.13-1.29, 1.48, 1.63-1.88, 1.213-1.240, 1.340-1.354, and 1.542-1.551

Part III (8)

Last content review/update: November 8, 2024

Investigator’s Brochure

As indicated in MEX-2, COFEPRIS is in the process of implementing the ICH Guideline for Good Clinical Practice E6 (R2) (MEX-22). G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts are in compliance with the Guideline for Good Clinical Practice E6 (R2) (MEX-22), regarding investigational product (IP) quality/manufacturing and investigator’s brochure (IB) requirements (also known as investigator’s manual in Mexico), while COFEPRIS-GCP complies with the Guideline for Good Clinical Practice E6 (R1) (MEX-32).

As set forth in GenHlthLaw, and G-HumResProt, MEX-84, and G-DIGIPRiS-ResProts, which are in compliance with (MEX-22), the applicant or sponsor is responsible for providing the investigators with an investigator’s brochure (IB). MEX-22 specifies that the sponsor is generally responsible for ensuring that an updated IB is made available to the investigator(s), and the investigators are responsible for providing the updated IB to the responsible ethics committees (ECs). The sponsor should also update the IB as relevant new information becomes available. According to MEX-84, G-DIGIPRiS-ResProts, and MEX-22, the IB should include the following elements (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Title
Confidentiality statement
Table of Contents
Summary
Introduction
Investigational product (IP) identification data (IP number, generic name of the drug or device, international nonproprietary name, trade name, if applicable)
Collection of clinical and preclinical IP data relevant to the study of IP(s) in human participants
Preclinical information (includes non-clinical pharmacology, pharmacokinetics and metabolism in animals, toxicology)
Clinical information (includes pharmacokinetics and metabolism in humans, safety and efficacy, experience during commercialization)
Data summary and guide for the investigator
Document version and version date (coinciding with the approving opinions of the ECs)
For drug authorization requests: (include IP physicochemical and pharmaceutical properties, formulation, presentation, manufacturing, labeling, storage, packaging and stability, when applicable, etc.)
For COFEPRIS-04-010-D modality (risk-free research (observational studies)) authorization requests: include prescribing information

MEX-84 further notes the purpose of the IB is to provide researchers and others involved in the trial with information to facilitate their understanding of the rationale for and compliance with key protocol features such as: dose, dose frequency/interval, administration methods, and safety monitoring. The IB also provides information to support the design of the clinical phase of the study subjects over the course of the clinical trial. The information in this document must be presented in a concise, objective, and balanced manner which allows the principal investigator, as well as the other parties involved in the trial, to assess the suitability of the proposed trial, emphasizing the relevant and updated scientific information on the IP to monitor participant safety.

See MEX-84, G-DIGIPRiS-ResProts, and MEX-22 for detailed IB guidelines.

Quality Management

As specified in COFEPRIS-GCP, GenHlthLaw, Reg-HlthProd, NOM-059-SSA1-2015, NOM-164-SSA1-2015, NOM-176-SSA1-1998, NOM-073-SSA1-2015, G-HumResProt, MEX-84, G-DIGIPRiS-ResProts, and MEX-22, the sponsor must verify that the products are manufactured in accordance with the current codes of Good Manufacturing Practices (GMPs). See NOM-059-SSA1-2015-Annexes to access the annexes to NOM-059-SSA1-2015.

In accordance with the GenHlthLaw, Reg-HlthProd, NOM-059-SSA1-2015, NOM-164-SSA1-2015, NOM-176-SSA1-1998, G-HumResProt, G-DIGIPRiS-ResProts, and MEX-22, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires that drug manufacturers ensure IPs meet the required safety, efficacy, and quality characteristics and are manufactured, handled, and stored in accordance with applicable GMPs and provide the following additional information (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Issue the corresponding certificate of analysis signed by the health officer to verify the drugs comply with the quality specifications indicated in the current edition of the Pharmacopoeia of the United Mexican States (Farmacopea de los Estados Unidos Mexicanos (FEUM)) and its supplements, or those specified in the pharmacopeias from other countries, if applicable (per NOM-176-SSA1-1998)
In case of foreign manufacture, the manufacturer must have a GMP certification, license, or document proving that the manufacturer has permission to manufacture medicines, issued by the competent authority in the country of origin (per Reg-HlthProd)

MEX-84 further specifies that the following IP documentation is required to demonstrate compliance with GMPs:

Letter under oath, declaring that the IP and placebo are manufactured under standards that ensure a product is safe for use and that it has the ingredients and potency it claims to have in accordance with established quality requirements, or
Certificate of good practices for the IP, or
Certificate of pharmaceutical product

Additionally, per GenHlthLaw, verification of GMP compliance must be conducted by the Ministry of Health (Secretaría de Salud) or the Ministry’s authorized third parties, or if necessary, recognition of the respective certificate issued by the competent authority of the country of origin, provided there are recognition agreements in place between the competent authorities from both countries. See MEX-36 for additional information on obtaining a GMP certificate.

NOM-059-SSA1-2015 also notes that the manufacture of IPs for use in clinical studies presents greater complexity than marketed drug products due to the lack of systematic procedures resulting from the variety of clinical trial designs. In addition to applying basic GMP principles, drugs for research use in Mexico must also be released in accordance with good clinical practices, and the personnel involved in IP production and control must be experienced in handling drugs in the clinical research phase and be familiar with GMPs.

In addition, per MEX-110, COFEPRIS is recognized as a National Regulatory Authority of Regional Reference of Medicines and Biological Products by the Pan American Health Organization (PAHO)/World Health Organization (WHO), and per MEX-111, is also a member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S).

3.2 and 10.1

2.12, 5.6, 7, and 8.2-8.3

XIII. Specific Sections of the Procedure on the Platform (V-VI)

Requirements (28-29)

4.3

Title V (Chapter I, Article 102) and Title XII (Chapter IV, Article 222)

Title II (Chapter I, Articles 7-9), Title IV (Chapter II, Article 113), Title V (Chapter II, Article 168 and 170), and Title VII

0, 1.2, 3.14, and 16

1

4.1

1-3, 6.1, and 9

Labeling

Last content review/update: July 2, 2024

Per the G-KenyaCT, investigational products (IPs) used in Kenyan clinical trials must be properly labelled. A final copy/version of the labelling must be submitted to the Pharmacy and Poisons Board (PPB) for approval and should contain the following minimum information:

Statement indicating that the product is for “clinical trial purpose only”
Recommended storage conditions
Protocol code or identification
Name, address, and telephone number of the sponsor, contract research organization, or investigator (the main contact for information on the product, clinical trial, and emergency unblinding)
Pharmaceutical dosage form, route of administration, quantity of dosage units, and in the case of open trials, the name/identifier and strength/potency
The batch and/or code number to identify the contents and packaging operation
A trial reference code allowing identification of the trial, site, investigator, and sponsor, if not given elsewhere
The trial participant identification number/treatment number and, where relevant, the visit number
The name of the investigator (if not included above)
Directions for use (reference may be made to a leaflet or other explanatory document intended for the trial participant or person administering the product)
Period of use (use-by date, expiry date, or re-test date as applicable), in month/year format and in a manner that avoids any ambiguity
The complete physical address of the manufacturing site

As indicated in the G-KenyaCT, it is recommended that an IP is not re-labeled wherever possible. It is, however, accepted that in certain cases it is necessary to re-label and the PPB will review applications for the extension of expiration dates based on sufficient evidence being provided by the applicant that an extended expiration date is warranted. A written justification and evidence should be provided to the PPB. Any re-labelling of remaining IPs from previously manufactured batches must be performed in accordance with good manufacturing practice (GMP) principles and is limited to an extension of the expiration date where sufficient evidence is available to support such extension. Any request for re-labelling should be accompanied by a certificate of analysis of the product from a PPB-recognized laboratory or World Health Organization (WHO) prequalified laboratories (KEN-18). After approval, the re-labelling must be carried out under the supervision of a pharmaceutical inspector on the ground. In case of use-date extension, an additional label should be affixed to the IP to indicate the new use date and repeat the batch number. It may be superposed on the old use date, but not on the original batch number. PPB will not approve re-labelling of a product if the proposed additional label obscures the original labelling. At all times, the original label should be visible. This operation may be performed onsite by the clinical trial monitor(s) or the clinical trial site pharmacist, in accordance with specific and standard operating procedures. The operation should be checked by a second person. Documented evidence of this additional labelling should be available in the trial documentation and in the batch records. KEN-34 indicates that all documents submitted to the PPB in a clinical trial application should be in English, including a pictorial sample of the IP with the labeling text.

The International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (KEN-14), which the G-KenyaCT requires following, states that the IP must be coded and labeled in a manner that protects the blinding, if applicable. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

5.13

1.48, 1.63, 1.307-1.317

Last content review/update: November 8, 2024

Investigational product (IP) labeling in Mexico must comply with the requirements set forth in COFEPRIS-GCP, NOM-164-SSA1-2015, NOM-059-SSA1-2015, and the Guideline for Good Clinical Practice E6 (R1) (MEX-32).

As delineated in COFEPRIS-GCP and NOM-059-SSA1-2015, the IP label must be written in Spanish and contain, at a minimum, the following information (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Name, address, and telephone number of the sponsor or main contact
Protocol identification number
Pharmaceutical form and route of administration
Manufacturer name and address
Lot number, identification code, and dosage form
Statements: “For clinical studies only” or "Permitted use only investigation ", "Forbidden marketing", and "Keep away from the reach of children"
Symbol or pictograms warning, if applicable
Expiration date
Storage conditions

NOM-164-SSA1-2015 also states that the IP label must indicate it is material under investigation.

In addition, MEX-22 indicates the sponsor should verify the IPs are coded and labeled in a manner that protects the blinding, if appropriate. In blinded trials, the IP coding system should include a mechanism that permits rapid identification of the product(s) in case of a medical emergency, but does not permit undetectable breaks of the blinding. A sample of the attached IP container label(s) should also be provided to document compliance with applicable labelling regulations and appropriateness of instructions provided to the study participants.

Per NOM-164-SSA1-2015 and NOM-059-SSA1-2015, IPs for use in clinical trials should be packaged in a way that protects the products from alteration, contamination, and damage during storage and shipment. Additionally, procedures or instructions for the control of packaging, labeling, and distribution operations should be prepared.

Per NOM-059-SSA1-2015, in the case of products packaged for blinded clinical studies, manufacturers must ensure that the unused products and supplies are completely (100%) retrieved.

5.13, 8.2.13 and 8.2.17

4.4

5.2

10.9.8

Product Management

Last content review/update: July 2, 2024

Supply, Storage, and Handling Requirements

Per the PPA, the Pharmacy and Poisons Board (PPB) is responsible for the regulation of investigational products (IPs), including all matters relating to the safety, packaging, and distribution of medicines. The PPB must ensure that all medicinal products manufactured in, imported into, or exported from the country conform to prescribed standards of quality, safety, and efficacy. Further, the PPB must ensure that the personnel, premises, and practices employed in the manufacture and storage of IPs complies with prescribed requirements.

Per the G-KenyaCT, research must be conducted in accordance with requirements set forth in the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (KEN-14). As defined in the G-KenyaCT and KEN-14, the sponsor must ensure the following (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Timely delivery of IPs to the investigator(s)
Records that document shipment, receipt, disposition, return, and destruction of the IPs are maintained
A system for retrieving IPs and documenting that this retrieval is maintained
A system for the disposition of unused IPs is maintained
Steps taken to ensure that the IPs are stable over the period of use
Sufficient quantities of the IPs used in the trials are maintained

To the extent stability permits, samples should be retained either until the analyses of the trial data are complete or as required by the applicable regulatory requirement(s), whichever represents the longer retention period.

As defined in the G-KenyaCT and KEN-14, the sponsor must also supply the investigator(s)/institution(s) with the IPs, including the comparator(s) and placebo, if applicable. The sponsor or the representative should not supply either party with the IP(s) until approval from the PPB and a favorable opinion letter from the local and national ethics committees (ECs) are obtained. In addition, the G-KenyaCT requires the following supply, storage, and handling processes:

Analysis or evaluation of samples is performed in accordance with the protocol and, where applicable, the contract/agreement, the work instruction, and associated methods
Adherence to the laboratories, policies, and standard operating procedures (SOPs)
Prior to the initiation of sample analysis or evaluation, it is often necessary to prepare a work instruction detailing the procedures, which will be used to conduct the analysis or evaluation
Have automated equipment for routine hematology, biochemistry, and serology tests
Have procedures for analyzer calibration and quality control
Regularly maintain all the equipment, including point-of-care equipment
Have a procedure for transporting samples safely and quickly from clinical areas to the laboratory
Have written procedures for all assays, and validate the assays
Have a stock control procedure to make sure that reagents and consumables are used within their expiry dates
Keep records, including source documents and final reports
Have a laboratory information management system, and validate and backup the system
Provide protective clothing and safety equipment for staff
Have a central alarm system for all fridges and freezers
Have an internal audit program

The G-KenyaCT also states that the sponsor must submit to the PPB a copy of the endorsed Clinical Trial Import License and/or evidence of delivery to the approved investigator(s)/institution(s) upon importing and supplying each product consignment. In addition, the IP must only be supplied to the investigator(s)/institution(s) named in the application for the Clinical Trial Import License/Clinical Trial Exemption for the purpose and use specified. The sponsor must inform the PPB in the event of any information changes including:

Information the sponsor receives that casts doubt on the continued validity of the submitted data
Information associated with the Clinical Trial Import License

See the G-KenyaCT for additional information on principal investigator requirements relating to the Clinical Trial Import License.

Record Requirements

As per the G-KenyaCT, the sponsor is required to maintain records that document IP(s) shipment, receipt, disposition, return, and destruction. The sponsor must also maintain a system for retrieving IPs and documenting this retrieval, and maintain a system for the disposition of unused IPs.

According to the G-KenyaCT, IP manufacturers or importers must also retain samples for each batch of bulk product, and the packaging components used for each finished batch, for at least two (2) years following the trial. The sponsor should maintain sufficient samples from each batch and keep a record of their analyses and characteristics for reference so that, if necessary, an independent laboratory could reconfirm the same data.

5.5, 5.12-5.14, and 7

Glossary of Terms, 1.13-1.29, 1.48, 1.63-1.88, 1.213-1.214, 1.307-1.317, 1.355-1.372. 1.491, 1.507-1.511, and 1.542-1.551

3B

Last content review/update: November 8, 2024

Supply, Storage, and Handling Requirements

COFEPRIS-GCP and the Guideline for Good Clinical Practice E6 (R2) (MEX-22) state the sponsor is responsible for supplying investigators with the investigational products (IP(s)) while ensuring that only the quantity of products necessary to carry out the study is provided, and that none of the products will be marketed or used for purposes unrelated to the investigation.

MEX-22 further specifies that the sponsor is responsible for supplying the investigator(s)/institution(s) with the IP(s) and for ensuring the timely delivery of the IPs. However, the sponsor should not supply an investigator/institution with the IP(s)) until all the required documentation is obtained, such as the favorable opinion of the ethics committee (EC) and approval from the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)).

The sponsor should ensure written procedures include instructions that the investigator/institution should follow for the handling and storage of IP(s), adequate and safe receipt of the IP(s), dispensing of the IP(s), retrieval of unused IP(s), return of unused IP(s) to the sponsor, and disposal of unused IP(s) by the sponsor (or alternative disposition if authorized by the sponsor and in compliance with the applicable regulatory requirement(s)).

Additionally, MEX-22 indicates the IP should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). The sponsor should determine acceptable storage temperatures, storage conditions (e.g., protection from light), storage times, reconstitution fluids and procedures, and devices for product infusion, if any, for the IPs, and inform all involved parties (e.g., monitors, investigators, pharmacists, storage managers) of these determinations. Additionally, the sponsor should:

Take steps to ensure that the IP(s) are stable over the period of use
Maintain sufficient quantities of the IP(s) used in the trials to reconfirm specifications, should this become necessary, and maintain records of batch sample analyses and characteristics. To the extent stability permits, samples should be retained either until the analyses of the trial data are complete or as required by the applicable regulatory requirement(s), whichever represents the longer retention period

Refer to MEX-22 for detailed sponsor-related IP requirements and MEX-36 for additional information on obtaining a GMP certificate.

COFEPRIS-GCP also delineates the sponsor is responsible for ensuring that IP manufacturing complies with NOM-073-SSA1-2015, which states that during the clinical trial, the manufacturer must validate the stability of the IP until the date of the last administration. The sponsor and the contract research organization (CRO) are responsible for ensuring that the research institution has a restricted storage area to protect the IPs and other products required for the investigation, including adequate temperature controls, humidity, and other conditions according to the manufacturer’s provisions. Additionally, the principal investigator is required to keep track of the receipt, storage, distribution, administration, destruction, or retrieval of the IP and other products required for the clinical study, in accordance with the research protocol provisions.

In addition, NOM-164-SSA1-2015 and NOM-059-SSA1-2015 indicate that there must be a procedure for the retrieval of IPs for clinical use that describes the responsibilities of all the members of the supply chain using the drug to include the manufacturer, the sponsor, the investigator, the clinical monitor, and the head of the research unit. NOM-164-SSA1-2015 further states that a system must be in place for the release of each lot of manufactured IPs and that a qualified person must approve the release. See NOM-059-SSA1-2015-Annexes to access the annexes to NOM-059-SSA1-2015.

According to MEX-84, the following IP documentation is also required to be submitted to COFEPRIS:

Letter under oath guaranteeing the shelf life (stability) of the IP from the date of manufacture to the date of the last administration that will be carried out as part of the investigational protocol, or a protocol and report of results of the accelerated and long-term stability study of the IP and placebo, guaranteeing its stability from the date of manufacture to the date of the last administration in the research protocol
Letter under oath, declaring that the IP and placebo are manufactured under standards that ensure a product is safe for use and that it has the ingredients and potency it claims to have in accordance with established quality requirements; a certificate of good practices for the IP; or a certificate of pharmaceutical product
Letter of description of import inputs that expresses the approximate quantity of the IP

MEX-84 further notes that compliance with GMP and product stability are not equivalent. In the case of a letter under oath, it is valid to declare together compliance with GMP and that the shelf life of the IP is guaranteed at least until the date of the last administration of the IP and/or placebo.

In addition, per G-DIGIPRiS-ResProts, a letter of import supplies should be provided to COFEPRIS that clearly establishes the quantity and description of supplies that will be imported during each stage of the study. The letter should include the IP or placebo (when applicable), pharmaceutical form, presentation, concentration, and number of participants to be enrolled in Mexico. A letter of the stability studies should also be provided to support the IP and the placebo comply with the physical, chemical, and biological parameters which must be complied with throughout its useful life, and to maintain established quality specifications during storage and use.

Record Requirements

As indicated in the MEX-22, the sponsor should:

Maintain records that document shipment, receipt, disposition, return, and destruction of the IP(s)
Maintain a system for retrieving IPs and documenting this retrieval (e.g., for deficient product recall, reclaim after trial completion, expired product reclaim)
Maintain a system for the disposition of unused IP(s) and for the documentation of this disposition

MEX-22 further states the investigator/institution and/or a pharmacist, or other appropriate individual who is designated by the investigator/institution, should maintain records of the IP's delivery to the trial site, the inventory at the site, the use by each participant, and the return to the sponsor or alternative disposition of unused product(s). These records should include dates, quantities, batch/serial numbers, expiration dates (if applicable), and the unique code numbers assigned to the IP(s) and trial participants. Investigators should maintain records that document adequately that the participants were provided the doses specified by the protocol and reconcile all IP(s) received from the sponsor.

Per NOM-059-SSA1-2015, the sponsor is also responsible for storing files related to the manufacture and control of the IP for at least five (5) years after product registration has been granted. Additionally, the sponsor must ensure that this documentation is safeguarded, and that the files are stored at the sponsor’s facilities or in specific facilities contracted for this purpose.

4.7 and 10.1-10.2

2.12, 4.6, 5.13-5.14, and 8.2.14-8.2.15

XIII. Specific Sections of the Procedure on the Platform (VI)

3.4, 4.3, 4.5, and 4.12

3.24, 10.2, and 16.10

10.9

10.27

Definition of Specimen

Last content review/update: July 2, 2024

Specimens are not defined in the Kenyan regulations. However, per KEN-26, the Kenya Medical Research Institute (KEMRI) identifies biological samples and specimens as including, but not limited to, blood samples, saliva, breast milk samples, mosquito parts samples, biological cultures, tissue and tissue samples, hair samples, human stool, and environmental samples used in human health research.

Submission Forms (Shipping)

Last content review/update: November 8, 2024

In Mexico, a specimen is referred to as a “product of human beings.” According to GenHlthLaw and Reg-HumSpecDisp, products of human beings include any tissues or substances, excreted or expelled by the human body as a result of normal physiological processes.

GenHlthLaw and Reg-HumSpecDisp also provide more specific definitions for specimens including germ cells, stem cells, blood and derivatives, plasma, tissue, cellular concentrates, and organs. Please refer to these sources for more detailed information.

Additionally, G-RECs-Op-2018 states that human biological material includes organs, tissues, tissue components, cells, and products and cadavers of human beings.

Chapter I (Article 6)

14

Title XIV (Chapter I, Article 314)

Specimen Import & Export

Last content review/update: July 2, 2024

Import/Export

Per the G-ECBiomedRes, biological material must not be imported nor exported without proper justification and authorization, which includes a signed material transfer agreement (MTA) approved by the relevant institutions and deposited with the National Commission for Science, Technology and Innovation (NACOSTI). For exports, a Kenyan investigator must be included in the team that is conducting the research in the recipient country. All biological samples and data collected during research belong to the local participating institutions and country.

In addition, KEN-37 has indicated that Kenya’s Pharmacy and Poisons Board (PPB) will approve of an export for overseas research if the following requirements are met:

PPB initial approval letter or annual approval letter
Ethics committee (EC) approval letter
MTA
Study protocol with a summary justification for the participants' sample exportation
Informed consent form that highlights the areas where study participants are informed about the exportation of their samples

The G-KenyaCT states that in the case of transfer of materials during research involving children, the sponsor or the representative or the principal investigator should provide to the EC an MTA including, but not limited to, the following information:

Identification of the provider and recipient
Definition of the trial and how the material will and will not be used
Maintenance of confidentiality of background of supporting data or information, if any
Indemnification and insurance

In addition, KEN-26 provides an example of the Kenya Medical Research Institute (KEMRI)'s procedures for handling requests to ship biological samples or specimens. KEN-17 also provides an example of an MTA form from the Kenyatta National Hospital-University of Nairobi (KNH-UoN) Ethics and Research Committee.

KNH-UoN ERC Material Transfer Request Form

Submission Forms

4.1 and 4.2

Glossary of Terms and 1.172

Last content review/update: November 8, 2024

Import

As delineated in GenHlthLaw, Reg-COFEPRIS, and Reg-HumSpecDisp, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is responsible for authorizing the import of specimens (referred to as “products of human beings” in Mexico).

According to G-ImprtPermit, institutions that import products of human beings including tissues, cells, blood and its components or derivatives intended for research, diagnosis, teaching, or treatment for therapeutic purposes, must comply with specific COFEPRIS documentation submission requirements to apply for an import permit. The documentation required to obtain an import permit specifically for research purposes is as follows (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Import or Export of Products of Human Beings form (original) (see MEX-24)
Proof of payment of rights (one (1) original; G-ImprtPermit also specifies that in terms of the Federal Rights Law, proof of payment of rights is applicable only to the application for a permit for the hospitalization of blood units, their components, and hematopoietic progenitor cells)
Document certifying the operation of the foreign establishment issued by the health authority of the country of origin (original)
Health license for the corresponding line of business (original)
Notice of operation for the corresponding line of business (original)
Authorization document issued by COFEPRIS for the protocol when it is intended for humans, or a summary of the study when in vitro is being carried out, where appropriate (original)
Letter of acceptance in which the establishment that will receive the samples indicates the reason and use of the samples (original)
Shipping letter in which the foreign establishment indicates the reason and use of sending the samples (original)
Power of attorney (accreditation of the legal representative)

G-ImprtPermit further notes that COFEPRIS has 45 business days to respond to the import request, and 15 business day to notify the applicant of missing or additional information required in a prevention letter. The applicant, in turn, has five (5) business days to respond COFEPRIS’s prevention letter. The import permit approval is valid for 180 business days. Refer to G-ImprtPermit for detailed information necessary to obtain import permits for teaching, diagnosis, and therapeutic purposes including the use of human blood (i.e., umbilical cord blood or hematopoietic progenitor cells) and corneas.

D-CargoTransprt bars exclusive cargo shipments to the Mexico City International Airport (AICM). See D-CargoTransprt and D-ModCargoTransprt for more details regarding the relocation of cargo shipments to other airports in Mexico.

Export

According to G-ExprtPermit, institutions that dispose of or export products of human beings including tissues, cells, blood and its components or derivatives that are intended for diagnosis, treatment, research, or teaching purposes must also submit documentation to COFEPRIS to apply for an export permit.

G-ExprtPermit indicates the following general documentation must be provided to export cells, tissues, and products of human beings and their components (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

Import or Export of Products of Human Beings form (see MEX-24)
*Proof of payment of fees (original and two (2) legible copies)
*Letter of acceptance of the establishment abroad (original)
Authorization letter issued by COFEPRIS for the protocol when it is intended for humans, or a summary of the study when in vitro is being carried out, where appropriate (original)
Notice of operation of health establishment (original)
Health license (original)
Power of attorney (original)

*G-ExprtPermit indicates this requirement is only applicable to exports for blood units, their components and hematopoietic progenitor cells.

G-ExprtPermit further notes that COFEPRIS has 45 business days to respond to the export request, and 15 business days to notify the applicant of missing or additional information required in a prevention letter. The applicant, in turn, has five (5) business days to respond to COFEPRIS’s prevention letter. The permit approval is valid for 180 business days.

In addition, G-ExprtPermit outlines the following required documentation to be submitted to COFEPRIS to export umbilical cord blood or hematopoietic progenitor cells, for cryopreservation, research, or therapeutic purposes:

Import or Export of Products of Human Beings form (original) (see MEX-24)
Proof of payment of fees (one (1) original and two (2) legible copies (per G-ExprtPermit); G-ExprtPermit also specifies that in terms of the Federal Rights Law, proof of payment of rights is applicable only to the application for a permit for the hospitalization of blood units, their components and hematopoietic progenitor cells)
Letter of acceptance of the establishment abroad (original)
Health license (original)
Notice of operation of health establishment (original); G-ExprtPermit indicates this is only applicable to permits to export cells, tissues, products of human beings and their components
Document issued by the health authority of the destination country that certifies the operation of the establishment (original)
Power of attorney (original)

See also G-ExprtPermit for detailed documentation to be submitted to export cells, tissues, and products of human beings and their components intended for scientific research.

Import/Export Permit Submission Procedures

MEX-24 indicates that an applicant may submit a request to obtain a permit to import or export specimens in print, in person via COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37), or electronically via the Mexican Digital Window for Foreign Trade (Ventanilla Única de Comercio Exterior Mexicano (VUCEM)) (MEX-114). Per G-ImprtPermit and G-ExprtPermit, the application should be submitted electronically via MEX-114 (Refer to MEX-114 for submission instructions). G-ImprtPermit and G-ExprtPermit state that to submit an application online, it is necessary to obtain an e.signature (also known as e.firma). MEX-49 explains that the e.signature is a secure, encrypted digital file that identifies an applicant, and can be used to carry out procedures electronically with various government agencies. An e.signature can be obtained from the Tax Administration Service (Servicio de administración tributaria (SAT)) as described in MEX-105.

See MEX-116 for instructions on completing MEX-24. See also G-ImprtPermitMod for the required documentation and submission procedures to modify an import/export permit for products of human beings including tissues, cells, and blood and its components or derivatives.

Chapter VI (Articles 89 and 100)

Requirements, Form, Term, Validity of Resolution, and Steps

Title I (Chapter I, Article 3), Title II (Chapter II, Articles 17 Bis), Title XII (Chapter XIII, Articles 283-286 Bis), and Title XVI (Chapter I, Article 375)

Chapter I (Article 3)

Consent for Specimen