Mexico
Regulatory Authority
Regulatory Authority
Scope of Assessment
Regulatory Fees
Ethics Committee
Ethics Committee
Scope of Review
Ethics Committee Fees
Authorizing Body
Clinical Trial Lifecycle
Submission Process
Submission Content
Timeline of Review
Trial Initiation
Safety Reporting
Progress Reporting
Sponsorship
Definition of Sponsor
Trial Authorization
Insurance
Compensation
Quality, Data & Records Management
Site/Investigator Selection
Informed Consent
Documentation Requirements
Required Elements
Compensation Disclosure
Participant Rights
Special Circumstances/Emergencies
Vulnerable Populations
Children/Minors
Pregnant Women, Fetuses & Neonates
Prisoners
Mentally Impaired
Investigational Products
Definition of Investigational Product
Manufacturing & Import
IMP/IND Quality Requirements
Labeling & Packaging
Product Management
Specimens
Definition of Specimen
Specimen Import & Export
QUICK FACTS
Clinical trial application language Spanish
Parallel regulatory and ethical review permitted No
Clinical trial registration required Yes
In-country sponsor presence/representation required Yes
Age of minors Under 18
Specimens export allowed Yes
Regulatory Authority > Regulatory Authority
Last content review/update: December 21, 2018
Requirements
(1) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter I, Articles 7 and 12), (Chapter II, Articles 13, 17 bis, 17 bis 1, and 17 bis 2) and Title V (Chapter I, Article 102)
(2) (Regulation) Regulation of the Federal Commission for the Protection Against Sanitary Risks (Reg-COFEPRIS – Spanish) (April 13, 2004)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Chapter I (Articles 1 and 3), Chapter II, Chapter III, and Chapter IV (Article 14)
(3) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title III (Chapter I, Article 62) and (Chapter II, Articles 65 and 69)
(4) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 5.2
(5) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble
(6) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Internal Evaluation of Your Application
(7) (Guidance) Guide for the Submission of Human Research Protocols – Observational Studies – HOMOCLAVE COFEPRIS 04-010-D (G-COFEPRIS-ObservStudies – Spanish) (Version 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Internal Evaluation of Your Application
(8) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Requirements for Applicant Information Changes – HOMOCLAVE COFEPRIS-09-012 (Modification) (G-COFEPRIS-ApplicMod – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Internal Evaluation of Your Application
(9) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Requirements for Amending Clinical and/or Preclinical Safety Information – HOMOCLAVE COFEPRIS-09-012 (Security Amendment) (G-COFEPRIS-AppSecurityAmdt – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Internal Evaluation of Your Application
Summary

Overview

As set forth in MXGenHlthLaw, Reg-COFEPRIS, HlthResRegs-MX, NOM-012-SSA3-2012, and MX-GCP-COFEPRIS, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios) (COFEPRIS)) is the regulatory authority responsible for approving all clinical studies for the use of health resources, procedures, or experimental activities in human beings and/or their biological samples, for scientific research purposes. COFEPRIS is authorized to monitor and verify approved clinical studies to be conducted in Mexico in accordance with the provisions of the aforementioned documents.

Under the terms of Reg-COFEPRIS and MXGenHlthLaw, the Secretariat of Health (la Secretaría de Salud (SSA)) supervises the regulation, control, and promotion of health through COFEPRIS, a decentralized administrative body. COFEPRIS is headed by a Federal Commissioner appointed by the President of Mexico, upon the Secretariat of Health’s recommendation. Per Reg-COFEPRIS and MXGenHlthLaw, the agency has technical, administrative, and operational autonomy in regulating, evaluating, controlling, promoting, and disseminating the conditions and requirements to prevent and manage health risks in the Mexican population.

On a related note, per Additional Resources (A) and (B), COFEPRIS was recognized as a National Regulatory Authority of Regional Reference of Medicines and Biological Products by the Pan American Health Organization/World Health Organization (PAHO/WHO) in 2012, and the agency’s certification was recently revalidated by PAHO. COFEPRIS was also invited to become a member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S) in January 2018.

Reg-COFEPRIS specifies that COFEPRIS comprises eight (8) administrative units and four (4) government advisory bodies that manage the agency’s organizational and operational responsibilities. Included among COFEPRIS’s administrative units, and central to the research protocol authorization process is the Sanitary Authorization Commission (la Comisión de Autorización Sanitaria (CAS)).

As delineated in Reg-COFEPRIS, MXGenHlthLaw, and Additional Resource (C), CAS is responsible for issuing, extending, or revoking clinical research authorizations. According to G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, G-COFEPRIS-ApplicMod, and G-COFEPRIS-AppSecurityAmdt, CAS’s work is performed by its Technical Area for the Evaluation of Human Research Protocols, also known as the Clinical Trials (Ensayos Clínicos (EC)) technical area.

Contact Information: General

COFEPRIS
Oklahoma Street No. 14
Colony Napoles
Delegation Benito Juárez
Mexico City
CP 03810

Contact Information: Technical Inquiries

As per Additional Resources (E), (F), and (G), for technical inquiries or those inquires requiring an official response, contact COFEPRIS’s Integral Services Center:

COFEPRIS
Centro Integral de Servicios
Oklahoma Street No. 14
Colony Napoles
Delegation Benito Juárez
Mexico City
CP 03810

Phone: Domestic General Inquiries: 01-800-033-5050
Phone: International General Inquiries: 01-800-033-5050 and 0052 (55) 5531-1643
Email: contactociudadano@cofepris.gob.mx or contacto@cofepris.gob.mx

Additional Resources
(B) (Website) PAHO Recertifies COFEPRIS as Regulatory Body (Spanish) (January 16, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(C) (Website) COFEPRIS – Sanitary Authorizations (Spanish) (December 13, 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(D) (Website) COFEPRIS – Contact (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(F) (Form) Authorizations, Certificates and Visits (FF-COFEPRIS-01) (Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Options to Carry Out Your Procedure
Regulatory Authority > Scope of Assessment
Last content review/update: December 21, 2018
Requirements
(1) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter II, Article 17 bis), and Title III (Chapter III, Article 41 Bis), Title V (Chapter I, Article 102), Title V (Chapter I, Article 98), and Title XVI (Chapter III, Article 391 bis)
(2) (Regulation) Regulation of the Federal Commission for the Protection Against Sanitary Risks (Reg-COFEPRIS – Spanish) (April 13, 2004)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Chapter I (Articles 1 and 3) and Chapter IV (Article 14)
(3) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title I (Chapter I, Articles 9 and 10), Title II (Chapter I, Article 14), Title III (Chapter I, Articles 62 and 74a) and (Chapter II, Articles 65, 66, and 69), and Title V (Chapter I, Articles 99, 102, 109-111)
(4) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 4.2, 5.2, 6.3, 9.2, and 10.3
(5) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble, 1.3, 1.7, and 2
(6) (Standard) Mexican Official Standard NOM-257-SSA1-2014, Regarding Biotechnological Medicines (NOM-257-SSA1-2014 – Spanish) (December 11, 2014)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 7
(7) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: 4.4, 7.2, and Annex 6
(8) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion for Pre-UHAP, Submission to COFEPRIS, and Internal Evaluation of Your Application
(9) (Guidance) Guide for the Submission of Human Research Protocols – Observational Studies – HOMOCLAVE COFEPRIS 04-010-D (G-COFEPRIS-ObservStudies – Spanish) (Version 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion for Pre-UHAP, Module IV, Submission to COFEPRIS, and Internal Evaluation of Your Application
(10) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Requirements for Applicant Information Changes – HOMOCLAVE COFEPRIS-09-012 (Modification) (G-COFEPRIS-ApplicMod – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion for Pre-UHAP, Submission to COFEPRIS, and Internal Evaluation of Your Application
(11) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Requirements for Amending Clinical and/or Preclinical Safety Information – HOMOCLAVE COFEPRIS-09-012 (Security Amendment) (G-COFEPRIS-AppSecurityAmdt – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Submission to COFEPRIS and Internal Evaluation of Your Application
(12) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Clinical Documentation – HOMOCLAVE COFEPRIS 09-012 (Documents) (G-COFEPRIS-ApplicDocsMod – Spanish) (Version No.1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion – Pre-UHAP – CCINSHAE and Internal Evaluation of Your Application
(13) (Guidance) Guide for the Submission of Human Research Protocol Amendments –Requirements for Health Institution or Establishment Changes – HOMOCLAVE COFEPRIS-09-012 (Others) (G-COFEPRIS-Applic-InstChges – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion – Pre-UHAP – CCINSHAE and Internal Evaluation of Your Application
(14) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Requirements for Including a New Center – HOMOCLAVE COFEPRIS-09-012 (G-COFEPRIS-AppNewCtr – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion – Pre-UHAP – CCINSHAE and Internal Evaluation of Your Application
(15) (Guidance) User’s Manual – National Registry of Clinical Trials (RNEC) – COFEPRIS Mexico (G-RNECManual – Spanish) (Version 1.0) (March 2013)
Sanitary Authorization Commission, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: I and V
Summary

Overview

In accordance with MXGenHlthLaw, Reg-COFEPRIS, HlthResRegs-MX, NOM-012-SSA3-2012, and MX-GCP-COFEPRIS, 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 authorization of research protocols 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. As discussed in the Regulatory Authority subtopic, COFEPRIS acts on behalf of the Secretariat of Health (la Secretaría de Salud (SSA)). MX-GCP-COFEPRIS and HlthResRegs-MX specify that the scope of COFEPRIS’s assessment includes all clinical trials (Phases I-IV).

As stated in HlthResRegs-MX, NOM-012-SSA3-2012, and Additional Resources (A) and (B), COFEPRIS’s review and approval of a request for protocol authorization is dependent upon obtaining a favorable decision from the health institution’s Research Ethics Committee (REC) (Comité de Ética de la Investigación (CEI)) and Research Committee (RC) (El Comité de Investigación (IC)) where the study is being conducted, and, when applicable, the Biosafety Committee ((El Comité de Bioseguridad (BC)). In addition, HlthResRegs-MX, G-RECs-Operation_2018, and MXGenHlthLaw explain that the REC provides ethics recommendations on protocols for research in human beings, including a review of the risks and benefits of the research and the informed consent document, and preparing ethics guidelines for conducting research on humans. Per HlthResRegs-MX, G-RECs-Operation_2018, and NOM-012-SSA3-2012, the REC must also approve the informed consent document. HlthResRegs-MX also states that the RC evaluates the technical quality and scientific merit of the proposed research, and its opinion must contain the opinion of the REC and, where applicable, the BC.

Refer to the Ethics Committee topic, Ethics Committee subtopic for detailed information on these three (3) committees.

As delineated in HlthResRegs-MX, NOM-012-SSA3-2012, and Additional Resources (A) and (B), because COFEPRIS’s review and approval of a protocol authorization request is dependent upon obtaining a favorable ethics decision, COFEPRIS and ethics committee (REC and RC, and BC as appropriate) reviews may not be conducted in parallel. NOM-012-SSA3-2012 and G-RECs-Operation_2018 also note that with regard to the REC review, the REC should review the protocol periodically throughout the project’s duration to ensure conformance with ethical principles and applicable regulations. In addition, per NOM-012-SSA3-2012, the REC’s favorable decision is only later submitted to COFEPRIS with the protocol authorization request.

Clinical Trial Review Process

As delineated in Reg-COFEPRIS, NOM-012-SSA3-2012, and Additional Resource (E), COFEPRIS’s Sanitary Authorization Commission (la Comisión de Autorización Sanitaria (CAS)) is responsible for recording, evaluating, and issuing opinions on authorization requests for human research protocols. According to G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, G-COFEPRIS-ApplicMod, and G-COFEPRIS-AppSecurityAmdt, CAS’s work is performed by its Technical Area for the Evaluation of Human Research Protocols, also known as the Clinical Trials (Ensayos Clínicos (EC)) technical area. Per Additional Resources (F) and (G), CAS’s EC conducts its work via COFEPRIS’s Integral Services Center (Centro Integral de Servicios (CIS)), a public service system established by COFEPRIS to facilitate the processing of agency procedures and services.

As indicated in G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, G-COFEPRIS-ApplicMod, G-COFEPRIS-ApplicDocsMod, G-COFEPRIS-Applic-InstChges, G-COFEPRIS-AppNewCtr, G-COFEPRIS-AppSecurityAmdt, and Additional Resources (A), (B), (C), (D), and (H), the applicant must submit an application to the CIS to request protocol authorization or modification. Protocol modifications may be submitted to amend research procedures, to remove or add research center(s)/research institution(s), or, to provide updated clinical and/or preclinical security/safety IP information.

However, per Additional Resources (I), (J), and (K), rather than submitting the application directly to the CIS, the applicant may first choose to obtain a pre-assessment evaluation of his/her application through an Enabled Pre-Assessment Support Unit (Unidad Habilitada de Apoyo al Predictamen (UHAP)) within the Coordinating Commission of National Institutes of Health and Hospitals of High Specialty (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 Additional Resource (L), COFEPRIS also signed an agreement with the Faculty of Medicine of the Autonomous University of Nuevo León (Facultad de Medicina de Universidad Autónoma de Nuevo León (UANL)) to enable UHAPs within the UANL to collaborate with the agency to conduct pre-assessment application evaluations. Refer to Additional Resources (M), (N), (O), and (P) for detailed information on the CCINSHAE, the IMSS, and the UANL UHAP application submission requirements and evaluation process.

Per Additional Resource (I), the CCINSHAE coordinates nine (9) UHAPs. However, Additional Resources (Q) and (R) state that the CCINSHAE oversees (12) UHAPs. Additional Resource (K) further indicates that the fee for requesting a UHAP-CCINSHAE pre-assessment is 60,000 Mexican Pesos. The cost is the same for all 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. As stated in Additional Resource (I), the advantage of this additional evaluation is that once a UHAP issues a favorable letter of pre-authorization, the applicant may include this response with his/her submission to COFEPRIS through the CIS to be reviewed by the EC.

Further, per HlthResRegs-MX, G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, G-COFEPRIS-ApplicMod, G-COFEPRIS-ApplicDocsMod, G-COFEPRIS-Applic-InstChges, G-COFEPRIS-AppNewCtr, and G-COFEPRIS-AppSecurityAmdt, receipt of a favorable pre-evaluation assessment also requires the EC to issue a response within a maximum of 30 business days as long as the applicant notifies the EC that his/her application was submitted with the pre-evaluation assessment. A UHAP pre-assessment may result in a favorable or unfavorable review. If the review is unfavorable, the applicant is required to respond within 30 calendar days to all the issues raised, or, the submission will be designated “rejected,” and the review will be concluded and returned to the applicant.

According to G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, G-COFEPRIS-ApplicMod, G-COFEPRIS-ApplicDocsMod, G-COFEPRIS-Applic-InstChges, G-COFEPRIS-AppNewCtr, G-COFEPRIS-AppSecurityAmdt, and Additional Resource (H), if the applicant chooses to send the application requesting protocol authorization directly to COFEPRIS, then CIS will assign a reference number to the application and send it to the EC in CAS for technical evaluation. If the EC responds favorably to the initial request, the authorization is approved, and the clinical study may begin. However, if the request is rejected, an objection is issued and the applicant must resubmit a request for continued processing after addressing all of the issues raised. In either case, the applicant must use the CIS reference number to track the official resolution of either an authorization or an objection of the request.

Per HlthResRegs-MX and G-RNECManual, once the applicant obtains an official authorization from COFEPRIS, he/she 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 (Additional Resource (S)). Established in 2013, RNEC includes all applications for authorization of research protocols in human subjects submitted to the CIS since 2013. The RNEC is in charge of the CAS’s EC 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.

Additional Resources
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Necessary Documents
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
(E) (Website) COFEPRIS – Sanitary Authorizations (Spanish) (December 13, 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(F) (Website) COFEPRIS – Integral Services Center (Spanish) (December 12, 2016)
Integral Services Center, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Integral Services Center, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Coordinating Commission of National Institutes of Health and High Specialty Hospitals (CCINSHAE), Secretariat of Health
Coordinating Commission of National Institutes of Health and High Specialty Hospitals (CCINSHAE), Secretariat of Health
Coordinating Commission of National Institutes of Health and High Specialty Hospitals (CCINSHAE), Secretariat of Health
(L) (Article) Agreement with the IMSS on Clinical Research (Spanish) (April 28, 2017)
Jaime, Dr. Rosa Guadalupe Legaspi, COFEPRIS Magazine – Protection and Health
(M) (Document) Generalizations for Presenting UHAP-CCINSHAE Documentation (Spanish) (Date Unavailable)
Enabled Pre-Assessment Support Unit (UHAP), Coordinating Commission of National Institutes of Health and High Specialty Hospitals (CCINSHAE), Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(N) (Document) Enabled Pre-Assessment Support Unit (UHAP) (Spanish) (Current as of December 20, 2018)
Mexican Social Security Institute (IMSS)
(O) (Website) Submitting a "Pre-Assessment Request" to a UANL UHAP (Spanish) (Current as of December 20, 2018)
Faculty of Medicine and University Hospital, Autonomous University of Nuevo León (UANL)
(P) (Flowchart) UNAL General Procedure of Authorization (Spanish) (Date Unavailable)
Faculty of Medicine of the Autonomous University of Nuevo León
(Q) (Document) List of Enabled Pre-Assessment Support Units – UHAP (Spanish) (Date Unavailable)
Sanitary Authorization Commission, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(R) (Article) Scientific Investigation in Mexico (Spanish) (February 2, 2017)
Bernal, Dr. Ana Luisa Sesman, COFEPRIS Magazine – Protection and Health
(S) (Website) COFEPRIS – National Registry of Clinical Trials (RNEC) - Registered Users Login (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Regulatory Authority > Regulatory Fees
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module II
(2) (Guidance) Guide for the Submission of Human Research Protocols – Observational Studies – HOMOCLAVE COFEPRIS 04-010-D (G-COFEPRIS-ObservStudies – Spanish) (Version 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module II
(3) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Clinical Documentation – HOMOCLAVE COFEPRIS 09-012 (Documents) (G-COFEPRIS-ApplicDocsMod – Spanish) (Version No.1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module II
(4) (Guidance) Guide for the Submission of Human Research Protocol Amendments –Requirements for Health Institution or Establishment Changes – HOMOCLAVE COFEPRIS-09-012 (Others) (G-COFEPRIS-Applic-InstChges – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module II
(5) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Requirements for Applicant Information Changes – HOMOCLAVE COFEPRIS-09-012 (Modification) (G-COFEPRIS-ApplicMod – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module II
(6) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Requirements for Including a New Center – HOMOCLAVE COFEPRIS-09-012 (G-COFEPRIS-AppNewCtr – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module II
(7) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Requirements for Amending Clinical and/or Preclinical Safety Information – HOMOCLAVE COFEPRIS-09-012 (Security Amendment) (G-COFEPRIS-AppSecurityAmdt – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module II
Summary

Overview

As indicated in G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, G-COFEPRIS-ApplicDocsMod, G-COFEPRIS-Applic-InstChges, G-COFEPRIS-ApplicMod, G-COFEPRIS-AppNewCtr, and G-COFEPRIS-AppSecurityAmdt, the applicant is responsible for paying a non-refundable fee (referred to as “Proof of Payment of Rights”) to submit a clinical research application to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios) (COFEPRIS)).

According to Additional Resources (A), (B), and (C), applicants may obtain the fee information for a specific procedure or service using COFEPRIS’s Integral Services Center (Centro Integral de Servicios (CIS)) (Additional Resource (B)). Per Additional Resources (A), (B) and (C), CIS is a public service system established by the Mexican government to facilitate the processing of agency procedures and services.

In order to navigate the CIS system, applicants need to determine the correct COFEPRIS procedure code to obtain the associated processing instructions and fees. Per Additional Resources (A), (B), and (C), applicants may schedule an appointment with CIS for assistance with this process. Applicants may also choose to use Additional Resources (D) and (E) to generate a “Help Sheet” to determine the correct procedural code to pay for an authorization request. The code is comprised of the following elements: format, procedure type, procedure subtype, and procedure modality.

To determine the correct COFEPRIS procedure code, Additional Resources (D) and (E) help the applicant map the unique alphanumeric code (i.e., Homoclave) to the specific procedure type, subtype, and modality. The system generates a payment password with the associated fee. In addition, the 2018 rates for various COFEPRIS authorization requests, import licenses, and other health services are provided in Additional Resource (E).

Regulatory Fees

Additional Resources (A), (F), (G), and (H) 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: 5,615.49 Mexican Pesos (Additional Resources (A) and (F))
  • Authorization of research protocol without risk (observational) in humans: 5,615.49 Mexican Pesos (Additional Resource (G))
  • Amendment or modification to the research protocol or inclusions to the protocol: 4,212 Mexican Pesos (Additional Resource (H))

Instructions for Payment for Authorization Requests

As explained in Additional Resources (B) and (I), applicants should make payments for these procedures and services through an authorized credit institution using E5cinco (See Additional Resource (I) for a link to participating financial institutions). E5cinco is an electronic scheme created to enable users to submit the Payment of Rights, Products, and Uses (Derechos, Productos y Aprovechamientos (DPAs)) to a participating credit institution through its Internet portal or banking window. E5cinco replaces the paper payment submission formerly available using official fiscal forms 5 and 16. See also Additional Resource (K) for detailed DPA payment instructions via E5cinco.

Additional Resources
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(B) (Website) COFEPRIS – Integral Services Center (Spanish) (December 12, 2016)
Integral Services Center, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(D) (Website) Help for Generating Proof of Payment Receipt (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Procedures (Trámites in Spanish) option in drop down menu and follow through system prompts
(E) (Website) Steps to Complete Proof of Payment Process (Spanish) (Current as of December 20, 2018)
Integral Services Center, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Structure File for Clinical Protocols
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Other Permits or Authorizations (p.10)
(G) (Website) Research Protocol Authorization Without (Observed) Risk in Humans (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(H) (Website) Amendment or Modification to the Research Protocol or Inclusions to the Protocol (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(I) (Website) E5cinco: Payment of Rights, Products and Uses (Spanish) (January 1, 2018)
Ministry of the Interior
Tax Administration Service (SAT)
(K) (Website) Procedure for Electronic Payment of DPAs (Spanish) (May 25, 2015)
Secretary of Public Function (SFP)
Ethics Committee > Ethics Committee
Last content review/update: December 21, 2018
Requirements
(1) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter I, Article 14), Title V (Chapter I, Articles 99-102, 104, 108, and 109)
(2) (Regulation) Agreement on General Provisions for the Integration and Functions of Research Ethics Committees and Hospitals Units with RECs in accordance with the National Bioethics Commission (Agreement_REC Operation Criteria – Spanish) (Effective Date: October 31, 2012)
Secretariat of Health
Relevant Sections: Preamble, Fourth, Sixth -Tenth, and Twelfth
(3) (Regulation) Agreement on Reforms and Additions to the General Provisions for the Integration and Functions of the Research Ethics Committees in accordance with the National Bioethics Commission (Agreement_RECRegistration – Spanish) (Effective Date: January 11, 2016)
Secretariat of Health
Relevant Sections: Article One (Twelfth, Twelfth Bis 1, Twelfth Bis 2, and Sixteenth)
(4) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: 3, 3.1, 3.3, 4.1, 4.3, 5.1, 5.2, 6.1, 6.2, 9, 11, and Annexes 1 and 2
(5) (Guidance) National Guidelines for integration and Operation of the Research Ethics Committee (REC) (G-RECs-Operation_Abridged) (Date Unavailable)
National Bioethics Commission (CONBIOETICA), Secretariat of Health
Relevant Sections: Research Ethics Committee, Conceptualization of the Research Ethics Committee – Control and Monitoring Function, The Ethics Research Committee – Integration/Members/Selection/Designation, REC Members Functions – Members Requirements, Results and Results of the Protocols’ Evaluation, Addendum: Procedures and Operational Activities
(6) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 0, 4, 5, 6.3, 9.1, and 9.2
(7) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title III (Chapter II, Article 33 and Chapter III, Article 41 Bis.) and Title V (Chapter I, Article 98)
(8) (Standard) Technical Rule Number 314, for the Registration and Monitoring of Health Research (TechStd-314 – Spanish) (Effective Date: July 26, 1988)
Secretariat of Health
Relevant Sections: Chapter I (Article 6) and Chapter II (Articles 8-10-11)
(9) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 2
Summary

Overview

As set forth in HlthResRegs-MX, Agreement_REC Operation Criteria, Agreement_RECRegistration, G-RECs-Operation_2018, G-RECs-Operation_Abridged, NOM-012-SSA3-2012, and Additional Resources (A) and (B), Mexico has a decentralized registration process for Research Ethics Committees (REC) (Comité de Ética de la Investigación (CEI)) operating through the National Bioethics Commission (La Comisión Nacional de Bioética (CONBIOÉTICA)). In addition, per HlthResRegs-MX and NOM-012-SSA3-2012, and Additional Resources (C), (D), (E), and (F), Research Committees (RCs) (El Comité de Investigación (IC)) and Biosafety Committees ((El Comité de Bioseguridad (BC)) within each health institution must also register with the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)).

Per HlthResRegs-MX, MXGenHlthLaw, and NOM-012-SSA3-2012, and Additional Resources (G) and (H), REC and RC approval is required for each trial site where a study is being conducted, and when applicable, BC approval is required as well. In addition, HlthResRegs-MX and MXGenHlthLaw explain that the REC provides ethics recommendations on protocols for research in human beings, including a review of the risks and benefits of the research, and prepares ethics guidelines for conducting research in humans. Per HlthResRegs-MX and NOM-012-SSA3-2012, the REC must also approve the informed consent document. HlthResRegs-MX states that the RC evaluates the technical quality and scientific merit of the proposed research, and its opinion must contain the REC opinion and, where applicable, the BC opinion. The BC, 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-MX, MXGenHlthLaw, and NOM-012-SSA3-2012. Pursuant to HlthResRegs-MX and NOM-012-SSA3-2012, the BC 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.

Refer to Additional Resources (C), (D), (E), and (F) for detailed RC and BC registration requirements and the application form. See also the Authorizing Body subtopic for additional CONBIOÉTICA REC registration requirements.

According to TechStd-314, the institution’s research area head must also register the REC, RC, and BC within 20 days following their establishment and provide committee information as required by the Secretariat. Additionally, he/she must register research projects within 20 business days following their authorization, and report annually on any registered ECs/projects during the first 10 business days of July each year. See TechStd-314 for institutional reporting requirements.

CONBIOÉTICA Composition

Please refer to Ethics Committee topic, Authorizing Body subtopic.

REC Composition

As per MXGenHlthLaw and G-RECs-Operation_Abridged, RECs must be autonomous and interdisciplinary gender-balanced groups composed of medical personnel from different specialties; professionals from nursing, social work, sociology, anthropology, psychology, philosophy, or law fields who have bioethics training; and, community representatives affected by the health condition under study or other health services users. In addition to the previously stated criteria, G-RECs-Operation_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-MX 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. NOM-012-SSA3-2012, by comparison, states that REC health professionals should have expertise in the subjects investigated at the institution, regardless of whether the professionals have experience in scientific methodology applied to research. Further, the community representatives should embody the moral, cultural, and social values of the research participants.

Per Agreement_REC Operation Criteria, Agreement_RECRegistration, and G-RECs-Operation_Abridged, 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, MXGenHlthLaw, G-RECs-Operation_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.

NOM-012-SSA3-2012 also 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-Operation_2018, G-RECs-Operation_Abridged, Agreement_REC Operation Criteria, and Agreement_RECRegistration note that the REC should comprise a president, at least four (4) members, one 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-Operation_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.

RC and BC Composition

As described in NOM-012-SSA3-2012, RCs and BCs should be multidisciplinary, consisting of health professionals from different specialties related to the health institution’s investigational research areas. The committees should also include professionals from other disciplines, and laypersons from the community who represent the moral, cultural, and social values of the research participants. The professionals may be based at the institution where the study is being conducted or from other medical institutions. In addition, per HlthResRegs-MX, the RC and BC should be comprised of at least three (3) scientists each with research expertise. The RC should include health institution members with scientific methodology knowledge and expertise preferably. The BC should include scientists with broad expertise and knowledge to ensure that research activities are performed under the best biosafety measures. BC scientists do not have to be on the health institution staff.

REC, RC, and BC Terms of Reference, Review Procedures, and Meeting Schedule

As set forth in Agreement_REC Operation Criteria, G-RECs-Operation_2018, G-RECs-Operation_Abridged, NOM-012-SSA3-2012, and MX-GCP-COFEPRIS, RECs should operate within written standard operating procedures (SOPs) to conduct their reviews. Agreement_REC Operation Criteria and G-RECs-Operation_2018 state that the health institution owner must approve the SOPs and issue a certificate of appointment to each of the REC members. HlthResRegs-MX, G-RECs-Operation_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 Agreement_REC Operation Criteria, G-RECs-Operation_2018, G-RECs-Operation_Abridged, and MX-GCP -COFEPRIS, the following minimum requirements must be met:

  • 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

For detailed REC procedures and information on other administrative processes, see Agreement_REC Operation Criteria, G-RECs-Operation_2018, G-RECs-Operation_Abridged, and MX-GCP-COFEPRIS.

As per G-RECs-Operation_2018 and G-RECs-Operation_Abridged, information and files relating to REC activities as well as any confidential project information should be preserved in the REC’s office according to its SOPs and current regulations. Further, per G-RECs-Operation_Abridged, once the research study is completed, documentation should be transferred to the institution’s central archives, with a backup saved in the REC’s database. It is the REC president’s responsibility to protect research protocol files for five (5) years following the end of the project’s conclusion.

See G-RECs-Operation_2018 and G-RECs-Operation_Abridged for additional REC recordkeeping requirements.

Additional Resources
(A) (Website) Registration Process of Research Ethics Committees (CEI) (Spanish) (July 10, 2018)
National Bioethics Commission, Secretariat of Health
(B) (Form) Application for Research Ethics Committee Registration (Spanish) (Date Unavailable)
National Bioethics Commission (CONBIOETICA), Secretariat of Health
(C) (Website) Research Committee Registration (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(D) (Website) Biosafety Committee Registration (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(E) (Website) Research and Biosecurity Committees Registration (Spanish) (September 28, 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(F) (Form) Application for Committee Registration (FF-COFEPRIS-09) (Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Necessary Documents
(I) (Document) Registration List of Research Ethics Committees (CEIs) (Spanish) (Date Unavailable)
Secretariat of Health
Ethics Committee > Scope of Review
Last content review/update: December 21, 2018
Requirements
(1) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: 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, 108, and 109)
(2) (Regulation) Agreement on General Provisions for the Integration and Functions of Research Ethics Committees and Hospitals Units with RECs in accordance with the National Bioethics Commission (Agreement_REC Operation Criteria – Spanish) (Effective Date: October 31, 2012)
Secretariat of Health
Relevant Sections: Preamble and Fifth
(3) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: 3.1-3.3, 4.3, 8.1, 8.2, 11, and Annexes 5 and 6
(4) (Guidance) National Guidelines for integration and Operation of the Research Ethics Committee (REC) (G-RECs-Operation_Abridged) (Date Unavailable)
National Bioethics Commission (CONBIOETICA), Secretariat of Health
Relevant Sections: Research Ethics Committee, Conceptualization of Research Ethics Committee, Requirements for the Evaluation of Protocols – Communication of the Decision, and Results and Results of the Protocols’ Evaluation
(5) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 0, 6.3, 8.4, 9.2, and 10.3
(6) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 2
Summary

Overview

According to HlthResRegs-MX, Agreement_REC Operation Criteria, G-RECs-Operation_2018, and G-RECs-Operation_Abridged, the primary scope of information assessed by the Research Ethics Committee (REC) (Comité de Ética de la 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-MX and G-RECs-Operation_2018, RECs must also pay special attention to reviewing informed consent and protecting the welfare of certain classes of participants deemed vulnerable. (See Informed Consent topic, and the subtopics of Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired for additional information about these populations.)

HlthResRegs-MX, G-RECs-Operation_2018, and G-RECs-Operation_Abridged 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-MX, G-RECs-Operation_2018, and G-RECs-Operation_Abridged for detailed ethical review guidelines.

Role in Clinical Trial Approval Process

Per HlthResRegs-MX, NOM-012-SSA3-2012, and Additional Resources (A) and (B), the applicant must obtain a favorable decision from the REC and the Research Committee (RC) (El Comité de Investigación (IC)) at the health institution where the study is being conducted, and, when applicable, a favorable decision from the Biosafety Committee ((El Comité de Bioseguridad (BC)). As per in MX-GCP-COFEPRIS, HlthResRegs-MX, NOM-012-SSA3-2012, and G-RECs-Operation_Abridged, 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)). Per NOM-012-SSA3-2012, the REC must assess and approve the research protocol at the beginning of the project, and periodically throughout the project’s duration. The REC’s favorable decision is later submitted to COFEPRIS as part of the application to obtain protocol authorization. Consequently, the REC and COFEPRIS reviews may not be conducted in parallel.

As delineated in G-RECs-Operation_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-Operation_Abridged also states that the REC’s decision must be communicated in writing to the applicant according to the committee’s established procedures, within a period not to exceed 30 days from the date of receiving his/her complete application.

Per G-RECs-Operation_Abridged, the researcher may submit a one-time objection to the REC’s decision within seven (7) working days after receiving notification. The REC will, in turn, address the researcher’s objection at the next regular committee session, and present its response within seven (7) working days. The REC’s decision is not permitted to be appealed at this point. G-RECs-Operation_2018 and G-RECs-Operation_Abridged also state that the approval of a new application is valid for one (1) year.

In addition, G-RECs-Operation_2018 and G-RECs-Operation_Abridged indicate 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.

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

Additional Resources
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Necessary Documents
Ethics Committee > Ethics Committee Fees
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: 4.2
(2) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 2.7
(3) (Regulation) Agreement on General Provisions for the Integration and Functions of Research Ethics Committees and Hospitals Units with RECs in accordance with the National Bioethics Commission (Agreement_REC Operation Criteria – Spanish) (Effective Date: October 31, 2012)
Secretariat of Health
Relevant Sections: Seventh, Ninth, and Eleventh
Summary

Overview

As set forth in G-RECs-Operation_2018, MX-GCP-COFEPRIS, and Agreement_REC Operation Criteria, Research Ethics Committees (RECs) 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-Operation_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 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-Operation_2018, REC financial support should not be used for purposes other than for its operation, and all activities must be handled with full transparency. Members should receive support 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 for receipt of documents, and safeguarding of documentation protocols, opinions, and minutes
  • Administrative assistance for REC activities
Additional Resources
No additional resources
Ethics Committee > Authorizing Body
Last content review/update: December 21, 2018
Requirements
(1) (Regulation) Decree Creating the Decentralized Body Called the National Bioethics Commission (Decree-CONBIOETICA – Spanish) (Effective Date: February 17, 2017)
Secretariat of Health
Relevant Sections: Preamble, Articles One - Four, and Seven
(2) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title III (Chapter III, Article 41 Bis.) and Title V (Chapter I, Article 98)
(3) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: 5.3, 11, and Annex 4
(4) (Guidance) National Guide for the Integration and Operation of Hospital Bioethics Committees (G-CHBs-Operation – Spanish) (5th Edition) (2015)
National Bioethics Commission, Secretariat of Health
Relevant Sections: Registry of the Hospital Bioethics Committees, Proof of Registration, Validity of the Registration, Renewal of the Registration, and Appendix 1
(5) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title V (Chapter I, Articles 99-102, 104, 108, and 109)
(6) (Regulation) Agreement on General Provisions for the Integration and Functions of Research Ethics Committees and Hospitals Units with RECs in accordance with the National Bioethics Commission (Agreement_REC Operation Criteria – Spanish) (Effective Date: October 31, 2012)
Secretariat of Health
Relevant Sections: Preamble, Fourth, Sixth-Tenth, Tenth-Second, Twelfth, and Annex 1
(7) (Regulation) Agreement on Reforms and Additions to the General Provisions for the Integration and Functions of the Research Ethics Committees in accordance with the National Bioethics Commission (Agreement_RECRegistration – Spanish) (Effective Date: January 11, 2016)
Secretariat of Health
Relevant Sections: Article One (Seventh, Twelfth, Twelfth Bis 1, Twelfth Bis 2, and Sixteenth)
(8) (Guidance) National Guidelines for integration and Operation of the Research Ethics Committee (REC) (G-RECs-Operation_Abridged) (Date Unavailable)
National Bioethics Commission (CONBIOETICA), Secretariat of Health
Relevant Sections: Research Ethics Committee, REC Members Functions, Results and Results of the Protocols’ Evaluation, and Assent and/or Record of the Ethics Research Committees
Summary

Overview

The National Bioethics Commission (La Comisión Nacional de Bioética (CONBIOÉTICA)) was established as a decentralized entity of the Secretariat of Health (la Secretaría de Salud (SSA)) in 2005 as specified in Decree-CONBIOETICA. According to Decree-CONBIOETICA and Additional Resource (A), the agency has technical and operational autonomy in defining and establishing national bioethics policies in medical care and health research. Per Decree-CONBIOETICA, MXGenHlthLaw, G-RECs-Operation_2018, and Additional Resource (B), CONBIOETICA is also responsible for promoting the organization and operation of Research Ethics Committees (RECs) and hospital bioethics committees (comités hospitalarios de bioetica (CHBs)) in public and private health institutions, for establishing and disseminating criteria to support development of REC activities, and for providing committee member training support.

G-CHBs-Operation and Additional Resources (C) and (D) indicates that CHBs must also register with CONBIOETICA, who is, in turn, required to issue a registration record within a maximum of 15 business days. CONBIOETICA’s registration is valid for three (3) years. Refer to G-CHBs-Operation and Additional Resources (C) and (D) for detailed CHB registration information.

CONBIOETICA Composition

As per Decree-CONBIOETICA, CONBIOETICA is a decentralized body of the SSA consisting of six (6) council members and one (1) president, who must be appointed by the Secretary of Health. The Secretary of Health must also appoint an executive director at the chairman of the board’s proposal.

Council members must remain in office for four (4) years, with the exception of the president, and are not permitted to be ratified for subsequent periods. The Secretary of Health may also invite distinguished members of the local and medical community to participate in the council who shall have the right to voice their opinions, but not to vote. All council members’ appointments are of an honorary nature with the exception of the chairman of the board.

See Decree-CONBIOETICA for detailed information on CONBIOETICA composition and responsibilities.

REC Registration and Auditing

As delineated in HlthResRegs-MX, Agreement_REC Operation Criteria, Agreement_RECRegistration, G-RECs-Operation_2018, G-RECs-Operation_Abridged, and according to Additional Resource (B), all RECs are required to register with CONBIOETICA in order to conduct health research in humans.

Agreement_RECRegistration, G-RECs-Operation_2018, and G-RECs-Operation_Abridged further state that CONBIOETICA has ten (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 in this timeframe, the application shall 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 G-RECs-Operation_Abridged, REC registration with CONBIOETICA will also allow for the creation of a database containing information pertaining to committee integration and operation for statistical and monitoring compliance.

G-RECs-Operation_2018 further notes that the application must be submitted to CONBIOETICA according to the form and requirements delineated in Annex 1 of Agreement_RECRegistration. Per Agreement_RECRegistration and Additional Resource (B), the REC registration form may be mailed or submitted electronically through CONBIOETICA’s website. However, G-RECs-Operation_Abridged requires the form to be submitted electronically. As explained in Agreement_RECRegistration, G-RECs-Operation_Abridged, and Additional Resource (B), 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. Refer to G-RECs-Operation_2018, G-RECs-Operation_Abridged, and Additional Resource (B) for detailed registration application instructions and requirements.

As delineated in Agreement_RECRegistration, G-RECs-Operation_2018, and G-RECs-Operation_Abridged, a registration renewal application must be submitted by the institutional head to CONBIOETICA 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 Agreement_RECRegistration, G-RECs-Operation_2018, and G-RECs-Operation_Abridged for detailed registration application and renewal registration application requirements.

In addition to CONBIOETICA’s REC registration requirement, per MXGenHlthLaw, G-RECs-Operation_2018, G-RECs-Operation_Abridged, Agreement_REC Operation Criteria, and Agreement_RECRegistration, 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 an REC (CEI) Installation Certificate (Additional Resource (G)) which stipulates its characteristics and functions. Refer to G-RECs-Operation_2018 and G-RECs-Operation_Abridged for detailed certificate requirements.

Contact Information: CONBIOÉTICA
CONBIOÉTICA
Calzada Arenal Street No. 134
Colony Arenal Tepepan
Delegation Tlalpan
Mexico City
CP 14610

Additional Resources
(A) (Website) National Bioethics Commission - What Do We Do? (Spanish) (Current as of December 20, 2018)
National Bioethics Commission, Secretariat of Health
(B) (Website) Research Ethics Committees (Spanish) (December 14, 2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: Registration Process of Research Ethics Committees (CEI)
(C) (Website) Hospital Bioethics Committee (Spanish) (December 14, 2018)
National Bioethics Commission, Secretariat of Health
National Bioethics Commission, Secretariat of Health
(E) (Document) Registration List of Research Ethics Committees (CEIs) (Spanish) (Date Unavailable)
Secretariat of Health
(F) (Form) Application for Research Ethics Committee Registration (Spanish) (Date Unavailable)
National Bioethics Commission (CONBIOETICA), Secretariat of Health
(G) (Form) CEI Installation Certificate (Spanish) (Date Unavailable)
National Bioethics Commission (CONBIOETICA), Secretariat of Health
Clinical Trial Lifecycle > Submission Process
Last content review/update: December 21, 2018
Requirements
(1) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter II, Article 17 bis) and Title III (Chapter III, Article 41 Bis), and Title V (Chapter I, Article 98)
(2) (Regulation) Regulation of the Federal Commission for the Protection Against Sanitary Risks (Reg-COFEPRIS – Spanish) (April 13, 2004)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Chapter I (Articles 1 and 3) and Chapter IV (Article 14)
(3) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title III (Chapter I, Article 62) and (Chapter II, Articles 65 and 69), Title II (Chapter I, Article 14), and Title V (Chapter I, Articles 99, 102, 109-111)
(4) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 5.2, 6.3, 9.2, and 10.3
(5) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble, 1.3, and 2
(6) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Modules I – II
(7) (Guidance) Guide for the Submission of Human Research Protocols – Observational Studies – HOMOCLAVE COFEPRIS 04-010-D (G-COFEPRIS-ObservStudies – Spanish) (Version 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Modules I-II
(8) (Guidance) Characteristics of Applications Related to Clinical Protocols of Bioequivalence in Humans – HOMOCLAVE COFEPRIS 04-010-B (G-IPDocAppReqs – Spanish) (Version 1.0) (December 2015)
Sanitary Authorization Commission, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Summary

Overview

In accordance with MXGenHlthLaw, Reg-COFEPRIS, HlthResRegs-MX, NOM-012-SSA3-2012, and MX-GCP-COFEPRIS, 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-MX, NOM-012-SSA3-2012, and Additional Resources (A) and (B), the applicant must also obtain a favorable decision from the Research Ethics Committee (REC) (Comité de Ética de la Investigación (CEI)) and the Research Committee (RC) (El Comité de Investigación (IC)) at the health institution where the study is being conducted, and, when applicable, a favorable decision from the Biosafety Committee (El Comité de Bioseguridad (BC)). In addition, HlthResRegs-MX and MXGenHlthLaw explain that the REC provides ethics recommendations on protocols for research in human beings, including a review of the risks and benefits of the research and the informed consent document, and preparing ethics guidelines for conducting research on humans. Per HlthResRegs-MX and NOM-012-SSA3-2012, the REC must also approve the informed consent document. Further, HlthResRegs-MX states that the RC evaluates the technical quality and scientific merit of the proposed research, and its opinion must contain the opinion of the REC and, where applicable, the BC.

As delineated in HlthResRegs-MX, NOM-012-SSA3-2012, and Additional Resources (A) and (B), because COFEPRIS’s review and approval of a protocol authorization request is dependent upon obtaining a favorable decision from the REC and RC, COFEPRIS and ethics committee (REC and RC) reviews may not be conducted concurrently. However, per HlthResRegs-MX, the REC, the RC, and the BC may meet together to decide whether to authorize a protocol to conduct research on humans, as appropriate. NOM-012-SSA3-2012 also notes that with regard to the REC review, the REC should review the protocol periodically throughout the project’s duration to ensure conformance with ethical principles and applicable regulations. (See the Submission Content subtopic for detailed submission requirements).

Delivery Address for Research Protocol Authorization Application

As per Additional Resources (B), (C), and (D), applications as well as technical inquiries, or those inquiries requiring an official response should be submitted to COFEPRIS’s Integral Services Center (Centro Integral de Servicios (CIS)):

COFEPRIS
Centro Integral de Servicios
Oklahoma Street No. 14
Colony Napoles
Delegation Benito Juárez
Mexico City
CP 03810

Phone: Domestic General Inquiries: 01­800­033­5050
Phone: International General Inquiries: 01-800-033-5050 and 0052 (55) 5531-1643

Email: contactociudadano@cofepris.gob.mx or contacto@cofepris.gob.mx

Assembly and Number of Copies

As indicated in G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, and Additional Resource (A), to request research protocol authorization, applicants must submit one (1) hard copy of the application and one (1) electronic copy on CD-ROM or USB. Additional Resource (A) further states that electronic format (Rich Text Format (RTF)) is preferable.

Application documentation should be presented as follows:

  • Each page of the application submission must be printed legibly and paginated in the upper left-hand corner (per G-IPDocAppReqs), or the upper right-hand corner (per G-COFEPRIS-ApplicReqs), with the page number (001) starting on the last page going forward
  • Only the proof of payment should not be paginated (per G-COFEPRIS-ApplicReqs and G-COFEPRIS-ObservStudies)
  • Each section should be separated by a colored sheet (per G-COFEPRIS-ObservStudies)
  • Information must be presented with a side clasp (right side per G-IPDocAppReqs) or (left side per G-COFEPRIS-ApplicReqs, without binding or folders
  • Information must be identified with a colored cover or sheet on the front side, and the type of application should be indicated with a label (see G-IPDocAppReqs for detailed instructions)
  • Information can be highlighted using a highlighter pen (per G-IPDocAppReqs)

Additionally, per G-COFEPRIS-ApplicReqs, and Additional Resources (A), (B), and (E), the Authorizations, Certificates and Visits form (Additional Resource (F)) should be included in the application submission, as well as the original proof of payment of rights with two (2) copies of the receipt.

Please refer to G-IPDocAppReqs, G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, and Additional Resource (A) for detailed protocol authorization application formatting requirements.

Clinical Trial Application Language Requirements

G-IPDocAppReqs, G-COFEPRIS-ApplicReqs , and G-COFEPRIS-ObservStudies state that all documentation related to submitting applications for research protocol authorization is required to be in Spanish; no documentation (e.g., protocol and researcher’s manual) should be submitted in English. Per G-IPDocAppReqs, legal documents issued in another language must be accompanied by a translation prepared by an expert translator.

Additional Resources
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Necessary Documents and Options to Carry Out Your Procedure
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(D) (Website) COFEPRIS – Contact (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(E) (Instructions Document) Instructions for Filling Out the Authorizations, Certificates and Visits Form (Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Homoclave, Name and Modality and Fast Filling Guide (Homoclaves COFEPRIS-04-010-A, COFEPRIS-04-010-B, and COFEPRIS-04-010-D)
(F) (Form) Authorizations, Certificates and Visits (FF-COFEPRIS-01) (Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(G) (Website) COFEPRIS – Integral Services Center (Spanish) (December 12, 2016)
Integral Services Center, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Clinical Trial Lifecycle > Submission Content
Last content review/update: December 21, 2018
Requirements
(1) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter II, Article 17 bis) and Title V (Chapter I, Article 98)
(2) (Regulation) Regulation of the Federal Commission for the Protection Against Sanitary Risks (Reg-COFEPRIS – Spanish) (April 13, 2004)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Chapter I (Articles 1 and 3) and Chapter IV (Article 14)
(3) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title III (Chapter I, Article 62) and (Chapter II, Articles 65 and 69)
(4) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 5.2, 6.2, 6.3, 9.2, and 10.3
(5) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble and 2
(6) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Modules I – VIII
(7) (Guidance) Guide for the Submission of Human Research Protocols – Observational Studies – HOMOCLAVE COFEPRIS 04-010-D (G-COFEPRIS-ObservStudies – Spanish) (Version 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Modules I-VIII
(8) (Guidance) National Guidelines for integration and Operation of the Research Ethics Committee (REC) (G-RECs-Operation_Abridged) (Date Unavailable)
National Bioethics Commission (CONBIOETICA), Secretariat of Health
Relevant Sections: Requirements for the Evaluation of Protocols
Summary

Overview

As set forth in MXGenHlthLaw, Reg-COFEPRIS, HlthResRegs-MX, NOM-012-SSA3-2012, and MX-GCP-COFEPRIS, Mexico requires an applicant to submit a request for research protocol authorization to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)). Per HlthResRegs-MX, NOM-012-SSA3-2012, and Additional Resources (A) and (B), the applicant must also obtain a favorable decision from the Research Ethics Committee (REC) (Comité de Ética de la Investigación (CEI)) and the Research Committee (RC) (El Comité de Investigación (IC)) at the health institution where the study is being conducted, and, when applicable, a favorable decision from the Biosafety Committee (El Comité de Bioseguridad (BC)).

COFEPRIS Requirements

As specified in G-COFEPRIS-ApplicReqs, the following documentation must be submitted to COFEPRIS as part of the approval process:

  • Authorizations, Certificates and Visits form
  • Original and two (2) copies of the proof of payment of rights
  • Research protocol
  • Acceptance letter from research institution head and responsible principal investigator (PI)
  • Sponsor letter of acceptance
  • Letter describing human and material resources to be allocated for research at institution(s)
  • Follow-up letter from sponsor providing monitoring/auditing plan
  • Model letter of informed consent (IC) in Spanish
  • IC document
  • Study schedule
  • Letter describing approximate total quantity of investigational products (IPs) requiring importation at each stage of the study; letter serves as acknowledgement of information, not authorization
  • Copy of study’s current financial or insurance budget
  • Copy of current REC and RC registration and BC registration, where applicable
  • Favorable opinion of REC, RC, and, where appropriate, BC
  • REC member list
  • REC member letters recusing themselves if on research team
  • REC letter describing study follow-up process
  • Letter of No Conflict of Interest and Confidentiality signed by REC members
  • Copy of sanitary license or notice of operation
  • Letter of authorization to carry out the research, signed by health institution owner
  • Where applicable, copy of agreement between research centers that have agreements for emergency medical care with other institutions
  • Letter describing resources available for emergency management
  • Adverse event report confidentiality letter from the PI
  • Summary of PI’s professional record/official professional documentation issued and registered by competent educational authorities
  • Summary of academic preparation and experience of medical personnel, paramedics and other experts involved in study
  • Letter describing research team delegation of responsibilities
  • Investigator’s manual
  • Letter describing the sponsoring institution’s resources for the study’s development
  • Copy of document indicating drugs used in study comply with the Good Practices of Manufacturing (GMP) and have the expected quality characteristics for IPs to be used in study, or, letter documenting GMPs
  • Status of stability studies, or letter documenting IP stability studies comply with applicable regulations

Refer to HlthResRegs-MX, G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, and Additional Resources (A), (B), and (C) for more detailed submission information.

Institutional REC Requirements

As indicated in G-RECs-Operation_Abridged and MX-GCP-COFEPRIS, the National Bioethics Commission (La Comisión Nacional de Bioética (CONBIOÉTICA)) requires the PIs to submit the following documentation for REC approval:

  • Research protocol
  • Protocol summary
  • Summary of previous studies
  • Summary of therapeutic product research
  • Documentation stating research participant, researcher, institution, and, if applicable, sponsor commitments
  • Report describing maintenance measures and life support for research participants and insurance policy agreements
  • Report on procedures and people responsible for keeping participants informed of study developments
  • Investigator resume
  • Statement specifying external funding source information, if applicable
  • Statement providing study costs and expenses, if no external funding source
  • Sponsor data report
  • Report on supporting material to be used for participant recruitment
  • System/mechanism to protect participant privacy and maintain confidentiality during study
  • Methodology to obtain informed consent
  • System and procedure to communicate results to participants
  • For previously rejected protocols, information on modifications made to address earlier issues
  • Informed consent letter
  • Investigator’s manual
  • Amendments to previously approved documentation
  • Required documentation for participants

See G-RECs-Operation_Abridged and MX-GCP-COFEPRIS for additional EC requirements.

Clinical Protocol

As set forth in G-RECs-Operation_Abridged and NOM-012-SSA3-2012, the research protocol should include the following elements:

  • Title
  • Theoretical framework
  • Definition of problem
  • Background
  • Rationale
  • Hypothesis (if applicable)
  • General objective (if applicable, specific objectives)
  • Materials and methods
  • Design (e.g., inclusion/exclusion criteria; information input, processing, analysis and interpretation)
  • Bibliographic references
  • 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

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.

Additional Resources
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Necessary Documents
(C) (Instructions Document) Instructions for Filling Out the Authorizations, Certificates and Visits Form (Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Homoclave, Name and Modality and Fast Filling Guide (Homoclaves COFEPRIS-04-010-A, COFEPRIS-04-010-B, and COFEPRIS-04-010-D)
(D) (Form) Authorizations, Certificates and Visits (FF-COFEPRIS-01) (Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Clinical Trial Lifecycle > Timeline of Review
Last content review/update: December 21, 2018
Requirements
(1) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title III (Chapter I, Articles 62 and 74a) and (Chapter II, Articles 65 and 69)
(2) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 5.2, 6.3, 9.2, and 10.3
(3) (Regulation) Regulation of the Federal Commission for the Protection Against Sanitary Risks (Reg-COFEPRIS – Spanish) (April 13, 2004)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Chapter I (Articles 1 and 3) and Chapter IV (Article 14)
(4) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion for Pre-UHAP, Submission to COFEPRIS, and Internal Evaluation of Your Application
(5) (Guidance) Guide for the Submission of Human Research Protocols – Observational Studies – HOMOCLAVE COFEPRIS 04-010-D (G-COFEPRIS-ObservStudies – Spanish) (Version 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion for Pre-UHAP, Submission to COFEPRIS, and Internal Evaluation of Your Application
(6) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Requirements for Applicant Information Changes – HOMOCLAVE COFEPRIS-09-012 (Modification) (G-COFEPRIS-ApplicMod – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion for Pre-UHAP, Submission to COFEPRIS, and Internal Evaluation of Your Application
(7) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Requirements for Amending Clinical and/or Preclinical Safety Information – HOMOCLAVE COFEPRIS-09-012 (Security Amendment) (G-COFEPRIS-AppSecurityAmdt – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Submission to COFEPRIS and Internal Evaluation of Your Application
(8) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Clinical Documentation – HOMOCLAVE COFEPRIS 09-012 (Documents) (G-COFEPRIS-ApplicDocsMod – Spanish) (Version No.1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion – Pre-UHAP – CCINSHAE and Internal Evaluation of Your Application
(9) (Guidance) Guide for the Submission of Human Research Protocol Amendments –Requirements for Health Institution or Establishment Changes – HOMOCLAVE COFEPRIS-09-012 (Others) (G-COFEPRIS-Applic-InstChges – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion – Pre-UHAP – CCINSHAE and Internal Evaluation of Your Application
(10) (Guidance) Guide for the Submission of Human Research Protocol Amendments – Requirements for Including a New Center – HOMOCLAVE COFEPRIS-09-012 (G-COFEPRIS-AppNewCtr – Spanish) (Version No. 1) (August 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Opinion – Pre-UHAP – CCINSHAE and Internal Evaluation of Your Application
(11) (Guidance) User’s Manual – National Registry of Clinical Trials (RNEC) – COFEPRIS Mexico (G-RNECManual – Spanish) (Version 1.0) (March 2013)
Sanitary Authorization Commission, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 5
(12) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: 3.3, 6.2, 8.1, and 8.2
(13) (Guidance) National Guidelines for integration and Operation of the Research Ethics Committee (REC) (G-RECs-Operation_Abridged) (Date Unavailable)
National Bioethics Commission (CONBIOETICA), Secretariat of Health
Relevant Sections: Communication of the Decision and Monitoring of the Protocol
Summary

Overview

As delineated in HlthResRegs-MX, NOM-012-SSA3-2012, and Additional Resources (A) and (B), 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 de la Investigación (CEI)) and the Research Committee (RC) (El Comité de Investigación (IC)), and where applicable, the Biosafety Committee (El Comité de Bioseguridad (BC)). Therefore, COFEPRIS and ethics committee (REC, RC, and BC) reviews may not be conducted in parallel. However, per HlthResRegs-MX, the REC, the RC, and the BC may meet together to decide whether to authorize a protocol to conduct research on humans, as appropriate.

COFEPRIS Approval

Pursuant to HlthResRegs-MX, COFEPRIS must approve a request for research protocol authorization within 30 working days from the day following an application’s filing.

As delineated in Reg-COFEPRIS, NOM-012-SSA3-2012, and Additional Resource (E), COFEPRIS’s Sanitary Authorization Commission (la Comisión de Autorización Sanitaria (CAS)) is responsible for recording, evaluating, and issuing opinions on requests for authorization of research protocols in human beings. According to G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, G-COFEPRIS-ApplicMod, G-COFEPRIS-AppSecurityAmdt, CAS’s work is performed by its Technical Area for the Evaluation of Human Research Protocols, also known as the Clinical Trials (Ensayos Clínicos (EC)) technical area. Per Additional Resources (F) and (G), CAS’s EC conducts its work via COFEPRIS’s Integral Services Center (Centro Integral de Servicios (CIS)), a public service system established by the Mexican government to facilitate the processing of agency procedures and services.

As indicated in G-COFEPRIS-ApplicReqs, G-COFEPRIS-ApplicMod, and Additional Resources (A), (C), (D), (F), (G), and (H), the applicant must submit an application to the CIS to request protocol authorization or modification. Protocol modifications may be submitted to amend research procedures, to remove or add research center(s)/research institution(s), or, to provide updated clinical and/or preclinical security/safety information.

Mexico also offers a pre-assessment evaluation that helps to facilitate COFEPRIS’s review. Per Additional Resources (I), (J), and (K), rather than submitting the application directly to the CIS, the applicant may first choose to obtain a pre-assessment evaluation of his/her application through an Enabled Pre-Assessment Support Unit (Unidad Habilitada de Apoyo al Predictamen (UHAP)) 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 Additional Resource (L), COFEPRIS also signed an agreement with the Faculty of Medicine of the Autonomous University of Nuevo León (Facultad de Medicina de Universidad Autónoma de Nuevo León (UANL)) to enable UHAPs within the UANL to collaborate with the agency to conduct pre-assessment application evaluations. Refer to Additional Resources (M), (N), (O), and (P) for detailed information on the CCINSHAE, the IMSS, and the UANL UHAP application submission requirements and evaluation process.

Per Additional Resource (I), the CCINSHAE coordinates nine (9) UHAPs. However, Additional Resources (Q) and (R) state that the CCINSHAE oversees (12) UHAPs. Additional Resource (B) further indicates that the fee for requesting a UHAP-CCINSHAE pre-assessment is 60,000 Mexican Pesos. The cost is the same for all 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. As stated in Additional Resource (I), the advantage of this additional evaluation is that once a UHAP issues a favorable letter of pre-authorization, the applicant may include this response with his/her submission to COFEPRIS through the CIS to be reviewed by the Ensayos Clínicos.

Further, per G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, G-COFEPRIS-ApplicMod, G-COFEPRIS-ApplicDocsMod, G-COFEPRIS-Applic-InstChges, G-COFEPRIS-AppNewCtr, and G-COFEPRIS-AppSecurityAmdt, receipt of a favorable pre-evaluation assessment also requires the EC to issue a response within a maximum of 30 business days as long as the applicant notifies the EC that his/her application was submitted with the pre-evaluation assessment. A UHAP pre-assessment may result in a favorable or unfavorable review. If the review is unfavorable, the applicant is required to respond within 30 calendar days to all the issues raised, or, the submission will be designated “rejected,” and the review will be concluded and returned to the applicant.

According to G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, G-COFEPRIS-ApplicMod, G-COFEPRIS-ApplicDocsMod, G-COFEPRIS-Applic-InstChges, G-COFEPRIS-AppNewCtr, G-COFEPRIS-AppSecurityAmdt, and Additional Resource (H), if the applicant chooses to send the application requesting protocol authorization directly to COFEPRIS, then CIS will assign a reference number to the application and send it to the EC in CAS for technical evaluation. If the EC responds favorably to the initial request, the authorization is approved, and the clinical study may begin. However, if the request is rejected, an objection is issued and the applicant must resubmit a request for continued processing after addressing all of the issues raised. In either case, the applicant must use the CIS reference number to track the official resolution of either an authorization or an objection of the request.

Per HlthResRegs-MX and G-RNECManual, once the applicant obtains an official authorization from COFEPRIS, he/she 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 (Additional Resource (S)). Established in 2013, RNEC includes all applications for authorization of research protocols in human subjects submitted to the CIS since 2013. The RNEC is in charge of the SAC’s Ensayos Clínicos 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.

REC Approval

As delineated in G-RECs-Operation_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-Operation_Abridged also states that the REC’s decision must communicated in writing to the applicant according to committee’s established procedures, within a period not to exceed 30 days from the date of receiving his/her completed application.

Per G-RECs-Operation_Abridged, the researcher may submit a one-time objection to the REC’s decision within seven (7) working days after receiving notification. The REC will, in turn, address the researcher’s objection at the next regular committee session and present its response within seven (7) working days. The REC’s decision is not permitted to be appealed at this point.

G-RECs-Operation_2018 and G-RECs-Operation_Abridged also state that the approval of a new application is valid for one (1) year.

In addition, G-RECs-Operation_2018 and G-RECs-Operation_Abridged indicate 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.

Additional Resources
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Options to Carry Out Your Procedure
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
(E) (Website) COFEPRIS – Sanitary Authorizations (Spanish) (December 13, 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(F) (Website) COFEPRIS – Integral Services Center (Spanish) (December 12, 2016)
Integral Services Center, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Integral Services Center, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Coordinating Commission of National Institutes of Health and High Specialty Hospitals (CCINSHAE), Secretariat of Health
Coordinating Commission of National Institutes of Health and High Specialty Hospitals (CCINSHAE), Secretariat of Health
Coordinating Commission of National Institutes of Health and High Specialty Hospitals (CCINSHAE), Secretariat of Health
(L) (Article) Agreement with the IMSS on Clinical Research (Spanish) (April 28, 2017)
Jaime, Dr. Rosa Guadalupe Legaspi, COFEPRIS Magazine – Protection and Health
(M) (Document) Generalizations for Presenting UHAP-CCINSHAE Documentation (Spanish) (Date Unavailable)
Enabled Pre-Assessment Support Unit (UHAP), Coordinating Commission of National Institutes of Health and High Specialty Hospitals (CCINSHAE), Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(N) (Document) Enabled Pre-Assessment Support Unit (UHAP) (Spanish) (Current as of December 20, 2018)
Mexican Social Security Institute (IMSS)
(O) (Website) Submitting a "Pre-Assessment Request" to a UANL UHAP (Spanish) (Current as of December 20, 2018)
Faculty of Medicine and University Hospital, Autonomous University of Nuevo León (UANL)
(P) (Flowchart) UNAL General Procedure of Authorization (Spanish) (Date Unavailable)
Faculty of Medicine of the Autonomous University of Nuevo León
(Q) (Document) List of Enabled Pre-Assessment Support Units – UHAP (Spanish) (Date Unavailable)
Sanitary Authorization Commission, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(R) (Article) Scientific Investigation in Mexico (Spanish) (February 2, 2017)
Bernal, Dr. Ana Luisa Sesman, COFEPRIS Magazine – Protection and Health
(S) (Website) COFEPRIS – National Registry of Clinical Trials (RNEC) - Registered Users Login (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Clinical Trial Lifecycle > Trial Initiation
Last content review/update: December 21, 2018
Requirements
(1) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title XII (Chapter I, Articles 194 and 194 bis) and (Chapter XIII, Articles 238-285), Title XVI (Chapter I, Articles 368 and 375)
(2) (Regulation) Regulation of the Federal Commission for the Protection Against Sanitary Risks (Reg-COFEPRIS – Spanish) (April 13, 2004)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Chapter I (Articles 1 and 3) and Chapter IV (Article 14)
(3) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: 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 99-101), and Title VI (Chapter I, Articles 113 and 117)
(4) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 5.2, 6.3, 9.1, 9.2, 10.3, and 10.4
(5) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble, 2, 4, 4.9-4.11, and 4.13
(6) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Modules III and VII
(7) (Guidance) Guide for the Submission of Human Research Protocols – Observational Studies – HOMOCLAVE COFEPRIS 04-010-D (G-COFEPRIS-ObservStudies – Spanish) (Version 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Modules III and VII
(8) (Standard) Mexican Official Standard NOM-220-SSA1-2016, Pharmacovigilance Installation and Operation (NOM-220-SSA1-2016 – Spanish) (Effective Date: January 15, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 7.4
(9) (Guidance) User’s Manual – National Registry of Clinical Trials (RNEC) – COFEPRIS Mexico (G-RNECManual – Spanish) (Version 1.0) (March 2013)
Sanitary Authorization Commission, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: I and V
Summary

Overview

In accordance with MXGenHlthLaw, Reg-COFEPRIS, HlthResRegs-MX, NOM-012-SSA3-2012, and MX-GCP-COFEPRIS, 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-MX, NOM-012-SSA3-2012, and Additional Resources (A) and (B), the applicant must also obtain a favorable decision from the Research Ethics Committee (REC) (Comité de Ética de la Investigación (CEI)) and the Research Committee (RC) (El Comité de Investigación (IC)) at the health institution where the study is being conducted, and, when applicable, a favorable decision from the Biosafety Committee (El Comité de Bioseguridad (BC)). No waiting period is required following the applicant’s receipt of these approvals.

As per MXGenHlthLaw, 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. (See the Investigational Products topic, Manufacturing & Import subtopic for additional information).

As stated in the HlthResRegs-MX, G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, and NOM-012-SSA3-2012, all investigators must possess appropriate qualifications, training, and experience.

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, if applicable, the sponsor must sign a letter of acceptance in which he/she agrees to assume the project obligations and rights stated in the letter. In the case of corporate entities, this position must be accepted by an individual empowered to do so or by a corporation’s legal representative, according to its organizational structure or incorporation regime.

MX-GCP-COFEPRIS further states that the letter should describe each institution and/or company to which the sponsor has assigned some activity in conducting research. The sponsor’s signature of this letter confirms that he/she assumes responsibility for the obligations and rights associated with the research project.

Additionally, MX-GCP-COFEPRIS indicates that the sponsor or his/her contract research organization (CRO) must establish a statement of funding, sponsorship, affiliations, contracts or agreements with other institutions involved, handling of any conflict of interest, incentives, and quantity and payments for research participants.

EC Confirmation of Review and Approval

Pursuant to MX-GCP-COFEPRIS, which requires the sponsor or his/her CRO to comply with the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs), the sponsor or his/her CRO should obtain written confirmation of an ethics committee’s favorable decision from the investigator or institution prior to the trial’s commencement. In addition, per MX-GCP-COFEPRIS, the sponsor or his/her CRO must ensure that the research center has a REC that will evaluate, approve, and follow up with the study. The PANDRH-GCPs also requires the sponsor or his/her CRO to obtain documented ethics committee approval. (See Ethics Committee topic, Scope of Review subtopic and Clinical Trial Lifecycle topic, Submission Content subtopic for additional details on the EC review process).

Mexican Clinical Trials Register

Per HlthResRegs-MX and G-RNECManual, once the applicant obtains an official authorization from COFEPRIS, he/she 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 (Additional Resource (E)).

Established in 2013, RNEC includes all applications for authorization of research protocols in human subjects submitted to COFEPRIS’s Integral Services Center (Centro Integral de Servicios (CIS)) since 2013. RNEC is in charge of the Technical Area for the Evaluation of Human Research Protocols, also known as the Clinical Trials (Ensayos Clínicos (EC)) technical area, within COFEPRIS’s Sanitary Authorization Commission (la Comisión de Autorización Sanitaria (CAS)), 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.

See G-RNECManual for detailed RNEC registration instructions.

Data Safety Monitoring Board

As delineated in the MX-GCP-COFEPRIS and the ICH-GCPs, the sponsor or his/her CRO may consider establishing an independent data monitoring committee (IDMC) 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 PANDRH-GCPs also indicates that the sponsor or his/her CRO may consider establishing an IDMC to monitor the trial’s progress.

G-COFEPRIS-ApplicReqs and G-COFEPRIS-ObservStudies further require the sponsor or his/her CRO to provide a follow-up letter to COFEPRIS describing the monitoring and auditing plan to be used during the investigation. The letter should include at least the following information:

  • Type of plan: audit or monitoring
  • Frequency of application
  • Responsibility for follow-up, and where appropriate, to quote the third party to carry out the activity
  • Objective and scope of follow-up
  • Evaluation tool
  • Methodology to carry out the scientific, technical, and ethical follow-up
  • Communication strategies between researcher, sponsor, and committees
  • Profile of the monitor or auditor
  • Classification of findings
  • Decision-making derived from findings according to their severity
  • Mechanism of notification to the principal investigator, committees, and COFEPRIS
  • Design of Corrective, Improvement or Preventive Action Plan
  • Format of results report through Annual Partial Technical Report
Additional Resources
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Necessary Documents
(C) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 5.11 and 5.5
IV Pan American Conference on Drug Regulatory Harmonization, Pan American Health Organization, Dominican Republic
Relevant Sections: 6.11 and 6.5
(E) (Website) COFEPRIS – National Registry of Clinical Trials (RNEC) - Registered Users Login (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(F) (Website) COFEPRIS – Integral Services Center (Spanish) (December 12, 2016)
Integral Services Center, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(G) (Website) COFEPRIS – Sanitary Authorizations (Spanish) (December 13, 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Clinical Trial Lifecycle > Safety Reporting
Last content review/update: January 04, 2019
Requirements
(1) (Standard) Mexican Official Standard NOM-220-SSA1-2016, Pharmacovigilance Installation and Operation (NOM-220-SSA1-2016 – Spanish) (Effective Date: January 15, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 4.21, 4.44-4.45, 4.53, 4.55-4.56, 4.72, 7.4, 7.5, 7.7, and 8.1-8.3
(2) (Guidance) Pharmacovigilance Guide for Safety Notifications Related to the Use of Medicines (G-PharmAENotif – Spanish) (January 25, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 1-3, 5.2, and 7
(3) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 4 .5, 8.7-8.10, and 10.9
(4) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title III (Chapters I (Article 64))
(5) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble, 3.6, 4.1, and 4.9
Summary

Overview

In accordance with NOM-220-SSA1-2016, G-PharmAENotif, and NOM-012-SSA3-2012, the following definitions provide a basis for a common understanding of Mexico’s safety reporting requirements:

  • 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 to Medication (SRAM) – Any clinical or laboratory manifestation that occurs after administration of one (1) or more drugs

Reporting Requirements for AEs/ADRs

As specified in NOM-220-SSA1-2016, 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 (severe cases from abroad should only be included in the final study safety report, if 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
  • Reports must be submitted when a drug shows a lack of effectiveness (therapeutic failure or therapeutic ineffectiveness) within a maximum of 15 calendar days of first knowledge of the AE/ADR, with as much clinical data as possible
  • 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-MX and NOM-012-SSA3-2012 state that the institution must notify and provide a report to the Secretariat of Health 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 Secretariat of Health. Per NOM-012-SSA3-2012, the principal investigator (PI), the Research Ethics Committee (REC), the institutional head(s) or the Secretariat 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. The investigator is responsible for submitting safety reports to the CNFV.

NOM-220-SSA1-2016 indicates that a pharmacovigilance study protocol should also be prepared and submitted to the Executive Director of Pharmacopeia and Pharmacovigilance through COFEPRIS’s Integral Services Center (Centro Integral de Servicios (CIS)). Once COFEPRIS has authorized the protocol, a digital copy must be submitted in PDF format to the CNFV by the same individual responsible for registering the study with the National Registry of Clinical Trials (Registro Nacional de Ensayos Clínicos (RNEC)) database (Additional Resource (C)). Refer to NOM-220-SSA1-2016 for detailed pharmacovigilance study protocol requirements and Additional Resource (F) for further information on National Pharmacovigilance Center guidelines and requirements.

Per NOM-220-SSA1-2016, notifiers are also required to submit a periodic safety report and a clinical safety report to the CNFV. NOM-220-SSA1-2016 indicates that a periodic safety report should be developed for all authorized medicines and vaccines, and a clinical safety report is required for all trials, sponsored or not, that have at least one (1) site or research center in Mexico.

Investigator Responsibilities

As specified in HlthResRegs-MX, NOM-012-SSA3-2012, and MX-GCP-COFEPRIS, the PI must report to the Research Ethics Committee (REC) (Comité de Ética de la Investigación (CEI)) all probable AEs or any AEs directly related to the research study.

Form Completion & Delivery Requirements

As per NOM-220-SSA1-2016 and G-PharmAENotif, notifiers must electronically submit all AEs/ADRs, SRAMs, and any other safety issues related to the use of medicines to the CNFV using NotiReporta. Per Additional Resource (A), NotiReporta is currently the only official means for notifiers, excluding patients and consumers, to send AE/ADR, SRAM, and any other safety notifications. Moreover, per Additional Resource (A), in cases where notifications were not initially reported in NotiReporta, notifiers are required to re-enter the full report one (1) time in order to include additional information. See NOM-220-SSA1-2016 and G-PharmAENotif for detailed reporting requirements and Additional Resources (G) and (H) for the SRAM reporting form and corresponding instructions.

Data Safety Monitoring Board

As delineated in the MX-GCP-COFEPRIS and the ICH-GCPs, the sponsor or his/her contract research organization (CRO) may consider establishing an independent data monitoring committee (IDMC) 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 PANDRH-GCPs also indicates that the sponsor or his/her CRO may consider establishing an IDMC to monitor the trial’s progress.

Additional Resources
(B) (Website) COFEPRIS – Integral Services Center (Spanish) (December 12, 2016)
Integral Services Center, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(C) (Website) COFEPRIS – National Registry of Clinical Trials (RNEC) - Registered Users Login (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(D) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 5.5 and 5.11
IV Pan American Conference on Drug Regulatory Harmonization, Pan American Health Organization, Dominican Republic
Relevant Sections: 6.5 and 6.11
(F) (Website) Pharmacovigilance Guidelines and Requirements (Spanish) (December 10, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(G) (Form) Notice of Suspected Adverse Drug Reactions (Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS)
(H) (Website) Report of Suspected Adverse Drug Reactions (Spanish) (Current as of December 27, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Clinical Trial Lifecycle > Progress Reporting
Last content review/update: January 04, 2019
Requirements
(1) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title VI (Chapter I (Articles 116 and 119-120)
(2) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 4.9- 4.10, 7.1, 7.4, and 10.10
(3) (Standard) Technical Rule Number 313, for the Presentation of Research Projects and Technical Reports in Health Care Institutions (TechStd-313 – Spanish) (Effective Date: July 26, 1988)
Secretariat of Health
Relevant Sections: Chapter I (Article 5), Chapter II (Article 9), and Chapter III (Articles 21-22 and 26-27)
Summary

Overview

As delineated in HlthResRegs-MX, NOM-012-SSA3-2012, and TechStd-313, the principal investigator (PI) is responsible for submitting progress and final reports on the status of a clinical trial to the Secretariat of Health (la Secretaría de Salud (SSA)). Per TechStd-313, the PI may classify the progress and final reports as restricted dissemination for statistical purposes, or open for general dissemination purposes. In addition, the PI should deliver a copy of the progress and final reports, as well as the research products (e.g., publications, reports), to the head of the research area of his/her institution, and where appropriate, to the institution where he/she has conducted the project.

Progress Reports

Per HlthResRegs-MX and NOM-012-SSA3-2012, the PI must prepare and submit a progress report (also referred to as a partial technical or technical-descriptive report) to the Secretariat of Health at any time, but at least once a year, to communicate progress and partial research study results. 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 de la Investigación (CEI)) and the Research Committee (RC) (El Comité de Investigación (IC)), and, if applicable, the Biosafety Committee (El Comité de Bioseguridad (BC)) of the institution where the research takes place. See Additional Resource (A) for the progress report form.

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

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

Annual Reports

In accordance with TechStd-313, in the event that the research project lasts more than one (1) year, the PI should present an annual report to the head of the research area in the institution where the project is being conducted. The report should present the progress and partial results of the study and describe the activities that have been carried out during the preceding year. The PI should include possible methodological and administrative variations that have occurred on the project and plans for the activities to be implemented in the following year, in order to request a budget, or, to justify the continuation of the currently authorized budget.

Final Study Reports

As set forth in HlthResRegs-MX and NOM-012-SSA3-2012, the PI is also required to submit a final report to the Secretariat 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 TechStd-313, the PI must present the final report before the head of the research area of his/her institution, and where appropriate, the institution where the study was conducted.

The specified elements for progress reports discussed in NOM-012-SSA3-2012 and TechStd-313 are also required for final reports. The results should include, at a minimum, the following elements:

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

See 7.4 of NOM-012-SSA3-2012 and Article 22 of TechStd-313 for required detailed report information.

HlthResRegs-MX further states that the PI is also required to submit a final report to the RC at the institution where the study was conducted. See Additional Resource (B) for the final report form.

Additional Resources
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS)
Sponsorship > Definition of Sponsor
Last content review/update: December 21, 2018
Requirements
(1) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 4.18 and 6.3
(2) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 1.5-1.6, 4.15, and 4.2
Summary

Overview

As set forth in NOM-012-SSA3-2012 and MX-GCP-COFEPRIS, a sponsor is defined as an individual or corporation willing to undertake responsibilities in order to participate and finance, in full or in part, a research project or protocol. The sponsor’s responsibilities must be specified in a written agreement.

NOM-012-SSA3-2012 further states that, if applicable, the sponsor should sign a letter of acceptance in which he/she agrees to the associated obligations and rights of the project or protocol as delineated in the agreement. In the case of corporate entities, the position must be accepted by an individual empowered to do so, or by a corporation’s legal representative, according to its organizational structure or incorporation regime.

Per MX-GCP-COFEPRIS, a sponsor may also hire a contract research organization (CRO) to conduct one (1) or more of the activities related to health research that are sponsored in the country. However, ultimate responsibility for all CRO activities remains with the sponsor.

Additionally, MX-GCP-COFEPRIS indicates that when a sponsor delegates responsibilities to the CRO, he/she must establish in writing each of the activities that are assigned. CROs of foreign origin must also have a registered address in Mexico, and an authorization to carry out clinical research activities in the country.

Additional Resources
No additional resources
Sponsorship > Trial Authorization
Last content review/update: December 21, 2018
Requirements
(1) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter II, Article 17 bis)
(2) (Regulation) Regulation of the Federal Commission for the Protection Against Sanitary Risks (Reg-COFEPRIS – Spanish) (April 13, 2004)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Chapter I (Articles 1 and 3) and Chapter IV (Article 14)
(3) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title III (Chapter I, Article 62) and (Chapter II, Articles 65 and 69)
(4) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 5.2
(5) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble
(6) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module I-VIII, and Internal Evaluation of Your Application
(7) (Guidance) Guide for the Submission of Human Research Protocols – Observational Studies – HOMOCLAVE COFEPRIS 04-010-D (G-COFEPRIS-ObservStudies – Spanish) (Version 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Internal Evaluation of Your Application
(8) (Standard) Mexican Official Standard NOM-220-SSA1-2016, Pharmacovigilance Installation and Operation (NOM-220-SSA1-2016 – Spanish) (Effective Date: January 15, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 7.4
Summary

Overview

In accordance with MXGenHlthLaw, Reg-COFEPRIS, HlthResRegs-MX, NOM-012-SSA3-2012, and MX-GCP-COFEPRIS, the applicant is responsible for submitting a request for research protocol authorization to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) to obtain approval to conduct a study.

As delineated in Reg-COFEPRIS, NOM-012-SSA3-2012, G-COFEPRIS-ApplicReqs, G-COFEPRIS-ObservStudies, and Additional Resources (A), (B), and (C), to complete the clinical trial application package, the applicant must submit a request for research protocol authorization to COFEPRIS’s Sanitary Authorization Commission (la Comisión de Autorización Sanitaria (CAS)). CAS’s work is performed by its Technical Area for the Evaluation of Human Research Protocols, also known as the Clinical Trials (Ensayos Clínicos (EC)) technical area via the Integral Services Center (Centro Integral de Servicios (CIS)).

As indicated in G-COFEPRIS-ApplicReqs and Additional Resource (D), to request research protocol authorization, applicants must submit one (1) hard copy of the application and one (1) electronic copy on CD-ROM or USB. Additional Resource (D) further states that electronic format (Rich Text Format (RTF)) is preferable. Refer to the Clinical Trial Lifecycle topic, Submission Process subtopic for detailed protocol authorization application formatting requirements.

In addition to the completed application, per HlthResRegs-MX, G-COFEPRIS-ApplicReqs, and Additional Resources (D), (E), and (F), the sponsor, his/her CRO, or the principal investigator (PI) must also submit the Authorizations, Certificates and Visits form (Additional Resource (G)), the favorable opinions of the Research Ethics Committee (REC) (Comité de Ética de la Investigación (CEI)) and Research Committee (RC) (El Comité de Investigación (IC)), and if applicable, the Biosafety Committee (El Comité de Bioseguridad (BC)), copies of the REC and RC registrations, the research protocol, the informed consent form, the acceptance letter from the research institution head and responsible PI, the investigator’s manual, and other documentation covered in the Clinical Trial Lifecycle topic, Submission Content subtopic.

G-COFEPRIS-ObservStudies further requires the sponsor or his/her CRO to provide a follow-up letter to COFEPRIS describing the monitoring and auditing plan to be used during the investigation. The letter should include at least the following information:

  • Type of plan: audit or monitoring
  • Frequency of application
  • Responsibility for follow-up, and where appropriate, to quote the third party to carry out the activity
  • Objective and scope of follow-up
  • Evaluation tool
  • Methodology to carry out the scientific, technical, and ethical follow-up
  • Communication strategies between researcher, sponsor, and committees
  • Profile of the monitor or auditor
  • Classification of findings
  • Decision-making derived from findings according to their severity
  • Mechanism of notification to the PI, committees, and COFEPRIS
  • Design of Corrective, Improvement or Preventive Action Plan
  • Format of results report through Annual Partial Technical Report

As set forth in NOM-220-SSA1-2016, the health record holder, 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).

Additional Resources
(A) (Website) COFEPRIS – Sanitary Authorizations (Spanish) (December 13, 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(B) (Website) COFEPRIS – Integral Services Center (Spanish) (December 12, 2016)
Integral Services Center, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(D) (Instructions Document) Instructions for Filling Out the Authorizations, Certificates and Visits Form (Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Homoclave, Name and Modality and Fast Filling Guide (Homoclaves COFEPRIS-04-010-A, COFEPRIS-04-010-B, and COFEPRIS-04-010-D)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Necessary Documents
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health and Federal Registry of Procedures and Services, Federal Commission for Regulatory Improvement (COFEMER), Ministry of Economy
(G) (Form) Authorizations, Certificates and Visits (FF-COFEPRIS-01) (Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Sponsorship > Insurance
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble, 4.1, and 4.14
(2) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module IV (11)
Summary

Overview

As set forth in MX-GCP-COFEPRIS, the sponsor or his/her 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 MX-GCP-COFEPRIS, which requires the sponsor or his/her CRO to comply with the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs), the sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator/the institution against claims arising from the trial, except for those claims arising from malpractice and/or negligence. The PANDRH-GCPs (Additional Resource (A)), a voluntary guidance that Mexico helped to draft, similarly states that the sponsor should provide insurance or indemnification against claims arising from the trial, if required by applicable requirements.

G-COFEPRIS-ApplicReqs further states that a copy of the current Global Insurance Policy certificate delineating the financial or insurance funding for the study should be included with the protocol submitted in the application package.

Additional Resources
IV Pan American Conference on Drug Regulatory Harmonization, Pan American Health Organization, Dominican Republic
Relevant Sections: Sections 6.8 and Annex 5 (1)
(B) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 5.8 and 8.2
Sponsorship > Compensation
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble, 4.1, 4.8, and 4.13
(2) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 5.14 and 10.6
(3) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter I, Article 14) (Chapter II, Article 21), and (Chapter V, Article 58)
(4) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title V (Chapter I, Article 100)
Summary

Overview

As specified in MX-GCP-COFEPRIS, the sponsor or his/her designated contract research organization (CRO) must establish a statement of funding and describe the quantity and payments to be allocated for research participants. 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.

HlthResRegs-MX further states that the health care institution and the sponsor or his/her CRO should take responsibility for the medical treatment of injuries, and, where appropriate, legally required compensation for the harmful consequences of a study involving subordinate groups. In addition, per HlthResRegs-MX and MXGenHlthLaw, it is also the associated health institution’s responsibility to provide medical attention to injured participants, 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 accordance with MX-GCP-COFEPRIS, which requires the sponsor or his/her CRO to comply with the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs), the informed consent form (ICF) should include an explanation of the compensation and/or treatment available to the participant in the event of trial-related injury. The PANDRH-GCPs (Additional Resource (A)), a voluntary guidance that Mexico helped to draft, similarly indicates that the ICF should contain compensation and/or treatment information available to the participant should any trial-related injuries occur.

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

Additional Resources
IV Pan American Conference on Drug Regulatory Harmonization, Pan American Health Organization, Dominican Republic
Relevant Sections: 4.4
(B) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.8
Sponsorship > Quality, Data & Records Management
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble, 3.5, 3.7, 4.1, 4.6, 4.8, and 4.13
(2) (Standard) Mexican Official Standard NOM-004-SSA3-2012, of the Clinical Record (NOM-004-SSA3-2012 – Spanish) (Effective Date: October 15, 2012)
Secretariat of Health
Relevant Sections: 5.4
(3) (Guidance) Guide for the Submission of Human Research Protocols – Observational Studies – HOMOCLAVE COFEPRIS 04-010-D (G-COFEPRIS-ObservStudies – Spanish) (Version 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module III
(4) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter I, Article 18) and Title III (Chapter I, Article 64)
(5) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 8.8
(6) (Standard) Mexican Official Standard NOM-220-SSA1-2016, Pharmacovigilance Installation and Operation (NOM-220-SSA1-2016 – Spanish) (Effective Date: January 15, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 7.5
Summary

Overview

According to MX-GCP-COFEPRIS, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires the sponsor or his/her contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs), and to ensure and control the quality of the research during a study. Per MX-GCP-COFEPRIS and the ICH-GCPs, the sponsor or his/her CRO is also responsible for establishing written standard operating procedures (SOPs) for each stage of the investigation. In addition, the sponsor or his/her 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.

As indicated in the ICH-GCPs, the sponsor or his/her CRO is also 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.

Further, the sponsor or his/her CRO must obtain the investigator(s)’s and the institution(s)’s agreement to:

  • Conduct the trial in compliance with the ICH-GCPs 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

The PANDRH-GCPs (Additional Resource (A)) states the same requirements as those set forth in the ICH-GCPs.

Electronic Data Processing System

As per ICH-GCPs and the PANDRH-GCPs, when using electronic trial data processing systems, the sponsor or his/her CRO must ensure that the electronic data processing system conforms to his/her established requirements for completeness, accuracy, reliability, and consistency of intended performance, and that he/she maintains SOPs for using these systems.

Record Management

As delineated in MX-GCP-COFEPRIS, 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, the ICH-GCPs, and Good Documentation Practices.

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 his/her health and the confidentiality of his/her 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.

In addition, as indicated in the ICH-GCPs and the PANDRH-GCPs, all sponsor-specific essential documents used in the trial should be retained for at least two (2) years after formal discontinuation of the trial or the last approval of a marketing application. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.

Audit Requirements

According to MX-GCP-COFEPRIS and the ICH-GCPs, the sponsor or his/her CRO must ensure and control the quality of the research through periodic monitoring visits and audits. The sponsor or his/her 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 PANDRH-GCPs also states that the sponsor may consider establishing an independent data monitoring committee (IDMC).

G-COFEPRIS-ObservStudies further requires the sponsor or his/her CRO to provide a follow-up letter to COFEPRIS describing the monitoring and auditing plan to be used during the investigation. The letter should include at least the following information:

  • Type of plan: audit or monitoring
  • Frequency of application
  • Responsibility for follow-up, and where appropriate, to quote the third party to carry out the activity
  • Objective and scope of follow-up
  • Evaluation tool
  • Methodology to carry out the scientific, technical, and ethical follow-up
  • Communication strategies between researcher, sponsor, and committees
  • Profile of the monitor or auditor
  • Classification of findings
  • Decision-making derived from findings according to their severity
  • Mechanism of notification to the PI, committees, and COFEPRIS
  • Design of Corrective, Improvement or Preventive Action Plan
  • Format of results report through Annual Partial Technical Report

MX-GCP-COFEPRIS requires the sponsor or his/her CRO to ensure and control the quality of the research through periodic monitoring visits and audits. MX-GCP-COFEPRIS 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-MX and NOM-012-SSA3-2012, the PI, the Research Ethics Committee (REC), the institutional head or other authorized institutional officers, or the Secretariat of Health 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.

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.

Multicenter Studies

As delineated in the ICH-GCPs and the PANDRH-GCPs, in the event of a multicenter clinical trial, the sponsor or his/her 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
Additional Resources
IV Pan American Conference on Drug Regulatory Harmonization, Pan American Health Organization, Dominican Republic
Relevant Sections: 5.9.5, 6.1.1, 6.1.2, 6.1.3, 6.2.3, 6.6.4, 6.5.2, and 6.5.3
(B) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.9, 5.1, 5.5, and 5.6
Sponsorship > Site/Investigator Selection
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble, 4.1-4.2, 4.5, 4.7, 4.9-4.11, 4.13, and 4.15
(2) (Guidance) Guide for the Submission of Human Research Protocols – Observational Studies – HOMOCLAVE COFEPRIS 04-010-D (G-COFEPRIS-ObservStudies – Spanish) (Version 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module VII
(3) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title III (Chapter I, Article 62) and Title VI (Chapter I, Articles 113 and 117)
(4) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 10.4
(5) (Standard) Mexican Official Standard NOM-206-SSA1-2002, which Establishes the Criteria of Operation and Attention in the Emergency Services of Health Care Facilities (NOM-206-SSA1-2002 – Spanish) (Effective Date: November 14, 2004)
Secretariat of Health
Relevant Sections: 0 and 1
Summary

Overview

According to MX-GCP-COFEPRIS, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) requires the sponsor or his/her contract research organization (CRO) to comply with the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs) for conducting clinical trials.

As set forth in MX-GCP-COFEPRIS, the sponsor or his/her 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. To this point, G-COFEPRIS-ObservStudies, also indicates that the institutional resources (e.g., areas, equipment, auxiliary laboratory services and cabinets, and number of personnel) for the study should be described in a written letter and included in the request for clinical trial authorization application package.

In addition, per HlthResRegs-MX, G-COFEPRIS-ObservStudies, and NOM-012-SSA3-2012, the sponsor or his/her CRO must confirm that the investigators are qualified by training and experience. MX-GCP-COFEPRIS indicates that the sponsor must establish in writing each of the research team member functions and responsibilities, and the financial agreement with the principal investigator (PI). The sponsor or his/her CRO must also establish a statement of funding, 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. Further, per the ICH-GCPs, 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 ensure that they agree to comply with good clinical practices.

Moreover, per MX-GCP-COFEPRIS, the sponsor and his/her CRO must ensure that research institutions uphold the following additional requirements:

  • Ensure resources and area for urgent care, or where appropriate, a written agreement with the health institution that will attend to the emergency. This agreement must comply with the provisions of NOM-206-SSA1-2002, "Regulation of Health Services.” This standard establishes the criteria for the operation and attention in providing emergency services in health care institutions.
  • Provide a restricted and sheltered storage area for the investigational product (IP) and other supplies required for research, with adequate controls of temperature, humidity, and other conditions as established by the manufacturer

Foreign Sponsor Responsibilities

MX-GCP-COFEPRIS indicates that CROs of foreign origin must have a registered address in Mexico, and an authorization or notice according to the activities to be carried out in the country. As specified in MX-GCP-COFEPRIS, the sponsor may transfer any or all of his/her study related duties and functions to a CRO. However, he/she is ultimately responsible for the execution of the research protocol and results of the clinical trial and must establish the delegated responsibilities in writing.

Data Safety Monitoring Board

According to MX-GCP-COFEPRIS and the ICH-GCPs, the sponsor or his/her CRO may consider establishing an independent data monitoring committee (IDMC) 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 PANDRH-GCPs (Additional Resource (A)), a voluntary guidance that Mexico helped to draft, also indicates that the sponsor may consider establishing an IDMC to monitor the trial’s progress.

Additional Resources
IV Pan American Conference on Drug Regulatory Harmonization, Pan American Health Organization, Dominican Republic
Relevant Sections: 6.5.2
(B) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 5.5.2 and 5.6
Informed Consent > Documentation Requirements
Last content review/update: December 21, 2018
Requirements
(1) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter I, Articles 20-22)
(2) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title V (Chapter I, Article 100)
(3) (Standard) Mexican Official Standard NOM-004-SSA3-2012, of the Clinical Record (NOM-004-SSA3-2012 – Spanish) (Effective Date: October 15, 2012)
Secretariat of Health
Relevant Sections: 0 (Introduction)
(4) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 3.1 and 3.9
(5) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: 1.2, 3.3, 10, and Annexes 5 and 6
(6) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Modules I, IV, and V
(7) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 4.3 and 10.6
Summary

Overview

In all Mexican clinical trials, a freely given informed consent is required from each participant in accordance with the requirements set forth in HlthResRegs-MX, MXGenHlthLaw, NOM-004-SSA3-2012, and MX-GCP-COFEPRIS, which require the principal investigator (PI) to comply with the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs). Per G-RECs-Operation_2018, the PI must also comply with consent requirements as delineated in the Declaration of Helsinki.

As per HlthResRegs-MX, G-RECs-Operation_2018, and G-COFEPRIS-ApplicReqs, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by a Research Ethics Committee (REC) and provided to the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) with the request for research protocol authorization. In addition to the ICF (also referred to as the Letter of Consent), G-COFEPRIS-ApplicReqs further specifies that the consent document must be sent to each participating research center, and should be personalized for each location, indicating the name and address, consistent with the authorization of each center, as well as the corporate name and management of the committees involved, and the version and date. (See the Informed Consent topic, Required Elements subtopic for details on what should be included in the form.)

HlthResRegs-MX, MX-GCP-COFEPRIS, and NOM-012-SSA3-2012 state that the PI must provide detailed research study information to the participant and/or his/her legal representative(s) or guardian(s). As delineated in HlthResRegs-MX, G-RECs-Operation_2018, NOM-012-SSA3-2012, and the ICH-GCPs, the ICF content should be presented with a clear explanation and provided in a format that facilitates understanding. Per NOM-012-SSA3-2012 and the ICH-GCPs, the participant and/or his/her legal representative(s) or guardian(s) should also be given adequate time to consider whether to participate.

Re-Consent

According to G-RECs-Operation_2018 and the ICH-GCPs, 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-Operation_2018 and the ICH-GCPs, the participant and/or his/her legal representative(s) or guardian(s) 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. The ICH-GCPs further state the communication of this information should be documented.

Language Requirements

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

Documentation Copies

As delineated in HlthResRegs-MX, G-RECs-Operation_2018, and the ICH-GCPs, the participant and/or his/her legal representative(s) or guardian(s), as well as two (2) witnesses must sign the ICF. The ICH-GCPs specifies that the ICF should be dated, and any updates must also be signed, and a copy of the amendments provided to the participant and/or his/her legal representative or guardian. If the participant does not know how to sign, he/she will provide a fingerprint, and will need to designate someone to sign his/her name on his/her behalf. A copy of the signed ICF will be provided to the participant and/or his/her legal representative or guardian. G-COFEPRIS-ApplicReqs states that the ICF must contain the document version and date.

Additional Resources
(A) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
(B) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.28, 2.9, and 4.8
Informed Consent > Required Elements
Last content review/update: December 21, 2018
Requirements
(1) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter I, Articles 20-22)
(2) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Modules IV and V
(3) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: 10, Annex 5, and Glossary
(4) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 3.1
(5) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 10.6 and 11.3
Summary

Overview

As delineated in HlthResRegs-MX and G-COFEPRIS-ApplicReqs, prior to beginning a clinical trial, the principal investigator (PI) is required to obtain Research Ethics Committee (REC) approval for the written informed consent form (ICF), and any other information provided to the research participant and/or his/her legal representative(s) or guardian(s). G-RECs-Operation_2018 further specifies that the PI should obtain informed consent from the research participants unless he/she has received explicit written approval from a REC indicating the informed consent is not required for justified reasons.

The Guideline for Good Clinical Practice E6(R1) (ICH-GCPs) state that the PI should present ICF content in easily understandable and non-technical language in both written and oral form. (MX-GCP-COFEPRIS requires the PI to comply with the ICH-GCPs.) HlthResRegs-MX, NOM-012-SSA3-2012, and G-RECs-Operation_2018 specifically note that the ICF content should be presented in written form.

No Coercion

As per HlthResRegs-MX, G-RECs-Operation_2018, and the ICH-GCPs, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant and/or his/her legal representative(s) or guardian(s) to waive or appear to waive his/her legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

ICF Required Elements

Based on G-RECs-Operation_2018, the ICF should include the following statements or descriptions, as applicable:

  • 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
  • Alternative treatments that may be beneficial to the participant)
  • Trial treatment(s) and the probability for random assignment to each treatment
  • 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 his/her confidential information relating to his/her privacy will be maintained
  • Confidentiality of records identifying the participant will be maintained, 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
  • The guarantee of receiving 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 his/her 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 ICH-GCPs also mention 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

See HlthResRegs-MX, NOM-012-SSA3-2012, G-COFEPRIS-ApplicReqs, G-RECs-Operation_2018, and the ICH-GCPs for additional details related to ICF requirements.

Also, see the Informed Consent topic, Compensation Disclosure and Vulnerable Population subtopics and the Specimens topic, Consent for Specimens subtopic for further information.

Additional Resources
(A) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.8
Informed Consent > Compensation Disclosure
Last content review/update: December 21, 2018
Requirements
(1) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter I, Article 21)
(2) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 10.6
(3) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: Annex 5
(4) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module IV
(5) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 3.1
(6) (Guidance) Guide for the Submission of Human Research Protocols – Observational Studies – HOMOCLAVE COFEPRIS 04-010-D (G-COFEPRIS-ObservStudies – Spanish) (Version 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module IV (7)
Summary

Overview

In accordance with HlthResRegs-MX, NOM-012-SSA3-2012, G-RECs-Operation_2018, G-COFEPRIS-ApplicReqs, and the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs), the informed consent form (ICF) should contain a statement describing the compensation or medical treatment a participant can receive for participating in a clinical trial. (MX-GCP-COFEPRIS requires the principal investigator (PI) to comply with the ICH-GCPs.)

Compensation for Participation in Research

As per the ICH-GCPs, the ICF should contain a statement with a description of the anticipated prorated payment to the participant(s) that is reasonably expected for participation in the trial.

Compensation for Injury

As per HlthResRegs-MX, NOM-012-SSA3-2012, G-RECs-Operation_2018, G-COFEPRIS-ApplicReqs, and the ICH-GCPs, the ICF should include a statement advising the participant about whether compensation and medical treatment is available in the event of any trial-related injury. G-COFEPRIS-ObservStudies also requires the ICF to contain a statement regarding the compensation that an institution would be legally entitled to in the event of damages due to study-related procedures, if applicable. NOM-012-SSA3-2012 assigns responsibility specifically to the principal investigator (PI) for preparing the ICF, stating that he/she must ensure an explanation is provided on compensation the participant is entitled to receive in the event his/her health is impaired as a result of the study. The PI should also communicate the continuing availability of free medical treatment in the event that the participant decides to withdraw from the study prior to its conclusion.

As delineated in HlthResRegs-MX, for informed consent to be considered valid, the participant or his/her legal representative must receive a clear and complete explanation on the availability of medical treatment and compensation he/she is legally entitled to by the institution in the case of study-related injuries.

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

Additional Resources
(A) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.8
Informed Consent > Participant Rights
Last content review/update: December 21, 2018
Requirements
(1) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter I, Articles 13 and 21)
(2) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 0, 5.3, and 11.3
(3) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: 1.1, 1.2, 3.2, and Annex 5
(4) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble and 3.1
(5) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module IV
Summary

Overview

In accordance with HlthResRegs-MX, NOM-012-SSA3-2012, G-RECs-Operation_2018, and the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs), Mexico’s ethical standards promote respect for all human beings and safeguard the rights of research participants. (MX-GCP-COFEPRIS requires the principal investigator (PI) to comply with the ICH-GCPs). HlthResRegs-MX and the ICH-GCPs state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process.

The Right to Participate, Abstain, or Withdraw

As stated in HlthResRegs-MX, NOM-012-SSA3-2012, G-RECs-Operation_2018, G-COFEPRIS-ApplicReqs, and the ICH-GCPs, the participant and/or his/her legal representative(s) or guardian(s) should be informed that participation is voluntary, that he/she may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As per HlthResRegs-MX, NOM-012-SSA3-2012, G-RECs-Operation_2018, G-COFEPRIS-ApplicReqs, and the ICH-GCPs, a potential research participant and his/her legal representative(s) or guardian(s) has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation 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-COFEPRIS-ApplicReqs, G-RECs-Operation_2018, and the ICH-GCPs, 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 ICH-GCPs states that the research participant and/or his/her legal representative(s) or guardian(s) should be provided with contact information for the individual responsible for addressing trial-related inquiries and/or his/her rights. G-RECs-Operation_2018 further specifies that names and contact information of the PI and the Research Ethics Committee (REC)’s president, including a 24-hour telephone number in case of emergency, should be provided.

The Right to Safety and Welfare

HlthResRegs-MX, NOM-012-SSA3-2012, G-RECs-Operation_2018, MX-GCP-COFEPRIS, and the ICH-GCPs that upholds the Declaration of Helsinki, clearly state that a research participant’s right to safety and the protection of his/her health and welfare must take precedence over the interests of science and society.

See the Informed Consent topic, and the subtopics of Required Elements and Vulnerable Populations for additional information regarding requirements for participant rights.

Additional Resources
(A) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: Introduction and 4.8
(B) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
Informed Consent > Special Circumstances/Emergencies
Last content review/update: December 21, 2018
Requirements
(1) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title III (Chapter II, Article 71)
(2) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title V (Chapter I, Article 100)
(3) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 3.1
Summary

Overview

HlthResRegs-MX and the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs) make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by special circumstances. Special circumstances can be medical emergencies or when a participant is mentally incapacitated. According to HlthResRegs-MX and MXGenHlthLaw, in order to carry out investigations on an incapacitated person, investigators must always obtain the written informed consent from the participant’s legal representative(s) or guardian(s). (MX-GCP-COFEPRIS requires the principal investigator (PI) to comply with the ICH-GCPs.)

Medical Emergencies

According to HlthResRegs-MX, 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) and the Research Committee (RC), and an informed consent form (ICF) signed by the research participant or his/her legal representative(s) or guardian(s).

The terms under which this documentation is obtained must meet the following requirements:

  • The REC and RC 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 and/or his/her legal representative(s) or guardian(s) unless the participant’s condition prevents him from signing the form, the legal representative(s) or guardian(s) are not available to sign the form, or stopping use of the drug constitutes an almost absolute risk of death to the participant.

The ICH-GCPs similarly states that in an emergency, if the signed ICF cannot be obtained from the participant, the consent of his/her legal representative(s) or guardian(s), if present, should be obtained. If the prior consent of the participant or his/her legal representative(s) or guardian(s) 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 his/her legal representative(s) or guardian(s) should provide consent as soon as possible.

Additional Resources
(A) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.8
Informed Consent > Vulnerable Populations
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: Annex 5
(2) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 3.1
(3) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title II (Chapters II and V)
Summary

Overview

As delineated in G-RECs-Operation_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-Operation_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.

Per the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs), vulnerable populations are similarly characterized 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. (MX-GCP-COFEPRIS requires the principal investigator (PI) to comply with the ICH-GCPs.)

G-RECs-Operation_2018 specifies that Research Ethics Committees (RECs) should ensure that additional security mechanisms are implemented to minimize the specific risks for each group. The ICH-GCPs similarly states that ethics committees must pay special attention to protecting participants who are from vulnerable populations.

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

Persons in Subordinate or Dependent Groups

As indicated in HlthResRegs-MX, 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 withdraw 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-Operation_2018, the following criteria must also be met to conduct a study with a subordinate population:

  • The principal investigator (PI) must clearly define the reasons why he/she plans 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-MX and G-RECs-Operation_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.

Research in Local Communities

HlthResRegs-MX provides specific requirements related to conducting research on participants in local communities. 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 Secretariat of Health’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
Additional Resources
(A) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.61
Informed Consent > Children/Minors
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module IV
(2) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title II (Chapters III)
(3) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: Annex 5
Summary

Overview

As delineated in G-COFEPRIS-ApplicReqs, a minor is defined as older than seven (7) years but less than 18 years of age.

Additionally, per HlthResRegs-MX, in all cases, a written informed consent must be obtained from those exercising parental authority, or the legal representative(s) or 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) may waive compliance with these requirements for justified reasons.

As set forth in G-RECs-Operation_2018, 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-Operation_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
  • In the text of the informed consent, it must be ensured that the information provided is appropriate for the understanding of minors

HlthResRegs-MX also indicates that when research is to be conducted on minors, it must be verified that similar studies have been previously carried out on adults and on immature animals, except when it is a question of studying conditions that are characteristic of the neonatal stage or specific conditions of certain ages.

Per G-RECs-Operation_2018 and HlthResRegs-MX, when two (2) persons exercise the parental authority of a minor, only the consent of one of them shall be permitted if there is irrefutable or manifest proof that the other is unable to provide it, proof of his/her negligence, or imminent risk to the minor’s health or life.

HlthResRegs-MX 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-MX, 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 the minor, and comparable with those characteristics of his/her 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

As delineated in G-COFEPRIS-ApplicReqs, assent is required when the minor is older than seven (7) years but less than 18 years of age.

Per G-RECs-Operation_2018 and G-COFEPRIS-ApplicReqs, assent must also be obtained from a minor who is deemed capable of providing assent or has a decreased intellectual capacity, and the minor must be informed about the study in a manner tailored to his/her emotional and intellectual maturity level, considering, at all times, the seriousness of the decision. G-COFEPRIS-ApplicReqs further states the assent should be personalized in Spanish for each participating research center including the version and date, center name and address, corporate name and management of the involved committees.

Additional Resources
No additional resources
Informed Consent > Pregnant Women, Fetuses & Neonates
Last content review/update: December 21, 2018
Requirements
(1) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter IV, Articles 41-55)
(2) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: Annex 5
(3) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title XIV (Chapter I, Article 318 and Chapter III, Article 330)
Summary

Overview

As per HlthResRegs-MX, 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-MX and G-RECs-Operation_2018 note that consent from the spouse or partner may only be waived in the case of his/her incapacity (or irrefutable or manifest inability) to provide it, or when there is imminent risk to the woman’s health or life, or the 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-MX.

HlthResRegs-MX and G-RECs-Operation_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-MX and G-RECs-Operation_2018 indicate that these studies are allowed when they are aimed at improving the pregnant woman’s health with minimal risk to the embryo or fetus, or, per HlthResRegs-MX, seek to increase the fetus’s viability, with minimal risk to the pregnant woman. G-RECs-Operation_2018 adds that the ICF should mention the possible risk to the fetus.

According to HlthResRegs-MX, 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-MX and G-RECs-Operation_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)’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-MX, 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

G-RECs-Operation_2018 also notes that to perform research on pregnant women; during labor, puerperium, or lactation; in live or still births; using embryos or fetuses; and for assisted fertilization, it is required to obtain the informed consent letter from the woman and of his/her spouse, or, depending on the case, provide previous information on the possible risks for the embryo, fetus or newborn.

Per HlthResRegs-MX, 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) comply with the requirements for conducting studies with minors

In addition, HlthResRegs-MX 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 MXGenHlthLaw. MXGenHlthLaw specifically prohibits the use, for any purpose, of embryonic or fetal tissues caused by induced abortions. G-RECs-Operation_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.

Additional Resources
No additional resources
Informed Consent > Prisoners
Last content review/update: December 21, 2018
Requirements
No applicable regulatory requirements
Summary

No relevant provisions

Additional Resources
No additional resources
Informed Consent > Mentally Impaired
Last content review/update: December 21, 2018
Requirements
(1) (Regulation) Research Regulation on General Health Law (HlthResRegs-MX – Spanish) (Effective Date: April 3, 2014)
Congress of the United Mexican States
Relevant Sections: Title II (Chapter I, Article 14 and Chapter III, Articles 34, 36-39)
Summary

Overview

Per HlthResRegs-MX, when the mental capacity and psychological state of the participant permits, his/her acceptance must also be obtained after the investigator(s) explain what they intend to do during a clinical study. The Research Ethics Committee (REC) 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-MX.

As indicated in HlthResRegs-MX, 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 will receive, and
  • The benefit is equal to or greater than other alternatives already established for diagnosis and treatment

In addition, per HlthResRegs-MX, 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 characteristic of his/her 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. 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 mentally incompetent participant.
Additional Resources
No additional resources
Investigational Products > Definition of Investigational Product
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 1.7
(2) (Standard) Mexican Official Standard NOM-012-SSA3-2012, Establishing the Criteria for the Execution of Research Projects for Human Health (NOM-012-SSA3-2012 – Spanish) (Effective Date: January 4, 2013)
Secretariat of Health
Relevant Sections: 4.16
(3) (Standard) Mexican Official Standard NOM-059-SSA1-2015, Good Manufacturing Practices of Medicines (NOM-059-SSA1-2015 – Spanish) (February 5, 2016) (Effective Date: August 5, 2016)
Secretariat of Health
Relevant Sections: 3.77
Summary

Overview

As delineated in MX-GCP-COFEPRIS and NOM-012-SSA3-2012, an investigational product (IP) is defined as any pharmaceutical form containing an active ingredient or placebo, a product of biological or biotechnological origin that is used or tested in a clinical trial for which there is insufficient scientific evidence to demonstrate its preventative, therapeutic, or rehabilitative effectiveness. NOM-059-SSA1-2015 further defines an IP as a product for which there is no previous experience in the country, has not been registered by the Secretariat of Health, and, therefore, has not been distributed commercially. This definition encompasses those products with marketing authorizations when they are used or assembled (formulated or packaged) in a different way from the approved forms, when they are used for an unapproved indication, or, when they are used to gain further information about an approved use. New chemical and biological entities, new formulations, combination products, and biocomparables with or without the release of some active ingredient are also included in this definition.

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

Additional Resources
No additional resources
Investigational Products > Manufacturing & Import
Last content review/update: December 21, 2018
Requirements
(1) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title V (Chapter I, Article 102), Title XII, (Chapter I, Articles 194, 194 Bis., 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)
(2) (Regulation) Regulation of the Federal Commission for the Protection Against Sanitary Risks (Reg-COFEPRIS – Spanish) (April 13, 2004)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Chapter I (Article 3)
(3) (Regulation) Regulation of Health Products (Reg-HlthProducts – Spanish) (Last Amended: March 14, 2014) (Effective: March 29, 2014)
Secretariat of Health
Relevant Sections: Title IV (Chapter I, Articles 99-100) and (Chapter II, Article 113), Title V (Chapter I, Article 132), Title VI (Chapter I, Article 160), (Chapter II, Articles 161-163 and 168-169) and (Chapter IV, Articles 193-194, and 196), and Title VII
(4) (Standard) Mexican Official Standard NOM-059-SSA1-2015, Good Manufacturing Practices of Medicines (NOM-059-SSA1-2015 – Spanish) (February 5, 2016) (Effective Date: August 5, 2016)
Secretariat of Health
Relevant Sections: 1
(5) (Standard) Mexican Official Standard NOM-164-SSA1-2015, Good Drug Manufacturing Practices (NOM-164-SSA1-2015 – Spanish) (Effective Date: August 2, 2016)
Secretariat of Health
Relevant Sections: 1
(6) (Guidance) Sanitary Import Permit for Narcotic or Psychotropic Drugs that are Not Registered – HOMOCLAVE COFEPRIS 01-010-A (G-COFEPRIS-UnregisteredDrugImprts – Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(7) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module VIII
Summary

Overview

According to MXGenHlthLaw, Reg-COFEPRIS, and Reg-HlthProducts, 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 MXGenHlthLaw, COFEPRIS, acting on behalf of the Secretariat of Health (la Secretaría de Salud (SSA)), also issued NOM-059-SSA1-2015 and NOM-164-SSA1-2013 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.

As indicated in MXGenHlthLaw and Reg-HlthProducts, drug manufacturers must submit a request to COFEPRIS to obtain a sanitary license prior to initiating any drug manufacturing activities. Reg-HlthProducts states that COFEPRIS must complete its review in 60 days, or the application will be deemed approved. Per MXGenHlthLaw, the sanitary license is valid for five (5) years. The sanitary license may be extended for an additional five (5) years if the extension is requested prior to the expiration of the current authorization, or the license will be cancelled or revoked.

Please refer to MXGenHlthLaw, Reg-HlthProducts, and Additional Resource (A) for detailed drug manufacturer submission requirements.

As delineated in MXGenHlthLaw, Reg-COFEPRIS, and Reg-HlthProducts, COFEPRIS is also responsible for authorizing the import of IPs. MXGenHlthLaw states that the applicant must be a resident of Mexico or have a legal representative submit an import request on his/her behalf. According to Reg-HlthProducts, G-COFEPRIS-UnregisteredDrugImprts, and Additional Resource (B), an applicant or his/her legal representative may submit a request to import an IP after COFEPRIS has approved his/her request for sanitary authorization 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.

Per Reg-HlthProducts, 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. Additionally, G-COFEPRIS-ApplicReqs indicates that a request for research protocol authorization must include a document stating that the IPs to be used in the clinical study comply with GMPs, and have the expected quality characteristics for the IP under investigation, or provide a letter declaring that the GMPs are valid.

Reg-HlthProducts 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-HlthProducts indicates that three (3) types of sanitary import permits may be issued:

  • Definitive import - which authorizes the entry of products to remain in the national territory for an unlimited time
  • Temporary import - which 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 - which authorizes the entry of products for their transfer from one 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-HlthProducts, G-COFEPRIS-UnregisteredDrugImprts, and Additional Resources (B) and (C) state an import request may be submitted to COFEPRIS’s Integral Services Center (Centro Integral de Servicios (CIS)) once the agency has authorized the protocol for research to be conducted on human beings. The following documentation should be included:

  • Authorizations, Certificates and Visits Form (see Additional Resource (C)) (Original)
  • Proof of payment of fees (Original and two (2) copies)
  • Health License or Notice of Operation (Copy)
  • Approval from the research protocol office authorized by COFEPRIS and its amendments, (only in the case of research on human beings)

In addition, Reg-HlthProducts 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-HlthProducts, the Secretariat of Health via COFEPRIS has 10 days to approve the request. If COFEPRIS does not respond within this timeframe, the request is deemed approved. Reg-HlthProducts 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.

Additional Resources
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Modality A.- Factory or Laboratory of Raw Materials for the Preparation of Medicines or Biological Products for Human Use (COFEPRIS-05-001-A) and Modality B.- Factory or Laboratory of Medicines or Biological Products, for Human Use (COFEPRIS-05-001-B)
(B) (Website) Health Permit for the Importation of Medicines and Raw Materials for Human Research (Spanish) (Current as of December 20, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Necessary Documents and Options to Carry Out Your Procedure
(C) (Form) Authorizations, Certificates and Visits (FF-COFEPRIS-01) (Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(D) (Website) COFEPRIS – Integral Services Center (Spanish) (December 12, 2016)
Integral Services Center, Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Investigational Products > IMP/IND Quality Requirements
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble, 4.1, and 4.11-4.12
(2) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title XII (Chapter IV, Article 222)
(3) (Regulation) Regulation of Health Products (Reg-HlthProducts – Spanish) (Last Amended: March 14, 2014) (Effective: March 29, 2014)
Secretariat of Health
Relevant Sections: Title IV (Chapter II, Article 113), Title V (Chapter II, Article 168), and Title VII
(4) (Guidance) Guide for the Submission of Human Research Protocols – HOMOCLAVE COFEPRIS 04-010-A (G-COFEPRIS-ApplicReqs – Spanish) (Version No. 2.3) (September 2016)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Module VIII
(5) (Standard) Mexican Official Standard NOM-059-SSA1-2015, Good Manufacturing Practices of Medicines (NOM-059-SSA1-2015 – Spanish) (February 5, 2016) (Effective Date: August 5, 2016)
Secretariat of Health
Relevant Sections: 11.25
(6) (Standard) Mexican Official Standard NOM-164-SSA1-2015, Good Drug Manufacturing Practices (NOM-164-SSA1-2015 – Spanish) (Effective Date: August 2, 2016)
Secretariat of Health
Relevant Sections: 0, 1.2, and 3.14
(7) (Standard) Mexican Official Standard NOM-176-SSA1-1998, Health Requirements for Manufacturers, Distributors and Suppliers of Drugs Used in the Manufacture of Medicinal Products for Human Use (NOM-176-SSA1-1998 – Spanish) (Effective Date: January 16, 2001)
Secretariat of Health
Relevant Sections: 1-3, 6.1, and 9
(8) (Standard) Mexican Official Standard NOM-073-SSA1-2015, Stability of Drugs and Medicines (NOM-073-SSA1-2015 – Spanish) (Effective Date: December 4, 2016)
Secretariat of Health
Relevant Sections: 4.1
Summary

Overview

In accordance with MX-GCP-COFEPRIS, the sponsor or his/her contract research organization (CRO) is responsible for complying with the principles of good clinical practice (GCP) as specified in the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs) and for providing investigators with an Investigator’s Brochure (IB). Per the ICH-GCPs, the IB must contain all of the relevant information on the investigational product(s) (IPs) obtained through the earlier research phases, including pharmacological, toxicological, pharmacokinetic, safety, efficacy, and adverse events data. The sponsor must also update the IB as significant new information becomes available.

IB Content Requirements

As specified in the ICH-GCPs, the IB must provide coverage of the following areas:

  • Physical, chemical, and pharmaceutical properties and formulation parameters
  • Non-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
  • Effects of IP in humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and postmarketing experiences)
  • Summary of data and guidance for the investigator(s)
  • Bibliography

See Section 7 of the ICH-GCPs for detailed content guidelines.

MX-GCP-COFEPRIS and the ICH-GCPs state that the sponsor is accountable for supplying the IP 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. As specified in MX-GCP-COFEPRIS, MXGenHlthLaw, Reg-HlthProducts, G-COFEPRIS-ApplicReqs, NOM-059-SSA1-2015, NOM-164-SSA1-2013, NOM-176-SSA1-1998, and NOM-073-SSA1-2015, and the ICH-GCPs, the sponsor must also verify that the products are manufactured in accordance with the current codes of Good Manufacturing Practices (GMPs).

Certificate of Analysis and Drug Manufacturing Certificate Requirements

In accordance with the MXGenHlthLaw, Reg-HlthProducts, NOM-059-SSA1-2015 and NOM-164-SSA1-2013, NOM-176-SSA1-1998, the ICH-GCPs, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios) (COFEPRIS)) requires that drug manufacturers ensure IPs are manufactured, handled, and stored in accordance with applicable GMPs and provide the following additional information:

  • 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 (la 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-HlthProducts)

Additionally, per MXGenHlthLaw, verification of GMP compliance must be conducted by the Secretariat of Health or his/her 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 competent authorities from both countries.

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.

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

Additional Resources
(B) (Website) PAHO Recertifies COFEPRIS as Regulatory Body (Spanish) (January 16, 2018)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
IV Pan American Conference on Drug Regulatory Harmonization, Pan American Health Organization, Dominican Republic
(D) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.1, 5.1, 5.14, and 7
Investigational Products > Labeling & Packaging
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: 4.4
(2) (Standard) Mexican Official Standard NOM-164-SSA1-2015, Good Drug Manufacturing Practices (NOM-164-SSA1-2015 – Spanish) (Effective Date: August 2, 2016)
Secretariat of Health
Relevant Sections: 5.2
(3) (Standard) Mexican Official Standard NOM-059-SSA1-2015, Good Manufacturing Practices of Medicines (NOM-059-SSA1-2015 – Spanish) (February 5, 2016) (Effective Date: August 5, 2016)
Secretariat of Health
Relevant Sections: 10.9
Summary

Overview

Investigational product (IP) labeling in Mexico must comply with the requirements set forth in MX-GCP-COFEPRIS, NOM-164-SSA1-2013, NOM-059-SSA1-2015, and the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs).

As delineated in MX-GCP-COFEPRIS and NOM-059-SSA1-2015, the sponsor must establish IP labeling that contains at a minimum the following information:

  • Protocol identification number
  • Lot number
  • Manufacturer’s name, address, and telephone number
  • Batch number, identification code, dosage form, and route of administration
  • Expiration date
  • Storage conditions
  • The following statements: “Forbidden marketing,” “Permitted use only for investigation,” “Keep out of reach of children,” and "Exclusively for clinical studies"
  • Label must be in Spanish
  • Symbol or pictogram warnings, if applicable

NOM-164-SSA1-2013 also states that the IP label must indicate it is material under investigation, and that 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. Further, per NOM-164-SSA1-2013 and NOM-059-SSA1-2015, 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. In addition, the ICH-GCPs indicate the sponsor should verify the IPs are coded and labeled in a manner that protects the blinding, if appropriate. According to NOM-059-SSA1-2015 and the ICH-GCPs, IPs should have packaging that prevents contamination and unacceptable deterioration during transport and storage.

Additional Resources
(A) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 5.13
Investigational Products > Product Management
Last content review/update: December 21, 2018
Requirements
(1) (Guidance) Guidelines for Good Clinical Practice in Health Research (MX-GCP-COFEPRIS – Spanish) (Effective Date: June 1, 2012)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Preamble, 3.4, 4.1, 4.11-4.12, and 4.5
(2) (Standard) Mexican Official Standard NOM-073-SSA1-2015, Stability of Drugs and Medicines (NOM-073-SSA1-2015 – Spanish) (Effective Date: December 4, 2016)
Secretariat of Health
Relevant Sections: 10.27
(3) (Standard) Mexican Official Standard NOM-164-SSA1-2015, Good Drug Manufacturing Practices (NOM-164-SSA1-2015 – Spanish) (Effective Date: August 2, 2016)
Secretariat of Health
Relevant Sections: 3.24, 10.2, and 16.10
(4) (Standard) Mexican Official Standard NOM-059-SSA1-2015, Good Manufacturing Practices of Medicines (NOM-059-SSA1-2015 – Spanish) (February 5, 2016) (Effective Date: August 5, 2016)
Secretariat of Health
Relevant Sections: 10.9
Summary

Overview

In accordance with MX-GCP-COFEPRIS, the sponsor or his/her contract research organization (CRO) is responsible for complying with the principles of good clinical practice (GCP) as specified in the Guideline for Good Clinical Practice E6(R1) (ICH-GCPs), and for providing investigators with an Investigator’s Brochure (IB). Per the ICH-GCPs, the IB must contain all of the relevant information on the investigational product(s) (IPs) obtained through the earlier research phases, including pharmacological, toxicological, pharmacokinetic, safety, efficacy, and adverse events data. The sponsor must also update the IB as significant new information becomes available.

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

Investigational Product Supply, Storage, and Handling Requirements

MX-GCP-COFEPRIS and the ICH-GCPs state the sponsor is responsible for supplying investigators with the 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.

As indicated in the ICH-GCPs, the sponsor should not supply the investigator(s)/institution(s) with the IP(s) until he/she obtains approvals from the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) and the institutional ethics committee. The ICH-GCPs also specify that the sponsor must ensure the following:

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

Refer to the ICH-GCPs for detailed sponsor-related IP requirements.

Per NOM-073-SSA1-2015, during the clinical trial, the manufacturer must validate the stability of the IP until the date of the last administration. MX-GCP-COFEPRIS further states that the sponsor and his/her 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, per MX-GCP-COFEPRIS, 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.

NOM-164-SSA1-2013 and NOM-059-SSA1-2015 also 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-SSA1-2013 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.

Record Requirements

As set forth in the ICH-GCPs, the sponsor should inform the investigator(s) and institution(s) in writing of the need for record retention and should notify the investigator(s) and institution(s) in writing when the trial-related pharmacy records are no longer needed.

All sponsor-specific essential documents should also be retained for at least two (2) years after the last approval of a marketing application in an ICH region, and until there are no pending or contemplated marketing applications in an ICH region, or at least two (2) years have elapsed since the formal discontinuation of clinical development of the IP. In addition, if the sponsor discontinues the clinical development of the IP, he/she should maintain all sponsor-specific essential documents for at least two (2) years after formal discontinuation or in conformance with applicable regulatory requirement(s).

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.

Additional Resources
(A) (ICH Guidance) Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.1, 5.1, 5.14, and 7
Specimens > Definition of Specimen
Last content review/update: December 21, 2018
Requirements
(1) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title XIV (Chapter I, Article 314)
(2) (Regulation) Regulation of the General Law of Health in Matters of Sanitary Control of the Disposition of Organs, Tissues and Corpses of Human Beings (Reg-HumanSpecDisposal) (Effective Date: February 21, 1985)
Secretariat of Health
Relevant Sections: Chapter I (Article 6)
(3) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: 14
Summary

Overview

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

MXGenHlthLaw and Reg-HumanSpecDisposal 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-Operation_2018 states that human biological material includes organs, tissues, tissue components, cells, and products and cadavers of human beings.

Additional Resources
No additional resources
Specimens > Specimen Import & Export
Last content review/update: December 21, 2018
Requirements
(1) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title I (Chapter I, Article 3), Title II (Chapter II, Articles 17 bis) and Title XII (Chapter XIII, Articles 283-285)
(2) (Regulation) Regulation of the Federal Commission for the Protection Against Sanitary Risks (Reg-COFEPRIS – Spanish) (April 13, 2004)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Chapter I (Article 3)
(3) (Regulation) Regulation of the General Law of Health in Matters of Sanitary Control of the Disposition of Organs, Tissues and Corpses of Human Beings (Reg-HumanSpecDisposal) (Effective Date: February 21, 1985)
Secretariat of Health
Relevant Sections: Chapter VI (Articles 89, 90, and 100)
(4) (Guidance) COFEPRIS 01-025 – Import Permit for Cells and Tissues, Including Blood Components and Derivatives and Other Human Products (G-ImprtPermit-HumanProds – Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
(5) (Guidance) COFEPRIS 01-024 – Export Permit for Cells and Tissues, Including Blood Components and Derivatives and Other Human Products (G-ExprtPermit-HumanProds – Spanish) (Date Unavailable)
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Summary

Overview

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

Import

According to G-ImprtPermit-HumanProds and Additional Resource (A), institutions that dispense or import products of human beings including tissues, cells, blood and its components or derivatives intended for research, diagnosis, teaching, or treatment for therapeutic purposes—including human blood, umbilical cord blood, hematopoietic progenitor cells, and corneas—must comply with specific COFEPRIS documentation submission requirements to apply for an import permit.

As delineated in G-ImprtPermit-HumanProds and Additional Resource (A), the documentation required to obtain an import permit specifically for research purposes is as follows:

  • Entry or Exit of Products of Human Beings form (see Additional Resource (B))
  • Proof of payment of rights in original and two (2) legible copies (per G-ImprtPermit-HumanProds); Additional Resource (A)) requires one (1) original and one (1) copy. Additional Resource (A) also specifies that in terms of the Federal Law on Rights, 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 accrediting the operation of the institution issued by the health authority of the country of origin
  • Copy of the health license or operating notice for the appropriate line of business
  • Copy of the 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

Refer to G-ImprtPermit-HumanProds and Additional Resource (A) 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.

Export

According to G-ExprtPermit-HumanProds and Additional Resource (C), institutions that dispense 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 submit documentation to COFEPRIS to apply for an export permit.

G-ExprtPermit-HumanProds indicates the following general documentation must be provided to export cell, tissues, and products of human beings and their components:

  • Entry or Exit of Products of Human Beings form (see Additional Resource (B))
  • Proof of payment of rights in original and two (2) legible copies
  • Letter of acceptance of the establishment abroad
  • Legible copy of the 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
  • Copy of the operating notice or sanitary license

In addition, G-ExprtPermit-HumanProds and Additional Resource (C) outline the following required documentation to be submitted to COFEPRIS to export umbilical cord blood or hematopoietic progenitor cells, for cryopreservation, research, or therapeutic purposes:

  • Entry or Exit of Products of Human Beings form (see Additional Resource (B))
  • Proof of payment of rights in original and two (2) legible copies (per G-ExprtPermit-HumanProds); Additional Resource (C) requires one original (1) and one (1) copy. Additional Resource (C) also specifies that in terms of the Federal Law on Rights, 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
  • Health license with the corresponding line of business
  • Document issued by the health authority of the destination country that accredits the operation of the establishment

See also Additional Resource (C) for detailed documentation to be submitted to export cell, tissues, and products of human beings and their components intended for scientific research.

Import/Export Submission Procedures

Additional Resources (A), (B) and (C), indicate that an applicant may submit an import/export permit in print or electronically. Per Additional Resources (A) and (C), to submit an application online, it is necessary to obtain an electronic signature (known as e.firma). Additional Resource (D) 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. Refer to Additional Resource (D) for instructions on how to obtain an electronic signature through the (Tax Administration Service (Servicio de Administración Tributaria (SAT))).

Additional Resources
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Necessary Documents and Options to Carry Out Your Procedure
(B) (Form) Import or Export of Human Products (FF-COFEPRIS-04) (Spanish) (Date Unavailable)
Federal Commission for Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Relevant Sections: Necessary Documents and Options to Carry Out Your Procedure
(D) (Website) Catalog of Procedures 2018. e.firma (Spanish) (January 25, 2018)
Tax Administration Service (SAT), Ministry of Finance and Public Credit
Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), Secretariat of Health
Specimens > Consent for Specimen
Last content review/update: December 21, 2018
Requirements
(1) (Legislation) General Health Law (MXGenHlthLaw – Spanish) (Effective Date: July 12, 2018)
Congress of the United Mexican States
Relevant Sections: Title V (Chapter I), Title XIV (Chapter I, Article 314) and (Chapter II, Articles 320-326)
(2) (Regulation) Regulation of the General Law of Health in Matters of Sanitary Control of the Disposition of Organs, Tissues and Corpses of Human Beings (Reg-HumanSpecDisposal) (Effective Date: February 21, 1985)
Secretariat of Health
Relevant Sections: Chapter II (Articles 10-15)
(3) (Guidance) National Guide for Integration and Operation of the Research Ethics Committees (G-RECs-Operation_2018 – Spanish) (6th Edition) (2018)
National Bioethics Commission, Secretariat of Health
Relevant Sections: 14
Summary

Overview

In accordance with MXGenHlthLaw, Reg-HumanSpecDisposal, and G-RECs-Operation_2018, prior to collecting, storing, or using a research participant’s human biological material, consent must be obtained from the participant or his/her legal representative. MXGenHlthLaw specifically states that the consent must be obtained in writing.

From an ethical perspective, G-RECs-Operation_2018 indicates it is important to consider including the following aspects in the informed consent (IC) for human biological materials use and storage:

  • The document should clarify that samples may not be used for any purpose other than the one initially requested, and in accordance with the protocol approved by the Research Ethics Committee (REC)
  • The collection, use, and storage of biological material must guarantee the confidentiality and privacy of the donor
  • The commercialization of biological material is prohibited
  • The investigator may not exercise undue influence by offering financial compensation to the donors of biological material
  • The collection and transfer of biological material should not, under any circumstances, put at risk the medical care and safety of the research participant
  • When the informed consent is revoked, the biological material collected for such purposes must no longer be used, unless the materials are irreversibly dissociated from the person. Data and biological material that are not irreversibly dissociated should be treated according to the wishes of the owner or donor in accordance with the International Declaration on Human Genetic Data
  • The REC should demand to establish time limits for the use of biological material and prohibit the unrestricted use of the material

In addition to the ethical matters raised in G-RECs-Operation_2018, MXGenHlthLaw and Reg-HumanSpecDisposal provide additional consent requirements for the donor and his/her legal representatives (referred to as secondary donors in Mexico).

According to MXGenHlthLaw, a person may choose to donate his/her organs, tissues, cells, and body by tacit or expressed consent. Expressed consent may be in writing and broadly cover the donation of a person’s body, or it may be limited to certain body parts. The consent may also note that the donation is being made to a specific institution(s)/person(s) as well as the manner, place, time, and any other conditions. Further, the donor’s legal representative may also grant the earlier described consent in writing on the donor’s behalf when he/she cannot do so.

While third parties may not revoke the donor’s expressed consent, the donor him/herself may revoke their consent at any time, without any liability on his/her part. Written consent is specifically required when the donor is living for the following:

  • The donation of organs and tissues
  • The donation of blood, blood components and stem cells

Reg-HumanSpecDisposal also notes that the donor may, at any time, revoke consent, without there being any liability on his/her part. Furthermore, in the event that the original donor has not revoked his/her consent in life, the donor’s legal representative revocation of consent will not be valid. Refer to Reg-HumanSpecDisposal for additional information on preferences for selecting the donor’s legal representatives.

In addition, the following restrictions apply with regard to consent by the individuals indicated below:

  • Tacit or expressed consent granted by minors or by persons unable to express their consent freely for any reason will not be valid
  • Per MXGenHlthLaw, all pregnant women are systematically asked for their consent to donate placental blood obtained from stem/progenitor cells for therapeutic or research purposes. However, expressed consent by a pregnant woman will only be admissible if the recipient is in danger of dying, provided that it does not endanger the woman or the fetus

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

MXGenHlthLaw also provides requirements to safeguard the confidentiality of a participant’s genetic data. A participant or his/her legal representative must provide his/her expressed consent and be informed of the results of his/her genetic exam and tests. Moreover, any scientific research, innovation, technological development and applications should be oriented to protect human health and respect the freedom and dignity of the participant(s).

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