Clinical research in China is regulated and overseen by the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) and the National Health Commission (NHC).

National Medical Products Administration

As per the DRR, the NMPA-Org, the DAL, the RegImplemDAL, the RegImplemDAL-Amndt, the SC-Opinions-No44, the NMPA-No50-2018, and the NMPA-No230-2015, the NMPA is the regulatory authority responsible for national drug registration management, which includes regulation of clinical trials. Per the DRR, NMPA’s Center for Drug Evaluation (CDE) is responsible for the evaluation of drug clinical trial applications, drug marketing authorization applications, supplementary applications, and overseas drug production registration applications. The NMPA grants permission for clinical trials to be conducted in China in accordance with the provisions of the DAL, the VaccineLaw, the DRR, the SC-Opinions-No44, the NMPA-No50-2018, and the NMPA-No230-2015. The drug category in which an applicant chooses to register determines the clinical trial application review and approval or filing process.

Per the SC-IRP and the SAMR-Org, China established the State Administration for Market Regulation (SAMR). The SAMR is a full ministry agency reporting directly to the State Council of the People's Republic of China. Under the SAMR is the NMPA, which regulates clinical trials.

As delineated in the NMPA-Org and CHN-78, the NMPA implements China’s guidelines, policies, and decision-making for the supervision and administration of drugs, medical devices, and cosmetics. It is responsible for safety supervision; standards management; drug registration; quality management; risk management; pharmacist licensing; inspection systems; international cooperation; guiding provincial and municipal drug administration; and other tasks assigned by the State Council and Party Central Committee. The NMPA is charged with accelerating the examination and approval of innovative drugs, establishing a system of listing license holders, promoting electronic review and approval, and improving efficiencies.

Per CHN-77, the following NMPA departments are involved with clinical trial application and drug registration:

• Drug Registration Management Department – formulates, supervises, and implements drug standards (including clinical trial quality management), technical guidelines, and registration
• Drug Administration Department – formulates and supervises the implementation of pharmaceutical production quality management standards for drugs, Chinese medicines, biological products, and special drugs (e.g., radioactive and toxic), and formulates and implements a drug adverse reaction monitoring and alert system

Per the DRR, the NMPA-No50-2018, and CHN-81, the NMPA includes the National Institutes for Food and Drug Control (NIFDC) and the CDE, which are directly involved in the clinical trial application and drug registration approval process. Other relevant institutes and organizations include the National Pharmacopoeia Commission, the Food and Drug Inspection Center, the Medical Device Technology Evaluation Center, the Administration Service Center, the Information Center, the Licensed Pharmacist Certification Center, the News and Publicity Center, and the International Exchange Center.

Further, the DRR delineates the responsibilities of the drug regulatory departments of provinces, autonomous regions, and municipalities directly under the Central Government. With respect to clinical trials, they are responsible for organizing the daily supervision and investigation of institutions conducting drug clinical trials; participating in drug registration verification and inspection organized by the NMPA; and other matters entrusted by the NMPA.

The roles of the CDE and the NIFDC in the clinical trial application review and approval process are discussed further in the Scope of Assessment section.

National Health Commission

Per the NHC-HGRmgt, the State Council’s NHC is responsible for China’s management of human genetic resources (HGR). (Note that per SC-Order777 and NHC-HGRmgt, management of HGR was transferred from the Ministry of Science and Technology (MOST) to NHC, effective May 1, 2024). The NHC-HGRmgt states that the original application process and online platform (CHN-6) remain unchanged. As indicated in CHN-24, the NHC is responsible for formulating health policies and systems in China, including health services, hospitals, special populations, drugs, traditional Chinese medicines, and disease control and prevention. See CHN-24 for a comprehensive list of NHC responsibilities and functions. (Please note that the MgmtHumanGen was amended by SC-Order777 to reflect the transfer of HGR management from MOST to the NHC, but the Rules-MgmtHGR has not been amended yet to show the transfer.)

The MgmtHumanGen and the Rules-MgmtHGR stipulate that MOST’s (now the NHC’s) HGR responsibilities include employing experts in the fields of biotechnology, medicine, health, ethics, law, etc. to form an expert review committee to review and approve international cooperative research. The Rules-MgmtHGR indicates that MOST (now the NHC) should support the rational use of HGR to carry out scientific research, develop the biomedical industry, improve diagnosis and treatment techniques, strengthen management and oversight of HGR, improve approval services and efficiency, and advance the standardization of approvals and information disclosure. MOST (now the NHC) is responsible for national efforts such as the investigation, administrative licensing, supervision and inspection, and administrative punishments of HGR. Regarding administrative licensing, licenses must be obtained for the collection and preservation of Chinese HGR and for international collaborations in certain situations. As needed, MOST (now the NHC) entrusts relevant organizations to carry out formal reviews and technical reviews of application materials for administrative licensing of HGR, as well as efforts such as filing, prior reporting, supervision and inspection, and administrative punishments. The science and technology departments (committees and bureaus) of provinces, autonomous regions, and municipalities directly under the Central Government, and the Science and Technology Bureau of the Xinjiang Production and Construction Corps, are responsible for the management of the following HGR in their regions:

• Oversight and inspection and routine management of HGR
• Investigation and handling of illegal cases of HGR within the scope of their authority
• As entrusted by MOST (now the NHC), carry out other efforts such as administrative licensing of HGR in their region

See Rules-MgmtHGR-Interp for a policy interpretation of the Rules-MgmtHGR.

Per HGR-WorkUpdt, the NHC’s China Biotechnology Development Center was entrusted to implement technical work related to the management of HGR. As described in CHN-4, the functions of the Center are:

• Coordinate and supervise the implementation of the management of HGR
• Examine and approve international cooperation projects involving HGR
• Accept applications for the export of HGR, and handle exports and export certificates
• Register and manage important genetic lineages and genetic resources in specific regions
• Manage other work related to HGR

The Rules-MgmtHGR also state that applications must pass a security review organized by MOST (now the NHC) if the study’s provision or opening of HGR information to foreign entities may impact China’s public health, national security, or the social public interest. In addition, per the Bioscrty-Law, MOST (now the NHC) regulates biotechnology safety under the National Security Commission pursuant to a Coordination Mechanism for National Biosecurity (CMNB). The CMNB consists of the competent State Council departments for health, agriculture and rural affairs, science and technology, and foreign affairs, as well as relevant military agencies, to analyze national biosecurity issues, and organize, coordinate, and drive national biosecurity work. MOST (now the NHC) and the other agencies under CMNB establish safety monitoring/reporting requirements, an early warning system, and implementing regulations.

Regarding monitoring and protecting HGR, as delineated in MgmtHumanGen, NHC (formerly the MOST) is also authorized to strengthen the protection of HGR in China, which involves conducting surveys and implementing a declaration and registration system for important genetic families and human genetic resources in specific regions. MOST (now the NHC) will enforce the regulations and levy fines for illegal HGR activities which include:

• Collecting HGR from important genetic families and specific regions in China without approval, or collecting HGR of the types and quantities specified by MOST (now the NHC) through special regulation
• Preserving Chinese HGR without approval
• Conducting international cooperative scientific research using Chinese HGR without approval
• Failing to pass the security review that may affect China's public health, national security, and social public interest to foreign organizations, individuals, and institutions that they establish or actually control, and
• Failing to file with MOST (now the NHC) the type, quantity, and use of the HGR in China before an international cooperative clinical trial begins

Other Considerations

Per CHN-59, China is a regulatory member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). CHN-49 summarizes the ICH guiding principles and provides Chinese translations, when available.

Please note: China is party to the Nagoya Protocol on Access and Benefit-sharing (CHN-30), which may have implications for studies of investigational products developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see CHN-55.

Contact Information

National Medical Products Administration (NMPA)

Per CHN-31, the following is the NMPA’s contact information:

National Medical Products Administration
No. 1 Beiluyuan Zhanlan Road
Xicheng District
Beijing 100037
P.R. China

Per CDE-Reloctn, the following is CDE’s contact information:

National Medical Products Administration
Center for Drug Evaluation
Building 1-5
District 2, No. 22 Guangde Street
Beijing Economic and Technological Development Zone
Beijing, 100076
P.R. China

Phone number: 010-68585566

National Health Commission

Per HGR-WorkUpdt, HGR-AppGuide, and CHN-4, following is the contact information for NHC’s HGR consultation:

National Health Commission
China Biotechnology Development Center
Rooms 1022 and 1001, Building 4
No. 16 West Fourth Ring Middle Road
Haidian District
Beijing, 100036
P.R. China

Contact: Zhu Min
Phone number: 010-88225151 or 010-88225168
Information system support: 17610386080
Email: ycb@cncbd.org.cn

Federal Commission for the Protection Against Sanitary Risks (COFEPRIS)

As set forth in GenHlthLaw, Reg-COFEPRIS, HlthResRegs, NOM-012-SSA3-2012, and COFEPRIS-GCP, the Federal Commission for the Protection Against Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)) is the regulatory authority responsible for approving all clinical studies 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 GenHlthLaw, the Ministry of Health (Secretaría de Salud) supervises the regulation, control, and promotion of health through COFEPRIS. Per MOH-Org, COFEPRIS, a decentralized administrative body, is overseen by the Ministry of Health’s head of the Undersecretariat of Prevention and Health Promotion. Reg-COFEPRIS and GenHlthLaw state that COFEPRIS is headed by a Federal Commissioner appointed by the President of Mexico, upon the Ministry’s recommendation. Per GenHlthLaw, the Ministry of Health is also responsible for supervising COFEPRIS. Per Reg-COFEPRIS and GenHlthLaw, 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.

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 (Comisión de Autorización Sanitaria (CAS)). As delineated in Reg-COFEPRIS, GenHlthLaw, and MEX-53, CAS is responsible for issuing, extending, or revoking research protocol authorizations. According to MEX-104, CAS’s work is performed by its protocols area.

Other Considerations

Per MEX-41, Mexico is a regulatory member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). As indicated in MEX-2, COFEPRIS is in the process of implementing the ICH Guideline for Good Clinical Practice E6 (R2) (MEX-22). However, COFEPRIS-GCP complies with the Guideline for Good Clinical Practice E6 (R1) (MEX-32).

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

Contact Information

As per MEX-71 and MEX-15, COFEPRIS’s contact information is as follows:

Comisión Federal para la Protección contra Riesgos Sanitarios
Oklahoma No. 14
Colonia Nápoles
Del. Benito Juárez
C.P. 03810, Ciudad de México

Note: Per MEX-37, MEX-15, and MEX-25, the preceding address should also be used to contact COFEPRIS’s Comprehensive Service Center (Centro Integral de Servicios (CIS)) (MEX-37) for technical inquiries or those inquiries requiring an official response.

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

Overview

National Medical Products Administration

In accordance with the DRR, the DAL, the NMPA-No50-2018, the SC-Opinions-No44, and the NMPA-No230-2015, the National Medical Products Administration (NMPA) is responsible for reviewing and approving clinical trial applications for drugs to be registered in China, as required. The DRR clarifies that the NMPA regulates clinical trials for drugs in development that are ultimately seeking market approvals in China. Per the DAL and the DRR, and as explained in CHN-7, CHN-18, and CHN-1, China adopted a drug marketing authorization holders (MAHs) system across China. All entities or drug research institutions holding drug marketing authorizations must take responsibility for drug safety, effectiveness, and quality controllability in the whole process of drug research and development, production, distribution, and use. Based on this system, the MAHs are also named as applicants or sponsors during clinical trials. The scope of the NMPA’s assessment includes Phase I through Phase IV clinical trials and bioequivalence studies. As stated in the DRR, clinical trials of drugs must be reviewed and approved by an ethics committee (EC). The DRR indicates that EC review may be submitted in parallel to NMPA’s review, but the study cannot be initiated until after review and approval by the EC. The DRR emphasizes a risk-based approach to drug registration and clinical trial approvals, following the principles of openness, fairness, and justice. This is guided by demonstrating clinical value, encouraging research and creation of new drugs, and promoting the development of generic drugs.

As delineated in the DRR, the SC-Opinions-No44, and the NMPA-No51-2016, the drug classification in which an applicant chooses to register determines the clinical trial application review and approval process. Per the DRR, the registration of drugs must be classified and managed in accordance with three (3) broad categories of Chinese medicines, chemical medicines, and biological products. The NMPA-No44-2020 and CHN-1 delineate the classifications within the chemical medicine category as follows:

• Class 1: Innovative drugs that have not been marketed in China or overseas (i.e., drugs that contain new compounds with clear structures and pharmacological effects, and have clinical values)
• Class 2: Modified new drugs that have not been marketed in China or overseas (i.e., drugs that have their structure, dosage form, formulation, process, route of administration, and indications optimized on the basis of known active ingredients and have significant clinical advantages)
• Class 3: Drugs manufactured by domestic applicants by imitating the original drugs that have been marketed overseas but not yet in China; such drugs must have the quality and efficacy consistent with the reference listed drug
• Class 4: Drugs manufactured by domestic applicants by imitating the original drugs that have been marketed in China; such drugs must have the quality and efficacy consistent with the reference formulations
• Class 5: Drugs that have been marketed overseas and are under application for being marketed in China

As per NMPA-No21-2021, the NMPA provides additional technical support to expedite the review and approval process of domestically unlisted drugs that have been listed overseas in the above Classes 3 and 5.

Per the DRR, the registration of biological products is classified according to innovative biological products, new medicines of improved biological products, and already listed biological products (including biological similar drugs). As delineated in the NMPA-No43-2020, biological products refer to preparations that use microorganisms, cells, animal or human-derived tissues, and bodily fluids as starting materials, and are made with biological technology for the prevention, treatment, and diagnosis of human diseases. In order to standardize the registration and management of biological products, biological products are divided into preventive biological products, therapeutic biological products, and in vitro diagnostic reagents managed by biological products. Preventive biological products refer to vaccine-like biological products used for human immunization to prevent and control the occurrence and prevalence of diseases, including immunization program vaccines and non-immunization program vaccines. Therapeutic biological products refer to biological products used in the treatment of human diseases, such as proteins, polypeptides and their derivatives prepared from engineered cells (such as bacteria, yeast, insect, plant, and mammalian cells) with different expression systems; cell therapy and gene therapy products; allergen products; microecological products; biologically active products extracted from human or animal tissues or bodily fluids or prepared by fermentation, etc. The following are descriptions of biological product classifications for both preventive and therapeutic uses:

• Class 1: Innovative vaccines that have not been marketed at home or abroad
• Class 2: Improved vaccines that improve the safety, effectiveness, and quality controllability of new products by improving the domestic or overseas marketed vaccine products, and have obvious advantages
• Class 3: Vaccines that have been marketed at home or abroad

Per the VaccineLaw, the NMPA must approve vaccine clinical trials. The NMPA-No32-2019 explains that the VaccineLaw strengthens the supervision and enforcement of vaccines and deepens the reform of the drug review and approval system. This includes strengthening the management of vaccine clinical trial institutions and investigating and punishing illegal activities related to applying for vaccine clinical trials (e.g., false data).

National Health Commission

Per the NHC-HGRmgt, the National Health Commission (NHC) is responsible for China’s management of human genetic resources (HGR). (Note that per SC-Order777 and NHC-HGRmgt, management of HGR was transferred from the Ministry of Science and Technology (MOST) to NHC, effective May 1, 2024. SC-Order777 amends the MgmtHumanGen to reflect the transfer of HGR management from MOST to NHC, but the Bioscrty-Law and the Rules-MgmtHGR have not been amended yet to show the transfer). Per the Bioscrty-Law and the MgmtHumanGen, MOST’s (now the NHC’s) scope of assessment is the collection, preservation, utilization, and external provision of HGR to ensure these activities:

• Do not endanger the public health, national security, and social public interests of China
• Are in accordance with ethics principles and reviews per relevant regulations
• Respect the privacy rights of HGR donors, obtain their prior informed consent, and protect their legitimate rights and interests, and
• Comply with the technical norms formulated by MOST (now the NHC)

See the Rules-MgmtHGR for the prescribed conditions when MOST (now the NHC) licenses must be obtained for the collection of Chinese HGR.

As delineated in the Rules-MgmtHGR, MOST (NHC) licenses must be obtained for the preservation of HGR, which involves storing HGR with legal sources under appropriate environmental conditions, ensuring their quality and safety, and using them for future scientific research, excluding temporary storage for teaching purposes. If the preservation also involves the collection of HGR, applicants only need to apply for an administrative license for the preservation of HGR, and do not need to separately apply for a collection license. Next, the Rules-MgmtHGR require administrative licenses for international scientific research cooperation that use and export HGR. If there is no export, only prior filing/notification with MOST (now the NHC) is required before initiating the international research cooperation.

Per the Rules-MgmtHGR, where multicenter clinical research is carried out, the sponsor or the primary site/unit (either the Chinese unit or a foreign party unit) may apply for administrative licensing or filing after the primary site/unit passes the ethics review. After the sponsor or primary site/unit obtains the administrative license or completes the filing, the medical and health institution(s) participating in the clinical research must submit the ethics review approval document of their site/unit, or the certification materials for the ethics review approval provided by the primary site/unit, along with the letter of commitment issued by the site/unit, to MOST (now the NHC). Following those submissions, the international cooperative clinical research can be carried out.

As delineated in the HGR-AppGuide, the scope of the administrative license for the collection of HGR applies to the following activities to be carried out within the territory of China:

• HGR collection activities for important genetic pedigrees – applies to blood-related groups with genetic diseases and/or with special hereditary physical or physiological characteristics, as well as the members of the group with genetic diseases and/or special hereditary physical or physiological characteristics involving three (3) generations or more.
• HGR collection activities in specific areas – applies to HGR from populations who have lived in isolation or special environments for a long time and have special physical characteristics or adaptive traits in physiological characteristics. Specific areas are not divided based on whether they are ethnic minority concentrated areas.
• HGR collection activities for large-scale population research with a population of more than 3,000 – includes but is not limited to cohort studies, cross-sectional studies, clinical studies, and constitutional studies.

Clinical Trial Review Process

National Medical Products Administration

As delineated in the DRR, the NMPA is the regulatory authority responsible for national drug registration management, which includes management of clinical trial applications. The NMPA’s Center for Drug Evaluation (CDE) is responsible for evaluating drug clinical trial applications, drug marketing authorization applications, supplementary applications, and re-registration applications for drugs produced overseas. The DRR states that applicants may communicate with major technical institutions including the CDE at key stages, such as before submitting a drug clinical trial application.

Communications and Pre-Application Protocol Review

Per the NMPA-No50-2018, the NMPA-No48-2020, and the NMPA-No51-2023, with regard to chemical drugs and biological products, the applicant must first request a communication meeting with the CDE to determine the integrity of the clinical trial application data and the feasibility of conducting the clinical trial. The NMPA-No51-2023 reaffirms the required communications between the applicant and the CDE and review of the clinical trial protocol before submitting the clinical trial application. The CDE conducts a preliminary review of the information provided by the applicant according to relevant requirements. The review team reviews the science, completeness, operability, and risk controllability of the clinical trial protocol, focusing on the basis for the research, safety, and whether the risk management measures of the drug support the conduct of clinical trials. In addition to clearly responding to the specific questions raised by the applicant, the submitted clinical trial protocol is reviewed to ensure participant protection. For confirmatory, or critical clinical trials, CDE must also evaluate the suitability of the target population, the science of the dosage and cycle and the primary endpoint indicators, the acceptability of statistical assumptions, the rationality of sample size estimation, the operability of the risk management plan, and the benefit/risk assessment elements. CDE’s review team communicates its findings by holding a meeting (face-to-face or online) or by giving a written reply and must provide the applicant with the minutes of the communication meeting or the written reply. See NMPA-No51-2023 for additional details on the pre-application communications and protocol review.

Clinical Trial Application Review

Per the NMPA-No50-2018, the NMPA’s Drug Registration Management Department is responsible for conducting administrative reviews of clinical trial applications, and then forwarding the submissions to the CDE for technical review. (Deviations from this general process are described further below in this section.) The DRR states that after completing the pharmacology, toxicology, and other studies supporting the clinical trials of the drug, the applicant must submit relevant research materials in accordance with the application requirements (See Submission Process and Submission Content sections for details). If the application materials meet the screening requirements, NMPA’s pharmaceutical, medical, and other technical personnel review the clinical trial applications for drugs.

Per the DRR, when reviewing the application, the CDE will conduct an associated review of the chemical raw materials, auxiliary materials, and packaging materials and containers used in direct contact with the pharmaceutical preparations. The CDE makes a risk-based decision on whether to initiate an on-site inspection based on the registered varieties, processes, facilities, and previous acceptance verification. For innovative drugs, improved new drugs, and biological products, on-site verification of drug registration manufacturing and inspection of pre-market drug manufacturing quality management must be conducted. If manufacturing verification is required, the applicant and the drug regulatory department of the province, autonomous region, or municipality directly under the Central Government where the applicant or manufacturer is located will be informed. The National Institutes for Food and Drug Control (NIFDC) (also referred to as the Procuratorate), or the drug inspection agency designated by the NMPA, will conduct the inspections and testing, as needed. The drug registration inspection of overseas-produced drugs must be implemented by the port drug inspection agency.

The NMPA-No51-2023 specifies that the CDE review team must evaluate the science, completeness, operability, and risk controllability of the clinical trial protocol in the application. If necessary, an expert consultation meeting may be held. For clinical trials that are approved after review, the technical review team’s conclusion and associated "Clinical Trial Approval Notice" must clearly state the indications, clinical trial protocol title, number, version number, version date, etc. The review team’s conclusion and notice may propose revisions or suggestions to the clinical trial protocol if necessary. For clinical trial protocols that require revisions, CDE will notify the applicant through a professional inquiry letter, clearly informing the applicant of the problems and revision opinions in the current protocol. The applicant must submit a revised clinical trial protocol within five (5) days, following the guidance in the Prcdrs-Changes. For clinical trial protocols that are deemed unfeasible, have participant safety risks, or other serious defects, and the applicant cannot revise and improve them within the time limit specified in the inquiry letter, the clinical trial application will not be approved. In the review team’s conclusion and the "Notice of Disapproval of Drug Clinical Trials", the applicant should be clearly informed of the reasons for the disapproval.

The NMPA-No51-2023 also states that before conducting subsequent phased drug exploratory clinical trials, a corresponding drug clinical trial protocol must be reviewed and approved by the EC. After completing exploratory clinical trials and before conducting confirmatory (or critical) clinical trials, an application for a communication meeting must be submitted to the CDE to evaluate the subsequent clinical trial protocol (if applicable).

With regard to vaccine clinical trials, the VaccineLaw indicates that the NMPA will review the clinical trial plan, the safety monitoring and evaluation system, the selection of participants, and whether there are effective measures according to the degree of risk to protect the legal rights of the participants. Vaccine clinical trials can only be carried out or organized by a tertiary medical institution that meets the conditions prescribed by the NMPA and the health and safety department of the State Council, or a disease prevention and control institution at or above the provincial level.

Per the DRR, the DAL, the NMPA-No50-2018, and CHN-14, a clinical trial application will be considered approved after 60 working days if the applicant does not receive a rejection or an inquiry for clarification from the NMPA. As specified in the DRR, drug clinical trials must be carried out within three (3) years after approval. If the drug clinical trial application is approved and no participant signs an informed consent form within three (3) years from the date of approval, the approval lapses. If it is still necessary to carry out the drug clinical trial, the applicant must re-apply. Upon approval/registration of the drug, the applicant receives a drug registration certificate, which is valid for five (5) years. An application for drug re-registration must be submitted six (6) months before the validity period expires.

The DRR states that to amend content in the original drug registration approval, the applicant must conduct sufficient research and verification on the change of the drug and fully evaluate the possible impact of the change on the drug. Data on the impact of safety, efficacy, and quality control must be submitted with the application for amendment. The NMPA-No51-2023 indicates that when changes to a clinical trial protocol are needed, the sponsor may first conduct a self-assessment of the changes in accordance with the relevant requirements of the DRR and the NMPA-No34-2022, and implement further work based on the results of the self-assessment. For substantial changes, the sponsor must submit materials in accordance with the relevant requirements of the NMPA-No34-2022. The CDE review team must review the supplementary application and notify the applicant of whether any/all of the proposed changes are approved. For changes that are not approved, CDE must clearly state the reasons. See NMPA-No51-2023 for definitions of substantial and non-substantial changes to a protocol. Also see Prcdrs-Changes for working procedures for other changes during the review of the clinical trial application.

Expedited Clinical Trial Review

The DRR authorizes regulatory pathways for priority review and approval (including for breakthrough therapeutic drugs), conditional approval, and special approval procedures. As per the SC-Opinions-No44, the NMPA-No230-2015, and the NMPA-No51-2016, a new drug classification system, priority review for innovative drugs and those deemed to have an urgent clinical need, and other changes help China to be more innovative and expedite reviews. With regard to priority review, per the NMPA-No230-2015 and the DRR, the NMPA may apply expedited review and approval procedures to applications for urgently needed drugs and vaccines that are intended to treat certain illnesses or patient populations (e.g., children or elderly people) that the State Council or the NMPA consider to be clinically in demand. The DRR expanded priority review to breakthrough therapeutic drugs, which are used to prevent and treat diseases with the following conditions: are seriously life threatening or seriously affect the quality of life, there are no effective prevention or treatment methods, and there is sufficient evidence to show that they have obvious clinical advantages. Applicants must apply to the CDE at the critical stage of the drug clinical trial. See CHN-69 for handling guidelines on priority review and approval.

The NMPA-No21-2024 describes NMPA’s pilot work plan for optimizing the review and approval of clinical trials for innovative drugs. This initiative aims to review and approve innovative drug clinical trial applications within 30 business days (a reduction from the 60 days as described above in the normal procedures). Pilot projects will be carried out in provinces (autonomous regions and municipalities) that meet the conditions laid out in NMPA-No21-2024. The scope of the pilot project is clinical trial applications for Class 1 innovative drugs (excluding cell and gene therapy products, vaccine products, etc.). Applicants are not subject to regional restrictions and must have at least three (3) innovative drug clinical trial applications approved at home and abroad, have extensive experience in clinical trial implementation and pharmacovigilance management, and be able to conduct a comprehensive risk assessment of clinical trial projects and develop an effective risk management plan before submitting a clinical trial application. In principle, the pilot institution must be a national medical center or national clinical medical research center in the pilot area and must have established a work system to provide clinical trial project establishment, ethics review, and contract review services before the applicant submits a new drug clinical trial application. See NMPA-No21-2024 for additional requirements on application submission and applicant and institutional eligibility. The applicant must initiate the clinical trial within 12 weeks after the approval of the clinical trial application. The pilot work will last for one (1) year and the experience of the pilot work will be summarized in July 2025. One (1) pilot project has been approved in Beijing and Shanghai as indicated in NMPA-No55-2024.

According to the NMPA-No82-2020, the NMPA establishes working procedures for the review of breakthrough therapy drugs, conditional approval of drug marketing priority review, and approval of drug marketing authorization. Sponsors can apply for expedited status for breakthrough therapeutic drugs in Phase I and II clinical trials—usually no later than before the commencement of Phase III clinical trials. Breakthrough drug procedures are designed to be used during clinical trials of drugs to prevent and treat patients with conditions that may be severely life-threatening or that may severely affect their quality of life. There are also no existing effective prevention and treatment methods nor is there sufficient evidence to show that the investigational drugs being tested have obvious clinical advantages compared with existing treatment methods. Also see CondtlAppl-Drugs for technical guidelines on the conditional approval of drugs for marketing.

Per the NMPA-No79-2018, the NMPA established a special review channel for urgently needed drugs that were already on the market in the United States, Europe, and Japan since 2008. Applicants may apply for a drug listing and proceed to conduct the clinical trials while the CDE conducts a technical review of the application materials.

The DRR also authorizes the CDE to conditionally approve breakthrough therapeutic drugs for marketing during clinical trials and vaccines that are urgently needed for major public health emergencies and the benefits outweigh the risks. The applicant must communicate to the CDE on the conditions for marketing with conditional approval and the research work to be completed after marketing, and submit an application for drug marketing approval after communication and confirmation. For the conditionally approved drugs and vaccines, risk management measures must be implemented after the drug is marketed, and the drug clinical trial must be completed within the prescribed time limit. Finally, the DRR authorizes the NMPA to implement special approval procedures for drugs required for public health emergencies. The circumstances, procedures, time limits, and requirements for special approval, will be subject to the NMPA’s procedures for specific approval of drugs.

For background on China’s reformation of the review and approval system to encourage innovation of drugs, see the SC-Opinions-No42. China’s regulatory pathways for expedited approvals and other reforms to the clinical trial submission and review process are described in the Submission Process and Submission Content sections. NMPA-No52-2018-Interp describes the requirements for clinical trial and drug registration applications using trial data generated entirely overseas, as well as data generated from simultaneous research occurring in China and abroad. CHN-11 also provides useful information on the NMPA’s overall clinical trial application review and approval process.

Overseas Data and Waiving Local Clinical Trials

The NMPA-No35-2017 and interpretations in NMPA-No52-2018-Interp describe requirements for clinical trial and drug registration applications to the NMPA using trial data generated entirely overseas, as well as data generated from simultaneous research occurring in China and abroad. With regard to the latter, researchers can conduct Phase I of multi-regional clinical trials (MRCT) of imported investigational new drugs and therapeutic biological products (excluding vaccines) simultaneously in China.

As per NMPA-No52-2018, clinical trial and drug registration applications for imported new drugs or therapeutic biological products using trial data generated entirely overseas do not need to be registered first in their own country in order to enter China. Overseas clinical trial data is acceptable for direct China registration provided that:

• The data is reliable, authenticated, and complies with the requirements of the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CHN-37)
• The data can assess the efficacy and safety for the target indication
• There are no ethnic sensitivities to Chinese local populations influencing efficacy and safety
• The data meets China’s drug registration requirements

See the NMPA-No52-2018 for additional details on the review and approval of overseas clinical trial data. For overseas clinical trial data completed before the enactment of NMPA-No35-2017, the NMPA will consider exemption from conducting local clinical trials, with the condition that the applications meet all other Chinese drug regulatory requirements.

For a running list (in reverse chronological order) of NMPA guidance on drug regulatory requirements, please refer to CHN-60.

National Health Commission

The MgmtHumanGen and the Bioscrty-Law prohibit foreign entities or individuals from collecting or preserving Chinese HGR in China, or providing Chinese HGR for use abroad, except under prescribed conditions to carry out scientific research activities, which must be conducted through collaboration with Chinese scientific research institutions, higher education institutions, medical institutions, or enterprises. Per the MgmtHumanGen and the Rules-MgmtHGR, the foreign entity and the Chinese entity must jointly file an application for approval to MOST (now the NHC), and the research must pass an ethics review in the countries (regions) where the partners are located. The only exception to the approval requirement is international collaborations in clinical trials that do not involve the export of Chinese HGR materials such as organs, tissues, or cells comprising the human genome, genes, or other genetic substances. Such clinical trial collaborations, however, must be filed with MOST (now the NHC) on its online platform (CHN-6), which will generate a record number. See HGR-InfoSys for background on CHN-6. Per HGR-InfoSys, for help with the online platform, contact Zhu Min with the NHC’s China Biotechnology Development Center at 010-88225151 or 010-88225168; or the information system support at 17610386080.

Per the HGR-AppGuide, following administrative screening, the NHC will confirm receipt through CHN-6 and organize a technical review. NHC must conduct its review and issue a decision within 20 working days. If the application is approved, NHC notifies the applicant of the approval through CHN-6 and a letter. If there are missing materials, NHC gives the applicant a one-time opportunity to correct the application and resubmit. If the application exceeds the scope of the license, NHC informs the applicant that the application is not approved.

The Bioscrty-Law prohibits engaging in biotechnology research, development, and application activities that endanger public health, damage biological resources, or destroy ecosystems and biodiversity. Units engaged in biotechnology clinical trials must be responsible for the safety of their biotechnology research, development, and application; adopt biosafety risk prevention and control measures; and formulate biosafety training, follow-up inspections, regular reports, etc. China is implementing a classified management system for biotechnology research and development activities into three (3) categories: high-risk, medium-risk, and low-risk. The risk classification standards are to be formulated, adjusted, and announced by the competent State Council departments for science and technology (now the NHC), health, agriculture, and rural areas. High-risk and medium-risk biotechnology research and development activities must include risk assessments and risk prevention/control and emergency plans for biosafety incidents. The Rules-MgmtHGR also states that clinical trial applications must pass a security review organized by MOST (now the NHC) if the study’s provision or opening of HGR information to foreign entities may impact China’s public health, national security, or the social public interest.

For additional details, see the HGR-FAQs for frequently asked questions on HGR applications. Also see the Submission Process and Submission Content sections and the Specimens topic for additional information on HGR regulatory management.

Overview

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

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

Clinical Trial Review Process

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

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

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

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

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

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

UHAP Evaluations

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

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

National Medical Products Administration

In accordance with the DRR, the applicant is required to pay a fee after the drug registration is approved by the National Medical Products Administration (NMPA). As per the NMPA-No75-2020 and CHN-14, the NMPA charges the following drug registration fees to review and approve clinical trials as part of the drug registration process (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• New drugs made in China: 192,000 Yuan
• New drugs made outside China: 376,000 Yuan
• Generic drugs made in China: 318,000 Yuan
• Generic drugs made outside China: 502,000 Yuan
• One-time import of drugs: 2,000 Yuan

As specified in NMPA-No75-2020 and CHN-14, the fees are based on one (1) active pharmaceutical ingredient or one (1) preparation as one (1) variety. If another specification is added, the registration fee will be increased by 20% according to the corresponding category.

For further guidance on fees associated with submitting supplementary applications and registering renewals for imported drugs and more, please refer to NMPA-No75-2020.

Payment Instructions

NMPA-No37-2022 indicates that to register a drug, the applicant should submit the drug registration application to NMPA’s Government Service Portal (CHN-71). The relevant center will conduct an administrative review. Next, the non-tax income collection management system of the Ministry of Finance will send an electronic payment code to the applicant in the form of a text message. The applicant can pay through the counter payment, self-service terminal, online payment, self-service POS card, bank exchange, or transfer and payment. The applicant will receive confirmation of electronic payment via email within 10 working days. Electronic payment documents have the same legal effect as paper instruments.

National Health Commission

Per HGR-AppGuide, the National Health Commission (NHC) does not charge a fee for an application for a human genetic resources (HGR) license in China.

Federal Commission for the Protection Against Sanitary Risks (COFEPRIS)

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

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

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

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

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

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

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

Payment Instructions

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

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

Overview

As per the Measures-Ethics, the RegEthics, the EC-Guide, the NMPA-GCP-No57-2020, the DRR, and the DAL, an ethics committee (EC) must approve a clinical trial application prior to a sponsor initiating a clinical trial. Per the NMPA-NHC-No101-2019, each institution that conducts biomedical research is required to have an EC that is responsible for reviewing the scientific and ethical rationality of drug clinical trial programs, reviewing and supervising the qualifications of drug clinical trial researchers, supervising the development of drug clinical trials, and ensuring the ethics review process is independent, objective, and fair. Per the Measures-Ethics, institutions conducting life sciences and medical research involving people must establish ECs to carry out ethics reviews of such research. When the institution does not establish an EC, or the EC is unable to meet the needs of the review, the institution may entrust another institutional EC or a regional EC and implement extended supervision through follow-up reviews.

As described in the EC-Guide, China’s ethics review landscape comprises ethics expert committees and institutional ECs. Ethics expert committees are divided into the National Medical Ethics Expert Committee and provincial medical ethics expert committees. They are mainly responsible for guidance, consultation, and training, and generally do not undertake specific ethics review tasks. Institutional ECs are established by medical and health institutions in accordance with relevant requirements, and are mainly responsible for ethics review, training, and consultation in their institutions. Per the Measures-Ethics, provincial-level health departments establish and manage regional ECs. The EC-Guide states that the regional ECs and institutional ECs have the same status and are subject to the same requirements. ECs at different levels and in different institutions should strictly perform their respective duties, carry out effective communication and collaboration, adhere to the independence, impartiality, and objectivity of ethics review, and ensure that all medical research complies with ethical standards and requirements to fully protect the safety and rights of research participants. Following are brief overviews of each type of EC:

• The National Medical Ethics Expert Committee formulates standards for the construction of institutional ECs and ethics review guidelines, including review content, review procedures, additional protection for special groups, and review time limits; publishes ethics review requirements for high-risk activities in scientific and technological ethics; and formulates standard requirements for ethics review application materials.
• The provincial medical ethics expert committees promote the implementation of the above-mentioned ethics review standards and operating guidelines within the administrative region, promotes the construction and operation of the institutional ECs in the region, and standardizes the work of ethics review. The provincial medical ethics expert committees can make supplementary adjustments to the above-mentioned ethics review standards and operating guidelines in light of the cultural customs of the region.
• The institutional EC establishes and improves the ethics review work system and operating procedures in accordance with the guidance of the national and the provincial medical ethics expert committees, improves the conflict of interest management and quality control mechanisms, and ensures that the ethics review process is independent, objective, and fair. ECs at different levels and in different institutions should strictly perform their respective duties, which includes conducting and ensuring ethics reviews that protect the safety and rights of research participants.

Note that per the Measures-Ethics-Interp, the main framework and provisions of the Measures-Ethics and the RegEthics are generally consistent and both regulations should be followed. Some provisions in the newer Measures-Ethics have been refined and improved in combination with the requirements of new laws and regulations and the actual conditions of colleges, universities, and research institutes. The RegEthics will be reviewed and revised to closely align with the Measures-Ethics. (ClinRegs will monitor and update the China profile, as needed.)

Ethics Committee Composition

Pursuant to the NMPA-GCP-No57-2020, the EC composition must meet health authority requirements, and include members of various categories with different gender compositions. The EC members must be trained in ethics review and be able to review ethical and scientific issues related to clinical trials.

Per the Measures-Ethics, the EC-Guide, and the RegEthics, ECs should have at least seven (7) members. The EC-Guide and the RegEthics state that the ECs should be composed of multidisciplinary specialists in biomedicine, management, ethics, law, sociology, statistics, and other areas that collectively represent the qualifications and experience to provide a fair scientific and ethics review. The RegEthics states that in areas where minority ethnic groups reside, the institution should consider including members of those groups on the EC. The EC-Guide indicates that there should be one (1) member who does not belong to the institution and has no close relationship with the project researchers (the same member can meet both requirements). As delineated in the Measures-Ethics, EC members must be selected from experts in the fields of life sciences, medicine, bioethics, law, and people from outside the institution, and there must be members of different sexes. Ethnic minority members must be considered in ethnic minority areas. EC members must have the corresponding ethics review capabilities, and regularly receive training on ethical knowledge of life sciences and medical research and knowledge of relevant laws and regulations.

The Measures-Ethics, the EC-Guide, and the RegEthics provide that the EC can hire an independent consultant if necessary. The Measures-Ethics and the RegEthics state that the independent consultant advises on specific project issues under review and does not participate in the voting. The EC-Guide further indicates that there should be clear institutional regulations on the qualifications, hiring procedures, and job responsibilities of independent consultants, and the hiring process of independent consultants should be recorded and filed.

The EC-Guide and the RegEthics provide that the EC composition should include a chairperson and vice chairpersons, who are elected by committee members. The number of vice chairpersons is not specified in the guidelines. When the chairperson is absent, the deputy chair performs the chairperson’s duties. ECs should not accept any research project applications that do not comply with national laws and regulations. In addition, the EC should refuse to review any projects in which they have a conflict of interest. See the EC-Guide for additional guidance on managing ECs.

Terms of Reference, Review Procedures, and Meeting Schedule

As per the Measures-Ethics, the RegEthics, the EC-Guide, and the NMPA-GCP-No57-2020, each institution must have written SOPs, including a process to be followed for conducting reviews. To ensure the independence, objectivity, and impartiality of the ethics review process, the Measures-Ethics stipulates that the SOPs must include conflict of interest management and quality control mechanisms. Further, the EC must formulate an ethics review system in emergency situations (e.g., epidemic outbreaks) and clarify the time limit for review.

Per the Measures-Ethics, scientific research managers and other relevant personnel must conduct bioethics education and training. The EC-Guide specifies that all committee members should undergo basic professional training in scientific research ethics before starting their EC service at a provincial or above-level scientific research course and receive an ethics training certificate. Participation in continuing education should be on a continuous basis to ensure improvement.

As delineated in the Measures-Ethics, the term of office for members of ECs that review life sciences and medical research involving people must not exceed one (1) year, and they may be re-elected. The EC must have one (1) chairman and several vice chairmen, who must be elected by EC members through consultation and then appointed by the institution. EC members, independent consultants, and their staff must sign confidentiality agreements on sensitive information learned during ethics review work. The EC must accept the supervision of the institution's management. The EC may decide to approve, disapprove, approve after revision, re-examine after revision, continue research, suspend, or terminate the research under review, and must explain its reasons. The decision must be approved by more than one-half of all members of the EC. Members must vote after full discussion of the ethical issues involved in the study, and opinions inconsistent with the review decision must be recorded in detail.

The RegEthics states that EC members should agree to disclose their names, occupations, and affiliations, and to sign the reviews, confidentiality agreements, and a conflict of interest declaration. Each EC member term is five (5) years, after which they can be reappointed. Each institution that establishes an EC should also provide financial compensation to its committee members. EC review and approval decisions must take place during formal meetings. The majority of the total EC membership should be present to conduct reviews.

In addition, the NMPA-GCP-No57-2020 requires the EC to establish and implement the following written documents:

• Provisions on the composition, establishment, and filing of the EC
• The meeting schedule, meeting notice, and meeting review process sequence
• The initial review and follow-up review procedures of the EC
• A rapid review and approval procedure for minor amendments to the experimental protocol agreed to by the EC
• Procedures for promptly notifying researchers of review opinions
• Procedures for appealing ethics review opinions

The RegEthics and the NMPA-GCP-No57-2020 state that written records of all meetings and resolutions should be preserved for five (5) years following the completion of a clinical trial.

Overview

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

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

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

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

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

Ethics Committee Composition

Research Ethics Committee Composition

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

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

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

Hospital Bioethics Committee Composition

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

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

Terms of Reference, Review Procedures, and Meeting Schedule

Research Ethics Committees

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

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

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

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

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

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

Hospital Bioethics Committees

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

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

Overview

According to the EC-Guide, the NMPA-GCP-No57-2020, and the NMPA-No11-2017, the primary scope of information assessed by the ethics committee (EC) relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial, in accordance with the requirements set forth in the Declaration of Helsinki (CHN-84). Per the Measures-Ethics and the RegEthics, ethics reviews and relevant personnel must comply with the Constitution of the People's Republic of China and Chinese laws and regulations. The Measures-Ethics indicates that life science and medical research involving humans must respect research participants and follow the principles of beneficence, non-harm, and fairness, and protect privacy and personal information. Per the RegEthics and the EC-Guide, the EC must also pay special attention to reviewing informed consent and to protecting the welfare of certain classes of participants deemed to be vulnerable (See the Vulnerable Populations section for additional information about these populations). In addition, the EC is responsible for ensuring a competent review of all ethical aspects of the clinical trial protocol; evaluating the possible risks and expected benefits to participants; confirming the suitability of the investigator(s), facilities, and methods; and verifying the adequacy of confidentiality safeguards.

Per Measures-Ethics, life science and medical research involving humans is defined as research activities using biological samples and information data (including health records and behaviors) of research participants, specifically including the following:

• Activities that use methods such as physics, chemistry, biology, and traditional Chinese medicine to conduct research on human reproduction, growth, development, aging, etc.
• Activities that use methods such as physics, chemistry, biology, traditional Chinese medicine, psychology, and other methods to conduct research on human physiology, psychological behavior, pathological phenomena, disease etiology and pathogenesis, as well as disease prevention, diagnosis, treatment, and rehabilitation
• Activities using new technologies or products to conduct experimental research on the human body
• Activities that use methods such as epidemiology, sociology, and psychology to collect, record, use, report, or store biological samples, information data, and other scientific research materials (including health records, behaviors, etc.) related to life sciences and medical issues

The GeneEdit-Ethics states that human genome editing research should have important scientific and social value, and should be limited to medical interventions for treatment or prevention. Non-medical genomic changes to research participants are prohibited. Researchers and institutions should follow the GeneEdit-Ethics for principles and ethical behavior to guide human genome editing research.

Note that per the Measures-Ethics-Interp, the main framework and provisions of the Measures-Ethics and the RegEthics are generally consistent and both regulations should be followed. Some provisions in the newer Measures-Ethics have been refined and improved in combination with the requirements of new laws and regulations and the actual conditions of colleges, universities, and research institutes. The RegEthics will be reviewed and revised to closely align with the Measures-Ethics. (ClinRegs will monitor and update the China profile, as needed.)

Role in Clinical Trial Approval Process

As per the RegEthics, the NMPA-GCP-No57-2020, the DRR, the DAL, and the SC-Opinions-No42, the National Medical Products Administration (NMPA) and the EC must approve a clinical trial application prior to a sponsor initiating a clinical trial. As stated in the DRR, clinical trials of drugs must be reviewed and approved by an EC. The DRR indicates that the EC review may be submitted in parallel to the NMPA’s review, but the study cannot be initiated until after review and approval by the EC. The NMPA-GCP-No57-2020 and the RegEthics also state that the EC must review and approve any protocol amendments prior to those changes being implemented.

Per the Rules-MgmtHGR, the collection, preservation, use, and external provision of China’s human genetic resources (HGR) must comply with ethical principles and pass the ethics review of ECs that have been registered with the relevant management departments. Further, applications for administrative licenses for international scientific research cooperation on HGR must pass an ethics review in the respective countries (regions) where both parties are located. Where the foreign party is truly unable to provide the ethics review certification materials of the country (region) where it is located, it may submit the proof that the foreign party unit recognizes the ethics review opinions of the Chinese unit.

The Measures-Ethics, the EC-Guide, and the NMPA-GCP-No57-2020 provide that the EC’s scope of review must include the following (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Whether the institutions and researchers are competent; the qualifications and experience of the investigator meet clinical research requirements
• Whether the research plan meets the required scientific and ethical principles, has scientific and social value, does not violate the provisions of laws and regulations, and does not harm the public interest
• The degree of risk compared to the expected study benefit
• The informed consent process and whether the relevant information provided is complete and easy to understand, and whether the method for obtaining consent was appropriate
• Whether confidentiality measures have been taken to protect the participants’ privacy, personal information, and data
• Whether the guidelines for the selection and exclusion of participants are appropriate and fair
• Whether the participants are clearly informed of their rights in the research, including the right to equal treatment and that they can withdraw from the research at any time without reason and not be treated unfairly because of this
• Whether the participant received reasonable compensation for participating in the research, and in case of damage or death, whether the treatment and compensation measures are appropriate; participants must not be charged research-related fees for participating in the research
• Whether there is a designated contact for handling and obtaining informed consent and answering questions related to participant safety
• Whether appropriate measures are taken to minimize participant risks
• Potential conflicts of interest
• When conducting non-therapeutic clinical trials, if the participants’ informed consent is implemented by their guardians instead, whether the trial protocol gives full consideration to the corresponding ethical issues, laws, and regulations
• Whether the corresponding ethical issues, laws, and regulations are fully considered in the trial plan if the trial protocol clearly states that the participants or their guardians cannot sign an informed consent form (ICF) before the trial in an emergency
• Whether participants are forced or induced to participate in clinical trials due to improper influence, including whether the ICF has content that waives legal rights or exempts researchers, institutions, or sponsors from being responsible
• Whether the method, content, and timing of the release of research results are reasonable

Per the Measures-Ethics and the EC-Guide, the EC will make one (1) of the following decisions (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Approval: The EC unconditionally approves an initial review of the research protocol and will conduct follow-up reviews. The research can start immediately after approval.
• Approval after modification: The EC conditionally approves a research protocol if the research leader accepts the EC’s proposed amendments.
• Review after modification: If the EC needs more substantive information about the research project under review, it will decide to suspend the deliberation until the committee receives new information.
• Approve continuation of research.
• Not approved: The EC votes against a research proposal. The reasons for disapproval must be communicated to the research leader, who is given an opportunity to defend the research.
• Suspension or termination of research: The EC suspends or terminates a research project.

The Measures-Ethics specifies that the EC must conduct the review and issue its opinion within 30 days of acceptance of the materials.

The Measures-Ethics states that before the implementation of research approved by the EC, researchers, ECs, and institutions must truthfully, completely, and accurately upload information to the registration platform (CHN-53), including research, ethics review opinions, and institutional review opinions in accordance with the requirements of the national medical research registration and filing information system, and promptly update the information according to the progress of the research. Researchers, ECs, and institutions are encouraged to upload information in real time during the study management process.

The NMPA-GCP-No57-2020 specifies that the EC must pay attention to and clearly require investigators to report in a timely manner the following: deviations or modifications to the trial protocol to eliminate emergency hazards to participants; changes that increase the risk to participants or significantly affect the implementation of clinical trials; all suspicious and unexpected serious adverse reactions; and new information that may adversely affect the safety of participants or the implementation of clinical trials. The EC has the right to suspend or terminate clinical trials, as needed. Finally, the EC must accept and properly handle requests from participants. Per the EC-Guide, if there are accidental injuries or violations during the research project, the EC has the right to request the suspension or termination of an approved research project. Further, the EC reviews amendments to the protocol and informed consent form, and reviews serious adverse events and violations of the protocol. The Measures-Ethics states that when a serious adverse event is reported, the EC must conduct a timely review to determine whether the measures taken by researchers to protect the personal safety and health rights and interests of research participants are adequate, reassess the risk-benefit ratio of the research, and issue review opinions.

As delineated in the NMPA-No34-2022, protocol changes that result in updating the investigator’s brochure, ICF, or other relevant documents should be reported to the EC by the sponsor. The Measures-Ethics indicates that if approved research requires revision of the research plan, informed consent, recruitment materials, or other materials provided to research participants, the researcher must submit the revised documents to the EC for review. Further, the EC must conduct follow-up reviews at least annually in accordance with relevant reports submitted by the investigators. The follow-up review must include the following considerations:

• Whether the research is conducted in accordance with the approved research plan and reported in a timely manner
• Whether the research content was changed without authorization during the research process
• Whether changes or new information increase the risk to research participants or significantly affect the implementation of the research
• Whether it is necessary to suspend or terminate the research early
• Other content that needs to be reviewed

Per the EC-Guide, the EC has the right to request regular follow-up reviews of approved research projects based on the possibility and degree of research risks. The RegEthics provides that the EC must designate members to conduct follow-up examinations of approved research projects. The number of members for follow-up review must not be less than two (2), and the review is required to be reported to the EC. Further, the EC may apply to the provincial medical ethics expert committees to provide advice on the ethics review of research that involves a relatively high-risk or special population.

Expedited Review

As delineated in the Measures-Ethics, the EC may conduct expedited review of research in the following circumstances:

• Research whose risk is not greater than the minimum risk
• Research in which the approved research protocol is slightly modified and does not affect the risk-benefit ratio of the research
• Follow-up review of approved research
• Research conducted by multiple institutions, when the EC of the participating institution confirms the ethics review opinion issued by the lead institution, etc.

Where the situation is urgent, an ethics review must be promptly carried out. In the case of emergencies such as outbreaks, ethics reviews and review opinions are generally carried out within 72 hours, but the requirements and quality of ethics reviews must not be reduced. For expedited review, the EC chairman designates two (2) or more members to conduct the ethics review and issue review opinions. The review opinions must be reported at the EC meeting. If it is discovered during this review that there is a change in the risk-benefit ratio of the research, there is a disagreement among the review members, or the review members propose that a meeting review is required, etc., then a full review procedure must be held.

During an outbreak of an epidemic, the EC-Guide advises ECs to adhere to the highest scientific and ethical standards for independent review of the research project to ensure balancing of quality and timeliness. The materials provided by the researcher can be simplified according to the situation. The EC should pay special attention to the informed consent process as participants may be improperly exploited due to their obvious vulnerability, especially when it involves high-risk and risk-uncertain research. It should be ensured that participants choose to participate voluntarily and independently after being fully informed and fully understanding the possible risks of research. Research participants or the legal representative/guardian must be allowed to withdraw from research unconditionally at any stage. See the EC-Guide for additional guidance on the EC review when there is a major epidemic risk.

Multicenter Studies

Per the Measures-Ethics, research carried out in multiple institutions may establish collaborative mechanisms for ethics review, ensuring that all institutions follow the principles of consistency and timeliness. Both the lead institution and the participating institution must organize an ethics review. The EC of the participating institution must conduct a follow-up review of the research in which the institution participates. Where establishments cooperate with enterprises and other institutions to carry out life science and medical research involving humans, the institutions must fully understand the overall situation of the research, clarify the scope of use and handling methods of biological samples and information data through agreements subject to ethics review and follow-up review, and supervise their proper disposal after the research is completed.

Per the EC-Guide, the review of international cooperative research projects requires ethics review by the lead unit. For cooperative research projects conducted in China, the trial protocols should be submitted to the EC for a single-review process and should be consistent, though the EC will accept that informed consent may vary slightly in different institutions. The RegEthics also provides that multicenter research may establish a collaborative review mechanism to ensure that the research institutions of each project follow the principles of consistency and timeliness. The lead agency EC is responsible for project review and confirmation of the ethics review results of participating institutions. ECs of the participating institutions must conduct an ethics review of the research in which the institution participates in a timely manner and provide feedback to the lead agency for review.

Exemption from Ethics Review

The Measures-Ethics states that ethics review may be exempted where human information data or biological samples are used to carry out life science and medical research involving humans if the research does not cause harm to the human body or does not involve sensitive personal information or commercial interests. This is to reduce unnecessary burdens on scientific research personnel and promote the development of life science and medical research involving people. The exemption may apply in the following circumstances:

• Using lawfully obtained public data or conducting research through data generated by observing and not interfering with public conduct
• Using anonymized information and data to carry out research
• Using existing human biological samples to carry out research, and the source of the biological samples complies with relevant laws and regulations and ethical principles; the relevant content and purpose of the research are within the scope of the informed consent; and the research does not involve the use of human germ cells, embryos, reproductive cloning, chimerism, and heritable gene manipulation
• Carrying out research using human-derived cell lines or cell lines derived from biobanks, where the relevant content and purpose of the research are within the scope authorized by the provider, and do not involve activities such as human embryonic and reproductive cloning, chimerism, and heritable gene manipulation

Overview

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

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

Role in Clinical Trial Approval Process

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

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

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

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

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

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

No applicable requirements.

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

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

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

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

No information is available on Hospital Bioethics Committee fees.

Overview

Per the NMPA-NHC-No101-2019, the National Medical Products Administration (NMPA) oversees and supervises the registration and filing of clinical trial institutions. Drug clinical trials must be conducted in registered clinical trial institutions that meet the applicable requirements, which include having an ethics committee (EC).

Registration, Auditing, and Accreditation

The RegEthics states that all biomedical research institutions in China should establish their own ECs. Per SC-Opinions-No42, the NMPA adopted a registration system for institutions with qualifying conditions to be entrusted to conduct clinical trials and operate ECs. An institution is entrusted to conduct clinical trials if it has an EC and the main investigators of clinical trials have senior professional titles and have participated in more than three (3) clinical trials, among other conditions. To apply for qualification, institutions must submit an application via the online filing system (CHN-82) and fulfill the requirements pursuant to the NMPA-NHC-No101-2019. Per the Measures-Ethics, institutions must register the EC within three (3) months of its establishment and upload the information to CHN-82. Medical and healthcare institutions must register with the appropriate oversight authority. Other institutions must register with the competent department at a higher level according to their administrative affiliation. The EC must submit the previous year's work report to the appropriate institutional department before March 31^st of each year, including:

• A list of personnel and resumes of committee members' work
• The EC charter
• Work systems or relevant work procedures
• Other relevant materials required by the appropriate department

When the above information changes, the institution must promptly update the information to the appropriate institutional department.

As delineated in the RegEthics and interpreted in CHN-41, the National Health Commission (NHC) is responsible for managing ECs nationwide, organizing the inspection and management of the national ethics review of biomedical research involving human beings, establishing the National Medical Ethics Expert Committee, and for developing policies relating to ethics review. The National Medical Ethics Expert Committee conducts research on major ethical issues in research involving humans and provides policy advice and guides the provincial ECs. Per CHN-3, China established a National Science and Technology Ethics Committee to strengthen the ethics governance system. Further, the SC-EthicalGov establishes principles and guides the committee in its responsibility to develop and coordinate the ethics governance system.

The EC-Guide describes the inspection and oversight mechanisms among the ECs in China. The National Medical Ethics Expert Committee formulates an inspection and evaluation indicator system for institutional ECs, including review quality, review efficiency, committee member capabilities, conflict of interest management, etc., to guide provincial medical ethics expert committees in carrying out ethics inspections within the region. The National Medical Ethics Expert Committee also inspects, evaluates, and supervises the work of provincial medical ethics expert committees. The provincial medical ethics expert committees are responsible for conducting regular inspections and evaluations of the ethics review work of medical institutions and regional ECs within the administrative area at the same level, making recommendations on how to manage non-standard ethics review work, and may establish an information disclosure mechanism based on actual conditions. Institutional ECs should check and evaluate the indicator system, continuously improve their operations, and actively cooperate in completing various inspections and evaluations. Regular self-evaluation is encouraged to improve work quality and review efficiency.

As delineated in the RegEthics, the provincial, autonomous regional, and municipal health authorities also have ECs set up under their own administration. The provincial medical ethics expert committees assists in promoting the institutionalization and standardization of the ethics review work of human biomedical research in its administrative region, and guides, inspects, and evaluates the work of the institutional ECs in the administrative region. It also performs training and consulting work. The local health administrative department at or above the county level supervises and manages the ethics review work of biomedical research involving people in its administrative region. Per the Measures-Ethics, provincial-level health departments, in conjunction with relevant departments, must formulate measures for the establishment and management of regional ECs. The regional EC must file with the provincial health department and upload information in CHN-82.

For additional information about oversight of ECs, including inspections, see the RegEthics.

Overview

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

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

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

Registration, Auditing, and Accreditation

Research Ethics Committees

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

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

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

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

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

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

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

Hospital Bioethics Committees

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

Overview

As per the DRR, the National Medical Products Administration (NMPA) grants permission for clinical trials to be conducted in China pursuant to the drug registration process, in accordance with the DAL, the VaccineLaw, and other laws and regulations. The NMPA-GCP-No57-2020, the DRR, the DAL, and the SC-Opinions-No44 require the sponsor to obtain NMPA and ethics committee (EC) approvals of a clinical trial application. As stated in the DRR, EC review may be submitted in parallel to the NMPA’s review, but the study cannot be initiated until after review and approval by the EC.

Per the NHC-HGRmgt, the National Health Commission (NHC) is responsible for China’s management of human genetic resources (HGR). (Note that per SC-Order777 and NHC-HGRmgt, management of HGR was transferred from the Ministry of Science and Technology (MOST) to NHC, effective May 1, 2024). The NHC-HGRmgt states that the original application process and platform (CHN-6) remain unchanged. Per the Rules-MgmtHGR, the collection, preservation, use, and external provision of China’s HGR must comply with ethical principles and pass the ethics review of ECs that have been registered with the relevant management departments. Further, with applications for administrative licenses for international scientific research cooperation, the HGR project must pass an ethics review in the respective countries (regions). As part of the application filing for international cooperative clinical trials, NMPA approvals, notices, and/or filing registration must be obtained in advance, along with the EC approvals. Therefore, EC and MOST (now the NHC) review cannot occur in parallel. (Please note that SC-Order777 amends the MgmtHumanGen to reflect the transfer of HGR management from MOST to the NHC, but the Rules-MgmtHGR has not yet been amended to show the transfer.)

Regulatory Submission

National Medical Products Administration

The NMPA-No50-2018 establishes the broad submission procedures for clinical trials, which are detailed below through implementing regulations and guidance. The DRR states that a Chinese legal entity must submit the drug registration application. Clinical trial applications are also considered drug registration applications. Overseas drug manufacturers without legal representation in China must apply for drug registration through Chinese legal persons to handle relevant drug registration matters.

The applicant should prepare materials and apply for a communication meeting with the NMPA’s Center for Drug Evaluation (CDE) in accordance with the requirements of the NMPA-No48-2020, which includes requirements for different categories of meetings involving applications for new drugs. The NMPA-No48-2020 includes the application form (Appendix 1) and communication meeting materials (Appendix 2). The meeting’s purpose is to determine the integrity of the clinical trial application data and the sponsor’s ability to ensure the participant’s safety. If existing or supplemental data can support the clinical trial, then the applicant can submit a clinical trial application after the meeting or after supplementing the data. The NMPA-No51-2023 reaffirms the required pre-trial meeting and states that the applicant must submit a communication application to the CDE before 1) applying for the first clinical trial of a new drug and 2) before completing the exploratory clinical trial and conducting the confirmatory (or critical) clinical trial. The NMPA-No23-2023 provides guidance on common issues and general requirements for the Phase III pre-clinical trial meeting with the CDE in regards to innovative drugs.

Per the NMPA-No50-2018, the applicant may directly submit a clinical trial application without requesting a communication meeting with the CDE in the following cases: they clearly understand the technical guidance; have sufficient experience in drug clinical trials; can ensure the quality of data in the application; or the application is for a multicentered international clinical trial being conducted in parallel that has permission to conduct the clinical trials in countries or regions with an established and functional regulatory and monitoring infrastructure. In addition, the NMPA-No48-2020 stipulates that the application for conditional approval and/or the application for priority review and approval procedures must be communicated and confirmed with the CDE before submittal. (See below for procedures on priority review and approval.)

CHN-14 states that Chinese legal entities must submit application materials to the NMPA/CDE for a formal process review (including checking the electronic materials as described below). NMPA will process clinical trial applications within five (5) working days if the study falls within the scope of its authority; the application materials are complete and comply with the prescribed format; and if all required supplementary materials are submitted. If accepted, the CDE then organizes and conducts its review of the clinical trial application on behalf of the NMPA. As required in the ElectronicApps-Rqts and the NMPA-No110-2022, all documents for drug registration applications (including clinical trial applications, letters of commitment, declarations, and supplemental material) must be submitted electronically on CD-ROM to the CDE, in accordance with the current regulations, technical requirements for electronic CD-ROMs of application materials, and electronic file structure of drug registration applications. The ElectronicApps-Rqts clarifies that the CDE no longer accepts paper documents for administrative licensing by mail, except for applications that were accepted before January 1, 2023 and must continue to submit supplementary material in paper format. The applicant or registered agent is required to electronically sign the electronic declaration materials; the application and electronic seal can be found in the CDE’s Applicant Window (CHN-58). For details on the cover requirements for CD-ROM cases and the cover of the file bag, refer to Annex 1 in ElectronicApps-Rqts.

As indicated in CDE-Reloctn, the applicant should fill in and submit the relevant information in the "Online Appointment for Submission of Materials" module under the "Online Appointment" item in the "Applicant's Window" column of CDE’s Applicant Window (CHN-58). To mail CDs and other application materials in electronic format, applicants should use the following mailing address:

Business Management Office of the Center for Drug Evaluation
State Drug Administration
Room 102, Building 2
District 2, No. 22 Guangde Street
Beijing Economic and Technological Development Zone
Beijing, 100076
P.R. China

Per the ElectronicApps-Rqts, after receiving the disc submitted by the applicant, the CDE will determine if the disc can be read normally, passes the electronic signature verification, and has no computer viruses. If the disc does not pass these reviews, the CDE will notify the applicant and request resubmittal; the original disc will be disposed of in accordance with the CDE’s destruction procedures. If accepted, the CDE will push the electronic documents to the "Drug Business Application System" and "Drug eCTD Registration System" and the applicant is notified by SMS.

The ElectronicApps-Rqts provides additional requirements on the arrangement of discs:

• Submit one (1) complete set of electronic application materials on CD-ROM (including clinical trial database, if applicable) for review
• Submit one (1) complete set of electronic declaration materials on CD-ROM (including clinical trial database, if applicable) for verification at the same time.
• For clinical trial database data, the relevant materials must be prepared in a separate set of CD-ROMs.

Additionally, the ElectronicApps-Rqts states that within five (5) working days after the acceptance of the drug registration application, the applicant must upload a Microsoft Word file of the application materials (e.g., pharmacy, non-clinical, and clinical reviews) through the CDE’s Applicant Window (CHN-58). The documents related to pharmaceutical materials (active pharmaceutical ingredients (APIs), pharmaceutical excipients, and pharmaceutical packaging materials) should be uploaded as PDF files. Further, per the DRR, supplementary materials (e.g., clinical trial research materials, consultations, and data submittals) are handled via the CDE’s Applicant’s Window (CHN-58).

Note that per CHN-14, all application materials must be in Chinese with the original language attached, and materials in other languages can be attached as reference. Chinese translations should be consistent with the original text.

The NMPA-No44-2020, the NMPA-No43-2020, and the NMPA-No10-2018 require applicants to apply the International Council for Harmonisation (ICH)’s M4: Common Technical Document for the Registration of Pharmaceuticals for Human Use (CTD) (CHN-38) to the registration applications for drugs, therapeutic biological products, and vaccines. See the NMPA-No16-2018 for guidance on Phase I clinical trial applications. To standardize the submission of drug clinical trial data, meet the newly revised drug registration application data requirements, and improve the efficiency of drug review, the NMPA-No16-2020 provides guidance on the content and format of clinical trial data. The guidance is based on the data submission requirements of international regulatory agencies, including the Clinical Data Interchange Standards Consortium (CDISC).

For administrative support, applicants can request a meeting and/or consult the NMPA’s Government Service Portal (CHN-71).

Bioequivalent Studies

Per the NMPA-No230-2015, for generic drugs, a bioequivalence study will only need to be filed with the NMPA. The applicant should submit record filing materials to the NMPA 30 days before submitting the bioequivalence studies. For the generic drug filing, the applicant must obtain EC approval and sign a clinical study agreement with the clinical site prior to filing the bioequivalent study. See CHN-70 for handling guidelines for bioequivalent drugs.

Priority and Special Procedures

In addition, the DRR authorizes regulatory pathways for priority review and approval (including for breakthrough therapeutic drugs), conditional approval and special approval procedures. Per CHN-69, after the registration application is transferred to the CDE, applicants can apply for accelerated review directly to the CDE at CHN-58. CHN-69 contains the application and additional procedures for submitting applications for priority review and approval. As per the SC-Opinions-No44, the NMPA-No230-2015, and the NMPA-No51-2016, a new drug classification system, priority review for innovative drugs and those deemed to have an urgent clinical need, and other changes help China to be more innovative and expedite reviews. As delineated in the NMPA-No23-2018, for drugs listed overseas and that treat seriously life-threatening conditions, if there is no ethnic difference in the study, they can submit the clinical trial data obtained overseas and directly apply for the drug listing registration.

Protocol Changes

As delineated in the NMPA-No34-2022, when there is a protocol change during a clinical trial, the sponsor should follow these submission guidelines:

• For substantial changes that may significantly increase the risk to participant safety, the sponsor must submit a clinical trial application as per the instructions above
• For substantial changes that do not significantly increase participant safety risk, but may significantly affect the scientific validity and the reliability of the data, the sponsor should submit a communication meeting application to the CDE (see above)
• Non-substantive changes can be implemented after being approved by the EC and filed with the NMPA
• After the protocol is changed, the sponsor must update the drug clinical trial registration (See the Initiation, Agreements & Registration section) and submit the relevant updates in progress reports

National Health Commission

Per the MgmtHumanGen and the Rules-MgmtHGR, the foreign entity and the Chinese entity must jointly file an application for approval to MOST (now the NHC) and pass an ethics review in the partners’ countries. The only exception to the MOST (now the NHC) approval requirement is international collaboration in clinical trials that do not involve the export of Chinese HGR materials such as organs, tissues, or cells comprising the human genome, genes, or other genetic substances—these must be filed with MOST (NHC), which will generate a record number (see below for steps) and pass an ethics review in the partners’ countries.

As stated in the HGR-AppGuide, the HGR license application must be submitted to NHC via the Human Genetic Resources Service System (CHN-6), including application information and supporting materials. After verification, the system posts updates for the applicant.

See HGR-InfoSys for background on the online platform and contact information. For help with the online platform, contact Zhu Min, NHC’s China Biotechnology Development Center, at 010-88225151 or 010-88225168; or the information system support at 17610386080.

Ethics Review Submission

Each institutional and regional EC has its own required submission procedures.

Overview

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

Regulatory Submission

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

Pre-submission Registrations

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

DIGIPRiS Submissions

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

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

CIS Submissions

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

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

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

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

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

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

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

Enabled Pre-Assessment Support Unit (UHAP) Evaluation Submissions

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

Ethics Review Submission

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

Regulatory Authority Requirements

National Medical Products Administration

As delineated in the NMPA-No51-2023, the applicant must submit the following materials to the National Medical Products Administration’s (NMPA) Center for Drug Evaluation (CDE) to have a communication meeting prior to submitting a clinical trial application for an exploratory clinical trial:

• The overall clinical development plan
• A complete first clinical trial protocol
• A risk management plan
• A subsequent clinical trial protocol, if applicable
• Non-clinical research review
• Pharmaceutical research review, etc.
• A clear statement of the issues to be communicated

Next, the NMPA-No51-2023 states that prior to completing the exploratory clinical trial, the applicant must submit the following to CDE for another meeting to discuss conducting the confirmatory (or critical) clinical trial and the subsequent clinical trial protocol:

• A preliminary analysis of the results of the early clinical trials that have been conducted
• A scientific, reasonable, complete, and feasible confirmatory (or critical) clinical trial protocol based on the existing clinical trial data
• A risk management plan
• A review of non-clinical studies
• A review of pharmaceutical studies, etc.

Per the DRR, after completing the pharmacology, toxicology, and other studies supporting the clinical trials of the drug, the applicant must submit relevant research materials to the NMPA. When applying for drug registration, the applicant must provide true, sufficient, and reliable data, materials, and samples to prove the safety, effectiveness, and quality controllability of the drug. In cases where overseas research materials and data are used to support drug registration, its source, research institution, or laboratory conditions, quality system requirements, and other management conditions should conform to prevailing international principles and applicable Chinese drug registration management requirements. CHN-14, CHN-70, and CHN-69 contain application materials and handling guidelines covering domestic drug and biological product clinical trial applications; imported drug and biological product clinical trial applications; priority review application procedures; and bioequivalence filing procedures. In general, the applications require information about the drug (e.g., names, formulation and ingredients, indications, and packaging), patents, the applicant, and the institution(s). In addition, the applications require a declaration attesting that the application and associated materials comply with the DAL, the DRR, and other applicable laws and regulations. The application and submitted data and samples must be true and legal, and they should not infringe on the rights and interests of others. The content of the electronic file submitted must be the same as the printed file. If any data is found to be false, the applicant bears the legal consequences caused by it.

The NMPA-No51-2023 requires the applicant to submit the following materials with the clinical trial application, in accordance with the NMPA-No44-2020 and the NMPA-No43-2020:

• A complete clinical research and development protocol
• A complete plan for the proposed clinical trial
• A risk management plan
• A framework for the subsequent clinical trial plan (if applicable)

The NMPA-No16-2018 provides guidance on technical information to be included in the application dossier for Phase I clinical trials:

• Introductory description and overall research plan
• Researcher’s manual (Investigator’s Brochure (IB))
• Clinical trial plan
• Pharmacy research information
• Pharmacology and toxicology information
• Description of previous clinical use experience
• Overseas research material

Per the SC-Opinions-No42, the NMPA-No10-2018, and CHN-14, that applicants should apply the International Council for Harmonisation (ICH)’s M4: Common Technical Document for the Registration of Pharmaceuticals for Human Use (CTD) (CHN-38) to the registration applications for drugs, therapeutic biological products, and vaccines.

See CHN-20 for additional analyses and overview of the China clinical trial application submission content.

National Health Commission

Per the NHC-HGRmgt, the National Health Commission (NHC) is responsible for China’s management of human genetic resources (HGR). (Note that per SC-Order777 and NHC-HGRmgt, management of HGR was transferred from the Ministry of Science and Technology (MOST) to NHC, effective May 1, 2024. Please note that SC-Order777 amends the MgmtHumanGen to reflect the transfer of HGR management from MOST to the NHC)). The NHC-HGRmgt states that the original application process and platform (CHN-6) remain unchanged.

The MgmtHumanGen requires that applications for a license to collect or preserve HGR meet the following conditions:

• Applicants prove legal person status
• The purpose of collection and/or preservation is clear and legal
• The collection and/or plan is reasonable
• In the case of preservation, the premises where the HGR will be deposited is legal
• Proof of passing ethics review
• Having a department and management system responsible for the management of collecting and/or preserving the HGR
• Having premises, facilities, equipment, and personnel suitable for collection and/or preservation activities

As delineated in the MgmtHumanGen, the application for international collaborative scientific research using China’s HGR must demonstrate:

• The research is not harmful to the public health, national security, or social public interests of China
• The two (2) parties to the cooperation are a Chinese entity and a foreign entity with legal person status and have the basis and ability to carry out relevant work
• The purpose and content of the cooperative research are clear and legal, and the duration is reasonable
• The cooperative research plan is reasonable
• The HGR to be used are of legal origin, and their types and quantities are consistent with the research content
• The research passed an ethics review of the respective countries (regions) of the cooperation parties
• The ownership of the research results is clear, and there is a reasonable and clear profit distribution plan

Information on the submission content for the HGR export license is summarized in the Specimen Import & Export section.

Ethics Committee Requirements

Each ethics committee (EC) has its own application form and clearance requirements that can differ significantly regarding the number of copies to be supplied and application format requirements.

The following list was compiled from the Measures-Ethics and the RegEthics to exemplify the common elements shared by the various application forms (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Application for Human Research Ethics Review (See CHN-27 for a sample institutional application)
• Application Protocol for Results of Research or Related Technologies
• Protocol
• Sample ICF (See Children/Minors section for additional information)
• Case Report Form
• Principal investigator(s) CV(s)
• NMPA approval letter
• Certificate of Analysis for the drug issued by the National Institutes for Food and Drug Control (NIFDC) or corresponding provincial, autonomous region, or municipal institutes
• IB
• Any additional feedback from other ECs participating on the protocol
• Statement of planned tasks
• Letter of intention for cooperation
• Letter of commitment on the reliability of research materials
• Scientific opinions
• Statement of no conflict of interest
• Proof of the source of biological samples and information data
• Site list
• Site profile(s)
• Product literature
• Insurance policy (if any)
• Materials provided to participants
• Information on the lead research investigator; the legal qualification certificate of the institution; and the source of research funding
• Recruitment advertisements and their release forms
• An explanation of the form of publication of research results
• Other relevant materials that the EC believes need to be submitted

Clinical Protocol

As delineated in the NMPA-GCP-No57-2020 and the ICH’s Guideline for Good Clinical Practice E6(R2) (CHN-37), the clinical protocol should include the following elements (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• General information
• Background information
• Trial topic, purpose(s), and objective(s)
• Sponsor name and address
• Trial site location
• Principal investigator(s) name(s), qualification(s), and address(es)
• Trial design, random selection method, and blinding level
• Inclusion criteria; participant treatment, inclusion, exclusion, and release procedures; and method of grouping participants
• Form, dosage, route, method, and frequency of administration; treatment period; usage order of concomitant medicines; and packaging and labeling description
• Investigational product registration, usage record, delivery, handling and storage conditions (See Investigational Products topic for detailed coverage of this subject)
• Efficacy assessment
• Safety assessment
• Statistics
• Direct access to source data/documents
• Quality control/quality assurance
• Ethics
• Data handling/recordkeeping
• Financing/insurance
• Clinical observations, on-site visits, and measures to ensure the participant’s compliance with trial procedures
• Rules regarding clinical trial termination and completion
• Adverse event recording requirements, and serious adverse event reporting methods (See Safety Reporting section for additional information)
• Proposed trial schedule and completion date
• Publication policy

For complete protocol requirements, please refer to Chapter 6 of the NMPA-GCP-No57-2020 and Section 6 of CHN-37.

Regulatory Authority Requirements

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

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

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

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

Ethics Committee Requirements

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

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

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

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

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

Clinical Protocol

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

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

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

Overview

As stated in the DRR, ethics committee (EC) review may be submitted parallel to the National Medical Products Administration (NMPA) review, but the study cannot be initiated until after review and approval by the EC.

Per the NHC-HGRmgt, the National Health Commission (NHC) is responsible for China’s management of human genetic resources (HGR). (Note that per SC-Order777 and NHC-HGRmgt, management of HGR was transferred from the Ministry of Science and Technology (MOST) to NHC, effective May 1, 2024). The Bioscrty-Law, the MgmtHumanGen, and the Rules-MgmtHGR, delineate that MOST (now the NHC) is responsible for China's management of HGR, which includes reviewing and approving research. Per the Rules-MgmtHGR, the collection, preservation, use, and external provision of China’s HGR must comply with ethical principles and pass the ethics review of ECs that have been registered with the relevant management departments. As part of the application filing for international cooperative clinical trials, NMPA approvals, notices, and/or filing registration must be obtained in advance. In addition, EC approvals must be submitted with the filing, so therefore cannot occur in parallel. (Please note that SC-Order777 amends the MgmtHumanGen to reflect the transfer of HGR management from MOST to the NHC, but the Bioscrty-Law and the Rules-MgmtHGR have not been amended to show the transfer.)

Regulatory Authority Approval

National Medical Products Administration

Per the DRR, upon application submittal, the NMPA will complete the administrative examination for completeness within five (5) days of receiving the application, and issue a notice of acceptance. If the application does not meet the technical requirements for review, the NMPA will notify the applicant, who must submit the additional information within five (5) days of the notice. According to CHN-14, the NMPA will process clinical trial applications within five (5) working days if the study falls within the scope of its authority; the application materials are complete and comply with the legally-prescribed format; and the applicant submits all supplementary application materials in accordance with the NMPA’s requirements. Per the DRR, the NMPA-No50-2018, and CHN-14, a clinical trial application will be considered approved after 60 working days if the applicant does not receive a rejection or an inquiry for clarification from the NMPA. These procedures do not apply in every situation and additional reforms are provided below.

The DRR indicates that the following is not included in the above time limits:

• Time taken by the applicant for supplementary information, rectification after verification, and verification of production processes, quality standards, and instructions as required
• Delays in the time of verification, inspection, and expert consultation meetings
• If the review and approval procedure is suspended, the time occupied during the period of suspension of the review and approval procedure
• Time taken by the initiation of overseas verification

The application review by the Center for Drug Evaluation (CDE) and inspections and testing by National Institutes for Food and Drug Control (NIFDC) can affect the timeline beyond 60 days, as needed. The CDE conducts technical reviews and the NIFDC tests drug samples. The NMPA-No51-2023 specifies that if necessary, an expert consultation meeting may be held. For clinical trials that are approved after review, the technical review team’s conclusion and associated "Clinical Trial Approval Notice" must clearly state the indications, clinical trial protocol title, number, version number, version date, etc. The review team’s conclusion and notice may propose revisions or suggestions to the clinical trial protocol if necessary. For clinical trial protocols that require revisions, CDE will notify the applicant through a professional inquiry letter, clearly informing the applicant of the problems and revision opinions in the current protocol. The applicant must submit a revised clinical trial protocol within five (5) days, following the guidance in the Prcdrs-Changes.

According to the NMPA-No82-2020, the NMPA timelines for review and decisions for expedited applications are as follows: The CDE will review the application for breakthrough drug procedures submitted by the applicant and, if necessary, organize an expert advisory committee for demonstration. The CDE must report the review results to the applicant within 45 days after receiving the application. If it is necessary to extend the review time limit, the extended time limit must not exceed one-half of the original review time limit. The CDE must publicize the specific information and reasons for the types of drugs to be included in the breakthrough therapy program, including the name of the drug, the applicant, the proposed indication (or functional indication), the application date, and the reason for the proposed inclusion. If there is no objection within five (5) days of the public announcement, it will be included in the breakthrough treatment drug program; if an objection is raised against the publicly announced product, a written opinion must be submitted to the CDE within five (5) days; the CDE must organize another review and make a decision within 15 days and notify all relevant parties.

Per the NMPA-No79-2018, for applications to conduct clinical trials with drugs treating rare diseases with urgently needed drugs already on the market in the United States, Europe, and Japan in the past decade, the CDE completes the technical review within three (3) months after acceptance; for other overseas new drugs, the technical review is completed within six (6) months after acceptance.

The NMPA-No21-2024 describes NMPA’s pilot work plan for optimizing the review and approval of clinical trials for innovative drugs. This initiative aims to review and approve innovative drug clinical trial applications within 30 business days (a reduction from the 60 days as described above in the normal procedures). The applicant must initiate the clinical trial within 12 weeks after the approval of the clinical trial application. The pilot work will last for one (1) year and the experience of the pilot work will be summarized in July 2025. For application and eligibility details see NMPA-No21-2024 and Scope of Assessment section.

For additional details on other expedited review pathways, see the Scope of Assessment section.

National Health Commission

Per the HGR-AppGuide, for HGR license applications, the NHC will pre-screen the electronic application to ensure it is complete. If the application does not pass, then the applicant will have one (1) opportunity to correct the submission. Per Rules-MgmtHGR, MOST (now the NHC) must make an administrative licensing decision on HGR license applications within 20 working days of acceptance. HGR-AppGuide reiterates the 20 working-day deadline by NHC, the agency currently authorized to approve HGC licenses. The Rules-MgmtHGR states that where an administrative licensing decision cannot be made within 20 working days, it may be extended by 10 working days with the approval of MOST (now the NHC), and the reason for the extension must be notified to the applicant. If it is necessary to conduct hearings, inspections, testing, quarantine, appraisals, and technical reviews, this additional time required must not be counted within the time limit, and the applicant must be notified in writing of the required time.

Ethics Committee Approval

In accordance with the Measures-Ethics, the EC must carry out an ethics review and issue its opinion within 30 days of acceptance. In urgent situations, an ethics review must be promptly carried out. In the case of emergencies such as outbreaks, ethics reviews and review opinions are generally carried out within 72 hours, and the requirements and quality of ethics reviews must not be reduced. Per the NMPA-GCP-No57-2020 and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CHN-37), the institutional EC should review a proposed clinical trial within a reasonable time. The EC’s recommendations should be issued in writing and should indicate an approval; an approval after necessary modifications have been made; a disapproval; or a decision to terminate or suspend an already approved trial.

Overview

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

Regulatory Authority Approval

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

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

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

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

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

Enabled Pre-Assessment Support Unit (UHAP) Evaluations

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

Ethics Committee Approval

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

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

Overview

Per the DRR, clinical trials must be conducted in institutions conducting drug clinical trials that comply with relevant regulations, and abide by the NMPA-GCP-No57-2020, including written approval from the ethics committee (EC) to the researcher before clinical trial implementation. Further, clinical trials of vaccines must be implemented or organized by China’s designated three-level medical institutions or disease prevention and control institutions at or above the provincial level that meet the prescribed conditions.

Per the NHC-HGRmgt, the National Health Commission (NHC) is responsible for China’s management of human genetic resources (HGR). (Note that per SC-Order777 and NHC-HGRmgt, management of HGR was transferred from the Ministry of Science and Technology (MOST) to NHC, effective May 1, 2024). The Bioscrty-Law, the MgmtHumanGen, and the Rules-MgmtHGR delineate that MOST (now the NHC) is responsible for China's management of HGR, which includes reviewing and approving research before initiation. Per the Rules-MgmtHGR, clinical trials involving the collection, preservation, use, and export of China’s HGR must be approved by ECs in the relevant institutions. Further, applications for administrative licenses for international cooperation clinical trials (without exports) using HGR must pass an ethics review in the partner countries and be filed with MOST (now the NHC) before initiating the study. The Rules-MgmtHGR also state that clinical trial applications must pass a security review organized by MOST (now the NHC) if the study’s provision or opening of HGR information to foreign entities may impact China’s public health, national security, or the social public interest.

Clinical Trial Agreement

As delineated in the NMPA-GCP-No57-2020 and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CHN-37), the sponsor must sign an agreement or contract with the participating institution(s). The NMPA-GCP-No57-2020 also states that before the trial begins, the sponsor and the investigator must sign a written agreement regarding the trial protocol, monitoring, auditing, and standard operating procedures, as well as each party’s responsibilities during the trial.

Per the NMPA-GCP-No57-2020, the agreement must include the following elements:

• Compliance with this specification and relevant clinical trial laws and regulations during the implementation of clinical trials
• Implementation of the trial protocol agreed to by the sponsor and investigator, and approved by the EC
• Compliance with data recording and reporting procedures
• Consent to supervision and inspection
• Retention period of necessary documents related to clinical trials
• The agreement on publishing articles and intellectual property rights

Clinical Trial Registration

Per the DRR, the sponsor must register the drug clinical trial plan and other information on the drug clinical trial registration and information disclosure platform before launching the drug clinical trial. The NMPA-No9-2020 requires the National Medical Products Administration (NMPA)'s Center for Drug Evaluation (CDE) to establish and maintain this registry (CHN-53). Before starting a clinical trial, the clinical trial information must be registered in any of these situations:

• The clinical trial has been approved by the NMPA
• The clinical trial of a chemical drug bioequivalence test was recorded and the record number obtained
• Phase IV clinical trials and post-marketing studies were conducted in accordance with the requirements of the drug registration certificate or NMPA notice
• Other situations required for registration according to the NMPA

Also see the handling guideline for clinical trial registration (CHN-13) for more information and frequently asked questions.

Governance

Pursuant to the NHC-ClinProjMgmt, medical institutions must develop internal rules and standard operating procedures (SOPs) for administering clinical studies; centralize financial management of clinical study projects; and maintain a project-based approval system and supervision throughout the study process. In addition to having an EC, medical institutions must also establish a Clinical Study Administration Committee and a subordinate body, and a Clinical Study Administration Division to handle daily project administration. For detailed requirements, see the NHC-ClinProjMgmt.

Overview

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

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

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

Clinical Trial Agreement

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

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

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

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

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

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

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

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

Clinical Trial Registration

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

Governance

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

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

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

Safety Reporting Definitions

In accordance with the NMPA-GCP-No57-2020, the following definitions provide a basis for a common understanding of China’s safety reporting requirements:

• Adverse Event (AE) – All adverse medical events that occur after participants receive the experimental drugs. They can be manifested as symptoms and signs, diseases, or abnormal laboratory tests, but they may not be causally related to the experimental drugs
• Serious Adverse Event (SAE) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization, results in persistent or significant disability or incapacity, or causes a congenital anomaly/birth defect after the participant receives the experimental drug during a clinical trial
• Adverse Drug Reaction (ADR) – Any adverse or undesired reactions that may be related to the experimental drugs that occur during clinical trials. There is at least a reasonable possibility of the causal relationship between the experimental drug and the adverse event (i.e., the correlation cannot be ruled out)
• Suspicious and Unexpected Serious Adverse Reactions (SUSAR) – Suspicious and unexpected serious clinical manifestations that exceed the existing information, such as the Investigator's Brochure (IB) of the trial drug, the instructions of the marketed drug, or the summary of product characteristics

In addition, the G-SftyRptStds includes “Serious Adverse Drug Reactions” (SADRs) as well as other important medical events, which require medical judgement to determine if measures are needed to prevent the occurrence of one (1) of the preceding.

See the NMPA-No31-2024 for NMPA’s guidance on evaluating the correlation between AEs and drugs used in clinical trials.

Safety Reporting Requirements

Investigator Responsibilities

Per the NMPA-GCP-No57-2020, the investigator should immediately report all SAEs in writing to the sponsor, and then provide a detailed and written follow-up report in a timely manner. However, this does not include SAEs that do not need to be reported immediately per the trial protocol or other documents (such as the investigator’s brochure). SAE reports and follow-up reports should indicate the participant’s identification code in the clinical trial, not the participant’s real name, citizenship number, and residential address. AEs and abnormal laboratory values that are important for the safety evaluation specified in the test plan must be reported to the sponsor in accordance with the requirements and time limit of the test plan. For reports involving deaths, the investigator should provide the sponsor and the ethics committee (EC) with other required information, such as autopsy reports and final medical reports.

The Measures-Ethics state that for research that has been approved for implementation, researchers must immediately report SAEs that occur during the research process to the EC. The EC must conduct a timely review to determine whether the measures taken by researchers to protect the personal safety and health rights and interests of research participants are adequate, reassess the risk-benefit ratio of the research, and issue review opinions.

Sponsor Responsibilities

Per the DRR, the sponsor must regularly submit a safety update report to the National Medical Products Administration (NMPA)'s Center for Drug Evaluation (CDE) via the Applicant’s Window (CHN-58). The safety update report during the research and development period should be submitted once a year, and within two (2) months after the full year following approval of the drug clinical trial. The CDE may require the sponsor to adjust the reporting cycle based on the review situation. Additional guidance on the safety update report is provided in the NMPA-No7-2020 and the NMPA-No65-2021. For international multicenter clinical trials, NMPA-No2-2015 states that sponsors should unify the collection and evaluation methods of AEs, use a unified glossary to code AEs, and establish a unified safety database for the collection and evaluation of SAEs. AE or SAE reports should comply with the relevant national and regional requirements.

The DRR requires the sponsor to report SUSARs and other potentially serious safety risks to the CDE in a timely manner in accordance with relevant requirements. The NMPA-GCP-No57-2020 and the G-SftyRptStds specify that the sponsor is responsible for the safety assessment of the drugs during the trial period. The G-SftyRptStds and the NMPA-No65-2021 state that during the clinical trial, the sponsor judges whether SUSARs are related to the drug. When the sponsor and the investigator cannot agree on the causal relationship between the AE and the drug, the experimental drug should not be ruled out and it must be reported. Also see NMPA-No102-2019 for guidelines on classifying AEs in clinical trials of investigational vaccines.

The NMPA-No16-2023 and the NMPA-No5-2020 state that a sound pharmacovigilance system should be established to monitor safety risks during drug clinical trials, which should include comprehensive drug data collection and risk monitoring, identification, assessment, and control. In addition, safety problems and risks should be discovered in a timely manner, and necessary risk management measures should be taken proactively, such as adjusting clinical trial plans, and suspending or terminating clinical trials, etc. The NMPA-No5-2020 provides guidance on evaluating and managing safety issues and requires sponsors to actively cooperate with clinical trial institutions and other relevant parties to strictly implement the main responsibility of safety risk management.

The NMPA-GCP-No57-2020 requires the sponsor to promptly notify the investigator, the clinical trial institution, and the drug regulatory authority of issues discovered in the clinical trial that may affect the safety of participants, the implementation of the clinical trial, and the consent of the ECs. Further, the sponsor must promptly report SUSARs to all participating investigators, clinical trial institutions, and ECs; sponsors must also report SUSARs to drug regulatory and health authorities. The NMPA-GCP-No57-2020 states that after receiving safety information from the sponsor, the investigator should sign the documentation and consider whether to treat the participant and make corresponding adjustments to the protocol.

The NMPA-No65-2021 and the G-SftyRptStds specify reporting timelines for unexpected death or serious life-threatening adverse reactions. The sponsor must submit the report as soon as possible after first learned, but not more than seven (7) days; and detailed follow-up information should be submitted within the next eight (8) days. For SUSARs, the report should be submitted as soon as possible after the first notification, but not more than 15 days. In addition to individual SUSAR reports, other potentially serious safety risk information should be reported to the CDE as soon as possible, and medical treatments should be decided upon for each situation. Generally, information that significantly affects the evaluation of the drug’s risks and benefits, changes in drug usage, or information that affects the overall drug development process, falls into this category. Domestic and foreign safety reports should be reported in Chinese. Further, the DAL states that if there is a safety problem or risk during the clinical trial, the sponsor must adjust the clinical trial plan, suspend or terminate the clinical trial, and report the issue to the NMPA.

See NMPA-No60-2021 for guidance on writing safety reference information in the investigator’s manual.

Form Completion & Delivery Requirements

As per the NMPA-No50-2018, the NMPA-No10-2018, and the G-SftyRptStds, investigators must comply with the rapid reporting requirements in the International Council for Harmonisation (ICH)’s E2A Guideline, Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (CHN-39), and ICH E2B(R3), Electronic Transmission of Individual Case Safety Reports (CHN-40). As indicated in the G-SftyRptStds, all SUSARs from clinical trials should be reported in compliance with E2A and E2B(R3). To comply with these requirements, the project’s electronic safety database must meet the E2B(R3)’s XML format and be submitted to the CDE in Chinese (CHN-58). Potentially serious security risks can be sent as a “Quick Report” through e-mail to: lcqjywjj@cde.org.cn. See NMPA-No17-2023 for frequently asked questions and answers related to rapid safety reporting. Additional questions pertaining to rapid reporting can be sent to ywjjxtwt@cde.org.cn.

According to the NMPA-No230-2015, in clinical trials of new drugs, which now only require a one-time approval, after the completion of Phase I and Phase II trials, the applicant should submit all test results and demonstrate that no safety problems were found before beginning the next phase of the trial. Furthermore, NMPA-No230-2015 states that the applicant must submit all adverse event data on time.

Safety Reporting Definitions

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

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

Safety Reporting Requirements

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

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

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

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

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

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

Investigator Responsibilities

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

Other Safety Reports

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

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

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

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

Form Completion & Delivery Requirements

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

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

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

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

Interim and Annual Progress Reports

The NMPA-GCP-No57-2020 and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CHN-37) require the investigator to submit an annual report on the clinical trial to the ethics committee (EC). In addition, the investigator must provide a progress report in accordance with requirements established by the EC. When there is a situation that significantly affects the implementation of clinical trials or increases the risks to participants, the investigator should report it in writing to the sponsor, the EC, and the clinical trial institution as soon as possible. The Measures-Ethics reiterates that the researcher must submit progress reports. The NMPA-No2-2015 requires sponsors and researchers to submit the progress of international multicenter clinical trials to the EC, including but not limited to enrollment, important decisions of the independent data supervision committee (if applicable), and safety information in their own countries and other countries/regions, so as to facilitate the EC’s understanding of the overall situation of the trial, conduct follow-up reviews, and protect the safety and rights of participants.

According to the NMPA-No230-2015, in clinical trials of new drugs, which now only require a one-time approval, after the completion of Phase I and Phase II trials, the applicant should submit all test results and demonstrate that no safety problems were found before beginning the next phase of the trial. Furthermore, NMPA-No230-2015 states that the applicant must submit an annual report on time.

CHN-37 states that the investigator should promptly provide written reports to the sponsor and the institutional EC on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants. In addition, the investigator should submit written summaries of the trial status to the institutional EC annually, or more frequently, if requested by the institutional EC. Per the Measures-Ethics researchers must promptly submit reports on suspension, termination, and completion to the EC.

Final Report

Per the NMPA-GCP-No57-2020, after the clinical trial is completed, the investigator must report to the clinical trial institution. The investigator must provide the EC with a summary of the clinical trial results and provide the sponsor with the clinical trial related reports required by the drug regulatory authority. Per the DRR, the sponsor must register clinical trial results on the Applicant’s Window (CHN-58).

Interim and Annual Progress Reports

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

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

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

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

Final Report

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

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

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

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

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

As per the DRR, the NMPA-GCP-No57-2020, and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CHN-37), a sponsor is defined as a company, institution, or organization that initiates a clinical trial, and is responsible for managing, financing, and monitoring the trial. The DRR further specifies that the enterprise or institution applicant must be able to bear corresponding legal responsibilities. Per the DRR, applicants who are approved to carry out clinical trials of drugs are referred to as “sponsors” of clinical trials. If the sponsor changes, the changed sponsor must bear the relevant responsibilities and obligations of the drug clinical trial.

Per the NMPA-GCP-No57-2020 and CHN-37, a sponsor can authorize a contract research organization (CRO) to carry out certain work and obligations regarding the clinical trial. The sponsor can entrust part or all of the work and tasks of its clinical trial to the CRO, but the sponsor is still the ultimate person responsible for the quality and reliability of the clinical trial data and should supervise the various tasks undertaken by the CRO. The CRO must implement quality assurance and quality control measures. Any work entrusted by the sponsor to the CRO must be documented in a signed agreement. The sponsor is still responsible for work and tasks that are not clearly entrusted to the CRO. The requirements for sponsors in this specification apply to CROs that undertake the work and tasks related to sponsors.

A sponsor may be domestic or foreign; however, per the DRR and CHN-11, a Chinese legal entity must submit the clinical trial application.

Per the DAL, the sponsor is also referred to as the “holder” of the drug registration certificate, which is an entity that has obtained a drug registration certificate and includes institutions that are responsible for clinical trials. The legal representative and principal person holding the drug registration certificate is fully responsible for the quality of the drug used in a clinical trial. When the holder of the certificate is an overseas entity, their designated legal person in China must fulfill the same obligations as the holder of the drug registration certificate and bear joint and several liability with the holder of the drug registration certificate.

Definition of Foreign Entities in Regard to Collecting or Preserving Human Genetic Resources

For purposes of obtaining a human genetic resources (HGR) license, the HGR-AppGuide defines foreign entities as institutions established or actually controlled by overseas organizations or individuals including the following:

• A foreign organization or individual that holds or indirectly holds more than 50% of the shares, equity, voting rights, property shares, or other similar interests of an institution
• A foreign organization or individual that holds or indirectly holds less than 50% of the shares, equity, voting rights, property shares, or other similar rights and interests of the institution, but the voting rights or other rights and interests they enjoy are sufficient to control or exert significant influence on the decision-making, management, and other behaviors of the institution
• Foreign organizations or individuals, through investment relationships, agreements, or other arrangements, are able to control or exert significant influence on the decision-making, management, and other behaviors of the institution
• Other circumstances prescribed by laws, administrative regulations, and rules.

The HGR-AppGuide indicates that domestically-invested actual controlling institutions located in Hong Kong and Macao are regarded as Chinese units.

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

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

Overview

Per the DRR, drug clinical trials must be conducted in institutions conducting drug clinical trials that comply with relevant regulations and abide by the clinical trial quality management standards. As set forth in the NMPA-GCP-No57-2020 and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37), the sponsor is responsible for selecting the investigator(s) and institution(s) for the clinical trial, taking into account the appropriateness and availability of the study site and facilities. The sponsor must also ensure that the investigator(s) are qualified by training and experience. 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 (IB). Additionally, the sponsor must define and allocate all study related duties and responsibilities to the relevant parties participating in the study. Furthermore, the sponsor must sign an agreement or contract with the participating institution(s). The NMPA-GCP-No57-2020 indicates that for clinical trials involving multiple institutions, the sponsor must be responsible for selecting the team leader unit. (See the Submission Content section for additional information on clinical trial application requirements). See the NMPA-GCP-No57-2020 for additional details on investigator and clinical trial institution requirements.

The NMPA-GCP-No57-2020 states that investigators and clinical trial institutions must possess the appropriate qualifications, training, and experience to assume responsibility for the trial. Further, they must be familiar with the trial protocol, IB, and related materials and information provided by the sponsor. They must be familiar with and abide by clinical trial regulations and laws and keep an authorization form for the division of responsibilities signed by the investigator. Researchers and clinical trial institutions must accept the supervision and inspection organized by the sponsor as well as by the National Medical Products Administration (NMPA). In addition, with the sponsor’s consent, investigators and clinical trial institutions can authorize qualified individuals or units to undertake clinical trial-related responsibilities and functions.

With regard to institutions, the DRR further delineates that drug clinical trials must be conducted in institutions that have the corresponding required conditions and are registered. For example, vaccine clinical trials must be implemented or organized by China’s designated three-level medical institutions or disease prevention and control institutions at or above the provincial level that meet the required conditions.

Institutional Registration

Per the SC-Opinions-No42 and the NMPA-NHC-No101-2019, the NMPA adopted a registration system for institutions with qualifying conditions to be entrusted to conduct clinical trials and operate ethics committees (ECs). This reform eases institutional burdens by removing the pre-approval accreditation requirements. Among other conditions, the NMPA-NHC-No101-2019 specifies that an institution is entrusted to conduct clinical trials if the main investigators of clinical trials have senior professional titles and have participated in more than three (3) clinical trials. The main investigator must supervise the implementation of drug clinical trials and the performance of each researcher in the performance of their work duties and take measures to implement the quality management of drug clinical trials to ensure the reliability and accuracy of the data. Institutions conducting drug clinical trials must submit a work summary report of clinical trials in the previous year before January 31 of each year. NMPA-No1-2024 provides guidance and templates to institutions conducting drug clinical trials on filling out this annual work summary report. NMPA-NHC-No101-2019 indicates that the NMPA is establishing a record management information platform for the registration and operation management of institutions conducting drug clinical trials, as well as the supervision and inspection by drug regulatory agencies.

For additional details on the registration conditions, operations management, supervision, and inspection of institutions, see the NMPA-NHC-No101-2019. Also see CHN-12 for additional details on registering institutions to carry out clinical trials in China.

Foreign Sponsor Responsibilities

The DRR requires foreign applicants/sponsors to designate Chinese legal entities to handle relevant drug registration matters.

Per the NHC-HGRmgt, the National Health Commission (NHC) is responsible for China’s management of human genetic resources (HGR). (Note that per SC-Order777 and NHC-HGRmgt, management of HGR was transferred from the Ministry of Science and Technology (MOST) to NHC, effective May 1, 2024).

Per the Rules-MgmtHGR, when data or information on human genetic resources (HGR) is provided or made available for use by foreign organizations, individuals, and institutions, the Chinese entity must notify MOST (now the NHC) in advance and may be required to pass a security review. The notification must report on the following:

• The purpose and use of providing or opening up the use of China’s HGR information to foreign entities
• The HGR data and backup copy of the information
• The basic circumstances of the foreign entities receiving the HGR information
• Risk assessments for the protection of Chinese HGR to foreign entities

This notification is not required during international scientific research that is licensed/recorded, where the Chinese unit provides the foreign party with information on HGR generated by the cooperation, and if the international cooperation agreement has stipulated that it will be used by the two (2) partners.

Note, that the Rules-MgmtHGR adopts a broad definition of “foreign units” that includes foreign organizations and institutions, as well as entities established or under “actual control” by foreign entities or individuals. See the Rules-MgmtHGR and Rules-MgmtHGR-Interp for specific guidelines for determining actual control.

Data and Safety Monitoring Board

The NMPA-GCP-No57-2020, CHN-37, and the NMPA-No65-2021 recommend establishing a Data and Safety Monitoring Board (DSMB) to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial. The EC-Guide indicates that any DSMB reports should be submitted to the EC during follow-up reviews, if applicable.

As delineated in G-SftyRptStds and the NMPA-No65-2021, the sponsor should appoint fulltime staff to monitor clinical trial safety information and manage serious adverse event reporting. Relevant standard operating procedures should be established, and all relevant personnel should be trained. The sponsor is also responsible to ensure staff understand the latest security information, conduct timely risk assessments, provide relevant information to inform participants and interested parties, and quickly report unexpected serious adverse reactions. Annex 3 to NMPA-No50-2018 requires that application materials for Phase I clinical trials focus on participant safety and describe the establishment of a drug safety committee and a pharmacovigilance system based on the clinical trial protocol.

NMPA-No2-2015 states that in large-scale international multicenter drug clinical trials, the establishment of independent data monitoring committees and endpoint determination committees for key indicators is usually considered. For critical clinical trials with relatively large sample sizes and relatively long research times, especially those driven by clinical events, it is necessary to establish an independent data supervision committee and establish clear working mechanisms and procedures. NMPA recommends that for studies in which Chinese patients account for more than 2%, Chinese experts be included in the global core independent data monitoring board. For situations where human factors may affect the determination of research results, such as international multicenter drug clinical trials where imaging evaluation results are the key evaluation endpoints, it is necessary to establish a unified endpoint judgment committee for the main research indicators to uniformly conduct independent evaluation and judgment of the main research indicators.

Multicenter Studies

Per NMPA-No2-2015, for international multicenter drug clinical trials, sponsors should ensure that investigators have the qualifications and ability to undertake the clinical trial. Sponsors should provide unified training for researchers, including training on clinical trial protocols, standard operating procedures, test record forms, computer use, etc. The training should clearly explain and translate various definitions; unify diagnosis, efficacy, and safety evaluation indicators; and ensure the consistency of researchers' understanding of clinical trial protocols and evaluation of relevant indicators.

In accordance with the NMPA-GCP-No57-2020 and CHN-37, to carry out multicenter clinical trials, the sponsor must ensure that all centers participating in the clinical trial comply with the trial protocol. The NMPA-GCP-No57-2020 specifies additional sponsor requirements:

• Provide the same test plan to each center; each center must comply with the same unified evaluation standards for clinical and laboratory data and instructions for filling out the case report form (CRF)
• Ensure each center uses the same CRF to record the test data obtained in clinical trials
• Indicate in the trial protocol if the investigator needs to increase the collection of experimental data, and provide the investigator with an additional CRF
• Develop a written document clarifying the responsibilities of the investigators in each center before the start of the clinical trial
• Ensure communication among researchers in each center

The NMPA-No35-2017 delineates that researchers can conduct Phase I of multi-regional clinical trials (MRCT) of imported investigational new drugs and therapeutic biological products (excluding vaccines) simultaneously in China. Upon completion of a MRCT in China, the marketing application of the imported drug can be submitted immediately and should comply with the DRR. See Submission Content section.

Overview

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

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

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

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

Foreign Sponsor Responsibilities

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

Data Safety Monitoring Board

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

Multicenter Studies

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

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

Insurance

As set forth in the NMPA-GCP-No57-2020, the sponsor is responsible for providing the investigator and clinical trial institution with legal and economic insurance or a guarantee related to the clinical trial, which must be compatible with the nature and degree of risk of the clinical trial. This insurance should not include damage caused by the investigator and the clinical trial institution itself. The International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (CHN-37) guides sponsors on providing insurance. See CHN-11 for an analysis of clinical trial insurance in China.

Per NMPA-No2-2015, for insurance provided by overseas insurance companies in international multicenter clinical trials, the sponsor should ensure that participants in China can effectively and fully claim compensation, and give priority to protecting the rights and interests of participants.

Compensation

Injury or Death

Per the Measures-Ethics, when research participants suffer research-related damages, they must receive timely and free treatment, and they must be compensated in accordance with laws and regulations and the agreement of both parties. In accordance with the NMPA-GCP-No57-2020 and the EC-Guide, the sponsor must take appropriate measures to ensure that the participants and researchers can be compensated. The sponsor must bear the costs of diagnosis and treatment for the damage or death of the participant related to the clinical trial, as well as the corresponding compensation. Further, the sponsor must provide free trial drugs to participants and pay for medical testing related to clinical trials.

In addition, CHN-37 provides guidance to sponsors on providing compensation to research participants in the event of trial-related injuries or death. The sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries.

Trial Participation

Per Measures-Ethics, research participants must not be charged research-related fees, and appropriate compensation must be given to the research participants for reasonable expenses incurred in the course of the research process.

Insurance

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

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

Compensation

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

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

Injury or Death

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

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

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

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

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

Trial Participation

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

Quality Assurance/Quality Control

Per the DRR, the management of drugs used in clinical trials must comply with the clinical trial quality management regulations specified in NMPA-GCP-No57-2020. As stated in the NMPA-GCP-No57-2020 and the NMPA-No65-2021, the sponsor must establish quality control (QC) and quality assurance (QA) systems for the clinical trial. The NMPA-GCP-No57-2020 and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37) specify that the quality management system for clinical trials should cover the entire process of clinical trials, including the design, implementation, recording, evaluation, result reports, and filing of clinical trials. NMPA-No65-2021 reiterates that sponsors must establish a quality management and pharmacovigilance system for investigational products (IPs). This system must collect safety information, monitor risk, identify and control safety problems in a timely manner, proactively take necessary risk control measures, and evaluate the effectiveness of risk control measures to protect participant safety.

Per the NMPA-GCP-No57-2020, quality management includes effective trial plan design, data collection methods and procedures, and information collection necessary for decision-making in clinical trials. The QA and QC methods for clinical trials should be consistent with the inherent risks of clinical trials and the importance of the information collected. Sponsors should ensure the operability of all aspects of clinical trials and avoid over-complication of trial procedures and data collection. The trial protocol, case report form (CRF), and other related documents should be clear, concise, and consistent. During an inspection by the National Medical Products Administration (NMPA), both the research and management teams should send personnel to participate.

The sponsor must conduct quality management based on risk. The key links and data that protect the rights and safety of participants and ensure the reliability of clinical trial results must be clearly defined when the sponsor formulates the trial plan. Risk should be considered from two (2) levels: 1) system level, such as facilities and equipment, standard operating procedures (SOPs), computerized systems, personnel, and suppliers; and 2) clinical trial level, such as trial drugs, trial design, data collection and recording, and the informed consent process. The risk assessment should consider the possibility of errors under existing risk control; the impact of the errors on the protection of participants’ rights and safety; and the extent to which the errors have been monitored. Control measures to reduce risks should be embodied in the design and implementation of the test plan, the monitoring plan, the contract with parties, SOPs, and various trainings. During clinical trials, quality management should be recorded and communicated with relevant parties in a timely manner to promote continuous improvement of risk assessment and quality. The sponsor must regularly evaluate the risk control measures based on new knowledge and experience during the clinical trial period to ensure the effectiveness and applicability of the current quality management. In addition, the sponsor’s quality management system must meet the following requirements:

• The sponsor is responsible for formulating, implementing, and updating the SOPs related to clinical trial QA and QC systems
• The entire process of clinical trials and laboratory testing must be carried out in strict accordance with the quality management SOPs, and each stage of data processing has QC to ensure that all data are reliable and the data processing process is correct
• The sponsor must sign a contract with all relevant parties, including investigators and clinical trial institutions, to clarify the responsibilities of each party
• The contract signed by the sponsor and the relevant parties must indicate that the sponsor and the NMPA can access the clinical trial site to consult the source data, source documents, and reports

To standardize the submission of drug clinical trial data, meet the drug registration application data requirements, and improve the efficiency of drug review, the NMPA-No16-2020 provides guidance on the content and format of clinical trial data. The guidance is based on the data submission requirements of international regulatory agencies, including the Clinical Data Interchange Standards Consortium (CDISC). In addition, the NMPA-No74-2020 has details on the management of records and data that must be provided to the NMPA during clinical trials in China. It indicates that data refers to the information generated during drug development, production, operation, and use, including text, values, symbols, images, audio, pictures, maps, barcodes, etc.

Per the NMPA-No2-2015, for international multicenter clinical trials when the main efficacy and important safety evaluation indicators are laboratory evaluation indicators, it is recommended to establish a central laboratory for unified testing. The laboratory should have the corresponding clinical laboratory qualifications. Where a regional central laboratory is established, the quality control consistency verification between laboratories must be carried out regularly to ensure the consistency and reliability of experimental results.

The NMPA-No48-2018 presents quality management guidelines for Phase III clinical trials using innovative drugs. The guide addresses information the sponsor should provide to the NMPA related to the active pharmaceutical ingredient and its production, considering participants’ safety, drug characteristics, dosage form and route of administration, development stage, target population, and severity of the disease.

Finally, the NMPA has issued the following quality management and technical guidelines for conduct during clinical trials. See each of these documents, for additional details:

• NMPA-No29-2024 – guidelines for pharmaceutical research and changes to biological products during clinical trials
• Risk-Prcdr – procedures for safety information assessment and risk management during clinical trials
• DctrlzCTs-Rare – technical guidelines for decentralized clinical trials using rare disease drugs
• GeneCTs-Rare – technical guidelines for clinical trials of gene therapy products for rare diseases
• PatientCtr-Risk, PatientCtr-Imp, and PatientCtr-Design – technical guidelines for patient-centered drug clinical trials, including design and risk assessment
• NMPA-No15-2023 – technical guidelines for clinical trials of chemical compound drugs
• NMPA-No34-2022 – guidelines for protocol changes during drug clinical trials
• NMPA-No32-2022 – guidelines for clinical trials of topically administered local effective drugs
• NMPA-No31-2022 – guidelines for conduct of research with in vivo gene therapy products
• NMPA-No30-2022 – guidelines for conduct of research involving immune cell therapy products
• NMPA-No29-2022 – guidelines for conduct of research with in vitro gene modification
• NMPA-No27-2022 – guidelines for conduct of research involving specific human immunoglobulins
• NMPA-No22-2021 – a research and development model to guide researchers in managing pharmaceutical changes of innovative drugs
• NMPA-No17-2022 – guidelines for clinical pharmacological research of biosimiliars
• NMPA-No4-2022 – guidelines for research of human bioavailability of bioequivalence of innovative drugs
• NMPA-No71-2021 – guidelines for research of drugs for rare diseases
• NMPA-No68-2021 – guiding principles for writing the clinical risk management plan
• NMPA-No66-2021 – guiding principles for multiplicity issues during drug clinical trials, which refers to multiple testing problems that can lead to errors and inappropriate interpretation of trial results
• NMPA-No63-2021 – guidelines for drug clinical trial data management and statistical analysis plan
• NMPA-No62-2021 – guidelines for the application of patient-reported outcomes in drug clinical development
• NMPA-No59-2021 – guidelines for analyzing the effectiveness of clinical studies of drugs
• NMPA-No50-2021 – guidelines for long-term follow-up for clinical research of gene therapy products
• NMPA-No6-2021 – guidelines for sponsors in adopting and implementing an adaptive design to improve the success and quality of the research results
• Chngs-MktChem – technical guidelines for pharmaceutical change research of listed chemicals
• Chngs-MktChemBio – technical guidelines for clinical changes in marketed chemicals and biological products
• NMPA-No21-2021 – technical requirements of pharmaceutical research and evaluation of overseas listed and domestic unlisted chemicals
• NMPA-No54-2020 – technical guidelines for clinical trials of improved chemical drugs
• Chngs-MktBio – technical guidelines for pharmaceutical change research of marketed biological products

Per the VaccineLaw, during the research and development phase for vaccines, the sponsor must establish a biosafety management system that strictly controls biosafety risks, strengthens biosafety management of pathogenic microorganisms (e.g., bacterial strains), protects the health of operators and the public, and safeguards against bacterial toxicity. The use of pathogenic microorganisms, such as strains, is legal and legitimate. The strains and cell strains used during research and development must have clear histories, biological characteristics, and generations. Detailed documentation and archives must be established to ensure that the source is legal, clear, and traceable; if the source is unknown, then it cannot be used.

As delineated in MgmtHumanGen, for international cooperative projects using human genetic resources (HGR), the sponsor must ensure the participation of the Chinese partner. During the study period, the Chinese partner and its researchers must fully participate in the research. All records and data information in the research process, and all backup documentation, must be accessible to the Chinese partner. Both the foreign and Chinese parties have the right to use the information developed with the HGR.

Monitoring Requirements

As per the NMPA-GCP-No57-2020, the purpose of monitoring is to ensure the rights and interests of participants in clinical trials, to ensure that the data in trial records and reports are accurate and complete, and to ensure that trials comply with the agreed protocol and relevant regulations. The NMPA-GCP-No57-2020 and CHN-37 require the sponsor to establish a systematic, prioritized, risk-based method to monitor clinical trials. NMPA-GCP-No57-2020 directs the sponsor to formulate audit procedures and an inspection plan with a special emphasis on protecting the rights and interests of participants, ensuring the authenticity of data, and managing risks in clinical trials. On-site supervision and centralized supervision should be conducted based on the combination of risks of clinical trials. The audit procedures must establish objectives, methods, frequency, and format content of audit reports. All problems observed and discovered by the auditors during the inspection process must be recorded in writing. The sponsor may conduct special inspections in addition to routine inspections. The sponsor selects a person independent of the clinical trial to serve as an inspector. Inspectors must have received corresponding training and inspection experience and be able to effectively perform inspection duties.

As indicated in NMPA-No2-2015, for international multicenter clinical trials, the sponsor or the contract research organization (CRO) entrusted by the sponsor must conduct supervision of each clinical trial center, the monitoring report must be archived, and the sponsor must periodically review the monitoring work. The sponsor or the CRO must formulate an audit plan and have a unified audit report template and audit result reporting system.

Further, NMPA-GCP-No57-2020 states that researchers and clinical trial institutions must agree to supervision and inspection organized by the sponsor and the NMPA. The sponsor must provide an inspection report or certificate when requested by the NMPA. In accordance with the DRR and CHN-8, NMPA’s Center for Drug Evaluation (CDE) will make a risk-based decision on whether to conduct an inspection of a clinical trial, based on the level of drug innovation and the past verification history of the clinical trial site. See NMPA-No56-2023 for NMPA’s management measures that standardize the supervision and inspection of institutions conducting drug clinical trials. In addition, NMPA-No22-2022 indicates that sponsors have the main responsibility for pharmacovigilance inspections during the conduct of a clinical trial. See NMPA-No22-2022 for key considerations during routine and causal inspections, evaluation criteria, risk factors, inspection methods, and other inspection implementation guidance.

The NMPA-No28-2020 further clarifies the link between on-site inspection of drug registration and the pre-market good manufacturing practice (GMP) compliance inspection. Based on the innovation and risk characteristics of an IP, the pre-market GMP compliance inspection will be conducted by the appropriate level regulatory authority (i.e., the CDE, province, autonomous region, or municipality). See the NMPA-No28-2020 for detailed inspection requirements.

Also, see the NMPA-GCP-No57-2020 and CHN-37 for additional guidance on audits and inspections. See NMPA-No11-2022 for guiding principles on use of risk-based statistical evaluation methods for centralized monitoring of drug clinical trials.

Premature Study Termination/Suspension

The NMPA-GCP-No57-2020 mandates that researchers, clinical trial institutions, and sponsors abide by the trial protocol, SOPs, and relevant laws and regulations. If non-compliance is found, the sponsor must take immediate measures to correct them and ensure the clinical trials are in compliance. The NMPA-GCP-No57-2020 and CHN-37 state that when an important compliance problem is discovered that may have a significant impact on the safety and rights of participants or the reliability of clinical trial data, the sponsor must conduct a root cause analysis in a timely manner and take appropriate corrective and preventive measures.

The NMPA-GCP-No57-2020 specifies that if the trial protocol is violated or there is a serious quality problem, the sponsor must hold the relevant personnel accountable and send a written report to the NMPA at CHN-58. When it is found that the investigator or clinical trial institution has serious non-compliance problems, the sponsor must terminate the investigator or clinical trial institution from continuing to participate in the clinical trial. The sponsor should also send a written report to the NMPA. At the same time, sponsors and researchers should take corresponding emergency safety measures to protect the safety and rights of participants. A sponsor who terminates or suspends clinical trials early must immediately notify the investigator, clinical trial institutions, and the NMPA, and explain the reasons.

Further, the NMPA-GCP-No57-2020 states that when a clinical trial is completed or terminated early, the sponsor must submit a clinical trial report to the NMPA. The clinical trial summary report must comprehensively, completely, and accurately reflect the clinical trial results. The safety and effectiveness data of the clinical trial summary report must be consistent with the clinical trial source data. The Measures-Ethics indicates that for research that has been approved for implementation, researchers must promptly submit reports on suspension and termination to the EC.

Quality Assurance/Quality Control

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

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

Monitoring Requirements

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

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

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

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

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

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

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

Premature Study Termination/Suspension

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

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

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

Electronic Data Processing System

Per the NMPA-GCP-No57-2020, the sponsor must meet the following requirements in electronic data processing during clinical trials:

• Select qualified personnel to supervise data processing, data verification, statistical analysis, and the writing of trial summary reports
• Use an electronic data management system that passes reliable system verification and meets the pre-set technical performance to ensure the integrity, accuracy, and reliability of the test data, and to ensure that the system is always valid for verification during the entire test process
• Have complete standard operating procedures (SOPs) that cover the setup, installation, and use of electronic data management; the SOPs must describe the verification, functional testing, data collection and processing, system maintenance, system safety, testing, change control, data backup, recovery, and system emergency plans
• Ensure the SOPs cover the responsibilities and training of sponsors, researchers, and clinical trial institutions when using computerized systems
• Prescribe in advance the method of data modification
• Ensure that the data conversion process is consistent with the original data and visibility is maintained during the process
• Ensure the security of the electronic data management system, and that unauthorized personnel cannot access it; keep a list of persons authorized to modify data; electronic data is backed up in time; clinical trials designed by blind methods are always blinded, including data entry and processing

In accordance with NMPA-GCP-No57-2020, when the information system of a clinical trial institution has the conditions for establishing a clinical trial electronic medical record, the researcher should use it first, and the corresponding computerized system should have complete authority management and audit trails, which can be traced to the creator or modifier of the record. Researchers must supervise the data collection. They must ensure that all clinical trial data are obtained from clinical trial source documents and trial records, and are accurate, complete, readable, and timely. The source data should be attributable, legible, original, accurate, complete, consistent, and durable. The modification of the source data must be explained and transparent. Relevant medical records should be included in the outpatient or inpatient medical record system. During the processing of clinical trial information, care must be taken to avoid illegal or unauthorized access, disclosure, dissemination, modification, damage, or loss of information. The record, processing, and preservation of clinical trial data must ensure the confidentiality of records and participant information. In the contract with the investigator and the clinical trial institution, the sponsor should clarify the retention time, cost, and handling of the documents.

Per the NMPA-No2-2015, international multicenter clinical trials must adopt a unified data processing center for data query, verification, storage, and analysis.

The NMPA-No74-2020 has additional guidance and requirements for the sponsor’s electronic system.

In addition, as per the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37), when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. Per CHN-37, the sponsor should base their approach to validate such systems on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. In addition, the sponsor should maintain SOPs for the systems that cover system setup, installation, and use. The responsibilities of the sponsor, investigator, and other parties should be clear, and the system users should be provided with training. Refer to CHN-37 for additional information.

Records Management

Per the NMPA-GCP-No57-2020 and CHN-37, the sponsor must retain the clinical trial data related to the sponsor and participating parties in the clinical trial. The transfer of data ownership must comply with the requirements of relevant laws and regulations. The sponsor must send written notification to the investigator and clinical trial institution about the requirements for preserving clinical trial records and when the trial-related records are no longer needed. At the beginning of a clinical trial, the investigator, clinical trial institution, and sponsor must establish archive management of the necessary documents. At the end of the clinical trial, an inspector must review and confirm the necessary documents of the investigator, clinical trial institution, and sponsor, and these documents must be properly kept in their respective clinical trial archives. Clinical trial documents must be retained for at least five (5) years after the trial drug is approved for marketing or after the termination of the clinical trial.

In addition, the NMPA-GCP-No57-2020 emphasizes that clinical trial essential documents are important to the National Medical Products Administration (NMPA)'s inspection of the clinical trial. Sponsors, investigators, and clinical trial institutions must confirm that they have appropriate storage conditions for preserving the essential documents. SOPs for document management should be formulated. The source data or its certified copy must be kept complete and readable during the retention period. In addition, the sponsor must ensure that the investigator can always consult and enter data in the case report form (CRF) reported to the sponsor during the trial. The data should not be controlled by the sponsor alone. The photocopies used as source documents should meet the requirements for certified copies. The NMPA-No37-2020 details the essential documents required for clinical trials to prove compliance with the NMPA-GCP-No57-2020. The NMPA-No74-2020 contains additional requirements on record management during a clinical trial.

Electronic Data Processing System

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

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

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

See MEX-32 for additional data processing requirements.

Records Management

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

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

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

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

Responsible Parties

For requirements on personal data protection, the PIPL delineates that personal information processors are organizations or individuals who independently determine the purpose and method of processing personal information during personal information processing activities.

Data Protection

Per the PIPL, the personal information processor must ensure the safety of the personal information processed, including following principles of openness and transparency, disclosing personal information processing rules, and clearly indicating the purpose, method, and scope of processing. The PIPL applies to the processing of personal information in China for people located within the country. In addition, the PIPL and the DataSec-Regs apply to data processing activities conducted outside of China involving personal information of people located in China under the following circumstances: (1) where the processing is for the purposes of providing products or services to individuals located in China, (2) where the processing is for analyzing and evaluating the behavior of individuals located in China, or (3) other circumstances stipulated by laws and regulations.

Per the PIPL, the processing of personal information should have a clear and reasonable purpose and should be directly related to the purpose of processing with the least impact on personal rights and interests. The personal information processor must follow the principles of lawfulness, fairness, necessity, and good faith when processing personal information, and must not process personal information through misleading, fraudulent, coercive, and other methods. The collection of personal information must be limited to the minimum scope for the purpose of processing, and personal information must not be collected excessively, while following the principles of openness and transparency. The personal information processor must disclose processing rules and clearly indicate the purpose, method, and scope of processing. When handling personal information, the data quality must be guaranteed, and any inaccuracy and incompleteness of personal information must not adversely affect personal rights and interests. For additional data protection details see the DataSec-Regs, which supplements the PIPL.

The PIPL states that for sensitive personal information, which includes medical health information, the personal information processor must adopt additional protective measures, including informing participants of the necessity of processing sensitive personal information and the impact on personal rights and interests. Unless otherwise provided by laws and administrative regulations, the retention period of personal information must be the shortest time necessary to achieve the processing purpose. Also see the Id-SPI for guidance on identifying sensitive personal information.

Further, the DataSec-Regs states that where a network data processor provides or entrusts other network data processors to process personal information and important data, they must agree to the following:

• The recipient of network data must fulfill its obligation to protect network data security and process personal information and important data in accordance with the agreed purpose, method, scope, etc.
• If two (2) or more network data processors jointly decide on the purpose and method of processing personal information and important data, they must agree upon their respective rights and obligations.

Per the PIPL and the DataSec-Regs, to send personal information outside of China, the personal information processor must meet one (1) of the following conditions (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Pass the security assessment organized by the national cybersecurity and information department (See below in Data Security)
• Conduct personal information protection certification by professional institutions in accordance with the requirements of the Cyberspace Administration of China (CAC)
• Enter into a contract with the overseas recipient in accordance with the standard contract formulated by the CAC stipulating the rights and obligations of both parties
• Other conditions stipulated by laws, administrative regulations, or national cyberspace administration departments
• Where China’s international treaties and agreements permit providing personal information to foreign recipients
• It is necessary to provide personal information overseas to conclude or perform a contract to which the individual is a part
• To implement cross-border human resources management in accordance with labor rules and regulations formulated in accordance with the law and collective contracts signed in accordance with the law, and providing employees' personal information overseas is necessary
• It is necessary to provide personal information overseas to perform legal duties or obligations
• In an emergency, it is necessary to provide personal information overseas in order to protect the life, health, or property safety of a natural person

The PIPL states that the personal information processor must inform the participant of the name of the foreign recipient, contact information, processing purpose, processing method, and types of personal information. In addition, per the PIPL and the DataSec-Regs, the foreign personal information processor must appoint a representative located in China to be responsible for matters related to personal information protection and report the representative’s contact information to the data protection regulators—the CAC.

The DataScrty requires the personal information processor to manage its data processing activities to ensure data security, promote data development and utilization, protect the legitimate rights and interests of individuals and organizations, and safeguard national sovereignty, security, and development interests. CAC-No11-2022 standardizes requirements for exporting “important data” and personal information to protect the rights and interests of personal information, preserve national security and the societal public interest, and promote the cross-border security and free flow of data. Important data is defined as data that, once tampered with, destroyed, leaked, or illegally obtained or used, might endanger national security, economic operations, social stability, public health, or safety in China. Also see the DataSec-Regs for additional requirements on doing risk assessments and handling and reporting on important data. Personal information processors must conduct security assessments of personal data collected and generated in China before exporting it to overseas data processors. Data export security assessments focus on assessing risks that data export activities may bring to national security, the public interest, or the lawful rights and interests of individuals or organizations. The DataTrsfr-Regs delineates exemptions from the requirements to conduct security assessments, for example in an emergency where it is necessary to provide personal information overseas in order to protect the life, health, or property safety of a natural person. If DataTrsfr-Regs conflicts with CAC-No11-2022, the DataTrsfr-Regs supersede.

When applicable, the DataScrty states that the assessment report must be submitted to CAC through the provincial-level department where the personal information processor is located, and include the following materials:

• Declaration form
• Self-assessment report on data export risks
• Data agreements between the data processor and the overseas recipient

The CAC-No11-2022 states that data export activities that have already been conducted before the implementation of CAC-No11-2022 are noncompliant and must be rectified within six (6) months of the effective date of CAC-No11-2022 (i.e., by March 1, 2023). See the CAC-No11-2022 for additional details on conducting the data export security assessment, the provincial inspections, appeal procedures, and CAC’s review actions and timeline.

Consent for Processing Personal Data

Per the PIPL, personal consent must be made voluntarily and with the participants’ full knowledge of the processing purpose, processing methods, and types of personal information processed. In an emergency, if it is not possible to obtain consent in a timely manner to protect the life, health, property, and safety of participants, the personal information processor must promptly notify the individual after the emergency is eliminated. (Note: consent to data processing is not the same as informed consent to the research described in the Informed Consent topic.) As indicated in the DataSec-Regs, individual consent is defined as specific and unambiguous consent given by an individual for specific processing of their personal information.

The DataSec-Regs supplements the PIPL, adding detailed protection requirements when personal information processing is based on individual consent:

• The collection of personal information must not be collected beyond the scope, and personal consent must not be obtained through misleading information, fraud, coercion, etc.
• When processing sensitive personal information such as biometrics, religious beliefs, specific identities, and medical health the individual's separate consent must be obtained
• When processing the personal information of a minor under the age of 14, the consent of the minor’s parent/legal guardian must be obtained
• Personal information must not be processed beyond the purpose, method, type, or retention period of the personal information that the individual has consented to
• Processors must not frequently seek consent after an individual has clearly expressed their disagreement with the processing of their personal information
• If the purpose, method, or type of personal information processing changes, the individual’s consent must be obtained again
• If laws and administrative regulations provide that written consent must be obtained for the processing of sensitive personal information, such provisions must apply

Responsible Parties

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

Data Protection

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

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

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

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

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

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

Consent for Processing Personal Data

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

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

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

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

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

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

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

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

Consent for Processing Personal Data of Minors

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

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

Obtaining Consent

In all Chinese clinical trials, a freely given informed consent is required to be obtained from each participant in accordance with the requirements set forth in the NMPA-GCP-No57-2020, the Measures-Ethics, the RegEthics, and the EC-Guide. In addition, China is implementing the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37) as a guidance document. As per the NMPA-GCP-No57-2020, the DAL, the EC-Guide, and CHN-37, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an ethics committee (EC) and provided to the National Medical Products Administration (NMPA) with the clinical trial application. Per the MgmtHumanGen, the ICF must also be provided to the Ministry of Science and Technology (MOST) (now National Health Commission (NHC)) as part of its application procedures for human genetic resource (HGR) licenses. In addition, per the VaccineLaw, in carrying out a vaccine clinical trial, the investigator is required to obtain a signed ICF from the participant or legal representative/guardian. (Note that per SC-Order777 and NHC-HGRmgt, management of HGR was transferred from MOST to NHC, effective May 1, 2024).

The NMPA-GCP-No57-2020, the Measures-Ethics, and CHN-37 state that the investigator, or a person designated by the investigator, must provide detailed research study information to the participant or the legal representative/guardian. As delineated in the NMPA-GCP-No57-2020, the Measures-Ethics, and the EC-Guide, the ICF content should be briefly and clearly presented orally or, in a written language, that is easy to understand, and commensurate with the comprehension level of the research participants. The participant and the legal representative/guardian should also be given adequate time to consider whether to participate. The Measures-Ethics indicates that ICFs must contain sufficient, complete, and accurate information, and be expressed in language, text, video images, and so forth that research participants can understand. Researchers must explain each item to the research participants in accordance with the content of the ICF.

As per the NMPA-GCP-No57-2020, CHN-37, and the EC-Guide, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or the legal representative/guardian to waive or appear to waive their legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence. The investigator should give the participant sufficient time to understand the ICF content, and the participant should make a decision whether or not to agree to participate in the study and sign the form. In psychological research, because informed consent may affect the participant’s response to the question, thereby affecting the accuracy of the research results, the investigator can fully inform the participant and obtain informed consent following the project study’s completion.

Per DctrlzCTs-Rare, for decentralized clinical trials of rare diseases, electronic informed consent may be used. When electronic informed consent is used, the informed consent process needs to be recorded, archived, and traceable. For rare disease participants with limited mobility, researchers can use remote informed consent to more quickly and easily obtain consent and ensure that all participants have the latest version in a timely manner. To use electronic informed consent in these scenarios, researchers must conduct evaluation and verification in advance and provide the participants with instructions and training. Before adopting electronic informed consent, the participants should be fully informed of the scope of data collection, access rights, etc. generated during the electronic informed consent process. During the informed consent process, researchers should ensure data security and the privacy of the participants (including their legal representative/guardian) are protected.

Per the MgmtHumanGen, to collect Chinese HGR for a clinical trial, the participant must agree to participate in the clinical trial in writing. Information provided to the participant must be comprehensive, complete, true, accurate, and must not conceal information nor be misleading or deceiving.

For specific consent requirements for human genome editing research, see the Consent for Specimen section.

Re-Consent

The NMPA-GCP-No57-2020 and CHN-37 require investigators to use the latest version of the ICF approved by the EC and, if necessary, participants in the clinical trial process should sign an updated ICF again. If new information may affect the participant’s continued participation in the trial, the investigator must promptly notify the participant and the legal representative/guardian and make corresponding records. Per the RegEthics and the Measures-Ethics, the investigator should obtain re-consent under the following circumstances (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• The research plan, scope, and content have changed
• Research using previously collected samples that were used for diagnosis and treatment and were labeled with personal identifiable labels
• Research using human biological samples or related clinical disease history data with subject-identifiable labels from existing biological sample repositories/databases
• The risks related to the research are increased or substantially increased
• The level of civil capacity of research participants has been raised
• Other changes occur during the research

Language Requirements

The NMPA-GCP-No57-2020, the Measures-Ethics, the RegEthics, and the EC-Guide require the ICF to be presented in oral or written form in a language that the participant is able to understand.

Documenting Consent

Per the NMPA-GCP-No57-2020, the Measures-Ethics, CHN-37, and the EC-Guide, the participant and the legal representative/guardian, and researchers who perform informed consent, should sign and date the ICF. Per the Measures-Ethics, when the research participants do not have the ability to express their consent in writing, the researcher must obtain their oral informed consent and have audio and video recordings and other process records and supporting materials.

Per the NMPA-GCP-No57-2020, CHN-37, and the EC-Guide, if the ICF is not signed by the participant, the relationship should be marked on the form. If the participant and the legal representative/guardian lack the ability to read, an impartial witness must witness the entire informed consent process. The witness should sign and date the ICF after the following steps have occurred:

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

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

Waiver of Consent

The EC-Guide and the RegEthics state that the EC may grant a waiver of informed consent when the following conditions are met (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• The risk that the subject may suffer does not exceed the minimum.
• The exemption from obtaining the informed consent of the subject does not have a negative impact on the participant’s rights and interests.
• The use of human bodily materials or data that can identify the information for research has made it impossible to find the participant, and the research project does not involve personal privacy and commercial interests.
• The biological sample donor has signed an ICF agreeing that the donated sample and related information can be used for all medical research.
• The exemption requires informed consent and does not mean that it is exempt from the review of the EC.

Obtaining Consent

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

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

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

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

Re-Consent

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

Language Requirements

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

Documenting Consent

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

Waiver of Consent

No information is currently available regarding waiver requirements.

Based on the NMPA-GCP-No57-2020, the Measures-Ethics, the EC-Guide, the RegEthics, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37), the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• The study purpose, procedures, and duration of the trial
• 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
• The participant’s responsibilities
• The approximate number of participants involved in the trial
• Those aspects of the trial that are experimental
• Treatment available to the participant as well as important potential risks and benefits associated with this treatment
• The alternative procedure(s) or course(s) of treatment that may be available to the participant, and their important potential benefits and risks
• The nature, form, and extent of compensation for participation
• Any expenses the participant needs to pay to participate in the trial
• The extent to which confidentiality of records identifying the participant will be maintained, and a statement that, when necessary, the sponsor, the ethics committee (EC), the National Medical Products Administration (NMPA), and drug authorities in the provinces, autonomous regions, and municipalities may be required to review participant data
• The scope and method of use of research data and research participants' personal data, and whether sharing and secondary use are carried out
• Any treatment and corresponding compensation the participant can expect to receive in the event of a trial-related injury
• The participant’s rights, including 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
• Precautions and protective measures for the participant before, during, and after the research
• The foreseeable circumstances and/or reasons under which the participant's participation in the trial may be terminated
• Contact information for the sponsor and investigator in the event of participant problems or injuries related to the trial
• Basic information about the researcher and qualification of research institution
• That records identifying the participant will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. If the results of the trial are published, the participant’s identity will remain confidential
• Whether the results of the study will be provided to the research participants
• That the participant or the legally acceptable representative will be informed in a timely manner if information becomes available that may be relevant to the participant’s willingness to continue participation in the trial
• When appropriate, the EC may require the following additional information: whether the research may put the participant at risk but the risk is not currently foreseeable; researchers can terminate a participant’s participation in the study without their consent; new major discoveries during the research will be provided to the participant; and whether there is a potential conflict of interest
• If applicable, how biological samples will be handled

Per the MgmtHumanGen, to collect Chinese human genetic resources (HGR) for a clinical trial, the investigator must provide advance information to the participant on the purpose of collection, the possible health impact, the protection measures of personal privacy, their participation is voluntary, and they have the right to withdraw unconditionally at any time.

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

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