Health Canada

As per the CanadaFDA, the CanadaFDR, and the G-CanadaCTApps, Health Canada (HC) is the competent authority responsible for clinical trial approvals, oversight, and inspections in Canada. The G-CanadaCTApps states that the HC grants permission for clinical trials to be conducted in the country, and regulates the sale and importation of drugs for use in clinical trials in accordance with the CanadaFDR provisions.

As per CAN-29, HC is one (1) of five (5) federal agencies within Canada’s “Health Portfolio” overseen by the Minister of Health. As delineated in CAN-23, HC’s Health Products and Food Branch (HPFB) is the national authority that regulates, evaluates, and monitors therapeutic and diagnostic product safety, efficacy, and quality, and reviews the information submitted in the clinical trial application. Per CanadaFDA, if the Minister believes on reasonable grounds that the use of a therapeutic product, other than the intended use, may present a risk of injury to health, the Minister may, by order, establish rules in respect of the importation, sale, conditions of sale, advertising, manufacture, preparation, preservation, packaging, labeling, storage, or testing of the therapeutic product for the purpose of preventing, managing, or controlling the risk of injury to health.

Per CAN-16, HPFB’s activities are carried out by nine (9) Directorates, including the Pharmaceutical Drugs Directorate (PDD) and the Biologic and Radiopharmaceutical Drugs Directorate (BRDD). Per CAN-18, PDD regulates pharmaceutical drugs for human use. Specifically, PPD:

• Reviews scientific information to assess the safety, efficacy, and quality of a prescription drug
• Assesses the potential benefits and risks of a prescription drug
• Reviews clinical trial applications for prescription drugs to ensure that the studies are well-designed and that participants will not be exposed to undue risk
• Monitors the evolving safety of drugs in development through the review of adverse reaction reports
• Makes non-marketed drugs available to health professionals for patients when conventional therapies have failed, are not suitable, or are not available
• Provides Canadians with science-based medical information they need to make informed choices

CAN-17 indicates that the BRDD regulates biological drugs, radiopharmaceuticals, and cells, tissues, and organs for human use, including clinical trials.

In addition, the G-CanadaCTApps indicates that the PDD’s Office of Clinical Trials (OCT) and the BRDD’s Office of Regulatory Affairs (ORA), among others, are directly involved with the clinical trial review and approval process for pharmaceutical, biological, and radiopharmaceutical drugs. CAN-18 states that the PDD Director General's Office oversees pharmaceutical clinical trials. Per the G-MDSA, the Therapeutic Products Classification Committee (TPCC) may be consulted when it is not clear whether a product should be classified as a drug or device. The committee makes recommendations on the classification of a product as either a drug, medical device, or combination product. When appropriate, other regulatory areas of HC may be asked to participate in the committee's discussion.

As per CAN-41, HC has established a regulatory innovation agenda, which aims to provide more regulatory flexibility to support innovative research and health product development. For more details, see CAN-41.

International Alignment

Per CAN-10, Canada is an official member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). CAN-50 indicates that HC adopted the ICH Guideline for Good Clinical Practice E6(R3) (CAN-52). The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence. More generally, CAN-50 notes HC-implemented ICH guidance takes precedence over other HC guidance when they are inconsistent. Also see CAN-50 for details on all the ICH guidelines implemented by HC. For any questions or comments, contact HC’s ICH Coordinator via email at ich@hc-sc.gc.ca.

Contact Information

According to the G-MDSA and CAN-18, Health Canada PDD contact information is as follows (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

Office of Clinical Trials
Pharmaceutical Drugs Directorate
Health Canada
Holland Cross, Tower B
1600 Scott Street, 5th Floor
Address Locator: 3105A
Ottawa, Ontario, Canada
K1A 0K9

Phone (General Enquiries): 613-957-0368
Fax (General Enquiries): 613-952-7756
General Inquiries: oct.enquiries-requetes.bec@hc-sc.gc.ca
Pre-CTA Meeting Requests: oct.pre.cta-dec.bec@hc-sc.gc.ca (per G-MDSA)

Per G-MDSA, the following is the contact information for biologic clinical trials:

Office of Regulatory Affairs
Biologic and Radiopharmaceutical Drugs Directorate
Health Products and Food Branch
Health Canada
Tunney’s Pasture
100 Eglantine Driveway
Address Locator: 0601C
Ottawa, Ontario, Canada
K1A 0K9

Phone: 613-957-1722
E-mail: brdd.ora@hc-sc.gc.ca

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 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.

For information about China’s clinical trial reforms, see SC-Opinions-No53 and CHN-47. To implement SC-Opinions-No53, the NMPA promulgated NMPA-No86-2025 and NMPA-No40-2025, which are summarized in the applicable sections of the China profile.

National Health Commission

Per the NHC-HGRmgt, the NHC is responsible for China’s management of human genetic resources (HGR), which was previously managed by the Ministry of Science and Technology (MOST). (Note: Some HGR sources in this profile still reference MOST.)

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. See CHN-15 and CHN-33 for NHC resources related to the management of HGR for clinical trials.

The MgmtHumanGen and the Rules-MgmtHGR stipulate that 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 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. NHC is responsible for national HGR efforts such as investigation, administrative licensing, supervision and inspection, and administrative punishments. Regarding administrative licensing, licenses must be obtained for the collection and preservation of Chinese HGR and for international collaborations in certain situations. As needed, 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 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 National Center for Biotechnology Development 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 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 Biosfty-Law, the NHC regulates biotechnology safety under the National Security Commission pursuant to a Coordination Mechanism for National Biosafety (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 biosafety issues, and organize, coordinate, and drive national biosafety work. The NHC and the other agencies under CMNB establish safety monitoring/reporting requirements and an early warning system, and implement regulations.

Regarding monitoring and protecting HGR, as delineated in MgmtHumanGen, NHC 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. 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 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 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. Per NMPA-No125-2025, the NMPA is implementing the ICH Guidelines for Good Clinical Practice E6(R3) (CHN-37), to which drug clinical trials conducted after March 31, 2026 are subject.

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

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

Phone number for Comprehensive Services at the Administrative Service Hall: 010-88331866; Complaints and Reports: x12315

Per CHN-44, the following is CDE’s contact information:

National Medical Products Administration
Center for Drug Evaluation
No. 22 Guangde Street
Beijing Economic and Technological Development Zone
Beijing, 100163
P.R. China

Phone number: 010-68585566
Fax: 010-68584181

National Health Commission

Per HGR-AppGuide and CHN-4, following is the contact information for NHC’s HGR consultation (Note: The information listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

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

Phone number: 010-88225151 or 010-88225168
Email: ycb@cncbd.org.cn

Overview

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

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

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

Clinical Trial Review Process

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

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

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

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

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

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

As per the G-Dcntrl, HC requires information about decentralized elements in the clinical trial application to review whether these elements were designed to minimize risk to participants, support appropriate oversight and monitoring throughout the trial, and help achieve trial objectives. Additionally, sponsors must attest that the trial, including all decentralized elements, will be conducted according to good clinical practice (GCP). Depending on the decentralized elements and activities within the proposed trial known at the time of application, HC will review how participant visits and clinical trial activities will be conducted (e.g., in person, by telephone or telehealth platform, or through third parties or vendors). See G-Dcntrl for more details about clinical trials with decentralized elements.

As delineated in the CanadaFDA and the G-Inspections, HC is authorized to implement an inspection strategy and to ensure compliance with CanadaFDA. The G-Inspections states that HC’s Regulatory Operations and Enforcement Branch (ROEB) monitors compliance, which is assessed through inspections and other compliance and enforcement activities, such as compliance verifications. Compliance verifications of clinical trials may be initiated when there are reasonable grounds to believe that non-compliance may have occurred or is occurring and that enforcement measures may be necessary (e.g., complaints received regarding specific trials, reports of adverse drug reaction(s), or reports from other regulatory authorities). The Clinical Trial Compliance Program within ROEB is responsible for clinical trial site selection for inspections in collaboration with the PDD and the BRDD. A risk-based approach is applied in the site selection process to minimize the potential health risks inherent to clinical trials involving human participants. The selection of sites for inspection is based on a variety of criteria to select sites throughout all levels of the drug assessment and regulatory approvals process. For clinical trial sites with decentralized elements, G-Dcntrl states that the main location of the clinical trial site associated with the qualified investigator (QI) is the primary point of contact for an inspection. HC inspectors may request documentation from sponsors and QIs to demonstrate adequate coordination, oversight, and monitoring of delegated parties, as well as the measures in place to protect participant safety. See the Risk-Insp for a risk classification guide used by ROEB; this guide describes how inspectors classify risk-based observations and assign a rating, promotes consistency, and provides examples of inspection observations.

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

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

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

Expanded Access Clinical Trial

The Expd-CTs explains that in Canada, an expanded access clinical trial is a type of clinical trial that provides access to investigational products (IPs) that have the potential to treat people living with medical conditions who do not qualify for other clinical trials or are not able to participate in one. When appropriate, expanded access clinical trials can use more flexible protocols and a decentralized model to facilitate access for a larger, potentially more diverse population of participants, in more accessible settings. Since expanded access clinical trials are a type of clinical trial under the CanadaFDR, they require a CTA for review by HC. HC will review applications for the sponsor’s evidence from previous studies that the proposed use of the IP would not endanger the health and safety of participants. HC assesses all CTAs on a case-by-case basis. CTAs for expanded access clinical trials follow the same review processes and timelines as other clinical trials. HC scientists and physicians review expanded access CTAs to assess whether:

• The risks in using the drug in the trial are considered and would not endanger health and safety
• The best interests of those taking part in the trial have been considered, including that drugs are used in the right way for the participants being studied
• The goals of the trial can be met

Per the Expd-CTs, group-level access to a drug in Canada is available only through an expanded access clinical trial and not through the individual-patient Special Access Program. Therefore, sponsors wishing to include a Canadian arm in an international expanded access program for multiple patients must do so through an expanded access clinical trial.

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), which was previously managed by the Ministry of Science and Technology (MOST). (Note: Some HGR sources in this profile still reference MOST.)

The MgmtHumanGen and the Biosfty-Law prohibit foreign entities or individuals from collecting or preserving Chinese HGR in China, or providing Chinese HGR for use abroad. Foreign entities that need to use Chinese HGR for scientific research may only do so through approved international cooperation with Chinese scientific research institutions, higher education institutions, medical institutions, or enterprises. Per the Biosfty-Law and the MgmtHumanGen, the regulatory authority’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 the NHC

The Rules-MgmtHGR states that the collection, preservation, use, and provision of HGR must comply with ethical principles and pass ethics review by an EC that has been filed with the relevant management departments. Activities must respect and protect the privacy rights and personal information rights and interests of HGR providers, obtain written informed consent in accordance with regulations, and ensure that their lawful rights and interests are not infringed. The collection, preservation, utilization, and provision of HGR overseas must comply with relevant requirements and technical specifications for scientific and technological activities.

Collection License

The Rules-MgmtHGR and the HGR-CollLic specify that collection activities conducted for clinical trials intended to obtain marketing authorization for a drug in China do not need a separate HGR collection license. To fulfill the Rules-MgmtHGR's goal to make administrative examination and approval services more efficient, this exemption defers to the separate national regulatory process that governs clinical trials under NMPA. Therefore, in the case of international clinical trials that qualify as international cooperative clinical trials and do not involve the export of HGR materials, it is only necessary to file with NHC (as explained in more detail below).

As delineated in the Rules-MgmtHGR, the HGR-AppGuide and the HGR-CollLic, to collect HGR outside of clinical trials for drugs intended for marketing authorization (e.g., cohort studies, cross-sectional studies, clinical studies, and physical fitness studies), the NHC assesses and approves HGR collection activities carried out in China in the following situations (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Important genetic pedigrees – Applies to blood-related groups with genetic diseases and/or special hereditary physical or physiological characteristics involving three (3) or more generations; important genetic pedigrees refer to a group of blood-related individuals who suffer from hereditary diseases, have special hereditary physical conditions or physiological characteristics, and whose members with hereditary diseases or special hereditary physical conditions or physiological characteristics span three or more generations; common diseases such as hypertension, diabetes, red-green color blindness, and hemophilia are not included in this category
• Specific-region HGR – Applies to HGR from populations that have lived in isolation or special environments for a long time and possess special physical characteristics or adaptive traits in physiological characteristics; not based on minority-populated areas
• Large-scale population research (>3,000 participants) – Applies to collection activities for large-scale population studies with more than 3,000 participants, including but not limited to cohort studies, cross-sectional studies, clinical studies, constitutional studies, and physical fitness studies; however, collection activities conducted as part of clinical trials intended to obtain marketing authorization for a drug or device in China are excluded from the HGR collection-license requirement under the Rules-MgmtHGR and the HGR-CollLic

The HGR-AppGuide and the HGR-CollLic state that within these categories, the NHC’s scope covers both HGR materials (such as cells, blood, tissues, semen, cerebrospinal fluid, effusions, smears, and hair with follicles) and HGR information (including genes, genomes, transcriptomes, epigenomes, ctDNA, and related disease or ethnicity data), while materials or data lacking genetic information fall outside the collection-license requirement. In addition, non-cellular human secretions, body fluids, swabs, and other data types without human genetic resource gene information do not need to be declared. See the Rules-MgmtHGR for more information. For additional analysis, see CHN-36.

Preservation License

As delineated in the Rules-MgmtHGR, 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. See HGR-PresLic for the preservation license service guide.

International Cooperation License and Filing

The MgmtHumanGen and the Rules-MgmtHGR delineate two (2) HGR pathways for international cooperation using HGR: 1) the international scientific research cooperation license, which is an administrative license required for international cooperation involving the use of China’s HGR in general scientific research; and 2) the international cooperative clinical trial filing, which is a record-filing procedure applicable to international clinical trials conducted for marketing authorization purposes and do not involve HGR exports. The first pathway requiring a license is subject to NHC review/approval and ethics review of the respective countries (regions) where both parties are located, or if the foreign entity is unable to provide evidence of ethical review in its country, it may submit evidence that the foreign entity recognizes the ethical review opinion of the Chinese unit. As indicated in NHC-HGR-FAQs, if an ongoing clinical trial project’s cooperating unit changes in nature to become a foreign unit, the project should be suspended and may continue only after the international scientific research cooperation is approved or the international cooperative clinical trial filing has obtained a filing number. For projects that have been filed for international cooperative clinical trials but need to be converted to an international scientific research cooperation license due to changes in conditions, the international cooperative research content should be suspended in a timely manner; a summary explanation should be uploaded as supporting material when applying for the new license; and the relevant research content may proceed only after obtaining the international scientific research cooperation license. See HGR-IntlSciLic, HGR-IntlCoop, and HGR-ExportLic for the relevant NHC service guides for the international cooperation and the export license. See NHC-HGR-FAQs, for NHC’s additional questions and answers on the international cooperation license and filing.

See NHC-HGR-FAQs, CHN-15, and CHN-33 for NHC resources related to HGR management and licensing. Also see the Specimens topic for more HGR guidance.

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. See CDE-No16-2025, for details on the design and conduct of vaccine clinical trials.

Per the DRR, the DAL, the NMPA-No50-2018, and Svc-DrugCTAprvl, 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 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 Svc-DrugCTPrty for handling guidelines on priority review and approval.

To further accelerate the development of innovative drugs, the NMPA-No86-2025 establishes a 30-day channel for clinical trial review and approval of innovative drugs. Under this mechanism, clinical trial applications that meet the requirements will be reviewed and approved within 30 working days after acceptance. The 30-day channel allows priority handling for key national (research and development) R&D varieties, early global development, and international multi-center trials to meet urgent clinical needs and strengthen domestic pharmaceutical capacity. Further, the 30-day approval process maintains International Council for Harmonisation (ICH) standards, full-lifecycle risk management, and seeks to strengthen collaboration among sponsors, clinical institutions, investigators, and ECs to ensure safety and efficient trial initiation. Applications must be Class 1 innovative drugs of chemical drugs or biological products, and one of the following conditions must be met:

• Key innovative drug varieties with obvious clinical value supported by the national policy system to support the development of innovative drugs in the whole chain
• Eligible innovative drugs for children, innovative drugs for rare diseases, and innovative drugs for traditional Chinese medicines announced by CDE of the NMPA
• Global synchronous research and development varieties, including Phase I and Phase II trials of global synchronous R&D, and Phase III international multi-center clinical trials led or co-led by principal investigators from Chinese drug clinical trial institutions

Per NMPA-No86-2025, applicants choosing the 30-day pathway must commit to initiating clinical trials within 12 weeks from the first participant’s informed consent). The CDE will accept and review applications within five (5) working days and complete the review within 30 working days. If difficult or complex issues require technical consultations or expert meetings, the review period will revert to the 60-day implied approval system. See NMPA-No40-2025 and Submission Process and Submission Content for details on the application process and content.

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. 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. Complementing the NMPA-No79-2018 and the NMPA-No82-2020, the NMPA-No3-2026 further expands the priority review and approval scope for overseas-marketed drugs to include novel and generic treatments. As indicated in the NMPA-No3Interp-2026, the NMPA also said it will not limit priority review eligibility with a list of urgently needed treatments. The NMPA-No3-2026 states that applicants may rely on overseas registration and clinical data, including full clinical, pharmaceutical and non-clinical dossiers, post-marketing safety reports, benefit-risk analyses across populations, and post-import risk-management plans, including post-marketing study plans. Submission of data from international multicenter clinical trials conducted in China is encouraged. Regarding generic drugs, NMPA clarified that applicants may, after assessment, be granted an exemption from domestic clinical trials, enabling immediate submission of an application for marketing authorization. After communicating with the CDE to reach a consensus, the applicant must submit a clinical trial application for the drug clinical trials, and CDE will decide whether to agree to carry out clinical trials within 30 days from the date of acceptance. For drug varieties that are exempt from drug clinical trials, applicants can directly apply for drug marketing authorization. See the NMPA-No3Interp-2026 for additional details.

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.

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 ICH’s Guideline for Good Clinical Practice (GCP). (Note: ICH GCP versions and official Chinese translations are available in the Efficacy section of China’s implementation page (CHN-49); as per NMPA-No125-2025, the E6(R3) version (CHN-37) will apply to all Chinese drug clinical trials conducted after March 31, 2026)
• 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 Biosfty-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 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 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 National Center for Biotechnology Development at 010-88225151 or 010-88225168; or the information system support at 17610386080. Further, as explained in HGR-Answrs-5, the quantity of HGR materials and information declared in administrative license or filing applications must not exceed the amounts specified in the approved research plan and informed consent documents.

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 NHC-HGR-FAQs states that the name of the project in the ethics review approval must be identical to the name of the NHC application. The research plan must remain within the scope of the approved cooperation agreement and may not exceed it. For requested changes to licensed international cooperation projects, research activities and participant screening should continue under the originally approved scope until NHC issues an approval for the changes. HGR-Answrs-5 indicates that applications to renew the validity period of an administrative license or filing must be submitted to NHC at least 30 working days before the expiration date of the license.

As delineated in the HGR-CollLic, HGR-PresLic, HGR-IntlSciLic, and HGR-ExportLic, upon receipt of the formal application materials, the NHC will determine acceptance, and if the materials are incomplete or do not conform to legal requirements, it will inform the applicant of all necessary corrections within five (5) working days. After the application is formally accepted, the NHC will make a decision to approve or disapprove within 20 working days, which may be extended by 10 working days if a decision cannot be made within the prescribed time limit due to special reasons and with approval from the head of the NHC. If the administrative licensing decision requires a hearing, inspection, testing, quarantine, appraisal, or technical review, the time required is not included in this limit, and the applicant must be notified in writing of the required time. Once the decision is made, the NHC will deliver the approval decision within 10 working days by mail or electronic delivery to the applicant’s designated address or email/website, and will also send a copy to the relevant provincial, autonomous region, or municipal HGR management department. As indicated in the HGR-IntlCoop, NHC receives electronic filing materials through the online platform and will not register applications that are incomplete or do not meet legal requirements, informing the applicant of the reasons. Applications with correctable errors may be returned for correction. Applications with complete and compliant materials undergo formal review and, once filed and assigned a case number, the applicant may begin international collaborative clinical trials.

The Biosfty-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 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.

Other Considerations

See the following additional NHC guidance on the scope of HGR assessment:

• Immortalized cell lines that have had sample-related information removed and cannot be traced back to individuals for production or scientific research are not included in the scope of HGR regulation (HGR-Answrs-1)
• International collaborative research involving blank substrates of HGR is permitted, provided it meets requirements for international cooperation, includes a complete research plan with a clear purpose and sample size rationale, and ensures substantive participation and benefit-sharing by Chinese entities. (HGR-Answrs-4)

For additional HGR resources, see CHN-15. Also see the Submission Process and Submission Content sections and the Specimens topic for additional information on HGR regulatory management.

According to CAN-56, there are no fees to submit a clinical trial application in Canada.

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 Svc-DrugCTAprvl, 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 Svc-DrugCTAprvl, 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.

Overview

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

Per CAN-35 and CAN-13, all proposed or ongoing research involving human participants carried out by, funded by, or otherwise under the auspices of Health Canada (HC) or the Public Health Agency of Canada (PHAC) must obtain approval from a joint EC representing those two (2) agencies—as well as complying with the CanadaFDR and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. This joint EC is known as the HC-PHAC REB. Further, if an institution is conducting an HC- or PHAC-funded project, the HC-PHAC REB must review and approve the research even if it has been previously reviewed and approved by another EC. See CAN-35 for details on the HC-PHAC REB’s development, responsibilities, and composition. HC’s operational policy (CAN-13) outlines policies and procedures that the joint HC-PHAC REB must follow when reviewing clinical trials.

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

Ethics Committee Composition

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

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

The G-TCPS2 mirrors these EC composition requirements, and also requires a Chair who is responsible for ensuring that the ethics review process conforms to the requirements of G-TCPS2. The Chair provides overall leadership for the EC and facilitates the review process based on institutional policies and procedures and the G-TCPS2. The Chair should monitor the EC’s decisions for consistency and ensure that these decisions are recorded accurately and communicated clearly to researchers in writing as soon as possible by the Chair or designate. Institutions must provide the necessary resources and adequate administrative support to enable the EC Chair to fulfill their responsibilities. As mentioned earlier, only CIHR-, NSERC-, and SSHRC-funded institutions are required to comply with this guidance as a condition of funding.

Also, see CAN-52 for additional guidance on EC composition, functions, and operations. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Terms of Reference, Review Procedures, and Meeting Schedule

According to G-TCPS2, institutions must have in place written procedures for the appointment, renewal, and removal of EC members, including Chairs. Further, institutions must have clear written policies describing the mandate of each EC. An institution may wish to use different models for the ethics review of research conducted under its auspices.

The G-TCPS2 states that an EC should have adequate expertise, experience, and training to understand the disciplines, methodologies, and approaches of the research that it considers for research ethics review. Institutions should ensure that all EC members receive appropriate education and training in ethics review of research involving humans, to enable them to fulfill their duties. This includes providing training opportunities for all members in core principles and understanding of the G-TCPS2, basic ethics standards, applicable institutional policies, and legal or regulatory requirements. It includes an understanding of the role and mandate of ECs and responsibilities of EC members. Training should be tailored to the types and complexities of the research that the EC reviews.

Per the G-TCPS2, when there is less than full attendance, decisions requiring full review should be made only when the members present have the specific expertise, relevant competence, and knowledge necessary to provide an adequate ethics review. Ad hoc advisors, observers, research ethics administration staff, and other attendees must not be counted toward quorum or permitted to vote; decisions made without quorum are not valid or binding. ECs must hold regular meetings and normally meet face to face to review research not assigned to delegated review. Where members are geographically dispersed or exceptional circumstances prevent attendance, participation by phone, videoconference, or other technology may be acceptable, provided quorum is maintained and the Chair ensures active participation. A schedule of EC meetings should be communicated to researchers, and ECs should establish a process for reaching decisions requiring full review, such as consensus or, where necessary, a vote.

G-TCPS2 indicates that proportionate review means the level of EC review is determined by the level of foreseeable risk to participants: the lower the risk, the lower the level of scrutiny through delegated review; the higher the risk, the higher the level of scrutiny through full-board review. Full EC review should be the default requirement for research involving humans. Where research is determined to involve minimal risk, an EC may authorize delegated review in accordance with its institutional policies and written procedures. Delegated reviewers may refer proposals to the full EC, and any proposed negative decision must be reviewed and endorsed by the full EC before it is communicated to the researcher. Delegated decisions must be well documented and formally reported to the full EC, which remains responsible for the ethics of all research involving humans within its jurisdiction. ECs must function impartially, provide researchers with a fair hearing, and provide reasoned and appropriately documented opinions and decisions. Approvals and refusals must be communicated in writing. Where members disagree, an effort should be made to reach consensus; if disagreement persists, the decision must be made in accordance with the EC’s agreed-upon and documented process. The EC makes the final determination regarding the nature and frequency of continuing research ethics review using a proportionate approach. At minimum, continuing review consists of an annual status report for multi-year projects and an end-of-study report for projects lasting less than one (1) year.

Regarding records, G-TCPS2 indicates that ECs must prepare and maintain comprehensive records, including all documentation related to the projects submitted to the EC for review, attendance at all EC meetings, and accurate minutes reflecting EC decisions. Where the EC denies ethics approval for a research proposal, the minutes must include the reasons for this decision. When deciding the retention period of their files, ECs should be guided by their institutional record-keeping policies and other relevant legal or regulatory requirements. Files, minutes, and other relevant documentation must be accessible to authorized representatives of the institution, researchers, sponsors, and funders when necessary to assist internal and external audits, or research monitoring, and to facilitate reconsideration or appeals. The minutes of EC meetings must clearly document the EC’s decisions, any dissents, and the reasons for them. EC decisions should be supported by clear references (e.g., date of decision, title of project), documentary basis for decision, the plan for continuing ethics review and timelines, reasons for decisions, and any conditions or limitations attached to the approval. Providing reasons for EC decisions is optional when ethics approval is granted. ECs should have written procedures for its management of record keeping and other submitted reports. EC must maintain reports and decisions on unanticipated issues or changes to approved research.

For examples of EC SOPs, see CAN-13 for the HC-PHAC REB operational policy.

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. In addition, 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.

The Meas-STEthics expands upon the ethical review system (e.g., as delineated in the Measures-Ethics and the RegEthics) to universities, scientific research institutions, medical and health institutions, enterprises, etc. for the review and management of scientific and technological ethics involving human research participants, including human testing, investigation, observation, and other research activities, as well as scientific and technological activities using human biological samples and personal information data. Units engaged in scientific and technological activities such as life sciences, medicine, and artificial intelligence must establish a science and technology EC if their research content involves sensitive areas of scientific and technological ethics. As delineated in the Meas-STEthics and explained in CHN-42, if a sector regulator (for example, the health authorities) has its own ethics rules for setting up ECs or running ethics review—and those rules follow the Meas-STEthics’s principles—then the sector rules apply. Therefore, for life-science and medical research involving humans, the Meas-STEthics generally applies alongside the Measures-Ethics and the RegEthics; and where the health authorities’ human participant ethics rules are consistent with the Meas-STEthics, those health-sector rules generally control the ethics review.

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.

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.

See the Meas-STEthics for composition requirements for science and technology ECs, as needed.

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 standard operating procedures (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.

See the Meas-STEthics requirements for science and technology ECs, as needed.

Overview

According to the CanadaFDR, the G-CanadaCTApps, and the G-TCPS2, the primary scope of information assessed by institutional ethics committees (ECs) (called Research Ethics Boards (REBs) in Canada) relates to maintaining and protecting the dignity and rights of human research participants and ensuring their safety throughout their participation in a clinical trial. ECs must also pay special attention to reviewing informed consent and protecting the welfare of certain classes of participants deemed vulnerable.

See the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which CAN-50 indicates that Health Canada (HC) has adopted, for additional EC responsibilities and requirements. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Role in Clinical Trial Approval Process

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

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

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

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

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

G-Dcntrl indicates that for clinical trials with decentralized elements a single EC can approve activities at a clinical trial site as well as decentralized trial elements. However, sponsors and qualified investigators may need to obtain their own additional provincial or institutional approvals or permissions, or meet community-specific requirements, to use institutional resources or gain access to specific locations or populations, such as Indigenous communities.

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

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.

The Meas-STEthics governs EC reviews of scientific and technological activities involving human research participants, including human testing, investigation, observation, and other research activities, as well as scientific and technological activities using human biological samples, personal information data, etc. and other scientific and technological activities that require scientific and technological ethics review in accordance with laws, administrative regulations, and relevant national regulations.

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.

See the Meas-STEthics and the Ethics Committee section for more information on science and technology ECs, and on whether their review is required alongside the life science and medical research EC. Also 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.

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

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

No applicable requirements.

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

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).

As delineated in the Meas-STEthics, the Ministry of Science and Technology (MOST) is responsible for coordinating and guiding the national science and technology ethics supervision work. The review and supervision of science and technology ethics is guided by the State Science and Technology Ethics Committee. Local and relevant industry authorities are responsible for the supervision and management of scientific and technological ethics review in their respective regions and systems. See the Meas-STEthics for additional information on oversight of science and technology ECs.

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

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

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

Regulatory Submission

Per the G-CanadaCTApps, CTAs (CAN-4) should be sent directly to the appropriate HPFB Directorate for review—the Pharmaceutical Drugs Directorate (PDD) for pharmaceutical drugs or the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) for biological drugs and radiopharmaceuticals.

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

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

Electronic Common Technical Document (eCTD) Electronic Submission

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

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

• Register as a trading partner with the U.S. Food & Drug Administration (FDA) at the FDA Electronic Submissions Gateway Next Generation (ESG NextGen) (CAN-51) to be able to send a regulatory transaction (Note: CAN-54 indicates that the new version of the platform, ESG NextGen, continues to support HC submissions.)
• Send regulatory transactions to HC by selecting “HC” as the center on the FDA ESG system; CTAs intended for HC will be automatically redirected.

For detailed information on how to become a trading partner and send regulatory transactions, refer to CAN-54, CAN-51, and CAN-25.

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

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

Media must be mailed to HC at the address below:

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

See the G-eCTD, CAN-54, CAN-34, CAN-36, CAN-25, and CAN-28 for details on registering as a trading partner for CESG transactions, how to use CESG, and submitting CTAs in eCTD format.

Non-eCTD Electronic Submission

For non-eCTD electronic submissions, G-Non-eCTD indicates that the CTA (CAN-4) must be provided in PDF format. Other files submitted should be in PDF format, unless otherwise specified in G-Non-eCTD. PDF documents should be generated from electronic source documents and not from scanned materials, except where access to an electronic source document is unavailable or where a signature is required. Documents that are more than 10 pages should be bookmarked. Sections, subsections, tables, figures, and appendices should be bookmarked, with no more than four (4) levels of bookmarks. Hyperlinks within the same PDF document are acceptable, but hyperlinks between different documents must not be used. Stakeholders are responsible for ensuring that hyperlinks function, and links must also include references to the applicable section or page. Documents that legally require signatures may be signed electronically, or the signature page may be printed, signed, scanned, and saved as a PDF. If only one (1) page of a multi-page document contains a signature, the scanned page should be included in the same location in the PDF. Each document should have only one (1) PDF file. The cover letter does not require a signature but should include the printed name, phone number, and email address of the contact person.

As explained in G-Non-eCTD, all regulatory transactions should be validated before being transmitted to HC. For the applicable requirements, including validation rules, see the Rules-Non-eCTD. Initial CTAs and CTA-As should be submitted on electronic media, accompanied by a paper copy of the cover letter, and sent directly to the Office of Clinical Trials within PDD for pharmaceuticals or the Office of Regulatory Affairs within BRDD for biologics and radiopharmaceuticals. The ElecSubms contains a zip file of the folder structure for clinical trial non-eCTD submissions. (Note: As per ElecSubms, G-Non-eCTD is only available upon request at no-reply.ereview.non-reponse@hc-sc.gc.ca. Please ensure the text 'non eCTD Guidance Document' is in the subject line of the email.)

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

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

All media should be labelled and contain the following information:

• Stakeholder Name
• Brand Name

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

As per the G-Non-eCTD, G-MDSA, CAN-18, and CAN-17, non-eCTD CTAs involving pharmaceutical drugs should be sent to PDD, and CTAs involving biologics and/or radiopharmaceuticals should be sent to BRDD at the addresses listed below (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

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

Office of Regulatory Affairs
Biologic and Radiopharmaceutical Drugs Directorate
Health Products and Food Branch
Ground Floor, Health Canada Building 6
100 Eglantine Driveway
Tunney’s Pasture
Address Locator: 0601C
Ottawa, Ontario, Canada
K1A 0K9

Telephone: 613-957-1722
E-mail: brdd.ora@hc-sc.gc.ca

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

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

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

Ethics Review Submission

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

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), which was previously managed by the Ministry of Science and Technology (MOST). (Note: Some HGR sources in this profile still reference MOST.) 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 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 the NHC review cannot occur in parallel. (Please note that the MgmtHumanGen was amended 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.) See CHN-15 for an overview of NHC resources related to the management of HGR.

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.)

Svc-DrugCTAprvl 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 Svc-DrugCTAprvl, 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 Svc-ChemDrug 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 Svc-DrugCTPrty, after the registration application is transferred to the CDE, applicants can apply for accelerated review directly to the CDE at CHN-58. Svc-DrugCTPrty 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, the drug classification system, priority review for innovative drugs and those deemed to have an urgent clinical need, and other changes help China to expedite reviews.

The NMPA-No86-2025 establishes a 30-day channel for clinical trial review and approval of innovative drugs. Under this mechanism, clinical trial applications that meet the requirements will be reviewed and approved within 30 working days after acceptance. The 30-day channel applies to clinical trials of Class 1 innovative drugs of chemical drugs, biological products, and traditional Chinese medicine, and application materials may be submitted as required if one (1) of the following conditions is met:

• Key innovative drug varieties with obvious clinical value supported by the national policy system for whole-chain innovative drug development
• Eligible innovative drugs for children, rare diseases, or traditional Chinese medicines announced by the CDE
• Global synchronous research and development (R&D) varieties, including phase I/II trials of global synchronous R&D and phase III international multi-center clinical trials led or co-led by principal investigators of Chinese drug clinical trial institutions

NMPA-No40-2025 states that before submitting a clinical trial application under this pathway, the applicant must conduct research in accordance with the relevant NMPA technical guidelines and fully assess whether existing data can support the clinical trial and whether risks are controllable, organizing materials per the ICH M4 CTD requirements, with any omissions explained. The applicant should indicate "Application for inclusion in the 30-day clinical trial application channel" in the application form. The NMPA-No86-2025 specifies that the applicant must submit the clinical trial application to CDE in accordance with the registration application procedures and requirements, indicate the 30-day channel in the application form, and submit the corresponding application materials.

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, applications to the NHC to collect, preserve, or export HGR must be submitted by a Chinese entity with legal person status. International cooperation activities that use China’s HGR require joint Chinese-foreign applications and ethics review approval in both partners’ countries, except for international clinical trials that do not involve the export of HGR materials, which require filing rather than approval with the NHC. The MgmtHumanGen and the Rules-MgmtHGR delineate China’s two (2) pathways for international cooperation using HGR: 1) the international scientific research cooperation license, which is an administrative license required for international cooperation involving the use of China’s HGR in general scientific research; and 2) the international cooperative clinical trial filing, which is a record-filing procedure applicable to international clinical trials conducted for marketing authorization purposes and do not involve HGR exports. Also see the Rules-MgmtHGR for details.

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. Per the HGR-CollLic, HGR-PresLic, HGR-IntlSciLic, and HGR-ExportLic, an application for an HGR collection, preservation, or export license, must be submitted by a Chinese applicant entity with legal-person status, which acts as the unit administrator. The unit administrator creates a new project in CHN-6 and authorizes an applicant (natural-person account) to enter the project information. After the applicant fills in the online form and the unit administrator reviews it, the system generates the application materials for download. The applicant uploads the signed and stamped review comments, and the unit administrator submits the formal application via the online platform. See HGR-InfoSys for background on the online platform and contact information. For help with the online platform, contact Zhu Min, NHC’s China National Center for Biotechnology Development, at 010-88225151 or 010-88225168; or the information system support at 17610386080.

The HGR-IntlCoop states that the filing (i.e., registration) of an international cooperative clinical trial filing must be jointly completed by the Chinese and foreign entities (with legal person status), and all parties must commit to the authenticity, accuracy, and completeness of the application materials. For multi-site clinical research, the lead institution must pass the ethical review before submission, and it applies for registration on behalf of all the sites. After the sponsor or lead unit completes the filing, the participating medical and health institutions must submit their own ethics review approval documents or proof of acceptance of the ethics review provided by the lead unit, along with a commitment letter, to the NHC before carrying out the international collaborative clinical research.

NHC-HGR-FAQs indicate that using HGR already approved for preservation does not require a new collection permit. For projects falling under both collection and international cooperation scope, applicants only need apply for the international scientific research cooperation license or international cooperative clinical trial filing. If the name on an approved collection or preservation permit changes, a major-matter change application must be submitted in accordance with the Rules-MgmtHGR. After a collection permit is approved, participating institutions can send the NHC their own ethics approval—or, instead, provide the certification documents and commitment letter issued by the institution that holds the approved collection license. HGR-Answrs-5 indicates that the number of HGR materials and information declared in the administrative licensing and filing projects of HGR must not exceed the number specified in the plan and informed consent in the application materials. If the licensee or filer needs to renew the validity period of the administrative license, the application must be submitted to the NHC 30 working days before the expiration of the validity period.

As per NHC-HGR-FAQs, the process-related guidance on the pathways for the international scientific research cooperation license and the international cooperative clinical trial filing is as follows:

• Foreign electronic data capture suppliers do not trigger international cooperation requirements when all other parties (sponsor, contract research organization (CRO), cooperating units) are Chinese
• The clinical trial sponsor name/listing must be consistent with the applicant for clinical trial approval, notice, or filing materials; if inconsistent, the applicant must submit relevant agreements and supporting materials to clarify rights and responsibilities
• If a partner unit becomes a foreign unit, the project must be suspended and may only continue after international scientific research cooperation is approved or the international cooperative clinical trial filing has obtained the filing number
• Projects funded by foreign parties but without substantive foreign participation, data access, or result-sharing do not require an international scientific research cooperation license or an international cooperative clinical trial filing
• If a filed international cooperative clinical trial needs to be converted to an international scientific research cooperation license, the international cooperative research content must be suspended, a summary explanation uploaded, and work may continue only after the license is obtained
• Previously approved international scientific research cooperation projects only need to undergo international cooperative clinical trial filing when a project change is required, based on the overall content of the change
• Other units in international cooperation include the sponsor, team leader unit, CRO, third-party laboratories, and any units that have access to HGR materials or information beyond the participating medical and health institutions
• CROs and third-party laboratories with foreign entities do not need to provide ethics review certification materials from their own countries or regions when applying for an international scientific research cooperation license

See CHN-32 for additional analysis.

Ethics Review Submission

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

Regulatory Authority Requirements

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

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

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

• Protocol
• Summary of potential risks/benefits
• Clinical trial attestation that includes drug information (chemistry, names, classifications, dosage, therapeutic purpose, human-sourced excipient, drug identification number or notice of compliance, manufacturing information); sponsor’s contact information; if the drug is to be imported, contact information for the sponsor’s representative in Canada who is responsible for the sale of the drug; and contact information for the qualified investigator at each site, if known at the time of submittal
• Contact information for each institutional ethics committee (EC) (known as Research Ethics Board (REB) in Canada) that approved the protocol, if known at the time of submitting the application (provided in the required Clinical Trial Site Information (CTSI) form (CAN-6))
• Contact information of any institutional EC that previously refused to approve the protocol, its reasons, and refusal date
• Investigator’s Brochure (IB)
• Informed consent form (ICF)
• Information about use of a human-sourced excipient
• Chemistry and manufacturing information
• Proposed date for trial commencement at each site, if known

Per the Mdrn-CTFrmwrk, for multi-site trials operating within a streamlined multi-site ethics review process, sponsors sometimes identify the same EC for all clinical trial sites. When providing information on a new site through CAN-6, sponsors only need to include the contact information for an EC once, as long as:

• The same EC has previously been identified as having approved other sites in that trial
• The EC's contact information has already been provided to HC in the context of the clinical trial, and continues to be up to date

Accordingly, as indicated in the Mdrn-CTFrmwrk, the form's section on EC approval may only contain the name of the approving board and the date of its approval.

Refer to the CanadaFDR, the G-FDR-0100, the G-CanadaCTApps, the G-DrugApp, the G-QltyBioCTs, and the G-QCM-PharmCTAs for detailed submission information.

Ethics Committee Requirements

Each institutional EC has its own application form and clearance requirements, which can differ significantly regarding the number of copies to be supplied and application format requirements.

The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ECs, requires clinical trial researchers to submit their research proposals for EC review and approval of their ethical acceptability prior to the start of recruitment of participants, data collection, access to data or collection of human biological materials. Researchers must submit sufficient details to enable the EC to make an informed review of the ethical acceptability of the research. In addition, they should include a plan for monitoring safety, efficacy/effectiveness (where feasible), and validity in their proposal for EC review. This plan must describe:

• How participant safety will be monitored and what actions will be taken in the event of a threat to participant safety
• How intervention efficacy will be monitored (where feasible) and what actions will be taken if efficacy is found to be greater than expected
• The criteria by which participants may be removed from a study for safety reasons
• The study-wide stopping rules (if any) by which studies may be stopped or amended due to evidence of inferior safety, superior efficacy or futility
• The reporting procedure that will be followed to ensure any information relevant to participant welfare or consent is reported clearly and in a timely fashion to the EC

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

Clinical Protocol

The CanadaFDR requires submission of a clinical trial protocol. Per G-FDR-0100, a protocol should describe the objectives, design, methodology, statistical considerations and organization of a clinical trial, and it should be consistent with the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52). The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence. CAN-50 indicates that HC adopted CAN-52.

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 (NMPA)’s 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. Svc-ChemDrug, Svc-DrugCTAprvl, and Svc-DrugCTPrty 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 Svc-DrugCTAprvl, 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 an overview of the China clinical trial application submission content.

As required in the NMPA-No40-2025, for innovative chemical drugs and biological products applying for the 30-day clinical trial review channel, the following submission content requirements apply:

• A clinical trial plan
• Data demonstrating that the protocol is risk-controllable and operable, with safety risk control measures and key elements supported by prior non-clinical and/or clinical research data with the design basis explained
• Supporting documents or review opinions from the lead unit of the Chinese clinical trial institution regarding acceptance of the clinical trial project and contract review, and from the EC regarding acceptance of the review
• The EC submission list should include at least: the signed clinical trial protocol, investigator’s brochure, draft informed consent form (ICF), risk management plan (RMP) during the research and development (R&D) period, and an evaluation report
• A statement confirming eligibility and relevant supporting materials and commitment letter confirming that the applicant will initiate the clinical trial within 12 weeks of approval
• For Phase I and Phase II applicants, supporting materials such as a globally synchronized R&D plan
• For Phase III international multicenter clinical trials, demonstration that the Chinese principal investigator (PI) led or co-led early participation as a member of the global steering committee/consulting advisory committee, and a protocol should include clinical research centers in two (2) or more countries, including China
• Documentation on pharmacovigilance experience in clinical trials and a RMP for the R&D period, jointly signed and confirmed by the PI of the applicant and the lead unit of the Chinese clinical trial institution

See NMPA-No40-2025 for appendices with additional application materials specific to clinical trials for innovative chemical drugs, biological products, and vaccines.

National Health Commission

Per the NHC-HGRmgt, the National Health Commission (NHC) is responsible for China’s management of human genetic resources (HGR), which was previously managed by the Ministry of Science and Technology (MOST). (Note: Some HGR sources in this profile still reference MOST.) The NHC-HGRmgt states that the original application process and platform (CHN-6) remain unchanged.

Per the MgmtHumanGen, HGR-CollLic, HGR-PresLic, HGR-ExportLic, and HGR-IntlSciLic, the following are required across the HGR collection, preservation, export, and international science research license applications:

• Application form completed on CHN-6
• Documents proving legal-person status
• Ethics review approval document (including review comments, list of reviewed materials, signed and stamped page, EC member sign-in sheet or attendance sheet, and version numbers and dates)
• Informed consent form text
• Other supporting documents
• Per the HGR-CollLic, for applications for a collection license, the following additional submission content is required:
• Data collection scheme
• Management system for human genetic resources collection
• HGR materials or information relevant to the project
• Cooperation agreement (if applicable)

Per the HGR-PresLic, for applications for a preservation license, the following additional submission content is required:

• Preservation plan (purpose, process, schedule)
• Preservation and management system (management mechanisms, responsibilities, sample entry and exit, registration, record management, training, security, confidentiality, emergency and disposal plans)
• Preservation technical documents (facility and equipment requirements, site environment management, personnel allocation, operating procedures, and quality control system documents)
• Legal source documentation for HGR
• Layout or floor plan of storage sites (if applicable)

As required in the HGR-ExportLic, for applications for an export license, the following additional submission content is required:

• Signed ICF clearly stating the sample is for export, with copies matching the number of export documents
• Research plan including a complete description of sample handling
• Agreement on the handling of remaining HGR (if applicable)
• Legal source documentation for HGR intended for export (if applicable)

As delineated in the HGR-IntlSciLic, for applications for an international scientific research cooperation license, the following additional submission content is required:

• International cooperation agreement (Chinese version) among the sponsor, lead institution, contract research organization, or third-party laboratory (if applicable)
• Supporting documents acknowledging acceptance of the Chinese ethics review (if the foreign party cannot provide home-country ethics approval)
• Research plan
• Ethics review approval documents for participating clinical medical and health institutions
• Clinical trial approval, notification, or filing (if applicable)
• Case registration materials (if applicable)
• Commitment letter from participating clinical medical and health institutions

For licensing or filing of international cooperation involving HGR, NHC-HGR-FAQs and HGR-IntlCoop indicate that the following must also be submitted to NHC (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Basic information of all collaborating parties
• Types, quantities, and uses of HGR involved in the research
• Research protocol
• Ethics review approval document from the lead institution
• Other supporting materials
• Relevant agreements and supporting materials if the clinical trial sponsor is not the same as the applicant, to clarify rights and responsibilities
• A summary explanation with supporting materials when converting from a filed clinical trial to an international scientific research cooperation license
• The international cooperation agreement(s) with required Chinese-signed and sealed versions depending on license or filing
• If all testing, analysis, and remaining-sample processing is local, the information may be submitted as an annex to the clinical trial 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 in the application forms (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Application for Human Research Ethics Review
• 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, the clinical protocol should include the following elements:

• General information
• Background information
• Trial topic, purpose(s), and objective(s)
• Trial Design
• Clinical and laboratory tests
• Selection and withdrawal of participants, such as inclusion, exclusion, and withdrawal criteria
• Treatment for participants
• A clear visit and follow-up plan
• Efficacy assessment
• Safety assessment
• Statistics
• Direct access to source data/documents
• Quality control/quality assurance
• Ethical issues
• Collection and management of test data

For complete protocol requirements, see Chapter 6 of the NMPA-GCP-No57-2020. Also refer to the ICH’s Guideline for Good Clinical Practice E6(R3) (CHN-37), to which all drug clinical trials conducted after March 31, 2026 will be subject, per NMPA-No125-2025.

As required in the NMPA-No40-2025, for innovative drugs applying for the 30-day clinical trial review channel, the applicant must submit a complete clinical trial protocol reviewed and signed by the PI of the lead unit of the Chinese clinical trial institution, reflecting product characteristics, R&D objectives, and prior research data.

Overview

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

Regulatory Authority Approval

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

As specified in the G-CanadaCTApps and the G-MDSA, during the review period, the Directorate may request additional information from the sponsor, who has two (2) calendar days to provide such information. The G-MDSA clarifies that, where warranted, HC can adjust the timelines to be longer or shorter based on the complexity of the request, communications with the sponsor, and/or circumstances of the review, including pausing the clock during the scientific review. The G-CanadaCTApps also states that HC will issue a Not Satisfactory Notice (NSN) if a timely response to requested information has not been provided. The G-MDSA indicates that the review of the submission will stop on the date the NSN is sent.

Ethics Committee Approval

The EC review and approval process timeline varies by institution. The G-TCPS2, which sets the ethical benchmark for all Canadian institutional ECs, recommends a proportionate approach to ethics review—the lower the level of risk, the lower the level of scrutiny (delegated review); the higher the level of risk, the higher the level of scrutiny (full board review). In either case, pursuant to the G-TCPS2, the institutional EC should make its decisions in an efficient and timely manner.

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

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), which was previously managed by the Ministry of Science and Technology (MOST). (Note: Some HGR sources in this profile still reference MOST.) The Biosfty-Law, the MgmtHumanGen, and the Rules-MgmtHGR, delineate that 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. Therefore, EC and the NHC review cannot occur in parallel.

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 Svc-DrugCTAprvl, 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 Svc-DrugCTAprvl, 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.

To further accelerate the development of innovative drugs, the NMPA-No86-2025 establishes a 30-day channel for clinical trial review and approval of innovative drugs. Under this mechanism, clinical trial applications that meet the requirements will be reviewed and approved within 30 working days after acceptance. CDE will make a screening decision for acceptance within five (5) working days. If the application for inclusion in the 30-day channel cannot be completed within 30 working days due to difficult and complex issues requiring technical consultations or expert meetings, the CDE will notify the applicant through CDE’s Applicant Window (CHN-58) within 20 working days after acceptance, and the overall time limit will be implemented according to 60 days. See the Scope of Assessment section for details on eligibility and scope. Per 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. Also see the NMPA-No3-2026 and the NMPA-No3Interp-2026 for the procedures on submitting an application to CDE for priority review and approval of overseas marketed drugs urgently needed for clinical use.

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. As delineated in the Rules-MgmtHGR, the HGR-CollLic, HGR-PresLic, HGR-IntlSciLic, and HGR-ExportLic, upon receipt of the formal application materials, the NHC will determine acceptance, and if the materials are incomplete or do not conform to legal requirements, it will inform the applicant of all necessary corrections within five (5) working days. After the application is formally accepted, the NHC will make a decision to approve or disapprove within 20 working days, which may be extended by 10 working days if a decision cannot be made within the prescribed time limit due to special reasons and with approval from the head of the NHC. If the administrative licensing decision requires a hearing, inspection, testing, quarantine, appraisal, or technical review, the time required is not included in this limit, and the applicant must be notified in writing of the required time. Once the decision is made, the NHC will deliver the approval decision within 10 working days by mail or electronic delivery to the applicant’s designated address or email/website, and will also send a copy to the relevant provincial, autonomous region, or municipal HGR management department. As indicated in the HGR-IntlCoop, NHC receives electronic filing materials through the online platform and will not register applications that are incomplete or do not meet legal requirements, informing the applicant of the reasons. Applications with correctable errors may be returned for correction. Applications with complete and compliant materials undergo formal review and once filed and assigned a case number, the applicant may begin international collaborative clinical trials.

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, 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

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

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

Clinical Trial Agreement

Prior to initiating trial activities, as delineated in the G-FDR-0100, agreements made by the sponsor with the qualified investigator, institution, service providers, and any other parties (e.g., independent data monitoring committee or adjudication committee) involved with the clinical trial should be documented. The sponsor is also responsible for obtaining agreements from all involved parties to permit monitoring and auditing by sponsors, inspections by regulatory authorities (domestic and foreign) and review by ECs, including providing direct access to source records and facilities, including those of service providers. Any of the sponsor's trial-related activities that are transferred to and assumed by a service provider should be documented in an agreement. The sponsor's trial-related activities that are not specifically transferred to and assumed by a service provider are retained by the sponsor.

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

G-Dcntrl indicates that sponsors and QIs are responsible for ensuring that all agreements supporting decentralized trial activities clearly define roles, responsibilities, and oversight expectations. Trial-related activities delegated to service providers should be documented in written agreements that establish how tasks will be performed, supervised, and documented; investigational products and data will be managed; and compliance with regulations and good clinical practice will be maintained.

See CAN-6, CAN-8, and CAN-19 for additional clinical trial forms. Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Clinical Trial Registration

As per the CT-Rgstrn, sponsors should register their clinical trial before it has opened for enrollment in Canada but no later than 21 calendar days after the date of enrollment of the first participant. HC considers the registration date as the date when the clinical trial registration materials are first submitted to a registry. For a multi-national clinical trial with one (1) or more Canadian sites, sponsors should add the Canadian site(s) to their existing registry record. Ideally, this should be done before opening for enrollment, but no later than 21 calendar days after the date of enrollment of the first participant at the Canadian site(s). Sponsors should register their clinical trial with an international clinical trial registry that complies with World Health Organization (WHO) international standards, including the International Clinical Trials Registry Platform (ICTRP) (CAN-60). Two (2) widely used registries that are publicly accessible and part of the WHO network are ClinicalTrials.gov (CAN-45), and the International Standardized Randomized Controlled Trial Number (ISRCTN) Registry (CAN-46). Sponsors should include the protocol code/number in their registry record.

Also see HC’s Clinical Trial Search Portal (CAN-59), which is a search tool to find information about Canadian clinical trials. It is not a registry, but some of the information is collected directly from international registries.

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), which was previously managed by the Ministry of Science and Technology (MOST). (Note: Some HGR sources in this profile still reference MOST.) The Biosfty-Law, the MgmtHumanGen, and the Rules-MgmtHGR delineate that NHC’s responsibilities include 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 the NHC before initiating the study. The Rules-MgmtHGR also state that clinical trial applications must pass a security review organized by 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, 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

Per the HGR-CollLic, for HGR collection licenses (if applicable), a cooperation agreement is required. The HGR-ExportLic requires an agreement on the handling of remaining HGR (if applicable) for an export license. As delineated in the HGR-IntlSciLic, for applications for an international scientific research cooperation license, an international cooperation agreement (Chinese version) and an agreement among the sponsor, lead institution, contract research organization, or third-party laboratory (if applicable) are required. For licensing or filing of international cooperation involving HGR, NHC-HGR-FAQs indicates that the following agreements are required: relevant agreements if the clinical trial sponsor is not the same as the applicant, to clarify rights and responsibilities; and the international cooperation agreement(s) with required Chinese-signed and sealed versions depending on license or filing.

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 service guideline for clinical trial registration (Svc-DrugCTReg) for more information and frequently asked questions.

Governance

Per the Meas-ClinRsrch-Inst, medical and health institutions conducting investigator-initiated clinical research must establish a clinical research management committee and designate a specialized clinical research management department responsible for clinical research management. The clinical research management committee—composed of relevant institutional leaders, functional department heads, and clinical research expert representatives—must be responsible for coordination, service, management, and supervision of the institution’s clinical research. Under the committee’s guidance, the clinical research management department must be responsible for project initiation review, process management, quality management, contract management, close-out management, and archive management, and coordinate scientific review and ethics review. Institutions must also establish an EC, provide working conditions, and ensure the EC independently conducts ethics reviews. Clinical research is subject to an institutional project-approval system and may not be implemented without the institution’s approval, and investigators must prepare a clinical research protocol and submit the protocol and related materials to the clinical research management department for full-process management. Where an institution is entrusted or funded by another institution to conduct clinical research, or participates in multi-center clinical research, it must execute a clinical research agreement with the commissioning/funding institution or the lead multi-center institution to clarify rights, obligations, and allocation of responsibilities.

Safety Reporting Definitions

According to the CanadaFDR and G-CanadaCTApps, the following definitions provide a basis for a common understanding of Canada’s safety reporting requirements:

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

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

For Health Canada (HC)’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100. Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Safety Reporting Requirements

Investigator Responsibilities

Per the G-FDR-0100, the collection, assessment, and reporting of AEs is a critical component of the conduct of any clinical trial. The assessment of the site AEs should be done by the qualified investigator (QI) or the delegated sub-investigator(s) for seriousness, expectedness, and causality determination, when they become aware. All SAEs should be reported immediately (after the QI reasonably becomes aware of the event) to the sponsor. The QI should also include an assessment of causality. In accordance with applicable regulatory requirements, the protocol may identify SAEs not requiring immediate reporting; for example, deaths or other events that are endpoints. Subsequent information should be submitted as a follow-up report, as necessary.

Sponsor Responsibilities

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

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

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

Other Safety Reports

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

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

Form Completion & Delivery Requirements

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

Additionally, the G-DSUR indicates that HC recommends that DSURs in electronic Common Technical Document (eCTD) format be submitted via the Common Electronic Submissions Gateway (CESG) (CAN-25). For information on eCTD format, refer to the ElecSubms. For technical questions on eCTD filings, contact ereview@hc-sc.gc.ca as instructed in the G-DSUR.

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. Also see CDE-No49-2025 for guiding principles on grading AEs during vaccine 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 the CDE-No21-2025 for safety information assessment and reporting in pediatric clinical trials. Also 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.

Interim and Annual Progress Reports

Pursuant to the CanadaFDR and the G-CanadaCTApps, investigators and sponsors share responsibility for submitting interim and annual reports on the status of a clinical trial. The investigator is required to provide annual progress reports to the institutional ethics committee (EC) and submit interim progress reports to the EC and Health Canada (HC) if there are any significant changes affecting the trial or risk to participants. The sponsor is required to submit annual reports (in the form of an updated Investigator’s Brochure (IB)) to HC. Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence. For HC’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

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

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

Final Report

While the CanadaFDR does not require submission of a final study report to HC, the CT-Rgstrn states that HC’s policy for reporting summary results aligns with international initiatives, including the Declaration of Helsinki (CAN-58). Sponsors should submit the summary results of their clinical trial within 12 months following primary study completion, which is the final study visit for collection of data on the primary outcome for the last participant in a global study, whether the clinical trial concluded according to the pre-specified protocol or stopped early. For clinical trials with more than one (1) primary outcome measure with different completion dates, the primary study completion is the date when data collection is completed for all primary outcome measures. In cases where submission of summary results within one (1) year of primary study completion will jeopardize the scientific integrity of the clinical trial, summary results may be submitted within one (1) year of study completion, which is the final study visit for collection of data on any remaining secondary outcome measures and adverse event information for the last participant in the global study, whether the clinical trial concluded according to the pre-specified protocol or stopped early. If a sponsor intends to apply for market authorization for the product studied or a new condition of use, the sponsor may defer submitting summary results until 30 calendar days after HC renders a decision on the application or the sponsor cancels or withdraws it, or up to 36 months following primary study completion, whichever is earlier. HC does not support deferral for products or new conditions of use that the sponsor does not intend to market or for which product development has stopped. Sponsors should submit the summary results of their clinical trial to the same registry where their trial is registered. (See Initiation, Agreements & Registration section for information on clinical trial registration.)

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

Interim and Annual Progress Reports

The NMPA-GCP-No57-2020 requires the investigator to submit an annual report on the clinical trial to the ethics committee (EC). NMPA-No230-2015 states that the aforementioned annual report must be submitted on time. In addition, per NMPA-GCP-No57-2020, 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.

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).

As per the CanadaFDR and the G-CanadaCTApps, a sponsor is defined as an individual, corporate body, institution, or organization that conducts a clinical trial. In accordance with the G-FDR-0100, a sponsor may transfer any or all of the sponsor's trial-related activities to a service provider in accordance with applicable regulatory requirements. However, the ultimate responsibility for the sponsor's trial-related activities, including protection of participants' rights, safety, and well-being and reliability of the trial data, resides with the sponsor.

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

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

As per the DRR and the NMPA-GCP-No57-2020, 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, 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, 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.

Overview

Per the CanadaFDR and the G-FDR-0100, every sponsor must ensure that a clinical trial is conducted in accordance with good clinical practice (GCP) and must also ensure that:

• At each clinical trial site, there is no more than one (1) qualified investigator (QI)
• At each clinical trial site, medical care and medical decisions, in respect of the clinical trial, are under the supervision of the QI
• Each individual involved in the conduct of the clinical trial is qualified by education, training, and experience to perform the tasks

The G-FDR-0100 explains that the sponsor’s selection and oversight of QIs and service providers are fundamental features of the oversight process. As stated in Mdrn-CTFrmwrk, a "qualified investigator" may be:

• A physician or dentist who is authorized under CanadaFDR to act as a qualified investigator
• An individual who has the education, training, and experience required to conduct the clinical trial in accordance with regulatory requirements, despite not meeting the regulatory requirement to be a physician or dentist in CanadaFDR

Mdrn-CTFrmwrk further specifies that in clinical trials where the investigator is not a physician or dentist, medical decisions with respect to the trial that are outside the licensed scope of practice of the investigator must be made by a qualified physician or dentist on the clinical trial team who is:

• Licensed to practice in the province or territory where the site is located
• Responsible for medical oversight and participant care, including medical decisions with respect to the trial

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

Per G-Dcntrl, for clinical trials with decentralized elements, sponsors and QIs should assess whether decentralized locations have sufficient funding, time, equipment, and staff to support trial conduct that complies with GCP. Considerations include local care and institutional practices, provincial or territorial requirements, training needs, and coordination and communication across locations. The main location and remote locations supervised by one (1) QI constitute a single clinical trial site. The main location must be identified on the Clinical Trial Site Information (CTSI) form (CAN-6) and receive EC approval before trial initiation.

For additional guidance on investigator selection, qualifications, and training, see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

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

Foreign Sponsor Responsibilities

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

Data and Safety Monitoring Board

The G-TCPS2 provides the following considerations to help researchers and ECs determine whether a Data and Safety Monitoring Board (DSMB) (known as an Independent Data-Monitoring Committee in Canada) is needed:

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

Also see CAN-52 for ICH guidance on DSMBs.

Multicenter Studies

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

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

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

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, 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 clinical trial institution registration management information system (CHN-82) 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 each researcher’s performance of their work duties, and take measures to implement the quality management of drug clinical trials to ensure the data’s reliability and accuracy. 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.

See CHN-82 for more information about the clinical trial institution registration management information system. For additional details on the registration conditions, operations management, supervision, and inspection of institutions, see the NMPA-NHC-No101-2019. Also see Svc-DrugCTInstReg 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), which was previously managed by the Ministry of Science and Technology (MOST). (Note: Some HGR sources in this profile still reference MOST.)

Per the Rules-MgmtHGR, when data or information on HGR is provided or made available for use by foreign organizations, individuals, and institutions, the Chinese entity must notify 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 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 full-time staff to monitor clinical trial safety information and manage serious adverse event reporting. Relevant standard operating procedures (SOPs) should be established, and all relevant personnel should be trained. The sponsor is also responsible for ensuring 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, SOPs, 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, 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.

Insurance

The CanadaFDR does not require the sponsor to provide insurance coverage to investigators, institutions, or trial participants. However, the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50, guides sponsors on providing insurance. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Compensation

Injury or Death

The Canadian regulations do not require compensation for trial participants in the event of trial-related injuries or death. However, the G-TCPS2, which sets the ethical benchmark for all Canadian institutional ethics committees (ECs) (known as Research Ethics Boards in Canada), provides that, during informed consent, participants should be given information about any payments, including compensation for injury.

Trial Participation

The Canadian regulations do not require compensation for trial participation. However, as per the G-TCPS2, the informed consent form (ICF) should contain a statement with a description of the anticipated prorated payment to the participant(s) that is reasonably expected for participation in the trial. Any compensation or incentive to participants must not be so excessive that it may unfairly influence participants or cause them to overlook important facts and risks.

Also see CAN-52, which guides sponsors on providing compensation.

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(R3) (CHN-37) guides sponsors on providing insurance, and all drug clinical trials conducted after March 31, 2026, will be subject, per NMPA-No125-2025.

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.

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.

Quality Assurance/Quality Control

As stated in the CanadaFDR, the sponsor must ensure that a clinical trial is conducted in accordance with good clinical practice and must ensure, among other things, that the trial is scientifically sound and clearly described in a protocol; the trial and use of the drug comply with the protocol and the CanadaFDR; and systems and procedures that assure the quality of every aspect of the trial are implemented. Regarding quality, the G-FDR-0100 explains that the sponsor is responsible for the establishment of a quality management system consisting of documented procedures (standard operating procedures (SOPs), protocol procedures, etc.) to assure the quality of every aspect of a clinical trial. The range and extent of oversight measures should fit the purpose and be tailored to the complexity of and risks associated with the trial. Quality management includes the design and implementation of efficient clinical trial protocols, including tools and procedures for trial conduct (including data collection and management), to ensure the protection of participants' rights, safety, and well-being, and the reliability of trial results. The sponsor should adopt a proportionate and risk-based approach to quality management, which involves incorporating quality into the design of the clinical trial (i.e., quality by design) and identifying those factors that are likely to have a meaningful impact on participants' rights, safety, and well-being, and the reliability of the results. The sponsor should describe the quality management approach in the clinical trial report.

In addition, G-FDR-0100 states that risks to critical-to-quality factors should be managed proactively and adjusted when new or unanticipated issues arise once the trial has begun. Risk review is a key component to risk-based quality management systems, and Health Canada (HC) expects that sponsors will be able to demonstrate that risk control measures are periodically reviewed and remain effective and relevant, considering emerging knowledge and experience throughout the trial.

Per G-Dcntrl, for trials with decentralized elements, sponsors and qualified investigators (QIs) should collaborate with trial sites and service providers to implement a quality management system covering decentralized activities and supporting compliance with HC regulations and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. Processes should identify, evaluate, control, communicate, and review risks affecting participant safety or the reliability of results, including risks arising from decentralized elements. Additional training, continuing quality checks, and competency assessments may be needed beyond SOPs. See G-Dcntrl for additional details.

Further, CAN-50, Canada implements the ICH Guidance E8(R1): General Considerations for Clinical Studies (CAN-49), which provides guidance on conduct during the clinical trial. Other relevant ICH guidance adopted per CAN-50 are the guidance on statistical principles for clinical trials (CAN-53) and the addendum on estimands and sensitivity analysis (CAN-39). The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Monitoring Requirements

As indicated in the G-FDR-0100, the sponsor should determine the appropriate extent and nature of monitoring based on identified risks. Factors to consider include the objective, purpose, design, complexity, blinding, number of trial participants, investigational product, current knowledge of the safety profile, and endpoints of the trial. Monitoring may include site monitoring (performed onsite and/or remotely) and centralized monitoring. The frequency of monitoring activities should also be determined based on identified risks. Monitoring activities and their frequency should be modified as appropriate using knowledge gained. Centralized monitoring processes provide additional monitoring capabilities that can complement and reduce the extent and/or frequency of site monitoring or be used on its own. Use of centralized data analytics can help identify systemic or site-specific issues, including protocol noncompliance and potential unreliable data. In addition to monitoring, a sponsor should perform audits in a manner that is proportionate to the risk associated with the conduct of the trial. See CAN-52 for additional guidance on sponsor responsibilities involving monitoring and auditing.

Further, per the G-FDR-0100, it is critical to include processes that will be followed to address situations of non-compliance, as well as to identify events that would require either a review or revision of the monitoring plan. HC expects these components to be clearly documented in risk-based monitoring plans. The sponsor should describe the requirements of monitoring reports (including their content and frequency) in the standard procedures. Reports of site and/or centralized monitoring should be provided to the sponsor in a timely manner for review and follow up. When needed, the report should describe findings requiring escalation for action and resolution. The sponsor should decide on the appropriate action to be taken, and these decisions and the resolution of the actions involved, where needed, should be recorded. For additional information on monitoring reports, refer to the U.S. Food & Drug Administration (FDA)’s Guidance for Industry: A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers.

Next, per the G-FDR-0100, if it is discovered that noncompliance significantly affects or has the potential to significantly affect human participant protection or reliability of trial results, the sponsor should perform a root cause analysis, implement appropriate corrective and preventive actions, and confirm their adequacy, unless otherwise justified. Where the sponsor identifies issues that are likely to significantly impact the rights, safety, or well-being of the trial participant(s) or the reliability of trial results (i.e., serious noncompliance), the sponsor should notify the HC and the institutional ethics committee (known as Research Ethics Boards in Canada).

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

Per G-Inspections, regulated parties (sponsors, qualified investigators, contract research organizations, and any other party involved in the conduct of clinical trials) have mandatory responsibilities under the CanadaFDA and can be inspected. Foreign entities that conduct regulated activities in Canada, or in relation to a product imported in Canada, are also subject to Canadian law. During an inspection or a compliance verification, a regulated party is required to provide all reasonable assistance and information necessary for the HC inspector to perform their duties, including providing evidence that its facility, equipment, and practices and procedures meet the applicable requirements. As indicated in G-Dcntrl, sponsors should oversee decentralized elements in clinical trials across all locations, including remote locations, with monitoring directed toward potential safety concerns, data quality, and reliable results. See the Risk-Insp for HC’s risk classification guide for observations related to inspections of clinical trials of human drugs.

Premature Study Termination/Suspension

The CanadaFDR and the G-CanadaCTApps state that if a trial is prematurely terminated or suspended, the sponsor should inform HC no later than 15 days after the termination or suspension. In addition, the sponsor should provide HC with the reason(s) for the termination or suspension and its impact on the proposed or ongoing clinical trials related to the drug in Canada by the sponsor. The sponsor should also promptly notify the qualified investigators of the termination or suspension and advise them in writing of any potential risks to the participants’ health. Further, the G-CanadaCTApps states that the sponsor’s notification to HC should include confirmation that the sale or importation of the drug to the discontinued sites has been stopped and that reasonable measures to ensure the return of all unused quantities of the drug will be taken. This notification must also be submitted for premature discontinuation of a clinical trial or clinical trial site outside Canada where there are ongoing trials with the drug in Canada. See G-FDR-0100 for additional information and interpretation of discontinuation, suspension, and cancellation. CAN-52 also provides guidance on premature termination or suspension.

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 specifies 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:

• CDE-No30-2025 – questions and answers on the study of pharmaceutical similarity of biosimilars
• CDE-No44-2025 – key elements and points of trial design for the elderly to participate in clinical trials of innovative drugs
• CDE-No16-2025 – guidelines on the design and conduct of vaccine clinical trials
• 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
• CDE-No17-2022 – guidelines for clinical pharmacological research of biosimilars
• 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 refer 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 verify 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 requires 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. Also see the CDE-No21-2025 for monitoring requirements in pediatric clinical trials.

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, 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 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 states 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.

Electronic Data Processing System

The G-FDR-0100 states that systems and processes that aid in data capture, management, and analyses, as well as those that help ensure the quality of the information generated from the clinical trial, should fit the purpose of the trial, capture the data required by the protocol, and be implemented in a way that is proportionate to the risks to participants and the importance of acquired data. Quality should be addressed in the design or adaptation of electronic systems for clinical trial purposes to ensure the integrity of relevant trial data. Any electronic system used to capture, process, manage, and/or archive clinical trial information should be adequately validated, and evidence of validation should be retained and readily available for inspection by Health Canada (HC) inspectors. The approach for validation should be based on a risk assessment that considers the intended use of the system; the purpose and importance of the data/record that are collected/generated, maintained, and retained in the system; and the potential of the system to affect the well-being, rights, and safety of trial participants and reliability of trial results. The responsibilities of the sponsor, qualified investigator (QI), and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use. The sponsor should periodically review the risk control measures to ascertain whether the implemented systems remain effective and relevant, considering experience and emerging knowledge.

Per the G-FDR-0100, any modifications or additions made to the electronic system (for example software upgrades or migration of data) can impact its intended functions by altering the quality of validated applications and the system itself. This may affect the integrity of electronic information and the reliability of the system. Therefore, adequate documented assessment and approval of changes to hardware or software during the clinical trial are required. The impact of such a change should be evaluated and documented, and partial validation of some components of the electronic system may be required.

G-Dcntrl states that computerized systems and digital health technologies used in decentralized activities should be suitable for their intended use and validated through a risk-based approach consistent with the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. Sponsors should address data transfer integrity, security, interoperability, audit trails, and cybersecurity, with documented procedures and training supporting system development, maintenance, and use. See G-Dcntrl for additional details.

For additional information on computerized system validation and electronic records, see CAN-52. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Records Management

As set forth in the CanadaFDR and the CanadaFDR1024, the sponsor must record, handle, and store all trial-related information to allow complete and accurate reporting, interpretation, and verification. The CanadaFDR requires the sponsor to maintain all trial-related records for a period of 15 years. Per the G-FDR-0100, the electronic system should allow for the retrieval of records and the generation of complete and accurate paper copies of the electronic source data. The system should provide audit trails for the entire 15-year record retention period. Records created, maintained, and processed by outsourced systems are subject to the same requirements as the data/records generated by company-owned systems.

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

G-Dcntrl states that records of agreements and contracts (paper or electronic) must be available or accessible from the main location of the clinical trial site. Per the Mdrn-CTFrmwrk, the sponsor is responsible for obtaining and retaining records for all EC approvals that may be required for participating sites, in accordance with applicable local requirements. The sponsor must retain records of all approvals for verification during clinical trial inspections. To meet this requirement, the sponsor must maintain complete and accurate records demonstrating EC approval for research undertaken at a clinical trial site.

Also see CAN-52 for additional guidance.

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, see the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R3) (CHN-37) for guidance on computerized systems, which all drug clinical trials conducted after March 31, 2026, will be subject, per NMPA-No125-2025.

Records Management

Per the NMPA-GCP-No57-2020, 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 an archive management system for 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.

Responsible Parties

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

Data Protection

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

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

G-Dcntrl states that for decentralized data collection through wearables, digital platforms, or remote monitoring, sponsors should consider where data is stored, who may access it, and how to prevent unauthorized sharing or reuse.

Consent for Processing Personal Data

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

The G-TCPS2 states that to seek broad consent for the storage and future unspecified use of data, researchers must provide prospective participants, or authorized third parties, with applicable information as set out in the informed consent requirements. See the Informed Consent topic, as well as the following details:

• The type, identifiability, and amount of data being collected and stored for re-use, and for what potential purpose
• The voluntariness of the participant’s consent, including any limitations on the feasibility of withdrawal
• A general description of the nature and types of future research that may be conducted, including whether the research might be conducted outside of Canada (if known)
• The risks and potential benefits of data storage and use in future unspecified research, including areas of uncertainty where risks cannot be estimated
• Access to a general description of the repository and its governance
• A statement regarding participants’ preference to being contacted for additional future research
• Whether the data could be shared with researchers who are not subject to the G-TCPS2
• Whether the research will (if known) or might include whole genome sequencing or similar technologies that may pose a substantial risk of re-identification of the participant or identification of material incidental findings (when appropriate)
• Whether linkage of data gathered in the research with other data about participants – either contained in public or personal records – is anticipated
• Separate options for consenting to participate in a specific research project and for consenting to the storage of data for future unspecified research

See Brd-Cnst for additional clarifications on broad consent for the storage and future unspecified use of data.

Per G-Dcntrl, when using digital tools for decentralized activities, there may be concerns about data storage, access, and reuse or sharing without consent. Sponsors and qualified investigators can work collaboratively with participants to ensure informed consent is maintained.

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. See CAC-No18-2025 for guidance on the requirements and processes for both self-initiated and regulator-requested compliance audit activities.

The Cyberscrty-Law is part of China’s core data and cyber regulatory framework (together with the PIPL and the DataScrty), and requires network operators to comply with the PIPL and other relevant laws and regulations when handling personal data.

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.

In addition, the Cyberscrty-Law requires that critical information infrastructure operators (CIIO) must store relevant personal data locally, and where it is necessary to transfer data overseas, the CIIO must first undergo a regulator-led security assessment. 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
• Conduct personal information protection certification by professional institutions in accordance with the requirements of the Cyberspace Administration of China (CAC) (see CAC-No20-2025 and SAMR-Std-PI)
• Enter into a contract with the overseas recipient in accordance with the standard contract formulated by the CAC (see CAC-No13-2023) stipulating the rights and obligations of both parties
• Comply with other conditions stipulated by laws, administrative regulations, or national cyberspace administration departments
• Comply with China’s international treaties and agreements that permit providing personal information to foreign recipients
• Meet requirements to provide personal information overseas to conclude or perform a contract to which the individual is a part
• Implement cross-border human resources management in accordance with labor rules and regulations formulated under the law and collective contracts signed in compliance with the law, and provide employees' personal information overseas
• Provide personal information overseas to perform legal duties or obligations
• Provide personal information overseas in order to protect the life, health, or property safety of a natural person in an emergency

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 personal information processors to manage 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 risk assessments and on handling and reporting 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. Also see QA-DataExprt for more information on data exports.

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.

Per the HGR-RptOpenUse, the National Health Commission (NHC) requires prior reporting before providing or making available to foreign entities the use of China’s human genetic resources (HGR) information—including data such as genes, genomes, transcriptomes, epigenetics, nucleic acid biomarkers such as ctDNA, and related information such as diseases and ethnicities. The Chinese information owner must report to the NHC in advance and submit a backup of the information. The advance report must include the purpose and intended use; information on China’s HGR provided or made available to foreign entities and information backup status; basic information on foreign entities receiving the information; and an assessment of potential risks to the protection of China’s HGR. Once the applicant entity obtains a registration number, it may then share the HGR information with foreign entities. Any change to the purpose, recipient, or other matters must be reported to the NHC before implementation.

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

Obtaining Consent

In all Canadian clinical trials, a freely given informed consent is required from each participant in accordance with the requirements set forth in the CanadaFDR and the G-TCPS2. Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence. For Health Canada (HC)’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

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

The G-TCPS2 states that the qualified investigator (QI) must provide detailed research study information to the participant or legal representative/guardian. The ICF content should be in plain language (i.e., non-technical and easy to understand) and provided in a format that facilitates understanding. For example, written documentation may be supplemented with audio and/or visual aids. The participant and legal representative/guardian should also be given adequate time to consider whether to participate.

As stated in Mdrn-CTFrmwrk, HC is moving from “written” to “documented” informed consent to allow new approaches for obtaining consent (e.g., remote or electronic platforms, electronic signatures, and documentation of consent where it is provided orally). Informed consent requirements will be considered met by HC where processes:

• Are appropriately documented
• Comply with good clinical practice and CAN-52 principles
• Ensure that consent is informed and given in accordance with the applicable laws governing consent

Per G-Dcntrl, sponsors must inform participants of the potential risks and anticipated benefits of any decentralized elements in a clinical trial. In designing and implementing consent processes across locations, sponsors should consider whether the approach may introduce additional cognitive or emotional demands for participants. Reasonable steps should be taken to minimize unnecessary burden while supporting informed and voluntary decision-making. Virtual meeting platforms and electronic signatures may make the informed consent process more efficient for those who live in remote areas. However, participants may face additional challenges in providing informed consent remotely. Sponsors and QIs should be careful not to create a disadvantage for those who face barriers such as reliable private internet access, digital literacy, or comfort with virtual tools, or prefer not to use virtual platforms. Trial-related documentation should support any proposed delegation of duties related to the informed consent process to trial personnel or other third party, any proposed virtual meeting to obtain informed consent, and the proposed medium of the documented record of participants providing their consent (for example, written, video, audio). The following should also be considered:

• Providing different methods of informed consent to those who request them, including in-person consent meetings and physical copies of the ICF
• Using virtual meeting platforms that include both audio and video features so that QIs (or delegated persons) and participants can take part in the informed consent process and discussion in real time, and interact virtually with a real person

Further, the G-FDR-0100 indicates that a clinical trial participant cannot be involved in any aspect of a clinical trial until they have gone through the informed consent process, with a trial staff member (doctor, study nurse, clinical trial coordinator, etc.) and signed the document indicating that they understand the information and have agreed to participate in the trial. Neither the QI, nor the QI site staff, should coerce or unduly influence a participant to participate or to continue their participation in a trial. A qualified physician should be available to answer any medical questions that the participant may have regarding their participation in the trial. Information should be as clear and concise as possible, use simple language, and avoid unnecessary volume and complexity. See CAN-52 for additional information.

For guidance from Canadian researchers on the core elements for obtaining consent to ensure transparency and improve participants’ understanding of their involvement in research studies, see CAN-57.

Re-Consent

Per the G-TCPS2, consent must be maintained throughout the research project. Researchers have a continuous duty to provide participants with all information relevant to their ongoing consent to participate in the research. Consent begins with the initial contact (e.g., recruitment) and carries through to the end of participation in the study. Throughout the clinical trial, researchers have a continuous responsibility to provide participants and ECs with all information relevant to participants’ ongoing consent to participate in the research. The researcher must also notify participants of any changes to the research project that may affect them. These changes may have ethical implications, may be relevant to their decision to continue in the study, or may be unique to the particular circumstances of individual participants. Specifically, researchers must disclose changes to the risks or potential benefits of the research.

The G-TCPS2 indicates that rather than an age-based approach to consent, researchers should use an approach based on decision-making capacity in compliance with any laws governing research participation. This includes those whose decision-making capacity is in the process of development, those whose decision-making capacity is diminishing or fluctuating, and those whose decision-making capacity remains only partially developed. Mechanisms should be in place from the outset to identify and address any changes that could affect consent. A change in participant capacity is an important element of ongoing consent.

Further, the G-TCPS2 states that within the limits of consent provided by the participant, researchers should disclose to the participant any material incidental findings discovered in the course of research. Incidental findings are considered to be material incidental findings if they are reasonably determined to have significant welfare implications for the participant or prospective participant. Where material incidental findings are foreseeable, researchers should inform participants during the initial consent process. In addition, researchers should develop a management plan for review by the EC. For more information on how to address material incidental findings, see G-ConsentMatIncFindings.

See CAN-52 for additional information.

Language Requirements

Per the G-FDR-0100, the ICF must be made available for each participant in either official language (French or English) or other language as appropriate. The G-TCPS2 requires the ICF to be presented in plain language that the participant is able to understand. If there is a language barrier, the QI should select an intermediary who has the necessary language skills to ensure effective communication.

Documenting Consent

As per the G-TCPS2, the participant or legal representative/guardian, as well as the QI, must sign and date the ICF. The G-FDR-0100 states that the QI should retain the signed ICF.

The G-TCPS2 further indicates that researchers can use a range of procedures to seek and document consent, including oral consent documented in field notes, and other forms of recording (e.g., a consent log, audio or video recordings, or other electronic means). Evidence of consent may also be documented via completed questionnaires (in person, by mail, by email, or other electronic means). ECs should consider the power relationship that might exist between researchers and participants, and whether a waiver of the requirement for signed written consent may affect the welfare of the participants. If researchers plan to obtain non-written consent, they must explain their strategy to the EC.

See CAN-52 for additional information.

Waiver of Consent

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

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

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(R3) (CHN-37), which all drug clinical trials conducted after March 31, 2026, will be subject, per NMPA-No125-2025. As per the NMPA-GCP-No57-2020, the DAL, and the EC-Guide, 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 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 NHC-HGRmgt, management of HGR was transferred from Ministry of Science and Technology (MOST) to NHC, effective May 1, 2024).

The NMPA-GCP-No57-2020 and the Measures-Ethics 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 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 requires 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, 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 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.

Based on the CanadaFDR and the G-TCPS2, the informed consent form (ICF) should generally include the following statements or descriptions in plain language, as applicable (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Information that the individual is being invited to participate in a research project
• The study involves research and an explanation of its purpose and duration
• The identity of the researcher and the funder/sponsor
• The procedures to be followed
• The participant’s responsibilities
• Any reasonably foreseeable risks or anticipated benefits to the participant and in general
• Information about any payments, including incentives for participants, reimbursement for participation-related expenses, and compensation for injury
• An assurance that prospective participants are under no obligation to participate and are free to withdraw at any time without prejudice to pre-existing entitlements
• An assurance that prospective participants will be given, in a timely manner throughout the course of the research project, information that is relevant to their decision to continue or withdraw from participation
• An assurance that prospective participants will be given information on their right to request the withdrawal of data or human biological materials, including any limitations on the feasibility of that withdrawal
• Information concerning the possibility of commercialization of research findings, and the presence of any real, potential, or perceived conflicts of interest on the part of the researchers, their institutions, or the research sponsors
• The measures to be undertaken for dissemination of research results and whether participants will be identified directly or indirectly
• The identity and contact information of a qualified designated representative who can explain scientific or scholarly aspects of the research to participants
• The identity and contact information of the appropriate individual(s) outside the research team whom participants may contact regarding possible ethical issues in the research
• An indication of what information will be collected about participants and for what purposes
• An indication of who will have access to information collected about the identity of participants
• A description of how confidentiality will be protected
• A description of the anticipated uses of data
• Information indicating who may have a duty to disclose information collected, and to whom such disclosures could be made
• A statement to the effect that, by consenting, participants have not waived any rights to legal recourse in the event of research-related harm
• Information on stopping rules and when researchers may remove participants from trial
• All other aspects of the clinical trial that are necessary for a person to make the decision to participate in the clinical trial

Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

Based on the NMPA-GCP-No57-2020, the Measures-Ethics, the EC-Guide, and the RegEthics, 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 without violating the principles of confidentiality, monitors, auditors, ethics committees (ECs), and inspectors from drug regulatory authorities may access the participants’ original medical records to verify the process and clinical trial 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
• 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.

Overview

In accordance with the CanadaFDR and the G-TCPS2, Canada’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The G-TCPS2 states that a participant’s rights must be clearly addressed in the informed consent form (ICF) and during the informed consent process. For Health Canada (HC)’s interpretation of the relevant provisions of the CanadaFDR, see the G-FDR-0100.

Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

The Right to Participate, Abstain, or Withdraw

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

The Right to Information

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

The Right to Privacy and Confidentiality

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

The Right of Inquiry/Appeal

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

The Right to Safety and Welfare

The G-FDR-0100 upholds the Declaration of Helsinki (CAN-58), which states that a research participant’s right to safety and the protection of their health and welfare must take precedence over the interests of science and society.

Overview

In accordance with the Declaration of Helsinki (CHN-84), principles set forth in the NMPA-GCP-No57-2020, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R3) (CHN-37) (which all drug clinical trials conducted after March 31, 2026, will be subject, per NMPA-No125-2025), China’s ethics standards safeguard the rights of research participants. Participants also have the right to receive the nationally available standard of health care, and the right to report any trial-related injuries or issues to the investigator(s) and the ethics committee (EC). The RegEthics states that the EC must protect the legitimate rights and interests of the participants, safeguarding their dignity, and promoting the development of biomedical research norms. As indicated in the NMPA-GCP-No57-2020, the EC-Guide, and the RegEthics, a participant’s rights must be clearly addressed in the informed consent form (ICF) and during the informed consent process. (See the Required Elements; Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information regarding requirements for participant rights.)

The Right to Participate, Abstain, or Withdraw

As set forth in the NMPA-GCP-No57-2020, the Measures-Ethics, the EC-Guide, and the RegEthics, the participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As delineated in the Measures-Ethics, the EC-Guide, the NMPA-GCP-No57-2020, and the RegEthics, a potential research participant or the legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study. (See the Required Elements section for more detailed information regarding participant rights.)

The Right to Privacy and Confidentiality

As per the Measures-Ethics, the EC-Guide, the RegEthics, and the NMPA-GCP-No57-2020, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. The NMPA-GCP-No57-2020 also states that it is the responsibility of the investigator(s) to safeguard the confidentiality of research data to protect the identity and records of research participants.

The Right of Inquiry/Appeal

The Measures-Ethics, the EC-Guide, and the NMPA-GCP-No57-2020 state that the research participant or the legal representative/guardian should be provided with contact information for the investigator(s) and the EC to address trial-related inquiries and/or to appeal against a violation of the participant’s rights. (See the Required Elements section for more detailed information regarding participant rights.)

The Right to Safety and Welfare

The NMPA-GCP-No57-2020 states that a research participant’s right to safety and the protection of health and welfare must take precedence over the interests of science and society.

G-FDR-0100 states that in emergency situations, when prior consent of the participant is not possible, the consent of the participant's legal representative/guardian (as defined by provincial requirements), if present, should be requested. When prior consent of the participant is not possible, and the participant's legal representative/guardian is not available, enrollment of the participant should require measures described in the protocol and/or elsewhere, with documented approval by the ethics committee (EC) (known as a research ethics board in Canada), to protect the participant's rights, safety, and well-being, and to ensure compliance with applicable regulatory requirements. The participant or the participant's legal representative/guardian should be informed about the trial as soon as possible, and consent should be requested as appropriate.

Also see the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R3) (CAN-52), which Canada has implemented per CAN-50. The G-FDR-0100 explains the relationship between the CanadaFDR and CAN-52, including additional guidance where needed or where CAN-52 does not apply. At all times, where the CanadaFDR exceeds the guidance set out in CAN-52, the CanadaFDR takes precedence.

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

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

The G-TCPS2 states that consent will not apply to public health activities undertaken by federal, provincial, and territorial public health officials operating under statutory powers during publicly declared health emergencies. The Ethcs-Emrgcy is an educational resource that provides ethical considerations, including for consent, to help institutions, ECs, and researchers protect participants and uphold public trust in the ethics review and conduct of research during publicly declared emergencies. It includes examples of practical applications from various publicly declared emergency contexts.

The EC-Guide states that during an emergency, clinical studies on human participants must not be conducted without prior review and approval by the ethics committee (EC). Per the NMPA-GCP-No57-2020, in an emergency, if the signed informed consent form (ICF) has not been obtained from the research participant or the legal representative/guardian, or if an effective treatment is lacking, but the investigational product could save the participant’s life, recover health, or alleviate pain, the clinical trial may be conducted. However, the method used on the participant must be explained clearly in the trial protocol as well as the relevant trial documentation, and the EC must approve the protocol in advance. The participant or the legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.

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.

Overview

Per the G-FDR-0100, the responsibility of an institutional ethics committee (EC) (known as a research ethics board in Canada) is to protect the rights, safety, and well-being of all human participants. An EC should pay special attention to trials that may include vulnerable human participants (elderly, children, mentally ill, prisoners, etc.). The G-TCPS2 states that in all Canadian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process.

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

Overview

As per the EC-Guide and the NMPA-GCP-No57-2020, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. The EC-Guide and the NMPA-GCP-No57-2020 define vulnerable persons as those who are relatively (or absolutely) incapable of safeguarding their interests, and consequently, are usually incapable of giving consent or refusing to give consent due to the restriction on their capacities or freedoms. These populations include people with low socioeconomic status and low education levels. The EC-Guide also defines vulnerability to include the following areas: economic, institutional fragility, cognitive, social, medical treatment, and compliance. The NMPA-GCP-No57-2020 also includes members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include persons in nursing homes, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

The NMPA-GCP-No57-2020, which upholds the principles of the Declaration of Helsinki (CHN-84) and the RegEthics, both require special attention to be provided to those participants who cannot give or refuse to give consent for themselves, and for those who will not benefit personally from the research. As per RegEthics, this population includes children, pregnant women, mentally impaired persons, and people with mental disorders. Also, the Measures-Ethics requires special protection for research participants involving specific groups, such as children, pregnant women, the elderly, persons with intellectual and mental disabilities. In addition, special attention should be paid to studies involving fertilized eggs, embryos, fetuses, or those that may be affected by assisted reproductive technologies.

Note: The EC-Guide clarifies that special protections for vulnerable populations must not mean that they are excluded during the recruitment process. Vulnerable people should also benefit from research and be encouraged to participate in clinical research.

For additional information, see the Children/Minors and Mentally Impaired sections.

Per CAN-35, because the G-TCPS2 does not specify an age of consent for children, the decision on whether to seek consent from children is based on whether they have the capacity to understand the research and the risks and benefits of their participation. Youth who have not reached the age of majority (either 18 or 19 depending on the province or territory) may still be old enough to provide their own consent. For children who are not sufficiently mature to provide consent but are able to understand the nature of study participation, researchers must obtain the child’s assent in addition to the consent of an authorized third party. The decision of a child not to assent must be respected regardless of whether third-party consent was obtained. (Note: CAN-35 offers practical guidance that is consistent with the G-TCPS2, but it is only required for research reviewed by the joint Health Canada (HC)-Public Health Agency of Canada (PHAC) Research Ethics Board (REB).)

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

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

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

As per the G-TCPS2, when the research participant is a child, the informed consent form (ICF) must be signed by the child’s parent/legal guardian. All pediatric participants, however, should be informed to the extent compatible with the child’s understanding, and if capable, the pediatric participant should sign and personally date the ICF.

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

Assent Requirements

G-FDR-0100 states that if minors are to be included in a trial, the EC should review the assent information considering the age, maturity, and psychological state of the minor population intended to be enrolled, as well as applicable regulatory requirements. Where a minor is to be included as a participant, age-appropriate assent information should be provided and discussed with the minor as part of the consent process, and assent from the minor to enroll in the trial should be obtained as appropriate. A process for consent should be considered if, during the trial, the minor reaches the age of legal consent, in accordance with applicable regulatory requirements.

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

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

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

For more details and guidance about best practices for research involving pediatric participants, see CAN-12.

As per MPL, minors refer to citizens who are under the age of 18.

In accordance with the NMPA-GCP-No57-2020, when the research participant is a child, the informed consent form (ICF) must be signed by the child’s parent/legal guardian. If the child can decide whether to participate, the ICF should also be approved by the child. The age of consent for children and minors is not defined in the currently available regulatory resources.

Per CDE-No21-2025, when children participate in drug clinical trials, good clinical practice should be strictly followed. Children aged eight (8) years and older are eligible to participate in the trial. The child has the capacity to decide whether to participate in a clinical trial, after obtaining the consent of the child’s parent/legal guardian. The child’s parent/legal guardian must sign an informed consent form, which has been approved by the ethics committee (EC). During the informed consent process, they should be clearly informed of the trial, including the expected benefits and risks. Special attention should be paid to the parent/legal guardian's awareness and emotions to avoid decisions about whether to participate in clinical trials under inappropriate mental conditions. Safety information communication for pediatric trials should consider children’s information comprehension and processing abilities and adjust how clinical information is presented. Communication-based risk control measures should be tailored to different audiences—children, doctors, guardians, and child participants—so that effective communication ensures understanding. The following should be explained, as appropriate, in the investigator’s brochure, informed consent form, and other clinical trial documents: recommendations for proper use of investigational products (IP); the effects on school attendance and physical activity; interactions with alcohol and other pharmacologically active substances; and the risk of administering the IP. Because children prefer illustrations, comics, and visual media, age-appropriate information tools should be used. When developing risk control measures, researchers should consider integration into daily life and accurately reflect the severity of the risk. Safety communication materials should help researchers, child participants, and parent/legal guardians discuss specific risks, including effects on reproduction, growth and development, cognition, potential long-term safety effects, and pregnancy complications.

Per NMPA-No11-2017, clinical trials may be conducted on children depending on existing knowledge of and extrapolation by research results in adults. Drugs that are intended for use in children should be evaluated in the appropriate age group for children and start in the high-age group followed by the low-age group. The EC-Guide stipulates the following conditions when children can participate in research:

• Only when it is shown that the research may be aimed at the prevention and mitigation of serious problems that affect the health and well-being of children
• Research that does not exceed the minimum risk
• Research that moderately exceeds the minimum risk, but is expected to directly benefit the child participants
• Research that moderately exceeds the minimum risk limit, but children may benefit from a population of participants

Per DctrlzCTs-Rare, for decentralized clinical trials of rare diseases, electronic informed consent may be used with children. Since rare diseases often occur in childhood, the use of multimedia interactive modes, such as video, audio, and charts, in the informed consent process will be more conducive to the understanding of child participants and help them to be fully informed.

Assent Requirements

No information is currently available regarding assent requirements for children or minors.

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

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

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

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

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

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