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 Ministry of Science and Technology (MOST).

National Medical Products Administration (NMPA)

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

Per the SC-IRP, the SAMR-Org, and CHN-21, 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 drug clinical trial institutions; participating in drug registration verification and inspection organized by 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. See CHN-61 for contact and logistical information for NMPA’s administrative service hall.

Ministry of Science and Technology (MOST)

The Bioscrty-Law and the MgmtHumanGen delineate that MOST is responsible for China's management of human genetic resources (HGR). In addition, per the Bioscrty-Law, MOST regulates biotechnology safety under the National Security Commission pursuant to a Coordination Mechanism for National Biosecurity (CMNB). The CMNB consists of the competent State Council departments for health, agriculture and rural affairs, science and technology (MOST), and foreign affairs, as well as relevant military agencies, to analyze national biosecurity issues, and organize, coordinate, and drive national biosecurity work. MOST and the other agencies under CMNB establish safety monitoring/reporting requirements, an early warning system, and implementing regulations.

The MgmtHumanGen stipulates that MOST’s 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 committee’s work involves collecting and preserving Chinese HGR, as well as license applications for the transportation, mailing, and carrying of HGR in China. MOST is also charged with strengthening the construction of e-government and facilitating the use of the internet for applicants; for example, see CHN-76. In addition, MOST is authorized to develop and strengthen examination and approval guidelines and model texts on the collection, preservation, utilization, and external provision of HGR in China. The administrative departments for science and technology in the provinces, autonomous regions, and municipalities directly under the Central Government are responsible for managing HGR in that administrative region. All levels of government are responsible for strengthening supervision and inspecting all aspects of the collection, preservation, utilization, and provision of HGR activities.

Per the Bioscrty-Law, the following HGR activities must be authorized by MOST:

• Collecting HGR of China’s important genetic families
• Preserving Chinese HGR
• Using Chinese HGR to carry out international scientific research cooperation
• Delivering, mailing, and exporting Chinese HGR

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

• Collecting HGR from important genetic families and specific regions in China without approval, or collecting HGR of the types and quantities specified by MOST through special regulation
• Preserving Chinese HGR without approval
• Conducting international cooperative scientific research using Chinese HGR without approval
• Failing to pass security review and provide or open to use information on HGR that may affect China's public health, national security, and social public interest to foreign organizations, individuals, and institutions that they establish or actually control, and
• Failing to file with MOST 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). Please note that the NMPA refers to ICH guidelines as foreign reference guidance and provides Chinese translations, when available, at CHN-49.

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

Contact Information

National Medical Products Administration (NMPA)

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

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

Ministry of Science and Technology (MOST)

Per, the HGR-Collection, the HGR-Preservation, the HGR-IntlApprovLicenseGuide, and the HGR-ExprtLicenseGuide, following is MOST’s contact information:

Ministry of Science and Technology
Office address:
Guoyi Hotel (transitional office)
No. 1 Wenxing East Street
Xicheng District
Beijing
P.R. China

Postal address:
No 15. Fuxing Road B
Haidian District
Beijing 100862
P.R. China

Overview

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 speed up the 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).

With regard to reviewing and approving international cooperative research and export license applications for human genetic resources (HGR), in accordance with the Bioscrty-Law and the MgmtHumanGen, the Ministry of Science and Technology (MOST) is responsible for the entire nation's efforts to manage HGR, comprising genetic material and data. MOST’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 ethical principles and ethical reviews per relevant regulations
• Respect the privacy rights of HGR donors, obtain their prior informed consent, and protect their legitimate rights and interests, and
• Comply with the technical norms formulated by MOST

Clinical Trial Review Process

National Medical Products Administration (NMPA)

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 overseas production drug re-registration applications. 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. Per the NMPA-No50-2018 and the NMPA-No48-2020, with regard to chemical drugs and biological products, the applicant should 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. 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.)

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 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. The drug registration inspection of overseas-produced drugs must be implemented by the port drug inspection agency.

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

Per the DRR, the DAL, and the NMPA-No50-2018, 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. 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 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 will achieve innovations and expedited reviews. With regard to priority review, per the NMPA-No230-2015 and the DRR, the NMPA may apply expedited review and approval procedures to applications for urgently needed drugs and vaccines that are intended to treat certain illnesses or patient populations (e.g., children or elderly people) that the State Council or the NMPA consider to be clinically in demand. The DRR expanded priority review to breakthrough therapeutic drugs, which are used to prevent and treat diseases with the following conditions: are seriously life threatening or seriously affect the quality of life, there are no effective prevention or treatment methods, and there is sufficient evidence to show that they have obvious clinical advantages. Applicants must apply to the CDE at the critical stage of the drug clinical trial. See CHN-69 for handling guidelines on priority review and approval.

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.

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 in the past decade. Applicants may apply for a drug listing and proceed to conduct the clinical trials while the CDE conducts a technical review of the application materials.

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

The NMPA-No34-2022 indicates that if there are protocol changes that have a significant impact on trial safety, scientific validity, or data reliability the sponsor should submit a new clinical trial application to the NMPA.

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. CHN-19 and CHN-43 describe the requirements for clinical trial and drug registration applications using trial data generated entirely overseas, as well as data generated from simultaneous research occurring in China and abroad. CHN-22, CHN-9, and CHN-11 also provide useful information on the NMPA’s overall clinical trial application review and approval process.

Ministry of Science and Technology (MOST)

The MgmtHumanGen and the Bioscrty-Law prohibit foreign entities or individuals from collecting or preserving Chinese HGR in China, or providing Chinese HGR for use abroad. However, foreign entities are permitted limited use of Chinese HGR 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, the foreign entity and the Chinese entity must jointly file an application for approval to MOST, and the research must pass ethical review in the countries (regions) where the partners are located. The only exception to the approval requirement is international collaborations in clinical trials that do not involve the export of Chinese HGR materials such as organs, tissues, or cells comprising the human genome, genes, or other genetic substances. Such clinical trial collaborations, however, must be filed with MOST on its online platform (CHN-76), which will generate a record number. See the HGR-IntlRecordMgtGuide, the HGR-IntlApprovLicenseGuide, and the HGR-ExprtLicenseGuide for details on the HGR processes and policies. See Submission Process and Submission Content sections and the Specimens topic for additional information on HGR regulatory management.

Regarding multi-center clinical research using HGR in international cooperative clinical trials, the HGR-IntlApprovLicenseGuide and the HGR-IntlRecordMgtGuide indicate that the lead unit can go through the ethical review process to apply for approval. Documentation showing EC approval and a letter of commitment signed and sealed by the lead unit should be submitted to the online platform (CHN-76).

The Bioscrty-Law prohibits engaging in biotechnology research, development, and application activities that endanger public health, damage biological resources, or destroy ecosystems and biodiversity. Units engaged in biotechnology clinical trials must be responsible for the safety of their biotechnology research, development, and application; adopt biosafety risk prevention and control measures; and formulate biosafety training, follow-up inspections, regular reports, etc. China is implementing a classified management system for biotechnology research and development activities into three (3) categories: high-risk, medium-risk, and low-risk. The risk classification standards are to be formulated, adjusted, and announced by the competent State Council departments for science and technology (Ministry of Science and Technology (MOST)), 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.

Overseas Data and Waiving Local Clinical Trials

The NMPA-No35-2017 and interpretations in CHN-43 adjust 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. This removes the need to conduct local clinical trials in addition to existing overseas research—a requirement that typically delayed projects by several years. Overseas clinical trial data is acceptable for direct China registration provided that:

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

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

For further guidance on the NMPA’s drug regulatory requirements, please refer to CHN-60.

National Medical Products Administration (NMPA)

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, NMPA-No53-2015, CHN-63, CHN-64, CHN-65, CHN-66, CHN-67, and CHN-68, the NMPA charges the following drug registration fees to review and approve clinical trials as part of the drug registration process:

• 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 the NMPA-No53-2015, the NMPA-No75-2020, CHN-63, CHN-64, CHN-65, CHN-66, CHN-67, and CHN-68, 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 the NMPA-No53-2015 and the NMPA-No75-2020.

Payment Instructions

Per CHN-61, payment should be submitted when the applicant receives a notice of acceptance from the NMPA, meaning the application passed the administrative screening. The applicant should pay the fee in accordance with the instructions on the notice of payment. For questions about payment matters, call the NMPA Administrative Acceptance Service Hall at 86-010-88331734 for drug administrative licensing.

In addition, NMPA-No37-2022 indicates that to register a drug, the applicant should submit the drug registration application to NMPA’s Administrative Acceptance Service Hall (CHN-71 and CHN-61). 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.

Ministry of Science and Technology (MOST)

Per HGR-Collection, HGR-Preservation, HGR-ImpFamilies-DeclReg, HGR-ExprtLicenseGuide, and HGR-IntlApprovLicenseGuide, there is no fee for review and approval from the Ministry of Science and Technology (MOST) for clinical trial-related activities using human genetic resources.

Overview

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

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 EC-Guide and the RegEthics, ECs should have at least seven (7) members. 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 ethical review. However, no strict parameters are required to be followed. In areas where minority ethnic groups reside, the institution should consider including members of those groups on the EC. The EC-Guide and the RegEthics provides that the EC can hire an independent consultant if necessary. The independent consultant advises on specific project issues under review and does not participate in the voting.

The EC-Guide and the RegEthics provide that the EC composition should include a chairperson and several vice chairpersons, all of whom 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 his/her duties.

ECs should not accept any research project applications that are against national laws and regulations. In addition, the EC should refuse to review any projects in which they have a conflict of interest. See the EC-Guide for additional guidance on managing ECs.

Terms of Reference, Review Procedures, and Meeting Schedule

As per the RegEthics, the EC-Guide, and the NMPA-GCP-No57-2020, each institution must have written SOPs, including a process to be followed for conducting reviews. 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. This training should be renewed every two (2) years in a continuing education program. In addition, they should have experience participating in drug clinical trials and obtain the good clinical practice (GCP) training certificate recognized by the National Medical Products Administration (NMPA). The RegEthics states that EC members should agree to disclose their names, occupations, and affiliations, and to sign the reviews, confidentiality agreements, and a conflict of interest declaration. Each EC member term is five (5) years, after which they can be reappointed. Each institution that establishes an EC should also provide financial compensation to its committee members. EC review and approval decisions must take place during formal meetings. The majority of the total EC membership should be present to conduct reviews.

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

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

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

Overview

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). The RegEthics specifies that the EC’s review must comply with the provisions of national laws and regulations and respect the participant’s willingness to participate in the research, while observing the principles of benefit, non-harm, and fairness.

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 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.

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.

The EC-Guide and the NMPA-GCP-No57-2020 provide that the EC’s scope of review must include the following (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source):

• Whether the qualifications and experience of the investigator meet clinical research requirements
• Whether the research plan meets the required scientific and ethical principles
• 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’ 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
• 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

Per the EC-Guide, the EC will make one (1) of the following decisions:

• 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.
• 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 EC-Guide delineates that the EC must give written notice of its decision to the applicant within 10 working days after the review. An approval is valid for no more than 12 months, at which point the EC will conduct a follow-up review. However, the EC may set more frequent follow-up reviews if it finds a higher degree of risk. The review schedule and plan approval date must be documented. 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.

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 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 Committee of Medical Ethics Experts to provide advice on the ethical review of research that involves a relatively high-risk or special population.

Per the EC-Guide, the review of international cooperative research projects requires ethical 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 ethical review results of participating institutions. ECs of the participating institutions must conduct an ethical review of the research in which the institution participates in a timely manner and provide feedback to the lead agency for review. CHN-45 provides more information on EC review.

No relevant provisions are currently available that provide ethics committee fee information.

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). 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.

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 ethical review of biomedical research involving human beings, establishing the National Committee of Medical Ethics Experts, and for developing policies relating to ethical review. The National Committee of Medical Ethics Experts 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.

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 Committee assists in promoting the institutionalization and standardization of the ethical 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 ethical review work of biomedical research involving people in its administrative region. For additional information about supervision and management of ECs, including inspections, see the RegEthics. For additional details and analysis of China’s ethics review system and structure, see CHN-45.

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. CHN-9 offers an analysis and overview of the NMPA application submission process and reforms.

Per the MgmtHumanGen, applications for collection, preservation, and use of human genetic resources (HGR) in research must be submitted to the Ministry of Science and Technology (MOST) for approval, as well as pass an ethics review in the partners’ country.

Regulatory Submission

National Medical Products Administration (NMPA)

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. 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 multi-centered 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.) The NMPA-No23-2023 provides guidance on common issues and general requirements for the Phase III pre-clinical trial meeting with CDE in regards to innovative drugs.

As described in CHN-61, drug registrations and associated clinical trial application forms should be submitted online to the NMPA’s Administrative Acceptance Service Hall (CHN-71 and CHN-61). According to CHN-61, applicants can call the NMPA Administrative Acceptance Service Hall with questions about administrative matters at: +86-010-88331793 (drug acceptance) and +86-010-88331734 (consultation of drug matters). Following administrative acceptance, per the DRR, clinical trial research materials, consultations, and data submittals are handled at the CDE’s Applicant’s Window (CHN-58).

The DRR clarifies that it regulates only clinical trials conducted for drugs seeking market approvals in China, which may include Phase I, II, III, IV, and bioequivalence studies. As delineated in the DRR, the NMPA-No51-2016, and the SC-Opinions-No44, the drug classification determines the drug and clinical trial registration pathway. (See the Scope of Review section for drug classification information.) See CHN-63, CHN-64, CHN-65, CHN-66, CHN-67, CHN-68, CHN-70, and CHN-69 for 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.

If a sponsor intends to carry out a bioequivalence test, he/she must carry out relevant research work in accordance with the filing plan after completing the filing of the bioequivalence test on the CDE’s website via CHN-58. Per the NMPA-No230-2015, for generic drugs, the bioequivalence study will only need to be filed with the NMPA (formerly it was a review and approval procedure). The applicant should submit record filing materials to the NMPA 30 days before submitting the bioequivalence studies. For the generic drug filing, the applicant must obtain EC approval and sign a clinical study agreement with the clinical site prior to filing the bioequivalent study. See CHN-70 for handling guidelines for bioequivalent drugs.

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

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 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

The NMPA-No44-2020, the NMPA-No43-2020, and the NMPA-No10-2018 require applicants to apply the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) 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).

Per NMPA-No194-2017, drug registration and clinical trial application materials must be in Chinese. Foreign language materials should be translated into Chinese. For foreign language materials with translations, the translation should be first and the original text should follow. The applicant is responsible for the accuracy of the translation.

Ministry of Science and Technology (MOST)

Per the MgmtHumanGen, the foreign entity and the Chinese entity must jointly file an application for approval to MOST and pass an ethics review in the partners’ countries. The only exception to the MOST approval requirement is international collaboration in clinical trials that do not involve the export of Chinese HGR materials such as organs, tissues, or cells comprising the human genome, genes, or other genetic substances—these must be filed with MOST, which will generate a record number (see below for steps) and pass an ethics review in the partners’ countries. See CHN-76 for MOST’s service webpage that contains HGR administrative license information, including service guides, contact information, decision results, handling, etc. The HGR-Procedures outlines the procedural steps in applying for MOST’s review and approval for collecting HGR, exporting HGR, HGR international cooperative research, and record filing (i.e., notifying) for an international clinical trial that does not involve the export of HGR. The following service guides detail the processes in even greater specificity:

• HGR-Collection covers license application procedures for collecting Chinese HGR in China
• HGR-DataUse covers filing procedures to transfer HGR data to foreign organizations
• HGR-Preservation covers license application procedures for preserving Chinese HGR in China in suitable environmental conditions to ensure its quality and safety for future scientific research activities
• HGR-ImpFamilies-DeclReg covers procedures for declaring and registering activities for the use of HGR from important genetic families and in specific areas of China
• HGR-IntlApprovLicenseGuide covers license application procedures for international cooperation in the use of Chinese HGR for research
• HGR-ExprtLicenseGuide covers license application procedures for international cooperation in exporting Chinese HGR for research (See the Specimens topic for more information on applying for an export license for HGR)
• HGR-IntlRecordMgtGuide covers filing procedures for clinical institutions to obtain authorization to use HGR in international cooperative clinical trials in China

As specified in the HGR-Collection, only a Chinese entity may apply for and hold a MOST license for the actual collection of Chinese HGR. See the HGR-Procedures and the HGR-Collection for details on submittal and review procedures.

Per the HGR-Procedures and the HGR-IntlApprovLicenseGuide, the following is the submission process for MOST’s review and approval of HGR international cooperative research. The applicant submits an electronic version of the application materials to the online platform (CHN-76). MOST will complete the pre-examination within five (5) working days after receiving the electronic version of the application materials. If the application materials are complete and conform to the prescribed form, the applicant may print the paper materials through pre-examination; if the application materials are incomplete or do not meet the requirements, the pre-examination will not be passed, and the applicant will be notified of the contents that need to be corrected through the online platform. For applicants that pass the pre-examination, they must print out the online, pre-accepted electronic application materials on A4 paper. The cover and signature stamp page should be printed single-sided and the rest of the document should be double-sided. There should be one (1) copy with plastic binding. Attachments should be bound to the application. After receiving and formally accepting a complete package of the paper application materials submitted by the applicant, MOST will conduct a formal examination within five (5) working days. MOST’s experts will conduct a technical review of the accepted application and develop an expert review opinion. MOST will publish the results on its website (CHN-76). If the approval is not granted, the reasons will be explained. If the approval is granted, MOST will send the approval decision letter to the provincial science and technology administrative department by mail within 10 working days and publish the mailing details on its website (CHN-76). The applicant should then go to the provincial science and technology administrative department to receive the approval decision letter with the acceptance form.

With regard to the record-filing procedure (i.e., notification) for an international clinical trial using HGR that will not leave the country, the HGR-Procedures and the HGR-IntlRecordMgtGuide specify that the applicant should submit the required materials to MOST through CHN-76. Following the submission and after the applicant receives the record number, the international cooperative clinical trial can begin. A legal entity established in accordance with Chinese law must handle the filing formalities. Documentation showing EC approval and a letter of commitment signed and sealed by the Chinese applicant should be submitted. MOST will publicly announce its decision, which will include the applicant’s record number. In the course of clinical trials, if there is a major change of event (e.g., research purpose, research content, research plan, or cooperation period), the Chinese sponsor must terminate the record, upload the summary report, and re-record the case. After obtaining a new record number, the sponsor can continue conducting the international cooperative clinical trial.

Per the HGR-Collection, HGR-IntlApprovLicenseGuide, HGR-Preservation, and the HGR-ExprtLicenseGuide, the following is the notification and application submission contact information for MOST:

Ministry of Science and Technology
China Biotechnology Development Center
1st Floor, Building 4, No. 16 Yard
Xisihuan Middle Road
Haidian District, 100039
P.R. China
Phone: 010-88225151

See the HGR-IntlApprovLicenseGuide, the HGR-ExprtLicenseGuide, and the HGR-Procedures for assembly and number of copies information related to HGR licenses.

Ethics Review Submission

Each EC has its own required submission procedures.

Regulatory Authority Requirements

National Medical Products Administration (NMPA)

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 National Medical Products Administration (NMPA). When applying for drug registration, the applicant must provide true, sufficient, and reliable data, materials, and samples to prove the safety, effectiveness, and quality controllability of the drug. In cases where overseas research materials and data are used to support drug registration, its source, research institution, or laboratory conditions, quality system requirements, and other management conditions should conform to prevailing international principles and applicable Chinese drug registration management requirements. CHN-63, CHN-64, CHN-65, CHN-66, CHN-67, CHN-68, CHN-70, and CHN-69 contain application materials and handling guidelines covering domestic drug and biological product clinical trial applications; imported drug and biological product clinical trial applications; priority review application procedures; and bioequivalence filing procedures. In general, the applications require information about the drug (e.g., names, formulation and ingredients, indications, and packaging), patents, the applicant, and the institution(s). In addition, the applications require a declaration attesting that the application and associated materials comply with the DAL, the DRR, and other applicable laws and regulations. The application and submitted data and samples must be true and legal, and they should not infringe on the rights and interests of others. The content of the electronic file submitted must be the same as the printed file. If any data is found to be false, the applicant bears the legal consequences caused by it.

The NMPA-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

Pursuant to the SC-Opinions-No42, the NMPA announced in the NMPA-No10-2018 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 and CHN-9 for additional analyses and overview of the China clinical trial application submission content.

Ministry of Science and Technology (MOST)

With regard to human genetic resources (HGR) licenses, the HGR-Procedures and CHN-56 summarize the license and application contents, which is regulated by the Ministry of Science and Technology (MOST).

The following service guides detail the submission content in greater specificity and include the templates:

• HGR-Collection covers license application procedures for collecting Chinese HGR in China and requires legal person qualification materials, ethics review approval, informed consent form (ICF), collection plan, HGR management system, and a cooperation agreement
• HGR-DataUse covers filing procedures to transfer HGR data to foreign organizations and requires the record information form, legal person qualification with electronic signature, and cooperative scientific research approval
• HGR-Preservation covers license application procedures for preserving Chinese HGR and requires legal person qualification, ICF, ethics review approval, preservation plan and management system, and preservation of technical documents
• HGR-ImpFamilies-DeclReg covers content requirements for declaring and registering activities for the use of HGR from important genetic families and in specific areas of China
• HGR-IntlApprovLicenseGuide covers license application procedures for international cooperation in the use of Chinese HGR for research and requires legal person qualification; two (2) letters of commitment (provided by participating medical institutions); research proposal text; ethics review approval; ICF; international cooperative agreement text; agreements involving the collection, transportation, testing, and destruction of HGR; clinical trial approval documents, notices, or filing announcement materials; and past administrative approval of the project
• HGR-ExprtLicenseGuide covers license application procedures for international cooperation in exporting Chinese HGR for research and requires legal person qualification, ethics review approval, and the ICF
• HGR-IntlRecordMgtGuide covers filing procedures for clinical institutions to obtain authorization to use HGR in international cooperative clinical trials in China; it requires legal person qualification, list of other participating clinical institutions, ICF, ethics review approval, the research plan, the international cooperative agreement, the cooperation agreement signed between the clinical institution and its commissioned testing institution, agreement texts involving the transshipment of HGR, clinical trial approval documents, notices, or filing announcement materials, and the letter of commitment (provided by participating medical institutions)

Additional 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 RegEthics and the EC-Guide to exemplify the common elements shared by the various application forms (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

• Application for Human Research Ethics Review (See CHN-35 and CHN-34 for sample institutional forms)
• 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
• 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
• Other relevant materials that the EC believes need to be submitted

Clinical Protocol

As delineated in the NMPA-GCP-No57-2020 and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CHN-37), the clinical protocol should include the following elements (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

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

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

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.

Regulatory Authority Approval

National Medical Products Administration (NMPA)

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. Per the DRR, the NMPA-No50-2018, CHN-63, CHN-64, CHN-65, CHN-66, CHN-67, and CHN-68, 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 time to conduct the following actions 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
• Where overseas verification is initiated, the time taken by this activity

The application review by the Center for Drug Evaluation (CDE) and inspections and testing by National Institutes for Food and Drug Control (NIFDC) will affect the timeline of review. The CDE conducts technical reviews and the NIFDC tests drug samples. 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.

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

Ministry of Science and Technology (MOST)

Pursuant to the HGR-Collection, the HGR-IntlApprovLicenseGuide, the HGR-Preservation, and the HGR-ExprtLicenseGuide, within 20 business days after formal acceptance, the Ministry of Science and Technology (MOST) will approve or disapprove licenses for the collection, use, preservation, and export of human genetic resources (HGR). If there are special reasons, MOST may extend this review period for an additional 10 business days.

Ethics Committee Approval

In accordance with the NMPA-GCP-No57-2020, an applicant must also submit the clinical trial application for review and approval by an institutional EC. Per the NMPA-GCP-No57-2020 and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CHN-37), the institutional EC should review a proposed clinical trial within a reasonable time. The EC’s recommendations should be issued in writing and should indicate an approval; an approval after necessary modifications have been made; a disapproval; or a decision to terminate or suspend an already approved trial. The EC-Guide delineates that the EC must give written notice of its decision to the applicant within 10 working days after the review.

Overview

 Per the DRR, clinical trials must be conducted in drug clinical trial institutions 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.

As delineated in MgmtHumanGen, an international clinical trial using human genetic resources (HGR) in country must be filed with the Ministry of Science and Technology (MOST) before it begins. MOST must also review and approve collections of HGR of important genetic families and specific areas in China or HGR as specified by MOST and international cooperative scientific research before a trial begins. See Clinical Trial Lifecycle and Specimens topics for more information.

Clinical Trial Agreement

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

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

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

Clinical Trial Registration

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

Before starting a clinical trial, the clinical trial information must be registered in any of these situations:

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

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.

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 IB). 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 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 EC with other required information, such as autopsy reports and final medical reports.

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) at 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.

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 ethics committees (EC). Further, the sponsor must promptly report SUSARs to all participating investigators, clinical trial institutions, and ECs; sponsors must also report SUSARs to drug regulatory and health authorities. The NMPA-GCP-No57-2020 states that after receiving safety information from the sponsor, the investigator should sign the documentation and consider whether to treat the participant and make corresponding adjustments to the protocol.

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

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

Form Completion & Delivery Requirements

As per the NMPA-No50-2018, the NMPA-No10-2018, and the G-SftyRptStds, investigators must comply with the rapid reporting requirements in the International Council for Harmonisation (ICH)’s E2A Guideline (Clinical Safety Data Management: Definitions and Standards for Expedited Reporting) (CHN-39), and ICH E2B (R3) (Electronic Transmission of Individual Case Safety Reports) (CHN-40). As indicated in the G-SftyRptStds, all SUSARs from clinical trials should be reported in compliance with E2A and E2B (R3). To comply with these requirements, the project’s electronic safety database must meet the E2B (R3)’s XML format and bes 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

The NMPA-GCP-No57-2020 and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (CHN-37) require the investigator to submit an annual report on the clinical trial to the ethics committee (EC). In addition, the investigator must provide a progress report in accordance with requirements established by the EC. When there is a situation that significantly affects the implementation of clinical trials or increases the risks to participants, the investigator should report in writing to the sponsor, the EC, and the clinical trial institution as soon as possible. Per the DRR and the NMPA-No65-2021, during the clinical trial, the sponsor must conduct an annual review and evaluation of the drug-related safety information. This annual safety update report should be submitted within two (2) months after the full year following approval of the drug clinical trial. The DRR clarifies that the Center for Drug Evaluation (CDE) may require the sponsor to adjust the reporting cycle based on the situation. Additional guidance on the safety update report is provided in the NMPA-No7-2020 and the NMPA-No65-2021.

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

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

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 the results of clinical trials on the Applicant’s Window (CHN-58).

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

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

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

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

Overview

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

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

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

Institutional Registration

Per the SC-Opinions-No42 and the NMPA-NHC-No101-2019, the NMPA adopted a registration system for institutions with qualifying conditions to be entrusted to conduct clinical trials and operate ethics committees (ECs). This reform eases institutional burdens by removing the pre-approval accreditation requirements. Among other conditions, the NMPA-NHC-No101-2019 specifies that an institution is entrusted to conduct clinical trials if the main investigators of clinical trials have senior professional titles and have participated in more than three (3) clinical trials. The main investigator must supervise the implementation of drug clinical trials and the performance of each researcher in the performance of their work duties and take measures to implement the quality management of drug clinical trials to ensure the reliability and accuracy of the data. The NMPA is establishing a drug clinical trial institution record management information platform for the registration and operation management of drug clinical trial institutions, as well as the supervision and inspection by drug regulatory agencies. For additional details on the registration conditions, operations management, supervision, and inspection of institutions, see the NMPA-NHC-No101-2019.

Foreign Sponsor Responsibilities

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

Data and Safety Monitoring Board

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

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

Multicenter Studies

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

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

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

Insurance

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

Compensation

Injury or Death

In accordance with the NMPA-GCP-No57-2020 and the EC-Guide, the sponsor must take appropriate measures to ensure that the participants and researchers can be compensated. The sponsor must bear the costs of diagnosis and treatment for the damage or death of the participant related to the clinical trial, as well as the corresponding compensation. Further, the sponsor must provide free trial drugs to participants and pay for medical testing related to clinical trials.

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

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, the NMPA-No112-2016, and the NMPA-No65-2021, the sponsor must establish quality control (QC) and quality assurance (QA) systems for the clinical trial. The NMPA-GCP-No57-2020 and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37) specify that the quality management system for clinical trials should cover the entire process of clinical trials, including the design, implementation, recording, evaluation, result reports, and filing of clinical trials. NMPA-No65-2021 reiterates that sponsors must establish a quality management and pharmacovigilance system for investigational products (IPs). This system must collect safety information, monitor risk, identify and control safety problems in a timely manner, proactively take necessary risk control measures, and evaluate the effectiveness of risk control measures to protect participant safety.

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

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

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

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

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

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

• NMPA-No15-2023 provides technical guidelines for clinical trials of chemical compound drugs
• NMPA-No34-2022 lays out guidelines for protocol changes during drug clinical trials
• NMPA-No32-2022 has guidelines for clinical trials of topically administered local effective drugs
• NMPA-No31-2022 has guidelines for conduct of research with in vivo gene therapy products
• NMPA-No30-2022 has guidelines for conduct of research involving immune cell therapy products
• NMPA-No29-2022 has guidelines for conduct of research with in vitro gene modification
• NMPA-No27-2022 has guidelines for conduct of research involving specific human immunoglobulins
• NMPA-No22-2021 describes a research and development model to guide researchers in managing pharmaceutical changes of innovative drugs
• NMPA-No17-2022 has guidelines for clinical pharmacological research of biosimiliars
• NMPA-No4-2022 has guidelines for research of human bioavailability of bioequivalence of innovative drugs
• NMPA-No71-2021 has guidelines for research of drugs for rare diseases
• NMPA-No68-2021 lays out guiding principles for writing the clinical risk management plan
• NMPA-No66-2021 offers guiding principles for multiplicity issues during drug clinical trials, which refers to multiple testing problems that can lead to errors and inappropriate interpretation of trial results
• NMPA-No63-2021 provides guidelines for drug clinical trial data management and statistical analysis plan
• NMPA-No62-2021 provides guidelines for the application of patient-reported outcomes in drug clinical development
• NMPA-No59-2021 offers guidelines for analyzing the effectiveness of clinical studies of drugs
• NMPA-No50-2021 has guidelines for long-term follow-up for clinical research of gene therapy products
• NMPA-No6-2021 aims to guide sponsors in adopting and implementing an adaptive design to improve the success and quality of the research results
• NMPA-No54-2020 describes the clinical features of new uses of chemical drugs and associated principles of clinical trial design and evaluation

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

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

Monitoring Requirements

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

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

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

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

Premature Study Termination/Suspension

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

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

Further, the NMPA-GCP-No57-2020 states that when a clinical trial is completed or terminated early, the sponsor must submit a clinical trial report to the NMPA. The clinical trial summary report must comprehensively, completely, and accurately reflect the clinical trial results. The safety and effectiveness data of the clinical trial summary report must be consistent with the clinical trial source data.

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 setting, 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 the visibility of the data conversion 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.

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

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

Records Management

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

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

Responsible Parties

For requirements on personal data protection, the PIPL delineates that the sponsor is a data processor and must independently determine the purpose and method of processing personal information.

Data Protection

Per the PIPL, the sponsor 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 of people located within the country. In addition, the PIPL applies to data processing activities conducted outside of China involving personal information of people located in China under the following circumstances: (1) where the processing is for the purposes of providing products or services to individuals located in China, (2) where the processing is for analyzing and evaluating the behavior of individuals located in China, or (3) other circumstances stipulated by laws and regulations.

Per the PIPL, the processing of personal information should have a clear and reasonable purpose and should be directly related to the purpose of processing with the least impact on personal rights and interests. The sponsor 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 sponsor 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 sensitive personal information, which includes medical health information, the sponsor 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.

Per the PIPL, to send personal information outside of China, the sponsor must meet one (1) of the following conditions:

• Pass the security assessment organized by the national cybersecurity and information department (See below in Data Security)
• Conduct personal information protection certification by professional institutions in accordance with the requirements of the Cyberspace Administration of China (CAC)
• Enter into a contract with the overseas recipient in accordance with the standard contract formulated by the CAC stipulating the rights and obligations of both parties
• Other conditions stipulated by laws, administrative regulations, or national cyberspace administration departments
• Where China’s international treaties and agreements permit providing personal information to foreign recipients

The sponsor must inform the participant of the name of the foreign recipient, contact information, processing purpose, processing method, and types of personal information. In addition, the foreign sponsor 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. For additional analysis of the China’s personal information protection legislation, see CHN-25.

The DataScrty requires the sponsor to manage its data processing activities to ensure data security, promote data development and utilization, protect the legitimate rights and interests of individuals and organizations, and safeguard national sovereignty, security, and development interests. CAC-No11-2022 standardizes requirements for exporting “important data” and personal information to protect the rights and interests of personal information, preserve national security and the societal public interest, and promote the cross-border security and free flow of data. Important data is defined as data that, once tampered with, destroyed, leaked, or illegally obtained or used, might endanger national security, economic operations, social stability, public health, or safety in China. Sponsors 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 assessment report must be submitted to CAC through the provincial-level department where the sponsor is located, and include the following materials:

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

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

Consent for Processing Personal Data

Per the PIPL, personal consent must be made voluntarily and with the participants’ full knowledge of the processing purpose, processing methods, and types of personal information processed. In an emergency, if it is not possible to obtain consent in a timely manner to protect the life, health, property, and safety of participants, the sponsor 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.)

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 RegEthics, and the EC-Guide. In addition, China is implementing the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37) as a guidance document. As per the NMPA-GCP-No57-2020, the DAL, the EC-Guide, and CHN-37, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an ethics committee (EC) and provided to the National Medical Products Administration (NMPA) with the clinical trial application. Per the MgmtHumanGen and CHN-56, the ICF must also be provided to the Ministry of Science and Technology (MOST) 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 and/or his/her legal representative(s) or guardian(s).

The NMPA-GCP-No57-2020 and CHN-37 state that the investigator, or a person designated by the investigator, must provide detailed research study information to the participant and/or his/her legal representative(s) or guardian(s). As delineated in the NMPA-GCP-No57-2020 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 his/her legal representative(s) or guardian(s) should also be given adequate time to consider whether to participate. As per the NMPA-GCP-No57-2020, CHN-37, and the EC-Guide, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant and/or his/her legal representative(s) and/or guardian(s) to waive or appear to waive his/her legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

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 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.

Re-Consent

The NMPA-GCP-No57-2020 and CHN-37 require investigators to use the latest version of the ICF approved by the EC and, if necessary, participants in the clinical trial process should sign an updated ICF again. If new information may affect the participant’s continued participation in the trial, the investigator must promptly notify the participant and his/her legal representative(s) or guardian(s) and make corresponding records. Per the RegEthics, the investigator should obtain re-consent under the following circumstances:

• 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
• Other changes occur during the research

Language Requirements

 The NMPA-GCP-No57-2020, 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, CHN-37, and the EC-Guide, the participant and his/her legal representative(s) or guardian(s), and researchers who perform informed consent, should sign and date the ICF. If the ICF is not signed by the participant, the relationship should be marked on the form. If the participant and his/her legal representative(s) or guardian(s) 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 his/her legal representative(s) and/or guardian(s)
• The participant and his/her legal representative(s) and/or guardian(s), 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 his/her legal representative(s) and/or guardian(s) 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: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

• 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 body 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 NMPA-GCP-No57-2020, the EC-Guide, the RegEthics, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37), the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.):

• The study purpose, procedures, and duration of the trial
• Any expected risks or discomforts to the participant
• Any expected benefits to the participant; if no benefit is expected, the participant should be informed of this point
• The participant’s responsibilities
• The approximate number of participants involved in the trial
• Those aspects of the trial that are experimental
• Treatment available to the participant as well as important potential risks and benefits associated with this treatment
• The alternative procedure(s) or course(s) of treatment that may be available to the participant, and their important potential benefits and risks
• The nature, form, and extent of compensation for participation
• Any expenses the participant needs to pay to participate in the trial
• The extent to which confidentiality of records identifying the participant will be maintained, and a statement that, when necessary, the sponsor, the EC, the National Medical Products Administration (NMPA), and drug authorities in the provinces, autonomous regions, and municipalities may be required to review participant data
• 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 and during 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.
• That the participant or the legally acceptable representative will be informed in a timely manner if information becomes available that may be relevant to the participant’s willingness to continue participation in the trial
• When appropriate, the ethics committee (EC) may require the following additional information: whether the research may put the participant at risk but the risk is not currently foreseeable; researchers can terminate a participant’s participation in the study without their consent; new major discoveries during the research will be provided to the participant; and whether there is a potential conflict of interest
• If applicable, how biological samples will be handled

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

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(R2) (CHN-37), China’s ethical 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.) See CHN-26 for an analysis of clinical trial participants’ rights in China.

The Right to Participate, Abstain, or Withdraw

As set forth in the NMPA-GCP-No57-2020, the EC-Guide, the RegEthics, and CHN-37, the participant or his/her legal representative(s) or guardian(s) should be informed that participation is voluntary, that he/she may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As delineated in the EC-Guide, the NMPA-GCP-No57-2020, the RegEthics, and CHN-37, a potential research participant and/or his/her legal representative(s) or guardian(s) has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation 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 EC-Guide, the RegEthics, the NMPA-GCP-No57-2020, and CHN-37, 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 EC-Guide, the NMPA-GCP-No57-2020, and CHN-37 state that the research participant and/or his/her legal representative(s) or guardian(s) 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 his/her rights. (See the Required Elements section for more detailed information regarding participant rights.)

The Right to Safety and Welfare

The NMPA-GCP-No57-2020 and CHN-37 state that a research participant’s right to safety and the protection of his/her health and welfare must take precedence over the interests of science and society.

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 and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37), in an emergency, if the signed informed consent form (ICF) has not been obtained from the research participant or his/her legal representative(s) or guardian(s), 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 and/or his/her legal representative(s) or guardian(s) 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 researcher must provide materials to the EC in a simplified format, including the informed consent form. The EC must pay special attention to the informed consent process and consider the special circumstances during the outbreak and the participant’s vulnerability. Because the participant’s autonomy is challenged, is vulnerable to improper use, and is subject to high risks, the EC must ensure that the participant is fully informed, understands the risk, and voluntarily chooses to participate.

Overview

As per the EC-Guide, the NMPA-GCP-No57-2020, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37), in all Chinese clinical trials, 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 and CHN-37 also include 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.

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. In addition, see CHN-26 for an analysis of clinical trial participants’ rights in China.

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

In accordance with the NMPA-GCP-No57-2020 and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37), when the research participant is a child, the informed consent form (ICF) must be signed by the child’s legal representative(s) or guardian(s). If the child can decide whether he/she is willing 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. See CHN-26 for an analysis of clinical trial participants’ rights in China.

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

Assent Requirements

No information is currently available.

While RegEthics lists pregnant women as a vulnerable population, there are no relevant provisions regarding any special consent procedures for pregnant women, fetuses, or neonates.

Per NMPA-No11-2017, any research studies of pregnant women should include a follow-up evaluation of these participants during pregnancy, as well as the fetuses and the children from that pregnancy.

If a research study is intended for lactating women, the researchers should test the secretion of the drug or its metabolites in human milk, if feasible. If lactating women are recruited into a clinical trial, the effects of the drug on their infants should be monitored and, if necessary, followed.

Pregnant women should be excluded from any research study if the investigational product is not intended for use during pregnancy. In this case, if a pregnancy occurs during the clinical trial, the study should be terminated and reported to the ethics committee for follow-up and evaluation of the pregnancy, fetus, and child.

In accordance with the NMPA-GCP-No57-2020 and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37), informed consent requirements for conducting clinical trials with pregnant or nursing women or fetuses follow the general requirements listed in the Required Elements section. Specifically, the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant.

The NMPA-GCP-No57-2020 and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37) list prisoners as a vulnerable population. Per CHN-37, because incarceration could affect their ability to make a voluntary decision regarding participation in research. A research study involving prisoners should ensure that these prospective participants are informed and are given the opportunity to make their own decisions without any interference from a higher authority. The ethics committee must also ensure that the study will be independently monitored to assure the dignity and rights of the prisoners involved in the research. In accordance with the NMPA-GCP-No57-2020 and CHN-37, informed consent requirements for conducting clinical trials with prisoners should follow the general requirements listed in the Required Elements section.

While the RegEthics lists mentally impaired people as a vulnerable population, there are no relevant provisions regarding any special consent procedures for them. The NMPA-GCP-No57-2020 and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37) allow the ethics committee to approve the participation of research participants who are incompetent, or mentally or physically incapable of giving consent under certain conditions. The informed consent form must be signed and dated by the participant’s legal representative(s) or guardian(s).

As delineated in the NMPA-GCP-No57-2020, investigational products (IPs) are defined as experimental and reference drugs used in a clinical trial.

The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37) define an IP as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial. This includes a product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form, when used for an unapproved indication, or when used to gain further information about an approved use.

Manufacturing

According to the DAL and the NMPA-No28-2020, the National Medical Products Administration (NMPA) is responsible for authorizing the manufacture of investigational products (IPs) in China. See CHN-11 for an analysis of the authorization procedure for manufacturing drugs in China.

Per the DAL and the NMPA-No28-2020, the holder of the drug registration certificate must obtain a drug production license (found at NMPA-No72-2019) to produce a drug or entrust a pharmaceutical production enterprise to produce it. If an entrusted production enterprise is used, the drug registration certificate holder and the entrusted production enterprise must sign an entrustment agreement and a quality agreement. Blood products, narcotic drugs, psychotropic drugs, medical toxic drugs, and pharmaceutical precursor chemicals cannot be entrusted to a pharmaceutical production enterprise for production, unless otherwise stipulated by the NMPA. According to CHN-29, a drug registration certificate is valid for five (5) years and renewable for another five (5) years; the renewal must be submitted six (6) months before the expiration.

As delineated in the DAL and the NMPA-No28-2020, the following conditions must be met for drug manufacturing:

• Pharmacy technicians, engineering, technical personnel, and skilled workers have been qualified according to law
• Sanitary plants and facilities are compatible with the production of pharmaceuticals
• Institutions, personnel, and equipment are capable of quality management and inspection of the produced drugs
• Rules and regulations are in place to ensure the quality of pharmaceuticals and compliance with quality management requirements

Specific guidance on drugs manufactured for clinical trials is provided in NMPA-No43-2022 (an annex to the NMPA-GMP), which states that the preparation and quality control of drugs for clinical trials must follow the requirements in the NMPA-GMP; minimize the risks of contamination, cross-contamination, confusion, and errors in the manufacturing process; and ensure the quality of clinical trial IPs to protect the safety of clinical trial participants. See NMPA-No43-2022 for detailed manufacturing requirements, including the quality management system, personnel, facilities and equipment, material management, file management, and management of the control drug.

The NMPA-GCP-No57-2020 specifies that the manufacture of clinical trial drugs must meet the relevant requirements for quality management. See NMPA-GMP, NMPA-No43-2022, NMPA-No28-2020, NMPA-No13-2015, and NMPA-No28-2016 for guidance on the quality management system during manufacturing. Per the DRR and the NMPA-No28-2020, the Center for Drug Evaluation (CDE) makes a risk-based decision on whether to initiate an on-site inspection of drug production based on the registered varieties, processes, facilities, and previous acceptance verification. However, on-site inspections must be conducted for innovative drugs, improved new drugs, and biological products.

The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37) also requires IPs to be manufactured, handled, and stored in accordance with applicable good manufacturing practices and used in accordance with the approved protocol.

Import

The DAL provides that prior to IP import, an NMPA import drug license must be obtained for each IP. Per CHN-18, before each import, the import agent must file for a record with the local agency at the port of entry, which issues a customs clearance notice of imported drugs and port inspection notice of imported drugs. According to CHN-28, importers must apply for the drug import license via the China International Trade Single Window online platform (CHN-2). For IP shipments, only a party authorized under the corresponding clinical trial approval can register and apply for the drug import license.

Per NMPA-No75-2020, there is a one-time fee of 2,000 Yuan for the import of drugs.

Pursuant to the NMPA-No35-2017, researchers can conduct Phase I of multi-regional clinical trials (MRCT) of imported IPs 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. This removes the need to conduct local clinical trials in addition to existing overseas research. Overseas clinical trial data may be acceptable for direct China registration provided that:

• The data is reliable, authenticated, and complies with CHN-37
• The data can assess the efficacy and safety for the target indication
• There are no ethnic sensitivities to Chinese local populations influencing efficacy and safety
• The data meets China drug registration requirements

See the NMPA-No52-2018 for additional details on the review and approval of overseas clinical trial data. For more information on application requirements, see the Submission Process and Submission Content sections.

Per NMPA-No230-2015 and CHN-18, the NMPA will prioritize the review and approval of foreign innovative drugs manufactured in China and drugs manufactured at a United States (U.S.) or European Union facility, and are simultaneously under review for marketing authorization by the U.S. Food and Drug Administration or the European Medicines Agency.

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

Investigator’s Brochure

In accordance with the NMPA-GCP-No57-2020 and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37), the sponsor is responsible for providing the investigators with an Investigator’s Brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs) including chemical, pharmaceutical, toxicological, pharmacological, and clinical information and data on the IP, including trials already completed or being conducted in other places.

As specified in the NMPA-GCP-No57-2020 and CHN-37, the IB must provide coverage of the following areas:

• Physical, chemical, and pharmaceutical properties and formulation parameters
• Pharmaceutical aspects
• Pharmacokinetics and metabolism
• Toxicological effects in any animal species tested under a single dose study, a repeated dose study, or a special study
• Results of clinical pharmacokinetic studies
• Information regarding safety, pharmacodynamics, efficacy, and dose responses obtained from prior clinical trials in humans

See the NMPA-GCP-No57-2020 and CHN-37 for detailed IB content guidelines.

Quality Documentation

Per the DAL, drug manufacturers are required to abide by quality management regulations, establish and improve the quality management system for drug production, and ensure that the entire process meets statutory requirements, including good manufacturing practice (GMP) standards in the NMPA-GMP and NMPA-No43-2022 (an annex to the NMPA-GMP). With respect to the manufacture of the clinical trial IP, NMPA-No43-2022 states that the manufacturing facility must establish a quality management system based on risks and a document system to ensure the effective operation of the quality management system. The sponsor must audit and confirm the quality management system of the entrusted manufacturing facility and sign an entrustment agreement and a quality agreement to clearly define the responsibilities of all parties to ensure that the clinical trial drug meets the intended use and quality requirements. Changes that may affect the safety of clinical trial drugs, such as changes in the preparation site, prescription process, batch size, quality standards, key raw and auxiliary materials, packaging materials of clinical trial drugs, and technology transfer, must be evaluated. Changes and assessments should be documented. Deviations from the preparation process, quality standards, and other deviations that may affect the quality of drugs for clinical trials should be investigated and evaluated, and corresponding records should be kept.

Per CHN-37, the sponsor must maintain a Certificate of Analysis to document the identity, purity, and strength of the IP(s) to be used in the clinical trial.

Investigational product (IP) labeling in China must comply with the requirements set forth in the NMPA-GCP-No57-2020, the ProvLabel, the DAL, and the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (CHN-37). The name, insert sheet, and label of any drug for which registration is applied must comply with the National Medical Products Administration (NMPA)’s requirements as mandated in the preceding regulations.

As per the NMPA-GCP-No57-2020, the sponsor is responsible for ensuring the proper packaging and labeling of the IPs. The IPs, comparator, and placebo products must be labeled in conformity with the clinical protocol, and be easily recognizable, correctly coded, and marked with special labels indicating that the product is to be used for clinical trial purposes.

Per NMPA-No43-2022 (an annex to the NMPA-GMP), to ensure the accuracy of IP labeling for clinical trials, operating procedures should be established that include measures to prevent mislabeling, such as balance calculation of label quantity, site clearance, and intermediate control inspection by trained personnel. Where blinded trials are involved, effective measures should also be taken to prevent labeling errors between the test drug and the reference drug (including placebo). For operations that need to remove the original product labels and packaging, corresponding measures should be taken to prevent contamination, cross-contamination, confusion, and errors between the test drug and the reference drug (including placebo). IP labels for clinical trial use must be clear and easy to identify, and contain the following contents:

• The sponsor of the clinical trial
• The name of the drug used in the clinical trial
• The batch number and/or serial number of the product and the packaging operation (the label information of the clinical trial IP used for the blinded test should be able to remain blinded)
• The clinical trial number or other unique code corresponding to the clinical trial
• The words "only for clinical trials" or similar instructions
• Validity period, expressed in a way such as XXXX (year)/XX (month)/XX (day) or XXXX (year)/XX (month) that can clearly indicate the year, month and day
• Specifications and instructions for use (the instructions for use or other written instructions provided to the participants may be attached, and the content should meet the requirements of the clinical trial protocol)
• Packaging specifications
• Storage conditions
• If the clinical trial drug is allowed to be taken home by the subjects, it must be specially marked to avoid misuse

NMPA-No43-2022 states that the inner and outer packaging must contain all of the label contents. If the size of the inner package label is too small to indicate all of the above contents, at least the first four (4) label contents in the bulleted list above must be included. If the validity period needs to be changed, the IP must be affixed with an additional label, and the additional label must be marked with the new validity period. The original batch number or drug code must not be overwritten when affixing additional labels. After the applicant's evaluation, the additional label operation of changing the validity period can be carried out in the institution conducting the clinical trial. The operation of affixing additional labels must be carried out in accordance with the operating procedures approved by the sponsor. Personnel must be trained and approved in these operating procedures, and the operation site must be reviewed and confirmed by personnel. Attachment of additional labels should be properly documented and traceable in clinical trial-related documents or batch records. The sponsor must conduct a quality review of the IPs with additional labels.

The ProvLabel and the DAL also provide labeling information that should be included on the outer packaging and immediate container of all drugs to be registered in China. (Note: the regulations provide overlapping and unique elements so each of the items listed below will not necessarily be in each source.)

• Adopted name in China
• Instructions
• Generic name
• License holder and their address
• Indications or functions
• Strength, dosage, and usage
• Production date and batch number
• Expiration (Should be marked as one (1) day or one (1) month earlier than the actual expiration date, depending on whether the date is labeled to a specific day or month)
• Manufacturer and their address
• Ingredients
• Adverse reactions
• Contraindications and precautions
• Storage information
• Approval number
• Labels and instructions for narcotic, psychotropic, medical toxic, radioactive, external, and non-prescription drugs must be printed with the prescribed marks

The label language must also be scientific, standardized, and accurate, and written in standard Chinese characters published by the National Language Commission. See ProvLabel and the DAL for detailed labeling instructions.

The NMPA-GCP-No57-2020 and CHN-37 state that the IP must be coded and labeled in a manner that protects the blinding, if applicable.

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

Supply, Storage, and Handling Requirements

Per NMPA-No43-2022, operating procedures should be established to ensure the accuracy of packaging investigational products (IPs) for clinical trials. The packaging of IPs for clinical trials should prevent and avoid its deterioration, contamination, damage, and errors during storage and transportation. The procedures should identify activities that open or change the packaging. The test drug and the reference drug are usually not allowed to be packaged in the same packaging line at the same time. For clinical trial IPs that need to be packaged simultaneously on the same packaging line, appropriate operating procedures and equipment should be in place, and relevant operators should be trained to avoid confusion and errors.

Further, NMPA-No43-2022 states that before approving the release of an IP for a clinical trial, the person responsible must evaluate the quality of each batch of IPs to ensure that they comply with laws, regulations, and technical requirements, including:

• Batch records
• Deviations and changes, subsequent investigations, and assessments
• Correct packaging and labels
• Production conditions
• Status of facilities, equipment, preparation process, and inspection method
• The release of raw and auxiliary materials and the inspection results of intermediate and finished products
• The relevant test results of the reference drug (including placebo) (if applicable)
• Stability study data and trends (if applicable)
• Storage conditions
• Qualification certificate of reference substance/standard product (if applicable)
• Audit report of the quality management system of the entrusted unit (if applicable)
• Proof of legal origin of the reference drug (if applicable)
• Other requirements related to the quality of the batch of clinical trial drugs

The delivery of IPs must be carried out according to the sponsor’s delivery instructions and specific requirements. The sponsor must select an appropriate transportation method according to the packaging, quality attributes, and storage requirements of the IP, take corresponding measures to prevent deterioration, damage, pollution, temperature control failure, etc., and confirm the IP is sent to designated clinical trial institutions. The IPs delivered to the clinical trial institutions must at least be accompanied by a certificate of conformity, a delivery list, and a receipt confirmation from the research institution. IPs must not be directly transferred from a clinical trial institution to another clinical trial institution. If necessary, the sponsor and the clinical trial institutions of both parties should have complete quality assessment and operating procedures for the transfer of IPs, which can only be implemented after full assessment and approval by the sponsor.

The NMPA-GCP-No57-2020 states that the sponsor must provide the IPs to investigators and clinical trial institutions. The sponsor must not provide the IPs until the clinical trial has obtained the approval of the ethics committee and the approval or filing of the National Medical Products Administration (NMPA). The sponsor must provide the investigator and the clinical trial institution with a written description of the IP, including directions for use and storage. Further, the sponsor must formulate procedures for the supply and management, including reception, storage, distribution, use, and recovery. The sponsor must ensure that the IPs are delivered to researchers and clinical trial institutions in a timely manner. The sponsor must also take measures to ensure the stability of the trial drug during the trial period. Investigators and clinical trial institutions are responsible for the management of IPs provided by the sponsor. They must assign qualified pharmacists or other personnel to manage IPs.

CHN-37 provides additional guidance that the sponsor must ensure:

• IP product quality
• IP manufactured according to good manufacturing practices (GMPs), as per NMPA-GMP and NMPA-No43-2022
• Proper coding, packaging, and labeling of the IP in accordance with the protocol, and special marking to indicate that the drug is specifically to be used in a clinical trial
• IP use record which includes information on the quantity, loading, shipment, receipt, dispensing and handling, and the reclamation and destruction of the unused drug
• Establishment of IP management and filing systems
• Acceptable storage temperatures, conditions, and times for the IP
• Timely delivery of the IP

Refer to the NMPA-GCP-No57-2020 and CHN-37 for detailed sponsor-related IP requirements.

Per the DAL, the sponsor—also referred to as the holder of a drug registration certificate—must establish a drug release procedure that includes reviewing the drug to ensure compliance with national drug standards, and releasing it only after the quality attorney signs it. Further, drug license holders, pharmaceutical production enterprises, and medical institutions must establish and implement a drug traceability system, in accordance with regulations.

Record Requirements

Per NMPA-No43-2022 (an appendix to NMPA-GMP), sponsors should set up investigational drug files, which are documents and records of the preparation, packaging, quality inspection, the release of products in batches, delivery, and transportation. These files should be retained until at least two (2) years after the IP is withdrawn from the market, or at least two (2) years after the termination of the clinical trial or the registration application if the IP fails to get marketing authorization. The files should at least contain the known or potential key quality attributes and key process parameters in the research stage, re-evaluated with the development of the product, and updated when necessary. The files can be the original documents or certified copies.

Per NMPA-GCP-No57-2020, the sponsor must keep records of the transportation, receipt, distribution, recovery, and destruction of the IPs; establish a recycling management system to ensure the recall of defective products and recovery after the clinical trial and expiration; and establish a disposal system. The entire management process of all IPs must be documented. Finally, the retained samples must be kept until the end of the clinical trial or the time limit required by relevant laws and regulations, whichever time period is longer. If the two (2) are inconsistent, the longer period must be used. The sponsor must keep clinical trial records for at least five (5) years after the IP is approved for marketing.

In addition, there must be clear documentation of the IP’s quality evaluation, such as approval for release, non-release or other decisions, and must be signed by the person responsible for release. Before the IP is shipped to the clinical trial institution, the sponsor must confirm the following contents and keep relevant records:

• The IP has been approved for release
• The relevant requirements necessary for the initiation of clinical trials have been met, such as the approval or consent of the ethics committee and the NMPA
• Inspection and confirmation of transportation conditions

Complete written records should be kept for the delivery of IPs, which usually include the name or code of the IP, dosage form, strength, batch number or drug code, quantity, expiration date, applicant, preparation unit, packaging form, and storage requirements. Records should also be kept of the receiving unit and address, contact information, shipping date, transportation method, and the temperature monitoring measures. If the transportation is entrusted to a third-party carrier, the relevant information of the carrier shall also be included. The content of the shipping record can be adjusted as needed for blinding.

The term “specimen” is not referenced within China. However, as per MgmtHumanGen, human genetic resources (HGR) are defined as including both human genetic resource materials and human genetic resource information. HGR materials refer to genetic materials, such as organs, tissues, and cells, which contain the human genome, genes, and their products. HGR information refers to genetic information or data generated by using the HGR materials. CHN-76 is the portal for China’s management of specimens.

Import

Per the QuarantineLaw, the AQSIQ-No160, and CHN-54, imports of human tissue, biological products, blood, and hemoproducts are subject to health and quarantine inspection. The importer is required to declare the items for inspection with local offices governed by the General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ). As described in CHN-46, AQSIQ operates 35 Entry-Exit Inspection and Quarantine Bureaus (CIQ) in China’s 31 provinces.

Per the AQSIQ-No160, the management of special articles is subject to risk control, which includes quarantine approval, inspection, and supervision as per risk levels upon assessment. Importers of special articles must apply for the quarantine approval by submitting the following documents to the local CIQ:

• A completed Application for Quarantine of Inbound/Outbound Special Articles (CHN-54)
• Specific descriptions of the special articles, including Chinese and English names, classification, composition, origin, purpose, import destination, etc.
• Approval documents from health authorities for inbound human blood, plasma, tissue, organs, cells, bone marrow, etc.
• For first-time importers, provide copies of the business license and the organization code certificate (copied)
• For first-time importers, firm information including management system certification status, address, place of production, laboratory setup, storage facilities, processing conditions, production processes, floor plan, etc.
• For first-time importers, biosafety documents including storage management rules, use management rules, waste disposal rules, professional management rules, emergency handling procedures, etc.

In addition, see QuarantineRules for more details on the procedures for the inspection and quarantine processes, the jurisdiction of AQSIQ and its local branches, and different levels of sample testing based on risk and the importer’s track record.

Export

The MgmtHumanGen and the Bioscrty-Law prohibit foreign entities or individuals from collecting or preserving China’s human genetic resources (HGR) in China, or providing Chinese HGR for use abroad. However, the regulation permits foreign entities with limited use of Chinese HGR 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, the foreign entity and the Chinese entity must jointly file an application for approval to the Ministry of Science and Technology (MOST), and the research must pass ethical 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, and their products. Such clinical trial collaborations, however, must be filed with MOST on its online platform (CHN-76), which will generate a record number. See the HGR-IntlRecordMgtGuide, the HGR-IntlApprovLicenseGuide, and the HGR-ExprtLicenseGuide for details on the HGR processes and policies. For analyses of China’s implementation of HGR regulations, see CHN-10 and CHN-16.

As delineated in MgmtHumanGen and the HGR-ExprtLicenseGuide, the applicant may apply for the export license separately, or with the application for international cooperative research (CHN-76). (See Regulatory Authority and Clinical Trial Lifecycle topics for details on MOST’s review and approval requirements for HGR collection and international cooperative research license applications.) Per the HGR-ExprtLicenseGuide, the export applicant must be a Chinese entity and the transportation, mailing, and carrying of Chinese HGR material must meet these conditions:

• There is no harm to public health, national security, and social public interests in China
• The activity has legal standing
• There are clear overseas partners and reasonable exit uses
• The collection of HGR materials is legal or from legal depository institutions
• The collection of HGR material passed an ethical review

Per the HGR-ExprtLicenseGuide and CHN-56, the following must be submitted:

• Application (see CHN-56 for a template) – after the online declaration is completed, the paper stamp is submitted; see below for information on the declaration
• Legal person qualification
• Informed consent
• Ethics review approval
• Chinese HGR international cooperative research approval decision
• Chinese HGR materials exit approval decision

Per the HGR-Procedures and the HGR-ExprtLicenseGuide, the applicant submits the electronic version of the materials through the online platform (CHN-76). To submit paper applications, the applicant should use the online, pre-accepted electronic application materials and print them double-sided on A4 paper; the cover and signature stamp page should be printed one-sided with plastic binding.

MOST will complete the pre-examination of electronic applications within five (5) working days after receiving the application. If the application materials are complete and conform to the prescribed form, the applicant may print the paper materials through pre-examination; if the application materials are incomplete or do not meet the requirements, the pre-examination shall not be passed, and the applicant is notified of the content that should be corrected in the online platform. After receiving the paper application materials submitted by the applicant, MOST will complete the formal examination within five (5) working days. An acceptance form will be issued once the application materials are confirmed to be completed and in conformance with the prescribed format. If the application materials are incomplete or do not conform to the prescribed format, the application will be returned.

MOST organizes experts to conduct technical reviews and form expert review opinions on the accepted applications. Next, MOST will approve or disapprove the application and publish the results on its website (CHN-76), including reasons why an application was not approved. MOST will send the approval decision letter to the provincial science and technology administrative department by mail within 10 working days and publish the mailing details on the website. The applicant should go to the provincial science and technology administrative department to receive the approval decision letter with the acceptance form.

The MgmtHumanGen indicates that the Ministry of Science and Technology (MOST) is responsible for China’s management of human genetic resources (HGR). As delineated in the MgmtHumanGen, HGR-Procedures, HGR-IntlApprovLicenseGuide, HGR-Collection, HGR-ExprtLicenseGuide, and HGR-IntlRecordMgtGuide, MOST, through its experts, is responsible for reviewing and approving license applications to collect HGR and conduct international collaborative projects using Chinese HGR. The applicant’s submission for these licenses must include the written informed consent of the provider of the HGR. CHN-56 summarizes the HGR license and application contents, including the consent form.

Per the MgmtHumanGen, to collect Chinese HGR for a clinical trial, the investigator must provide advance information to the participant on the purpose of collection, the possible impact on health, the protection of personal privacy, their participation is voluntary, and they have the right to withdraw unconditionally at any time. The participant must agree in writing. Information provided to the participant must be comprehensive, complete, true, accurate, and must not conceal information nor be misleading or deceiving.