2. General Questions

2.1 Name of Regulatory Authority

The National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) is the regulatory authority responsible for national drug registration management, which includes regulation of clinical trials.

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 Drug Administration’s Law of the People’s Republic of China (DAL), the Vaccine Administration Law (VaccineLaw), the Drug Registration Regulation Order No. 27 (DRR), the Opinions on reforming the review and Approval System for Drugs and Medical Devices (No. 44) (SC-Opinions-No44), Adjusting the Review and Approval Procedures for Drug Clinical Trials (no. 50 of 2018) (NMPA-No50-2018), and Several Policies for Drug Registration Review and Approval (no. 230 of 2015) (NMPA-No230-2015).

2.2 Name of Ethics Committee

An ethics committee (EC) must approve a clinical trial application prior to a sponsor initiating a clinical trial.

The National Health Commission (NHC) is responsible for managing ECs nationwide, establishing the National Committee of Medical Ethics Experts, and for developing policies relating to ethical review.

Provincial, autonomous regional, and municipal health authorities also have ECs set up under their own administration. The Provincial Committee of Medical Ethics Experts assists in promoting the institutionalization and standardization of the ethical review work of human biomedical research across the regions, and guides, inspects, and evaluates the work of institutional ECs engaged in research involving human beings. The local health department at or above the county level is responsible for the supervision and management of the ethical review work of biomedical research involving people in its region.

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.

https://clinregs.niaid.nih.gov/country/china#ethics_committee

http://www.nhc.gov.cn/fzs/s3576/201610/84b33b81d8e747eaaf048f68b174f829.shtml

https://trust-project.eu/wp-content/uploads/2016/03/Chinese-Ethics-Review-System.pdf

2.3 Clinical Trial Application Language

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.

https://www.nmpa.gov.cn/zhuanti/ypqxgg/ggzhcfg/20171130203401214.html?type=pc&m=

2.4 Is regulatory approval required from both regulatory authorities and/or EC?

Yes. NMPA and the EC must approve a clinical trial application prior to a sponsor initiating a clinical trial. 

2.5 Can regulatory authority and EC submission be done in parallel?

Yes. The EC review may be submitted in parallel to the regulatory authority review, but the study cannot be initiated until after review and approval by the EC. 

2.6 Requirement of any import permit/license before investigational product/study product is shipped from point of origin

Regulatory requirements for importing IMPs into China:

• National Medical Products Administration (NMPA) oversees the import of IMP and issues the Import License.
• Before each import, the importation shall be notified to the local authority which issues the customs clearance for import.
• All the documents need to be translated into Chinese.
• Upon issuance of the import permit, the sponsor needs to complete the process of importation within a limited time.

To import the IMPs and their supportive products you may require a Certificate of Analysis (COA), Certificate of Origin (CoO), Manufacturing Certificate (MC), certificate of compliance (CoC), etc. The requirements for each product may vary.

2.7 Biological Specimen Export Requirements

Yes. All movement of human samples requires prior approval from the Office of Human Genetic Resources (OHGRA). Links to the key guidelines are provided below. These guidelines are only available in Chinese. 

https://fuwu.most.gov.cn/html/jcxtml/20181218/2837.html?tab=fwzn

2.8 Are studies of GMOs permitted (e.g., GMOs used in vaccines/vaccine manufacture and other modified products)?

Yes, NMPA has incorporated GMOs into its drug management systems. GMO production needs to be strictly in accordance with GMP standards; safety and efficacy should be assessed through scientifically designed clinical trials. In China’s current Drug Registration Regulation, GMOs are listed as category 3 of therapeutic biological products.

Since 2017, pre-IND meetings with the Centre for Drug Evaluation (CDE) have been encouraged by the NMPA, to discuss the protocol design or other critical development questions. It is highly recommended to have a pre-IND meeting prior to starting a GMO trial in China. The pre-IND meeting allows researchers to gather important advice and understanding of requirements. Currently, it takes approximately two to four months to get a response from CDE. CDE will make the final decision on whether a face-to-face meeting or written response is appropriate.

After getting alignment with CDE on the application, IND can be submitted. It takes 60 working days to get the approval notification from CDE.

2.9 Is in-country sponsor presence/representation required?

Yes. A sponsor may be domestic or foreign. However, a Chinese legal entity must submit the clinical trial application.

2.10 Is there any mandatory requirement to identify a local PI or can a PI be based in a foreign country?

Yes. The PI must be a locally-based physician with local accreditation.

2.11 Is there any mandatory requirement to identify a local chief or coordinating investigator?

Yes. The NMPA-GCP-No57-2020 (Guidance) Quality Management Practices for Drug Clinical Trials indicates that for clinical trials involving multiple institutions, the sponsor must be responsible for selecting the team leader unit.

2.12 If the applicant is CRO or a third party, does regulatory authority need any authorization or transfer of obligations from the sponsor? Does the authorization letter need to be notarized and/or apostilled?

A sponsor may transfer any or all of the sponsor's trial-related duties and functions to a CRO.
The ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor. This needs to be documented in an authorization letter. There is a template for this from NMPA. The document does not need to be notarized or apostilled.

2.13 Is there a requirement to register clinical trials on a local registry or database?

Yes. The Chinese Clinical Trial Register (CHICTR) is used to register clinical trials conducted in China.

CHICTR

2.14 What is the local requirement for clinical study documents archival; minimum of years for the archival, specific format followed (electronic/paper and/or both)?

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. This requirement applies to either paper or electronic files.

https://www.nmpa.gov.cn/yaopin/ypggtg/20200426162401243.html

2.15 Requirements around periodic safety reporting and timelines on SAEs/AEs/ADRs/SUSARs/DSURs.

Reporting Requirements for AE/ADRs

Investigator Responsibilities

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

The sponsor must regularly submit a safety update report to the CDE. 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 following guidelines:

• https://www.cde.org.cn/main/news/viewInfoCommon/afced30f3c45431f04b47a7f3faee971
• https://www.nmpa.gov.cn/xxgk/ggtg/qtggtg/20210513151827179.html?type=pc&m=

The Sponsor is required to report SUSARs and other potentially serious safety risks to the CDE in a timely manner in accordance with relevant requirements. 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. The NMPA guidance requires sponsors to actively cooperate with clinical trial institutions and other relevant parties to strictly implement the main responsibility of safety risk management. Pharmacovigilance and quality management systems should be established; risk monitoring, identification, assessment, and control should be carried out; safety problems and risks should be discovered in time; and necessary risk management measures should be taken proactively, such as adjusting clinical trial plans, and suspending or terminating clinical trials, etc.

http://www.cjpi.org.cn/zryyxxw/cfdazsjg/ypspzx/webinfo/2018/06/1523831677725358.htm

NMPA guidance 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.

NMPA specifies reporting timelines for unexpected death or serious life-threatening adverse reactions. The sponsor must submit the report as soon as possible after first learning, 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. According to the regulation, 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.

https://www.nmpa.gov.cn/xxgk/ggtg/qtggtg/20210513151827179.html

https://www.nmpa.gov.cn/yaopin/ypggtg/20200426162401243.html

2.16 Requirement on any periodic clinical study update, specific template, and its frequency (e.g., interim or annual progress report and final report, etc.)? 

Investigators must provide clinical trial progress reports as follows:

Interim and Annual Progress Reports

The investigator is required 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 the 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. 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.

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.

Investigators 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

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.

https://www.nmpa.gov.cn/yaopin/ypggtg/20200426162401243.html

2.17 Do the country regulations allow a Decentralized Clinical Trial (DCT) model (e.g., eICF, ePROs administration, remote investigator site, etc.)?

In July 2023, NMPA released three guidelines outlining patient-centered clinical trials which include information on decentralized trials. 

The three guidelines released were: 

• Technical Guidance for Patient-Centered Drug Clinical Trial Design (English Translation)
• Technical Guidelines for Patient-Centered Drug Benefit-Risk Assessment (Trial) (English Translation)
• Technical Guiding Principles for the Implementation of Patient-Centered Drug Clinical Trials (English Translation)

These guidelines support the conduct of decentralized clinical trials. 

2.18 Has a fully virtual trial (DCT) been conducted in the country yet? If so, please provide an example including the registration number and any link to it, whether COVID/non-COVID trials.

There have been some cases of DCT trials in early phase development or Phase IV studies, or some orphan drugs, but there are no known examples of a fully decentralized pivotal clinical trial. 

DCTs are an emerging trend and have been documented by academics and regulators:

http://www.bjchp.gov.cn/cpqzf/xxgk2671/ztzl/lqzb/cp5417259/index.html

2.19 Are there any non-regulatory DCT initiatives in the country, such as where investigator sites and local CROs founded an alliance?

There is strong interest from CROs and investigators, but not an alliance as yet.

2.20 Does the local regulation require notification of “serious breaches” of GCP or the trial protocol (that is a breach that is likely to affect to a significant degree either the safety or physical or mental integrity of the subjects of the trial; or the scientific value of the trial)?

Yes, NMPA follows the ICH principles in regard to GCP.

2.21 Does RA/CA require insurance and indemnity to cover the sponsor and investigator’s potential liability?

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. The sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator and the institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence.

https://www.lexology.com/library/detail.aspx?g=a6860ee7-d82e-47c7-9d24-b18c9f525813

https://clinregs.niaid.nih.gov/country/china#compensation_disclosure