Clinical Research Regulation For China
Regulatory Authority
Regulatory Authority
Scope of Assessment
Regulatory Fees
Ethics Committee
Ethics Committee
Scope of Review
Ethics Committee Fees
Authorizing Body
Clinical Trial Lifecycle
Submission Process
Submission Content
Timeline of Review
Trial Initiation
Safety Reporting
Progress Reporting
Sponsorship
Definition of Sponsor
Trial Authorization
Insurance
Compensation
Quality, Data & Records Management
Site/Investigator Selection
Informed Consent
Documentation Requirements
Required Elements
Compensation Disclosure
Participant Rights
Special Circumstances/Emergencies
Vulnerable Populations
Children/Minors
Pregnant Women, Fetuses & Neonates
Prisoners
Mentally Impaired
Investigational Products
Definition of Investigational Product
Manufacturing & Import
IMP/IND Quality Requirements
Labeling & Packaging
Product Management
Specimens
Definition of Specimen
Specimen Import & Export
QUICK FACTS
Clinical trial application language Standard Chinese (overseas trial data also in original language)
Regulatory authority & ethics committee review may be conducted at the same time Yes
Clinical trial registration required Yes
In-country sponsor presence/representation required For application submissions & trials using genetic resources
Age of minors Unspecified
Specimens export allowed Yes
Regulatory Authority > Regulatory Authority
Last content review/update: February 17, 2021
Requirements
(1) (Legislation) Biosecurity Law of the People's Republic of China (Bioscrty-Law – Standard Chinese) (Effective April 15, 2021)
National People’s Congress
Relevant Sections: Chapter II (Articles 10-11) and Chapter VI (Articles 53-57)
(2) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter I (Articles 2 and 5-10) and Chapter II
(3) (Legislation) State Council Institutional Reform Plan (SC-IRP – Standard Chinese) (March 17, 2018)
National People’s Congress
(4) (Legislation) Vaccine Administration Law (VaccineLaw – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter I (Article 8), Chapter II (Article 16), and Chapter II (Articles 14-16)
(5) (Regulation) Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50-2018 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
(6) (Regulation) Decision of the State Council on Amending Some Administrative Regulations (Decree No. 709) (RegImplemDAL-Amndt – Standard Chinese (Effective March 2, 2019)
State Council
Relevant Sections: 39
(7) (Regulation) Human Genetic Resources – Approval for Export, Administrative Licensing Service Guide (HGR-ExportLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 9
(8) (Regulation) Human Genetic Resources – Collection and Approval of HGR in China, Administrative Licensing Service Guide (HGR-Collection – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 9
(9) (Regulation) Human Genetic Resources – International Cooperative Research Approval, Administrative Licensing Service Guide (HGR-IntlApprovalLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 9
(10) (Regulation) Human Genetic Resources – Preservation of HGR in China, Administrative Licensing Service Guide (HGR-Preservation – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 9
(11) (Regulation) National Medical Products Administration's Functional Allocation, Internal Organization and Staffing Requirements (NMPA-Org – Standard Chinese) (Effective July 29, 2018)
State Council
Relevant Sections: Articles 1, 2, and 3
(12) (Regulation) Opinions on Reforming the Review and Approval System for Drugs and Medical Devices (No. 44 of 2015) (SC-Opinions-No44 – Standard Chinese) (August 9, 2015)
State Council
(13) (Regulation) Provisions on the Jurisdictions, Departments and Staffing of the State Administration for Market Regulation (SAMR-Org – English, unofficial translation) (Standard Chinese) (Effective July 30, 2018)
State Council
Relevant Sections: Articles 1-4
(14) (Regulation) Regulations for Implementation of the Drug Administration Law of the People’s Republic of China (Decree No. 360) (RegImplemDAL – Standard Chinese) (Effective September 15, 2002) (Amended February 6, 2016)
State Council
Relevant Sections: Chapter V (Articles 29 and 30)
(15) (Regulation) Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230-2015 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(16) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter I (Articles 1-6), Chapter III (Articles 20-33), and Chapter VIII (Articles 104-107)
(17) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (GoogleTranslate-MgmtHumanGen) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter I (Articles 4-5), Chapter II (Article 11), Chapter IV, and Chapter V (Article 36)
Summary

Overview

National Medical Products Administration

As per the DRR, the NMPA-Org, the DAL, the RegImplemDAL, the RegImplemDAL-Amndt, the SC-Opinions-No44, the NMPA-No50-2018, the NMPA-No230-2015, and CHN-23, 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 management of clinical trial applications. 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 restructured 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. Among the functional changes, 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 Regulatory Authority topic, Scope of Assessment subtopic.

Ministry of Science and Technology

The Bioscrty-Law and the MgmtHumanGen delineate that the Ministry of Science and Technology (MOST) is responsible for China's management of human genetic resources (HGR). In addition, per the Bioscrty-Law, MOST will regulate biotechnology safety under the National Security Commission pursuant to a Coordination Mechanism for National Biosecurity (CMNB). The CMNB consists of the competent departments of the State Council 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 will 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 cooperation research. The committee’s work involves collecting and preserving China’s 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 or 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 China’s HGR
  • Using China’s HGR to carry out international scientific research cooperation
  • Delivering, mailing, and exporting China’s 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 China's HGR without approval
  • Conducting international cooperation scientific research using China’s 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 cooperation clinical trial begins

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. ClinRegs lists referenced ICH guidelines as Additional Resources throughout the profile.

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

The following is the NMPA’s contact information:

National Medical Products Administration
No. 1 Beiluyuan, Zhanhan Road
Xicheng District
Beijing 100037
P.R. China
Phone: 68311166
Website: http://www.nmpa.gov.cn

The following is MOST’s contact information:

Ministry of Science and Technology
No. 15 Fuxing Road
Beijing 100862
P.R. China

Website: http://www.most.gov.cn/

Application Submissions Contact Information

Drug registrations and associated clinical trial application forms should be sent to NMPA’s Administrative Acceptance Service Hall (CHN-71) and address below. Following administrative acceptance, clinical trial consultations and data submittals are handled at NMPA CDE’s Applicant’s Window (CHN-58).

NMPA Administrative Acceptance Service Center
1st Floor, Gate 3, Dacheng Plaza
28 Xuanwumen West Street
Xicheng District
Beijing 100053
P.R. China
Phone: +86-010-88331793 (drug acceptance); +86-010-88331734 (consultation of drug matters)
Email: xzslfwdt@nmpa.gov.cn

Per the HGR-Collection, HGR-IntlApprovalLicenseServiceGuide, HGR-Preservation, and the HGR-ExportLicenseServiceGuide, the following is 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

Additional Resources
(1) (Article) China’s New State Administration for Market Regulation: What to Know and What to Expect (CHN-21) (April 3, 2018)
Wang, Katherine; Ropes & Grey
(2) (Article) Should You Look at China for Your Next Clinical Trial? (CHN-23) (September 18, 2018)
Miseta, Ed; Clinical Leader
(3) (Document) Nagoya Protocol on Access and Benefit-sharing (CHN-30) (2011)
Convention on Biological Diversity, United Nations
(4) (Webpage) Administrative Acceptance Service Hall: Things to Know (CHN-61 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(5) (Webpage) Administrative License (CHN-76 - Standard Chinese) (Current as of October 30, 2020)
Ministry of Science and Technology
(6) (Webpage) Applicant's Window (CHN-58 - Standard Chinese) (Current as of October 30, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(7) (Webpage) Country Profile: China (CHN-55) (Current as of October 30, 2020)
Access and Benefit-sharing Clearing-house, Convention on Biological Diversity, United Nations
(8) (Webpage) ICH Guidelines (CHN-49 - Standard Chinese) (Current as of October 30, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(9) (Webpage) Internal Organization (CHN-77 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Drug Registration Management Department and Drug Administration Department
(10) (Webpage) Main Duties of National Medical Products Administration (CHN-78 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(11) (Webpage) Members and Observers (CHN-59) (Current as of October 30, 2020)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(12) (Webpage) National Medical Products Administration (CHN-81) (Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Address, NMPA Organizations, and Affiliated Institutions
(13) (Webpage) Online Service Hall of the National Medical Products Administration (CHN-71 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Regulatory Authority > Scope of Assessment
Last content review/update: February 17, 2021
Requirements
(1) (Legislation) Biosecurity Law of the People's Republic of China (Bioscrty-Law – Standard Chinese) (Effective April 15, 2021)
National People’s Congress
Relevant Sections: Chapter VI (Articles 53-59)
(2) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter I (Article 6), Chapter II (Article 19), and Chapter III (Article 38)
(3) (Legislation) Vaccine Administration Law (VaccineLaw – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: 1-2 and 16-18
(4) (Regulation) Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50-2018 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1-4 and Annexes 1-3
(5) (Regulation) Human Genetic Resources – Approval for Export, Administrative Licensing Service Guide (HGR-ExportLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
(6) (Regulation) Human Genetic Resources – International Cooperative Clinical Trials, Record and Filing Management Service Guide (HGR-IntlRecordMgtServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1-3
(7) (Regulation) Human Genetic Resources – International Cooperative Research Approval, Administrative Licensing Service Guide (HGR-IntlApprovalLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
(8) (Regulation) Notice on Propaganda and Implementation of the Vaccine Administration Law (No. 23 of 2019) (NMPA-No32-2019 – Standard Chinese) (July 25, 2019)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 4
(9) (Regulation) Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices (No. 42 of 2017) (SC-Opinions-No42 – Standard Chinese) (October 8, 2017)
Chinese Communist Party’s Central Committee and State Council
(10) (Regulation) Opinions on Reforming the Review and Approval System for Drugs and Medical Devices (No. 44 of 2015) (SC-Opinions-No44 – Standard Chinese) (August 9, 2015)
State Council
Relevant Sections: 1-8, 11-12, and 14
(11) (Regulation) Release of Administrative Measures for the Communication of Drug R & D and Technical Review (No. 74 of 2018) (NMPA-No74-2018 – Standard Chinese) (September 30, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1 and 2
(12) (Regulation) Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230-2015 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(13) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter I (Articles 2-7), Chapter II (Articles 9-10, 13-16), Chapter III (Articles 20-26, 41, 45-49), Chapter VIII (Article 104)
(14) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (GoogleTranslate-MgmtHumanGen) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter I (Articles 1-4 and 7-9), Chapter II (Article 11), and Chapter III (Articles 21-22)
(15) (Guidance) Registration Classification and Application Information for Biological Products (No. 43 of 2020) (NMPA-No43-2020 – Standard Chinese) (Effective July 1, 2020 (registration) and October 1, 2020 (application))
National Medical Products Administration, State Administration for Market Regulation, State Council
(16) (Guidance) Registration Classification and Application Information for Chemical Drugs (No. 44 of 2020) (NMPA-No44-2020 – Standard Chinese) (Effective July 1, 2020 (registration) and October 1, 2020 (application))
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1 and 2
(17) (Notice) Publication of the Work Plan for the Reform of the Classification and Registration of Chemical Drugs (No. 51 of 2016) (NMPA-No51-2016 – Standard Chinese) (March 4, 2016)
National Medical Products Administration, State Administration for Market Regulation, State Council
Summary

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) (the Chinese name translates as “State Drug Administration”) is responsible for reviewing and approving clinical trial applications for drugs to be registered in China, as required. The DRR clarifies that 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 DRR stipulates that foreign applicants should designate an enterprise legal person in China to handle relevant drug registration matters.

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. Within the chemical medicine category, the classifications are innovative drugs, new uses of improved chemical drugs, generic drugs, and drugs marketed overseas but not in China. The NMPA-No44-2020 and CHN-1 delineate the classifications:

  • Class 1: Innovative drugs that have not been marketed in China or overseas. They refer to 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; they refer to 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

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. Following are the descriptions of biological product classifications for both prevention 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

The DRR states that a Chinese legal entity must submit the drug registration application. The DRR establishes that drug registration refers to applicants for clinical trials of drugs, marketing approval of drugs, re-registration, and other supplementary applications. 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 Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics 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.

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.

Per the VaccineLaw, the NMPA must approve vaccine clinical trials. 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. 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

As delineated in the DRR, NMPA is the regulatory authority responsible for national drug registration management, which includes management of clinical trial applications. 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-No74-2018, with regard to new drugs, 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. As required in the NMPA-No50-2018, if the existing data, numerical data, or supplemented data can support the clinical trial, the applicant can submit the clinical trial application after the communication meeting or following the submission of supplemental data. The applicant may directly submit a clinical trial application without requesting a communication meeting with the CDE if: 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.

Per the NMPA-No50-2018, the NMPA’s Drug Registration Management Department is responsible for conducting an administrative review of a clinical trial application, and then forwarding the submission to the CDE for technical review. (Deviations from this general process are described further below in this section.)

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 a 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 NMPA will conduct the inspections and testing. The drug registration inspection of overseas-produced drugs must be implemented by the port drug inspection agency.

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.

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 Clinical Trial Lifecycle topic, Submission Process, Submission Content, and Timeline of Review subtopics.

CHN-22 and CHN-11 also provide useful information on the NMPA’s overall clinical trial application review and approval process.

The MgmtHumanGen and the Bioscrty-Law prohibit foreign entities or individuals from collecting or preserving China’s HGR in China, or providing China’s HGR for use abroad. However, the regulation permits foreign entities with limited use of China’s 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 China 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 at CHN-76, which will generate a record number. See the HGR-IntlRecordMgtServiceGuide, the HGR-IntlApprovalLicenseServiceGuide, and the HGR-ExportLicenseServiceGuide for details on the HGR processes and policies. See Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics and the Specimens topic for additional information on HGR regulatory management.

Regarding multi-center clinical research using HGR in international cooperation clinical trials, the HGR-IntlApprovalLicenseServiceGuide and the HGR-IntlRecordMgtServiceGuide 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).

Additional Resources
(1) (Article) China (CHN-22) (April 2020)
Kingham, Richard; The Life Sciences Law Review, Edition 8
Relevant Sections: Introduction and Regulatory Regime
(2) (Article) China and the Evolving Regulatory Landscape (CHN-9) (September 4, 2019)
Baruah, Megha; European Pharmaceutical Review
Relevant Sections: Table 1
(3) (Article) China National Drug Administration Sets Guidelines for Overseas Drug Trial Data (CHN-19) (August 9, 2018)
Liao, Todd; Morgan Lewis
(4) (Article) China’s National Medical Products Administration Finalizes Two Implementing Rules of the Drug Administration Law (CHN-18) (April 2, 2020)
Li, Lei and Yang, Chen; Sidley Austin LLP
(5) (Article) Interpretation of the Technical Guiding Principles for Accepting Data from Overseas Clinical Trials of Drugs (CHN-43 - Standard Chinese) (July 10, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
(6) (Article) Life Sciences: Product Regulation and Liability in China (CHN-11) (January 7, 2019)
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Clinical Trials
(7) (Article) National Medical Products Newsletter, 2020. Volume 5 (CHN-1) (May 2020)
China Center for Food and Drug International Exchange (CCFDIE)
Relevant Sections: NMPA Issues Requirements for Registration Classification and Application Dossiers of Chemical Drugs
(8) (Article) The Regulatory Requirements and Key Points of Drug Clinical Trials Registration in China (CHN-7) (May 20, 2020)
Yao, Zhuxing and Wang, Haixue; Applied Clinical Trials
(9) (Webpage) Administrative License (CHN-76 - Standard Chinese) (Current as of October 30, 2020)
Ministry of Science and Technology
Relevant Sections: Human Genetic Resource Management
Regulatory Authority > Regulatory Fees
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Issuing the Registration Fees for Drugs and Medical Device Products (No. 53 of 2015) (NMPA-No53-2015 – Standard Chinese) (May 27, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annex 1 – Drugs, medical equipment, products registered fees and Annex 2 – Drug Registration Implementation Detail (Trial)
(2) (Regulation) Re-issuance of Drug Registration Fees (No. 75 of 2020) (NMPA-No75-2020 – Standard Chinese) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(3) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter VI (Article 85)
Summary

Overview

In accordance with the DRR, the applicant is required to pay a fee per applicable regulations. As per the NMPA-No75-2020, NMPA-No53-2015, CHN-63, CHN-64, CHN-65, CHN-66, CHN-67, and CHN-68, the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) 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 Renminbi
  • New drugs made outside China: 376,000 Renminbi
  • Generic drugs made in China: 318,000 Renminbi
  • Generic drugs made outside China: 502,000 Renminbi

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.

Additional Resources
(1) (Webpage) Approval of Clinical Trials of Domestic Chemicals, Handling Guideline (CHN-63 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Charges
(2) (Webpage) Approval of Clinical Trials of Domestic Preventive Biological Products, Handling Guideline (CHN-65 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Charges
(3) (Webpage) Approval of Clinical Trials of Domestic Therapeutic Biological Products, Handling Guideline (CHN-64 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Charges
(4) (Webpage) Approval of Clinical Trials of Imported Chemicals, Handling Guideline (CHN-66 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Charges
(5) (Webpage) Approval of Clinical Trials of Imported Preventive Biological Products, Handling Guideline (CHN-68 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Charges
(6) (Webpage) Approval of Clinical Trials of Imported Therapeutic Biological Products, Handling Guideline (CHN-67 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Charges
Ethics Committee > Ethics Committee
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Administrative Measures for the Clinical Study Projects of Medical Institutions (NHC-ClinProjMgmt - Standard Chinese) (Effective October 16, 2014)
National Health Commission, State Council
Relevant Sections: Chapters I, II, III, IV, V, and VI
(2) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 1 (Articles 1-6), Chapter 2 (Articles 7-13), and Chapter 3 (Articles 17 and 21), Chapter 5 (Articles 40-43)
(3) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Articles 12-15)
(4) (Notice) Administration of Drug Clinical Trial Institutions (No. 101 of 2019) (NMPA-NHC-No101-2019 – Standard Chinese) (Effective December 1, 2019)
National Medical Products Administration, State Administration for Market Regulation, State Council, and the National Health Commission
Relevant Sections: 5 and 13
(5) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (GoogleTranslate-EthicsGuide) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Articles 5, 6, 8, 9, 10, and 12) and Chapter V (Article 22)
Summary

Overview

China has a decentralized process for the ethical review of clinical trial applications, and requires institutional level ethics committee (EC) approval for each trial site. China’s ethical review process is implemented through a three-tiered framework consisting of a national EC, provincial ECs, and institutional level ECs.

As delineated in the RegEthics and interpreted in CHN-41, 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. 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 and CHN-12, in response to scandals involving gene editing technology, China has approved establishing a National Science and Technology Ethics Committee to strengthen the ethics governance system with comprehensive coverage, clear orientation, and orderly coordination.

The 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 in the region, and guides, inspects, and evaluates the work of institutional ECs engaged in research involving human beings in the administrative region. 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. For additional details and analysis of China’s ethics review system and structure, see CHN-45.

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, a Clinical Study Administration Division, to handle daily project administration. For detailed requirements, see the NHC-ClinProjMgmt, CHN-14, and CHN-13.

EC Composition

Pursuant to the NMPA-GCP-No57-2020, the composition of the EC must meet the requirements of the health authorities, and include members of various categories with different gender compositions. The members of the EC must be trained in ethics review and be able to review ethical and scientific issues related to clinical trials. The EthicsGuide states institutional ECs must have at least five (5) members representing a balanced gender composition. However, per 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 RegEthics provides that the EC can hire an independent consultant if necessary. The independent consultant advises on specific issues of the project under review and does not participate in the voting.

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. The EC may also appoint or invite an independent consultant on an as needed basis for research projects.

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.

Terms of Reference, Review Procedures, and Meeting Schedule

As per the RegEthics, the EthicsGuide, and the NMPA-GCP-No57-2020, each institution must have written SOPs, including a process to be followed for conducting reviews. The RegEthics and the EthicsGuide state 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. The term of each EC member 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, the EthicsGuide, 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.

Additional Resources
(1) (Article) China Aims to Tighten Supervision Over Clinical Studies (CHN-14) (October 31, 2014)
Wang, Katherine; Ropes & Gray
(2) (Article) China Approves Ethics Advisory Group after CRISPR-babies Scandal (CHN-12) (August 8, 2019)
Jia, Hepeng; Nature
(3) (Article) China Sets New Requirements for Hospitals Running Clinical Trials (CHN-13) (November 10, 2014)
Brennan, Zachary; William Reed Business Media
(4) (Article) Interpretation of the "Methods for Ethical Examination of Biomedical Research Concerning People" (CHN-41 - Standard Chinese) (November 4, 2016)
National Health Commission
(5) (Article) Xi Jinping Hosted the Ninth Meeting of the Central Committee for Comprehensive Deepening Reform (CHN-3) (July 24, 2019)
Xinhua News Agency
(6) (Document) The Chinese Ethical Review System and its Compliance Mechanisms (CHN-45) (2016)
Xinqing, Z., Wenxia, Z., Yandong, Z.; TRUST Equitable Research Partnerships
Relevant Sections: China’s Ethics Review System and Its Structure
Ethics Committee > Scope of Review
Last content review/update: October 30, 2020
Requirements
(1) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter II (Articles 19-20)
(2) (Regulation) Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices (No. 42 of 2017) (SC-Opinions-No42 – Standard Chinese) (October 8, 2017)
Chinese Communist Party’s Central Committee and State Council
(3) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter III (Articles 25-26)
(4) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 1, Chapter 2 (Article 8), Chapter 3 (Articles 18, 20, 22-25, 27-29, and 32), and Chapter 7 (Article 50)
(5) (Guidance) Guidelines for General Consideration of the Publication of Drug Clinical Trials (No. 11 of 2017) (NMPA-No11-2017 – Standard Chinese) (January 18, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
(6) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1 (Article 3) and Chapter 3 (Article 12)
(7) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (GoogleTranslate-EthicsGuide) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter I (Articles 1 and 2), Chapter III (Articles 10 and 13), Chapter IV (Article 18), Chapter V (Articles 28 and 30), Chapter VI (Article 34), and Appendix 1
Summary

Overview

According to the EthicsGuide, 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.

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 Informed Consent topic, and the subtopics of Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired for additional information about these populations). 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 EthicsGuide, the NMPA-GCP-No57-2020, the DRR, the DAL, and the SC-Opinions-No42, the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) 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 NMPA-GCP-No57-2020 specifies that the EC’s scope of review must include:

  • Reviewing the following documents: the trial protocol and revisions; the informed consent form (ICF) and other written material provided to participants; the method and information of recruiting participants; the investigator's manual; existing safety information; compensation information; proof of investigator qualifications; and other documents required by the EC to perform its duties
  • The science and ethics of clinical trials
  • Qualifications of researchers
  • 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
  • If the trial protocol clearly states that the participants or their guardians cannot sign an ICF before the trial in an emergency whether the corresponding ethical issues, laws, and regulations are fully considered in the trial plan
  • 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

The EC must conduct its review within a reasonable time limit and give clear written opinions. The EC’s opinions must indicate one of the following: agree; agree after necessary amendments; disagree; or terminate or suspend. The opinion must state the content to be revised or the reason for rejection. In addition, 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. The EC must conduct regular follow-up review of clinical, and the frequency of review should be based on the risk level of the subjects, but at least once a year. Finally, the EC must accept and properly handle requests from participants.

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.

As delineated in the EthicsGuide, if a multicenter clinical trial is being conducted, the first institutional EC to review the protocol may collaborate with the subsequent participating ECs during the protocol review process. However, the participating ECs have the power to approve or disapprove the research conducted in their own 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 shall 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 the EC review.

There is no stated expiration date for an EC approval in the RegEthics, the EthicsGuide, the NMPA-GCP-No57-2020, the DRR, or the DAL.

Additional Resources
(1) (Document) The Chinese Ethical Review System and its Compliance Mechanisms (CHN-45) (2016)
Xinqing, Z., Wenxia, Z., Yandong, Z.; TRUST Equitable Research Partnerships
Relevant Sections: China’s Ethics Review System: Current Status, Problems, and Responses
(2) (International Guidance) Declaration of Helsinki (CHN-84) (October 19, 2013)
World Medical Association
Ethics Committee > Ethics Committee Fees
Last content review/update: October 30, 2020
Requirements
No applicable regulatory requirements
Summary

No relevant provisions.

Additional Resources
No additional resources
Ethics Committee > Authorizing Body
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices (No. 42 of 2017) (SC-Opinions-No42 – Standard Chinese) (October 8, 2017)
Chinese Communist Party’s Central Committee and State Council
(2) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 1 (Articles 5 and 6), Chapter 2 (Article 7), and Chapter V
(3) (Notice) Administration of Drug Clinical Trial Institutions (No. 101 of 2019) (NMPA-NHC-No101-2019 – Standard Chinese) (Effective December 1, 2019)
National Medical Products Administration, State Administration for Market Regulation, State Council, and the National Health Commission
Summary

Overview

The RegEthics states that all biomedical research institutions in China should establish their own ethics committee(s) (ECs). Per SC-Opinions-No42, the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) 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 the main investigators of clinical trials have senior professional titles and have participated in more than three (3) clinical trials. 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, the National Committee of Medical Ethics Experts provides policy and guidance that must be followed by ECs nationwide. With respect to supervision and management of ECs, the RegEthics delineates that the National Health Commission (NHC) is responsible for organizing the inspection and management of the national ethical review of biomedical research involving human beings, and the establishment of the National Committee of Medical Ethics Experts. The National Committee of Medical Ethics Experts is responsible for conducting research on major ethical issues in biomedical research involving humans, providing policy advice and guiding provincial medical ethics.

The provincial health administrative departments established a Provincial Medical Ethics Expert Committee. 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.

Additional Resources
(1) (Webpage) Drug and Medical Device Clinical Trial Institution Filing System (CHN-82 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Clinical Trial Lifecycle > Submission Process
Last content review/update: February 17, 2021
Requirements
(1) (Legislation) Biosecurity Law of the People's Republic of China (Bioscrty-Law – Standard Chinese) (Effective April 15, 2021)
National People’s Congress
Relevant Sections: Chapter VI (Articles 53-57)
(2) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter II (Articles 19-20)
(3) (Legislation) Vaccine Administration Law (VaccineLaw – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter I (Article 8), Chapter II (Article 16)
(4) (Regulation) Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50-2018 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Introduction, Sections 1-3, and Annex 1 (Communication meeting application form), Annex 2 (Communication meeting materials), and Annex 3 (Phase I clinical trial application materials)
(5) (Regulation) Guidelines for Acceptance and Review of Drug Registration (Trial) (No. 194 of 2017) (NMPA-No194-2017 – Standard Chinese) (November 30, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annexes 1 - 8
(6) (Regulation) Human Genetic Resources – Approval for Export, Administrative Licensing Service Guide (HGR-ExportLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1 and 8-11
(7) (Regulation) Human Genetic Resources – Collection and Approval of HGR in China, Administrative Licensing Service Guide (HGR-Collection – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1 and 8-11
(8) (Regulation) Human Genetic Resources – International Cooperative Clinical Trials, Record and Filing Management Service Guide (HGR-IntlRecordMgtServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1-3
(9) (Regulation) Human Genetic Resources – International Cooperative Research Approval, Administrative Licensing Service Guide (HGR-IntlApprovalLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1 and 8-11
(10) (Regulation) Human Genetic Resources – Preservation of HGR in China, Administrative Licensing Service Guide (HGR-Preservation – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1 and 8-11
(11) (Regulation) Human Genetic Resources – Scope and Procedures of Filing for the Use of China's HGR Information, Service Guide (HGR-DataUse – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 2-3
(12) (Regulation) Important Genetic Families and Human Genetic Resources in Specific Areas, Declaration and Registration Measures (Interim) (HGR-ImpFamilies-DeclReg – Standard Chinese) (July 1, 2019)
Ministry of Science and Technology
Relevant Sections: 5 and Annex 1
(13) (Regulation) Matters Relating to the Optimization of Drug Registration Review and Approval (No. 23 of 2018) (NMPA-No23-2018 – Standard Chinese) (May 17, 2018)
National Medical Products Administration, State Administration for Market Regulation, and the National Health Commission, State Council
Relevant Sections: Annexes 1-3
(14) (Regulation) Opinions on Reforming the Review and Approval System for Drugs and Medical Devices (No. 44 of 2015) (SC-Opinions-No44 – Standard Chinese) (August 9, 2015)
State Council
Relevant Sections: 1-8, 11-12, and 14
(15) (Regulation) Release of Administrative Measures for the Communication of Drug R & D and Technical Review (No. 74 of 2018) (NMPA-No74-2018 – Standard Chinese) (September 30, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 and Appendix 1
(16) (Regulation) Service Platform Human Genetic Resource Management (HGR-Procedures – Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Relevant Sections: 1 and 3-5
(17) (Regulation) Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230-2015 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(18) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter I (Articles 1-5), Chapter II (Article 13), Chapter III (Articles 20-26 and 32), and Chapter IV (59-75), and Chapter VII (Article 96)
(19) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (GoogleTranslate-MgmtHumanGen) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter I (Articles 4-5), Chapter II (Article 11), Chapter IV, and Chapter V (Article 36)
(20) (Guidance) Guidelines for Submission of Drug Clinical Trial Data (No. 16 of 2020) (NMPA-No16-2020 – Standard Chinese) (Effective October 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1
(21) (Guidance) Registration Classification and Application Information for Biological Products (No. 43 of 2020) (NMPA-No43-2020 – Standard Chinese) (Effective July 1, 2020 (registration) and October 1, 2020 (application))
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Part One (2) and Part Two (2)
(22) (Guidance) Registration Classification and Application Information for Chemical Drugs (No. 44 of 2020) (NMPA-No44-2020 – Standard Chinese) (Effective July 1, 2020 (registration) and October 1, 2020 (application))
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 3
(23) (Guidance) Working Procedures for Review of Breakthrough Therapeutics (No. 82 of 2020) (NMPA-No82-2020 – Standard Chinese) (Effective July 8, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(24) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Article 12)
(25) (Circular) Technical Guidelines for the Application of Phase I Clinical Trials of New Drugs (No. 16 of 2018) (NMPA-No16-2018 – Standard Chinese) (January 11, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annex
(26) (Notice) Application of the Second Level Guiding Principles of the International Human Drug Registration Technical Coordination Committee (No. 10 of 2018) (NMPA-No10-2018 – Standard Chinese) (January 25, 2018)
State Council
Relevant Sections: 1
(27) (Notice) Publication of the Work Plan for the Reform of the Classification and Registration of Chemical Drugs (No. 51 of 2016) (NMPA-No51-2016 – Standard Chinese) (March 4, 2016)
National Medical Products Administration, State Administration for Market Regulation, State Council
Summary

Overview

As per the DRR, the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) 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. NMPA’s Center for Drug Evaluation (CDE) is responsible for the evaluation of clinical trial applications. 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. Each EC has its own required submission procedures, which can differ significantly regarding the application format and number of copies.

As per the NMPA-No50-2018, the applicant should comply with the following review and approval procedures for clinical trials. (More detail on the contents and timing are provided in the Submission Content and Timeline of Review subtopics). The applicant should prepare materials and apply for a communication meeting with the NMPA’s CDE in accordance with the requirements of the NMPA-No74-2018, which includes requirements for different categories of meetings involving applications for new drugs. The NMPA-No74-2018 includes the application form (Appendix 1), which should be submitted to the CDE via its Applicant Window at CHN-58. 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 data or supplemented 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 DRR, after completing the pharmacology, toxicology, and other studies supporting the clinical trials of the drug, the applicant must submit relevant research materials to NMPA. Drug registrations and associated clinical trial application forms should be sent to NMPA’s Administrative Acceptance Service Hall (CHN-71 and CHN-61). Following administrative acceptance, clinical trial consultations and data submittals are handled at NMPA 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 Regulatory Authority topic, Scope of Review subtopic for information on the drug classifications.) If a sponsor intends to carry out a bioequivalence test, he/she must, after completing the filing of the bioequivalence test on the CDE’s website via the Applicant’s Window (CHN-58), carry out relevant research work in accordance with the filing plan. 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. The receiving personnel at the Administrative Acceptance Service Hall examine the application materials to verify that they comply with the administrative requirements. If the application is rejected, the applicant will be notified in person or within five (5) days of what must be corrected. Per the DRR, the DAL, and the NMPA-No50-2018, NMPA’s CDE must decide upon a drug clinical trial application within 60 days from the date of acceptance, and the applicant must be notified of the result by the CDE via the Applicant’s Window (CHN-58). If the notification is not given within the time limit, approval is implied and the applicant may develop the drug according to the submitted plan. The DRR specifies that applicants who are approved to conduct clinical trials are clinical trial sponsors (hereinafter referred to as sponsors). Clinical trials must be implemented within three (3) years after approval. If no participant has signed an informed consent within three (3) years from the date of approval, the clinical trial license will automatically become invalid.

In addition, 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. Pursuant to NMPA-No230-2015, if one (1) of the prescribed conditions are met, a separate queue will be implemented to speed up the examination and approval. The conditions are: innovative drugs with a plan to transfer their manufacturing site to China; global Clinical Trial Application (CTA) applied in China in parallel with the United States or the European Union; innovative drugs for HIV/AIDS, viral hepatitis, rare disease(s), malignant tumors and pediatric indications; newly-launched generic drugs. Further, the NMPA-No82-2020, 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 as 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. In addition, 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.

Per CHN-69, after the registration application is transferred to CDE, applicants can apply for accelerated review directly to CDE at the Applicant’s Window (CHN-58). CHN-69 contains the application and additional procedures for submitting applications for priority review and approval. (See Clinical Trial Lifecycle, Timeline of Review subtopic for additional details on expedited review.)

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 China’s HGR for use abroad. However, the regulation permits foreign entities with limited use of China’s HGR 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 pass an ethics review in the partners’ countries. The only exception to the approval requirement is international collaboration in clinical trials that do not involve the export of China HGR materials such as organs, tissues, or cells comprising the human genome, genes, or other genetic substances. Such clinical trial collaboration, however, 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-IntlApprovalLicenseServiceGuide covers license application procedures for international cooperation in the use of Chinese HGR for research
  • HGR-ExportLicenseServiceGuide 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-IntlRecordMgtServiceGuide 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-IntlApprovalLicenseServiceGuide, 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 at 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-IntlRecordMgtServiceGuide 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 cooperation 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 cooperation clinical trial.

Delivery Information for Clinical Trial Application

Per CHN-61, drug registrations and associated clinical trial application forms should be sent to NMPA’s Administrative Acceptance Service Hall (CHN-71 and CHN-61). Per the DRR, clinical trial research materials should be submitted to the CDE via the online Applicant’s Window (CHN-58). (Note that only Chinese legal persons can register for an account on the Applicant’s Window.)

NMPA Administrative Acceptance Service Center
1st Floor, Gate 3, Dacheng Plaza
28 Xuanwumen West Street
Xicheng District
Beijing 100053
P.R. China
Phone: +86-010-88331793 (drug acceptance); +86-010-88331734 (consultation of drug matters)
Email:
xzslfwdt@nmpa.gov.cn

Some HGR applications may be delivered to MOST at the address listed below. See the requirements in the various service guides for more detail.

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

Assembly and Number of Copies

The NMPA-No44-2020, the NMPA-No43-2020, and the NMPA-No10-2018 require applicants to apply the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) M4: Common Technical Document for the Registration of Pharmaceuticals for Human Use (CTD) (See CHN-38). M4 must be applied to the registration applications for drugs, therapeutic biological products, and vaccines. Further, per the NMPA-No16-2018, the applications of Phase I clinical trials must be submitted in electronic and hard copy formats and may be provided on a CD. 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 Association (CDISC).

Per the NMPA-No194-2017, the applicant must submit four (4) copies of the chemical and biologic clinical trial applications, with at least one (1) original. Application materials are provided in CHN-63, CHN-64, CHN-65, CHN-66, CHN-67, CHN-68, CHN-70, and CHN-69.

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

Clinical Trial Application Language Requirements

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.

Additional Resources
(1) (Article) China and the Evolving Regulatory Landscape (CHN-9) (September 4, 2019)
Baruah, Megha; European Pharmaceutical Review
(2) (International Guidance) ICH Harmonised Guideline: The Common Technical Document for the Registration of Pharmaceuticals for Human Use (M4) (CHN-38) (Step 5 Versions) (Modules range from 2002-2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(3) (Webpage) 7 Things to Know about the China Pharmaceutical Industry (CHN-80) (Current as of October 30, 2020)
Synchrogenix
Relevant Sections: 7
(4) (Webpage) Administrative Acceptance Service Hall: Things to Know (CHN-61 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(5) (Webpage) Administrative License (CHN-76 - Standard Chinese) (Current as of October 30, 2020)
Ministry of Science and Technology
Relevant Sections: Human Genetic Resource Management
(6) (Webpage) Applicant's Window (CHN-58 - Standard Chinese) (Current as of October 30, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(7) (Webpage) Approval of Clinical Trials of Domestic Chemicals, Handling Guideline (CHN-63 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(8) (Webpage) Approval of Clinical Trials of Domestic Preventive Biological Products, Handling Guideline (CHN-65 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(9) (Webpage) Approval of Clinical Trials of Domestic Therapeutic Biological Products, Handling Guideline (CHN-64 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(10) (Webpage) Approval of Clinical Trials of Imported Chemicals, Handling Guideline (CHN-66 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(11) (Webpage) Approval of Clinical Trials of Imported Preventive Biological Products, Handling Guideline (CHN-68 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(12) (Webpage) Approval of Clinical Trials of Imported Therapeutic Biological Products, Handling Guideline (CHN-67 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(13) (Webpage) Bioequivalence of Chemical Generic Drugs and Clinical Trial Filing, Handling Guideline (CHN-70 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(14) (Webpage) Online Service Hall of the National Medical Products Administration (CHN-71 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(15) (Webpage) Priority Review and Approval of Drug Registration Applications, Handling Guideline (CHN-69 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
Clinical Trial Lifecycle > Submission Content
Last content review/update: February 17, 2021
Requirements
(1) (Legislation) Biosecurity Law of the People's Republic of China (Bioscrty-Law – Standard Chinese) (Effective April 15, 2021)
National People’s Congress
Relevant Sections: Chapter VI (Articles 53-57)
(2) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter II (Articles 19-20)
(3) (Regulation) Decision Concerning the Adjustment of Imported Drug Registration and Administration (No. 35 of 2017) (NMPA-No35-2017 – Standard Chinese) (October 10, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
(4) (Regulation) Human Genetic Resources – Approval for Export, Administrative Licensing Service Guide (HGR-ExportLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1, 7-8, and Annex 1
(5) (Regulation) Human Genetic Resources – Collection and Approval of HGR in China, Administrative Licensing Service Guide (HGR-Collection – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1, 7-8, and Annex 1
(6) (Regulation) Human Genetic Resources – International Cooperative Clinical Trials, Record and Filing Management Service Guide (HGR-IntlRecordMgtServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 3 and Annex 1
(7) (Regulation) Human Genetic Resources – International Cooperative Research Approval, Administrative Licensing Service Guide (HGR-IntlApprovalLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1, 7-8, Annex 1
(8) (Regulation) Human Genetic Resources – Preservation of HGR in China, Administrative Licensing Service Guide (HGR-Preservation – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1, 7-8, and Annex 1
(9) (Regulation) Human Genetic Resources – Scope and Procedures of Filing for the Use of China's HGR Information, Service Guide (HGR-DataUse – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 3 and Annexes 1-2
(10) (Regulation) Important Genetic Families and Human Genetic Resources in Specific Areas, Declaration and Registration Measures (Interim) (HGR-ImpFamilies-DeclReg – Standard Chinese) (July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Annex 1
(11) (Regulation) Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices (No. 42 of 2017) (SC-Opinions-No42 – Standard Chinese) (October 8, 2017)
Chinese Communist Party’s Central Committee and State Council
(12) (Regulation) Service Platform Human Genetic Resource Management (HGR-Procedures – Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Relevant Sections: 1 and 3-5
(13) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter I (Article 5), Chapter II (Articles 9-10), Chapter III (Articles 20-26)
(14) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (GoogleTranslate-MgmtHumanGen) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter I (Articles 1-4 and 7-9)
(15) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Article 19)
(16) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 6
(17) (Circular) Technical Guidelines for the Application of Phase I Clinical Trials of New Drugs (No. 16 of 2018) (NMPA-No16-2018 – Standard Chinese) (January 11, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annex
(18) (Circular) Technical Guiding Principles for Accepting Data from Overseas Clinical Trials of Drugs (No. 52 of 2018) (NMPA-No52-2018 – Standard Chinese) (July 6, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
(19) (Notice) Application of the Second Level Guiding Principles of the International Human Drug Registration Technical Coordination Committee (No. 10 of 2018) (NMPA-No10-2018 – Standard Chinese) (January 25, 2018)
State Council
Relevant Sections: 1
(20) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (GoogleTranslate-EthicsGuide) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Articles 5, 6, 8, 9, 10, and 12), Chapter IV (Articles 18-21), and Chapter V (Article 22)
Summary

Overview

In accordance with DRR and the DAL, the sponsor must apply to the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) and an ethics committee (EC) to conduct a clinical trial for all drugs that will be registered in China. As stated in the DRR, EC review may be submitted parallel to NMPA’s review, but the study cannot be initiated until after review and approval by the EC. The DRR also 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.

NMPA Requirements

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 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 exactly 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, 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) (See CHN-38). M4 must be applied to the registration applications for drugs, therapeutic biological products, and vaccines.

The NMPA-No35-2017 and interpretations in CHN-43 adjust 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. 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 for the NMPA-No52-2018 requirements for clinical trial and drug registration applications of imported new drugs or therapeutic biological products using trial data generated entirely overseas, they 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 can be acceptable for direct China registration provided that:

  • The data is reliable, authenticated, and complies with the requirements of the ICH's Guideline for Good Clinical Practice 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 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, NMPA will consider approval of these drug registrations exempted from conducting clinical trials, with the condition that the applications meet all other Chinese drug regulatory requirements.

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

Ministry of Science and Technology (MOST) Requirements

With regard to reviewing and approving human genetic resources (HGR) licenses, and in accordance with the Bioscrty-Law and the MgmtHumanGen, the Ministry of Science and Technology (MOST) is responsible for China's efforts to manage HGR, comprising genetic material and data. MOST’s online platform (CHN-76) provides links to procedures, requirements, and online submissions. The HGR-Procedures and CHN-56 summarize the license and application contents.

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-IntlApprovalLicenseServiceGuide 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 cooperation 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-ExportLicenseServiceGuide 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-IntlRecordMgtServiceGuide 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 cooperation 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 Specimens topic, Specimen Import & Export subtopic.

EC Requirements

Each 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 EthicsGuide to exemplify the common elements shared by the various application forms:

  • 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 Informed Consent topic, Children/Minors subtopic 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 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 Clinical Trial Lifecycle topic, Safety Reporting subtopic for additional information)
  • Proposed trial schedule and completion date
  • Publication policy

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

Additional Resources
(1) (Article) China and the Evolving Regulatory Landscape (CHN-9) (September 4, 2019)
Baruah, Megha; European Pharmaceutical Review
(2) (Article) Interpretation of the Technical Guiding Principles for Accepting Data from Overseas Clinical Trials of Drugs (CHN-43 - Standard Chinese) (July 10, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
(3) (Form) Application for Human Research Ethics Review (CHN-35 - Standard Chinese) (Date Unavailable)
Independent Ethics Committee, Shanghai Clinical Research Center
(4) (Form) Human Research Ethics Review Application Documents (CHN-34 - Standard Chinese) (Date Unavailable)
Independent Ethics Committee, Shanghai Clinical Research Center
(5) (International Guidance) ICH Harmonised Guideline: The Common Technical Document for the Registration of Pharmaceuticals for Human Use (M4) (CHN-38) (Step 5 Versions) (Modules range from 2002-2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(6) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 6
(7) (Webpage) Administrative Acceptance Service Hall: Things to Know (CHN-61 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(8) (Webpage) Administrative License (CHN-76 - Standard Chinese) (Current as of October 30, 2020)
Ministry of Science and Technology
(9) (Webpage) Applicant's Window (CHN-58 - Standard Chinese) (Current as of October 30, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(10) (Webpage) Approval of Clinical Trials of Domestic Chemicals, Handling Guideline (CHN-63 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(11) (Webpage) Approval of Clinical Trials of Domestic Preventive Biological Products, Handling Guideline (CHN-65 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(12) (Webpage) Approval of Clinical Trials of Domestic Therapeutic Biological Products, Handling Guideline (CHN-64 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(13) (Webpage) Approval of Clinical Trials of Imported Chemicals, Handling Guideline (CHN-66 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(14) (Webpage) Approval of Clinical Trials of Imported Preventive Biological Products, Handling Guideline (CHN-68 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(15) (Webpage) Approval of Clinical Trials of Imported Therapeutic Biological Products, Handling Guideline (CHN-67 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(16) (Webpage) Bioequivalence of Chemical Generic Drugs and Clinical Trial Filing, Handling Guideline (CHN-70 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(17) (Webpage) Integrated System Catalogue, Human Genetic Resource Management (CHN-56 - Standard Chinese) (Current as of October 30, 2020)
Ministry of Science and Technology
(18) (Webpage) National Medical Products Administration – Drug Regulatory Documents (CHN-60 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(19) (Webpage) Online Service Hall of the National Medical Products Administration (CHN-71 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(20) (Webpage) Priority Review and Approval of Drug Registration Applications, Handling Guideline (CHN-69 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
Clinical Trial Lifecycle > Timeline of Review
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50-2018 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1-4 and Annexes 1-3
(2) (Regulation) Matters Relating to the Optimization of Drug Registration Review and Approval (No. 23 of 2018) (NMPA-No23-2018 – Standard Chinese) (May 17, 2018)
National Medical Products Administration, State Administration for Market Regulation, and the National Health Commission, State Council
(3) (Regulation) Opinions on Reforming the Review and Approval System for Drugs and Medical Devices (No. 44 of 2015) (SC-Opinions-No44 – Standard Chinese) (August 9, 2015)
State Council
Relevant Sections: 1-8, 11-12, and 14
(4) (Regulation) Release of Administrative Measures for the Communication of Drug R & D and Technical Review (No. 74 of 2018) (NMPA-No74-2018 – Standard Chinese) (September 30, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapters 1 and 7
(5) (Regulation) Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230-2015 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(6) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter II (Article 13), Chapter III (Articles 23 and 25-26), Chapter IV (Articles 59-75) and Chapter VII (Articles 94-96, and 103)
(7) (Guidance) Working Procedures for Review of Breakthrough Therapeutics (No. 82 of 2020) (NMPA-No82-2020 – Standard Chinese) (Effective July 8, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(8) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Articles 12 and 13)
(9) (Notice) Publication of the Work Plan for the Reform of the Classification and Registration of Chemical Drugs (No. 51 of 2016) (NMPA-No51-2016 – Standard Chinese) (March 4, 2016)
National Medical Products Administration, State Administration for Market Regulation, State Council
(10) (Notice) Relevant Issues Concerning the Review and Approval of New Overseas Drugs for Clinical Urgent Needs (No. 79 of 2018) (NMPA-No79-2018 – Standard Chinese) (October 23, 2018)
National Medical Products Administration, State Administration for Market Regulation, and the National Health Commission, State Council
Summary

Overview

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

NMPA Approval

While China has adopted reforms to speed up the process (described below), according to CHN-22, it can still take one (1) to two (2) years in some cases. For example, if the NMPA has queries or negative feedback is returned to the applicant. As stated in CHN-6, the NMPA review and approval process can be longer for imported drugs due to the additional time required by the Center for Drug Evaluation (CDE) to conduct its technical review and the National Institutes for Food and Drug Control (NIFDC) to test drug samples and review standards.

To help facilitate the review process, the NMPA-No50-2018 and the NMPA-No74-2018 specify that 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. The NMPA-No74-2018 specifies deadlines and procedures and indicates that the applicant must include the meeting materials in the application. 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 NMPA. Drug registrations and associated clinical trial application forms should be sent to NMPA’s Administrative Acceptance Service Hall (CHN-71 and CHN-61). Following administrative acceptance, clinical trial consultations and data submittals are handled at NMPA CDE’s Applicant’s Window (CHN-58). 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 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 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, 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 as 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. The timelines for review and decisions are as follows: CDE will review the application for breakthrough drug procedures submitted by the applicant and, if necessary, organize an expert advisory committee for demonstration. 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. 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 CDE within five (5) days; CDE must organize another review and make a decision within 15 days and notify all relevant parties.

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 application materials. For applications to conduct clinical trials with drugs treating rare diseases, the CDE completes the technical review within three (3) months after acceptance; for other overseas new drugs, the technical review is completed within six (6) months after acceptance. The NMPA-No23-2018 states that for drugs that have been listed overseas and 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.

The DRR also authorizes 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 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 NMPA to implement special approval procedures for drugs required for emergency public health emergencies. The circumstances, procedures, time limits, and requirements for special approval, will be subject to NMPA’s procedures for specific approval of drugs.

In another reform directed at streamlining the review process, per the NMPA-No230-2015, the NMPA adopted a one-time approval for clinical trial applications of new drugs. For additional details, see the Regulatory Authority topic, Scope of Assessment subtopic. In addition, 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.

EC 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.

Additional Resources
(1) (Article) China (CHN-22) (April 2020)
Kingham, Richard; The Life Sciences Law Review, Edition 8
Relevant Sections: Approval Timeline
(2) (Article) China Adds 30 Drugs to its "Urgently Needed" List (CHN-24) (April 2, 2019)
Hogan Lovells
(3) (Article) China Drug Regulator Calling on International Pharmaceutical Companies to Bring “Urgently-Needed” New Drugs to China (CHN-6) (August 9, 2018)
Hogan Lovells
(4) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 3.1.2
(5) (Webpage) Administrative Acceptance Service Hall: Things to Know (CHN-61 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(6) (Webpage) Applicant's Window (CHN-58 - Standard Chinese) (Current as of October 30, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(7) (Webpage) Approval of Clinical Trials of Domestic Chemicals, Handling Guideline (CHN-63 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(8) (Webpage) Approval of Clinical Trials of Domestic Preventive Biological Products, Handling Guideline (CHN-65 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(9) (Webpage) Approval of Clinical Trials of Domestic Therapeutic Biological Products, Handling Guideline (CHN-64 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(10) (Webpage) Approval of Clinical Trials of Imported Chemicals, Handling Guideline (CHN-66 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(11) (Webpage) Approval of Clinical Trials of Imported Preventive Biological Products, Handling Guideline (CHN-68 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(12) (Webpage) Approval of Clinical Trials of Imported Therapeutic Biological Products, Handling Guideline (CHN-67 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
(13) (Webpage) Bioequivalence of Chemical Generic Drugs and Clinical Trial Filing, Handling Guideline (CHN-70 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information and Process
(14) (Webpage) Online Service Hall of the National Medical Products Administration (CHN-71 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(15) (Webpage) Priority Review and Approval of Drug Registration Applications, Handling Guideline (CHN-69 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Basic Information, Process, and Application Materials
Clinical Trial Lifecycle > Trial Initiation
Last content review/update: October 30, 2020
Requirements
(1) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter II (Articles 19-20)
(2) (Regulation) Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50-2018 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annex 3
(3) (Regulation) Regulations for Drug Clinical Trial Registration and Information Disclosure Management (No. 9 of 2020) (NMPA-No9-2020 – Standard Chinese) (Effective July 1, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapters 1 and 2
(4) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter II (Articles 9 and 10) and Chapter III (Articles 25-26, and 33)
(5) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (GoogleTranslate-MgmtHumanGen) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter V (Article 36)
(6) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapters 1 and 2
(7) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Article 4), Chapter 3 (Article 12), Chapter 4 (Articles 16 and 19), and Chapter 5 (Articles 32, 36, and 38)
(8) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (GoogleTranslate-EthicsGuide) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Glossary of Terms, Chapter 3 (Article 15), and Chapter 4
Summary

Overview

In accordance with the NMPA-GCP-No57-2020, the DRR, the DAL, the RegEthics, and the EthicsGuide, the sponsor must apply to the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) and an ethics committee (EC) to conduct a clinical trial for all drugs to be registered in China. As stated in the DRR, EC review may be submitted parallel to NMPA review, but the study cannot be initiated until after review and approval by the EC. Clinical trial applications are also considered drug registration applications. The DRR states that a Chinese legal entity must submit the drug registration application. Overseas drug manufacturers without legal representation in China must apply for drug registration through Chinese legal persons who will handle relevant drug registration matters.

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, investigator's brochure, 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 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. 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. 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 cooperation 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. As stated in the NMPA-GCP-No57-2020 and CHN-37, all investigators must possess appropriate qualifications, training, and experience.

EC Confirmation of Review and Approval

The NMPA-GCP-No57-2020 mandate that the sponsor receive written confirmation of EC review and approval of the protocol prior to the trial’s commencement.

(See Ethics Committee topic, Scope of Review subtopic and Clinical Trial Lifecycle topic, Submission Content subtopic for additional details on the EC review process).

Clinical Trials Registry

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 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 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 NMPA

Data and Safety Monitoring Board

Per the EthicsGuide, the sponsor is required to establish a Data and Safety Monitoring Board (DSMB) and submit its composition to the EC prior to the trial’s commencement. The DSMB’s duty is to regularly assess the progress of the trial, analyze safety data, and monitor the trial. For additional details on DSMB requirements, see the EthicsGuide. The NMPA-GCP-No57-2020 states that a DSMB is established by the sponsor to regularly review the progress of clinical trials, safety data, and efficacy.

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.

The NMPA-GCP-No57-2020 and CHN-37 recommend establishing a 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.

Additional Resources
(1) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.17, 1.25, 4.1, 5.1.2, 5.5.2, 5.6, and 8.2.6
(2) (Webpage) Drug Clinical Trial Registration and Information Disclosure Platform (CHN-53 - Standard Chinese) (Current as of October 30, 2020)
Center for Drug Reevaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
Clinical Trial Lifecycle > Safety Reporting
Last content review/update: February 17, 2021
Requirements
(1) (Legislation) Biosecurity Law of the People's Republic of China (Bioscrty-Law – Standard Chinese) (Effective April 15, 2021)
National People’s Congress
Relevant Sections: Chapter II (Articles 10-11 and 14) and Chapter IV (Articles 34-40)
(2) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter II (Article 22)
(3) (Regulation) Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50-2018 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 16 and Annex 3
(4) (Regulation) Regulations for Management of Safety Update Reports During R&D (No. 7 of 2020) (NMPA-No7-2020 – Standard Chinese) (Effective July 1, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(5) (Regulation) Regulations for Safety Information Evaluation and Management During Drug Clinical Trials (No. 5 of 2020) (NMPA-No5-2020 – Standard Chinese) (Effective July 1, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(6) (Regulation) Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230-2015 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(7) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter II (Article 28)
(8) (Guidance) Standards and Procedures for the Rapid Reporting of Safety Data during Clinical Trials (G-SftyRptStds – Standard Chinese) (April 27, 2018)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1-17
(9) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Article 4), Chapter 4 (Article 26), and Chapter 5 (Article 48)
(10) (Notice) Application of the Second Level Guiding Principles of the International Human Drug Registration Technical Coordination Committee (No. 10 of 2018) (NMPA-No10-2018 – Standard Chinese) (January 25, 2018)
State Council
Relevant Sections: 2
(11) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (GoogleTranslate-EthicsGuide) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Glossary of Terms
Summary

Overview

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.

Reporting Requirements for AE/ADRs

Per the DRR, the sponsor must regularly submit a safety update report to the National Medical Products Administration’s (NMPA) (the Chinese name translates as “State Drug Administration”) 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. 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 NMPA-No7-2020.

The DRR requires the sponsor to report SUSARs and other potentially serious safety risks to 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 trial drugs during the drug trial period. The G-SftyRptStds states 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. The NMPA-No5-2020 provides guidance on evaluating and managing safety issues in accordance with the G-SftyRptStds. It requires sponsors to actively cooperate with clinical trial institutions and other relevant parties to strictly implement the main responsibility of safety risk management. A pharmacovigilance system and system 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.

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 it and consider treating the participant and whether to make corresponding adjustments to the protocol.

The G-SftyRptStds specifies reporting timelines for unexpected death or serious life-threatening adverse reactions. The report should be submitted 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 CDE as soon as possible and medical treatments should be decided upon for each situation. Generally, information that significantly affects the evaluation of the risk and benefit of drugs, 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 NMPA.

The NMPA-GCP-No57-2020 expands upon investigator responsibilities. Except for SAEs that do not need to be reported immediately per the trial protocol or other documents (such as the IB), 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. 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.

As per the NMPA-No50-2018, the NMPA-No10-2018, the G-SftyRptStds, and CHN-72, 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 of E2A and E2B (R3). To comply with these requirements, the project’s electronic safety database must meet the E2B (R3)’s XML format and be submitted to NMPA’s CDE in Chinese (CHN-58). Potentially serious security risks can be sent as a “Quick Report” through e-mail to: lcqjywjj@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.

Data and Safety Monitoring Board

Per the EthicsGuide, the sponsor is also required to establish a Data and Safety Monitoring Board (DSMB) to assess the progress of the trial regularly, analyze safety data, and monitor the pilot program. The NMPA-GCP-No57-2020 states that a DSMB is established by the sponsor to regularly review the progress of clinical trials, safety data, and efficacy.

As delineated in G-SftyRptStds, the sponsor should appoint full-time staff to monitor clinical trial safety information and manage SAE 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.

The ICH’s Guideline for Good Clinical Practice E6(R2) (CHN-37) recommends establishing a 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.

Biotechnology Safety Monitoring and Reporting

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 will be formulated, adjusted, and announced by the competent departments of the State Council 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.

Additional Resources
(1) (International Guidance) ICH Guideline E2B (R3) on Electronic Transmission of Individual Case Safety Reports (ICSRs) - Data Elements and Message Specification - Implementation Guide (CHN-40) (Step 5 Version) (July 2013)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(2) (International Guidance) ICH Harmonised Tripartite Guideline: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A) (CHN-39) (Step 4 Version) (October 27, 1994)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(3) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.25 and 5.5.2
(4) (Webpage) Applicant's Window (CHN-58 - Standard Chinese) (Current as of October 30, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(5) (Webpage) The New Standards and Procedures for the Expedited Reports of Safety Data During Clinical Trials Released by China (CHN-72) (May 15, 2018)
ZM Company
Clinical Trial Lifecycle > Progress Reporting
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230-2015 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(2) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter III (Article 33)
(3) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 4 (Article 28)
Summary

Overview

Per the NMPA-GCP-No57-2020, investigators must provide clinical trial progress reports.

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, EC, and clinical trial institution as soon as possible.

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).

Additional Resources
(1) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.10 and 4.13
(2) (Webpage) Applicant's Window (CHN-58 - Standard Chinese) (Current as of October 30, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
Sponsorship > Definition of Sponsor
Last content review/update: October 30, 2020
Requirements
(1) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter III (Articles 30, 38, and 40)
(2) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter II (Article 9) and Chapter III (Articles 23 and 29)
(3) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Article 7) and Chapter 5 (Article 33)
Summary

Overview

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. For work and tasks that are not clearly entrusted to the CRO, the responsibilities of the work and tasks are still the responsibility of the sponsor. 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, but, 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 marketing license,” 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 marketing license is fully responsible for the quality of the drug used in a clinical trial. When the holder of the license is an overseas entity, their designated legal person in China must fulfill the same obligations as the holder of the drug marketing license and bear joint and several liability with the holder of the drug marketing license.

Additional Resources
(1) (Article) Life Sciences: Product Regulation and Liability in China (CHN-11) (January 7, 2019)
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Are any legislative changes proposed or expected in the near future?
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.53, 1.54, and 5.2
Sponsorship > Trial Authorization
Last content review/update: October 30, 2020
Requirements
(1) (Legislation) Vaccine Administration Law (VaccineLaw – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: 16-18
(2) (Regulation) Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50-2018 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 16
(3) (Regulation) Notice on Propaganda and Implementation of the Vaccine Administration Law (No. 23 of 2019) (NMPA-No32-2019 – Standard Chinese) (July 25, 2019)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 4
(4) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter II (Article 9 and 10), Chapter III (Article 23) and Chapter VII (Articles 94-96)
(5) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 5 (Articles 40-43)
(6) (Circular) Technical Guidelines for the Application of Phase I Clinical Trials of New Drugs (No. 16 of 2018) (NMPA-No16-2018 – Standard Chinese) (January 11, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annex
(7) (Notice) Application of the Second Level Guiding Principles of the International Human Drug Registration Technical Coordination Committee (No. 10 of 2018) (NMPA-No10-2018 – Standard Chinese) (January 25, 2018)
State Council
Summary

Overview

In accordance with the NMPA-No50-2018, the sponsor or its contract research organization (CRO) is responsible for submitting a clinical trial application to the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) to obtain approval to conduct a study. Per the NMPA-GCP-No57-2020, before the start of a clinical trial, the sponsor must submit relevant clinical trial materials to NMPA, and obtain the appropriate license for the clinical trial or complete the requisite filing. The sponsor must obtain the following information from the investigator and clinical trial institution: the name and address of the ethics committee (EC), the list of EC members participating in the review, the review statement in compliance with relevant laws and regulations, and the documents approved by the EC. When the sponsor is developing a clinical trial program, it must have sufficient safety and effectiveness data to support its route of administration, dosage, and duration of continuous medication. When important new information is obtained, the sponsor must update the Investigator's Brochure (IB) in a timely manner.

The DRR states that a Chinese legal entity must submit the drug registration application. Overseas drug manufacturers without legal representation in China must apply for drug registration through Chinese legal persons to handle relevant drug registration matters.

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 NMPA. Drug registrations and associated clinical trial application forms should be sent to NMPA’s Administrative Acceptance Service Hall (CHN-71 and CHN-61). Following administrative acceptance, clinical trial consultations and data submittals are handled at NMPA’s Center for Drug Evaluation (CDE)’s Applicant’s Window (CHN-58). (Note that only Chinese legal persons can register for an account on the Applicant’s Window.) 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. (See Clinical Trial Lifecycle topic, Submission Process and Content subtopics for handling guidelines and content.) 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
  • IB
  • Clinical trial plan
  • Pharmacy research information
  • Pharmacology and toxicology information
  • Description of previous clinical use experience
  • Overseas research material

Per the NMPA-No50-2018 and CHN-61, the electronic files and a hard copy of the application must be submitted to NMPA. The NMPA Administrative Acceptance Service Center provides links to download and submit applications, and to check the status of an application. 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). M4 must be applied to the registration applications for drugs, therapeutic biological products, and vaccines. Further, the NMPA-No16-2018 states that the applications of Phase I clinical trials must be submitted in electronic and hard copy formats and may be provided on a CD.

In accordance with the DRR 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. Upon submittal, the NMPA’s CDE 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, then the CDE will notify the applicant, who must submit the additional information within five (5) days of the CDE’s notice. If the applicant has not received any other questions from the CDE within 60 days from the date of the supplementary information, then the clinical trial may be initiated with the revised plan.

Per the VaccineLaw, the sponsor of the vaccine clinical trial must submit a clinical trial plan, establish a clinical trial safety monitoring and evaluation system, carefully select the subjects, reasonably set the subject group and age group, and take effective measures according to the degree of risk to protect the legal rights of the participant. 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 when applying for vaccine clinical trials (e.g., false data).

Additional documentation that must be submitted is covered in the Clinical Trial Lifecycle topic, Submission Content subtopic.

Clinical Trial Agreement

Per the NMPA-GCP-No57-2020, the sponsor, investigator, and the clinical trial institution must sign a written agreement that specifies the responsibilities, rights, and interests of all parties to the clinical trial, as well as the possible conflicts of interest. The clinical trial expenses detailed in the contract must be reasonable and comply with market laws. The sponsor, investigator, and clinical trial institution must sign the agreement. 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
Additional Resources
(1) (Article) China and the Evolving Regulatory Landscape (CHN-9) (September 4, 2019)
Baruah, Megha; European Pharmaceutical Review
(2) (Article) China FDA Announces Implementation Scheme to Improve the Drug Approval System (CHN-15) (November 19, 2015)
Wang, Katherine; Ropes & Gray
(3) (International Guidance) ICH Harmonised Guideline: The Common Technical Document for the Registration of Pharmaceuticals for Human Use (M4) (CHN-38) (Step 5 Versions) (Modules range from 2002-2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(4) (Webpage) Administrative Acceptance Service Hall: Things to Know (CHN-61 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(5) (Webpage) Applicant's Window (CHN-58 - Standard Chinese) (Current as of October 30, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(6) (Webpage) Online Service Hall of the National Medical Products Administration (CHN-71 - Standard Chinese) (Current as of October 30, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Sponsorship > Insurance
Last content review/update: October 30, 2020
Requirements
(1) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 5 (Article 39)
Summary

Overview

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.

Additional Resources
(1) (Article) Life Sciences: Product Regulation and Liability in China (CHN-11) (January 7, 2019)
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Clinical Trials, Insurance
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 5.8
Sponsorship > Compensation
Last content review/update: October 30, 2020
Requirements
(1) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 5 (Article 39)
Summary

Overview

In accordance with the NMPA-GCP-No57-2020, 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. (See Informed Consent topic, Compensation Disclosure subtopic for more information on participant compensation rights).

In addition, the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (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.

Additional Resources
(1) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.8 and 5.8
Sponsorship > Quality, Data & Records Management
Last content review/update: October 30, 2020
Requirements
(1) (Legislation) Vaccine Administration Law (VaccineLaw – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: 11 and 17
(2) (Regulation) Decision Concerning the Adjustment of Imported Drug Registration and Administration (No. 35 of 2017) (NMPA-No35-2017 – Standard Chinese) (October 10, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
(3) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter I (Article 3) and Chapter III (Articles 25, 28-31, and 46-47)
(4) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (GoogleTranslate-MgmtHumanGen) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter III (Article 24)
(5) (Guidance) Guidelines for Submission of Drug Clinical Trial Data (No. 16 of 2020) (NMPA-No16-2020 – Standard Chinese) (Effective October 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(6) (Guidance) Guidelines for the Preservation of Essential Documents for Drug Clinical Trials (No. 37 of 2020) (NMPA-No37-2020 – Standard Chinese) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(7) (Guidance) Requirements for Drug Records and Data Management for Trial Implementation (No. 74 of 2020) (NMPA-No74-2020 – Standard Chinese) (Effective December 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(8) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 4 (Article 16 and 25) and Chapters 5 and 8
(9) (Circular) Information Guide for Innovative Medicine (Chemicals) Phase III Clinical Trial Pharmaceutical Research (No. 48 of 2018) (NMPA-No48-2018 - Standard Chinese) (March 9, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
(10) (Notice) Publication of Technical Guidelines for Clinical Trial Data Management (No. 112 of 2016) (NMPA-No112-2016 – Standard Chinese) (July 27, 2016)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Overview and II(A) The Responsibility of the Relevant Personnel
Summary

Overview

Per the DRR, the management of drugs used in clinical trials must comply with the clinical trial quality management regulations, NMPA-GCP-No57-2020. As stated in the NMPA-GCP-No57-2020 and the NMPA-No112-2016, 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. 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 methods of QA and QC of 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) (the Chinese name translates as “State Drug Administration”), 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 the rights and safety of participants; 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 is 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 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 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 Association (CDISC). In addition, the NMPA-No74-2020 has details on the management of records and data that must be provided to 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 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.

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 cooperation 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.

Electronic Data Processing System

As per the NMPA-GCP-No57-2020, the sponsor must meet the following requirements in electronic data processing:

  • 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 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 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.

Record 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 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 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.

Audit 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, researchers and clinical trial institutions must agree to supervision and inspection organized by the sponsor and NMPA. The sponsor must provide an inspection report or certificate when requested by NMPA. In accordance with the DRR and CHN-8, NMPA’s Center for Drug Evaluation (CDE) will make a risk-based decision on whether to conduct an inspection of a clinical trial, based on the level of drug innovation and the past verification history of the clinical trial site.

See the NMPA-GCP-No57-2020 and CHN-37 for additional guidance on audits and inspections.

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 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 NMPA, and explain the reasons.

When a clinical trial is completed or terminated early, the sponsor must submit a clinical trial report to 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.

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 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 Clinical Trial Lifecycle topic, Submission Content subtopic.

Additional Resources
(1) (Article) China Promulgates Revised Drug Registration Regulation (CHN-8) (April 29, 2020)
Covington
Relevant Sections: Clinical Trial Inspections
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.65, 5.0, 5.1, 5.2, 5.5, 5.18, 5.19, 5.21, 5.23, 6.10, and 8
(3) (Webpage) Applicant's Window (CHN-58 - Standard Chinese) (Current as of October 30, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
Sponsorship > Site/Investigator Selection
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50-2018 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annex 3
(2) (Regulation) Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices (No. 42 of 2017) (SC-Opinions-No42 – Standard Chinese) (October 8, 2017)
Chinese Communist Party’s Central Committee and State Council
Relevant Sections: 1 and 2
(3) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter II (Articles 9 and 10) and Chapter III (Article 22)
(4) (Guidance) Standards and Procedures for the Rapid Reporting of Safety Data during Clinical Trials (G-SftyRptStds – Standard Chinese) (April 27, 2018)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 8
(5) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 4 (Articles 16-17) and Chapter 5 (Articles 37-38)
(6) (Notice) Administration of Drug Clinical Trial Institutions (No. 101 of 2019) (NMPA-NHC-No101-2019 – Standard Chinese) (Effective December 1, 2019)
National Medical Products Administration, State Administration for Market Regulation, State Council, and the National Health Commission
(7) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (GoogleTranslate-EthicsGuide) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Article 15) and Chapter 4
Summary

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. 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 Clinical Trial Lifecycle topic, Submission Content subtopic for additional information on clinical trial application requirements). See the NMPA-GCP-No57-2020 for additional details on investigator and clinical trial institution requirements.

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, the 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 required conditions.

Institutional Registration

Per the SC-Opinions-No42, the NMPA-NHC-No101-2019, and CHN-5, the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) 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. 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.

Data and Safety Monitoring Board

As per the EthicsGuide, the sponsor is also required to establish a Data and Safety Monitoring Board (DSMB) prior to a trial’s commencement, and submit its composition to the EC. The EthicsGuide, the NMPA-GCP-No57-2020, and CHN-37 indicate that the DSMB’s duty is to regularly assess the progress of the trials, analyze safety data, and monitor the trial. The NMPA-GCP-No57-2020 and CHN-37 further states that a DSMB recommends to the sponsor whether to continue, modify, or stop a trial.

As delineated in G-SftyRptStds, 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.

Foreign Sponsor Responsibilities

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

Additional Resources
(1) (Article) Provisions on the Filing and Management of Drug Clinical Trial Institutions (CHN-5) (December 6, 2019)
Xinhuanet
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.25, 5.5, and 5.6
Informed Consent > Documentation Requirements
Last content review/update: October 30, 2020
Requirements
(1) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter II (Article 21)
(2) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (GoogleTranslate-MgmtHumanGen) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter I (Article 9) and Chapter II (Article 12)
(3) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Articles 18, 19, and 28) and Chapter 4 (Articles 33-39)
(4) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1 (Article 3), Chapter 3 (Article 12), and Chapter 4 (Article 23)
(5) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (GoogleTranslate-EthicsGuide) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter V (Articles 28 and 30) and Appendix 1 (Section 5)
Summary

Overview

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 EthicsGuide. 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 EthicsGuide, 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) (the Chinese name translates as “State Drug Administration”) with the clinical trial application. (See the Informed Consent topic, Required Elements subtopic for details on what should be included in the form.) The RegEthics provides that the EC may apply for the provincial medical ethics expert committee to provide advice on the ethical review of research involving a relatively high risk or special population. 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. See Specimens topic and Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics for more details.

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 EthicsGuide, 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.

The RegEthics further states that the ICF must contain necessary and complete information expressed in a language that the participant can understand. The investigator must explain each ICF item to the participant, including:

  • Purpose, significance, and expected effects
  • Risks and benefits
  • Whether there are other measures or treatment options that are beneficial to the participant
  • The scope and measures of confidentiality
  • Compensation
  • Voluntary participation and the right to opt out
  • The contact person to report problems

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.

The following cases may be exempted from signing the ICF after examination and approval by the EC:

  • The specimen or data that can identify the participant can be used for research but the participant cannot be found 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

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

CHN-4 states that all clinical trial applications and supporting materials, including the ICF, must be in Chinese. The NMPA-GCP-No57-2020, the RegEthics, and the EthicsGuide require the ICF to be presented in oral or written form in a simple language that the participant is able to understand.

Documentation Copies

Per the NMPA-GCP-No57-2020 and CHN-37, the participant and his/her legal representative(s) or guardian(s), and researchers who perform informed consent should sign and date the ICF. If not signed by the participant, the relationship should be marked. 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.

Additional Resources
(1) (Article) China’s State Food and Drug Administration Discusses Drug Applications: A Q&A with Officers of the Departments of State Food and Drug Administration, China, moderated by Ji Xie (CHN-4) (November 2, 2010)
Pharmaceutical Technology
Relevant Sections: Pages 66-70
(2) (Article) Life Sciences: Product Regulation and Liability in China (CHN-11) (January 7, 2019)
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Clinical Trials Authorization
(3) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 2, 4.4, 4.8, 8.2, and 8.3
(4) (Webpage) Integrated System Catalogue, Human Genetic Resource Management (CHN-56 - Standard Chinese) (Current as of October 30, 2020)
Ministry of Science and Technology
Informed Consent > Required Elements
Last content review/update: October 30, 2020
Requirements
(1) (Legislation) Vaccine Administration Law (VaccineLaw – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: 18
(2) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (GoogleTranslate-MgmtHumanGen) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter II (Article 12)
(3) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 4 (Articles 33-37)
(4) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1 (Article 3) and Chapter 4 (Articles 23-24)
(5) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (GoogleTranslate-EthicsGuide) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 5 (Articles 28 and 30) and Appendix 1 (Sections 4 and 5)
Summary

Overview

As delineated in the NMPA-GCP-No57-2020, the EthicsGuide, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37), prior to beginning a clinical trial, the investigator is required to obtain ethics committee (EC) approval for the written informed consent form (ICF), and any other information being provided to the research participant and/or his/her legal representative(s) or guardian(s). Per the VaccineLaw, in carrying out a vaccine clinical trial, the investigator is required to obtain a written ICF from the participant and/or his/her legal representative(s) or guardian(s).

The NMPA-GCP-No57-2020, the EthicsGuide, the RegEthics, and CHN-37 state that information should be presented in easily understandable language, and may be presented in written and/or oral form. Adequate time should be given to the participant and/or his/her legal representative(s) or guardian(s) to inquire about the details of the study and have all questions answered to his/her satisfaction.

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 impact on health, the protection measures of personal privacy, their participation is voluntary, and they have the right to withdraw unconditionally at any time. The participant must agree to participate in the clinical trial in writing. Information provided to the participant must be comprehensive, complete, true, and accurate, and must not conceal information nor be misleading or deceiving.

No Coercion

As per the NMPA-GCP-No57-2020 and CHN-37, 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 to appear to waive his/her legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

ICF Required Elements

Based on the NMPA-GCP-No57-2020, the EthicsGuide, the RegEthics, and CHN-37, the 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, the 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 participants 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 subject, 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 participants 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 participants before and during the research
  • The foreseeable circumstances and/or reasons under which the subject'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

See the Informed Consent topic, Compensation Disclosure and Vulnerable Populations subtopics for additional information.

Additional Resources
(1) (Article) Legal Protection of the Rights of Clinical Trial Subjects in China (CHN-26) (March 26, 2018)
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.4 and 4.8
Informed Consent > Compensation Disclosure
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 4 (Articles 36-37)
(2) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 4 (Article 24)
(3) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (GoogleTranslate-EthicsGuide) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Appendix 1 (Sections 4 and 5)
Summary

Overview

In accordance with the NMPA-GCP-No57-2020, the EthicsGuide, the RegEthics, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37), the informed consent form (ICF) should contain a statement describing the compensation or medical treatment a participant can receive for participating in a clinical trial.

Compensation for Participation in Research

As stated in the EthicsGuide, the RegEthics, and the NMPA-GCP-No57-2020, the ICF should contain a statement with a description of the nature, form, and extent of compensation for study participation. The ICF should also inform the participants if they will need to pay for any expenses in order to participate in the trial.

Per CHN-37, the ICF should contain a statement with a description of the anticipated prorated payment to the participant(s) that is reasonably expected for participation in the trial. Any compensation or incentive to participants must not be so excessive that it may unfairly influence participants, or cause them to overlook important facts and risks.

Compensation for Injury

As per the NMPA-GCP-No57-2020, the EthicsGuide, the RegEthics, and CHN-37, the ICF should include a statement advising the participant that compensation and medical treatment is available in the event of any trial-related injury.

Additional Resources
(1) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 3.1 and 4.8
Informed Consent > Participant Rights
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Articles 18 and 19) and Chapter 4 (Articles 33-39)
(2) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1 (Article 3) and Chapter 4 (Articles 23-24)
(3) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (GoogleTranslate-EthicsGuide) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Appendix 1 (Section 4)
Summary

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 EthicsGuide, 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 Informed Consent topic, and the subtopics of Required Elements; Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired for additional information regarding requirements for participant rights.)

The Right to Participate, Abstain, or Withdraw

As set forth in the NMPA-GCP-No57-2020, the EthicsGuide, 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 EthicsGuide, 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 Informed Consent topic, Required Elements subtopic for more detailed information regarding participant rights.)

The Right to Privacy and Confidentiality

As per the EthicsGuide, 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 EthicsGuide, 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 Informed Consent topic, Required Elements subtopic 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.

Additional Resources
(1) (Article) Legal Protection of the Rights of Clinical Trial Subjects in China (CHN-26) (March 26, 2018)
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
(2) (International Guidance) Declaration of Helsinki (CHN-84) (October 19, 2013)
World Medical Association
(3) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 3.1 and 4.8
Informed Consent > Special Circumstances/Emergencies
Last content review/update: October 30, 2020
Requirements
(1) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Article 12) and Chapter 4 (Articles 23-24)
Summary

Overview

The NMPA-GCP-No57-2020 and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (CHN-37) make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by special circumstances. Special circumstances can be medical emergencies, or when a participant is mentally incapacitated.

Medical Emergencies

As per the NMPA-GCP-No57-2020 and 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 ethics committee (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.

Additional Resources
(1) (Article) Legal Protection of the Rights of Clinical Trial Subjects in China (CHN-26) (March 26, 2018)
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.8
Informed Consent > Vulnerable Populations
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Article 18)
(2) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1, (Article 3), Chapter 2 (Article 11), Chapter 3 (Article 12), and Chapter 4 (Article 23)
(3) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (GoogleTranslate-EthicsGuide) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Appendix 1 (Section 8) and Glossary
Summary

Overview

As per the EthicsGuide, 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 EthicsGuide 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. 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.

As per the EthicsGuide, trials involving vulnerable persons must meet the following requirements:

  • The trial can only be performed well if the vulnerable persons act as research participants
  • The trial targets specific diseases or health problems of the vulnerable population
  • When the trial cannot directly provide the possibility of benefiting vulnerable persons, the risk of the trial should not exceed a minimal risk, unless the ethics committee (EC) agrees to slightly increase the extent of the risk
  • When a participant cannot provide complete informed consent, his/her legal representative(s) or guardian(s) must provide consent

For additional information, see the Informed Consent topic and the subtopics of Children/Minors and Mentally Impaired.

Additional Resources
(1) (Article) Legal Protection of the Rights of Clinical Trial Subjects in China (CHN-26) (March 26, 2018)
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
(2) (International Guidance) Declaration of Helsinki (CHN-84) (October 19, 2013)
World Medical Association
(3) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.61, 3.1, and 4.8
Informed Consent > Children/Minors
Last content review/update: October 30, 2020
Requirements
(1) (Guidance) Guidelines for General Consideration of the Publication of Drug Clinical Trials (No. 11 of 2017) (NMPA-No11-2017 – Standard Chinese) (January 18, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: (B) (3) Special Consideration, Special Population
(2) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Article 11) and Chapter 4 (Article 23)
Summary

Overview

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.

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.

Additional Resources
(1) (Article) Legal Protection of the Rights of Clinical Trial Subjects in China (CHN-26) (March 26, 2018)
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.8
Informed Consent > Pregnant Women, Fetuses & Neonates
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Article 18)
(2) (Guidance) Guidelines for General Consideration of the Publication of Drug Clinical Trials (No. 11 of 2017) (NMPA-No11-2017 – Standard Chinese) (January 18, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: (B) (3) Special Consideration, Special Population
(3) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 4 (Article 24)
Summary

Overview

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 Informed Consent topic, Required Elements subtopic. 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.

Additional Resources
(1) (Article) Legal Protection of the Rights of Clinical Trial Subjects in China (CHN-26) (March 26, 2018)
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.8
Informed Consent > Prisoners
Last content review/update: October 30, 2020
Requirements
(1) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Article 11)
Summary

Overview

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 Informed Consent topic, Required Elements subtopic.

Additional Resources
(1) (Article) Legal Protection of the Rights of Clinical Trial Subjects in China (CHN-26) (March 26, 2018)
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.61
Informed Consent > Mentally Impaired
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (GoogleTranslate-RegEthics) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Article 18)
(2) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 4 (Article 23)
Summary

Overview

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 (EC) 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 (ICF) must be signed and dated by the participant’s legal representative(s) or guardian(s).

Additional Resources
(1) (Article) Legal Protection of the Rights of Clinical Trial Subjects in China (CHN-26) (March 26, 2018)
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.61 and 3.1
Investigational Products > Definition of Investigational Product
Last content review/update: October 30, 2020
Requirements
(1) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Article 11)
Summary

Overview

As delineated in the NMPA-GCP-No57-2020, investigational products 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 it 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.

Additional Resources
(1) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.33
Investigational Products > Manufacturing & Import
Last content review/update: October 30, 2020
Requirements
(1) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter I (Articles 5-7), Chapter III (Article 30-33), Chapter IV (Articles 41-47A), and Chapter X (Articles 98-100 and 103)
(2) (Regulation) Decision Concerning the Adjustment of Imported Drug Registration and Administration (No. 35 of 2017) (NMPA-No35-2017 – Standard Chinese) (October 10, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
(3) (Regulation) Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230-2015 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(4) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (GoogleTranslate-DRR) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter I (Articles 3 and 9) and Chapter III (Article 47)
(5) (Guidance) Measures for the Supervision and Administration of Drug Production (No. 28 of 2020) (NMPA-No28-2020 – Standard Chinese) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter I, Chapter II (Articles 6-7), Chapter III (Article 47), and Chapter IV (Article 52)
(6) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1 (Article 8) and Chapter 5 (Articles 44-45)
(7) (Circular) Technical Guiding Principles for Accepting Data from Overseas Clinical Trials of Drugs (No. 52 of 2018) (NMPA-No52-2018 – Standard Chinese) (July 6, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: I-V
(8) (Notice) Use of the New Version of the Drug Production License and Other Licenses (NMPA-No72-2019 – Standard Chinese) (July 25, 2019)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Attachment 2
Summary

Overview

According to the DAL and the NMPA-No28-2020, the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) is responsible for authorizing the manufacture of investigational products (IPs) in China. Per the DAL and the DRR, and as explained in CHN-18, NMPA established a drug marketing authorization holders (MAHs) system across China. All entities or drug research institutions holding drug marketing authorizations are regarded as MAHs, who 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 DRR and the NMPA-No28-2020 stipulate that foreign applicants should designate an enterprise legal person in China to handle relevant drug registration matters.

Per the DAL and the NMPA-No28-2020, the holder of a drug marketing license may produce the drug or entrust a pharmaceutical production enterprise to produce it. For the former, the holder of the drug marketing license must obtain a drug production license, which can be found at NMPA-No72-2019. If an entrusted production enterprise is used, the drug marketing license 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 NMPA.

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

The NMPA-GCP-No57-2020 specifies that the manufacture of clinical trial drugs must meet the relevant requirements for quality management as laid out in the NMPA-No28-2020. 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.

The NMPA is also responsible for authorizing the import of IPs. The DAL provides that prior to IP import or manufacture, a 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.

Pursuant to the NMPA-No35-2017, 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 for the NMPA-No52-2018 requirements for clinical trial and drug registration applications of imported new drugs or therapeutic biological products using trial data generated entirely overseas, they 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 can 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 Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics.

Per NMPA-No230-2015 and CHN-18, NMPA will prioritize the review and approval of foreign innovative drugs manufactured in China and drugs manufactured at a U.S. or EU 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 investigational products developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see CHN-55.

Additional Resources
(1) (Article) China’s National Medical Products Administration Finalizes Two Implementing Rules of the Drug Administration Law (CHN-18) (April 2, 2020)
Li, Lei and Yang, Chen; Sidley Austin LLP
(2) (Article) Life Sciences: Product Regulation and Liability in China (CHN-11) (January 7, 2019)
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Trends and developments and Supply
(3) (Document) Nagoya Protocol on Access and Benefit-sharing (CHN-30) (2011)
Convention on Biological Diversity, United Nations
(4) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 2.12, 5.13, and 6
(5) (Webpage) Country Profile: China (CHN-55) (Current as of October 30, 2020)
Access and Benefit-sharing Clearing-house, Convention on Biological Diversity, United Nations
Investigational Products > IMP/IND Quality Requirements
Last content review/update: October 30, 2020
Requirements
(1) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter II (Articles 24-25) and Chapter IV (Article 43-44)
(2) (Guidance) Amendments to Good Manufacturing Practice for Drugs (No. 28) (NMPA-GMPsAmnd – Standard Chinese) (June 30, 2016)
National Medical Products Administration, State Administration for Market Regulation, State Council
(3) (Guidance) Good Manufacturing Practices for Drugs (No. 3) (NMPA-GMPs – Standard Chinese) (Effective May 18, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(4) (Guidance) Measures for the Supervision and Administration of Drug Production (No. 28 of 2020) (NMPA-No28-2020 – Standard Chinese) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter IV (Articles 49-52)
(5) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 4 (Article 21), Chapter 5 (Article 37), and Chapter 7
Summary

Overview

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.

Per the DAL, the IP manufacturer must 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 standards in the NMPA-GMPs and the NMPA-GMPsAmnd. The legal representative and principal responsible person of the drug production enterprise are fully responsible for the drug production activities of the enterprise.

IB Content Requirements

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 content guidelines.

The NMPA-GCP-No57-2020 states that the sponsor must also provide the clinical trial drugs to investigators and clinical trial institutions. The sponsor must not provide the drugs 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 Chinese name translates as “State Drug Administration”). The sponsor must provide the investigator and the clinical trial institution with a written description of the drug, including directions for its use and storage. Further, the sponsor must formulate procedures for supply and management, including reception, storage, distribution, use, and recovery. The sponsor must ensure that the drugs 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. (See Investigational Products topic, Product Management subtopic for additional information on IP supply, storage, and handling requirements).

Per the NMPA-GCP-No57-2020, 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.

Continuous Compliance

As 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-GMPs and the NMPA-GMPsAmnd. The legal entity or person is fully responsible for the manufacturing activities of the enterprise throughout the whole process. The NMPA-No28-2020 further clarifies the link between on-site inspection of drug registration and the pre-market 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., NMPA’s Center for Drug Evaluation (CDE), province, autonomous region, or municipality). See the NMPA-No28-2020 for detailed inspection requirements. In addition, the sponsor’s internal inspection and audit requirements are provided in the NMPA-GCP-No57-2020, which includes providing an inspection/audit report to regulatory authorities when needed.

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.

Additional Resources
(1) (Article) Life Sciences: Product Regulation and Liability in China (CHN-11) (January 7, 2019)
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Supply
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 7
Investigational Products > Labeling & Packaging
Last content review/update: October 30, 2020
Requirements
(1) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter IV (Articles 46 and 48-49)
(2) (Guidance) Provisions for Drug Insert Sheets and Labels (SFDA Decree No.24) (ProvLabel – English, unofficial translation) (Standard Chinese) (Effective June 1, 2006)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapters I and III
(3) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 5 (Article 44)
Summary

Overview

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) (the Chinese name translates as “State Drug Administration”)’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.

The ProvLabel and the DAL state that the following labeling information 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 drugs, psychotropic drugs, medical toxic drugs, radioactive drugs, external drugs, 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. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

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

Additional Resources
(1) (Article) Life Sciences: Product Regulation and Liability in China (CHN-11) (January 7, 2019)
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Labelling
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 5.13
Investigational Products > Product Management
Last content review/update: October 30, 2020
Requirements
(1) (Legislation) Drug Administration Law of the People's Republic of China (DAL – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter III (Articles 33 and 36)
(2) (Guidance) Amendments to Good Manufacturing Practice for Drugs (No. 28) (NMPA-GMPsAmnd – Standard Chinese) (June 30, 2016)
National Medical Products Administration, State Administration for Market Regulation, State Council
(3) (Guidance) Good Manufacturing Practices for Drugs (No. 3) (NMPA-GMPs – Standard Chinese) (Effective May 18, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(4) (Guidance) Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (GoogleTranslate-NMPA-GCP-No57-2020) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 5 (Article 44)
Summary

Overview

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. The IP pre-clinical study documents supplied by the investigator must also include formulation, manufacturing process, and quality inspection results of the IP. The information should conform to the requirements of the respective corresponding phases of the clinical trial.

Investigational Product Supply, Storage, and Handling Requirements

The NMPA-GCP-No57-2020 states that the sponsor must also 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 Chinese name translates as “State Drug Administration”). The sponsor must provide the investigator and the clinical trial institution with a written description of the IP, including directions for the 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. In addition, 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 retention period of the retained samples must be kept within the storage period of the IP until the end of the clinical trial or the time limit required by relevant laws and regulations. If the two (2) are inconsistent, the longer period must be used.

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

  • IP product quality
  • IP manufactured according to good manufacturing practices (GMPs) as per the NMPA-GMPs and the NMPA-GMPsAmnd
  • 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 management and filing systems for the IPs
  • Acceptable storage temperatures, conditions, and times for the IP
  • Timely delivery of the IP(s)

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 marketing license—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

The NMPA-GCP-No57-2020 requires the sponsor to keep clinical trial records for at least five (5) years after the IP is approved for marketing.

Additional Resources
(1) (Article) Life Sciences: Product Regulation and Liability in China (CHN-11) (January 7, 2019)
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Are any legislative changes proposed or expected in the near future?
(2) (International Guidance) Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2) (CHN-37) (Step 5 Version) (November 16, 2016)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 5.5, 5.12, 5.13, 5.14, and 7
Specimens > Definition of Specimen
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (GoogleTranslate-MgmtHumanGen) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter One (Article 2)
Summary

Overview

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 (HGR materials) and human genetic resource information (HGR information). HGR materials refers 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.

Additional Resources
(1) (Article) Using Biospecimens Collected Abroad in Future Research: Key Considerations (CHN-27) (April 19, 2017)
Bavasi, H., Thornton, L., Peloquin, D., and Barnes, M.; Medical Research Law & Policy Report, Bloomberg Law
(2) (Webpage) Administrative License (CHN-76 - Standard Chinese) (Current as of October 30, 2020)
Ministry of Science and Technology
Specimens > Specimen Import & Export
Last content review/update: February 17, 2021
Requirements
(1) (Legislation) Biosecurity Law of the People's Republic of China (Bioscrty-Law – Standard Chinese) (Effective April 15, 2021)
National People’s Congress
Relevant Sections: Chapter VI (Articles 53-59)
(2) (Legislation) Rules for the Implementation of Frontier Health and Quarantine Law of the People’s Republic of China (QuarantineLaw – Standard Chinese) (March 6, 1989)
National People’s Congress
Relevant Sections: Article 11
(3) (Regulation) AQSIQ Decree No. 160 on Inbound/Outbound Special Articles Quarantine Regulations (AQSIQ-No160 - Standard Chinese) (Effective March 1, 2015)
General Administration of Quality Supervision, Inspection & Quarantine
Relevant Sections: Chapters 1 and 2
(4) (Regulation) China Entry-Exit Inspection and Quarantine Process Management Rules (QuarantineRules – English, unofficial translation) (Effective November 1, 2017)
General Administration of Quality Supervision, Inspection & Quarantine
(5) (Regulation) Human Genetic Resources – Approval for Export, Administrative Licensing Service Guide (HGR-ExportLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1-19 and all attachments
(6) (Regulation) Human Genetic Resources – International Cooperative Clinical Trials, Record and Filing Management Service Guide (HGR-IntlRecordMgtServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1-3
(7) (Regulation) Human Genetic Resources – International Cooperative Research Approval, Administrative Licensing Service Guide (HGR-IntlApprovalLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
(8) (Regulation) Service Platform Human Genetic Resource Management (HGR-Procedures – Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Relevant Sections: 4
(9) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (GoogleTranslate-MgmtHumanGen) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter I (Articles 1-4 and 7-9), Chapter II (Article 11), and Chapter III (Articles 21-22)
Summary

Overview

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 China’s HGR for use abroad. However, the regulation permits foreign entities with limited use of China’s 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 China 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 at CHN-76, which will generate a record number. See the HGR-IntlRecordMgtServiceGuide, the HGR-IntlApprovalLicenseServiceGuide, and the HGR-ExportLicenseServiceGuide for details on the HGR processes and policies.

Per the QuarantineLaw, the AQSIQ-No160, and CHN-54, imports of human tissue, biological, 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, and 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:

  • The completed form of the Application for Quarantine of Inbound/Outbound Special Articles (See CHN-54 for form)
  • 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, 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.

As delineated in MgmtHumanGen and the HGR-ExportLicenseServiceGuide, the export of China HGR materials in approved international collaborations are subject to prior approval by MOST. 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-ExportLicenseServiceGuide, 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-ExportLicenseServiceGuide 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
  • China HGR international cooperative research approval decision
  • China HGR materials exit approval decision

Per the HGR-Procedures and the HGR-ExportLicenseServiceGuide, the applicant submits the electronic version of the materials through the online platform at CHN-76. To submit paper applications, 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 correct 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.

Additional Resources
(1) (Article) China’s State Council Publishes New Regulations on the Management of Human Genetic Resources (CHN-16) (June 14, 2019)
Wang, Katherine; Ropes and Gray
(2) (Article) Key Points of Concern for the Pharmaceutical Industry under the New Regulations of Human Genetic Resources: Interpretation of the Regulations on the Management of Human Genetic Resources (CHN-10) (June 10, 2019)
Global Law Office, Lexology
(3) (Webpage) Administrative License (CHN-76 - Standard Chinese) (Current as of October 30, 2020)
Ministry of Science and Technology
Relevant Sections: Human Genetic Resource Management
(4) (Webpage) General Administration of Quality Supervision, Inspection & Quarantine – About Us (CHN-46) (Current as of October 30, 2020)
General Administration of Quality Supervision, Inspection & Quarantine
(5) (Webpage) Integrated System Catalogue, Human Genetic Resource Management (CHN-56 - Standard Chinese) (Current as of October 30, 2020)
Ministry of Science and Technology
Relevant Sections: China's human genetic resources materials exit approval
(6) (Webpage) Sanitary Quarantine Approval for Special Items (CHN-54) (Current as of April 16, 2020)
General Administration of Customs
Specimens > Consent for Specimen
Last content review/update: October 30, 2020
Requirements
(1) (Regulation) Human Genetic Resources – Approval for Export, Administrative Licensing Service Guide (HGR-ExportLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 8
(2) (Regulation) Human Genetic Resources – Collection and Approval of HGR in China, Administrative Licensing Service Guide (HGR-Collection – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 8
(3) (Regulation) Human Genetic Resources – International Cooperative Clinical Trials, Record and Filing Management Service Guide (HGR-IntlRecordMgtServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 8
(4) (Regulation) Human Genetic Resources – International Cooperative Research Approval, Administrative Licensing Service Guide (HGR-IntlApprovalLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 8
(5) (Regulation) Service Platform Human Genetic Resource Management (HGR-Procedures – Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Relevant Sections: 1, 3, and 4
(6) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (GoogleTranslate-MgmtHumanGen) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter IV (Article 31)
Summary

Overview

The MgmtHumanGen indicates that the Ministry of Science and Technology (MOST) is responsible for China's efforts on the management of human genetic resources (HGR). As delineated in the MgmtHumanGen, HGR-Procedures, HGR-IntlApprovalLicenseServiceGuide, HGR-Collection, HGR-ExportLicenseServiceGuide, and HGR-IntlRecordMgtServiceGuide, 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.

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, and that 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, and accurate, and must not conceal information nor be misleading or deceiving.

Additional Resources
(1) (Article) Using Biospecimens Collected Abroad in Future Research: Key Considerations (CHN-27) (April 19, 2017)
Bavasi, H., Thornton, L., Peloquin, D., and Barnes, M.; Medical Research Law & Policy Report, Bloomberg Law
(2) (Webpage) Integrated System Catalogue, Human Genetic Resource Management (CHN-56 - Standard Chinese) (Current as of October 30, 2020)
Ministry of Science and Technology
Sections Country Announcement
Country Announcement
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COVID-19 Guidance

On August 14, 2020, China's National Medical Products Administration (NMPA) issued five guiding principles including the "Technical Guidelines for the Research and Development of Vaccines for Prevention of New Coronavirus (Trial)" (No. 21 of 2020)

Google Translate Links: The Google Translate links provided in the profile are for information purposes only and may not always work as expected. ClinRegs does not control the quality or accuracy of translated content.

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