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: July 06, 2020
Requirements
(1) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (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 104-07)
(2) (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
(3) (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 5-7) and Chapter II
(4) (Legislation) Vaccine Administration Law (VaccineLaw – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: Chapter I (Article 8) and Chapter II (Article 16), Chapter II (Articles 14-16)
(5) (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)
(6) (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)
National Medical Products Administration, State Administration for Market Regulation, State Council
(7) (Regulation) Announcement on Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
(8) (Regulation) Announcement on Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(9) (Notice) Study, Promotion and Implementation of the Drug Administration Law (No. 45 of 2019) (NMPA-No45) (September 25, 2019)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 4
(10) (Legislation) State Council Institutional Reform Plan (SC-IRP – Standard Chinese) (March 17, 2018)
National People’s Congress
(11) (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
(12) (Guidance) Principles and Procedures for Drug Review and Evaluation (CDEProcs Standard Chinese) (April 13, 2011)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter I (Article 3) and Chapter II (Sections 1 and 2)
(13) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (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)
(14) (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 and 2
(15) (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
(16) (Regulation) Human Genetic Resources – Materials Exit Approval (HGR-ExitLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 9
Summary

Overview

National Medical Products Administration

As per the DRR, the NMPA-Org, the DAL, the RegImplemDAL, the SC-Opinions-No44, the NMPA-No50, the NMPA-No230, and Additional Resources (A) and (B), 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 re-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 RegImplemDAL, the SC-Opinions-No44, the NMPA-No50, and the NMPA-No230. 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 Additional Resource (C), 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 Additional Resource (D), 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 Additional Resource (E), 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, the CDEProcs, and Additional Resource (F), 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 MgmtHumanGen delineates that the Ministry of Science and Technology (MOST) is responsible for China's management of human genetic resources (HGR). 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 Additional Resource (G). 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.

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. Per Additional Resource (H), MOST will define at a later date these terms: important families, specific areas, and exceeding specific amounts
  • 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 Additional Resource (K), 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 Additional Resource (L). ClinRegs lists referenced ICH guidelines as Additional Resources throughout the profile.

Contact Information

The following is the NMPA’s contact information:

National Medical Products Administration
No. 1 North Luyuan, Exhibition Road
Xicheng District
Beijing 100037
P.R. China
Phone: 68313344
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

Per Additional Resources (I) and (J), clinical trial applications and correspondence should be sent to NMPA’s Administrative Acceptance Service Center:

NMPA Administrative Acceptance Service Center
Beijing West 1st and 3rd Floors
Dacheng Square, No. 28
Xuanwumen West Street, City 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-IntlRecordMgtServiceGuide, HGR-IntlApprovalLicenseServiceGuide, and the HGR-ExitLicenseServiceGuide, the following is notification and application submission contact information for MOST:

Ministry of Science and Technology
1st Floor, Building 4
No. 16 West Fourth Ring Road
Haidian District
Beijing 100039
P.R. China
Phone: 010-88225151

Additional Resources
National Medical Products Administration, State Administration for Market Regulation, State Council
Miseta, Ed; Clinical Leader
Wang, Katherine; Ropes & Grey
(D) (Website) Main Duties of National Medical Products Administration (Standard Chinese) (Current as of April 16, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(E) (Website) Internal Organization (Standard Chinese) (Current as of April 16, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Drug Registration Management Department and Drug Administration Department
(F) (Website) National Medical Productions Administration (Standard Chinese) (Current as of April 16, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Address, NMPA Organizations, and Affiliated Institutions
(G) (Website) Administrative License (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Relevant Sections: Human Genetic Resource Management
Cyranoski, David; Nature
(I) (Website) Administrative Acceptance Service Hall: Things to Know (Standard Chinese) (Current as of April 16, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(J) (Website) Ministry of Science and Technology Government Service Platform (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
(K) (Website) Members and Observers (Current as of April 16, 2020)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(L) (Website) ICH Guidelines (Current as of April 16, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
Regulatory Authority > Scope of Assessment
Last content review/update: July 06, 2020
Requirements
(1) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (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)
(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 19)
(3) (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, 30, and 36)
(4) (Regulation) Announcement on Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50 – 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) 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)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1-8, 11-12, and 14
(6) (Regulation) Announcement on Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(7) (Notice) Publication of the Work Plan for the Reform of the Classification and Registration of Chemical Drugs (No. 51 of 2016) (SC-Notice-No51 – Standard Chinese) (March 4, 2016)
National Medical Products Administration, State Administration for Market Regulation, State Council
(8) (Legislation) Vaccine Administration Law (VaccineLaw – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: 1-2 and 16-18
(9) (Regulation) Notice on Propaganda and Implementation of the Vaccine Administration Law (No. 23 of 2019) (NMPA-No32 – Standard Chinese) (July 25, 2019)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 4
(10) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter I (Articles 1-4 and 7-9) and Chapter II (Article 11 and 21-22), Chapter iii (Article 22)
(11) (Regulation) Announcement on the Release of Administrative Measures for the Communication of Drug R & D and Technical Review (No. 74 of 2018) (NMPA-No74 – Standard Chinese) (September 30, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1 and 2
(12) (Guidance) Principles and Procedures for Drug Review and Evaluation (CDEProcs Standard Chinese) (April 13, 2011)
National Medical Products Administration, State Administration for Market Regulation, State Council
(13) (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
(14) (Regulation) Opinions on Encouraging Drug Innovation to Implement Priority Review and Approval (No. 126 of 2017) (NMPA-No126 – Standard Chinese) (December 21, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter I (Article 3) and Chapter II (Sections 1 and 2)
(15) (Regulation) Announcement on Matters Relating to the Optimization of Drug Registration Review and Approval (No. 23 of 2018) (NMPA-No23 – Standard Chinese) (May 17, 2018)
National Medical Products Administration, State Administration for Market Regulation, and the National Health Commission, State Council
(16) (Regulation) Decision Concerning the Adjustment of Imported Drug Registration and Administration (No. 35 of 2017) (SC-Decision-No35 – Standard Chinese) (October 10, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
(17) (Circular) Technical Guiding Principles for Accepting Data from Overseas Clinical Trials of Drugs (No. 52 of 2018) (NMPA-No52 – Standard Chinese) (July 6, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
(18) (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 and 2
(19) (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: 7 and 9
(20) (Regulation) Human Genetic Resources – Materials Exit Approval (HGR-ExitLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 9
Summary

Overview

In accordance with the DRR, the DAL, the RegImplemDAL, the NMPA-No50, the SC-Opinions-No44, and the NMPA-No230, 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.

As delineated in the DRR, the SC-Opinions-No44, and the SC-Notice-No51, the drug classification in which an applicant chooses to register determines the clinical trial application review and approval process. As explained in Additional Resource (A), NMPA reduced the number of drug registration categories, in effect revising the specific classifications in the SC-Notice-No51.

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, and generic drugs. Per Additional Resource (A), the DRR does not define the terms “innovative drug,” “new drug,” or “generic drug”. Other regulations and policies have contained definitions, but it is not clear if China is maintaining these definitions with implementation of the DRR.

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). The regulation indicates that detailed classification and application requirements will be organized and formulated by the NMPA according to the product characteristics, innovation level, and review management needs of registered medicines, and will be announced to the public. According to Additional Resource (A), the meaning of the third category of biologics is unclear and not defined in the DRR.

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 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 explains that the new legislation VaccineLaw, which took effect December 1, 2019, 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).

According to the DRR, foreign applicants must designate legal persons within China to handle relevant drug registration matters.

With regard to reviewing and approving international cooperative research and export license applications for human genetic resources (HGR), in accordance with 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 and the NMPA-No74, 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, 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 CDEProcs, and the NMPA-No50, 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, 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. (See the Clinical Trial Lifecycle topic, Submission Process subtopic for detailed submission requirements.) In addition to the 60-day implied approval, other reforms include the following:

  • The NMPA-No230 establishes a one-time approval procedure for new drug clinical trial applications (formerly, new approvals were needed for each clinical trial phase). Under this scheme, the NMPA will evaluate the scientific protocol and safety issues. Applicants should submit the research results and next-phase clinical trial protocol after completing Phase I and II studies. If there are no safety issues, the applicants can move into the next phase of the trial after communicating with the CDE.)
  • Under the NMPA-No230, for generic drugs, the bioequivalent study will only need to be filed with the NMPA (formerly it was a review and approval procedure). 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.
  • The DAL and the DRR support regulatory pathways for expedited approvals. See Clinical Trial Lifecycle, Submission Process subtopic for additional details.
  • Per the NMPA-No230, expedited review is potentially available for drugs that fit within the new drug classification and those 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. Further, per the NMPA-No126, priority review may also be possible for drugs that are in simultaneous development in the European Union and the United States. NMPA-No23 states that for drugs 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 SC-Decision-No35, the NMPA-No52, and interpretations in Additional Resources (E) and (F), adjust requirements for clinical trial and drug registration applications using trial data that is generated entirely overseas, as well as data that is 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 requirements for clinical trial and drug registration applications of imported new drugs or therapeutic biological products using trial data that is 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. Per the NMPA-No52, overseas clinical trial data can be acceptable for direct China registration as long as the application meets all other Chinese drug regulatory requirements. See Clinical Trial Lifecycle topic, Submission Content subtopic and Additional Resource (G) for additional guidance on these decisions.

Additional Resources (H) and (I) also provide useful information on the NMPA’s overall clinical trial application review and approval process. NMPA developed an infographic to depict the steps in the drug clinical trial application process (Additional Resource (J)).

The MgmtHumanGen prohibits 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. 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 are 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 Additional Resource (K), which will generate a record number. See the HGR-IntlRecordMgtServiceGuide, the HGR-IntlApprovalLicenseServiceGuide, and the HGR-ExitLicenseServiceGuide 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 (Additional Resource (K)).

Per Additional Resource (M), China issued draft regulations restricting the use of gene editing during clinical studies. (ClinRegs will monitor this development and update the profile, as needed.) For more information on HGR, see the Specimens topic.

Additional Resources
Covington
Relevant Sections: Drug Registration Categories
(B) (Article) China and the Evolving Regulatory Landscape (September 4, 2019)
Baruah, Megha; European Pharmaceutical Review
Relevant Sections: Table 1
Yang, Chen and Su, Ling; Sidley, Global Life Sciences
Wang, Katherine; Ropes & Gray
National Medical Products Administration, State Administration for Market Regulation, State Council
National Medical Products Administration, State Administration for Market Regulation, State Council
Liao, Todd; Morgan Lewis
(H) (Article) China (April 2020)
Kingham, Richard; The Life Sciences Law Review, Edition 8
Relevant Sections: Introduction and Regulatory Regime
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Clinical Trials
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(K) (Website) Ministry of Science and Technology Government Service Platform (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
(L) (Website) Administrative License (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Relevant Sections: Human Genetic Resource Management
Regulatory Authority > Regulatory Fees
Last content review/update: July 06, 2020
Requirements
(1) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter VI (Article 85)
(2) (Regulation) Issuing the Registration Fees for Drugs and Medical Device Products (No. 53 of 2015) (NMPA-No53 – 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)
Summary

Overview

In accordance with the DRR, the applicant is required to pay a fee per applicable regulations. As per the NMPA-No53, and as described in Additional Resources (A) and (B), 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

For further guidance on fees associated with submitting supplementary applications and registering renewals for imported drugs and more, please refer to the NMPA-No53 and Additional Resource (A).

Additional Resources
Wong, A., Michishita, R., and Pountney, D.; Bird & Bird
(C) (Website) Smoother Regulatory Process for China (September 8, 2016)
Zhang, Kai; Applied Clinical Trials
Relevant Sections: Shortening the application timeline
Ethics Committee > Ethics Committee
Last content review/update: July 06, 2020
Requirements
(1) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (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)
(2) (Notice) Administration of Drug Clinical Trial Institutions (No. 101 of 2019) (NMPA-NHC-No101 – 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
(3) (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
(4) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (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)
(5) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Articles 9 and 11)
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 Additional Resource (A), 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 Additional Resources (B) and (C), 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 Additional Resource (D).

Per the NMPA-NHC-No101, 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, and Additional Resources (E) and (F).

EC Composition

The EthicsGuide and the NMPA-GCPs state 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-GCPs, each institution must have written SOPs, including a process to be followed for conducting reviews. 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. Written records of all meetings and resolutions should be preserved for five (5) years following the completion of a clinical trial.

Additional Resources
National Health Commission
Jia, Hepeng; Nature
Xinqing, Z., Wenxia, Z., Yandong, Z.; TRUST Equitable Research Partnerships
Relevant Sections: China’s Ethics Review System and Its Structure
Wang, Katherine; Ropes & Gray
Brennan, Zachary; William Reed Business Media
Ethics Committee > Scope of Review
Last content review/update: July 06, 2020
Requirements
(1) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (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
(2) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1 (Articles 1 and 4), Chapter 3 (Articles 8, 9, 12, and 14), Chapter 6 (Articles 32, 35, and 43), and Appendix 1
(3) (Guidance) Guidelines for General Consideration of the Publication of Drug Clinical Trials (No. 11 of 2017) (NMPA-No11 – Standard Chinese) (January 18, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
(4) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (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) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter III (Articles 25-26)
(6) (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)
(7) (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)
(8) (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
Summary

Overview

According to the EthicsGuide, the NMPA-GCPs, and the NMPA-No11, 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. 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-GCPs, the DRR, the DAL, the RegImplemDAL, 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-GCPs and the RegEthics also state that the EC must review and approve any protocol amendments prior to those changes being implemented.

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 shall 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. Additional Resource (B) provides more information on the EC review.

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

Additional Resources
(A) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
Xinqing, Z., Wenxia, Z., Yandong, Z.; TRUST Equitable Research Partnerships
Relevant Sections: China’s Ethics Review System: Current Status, Problems, and Responses
Ethics Committee > Ethics Committee Fees
Last content review/update: April 16, 2020
Requirements
No applicable regulatory requirements
Summary

No relevant provisions.

Additional Resources
No additional resources
Ethics Committee > Authorizing Body
Last content review/update: April 16, 2020
Requirements
(1) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 1 (Articles 5 and 6), Chapter 2 (Article 7), and Chapter V
(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) (Notice) Administration of Drug Clinical Trial Institutions (No. 101 of 2019) (NMPA-NHC-No101 – 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. This reform eases institutional burdens by removing the pre-approval accreditation requirements. 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 and fulfill the requirements pursuant to the NMPA-NHC-No101. Additional Resource (A) provides a status update on implementing the filing system.

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 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
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1 (background)
Clinical Trial Lifecycle > Submission Process
Last content review/update: July 06, 2020
Requirements
(1) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (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 Chapter IV (59-75), and Chapter VII (Article 96)
(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) 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)
(5) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Articles 10 and 11), Chapter 6 (Article 36), and Appendix 2 (1)
(6) (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)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1-8, 11-12, and 14
(7) (Regulation) Announcement on Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50 – 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)
(8) (Regulation) Announcement on the Release of Administrative Measures for the Communication of Drug R & D and Technical Review (No. 74 of 2018) (NMPA-No74 – Standard Chinese) (September 30, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 and Appendix 1
(9) (Regulation) Announcement on Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(10) (Notice) Publication of the Work Plan for the Reform of the Classification and Registration of Chemical Drugs (No. 51 of 2016) (SC-Notice-No51 – Standard Chinese) (March 4, 2016)
National Medical Products Administration, State Administration for Market Regulation, State Council
(11) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (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)
(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) Human Genetic Resources – Collection Service Guidelines for Administrative Licensing Matters (HGR-Collection – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1-16 and all attachments
(14) (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 and all attachments
(15) (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: 1-16 and all attachments
(16) (Regulation) Human Genetic Resources – Materials Exit Approval (HGR-ExitLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1-18 and all attachments
(17) (Notice) Application of the Second Level Guiding Principles of the International Human Drug Registration Technical Coordination Committee (No. 10 of 2018) (NMPA-No10 – Standard Chinese) (January 25, 2018)
State Council
Relevant Sections: 1
(18) (Circular) Technical Guidelines for the Application of Phase I Clinical Trials of New Drugs (No. 16 of 2018) (G-Phase1-CTApp – Standard Chinese) (January 11, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annex
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, the RegImplemDAL and other laws and regulations. NMPA’s Center for Drug Evaluation (CDE) is responsible for the evaluation of clinical trial applications. The NMPA-GCPs, the DRR, the DAL, the RegImplemDAL, 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, 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 Center for Drug Evaluation (CDE) in accordance with the requirements of the NMPA-No74, which includes requirements for different categories of meetings involving applications for new drugs. The NMPA-No74 includes the application form (Appendix 1), which should be submitted to the CDE via its online user platform at Additional Resource (A). 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 the CDE using the Applicant’s Window (Additional Resource (A)) or the Administrative Acceptance Service Hall (Additional Resource (B)). Drug clinical trials are divided into phase I, phase II, phase III, and phase IV clinical trials, and bioequivalence trials. As delineated in the DRR, the SC-Notice-No51, 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 (Additional Resource (A)), carry out relevant research work in accordance with the filing plan.

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, and the SC-Notice-No51, 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. (See Clinical Trial Lifecycle, Timeline of Review subtopic for additional details on expedited review.)

The MgmtHumanGen prohibits 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. 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 Additional Resource (L) 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 service guides—HGR-Collection, HGR-IntlRecordMgtServiceGuide, the HGR-IntlApprovalLicenseServiceGuide, and the HGR-ExitLicenseServiceGuide—detail the processes in even greater specificity. (See the Specimens topic for more information on applying for an export license for HGR.)

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 Additional Resource (K). 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 (Additional Resource (L)). 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 (Additional Resource (L)). 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 the online platform at Additional Resource (K). 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 to the online platform (Additional Resource (K)). MOST will publicly announce its decision (Additional Resource (L)), 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.

Additional Resource (M) provides an infographic of the drug registration and information disclosure process.

Delivery Information for Clinical Trial Application

Per the DRR, clinical trial applications should be submitted to the CDE via the online Applicant’s Window (Additional Resource (A)). (Note that only Chinese legal persons can register for an account on the Applicant’s Window.) Hard copies can be delivered to the Administrative Acceptance Service Center of NMPA. Additional Resource (B) contains the most recent contact information for the Center:

NMPA Administrative Acceptance Service Center
Beijing West 1st and 3rd Floors
Dacheng Square, No. 28
Xuanwumen West Street, City 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
1st Floor, Building 4
No. 16 West Fourth Ring Road
Haidian District
Beijing, 100039
P.R. China
Phone: 010-88225151

Assembly and Number of Copies

The NMPA announced in the NMPA-No10 that applicants should 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 Additional Resource (G)). M4 must be applied to the registration applications for class 1 drugs, class 1 therapeutic biological products, and class 1 vaccines. Further, per the G-Phase1-CTApp, the applications of Phase I clinical trials must be submitted in electronic and hard copy formats and may be provided on a CD.

As per Additional Resources (H) and (I), China is developing an eCTD system to meet uniform drug registration application data format and requirements and improve the quality of applications. (The ClinRegs team will monitor this development and provide updates as appropriate.)

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

Clinical Trial Application Language Requirements

Per Additional Resource (J), when submitting overseas clinical trial data for drug registration, the applicant should provide the original text and a Chinese translation.

Additional Resources
(A) (Website) Applicant's Window (Current as of July 5, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(B) (Website) Administrative Acceptance Service Hall: Things to Know (Standard Chinese) (Current as of April 16, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
National Medical Products Administration, State Administration for Market Regulation, State Council
(D) (Article) China and the Evolving Regulatory Landscape (September 4, 2019)
Baruah, Megha; European Pharmaceutical Review
Relevant Sections: Table 1
(E) (Website) Smoother Regulatory Process for China (September 8, 2016)
Zhang, Kai; Applied Clinical Trials
Wang, Katherine; Ropes & Gray
Relevant Sections: Simplifying the approval process for clinical trials
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(I) (Website) 7 Things to Know about the China Pharmaceutical Industry (Current as of April 16, 2020)
Synchrogenix
Relevant Sections: 7
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 4
(K) (Website) Ministry of Science and Technology Government Service Platform (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
(L) (Website) Administrative License (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Relevant Sections: Human Genetic Resource Management
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
Clinical Trial Lifecycle > Submission Content
Last content review/update: July 06, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Article 10), Chapter 4 (Article 17), and Chapter 6 (Article 35)
(2) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (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)
(3) (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)
(4) (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)
(5) (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)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1-8, 11-12, and 14
(6) (Notice) Publication of the Work Plan for the Reform of the Classification and Registration of Chemical Drugs (No. 51 of 2016) (SC-Notice-No51 – Standard Chinese) (March 4, 2016)
National Medical Products Administration, State Administration for Market Regulation, State Council
(7) (Regulation) Opinions on Encouraging Drug Innovation to Implement Priority Review and Approval (No. 126 of 2017) (NMPA-No126 – Standard Chinese) (December 21, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
(8) (Regulation) Announcement on Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(9) (Circular) Technical Guidelines for the Application of Phase I Clinical Trials of New Drugs (No. 16 of 2018) (G-Phase1-CTApp – Standard Chinese) (January 11, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annex
(10) (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
(11) (Notice) Application of the Second Level Guiding Principles of the International Human Drug Registration Technical Coordination Committee (No. 10 of 2018) (NMPA-No10 – Standard Chinese) (January 25, 2018)
State Council
Relevant Sections: 1
(12) (Regulation) Decision Concerning the Adjustment of Imported Drug Registration and Administration (No. 35 of 2017) (SC-Decision-No35 – Standard Chinese) (October 10, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
(13) (Circular) Technical Guiding Principles for Accepting Data from Overseas Clinical Trials of Drugs (No. 52 of 2018) (NMPA-No52 – Standard Chinese) (July 6, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
(14) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter I (Articles 1-4 and 7-9)
(15) (Regulation) Notice on the Opening and Operation of the Online Declaration System for the Collection, Trading, Export and Exit Approval of Human Genetic Resources (State Science and Technology Office Letter No. 758) (S&T-Circular-HGRNo758 – Standard Chinese) (October 14, 2016)
Ministry of Science and Technology
(16) (Regulation) Human Genetic Resources – Collection Service Guidelines for Administrative Licensing Matters (HGR-Collection – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1 and 7-8
(17) (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
(18) (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
(19) (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
(20) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Article 19)
(21) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (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 the NMPA-GCPs, the DRR, the DAL, and the RegImplemDAL, 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.

In accordance with the SC-Opinions-No44, the SC-Notice-No51, the NMPA-No126, the NMPA-No230, and as described in Additional Resources (A) and (B), China implemented reforms to streamline the review and approval process, including a one-time approval procedure for new drug clinical applications (formerly, new approvals were needed for each clinical trial phase) and priority review for certain drugs. In addition, for generic drugs, the bioequivalent study will only need to be filed with the NMPA (formerly it was a review and approval procedure). 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.

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 the CDE using the Applicant’s Window (Additional Resource (C)). 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. The specific requirements of the submission content are identified in the online application at the Applicant’s Window. (Note that only Chinese legal persons can register for an account on the Applicant’s Window.)

The G-Phase1-CTApp 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 (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 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 Additional Resource (M)). M4 must be applied to the registration applications for class 1 drugs, class 1 therapeutic biological products, and class 1 vaccines.

The SC-Decision-No35 and interpretations in Additional Resources (D) and (E), 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 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 International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum)
  • 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 for additional details on the review and approval of overseas clinical trial data. For overseas clinical trial data completed before the enactment of SC-Decision-No35, 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 Additional Resource (F).

Ministry of Science and Technology (MOST) Requirements

With regard to reviewing and approving international cooperative research and export license applications for human genetic resources (HGR), and in accordance with the MgmtHumanGen, the Ministry of Science and Technology (MOST) is responsible for China's efforts to manage human genetic resources (HGR), comprising genetic material and data. Per S&T-Circular-HGRNo758, those seeking to collect and export HGR must submit an online declaration through the National Science and Technology Management Information System Declaration Center (Additional Resource (G)).

As specified in the HGR-Collection, only the 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 the submission content requirements.

As per the HGR-Procedures, the HGR-IntlApprovalLicenseServiceGuide, and Additional Resource (H), the following documentation must be submitted to MOST as part of the HGR license review and approval process for international cooperative research:

  • Original application – after the online declaration is completed (Additional Resource (G)), the paper stamp is submitted (See the HGR-IntlApprovalLicenseServiceGuide and Additional Resource (H) for the application)
  • Copy of legal person qualification
  • Copy of ethics committee (EC) approval – foreign language documents must be accompanied by corresponding Chinese translations
  • Copy of informed consent
  • Copy of research plan
  • Copy of international cooperation agreement with Chinese translations
  • Copy of agreements on the collection, shipment, detection, and destruction of HGR
  • Clinical trial approvals, notices, or filing materials
  • Commitment – letter electronically signed and stamped that is provided by the participating medical institutions

As per the HGR-Procedures, the HGR-IntlRecordMgtServiceGuide, and Additional Resource (H), the following documentation must be submitted to MOST’s online platform (Additional Resource (I)) for record filing (i.e., notification) of an international clinical trial wherein the HGR is not being exported:

  • Filing information form – the signature page should be signed and sealed (See the HGR-IntlRecordMgtServiceGuide and Additional Resource (H) for the form)
  • Legal person qualification material
  • Informed consent form
  • EC approval – foreign language documents must be accompanied by corresponding Chinese translations
  • Research plan
  • International cooperation agreement
  • Signed and sealed cooperation agreement between the clinical trial institution and its entrusted testing agency
  • Protocol documents relating to trans-shipment of HGR
  • Clinical trial approvals, notices, or filing materials
  • Commitment – letter electronically signed and stamped that is provided by the participating medical institutions

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 Additional Resources (K) and (L) 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

See Additional Resource (L) for an example of an institutional EC’s ethics application requirements and process.

Clinical Protocol

As delineated in the NMPA-GCPs and the ICH-GCPs-Addendum, 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 Article 17 of the NMPA-GCPs and Section 6 of the ICH-GCPs-Addendum.

Additional Resources
(A) (Article) China and the Evolving Regulatory Landscape (September 4, 2019)
Baruah, Megha; European Pharmaceutical Review
Wang, Katherine; Ropes & Gray
(C) (Website) Applicant's Window (Current as of July 5, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
National Medical Products Administration, State Administration for Market Regulation, State Council
National Medical Products Administration, State Administration for Market Regulation, State Council
(F) (Website) National Medical Products Administration – Drug Regulatory Documents (Standard Chinese) (Current as of April 16, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
(G) (Website) National Science and Technology Management Information System Declaration Center (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
(H) (Website) Integrated System Catalogue, Human Genetic Resource Management (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
(I) (Website) Ministry of Science and Technology Government Service Platform (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
(J) (Website) Administrative License (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Relevant Sections: Human Genetic Resource Management
(K) (Form) Application for Human Research Ethics Review (Standard Chinese) (Date Unavailable)
Independent Ethics Committee, Shanghai Clinical Research Center
(L) (Form) Human Research Ethics Review Application Documents (Standard Chinese) (Date Unavailable)
Independent Ethics Committee, Shanghai Clinical Research Center
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 6
Clinical Trial Lifecycle > Timeline of Review
Last content review/update: July 06, 2020
Requirements
(1) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (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)
(2) (Regulation) Announcement on Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1-4 and Annexes 1-3
(3) (Regulation) Announcement on the Release of Administrative Measures for the Communication of Drug R & D and Technical Review (No. 74 of 2018) (NMPA-No74 – Standard Chinese) (September 30, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1
(4) (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)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1-8, 11-12, and 14
(5) (Regulation) Announcement on Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(6) (Notice) Publication of the Work Plan for the Reform of the Classification and Registration of Chemical Drugs (No. 51 of 2016) (SC-Notice-No51 – Standard Chinese) (March 4, 2016)
National Medical Products Administration, State Administration for Market Regulation, State Council
(7) (Regulation) Opinions on Encouraging Drug Innovation to Implement Priority Review and Approval (No. 126 of 2017) (NMPA-No126 – Standard Chinese) (December 21, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
(8) (Notice) Relevant Issues Concerning the Review and Approval of New Overseas Drugs for Clinical Urgent Needs (No. 79 of 2018) (NMPA-No79 – Standard Chinese) (October 23, 2018)
National Medical Products Administration, State Administration for Market Regulation, and the National Health Commission, State Council
(9) (Regulation) Announcement on Matters Relating to the Optimization of Drug Registration Review and Approval (No. 23 of 2018) (NMPA-No23 – Standard Chinese) (May 17, 2018)
National Medical Products Administration, State Administration for Market Regulation, and the National Health Commission, State Council
(10) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Article 13)
Summary

Overview

As stated in the DRR, and according to Additional Resource (A), 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 Additional Resource (B), 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 Additional Resource (C), 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.

Per the DRR and the NMPA-No50, 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. To help facilitate the review process, the NMPA-No50 and the NMPA-No74 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. Upon application submittal, the 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, 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. 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, and the SC-Notice-No51, 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 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.

Further, per the NMPA-No126, priority review may also be possible for drugs that are in simultaneous development in the European Union and the United States. Per the NMPA-No79, 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. See Additional Resources (C), (D), (E), and (F) for more information on the urgently needed drugs. 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. NMPA-No23 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. For more information about reforms to priority review and approval, see Additional Resource (G).

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, 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, 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.

For further guidance on NMPA timelines for supplementary application submissions and registration renewals for imported drugs and more, please refer to Additional Resource (H).

EC Approval

An applicant must also submit the clinical trial application for review and approval by an institutional EC. The NMPA-GCPs states that the EC should hold a meeting as soon as possible after receiving the application to review and discuss it. Per the ICH-GCPs-Addendum, the institutional EC should review a proposed clinical trial within a reasonable time. The NMPA-GCPs and the ICH-GCPs-Addendum provide that 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
(A) (Website) Regulatory Timelines in the Asia-Pacific (December 30, 2016)
George Clinical
Relevant Sections: China
(B) (Article) China (April 2020)
Kingham, Richard; The Life Sciences Law Review, Edition 8
Relevant Sections: Approval Timeline
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
Hogan Lovells
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(G) (Presentation) New CFDA Requirements and its Implementation (September 4, 2018)
Yi Yang, PharmaSUG Single Day Event
Relevant Sections: Priority Review and Approval
(H) (Website) NMPA Drug Regulatory Developments (Standard Chinese) (Current as of April 16, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 3.1.2
Clinical Trial Lifecycle > Trial Initiation
Last content review/update: July 06, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Articles 6 and 7), Chapter 3 (Article 10), Chapter 4 (Article 17), and Chapter 6 (Articles 35 and 43)
(2) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (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)
(3) (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)
(4) (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)
(5) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapters 1 and 2
(6) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (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
(7) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter V (Article 36)
(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: 8
(9) (Regulation) Announcement on Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annex 3
Summary

Overview

In accordance with the NMPA-GCPs, the DRR, the DAL, the RegImplemDAL, 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 and Additional Resource (A) also state 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-GCPs states that investigators must possess the appropriate qualifications, training, and experience to assume responsibility for the trial. Per the DRR, clinical trials must be conducted in drug clinical trial institutions that comply with relevant regulations, and abide by the drug clinical trial quality management standards. 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 ICH-GCPs-Addendum, the sponsor must sign an agreement or contract with the participating institution(s). The NMPA-GCPs 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 ICH-GCPs-Addendum, all investigators must possess appropriate qualifications, training, and experience.

EC Confirmation of Review and Approval

The NMPA-GCPs 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).

Chinese Clinical Trial Registry (ChiCTR) Recording Requirements

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. According to Additional Resources (D) and (E), all clinical trials approved by the NMPA and conducted in China should be registered on the Chinese Clinical Trial Registry (ChiCTR). According to Additional Resource (E), the sponsor should register before commencing the trial. The ChiCTR website provides complete details on registration procedures.

According to Additional Resource (F), clinical trials should also be registered on NMPA’s Center for Drug Evaluation (CDE) website: Chinadrugtrials.org.cn.

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.

As delineated in G-SftyRptStds, the sponsor should appoint full-time 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 for ensuring staff understand the latest security information, conduct timely risk assessments, provide relevant information to inform participants and interested parties, and quickly report unexpected serious adverse reactions. Annex 3 to NMPA-No50 requires that application materials for Phase 1 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-GCPs-Addendum 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.

Additional Resources
EU SME Centre, Beijing, China
Relevant Sections: Imported Drugs Need Pre-market Approval Before Entering the Chinese Market; Biological Products Registration; Annexes 2 and 3; and Links to the Chinese Administration Webpages
(B) (Article) China and the Evolving Regulatory Landscape (September 4, 2019)
Baruah, Megha; European Pharmaceutical Review
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
(D) (Website) Chinese Clinical Trial Registry (ChiCTR) (Standard Chinese) (Current as of April 16, 2020)
Chinese Clinical Trial Registry, Sichuan, China
(E) (Website) Chinese Clinical Trial Registry (ChiCTR) Frequently Asked Questions (Current as of April 16, 2020)
Chinese Clinical Trial Registry, Sichuan, China
(F) (Website) What Drug Clinical Trials are Covered by This Platform? (Standard Chinese) (Current as of April 16, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
Clinical Trial Lifecycle > Safety Reporting
Last content review/update: July 06, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1 (Articles 6 and 10), Chapter 3 (Article 10), Chapter 4 (Article 7), Chapter 5 (Articles 25 and 26), and Chapter 6 (Articles 36, 39, and 40)
(2) (Guidance) Provisions for Reporting and Monitoring of Adverse Drug Reactions (ADRGuide – English, unofficial translation) (March 20, 2012)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 6 (Article 29)
(3) (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
(4) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter II (Article 28)
(5) (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)
(6) (Regulation) Announcement on Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 16 and Annex 3
(7) (Notice) Application of the Second Level Guiding Principles of the International Human Drug Registration Technical Coordination Committee (No. 10 of 2018) (NMPA-No10 – Standard Chinese) (January 25, 2018)
State Council
Relevant Sections: 2
(8) (Regulation) Announcement on Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(9) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (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-GCPs and the ADRGuide, the following definitions provide a basis for a common understanding of China’s safety reporting requirements:

  • Adverse Event (AE) – An untoward medical event in a patient or clinical investigation participant who is administered a drug, and which does not necessarily have a causal relationship with the treatment
  • Serious Adverse Event (SAE) – Any untoward medical occurrence resulting in death, disability/incapacity, effect on work capability, congenital anomaly, is life threatening, requires in-patient hospitalization, or prolongation of hospitalization that occurs during a clinical trial
  • Adverse Drug Reaction (ADR) – A harmful reaction that occurs irrespective of the intended use or unexpectedly when a qualified drug is used in its normal dose and administration method
  • Serious Adverse Drug Reaction (SADR) – A drug reaction that results in death; cancer, deformity or birth defect; permanent or distinctive impairment and physical disabilities; permanent organ damage, hospitalization or prolonged hospitalization; or is life-threatening

The G-SftyRptStds includes 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. It also provides guidance on serious unexpected serious adverse reactions (SUSAR). They occur when the nature, severity, frequency, or consequences are unlike previous drug tests or the expected risks from relevant information (e.g., investigator’s brochure).

Reporting Requirements for AE/ADRs

Per the DRR, the sponsor must regularly submit a safety update report to the CDE at the Applicant’s Window (Additional Resource (A)). 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.

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. As delineated in the NMPA-GCPs, the investigator is responsible for reporting all AEs/ADRs and SAEs/SADRs to the sponsor. The investigator and his/her institution must immediately report all expected and unexpected SAEs to the sponsor, the provincial, autonomous regional, or municipal drug authority and to the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”), and the ethics committee (EC) within 24 hours of occurrence. The sponsor and the investigator are also required to study the SAEs immediately after the occurrence and take necessary measures to ensure participant safety and welfare. Other investigators conducting clinical trials on the same drug must also be contacted. However, in contrast, the G-SftyRptStds specifies that 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. 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.

As per the NMPA-No50, the NMPA-No10, the G-SftyRptStds, and Additional Resource (B), 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) (Additional Resource (C)), and ICH E2B (R3) (Electronic Transmission of Individual Case Safety Reports) (Additional Resource (D)). 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 Center for Drug Evaluation (CDE) in Chinese. The investigator may submit the report via the GATEWAY account or on CDE’s website under the registered account for “pharmacovigilance submittal.” Finally, other potentially serious security risks can be sent as a “Quick Report” through e-mail to: lcqjywjj@cde.org.cn.

According to the NMPA-No230, 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 states that the applicant must submit all adverse event data on time.

Per Additional Resource (E), applicants are required to submit drug monitoring protocols and annual reports to the Adverse Drug Reactions Monitoring Center during each clinical trial stage, and after approval of the investigational drug product.

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.

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 requires that application materials for Phase 1 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-GCPs-Addendum 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.

Additional Resources
(A) (Website) Applicant's Window (Current as of July 5, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(E) (Website) Center for Drug Reevaluation, NMPA – National Center for ADR Monitoring, China (Standard Chinese) (Current as of April 16, 2020)
Center for Drug Reevaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.25 and 5.5.2
Clinical Trial Lifecycle > Progress Reporting
Last content review/update: July 06, 2020
Requirements
(1) (Regulation) Announcement on Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(2) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 5 (Article 30), Chapter 6 (Article 42), and Chapter 8 (Article 51)
(3) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter III (Article 33)
Summary

Overview

According to the NMPA-No230, 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 states that the applicant must submit an annual report on time.

Per Additional Resource (A), applicants are required to submit drug monitoring protocols and annual reports to the Adverse Drug Reactions Monitoring Center during each clinical trial stage, and after approval of the investigational drug product.

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

Per the DRR, the sponsor must register the results of clinical trials after completion with the CDE using the Applicant’s Window (Additional Resource (C)). In accordance with the NMPA-GCPs, the investigator is responsible for preparing the final report following the conclusion of a clinical trial and then forwarding the report to the sponsor. The sponsor, in turn, must submit the report to the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”).

As per the NMPA-GCPs, the final report must conform to the protocol and contain the following elements:

  • Actual number of participants/cases that randomly participated in each treatment group; participant dropouts, and those released from the trial accompanied by the reason for each
  • Comparison of baseline characteristics among different treatment groups
  • Statistical and clinical analysis for all of the indexes of the therapeutic effects evaluation
  • Safety evaluation containing a statistical analysis of adverse events with a detailed description of each, and laboratory indexes included
  • Assessment of the therapeutic effects in a multicenter trial, and the effects among each center
  • Summary of the relationship between the therapeutic effects and safety as well as risks and benefits associated with the investigational products
Additional Resources
(A) (Website) Center for Drug Reevaluation, NMPA – National Center for ADR Monitoring, China (Standard Chinese) (Current as of April 16, 2020)
Center for Drug Reevaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.10 and 4.13
(C) (Website) Applicant's Window (Current as of July 5, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
Sponsorship > Definition of Sponsor
Last content review/update: July 06, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 6 (Article 32) and Chapter 10 (Article 38)
(2) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (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) (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)
Summary

Overview

As per the DRR, the NMPA-GCPs, and the ICH-GCPs-Addendum, 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.

A sponsor can authorize a contract research organization (CRO) to carry out certain work and obligations regarding the clinical trial. The ICH-GCPs-Addendum further specifies that any trial-related responsibilities transferred to and assumed by a CRO should be specified in writing, and those obligations not covered by the written description shall be deemed not to have been transferred. However, although a sponsor may transfer all of his/her trial-related duties and functions to a CRO, he/she is ultimately responsible for the study data’s quality and integrity.

A sponsor may be domestic or foreign, but, per the DRR and Additional Resource (B), 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
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.53, 1.54, and 5.2
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Are any legislative changes proposed or expected in the near future?
Sponsorship > Trial Authorization
Last content review/update: July 06, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 6 (Article 32)
(2) (Regulation) Announcement on Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 16
(3) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (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)
(4) (Circular) Technical Guidelines for the Application of Phase I Clinical Trials of New Drugs (No. 16 of 2018) (G-Phase1-CTApp – Standard Chinese) (January 11, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annex
(5) (Notice) Application of the Second Level Guiding Principles of the International Human Drug Registration Technical Coordination Committee (No. 10 of 2018) (NMPA-No10 – Standard Chinese) (January 25, 2018)
State Council
(6) (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)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 1-8, 11-12, and 14
(7) (Notice) Publication of the Work Plan for the Reform of the Classification and Registration of Chemical Drugs (No. 51 of 2016) (SC-Notice-No51 – Standard Chinese) (March 4, 2016)
National Medical Products Administration, State Administration for Market Regulation, State Council
(8) (Regulation) Opinions on Encouraging Drug Innovation to Implement Priority Review and Approval (No. 126 of 2017) (NMPA-No126 – Standard Chinese) (December 21, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
(9) (Regulation) Announcement on Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
(10) (Legislation) Vaccine Administration Law (VaccineLaw – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: 16-18
(11) (Regulation) Notice on Propaganda and Implementation of the Vaccine Administration Law (No. 23 of 2019) (NMPA-No32 – Standard Chinese) (July 25, 2019)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: 4
Summary

Overview

In accordance with the NMPA-GCPs and the NMPA-No50, 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.

The DRR and Additional Resource (A) state 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 the Center for Drug Evaluation (CDE)’s Applicant’s Window (Additional Resource (B)). 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. The specific requirements of the submission content are identified in the online application on the Applicant’s Window website. (Note that only Chinese legal persons can register for an account on the Applicant’s Window.) The G-Phase1-CTApp 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)
  • Clinical trial plan
  • Pharmacy research information
  • Pharmacology and toxicology information
  • Description of previous clinical use experience
  • Overseas research material

Per the NMPA-No50 and Additional Resource (C), the electronic files and a hard copy of the application must be submitted to the NMPA Administrative Acceptance Service Center. 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 that applicants should apply the International Council for Harmonisation (ICH)’s M4: Common Technical Document for the Registration of Pharmaceuticals for Human Use (CTD) (Additional Resource (D)). M4 must be applied to the registration applications for class 1 drugs, class 1 therapeutic biological products, and class 1 vaccines. Further, the G-Phase1-CTApp 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, 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.

In accordance with the SC-Opinions-No44, the SC-Notice-No51, the NMPA-No126, and the NMPA-No230, and as described in Additional Resources (D) and (E), China has implemented reforms to streamline the review and approval process, including a one-time approval procedure for new drug clinical applications (formerly, new approvals were needed for each clinical trial phase). In addition, for generic drugs, the bioequivalent study will only need to be filed with the NMPA (formerly it was a review and approval procedure). 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.

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 explains that the new legislation VaccineLaw, which took effect December 1, 2019, 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.

Additional Resources
EU SME Centre, Beijing, China
Relevant Sections: Imported Drugs Need Pre-market Approval Before Entering the Chinese Market; Biological Products Registration; Annexes 2 and 3; and Links to the Chinese Administration Webpages
(B) (Website) Applicant's Window (Current as of July 5, 2020)
Center for Drug Evaluation, National Medical Products Administration, State Administration for Market Regulation, State Council
(C) (Website) Administrative Acceptance Service Hall: Things to Know (Standard Chinese) (Current as of April 16, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(E) (Article) China and the Evolving Regulatory Landscape (September 4, 2019)
Baruah, Megha; European Pharmaceutical Review
Wang, Katherine; Ropes & Gray
Sponsorship > Insurance
Last content review/update: April 16, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 6 (Article 43)
Summary

Overview

As set forth in the NMPA-GCPs, the sponsor is responsible for providing insurance coverage for any unforeseen injury to research participants. The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum) guides sponsors on providing insurance.

Additional Resources
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 5.8
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Clinical Trials, Insurance
Sponsorship > Compensation
Last content review/update: April 16, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 6 (Article 43) and Appendix 2
Summary

Overview

In accordance with the NMPA-GCPs, the sponsor is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death. The sponsor must also ensure that participants who suffer any trial-related injuries are provided with free medical treatment for such injuries. (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) (ICH-GCPs-Addendum) 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
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: July 06, 2020
Requirements
(1) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (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)
(2) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Article 7), Chapter 4 (Article 16), Chapter 6 (Articles 32, 33, 38, 39, and 41), Chapter 11 (Articles 52, 53, 61, and 63), Chapter 12 (Article 66), and Appendix 2
(3) (Notice) Publication of Technical Guidelines for Clinical Trial Data Management (No. 112 of 2016) (NMPA-No112 – 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
(4) (Notice) Handling of the Relevant Issues Concerning the Verification of Drug Clinical Trial Data (No. 63 of 2017) (NMPA-No63) (May 22, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Responsibilities of the applicant, drug clinical trial institution and contract study organization
(5) (Circular) Information Guide for Innovative Medicine (Chemicals) Phase III Clinical Trial Pharmaceutical Research (No. 48 of 2018) (G-NMPA-No48) (March 9, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
(6) (Legislation) Vaccine Administration Law (VaccineLaw – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: 11 and 17
(7) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter III (Article 24)
(8) (Regulation) Decision Concerning the Adjustment of Imported Drug Registration and Administration (No. 35 of 2017) (SC-Decision-No35 – Standard Chinese) (October 10, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
Summary

Overview

Per the DRR, the management of drugs used in clinical trials must comply with the clinical trial quality management regulations. As stated in the NMPA-GCPs and NMPA-No112, the sponsor must establish quality control (QC) and quality assurance (QA) systems for the clinical trial. The sponsor must develop quality management evaluation procedures, the quality management plan and operation guide, and set up an inspection department. In addition, the sponsor and the investigator are required to prepare standard operating procedures (SOPs) outlining their respective responsibilities to ensure that the trial is conducted in compliance with the protocol and the NMPA-GCPs. Both the sponsor and the investigator must sign a written agreement verifying that both parties agree to the trial protocol approved by an ethics committee (EC); the monitoring and auditing practices; the SOPs; and their respective duties.

According to NMPA-No63, the sponsor, institution, investigators, and contract research organizations are legally responsible for ensuring that the clinical trial data is accurate and complete.

In addition, per the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum), the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

  • During protocol development, identify processes and data that are critical to ensure participant protection and the reliability of trial results
  • Identify risks to critical trial processes and data
  • Evaluate the identified risks against existing risk controls
  • Decide which risks to reduce and/or which risks to accept
  • Document quality management activities and communicate to those involved in or affected by these activities
  • Periodically review risk control measures to ascertain whether the implemented quality management activities are effective and relevant
  • In the clinical study report, describe the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken

The G-NMPA-No48 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 ICH-GCPs-Addendum, 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 the ICH-GCPs-Addendum, 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 the ICH-GCPs-Addendum for additional information.

Record Management

As set forth in the NMPA-GCPs, all clinical trial data must be stored and managed in accordance with Appendix 2. The sponsor should inform the investigator(s) that the investigator must retain trial documentation for five (5) years following the trial’s completion. In addition, the sponsor must appoint a qualified monitor, who the investigator must also approve. The sponsor should also retain all trial-related documents and materials for five (5) years after the investigational product has been approved for marketing.

In addition, the ICH-GCPs-Addendum states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

Audit Requirements

As per the NMPA-GCPs, the sponsor; the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”); and provincial, autonomous region, or municipal drug authorities should authorize an auditor to carry out systematic checks on clinical trial operations and the document filing system to ensure the trial is in compliance with the protocol, the SOPs, and relevant regulations. The auditor must also verify that the data is recorded accurately, timely, and completely. Personnel not directly involved in the clinical trial must conduct the audit. In accordance with the DRR and Additional Resource (B), 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.

Further, per the ICH-GCPs-Addendum, the sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose onsite monitoring, a combination of onsite and centralized monitoring, or, where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan).

Premature Study Termination/Suspension

The NMPA-GCPs state that if the sponsor chooses, or is required to terminate a study, he/she must immediately inform the investigator(s), institution(s), the EC, and the NMPA, and explain the reason. Per the DRR under any of the following circumstances, the sponsor may be required to adjust the drug clinical trial program, suspend, or terminate the drug clinical trial:

  • The EC fails to perform its duties
  • Failure to effectively guarantee the safety of the participants
  • The sponsor fails to submit the safety update report as required
  • The sponsor fails to deal with and report suspicious and unexpected serious adverse reactions as required
  • There is evidence to prove that the study drug is invalid
  • There are quality problems with the drugs used in a clinical trial
  • There is falsification during the clinical trial
  • Other circumstances that violate the quality management standards

When a large-scale and unexpected serious adverse reaction occurs in a drug clinical trial, or there is evidence to prove that there is a serious quality problem with the drug used in the clinical trial, the sponsor and the drug clinical trial institution must immediately stop the clinical trial. The NMPA may adjust, suspend, or terminate clinical trials. After a clinical trial is ordered to be suspended, the sponsor intending to continue the drug clinical trial must submit a supplementary application for resuming the drug clinical trial after completing the rectification, and the drug clinical trial may be continued only after the review and approval. If a clinical trial is ordered to be terminated, a new application must be submitted.

According to the ICH-GCPs-Addendum, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions.

Multicenter Studies

In the event of a multicenter clinical trial, the sponsor and the principal investigators of each center must jointly discuss the protocol.

The SC-Decision-No35 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.

Per Additional Resource (A), for international multicenter clinical trials, the NMPA requires the following:

  • Multicenter clinical data for drug registration in China must involve at least two (2) countries, including China
  • Overseas applicants must conduct a holistic evaluation of the global clinical trial data set and a trending analysis of the data from the trial participants in Asia and China; Chinese participants must be representative of the relevant patient population in Chinese medical practice
  • Overseas applicants must ascertain whether the Chinese trial participant sample size sufficiently supports the conclusion that the investigational product is safe and effective for Chinese participants and meets the statistical requirements and the relevant laws and regulations
  • Overseas applicants must comply with accepted Good Clinical Practice and ethical standards and allow the NMPA to inspect trial sites, which can be any of the domestic or foreign sites in the multicenter clinical trial

As delineated in the ICH-GCPs-Addendum, in the event of a multicenter clinical trial, the sponsor must ensure that all investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor.

Additional Resources
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
Covington
Relevant Sections: Clinical Trial Inspections
Sponsorship > Site/Investigator Selection
Last content review/update: July 06, 2020
Requirements
(1) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (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)
(2) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Article 6) and Chapter 6 (Articles 33 and 34)
(3) (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
(4) (Notice) Administration of Drug Clinical Trial Institutions (No. 101 of 2019) (NMPA-NHC-No101 – Standard Chinese) (Effective December 1, 2019)
National Medical Products Administration, State Administration for Market Regulation, State Council, and the National Health Commission
(5) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Article 15) and Chapter 4
(6) (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
(7) (Regulation) Announcement on Adjusting the Review and Approval Procedures for Drug Clinical Trials (No. 50 of 2018) (NMPA-No50 – Standard Chinese) (July 24, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Annex 3
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-GCPs and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum), 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). (See the Clinical Trial Lifecycle topic, Submission Content subtopic for additional information on clinical trial application 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, and Additional Resource (B), 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 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.

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 and the ICH-GCPs-Addendum indicate that the DSMB’s duty is to regularly assess the progress of the trials, analyze safety data, and monitor the trial. The ICH-GCPs-Addendum 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 requires that application materials for Phase 1 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 and Additional Resource (C) require foreign applicants/sponsors to designate Chinese legal entities to handle relevant drug registration matters.

Additional Resources
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.25, 5.5, and 5.6
EU SME Centre, Beijing, China
Relevant Sections: Imported Drugs Need Pre-market Approval Before Entering the Chinese Market; Biological Products Registration; Annexes 2 and 3; and Links to the Chinese Administration Webpages
Informed Consent > Documentation Requirements
Last content review/update: July 06, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Articles 8, 12, 14, and 15), Chapter 4 (Article 15), Chapter 5 (Article 24), and Chapter 13 (Article 68)
(2) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Articles 18, 19, and 28) and Chapter 4 (Articles 33-39)
(3) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (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)
(4) (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)
(5) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter I (Article 9) and Chapter II (Article 12)
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-GCPs, the RegEthics, and the EthicsGuide. In addition, China is implementing the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum) as a guidance document.

As per the NMPA-GCPs, the DAL, the EthicsGuide, and the ICH-GCPs-Addendum, 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 Additional Resource (B), 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-GCPs and the ICH-GCPs-Addendum 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-GCPs 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

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

According to the ICH-GCPs-Addendum, any change in the ICF due to a protocol modification should be approved by the EC before such changes are implemented. The participant and/or his/her legal representative(s) or guardian(s) will also be required to re-sign the revised ICF and receive a copy of any amended documentation.

Language Requirements

Additional Resource (C) states that all clinical trial applications and supporting materials, including the ICF, must be in Chinese. The NMPA-GCPs, 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

As per the NMPA-GCPs, the participant and/or his/her legal representative(s) or guardian(s) as well as the investigator must sign and date the ICF. The investigator should retain a copy of the signed ICF, and one (1) copy should be sent to the sponsor.

According to the ICH-GCPs-Addendum, where the participant is illiterate and/or his/her legal representative(s) or guardian(s) is illiterate, an impartial witness should be present during the entire informed consent discussion. 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
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 2, 4.4, 4.8, 8.2, and 8.3
(B) (Website) Integrated System Catalogue, Human Genetic Resource Management (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Clinical Trials Authorization
Informed Consent > Required Elements
Last content review/update: April 16, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Article 12), Chapter 4 (Article 15), and Chapter 5 (Article 24)
(2) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (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)
(3) (Legislation) Vaccine Administration Law (VaccineLaw – Standard Chinese) (Effective December 1, 2019)
National People’s Congress
Relevant Sections: 18
(4) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 4 (Articles 33-37)
(5) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter II (Article 12)
Summary

Overview

As delineated in the NMPA-GCPs, the EthicsGuide, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum), 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-GCPs, the EthicsGuide, the RegEthics, and the ICH-GCPs-Addendum 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 ICH-GCPs-Addendum, 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-GCPs, the EthicsGuide, the RegEthics, and the ICH-GCPs-Addendum, 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 subtopic and Vulnerable Populations subtopic for additional information.

Additional Resources
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.4 and 4.8
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
Informed Consent > Compensation Disclosure
Last content review/update: April 16, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Article 14)
(2) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Appendix 1 (Sections 4 and 5)
(3) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 4 (Articles 36-37)
Summary

Overview

In accordance with the NMPA-GCPs, the EthicsGuide, the RegEthics, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum), 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 and the RegEthics, 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 the ICH-GCPs-Addendum, 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-GCPs, the EthicsGuide, the RegEthics, and the ICH-GCPs-Addendum, 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
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: April 16, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1 (Article 4), Chapter 3 (Articles 8 and 14), Appendix 1 (Declaration of Helsinki) (Sections B and C)
(2) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Articles 18 and 19) and Chapter 4 (Articles 33-39)
(3) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (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 principles set forth in the NMPA-GCPs and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum), 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-GCPs, 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-GCPs, the EthicsGuide, the RegEthics, and the ICH-GCPs-Addendum, 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-GCPs, the RegEthics, and the ICH-GCPs-Addendum, 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, and the ICH-GCPs-Addendum, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. The NMPA-GCPs 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 and the ICH-GCPs-Addendum 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-GCPs and the ICH-GCPs-Addendum 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
(A) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 3.1 and 4.8
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
Informed Consent > Special Circumstances/Emergencies
Last content review/update: April 16, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Articles 12, 14, and 15) and Chapter 5 (Article 22)
Summary

Overview

The NMPA-GCPs and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum) 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-GCPs and the ICH-GCPs-Addendum, 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. Moreover, the NMPA-GCPs states that the investigator is required to conduct the trial in a medical institution with good medical treatment facilities, laboratory equipment, and personnel. The institution must have all the necessary resources to handle emergency situations to ensure participant safety.

Per the ICH-GCPs-Addendum, 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
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.8
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
Informed Consent > Vulnerable Populations
Last content review/update: April 16, 2020
Requirements
(1) (Notice) Issuance of Guidelines for the Ethical Review of Drug Clinical Trials (No. 436 of 2010) (EthicsGuide – Standard Chinese) (November 2, 2010)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Appendix 1 (Section 8) and Glossary
(2) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Appendix 1 (Section A)
(3) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Article 18)
Summary

Overview

As per the EthicsGuide and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum), 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 defines 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 ICH-GCPs-Addendum also includes members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include persons in nursing homes, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

The NMPA-GCPs, which upholds the principles of the Declaration of Helsinki 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
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.61, 3.1, and 4.8
(B) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
Informed Consent > Children/Minors
Last content review/update: April 16, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Article 15) and Appendix 1 (Declaration of Helsinki) (Section B)
(2) (Guidance) Guidelines for General Consideration of the Publication of Drug Clinical Trials (No. 11 of 2017) (NMPA-No11 – Standard Chinese) (January 18, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: (B) (3) Special Consideration, Special Population
Summary

Overview

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

In accordance with the NMPA-GCPs and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum), 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, 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
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.8
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
Informed Consent > Pregnant Women, Fetuses & Neonates
Last content review/update: April 16, 2020
Requirements
(1) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (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 – Standard Chinese) (January 18, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: (B) (3) Special Consideration, Special Population
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, 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 International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum), 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
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 4.8
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
Informed Consent > Prisoners
Last content review/update: April 16, 2020
Requirements
(1) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Article 18)
Summary

Overview

While RegEthics does not list prisoners as a vulnerable population, Additional Resource (A) indicates that prisoners are strictly restricted to join clinical trials due to their restricted right of self-determination.

According to the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum), prisoners are considered vulnerable 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.

Additional Resources
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.61
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
Informed Consent > Mentally Impaired
Last content review/update: April 16, 2020
Requirements
(1) (Regulation) Regulations on Ethical Reviews of Biomedical Research Involving Humans (RegEthics – Standard Chinese) (Effective December 1, 2016)
National Health Commission
Relevant Sections: Chapter 3 (Article 18)
(2) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 3 (Article 15) and Appendix 1 (Declaration of Helsinki) (Section B)
Summary

Overview

While RegEthics lists mentally impaired people as a vulnerable population, there are no relevant provisions regarding any special consent procedures for them. The NMPA-GCPs and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum) 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 outlined below. The informed consent form (ICF) must be signed and dated by the participant’s legal representative(s) or guardian(s).

In accordance with the Declaration of Helsinki, the NMPA-GCPs states legally incompetent participants should only be included in research studies when the research is necessary to promote the health of the population represented, and the research cannot instead be performed on legally competent participants.

Research to be conducted on participants from whom it is not possible to obtain consent, including proxy or advance consent, should be done only if the physical or mental condition that prevents obtaining informed consent is a necessary characteristic of the research population. The reasons for involving these participants should be delineated in the protocol for the EC’s consideration and approval. The protocol should also state that consent to remain in the research must be obtained as soon as possible from the legal representative(s) or guardian(s).

Additional Resources
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.61 and 3.1
(B) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
Ren, Y., Jin, X., Jiang, S., Jiang, B.; The Journal of Biomedical Research
Investigational Products > Definition of Investigational Product
Last content review/update: April 16, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 13 (Article 68)
Summary

Overview

As delineated in the NMPA-GCPs, an investigational product is defined as a study drug, comparator, or placebo used in a clinical trial.

The International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum) 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
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 1.33
Investigational Products > Manufacturing & Import
Last content review/update: July 06, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 1 (Article 1), Chapter 2 (Article 6), and Chapter 6 (Article 35)
(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 III (Article 32), Chapter IV (Articles 41-47A), and Chapter X (Articles 98-100 and 103)
(3) (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 II and Chapter V (Articles 29, 30, 36, 38 and 42)
(4) (Regulation) Drug Registration Regulation (Order No. 27) (DRR – Standard Chinese) (Effective July 1, 2020)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter III (Article 47)
(5) (Regulation) Decision Concerning the Adjustment of Imported Drug Registration and Administration (No. 35 of 2017) (SC-Decision-No35 – Standard Chinese) (October 10, 2017)
National Medical Products Administration, State Administration for Market Regulation, State Council
(6) (Circular) Technical Guiding Principles for Accepting Data from Overseas Clinical Trials of Drugs (No. 52 of 2018) (NMPA-No52 – Standard Chinese) (July 6, 2018)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: I-V
(7) (Regulation) Announcement on Several Policies for Drug Registration Review and Approval (No. 230 of 2015) (NMPA-No230 – English, unofficial translation) (Standard Chinese) (November 11, 2015)
National Medical Products Administration, State Administration for Market Regulation, State Council
Summary

Overview

According to the NMPA-GCPs, the DAL, and the RegImplemDAL, 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. The NMPA-GCPs specifies that the NMPA will only approve the manufacture of an IP after the clinical trial application has been approved.

Per the DAL, 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. 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, 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

Per the DRR, 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) (ICH-GCPs-Addendum) 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 and the RegImplemDAL provide that prior to IP import or manufacture, a NMPA import drug license must be obtained for each IP. Per Additional Resource (A), 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 SC-Decision-No35, 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 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 ICH-GCPs-Addendum
  • 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 for additional details on the review and approval of overseas clinical trial data. For overseas clinical trial data completed before the enactment of SC-Decision-No35, 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 more information on application requirements, see the Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics.

Per NMPA-No230 and Additional Resource (A), 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.

In addition, the drug testing institute (the National Institutes for Food and Drug Control (NIFDC)) or a corresponding institute on the provincial, autonomous regional, or municipal level) must conduct sample testing and specifications verification of the IP in order to issue a Certificate of Analysis as part of the NMPA’s approval requirements for all registered drugs. Per Additional Resource (A), the inspection report will be issued within 20 days of the sampling. (See Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics for detailed application requirements).

Additional Resources
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Trends and developments and Supply
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 2.12, 5.13, and 6
Investigational Products > IMP/IND Quality Requirements
Last content review/update: July 06, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Article 6) and Chapter 6 (Articles 34 and 37)
(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 24-25) and Chapter IV (Article 43)
(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) 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
(5) (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 II (Articles 3, 4, and 8) and Chapter V (Article 35)
Summary

Overview

In accordance with the NMPA-GCPs and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum), 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. 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 per the NMPA-GCPs, the IP pre-clinical study documents supplied by the sponsor must 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.

As specified in the ICH-GCPs-Addendum, 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 ICH-GCPs-Addendum for detailed content guidelines.

In addition, the NMPA-GCPs states that the sponsor must also supply the investigator(s) with the IP, reference product, comparator, or placebo. As per the NMPA-GCPs, the sponsor should also ensure that the products are manufactured in accordance with Good Manufacturing Practices (GMP) as laid down in the NMPA-GMPs and the NMPA-GMPsAmnd. (See Investigational Products topic, Product Management subtopic for additional information on IP supply, storage, and handling requirements).

Certificate of Analysis and Drug Manufacturing Certificate Requirements

In accordance with the DAL and the RegImplemDAL, the National Medical Products Administration (NMPA) (the Chinese name translates as “State Drug Administration”) requires the drug testing institute, the National Institutes for Food and Drug Control (NIFDC), or a corresponding institute on the provincial, autonomous regional, or municipal level to issue a Certificate of Analysis (CoA) once sample testing and specifications verification have been completed for the IP. The CoA must be submitted to the Center for Drug Evaluation (CDE) as part of the NMPA review and approval process. (See Clinical Trial Lifecycle topic, Submission Process and Submission Content subtopics for detailed application requirements).

In addition, as per the DAL and the RegImplemDAL, drug manufacturers are required to obtain a Drug Manufacturing Certificate from the NMPA and comply with applicable GMP requirements as laid down in the NMPA-GMPs and the NMPA-GMPsAmnd in order to manufacture all IPs. When applying for clinical trials, the applicant must provide proof documents issued by drug regulatory authorities of the manufacturing country or region to prove GMP compliance of the manufacturers.

Per the ICH-GCPs-Addendum, 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
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 7
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Supply
Investigational Products > Labeling & Packaging
Last content review/update: July 06, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 6 (Article 37) and Chapter 10 (Article 57)
(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) (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)
(4) (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 VI
Summary

Overview

Investigational product (IP) labeling in China must comply with the requirements set forth in the NMPA-GCPs, the ProvLabel, the DAL, the RegImplemDAL, and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum). 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-GCPs, 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 ICH-GCPs-Addendum states 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 Product topic, Product Management subtopic for additional information on IP labeling requirements).

Additional Resources
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 5.13
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Labelling
Investigational Products > Product Management
Last content review/update: April 16, 2020
Requirements
(1) (Guidance) China Good Clinical Practice (NMPA-GCPs – Standard Chinese) (Effective September 1, 2003)
National Medical Products Administration, State Administration for Market Regulation, State Council
Relevant Sections: Chapter 2 (Article 7), Chapter 3 (Article 10), Chapter 4 (Article 17), Chapter 6 (Articles 35 and 43), Chapter 8 (Article 52), and Appendix 2
(2) (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
(3) (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
(4) (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)
Summary

Overview

In accordance with the NMPA-GCPs and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (ICH-GCPs-Addendum), 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

As defined in the NMPA-GCPs and the ICH-GCPs-Addendum, the sponsor must supply the investigator(s) with the IP, reference product, and the comparator or placebo.

Per the NMPA-GCPs and the ICH-GCPs-Addendum, the sponsor must ensure the following:

  • 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-GCPs and the ICH-GCPs-Addendum 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 sponsor is required to keep the clinical trial data for five (5) years after approval of the IP for marketing. In addition, all of the trial data must be stored and managed as delineated in Appendix 2 of the NMPA-GCPs.

Additional Resources
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 5.5, 5.12, 5.13, 5.14, and 7
Wang, Katherine and Wu, Tina; Ropes & Gray
Relevant Sections: Are any legislative changes proposed or expected in the near future?
Specimens > Definition of Specimen
Last content review/update: April 16, 2020
Requirements
(1) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (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
(A) (Website) Ministry of Science and Technology Government Service Platform (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Bavasi, H., Thornton, L., Peloquin, D., and Barnes, M.; Medical Research Law & Policy Report, Bloomberg Law
Specimens > Specimen Import & Export
Last content review/update: April 16, 2020
Requirements
(1) (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
(2) (Regulation) AQSIQ Decree No. 160 on Inbound/Outbound Special Articles Quarantine Regulations (AQSIQ-No160) (Effective March 1, 2015)
General Administration of Quality Supervision, Inspection & Quarantine
Relevant Sections: Chapters 1 and 2
(3) (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
(4) (Regulation) Notice on the Opening and Operation of the Online Declaration System for the Collection, Trading, Export and Exit Approval of Human Genetic Resources (State Science and Technology Office Letter No. 758) (S&T-Circular-HGRNo758 – Standard Chinese) (October 14, 2016)
Ministry of Science and Technology
(5) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: 4 and 27
(6) (Regulation) Human Genetic Resources – Materials Exit Approval (HGR-ExitLicenseServiceGuide – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 1-19 and all attachments
(7) (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
Summary

Overview

Per the QuarantineLaw, the AQSIQ-No160, and Additional Resource (A), 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 Additional Resource (B), 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 Additional Resource (A 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.

Per S&T-Circular-HGRNo758, those seeking to collect and export human genetic resources must submit an online declaration through the National Science and Technology Management Information System Declaration Center (Additional Resource (F)). Declarations by mail will no longer be accepted.

As delineated in MgmtHumanGen and the HGR-ExitLicenseServiceGuide, the export of China HGR materials in approved international collaborations are subject to prior approval by the Ministry of Science and Technology (MOST). The applicant may apply for the export license separately, or with the application for international cooperative research. (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-ExitLicenseServiceGuide, 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-ExitLicenseServiceGuide and Additional Resource (C), the following must be submitted:

  • Application (see Additional Resource (C) 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-ExitLicenseServiceGuide, the applicant submits the electronic version of the materials through the online platform at Additional Resource (D). 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 (Additional Resource (E)), 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
(A) (Website) Sanitary Quarantine Approval for Special Items (Current as of April 16, 2020)
General Administration of Customs
General Administration of Quality Supervision, Inspection & Quarantine
(C) (Website) Integrated System Catalogue, Human Genetic Resource Management (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Relevant Sections: China's human genetic resources materials exit approval
(D) (Website) Ministry of Science and Technology Government Service Platform (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
(E) (Website) Administrative License (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Relevant Sections: Human Genetic Resource Management
(F) (Website) National Science and Technology Management Information System Declaration Center (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Wang, Katherine; Ropes and Gray
Specimens > Consent for Specimen
Last content review/update: April 16, 2020
Requirements
(1) (Regulation) Management of Human Genetic Resources (No. 717) (MgmtHumanGen – Standard Chinese) (Effective July 1, 2019)
Ministry of Science and Technology
Relevant Sections: Chapter IV (Article 31)
(2) (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
(3) (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: 11
(4) (Regulation) Human Genetic Resources – Collection Service Guidelines for Administrative Licensing Matters (HGR-Collection – Standard Chinese) (Date Unavailable)
Ministry of Science and Technology
Relevant Sections: 11
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, and HGR-Collection, MOST, through its experts, is responsible for reviewing and approving license applications to collect HGR and conduct international collaborative projects using Chinese HGR. Per Additional Resource (A), the applicant’s submission 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
(A) (Website) Integrated System Catalogue, Human Genetic Resource Management (Standard Chinese) (Current as of April 16, 2020)
Ministry of Science and Technology
Bavasi, H., Thornton, L., Peloquin, D., and Barnes, M.; Medical Research Law & Policy Report, Bloomberg Law
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)

New Requirements

The NMPA has recently released the following requirements, which the ClinRegs team is reviewing and will incorporate into the China profile this year.

  • Drug Clinical Trial Registration and Information Disclosure Management (No. 9 of 2020) (NMPA-No9-2020 – Standard Chinese) (Effective July 1, 2020)

  • Safety Information Evaluation and Management During Drug Clinical Trials (No. 5 of 2020) (NMPA-No5-2020 – Standard Chinese) (Effective July 1, 2020)

  • Management of Safety Update Reports During R&D (No. 7 of 2020) (NMPA-No7-2020 – Standard Chinese) (Effective July 1, 2020)

  • Registration Classification and Application Information Requirements for Biological Products (No. 43 of 2020) (NMPA-No43-2020 – Standard Chinese) (Effective July 1, 2020 (registration) and October 1, 2020 (application))

  • Guidelines for the Preservation of Essential Documents for Drug Clinical Trials (No. 37 of 2020) (NMPA-No37-2020 – Standard Chinese) (Effective July 1, 2020)

  • Quality Management Practices for Drug Clinical Trials (No. 57 of 2020) (NMPA-GCP-No57-2020 – Standard Chinese) (Effective July 1, 2020)

  • Measures for the Supervision and Administration of Drug Production (No. 28 of 2020) (NMPA-No28-2020 – Standard Chinese) (Effective July 1, 2020)

  • Working Procedures for Review of Breakthrough Therapeutics (No. 82 of 2020) (NMPA-No82-2020 – Standard Chinese) (Effective July 8, 2020)

  • Guidelines for Submission of Drug Clinical Trial Data (No. 16 of 2020) (NMPA-No16-2020 – Standard Chinese) (Effective October 1, 2020)

  • Requirements for Drug Records and Data Management for Trial Implementation (No. 74 of 2020) (NMPA-No74-2020 – Standard Chinese) (Effective December 1, 2020)

This message was updated on August 18, 2020
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