National Medical Products Administration and National Health Commission Announcement on the Release of Good Clinical Practice for Drug Trials (2020 No. 57)

Announcement by the National Medical Products Administration and the National Health Commission on the Release of the Good Clinical Practice for Drugs (2020 No. 57 of the Year )

　 To deepen the reform of the drug review and approval system, encourage innovation, further promote the standardized research and quality improvement of drug clinical trials in China, the National Medical Products Administration, together with the National Health Commission, has organized the revision of the "Good Clinical Practice for Drugs," which is hereby released and shall be implemented from July 1, 2020. Effective from July 1, 2020.
　　Hereby announced.

　　National Medical Products Administration National Health Commission
　　　　　　　　　　　　　　　2020 April 23, Year

Good Clinical Practice for Drugs

 

Chapter 1  General Provisions

Article 1   To ensure the standardization of the drug clinical trial process, the scientific, authentic, and reliable nature of data and results, and to protect the rights and safety of subjects, this standard is formulated in accordance with the "Drug Administration Law of the People's Republic of China," "Vaccine Administration Law of the People's Republic of China," and the "Implementation Regulations of the Drug Administration Law of the People's Republic of China." This standard applies to drug clinical trials conducted for drug registration applications. Related activities of drug clinical trials shall comply with this standard.

Article 2   The Good Clinical Practice for Drugs is the quality standard for the entire process of drug clinical trials, including protocol design, organization and implementation, monitoring, auditing, recording, analysis, summary, and reporting.

Article 3   Drug clinical trials shall comply with the principles of the "Declaration of Helsinki of the World Medical Association" and related ethical requirements. The rights and safety of subjects are the primary considerations, taking precedence over scientific and social benefits. Ethical review and informed consent are important measures to protect the rights of subjects.

Article 4   Drug clinical trials shall have sufficient scientific basis. Clinical trials shall weigh the expected risks and benefits to subjects and society, and may only be conducted or continued when the expected benefits outweigh the risks.

Article 5   The trial protocol shall be clear, detailed, and operable. The trial protocol may only be executed after obtaining approval from the ethics committee.

Article 6   Researchers shall comply with the trial protocol during the clinical trial process. Any medical judgment or clinical decision shall be made by clinical doctors. Personnel participating in the implementation of clinical trials shall have the education, training, and experience necessary to undertake clinical trial work.

Article 7   All paper or electronic materials of clinical trials shall be properly recorded, processed, and preserved, capable of accurate reporting, interpretation, and verification. The privacy of subjects and the confidentiality of their related information shall be protected.

Article 8   The preparation of investigational drugs shall comply with the relevant requirements of Good Manufacturing Practice for clinical trial drugs. The use of investigational drugs shall comply with the trial protocol.

Article 9   The quality management system of clinical trials shall cover the entire process of clinical trials, focusing on subject protection, reliability of trial results, and compliance with relevant laws and regulations.

Article 10   The implementation of clinical trials shall comply with the principle of avoiding conflicts of interest.

 

Chapter 2  Terms and Definitions

Article 11   The meanings of the following terms in this standard are:

(1) Clinical trial refers to trials conducted on humans (patients or healthy subjects) aimed at discovering or verifying the clinical medical, pharmacological, and other pharmacodynamic effects, adverse reactions of an investigational drug, or the absorption, distribution, metabolism, and excretion of the investigational drug, to determine the efficacy and safety of the drug through systematic testing.

(2) Compliance in clinical trials refers to all parties involved in the clinical trial adhering to the requirements related to the clinical trial, this standard, and relevant laws and regulations.

(3) Non-clinical research refers to biomedical research not conducted on humans.

(4) Independent Data Monitoring Committee (Data and Safety Monitoring Committee, Monitoring Committee, Data Monitoring Committee) refers to an independent committee established by the sponsor that regularly evaluates the progress, safety data, and important efficacy endpoints of the clinical trial and advises the sponsor on whether to continue, adjust, or stop the trial.

(5) Ethics Committee refers to a committee composed of personnel from medical, pharmaceutical, and other backgrounds, whose responsibility is to independently review, approve, and follow up on the trial protocol and related documents, and the methods and materials used to obtain and record informed consent from subjects, ensuring the protection of subjects' rights and safety.

(6) Investigator refers to the person responsible at the trial site who conducts the clinical trial and is responsible for the quality of the clinical trial and the rights and safety of subjects.

(7) Sponsor refers to the individual, organization, or institution responsible for initiating, managing, and providing funding for the clinical trial.

(8) Contract Research Organization refers to an entity authorized by contract to perform certain duties and tasks of the sponsor or investigator in the clinical trial.

(9) Subject refers to a person participating in a clinical trial and receiving the investigational drug, including patients and healthy subjects.

(10) Vulnerable subjects refer to subjects who lack or have lost the ability to protect their own will and rights, whose voluntary participation in clinical trials may be improperly influenced by the expected benefits of the trial or fear of retaliation for refusal. This includes: students and subordinates of investigators, employees of sponsors, military personnel, prisoners, patients with incurable diseases, patients in critical condition, residents of welfare institutions, homeless persons, minors, and persons incapable of giving informed consent.

(11) Informed consent refers to the process by which subjects are informed of all aspects that may affect their decision to participate in the clinical trial and confirm their voluntary agreement to participate. This process shall be documented by a written informed consent form signed and dated by the subject.

(12) Impartial Witness: An individual unrelated to the clinical trial and not unfairly influenced by personnel involved in the clinical trial, who, when the subject or their guardian is illiterate, acts as an impartial witness to read the informed consent form and other written materials and to witness the informed consent.

(13) Monitoring: The action of supervising the progress of a clinical trial to ensure that it is conducted, recorded, and reported in accordance with the trial protocol, standard operating procedures, and relevant laws and regulations.

(14) Monitoring Plan: A document describing the monitoring strategy, methods, responsibilities, and requirements.

(15) Monitoring Report: A written report submitted by the monitor to the sponsor after each on-site visit or other clinical trial-related communication, as stipulated by the sponsor's standard operating procedures.

(16) Audit: A systematic and independent examination of clinical trial-related activities and documents to assess whether the implementation of clinical trial activities, recording, analysis, and reporting of trial data comply with the trial protocol, standard operating procedures, and relevant laws and regulations.

(17) Audit Report: A written evaluation report on audit results prepared by an auditor appointed by the sponsor.

(18) Inspection: The act by the drug regulatory authority to review and inspect relevant documents, facilities, records, and other aspects of a clinical trial. Inspections can be conducted at the trial site, the sponsor's or contract research organization's location, or other places deemed necessary by the regulatory authority.

(19) Direct Access: The direct examination, analysis, verification, or copying of important records and reports for evaluating drug clinical trials. Any party conducting direct access must take reasonable measures according to relevant laws and regulations to protect the privacy of subjects and prevent disclosure of the sponsor's proprietary and other confidential information.

(20) Trial Protocol: A document describing the objectives, design, methodology, statistical considerations, and organization of a clinical trial. The protocol usually also includes the background and theoretical basis of the clinical trial, which may also be provided in other reference documents. The protocol includes the original and its amendments.

(21) Investigator's Brochure: A compilation of clinical and non-clinical research data related to the investigational medicinal product used in the clinical trial.

(22) Case Report Form: A paper or electronic document designed according to the trial protocol requirements to report subject-related information to the sponsor.

(23) Standard Operating Procedures: Detailed written requirements established to ensure consistency in performing a specific operation.

(24) Investigational Medicinal Product: The investigational drug and comparator drug used in a clinical trial.

(25) Comparator Drug: Other investigational drugs, marketed drugs, or placebos used in clinical trials for comparison with the investigational drug.

(26) Adverse Event: Any unfavorable medical occurrence in a subject administered an investigational medicinal product, which may manifest as symptoms, signs, diseases, or abnormal laboratory findings, but not necessarily causally related to the investigational product.

(27) Serious Adverse Event: An adverse medical event occurring after administration of an investigational medicinal product that results in death, is life-threatening, causes permanent or severe disability or loss of function, requires hospitalization or prolongation of existing hospitalization, or involves congenital anomaly or birth defect.

(28) Adverse Drug Reaction: Any harmful or unintended response to an investigational medicinal product occurring during a clinical trial, where there is at least a reasonable possibility of a causal relationship between the investigational product and the adverse event, meaning the association cannot be ruled out.

(29) Suspected Unexpected Serious Adverse Reaction: A serious adverse reaction whose nature and severity exceed those described in the investigator's brochure, marketed drug labeling, or summary of product characteristics, and is both suspected and unexpected.

(30) Subject Identification Code: A unique code assigned to a subject in a clinical trial to identify their identity. Researchers use this code instead of the subject's name when reporting adverse events and other trial-related data to protect privacy.

(31) Source Documents: Original records, documents, and data generated during a clinical trial, such as hospital medical records, medical images, laboratory records, memos, subject diaries or assessment forms, dispensing records, instrument-generated data, microfilms, photographic negatives, magnetic media, X radiographs, subject files, and clinical trial-related documents and records maintained by pharmacy, laboratory, and medical technology departments, including verified copies. Source documents include source data and may exist in paper or electronic form.

(32) Source Data: All information recorded in original records or verified copies related to a clinical trial, including clinical findings, observations, and other activities necessary to reconstruct and evaluate the clinical trial.

(33) Essential Documents: Documents that individually or collectively allow evaluation of the conduct of a clinical trial and the quality of the data produced.

(34) Verified Copy: A copy that has been reviewed and verified to be identical in content and structure to the original, signed and dated by the reviewer or generated directly by a validated system, and may exist in paper or electronic form.

(35) Quality Assurance: Planned and systematic actions established in a clinical trial to ensure that the trial is conducted and data are generated, recorded, and reported in compliance with the protocol and applicable laws and regulations.

(36) Quality Control: Technical and operational activities implemented within the quality assurance system of a clinical trial to verify that all trial-related activities meet quality requirements.

(37) Trial Site: The location where clinical trial-related activities are conducted.

(38) Blinding: The procedure in a clinical trial by which one or more parties are kept unaware of the treatment assignments. Single-blind usually means the subject is unaware; double-blind means the subject, investigator, monitor, and data analyst are all unaware of the treatment assignments.

(39) Computerized System Validation: The process of establishing and documenting that a computerized system throughout its lifecycle—from design to decommissioning or transition to another system—meets specified requirements. The validation plan should be based on a risk assessment considering the system's intended use, potential impact on subject protection, and reliability of clinical trial results.

(40) Audit Trail: Records that allow reconstruction and traceability of the sequence of events.

 

Chapter 3  Ethics Committee

Article 12   The responsibility of the Ethics Committee is to protect the rights and safety of subjects, with special attention to vulnerable subjects.

(1) Documents that the Ethics Committee should review include: trial protocols and protocol amendments; informed consent forms and their updates; methods and information for recruiting subjects; other written materials provided to subjects; investigator's brochure; existing safety data; documents containing subject compensation information; proof of investigator qualifications; and other documents necessary for the Ethics Committee to fulfill its duties.

(2) The Ethics Committee should review the scientific and ethical aspects of the clinical trial.

(3) The Ethics Committee should review the qualifications of the investigators.

(4) To better assess whether the rights and safety of subjects and basic medical care can be ensured in clinical trials, the Ethics Committee may request information and materials beyond the content of the informed consent form.

(5) When conducting non-therapeutic clinical trials (i.e., trials without expected direct clinical benefit to subjects), if the informed consent of the subject is given by their guardian, the Ethics Committee should pay special attention to whether the trial protocol sufficiently considers the corresponding ethical issues and laws and regulations.

(6) If the trial protocol clearly states that in emergency situations the subject or their guardian cannot sign the informed consent form before the trial, the Ethics Committee should review whether the trial protocol sufficiently considers the corresponding ethical issues and laws and regulations.

(7) The Ethics Committee should review whether subjects are forced, induced, or otherwise improperly influenced to participate in the clinical trial. The Ethics Committee should review that the informed consent form does not contain content that causes subjects or their guardians to waive their legal rights, nor content that exempts investigators, clinical trial institutions, sponsors, and their agents from their responsibilities.

(8) The Ethics Committee should ensure that the informed consent form and other written materials provided to subjects explain the information about compensation to subjects, including the method, amount, and plan of compensation.

(9) The Ethics Committee should complete the review or filing process of clinical trial-related materials within a reasonable time limit and provide clear written review opinions. The review opinions should include the name of the clinical trial reviewed, documents (including version numbers), and dates.

(10) The Ethics Committee's review opinions include: approval; approval after necessary modifications; disapproval; termination or suspension of approved studies. The review opinions should specify the required modifications or reasons for disapproval.

(11) The Ethics Committee should pay attention to and explicitly require investigators to promptly report: deviations or modifications of the trial protocol implemented to eliminate urgent harm to subjects; changes that increase subject risk or significantly affect the implementation of the clinical trial; all suspected and unexpected serious adverse reactions; new information that may adversely affect subject safety or the conduct of the clinical trial.

(12) The Ethics Committee has the authority to suspend or terminate clinical trials that are not conducted according to relevant requirements or where subjects experience unexpected serious harm.

(13) The Ethics Committee should conduct regular follow-up reviews of ongoing clinical trials, with the frequency of review determined by the risk level to subjects, but at least once a year.

(14) The Ethics Committee should accept and properly handle relevant complaints from subjects.

Article 13   The composition and operation of the Ethics Committee should meet the following requirements:

(1) The composition of the Ethics Committee members and filing management should comply with the requirements of the health administrative department.

(2) All members of the Ethics Committee should receive training in ethical review and be capable of reviewing ethical and scientific issues related to clinical trials.

(3) The Ethics Committee should perform its duties according to its system and standard operating procedures, with written records of reviews indicating meeting times and discussion content.

(4) Voting members of the Ethics Committee should participate in the review and discussion during meetings, including members from various categories, with different gender composition, and meeting the required number. Meeting review opinions should be documented in writing.

(5) Members who vote or provide review opinions should be independent of the clinical trial project under review.

(6) The Ethics Committee should have detailed information about its members and ensure that members are qualified for ethical review.

(7) The Ethics Committee should require investigators to provide various materials needed for ethical review and answer questions raised by the Ethics Committee.

(8) The Ethics Committee may invite relevant experts outside the members to participate in the review as needed, but they cannot participate in voting.

Article 14   The Ethics Committee should establish and implement the following written documents:

(1) Regulations on the composition, formation, and filing of the Ethics Committee.

(2) Procedures for scheduling Ethics Committee meetings, meeting notifications, and review processes.

(3) Procedures for initial review and follow-up review by the Ethics Committee.

(4) Procedures for expedited review and approval of minor amendments to approved trial protocols by the Ethics Committee.

(5) Procedures for timely notification of review opinions to investigators.

(6) Procedures for re-review in case of differing opinions on ethical review decisions.

Article 15   The Ethics Committee should retain all records of ethical reviews, including written records of ethical reviews, member information, submitted documents, meeting minutes, and related correspondence. All records should be kept for at least until the clinical trial ends. 5 Researchers, sponsors, or drug regulatory authorities may request the Ethics Committee to provide its standard operating procedures and the list of ethical review members.

 

Chapter 4  Investigators

Article 16   Qualifications and requirements that investigators and clinical trial institutions should possess include:

(1) Possess practicing qualifications at the clinical trial institution; have the professional knowledge, training experience, and ability required for clinical trials; and be able to provide the latest work resume and relevant qualification documents according to the requirements of sponsors, Ethics Committees, and drug regulatory authorities.

(2) Be familiar with the trial protocol, investigator's brochure, and information related to the investigational drug provided by the sponsor.

(3) Be familiar with and comply with this standard and relevant laws and regulations on clinical trials.

(4) Keep a copy of the delegation of duties authorization form signed by the investigator.

(5) Investigators and clinical trial institutions shall accept monitoring and auditing organized by the sponsor, as well as inspections by drug regulatory authorities.

(6) When investigators and clinical trial institutions authorize individuals or units to undertake responsibilities and functions related to clinical trials, they shall ensure that these parties have the corresponding qualifications and establish complete procedures to ensure the execution of clinical trial-related duties and functions, producing reliable data. Authorization of units outside the clinical trial institution to undertake trial-related responsibilities and functions must obtain the sponsor's consent.

Article 17   Investigators and clinical trial institutions shall have the necessary conditions to complete the clinical trial:

(1) Investigators have the ability to enroll a sufficient number of subjects within the agreed trial period according to the trial protocol.

(2) Investigators have sufficient time to implement and complete the clinical trial within the agreed trial period.

(3) Investigators have the authority to manage personnel participating in the clinical trial during the trial period and have access to the medical facilities required for the clinical trial to conduct it correctly and safely.

(4) Investigators ensure that all personnel participating in the clinical trial fully understand the trial protocol and investigational drugs, clearly define their respective roles and responsibilities in the trial, and ensure the authenticity, completeness, and accuracy of clinical trial data.

(5) Investigators supervise all research personnel in executing the trial protocol and take measures to implement quality management of the clinical trial.

(6) Clinical trial institutions shall establish corresponding internal management departments responsible for the management of clinical trials.

Article 18   Investigators shall provide appropriate medical treatment to subjects:

(1) Investigators who are clinical doctors or authorized clinical doctors shall bear all medical decision-making responsibilities related to the clinical trial.

(2) During the clinical trial and follow-up period, for adverse events related to the trial, including clinically significant laboratory abnormalities, investigators and clinical trial institutions shall ensure that subjects receive proper medical treatment and truthfully inform the subjects of the relevant situation. When investigators become aware that subjects have comorbidities requiring treatment, they shall inform the subjects and pay attention to concomitant medications that may interfere with clinical trial results or subject safety.

(3) With the subject's consent, investigators may inform relevant clinical doctors about the subject's participation in the trial.

(4) Subjects may withdraw from the clinical trial without reason. While respecting the personal rights of subjects, investigators should try to understand the reasons for withdrawal.

Article 19   Communication between investigators and the ethics committee includes:

(1) Before implementing the clinical trial, investigators shall obtain written consent from the ethics committee; subjects cannot be screened before obtaining the ethics committee's written consent.

(2) Before and during the clinical trial, investigators shall provide the ethics committee with all documents required for ethical review.

Article 20   Investigators shall comply with the trial protocol.

(1) Investigators shall conduct the clinical trial according to the trial protocol approved by the ethics committee.

(2) Without the consent of the sponsor and ethics committee, investigators shall not modify or deviate from the trial protocol, except for changes related only to clinical trial management such as timely elimination of urgent hazards to subjects or replacement of monitors, phone numbers, etc.

(3) Investigators or their designated research personnel shall record and explain deviations from the trial protocol.

(4) To eliminate urgent hazards to subjects, if investigators modify or deviate from the trial protocol without ethics committee consent, they shall promptly report to the ethics committee and sponsor with reasons, and report to the drug regulatory authority if necessary.

(5) Investigators shall take measures to avoid the use of concomitant medications prohibited by the trial protocol.

Article 21   Investigators and clinical trial institutions have management responsibilities for investigational drugs provided by the sponsor.

(1) Investigators and clinical trial institutions shall appoint qualified pharmacists or other personnel to manage investigational drugs.

(2) The receipt, storage, distribution, recovery, return, and disposal of unused investigational drugs at clinical trial institutions shall comply with relevant regulations and be recorded.

Records of investigational drug management shall include date, quantity, batch number, / serial number, expiration date, allocation code, signature, etc. Investigators shall keep records of the quantity and dosage of investigational drugs used by each subject. The quantity used and remaining shall be consistent with the quantity provided by the sponsor.

(3) Storage of investigational drugs shall comply with corresponding storage conditions.

(4) Investigators shall ensure investigational drugs are used according to the trial protocol and explain the correct usage to subjects.

(5) Investigators shall randomly sample and retain investigational drugs used in bioequivalence trials. Clinical trial institutions shall keep retained samples for at least years after drug marketing. 2 Clinical trial institutions may entrust qualified independent third parties to store retained samples but shall not return them to the sponsor or third parties related to the sponsor's interests.

Article 22   Investigators shall comply with the randomization procedures of the clinical trial.

Blinded trials shall implement unblinding according to the trial protocol requirements. In case of accidental unblinding or emergency unblinding due to serious adverse events, investigators shall provide a written explanation to the sponsor.

Article 23   Researchers implementing informed consent shall comply with the ethical principles of the Declaration of Helsinki and meet the following requirements:

(1) Researchers shall use the latest version of the informed consent form and other information provided to subjects approved by the ethics committee. If necessary, subjects in the clinical trial process shall re-sign the informed consent form.

(2) When researchers obtain new information that may affect the subject's continued participation in the trial, they shall promptly inform the subject or their guardian and make corresponding records.

(3) Researchers shall not use improper methods such as coercion or inducement to influence subjects to participate in or continue clinical trials.

(4) Researchers or designated research personnel shall fully inform subjects of all relevant matters concerning the clinical trial, including written information and the ethics committee's consent opinions.

(5) Both oral and written materials provided to subjects, such as the informed consent form, shall use plain and understandable language and expressions to facilitate understanding by subjects or their guardians and witnesses.

(6) Before signing the informed consent form, researchers or designated research personnel shall give subjects or their guardians sufficient time and opportunity to understand the details of the clinical trial and answer in detail any questions related to the clinical trial raised by the subjects or their guardians.

(7) Subjects or their guardians, as well as the researchers executing the informed consent, shall sign and date the informed consent form respectively. If the signer is not the subject themselves, the relationship shall be noted.

(8) If the subject or their guardian lacks reading ability, a fair witness shall witness the entire informed consent process. Researchers shall explain the content of the informed consent form and other written materials in detail to the subject or their guardian and the witness. If the subject or their guardian agrees orally to participate in the trial, they should sign the informed consent form as much as possible if capable. The witness shall also sign and date the informed consent form to certify that the subject or their guardian has been accurately explained the informed consent form and other written materials by the researcher, understands the relevant content, and agrees to participate in the clinical trial.

(9) Subjects or their guardians shall receive the original or a copy of the signed and dated informed consent form and other written materials provided to the subjects, including the original or copy of the updated informed consent form and revised texts of other written materials provided to the subjects.

(10) If the subject lacks civil capacity, written informed consent shall be obtained from their guardian; if the subject has limited civil capacity, written informed consent shall be obtained from both the subject and their guardian. When the guardian consents on behalf of the subject, the subject shall be informed of relevant clinical trial information within their understanding, and the subject should sign and date the informed consent form personally as much as possible.

(11) In emergency situations where informed consent cannot be obtained from the subject before participating in the clinical trial, the guardian may provide informed consent on behalf of the subject. If the guardian is also absent, the subject's inclusion method shall be clearly stated in the trial protocol and other documents and obtain written consent from the ethics committee; meanwhile, informed consent allowing the subject or their guardian to continue participation in the clinical trial shall be obtained as soon as possible.

(12) When subjects participate in non-therapeutic clinical trials, the subjects themselves shall sign and date the informed consent form.

Non-therapeutic clinical trials may be consented to by guardians on behalf of subjects only if the following conditions are met: the clinical trial can only be conducted on subjects without the capacity to give informed consent; the expected risk to subjects is low; negative impacts on subjects' health have been minimized, and laws and regulations do not prohibit such clinical trials; the inclusion of such subjects has been reviewed and approved by the ethics committee. Such clinical trials should, in principle, only be conducted on patients with diseases or conditions applicable to the investigational drug. Subjects should be closely monitored during the clinical trial, and if they exhibit excessive pain or discomfort, they should be withdrawn from the trial and given necessary treatment to ensure their safety.

(13) The medical history records shall document the specific time and personnel involved in obtaining the subject's informed consent.

(14) When children are subjects, informed consent shall be obtained from their guardians and signed. When children are capable of making decisions to consent to participate in clinical trials, their own consent shall also be obtained. If the child subject does not agree to participate or decides to withdraw midway, the child's decision shall prevail even if the guardian has consented or wishes to continue participation, except in therapeutic clinical trials for severe or life-threatening diseases where the researcher and guardian believe that not participating would endanger the child's life; in such cases, the guardian's consent allows the child to continue participation. During the clinical trial, if the child subject reaches the condition to sign informed consent, they must sign it personally before continuing.

Article 24   The informed consent form and other materials provided to subjects shall include:

(1) Overview of the clinical trial.

(2) Purpose of the trial.

(3) Trial treatment and the possibility of random assignment to different groups.

(4) Trial procedures that subjects need to follow, including invasive medical procedures.

(5) Obligations of the subjects.

(6) Experimental content involved in the clinical trial.

(7) Risks or inconveniences that the trial may cause to subjects, especially risks affecting embryos, fetuses, or nursing infants.

(8) Expected benefits of the trial and the possibility of no benefit.

(9) Other available drugs and treatment methods, along with their important potential benefits and risks.

(10) Compensation and treatment available if subjects suffer trial-related harm.

(11) Compensation that subjects may receive for participating in the clinical trial.

(12) Expected expenses for subjects participating in the clinical trial.

(13) Participation in the trial is voluntary; subjects may refuse to participate or have the right to withdraw at any stage without discrimination or retaliation, and their medical treatment and rights will not be affected.

(14) Without violating confidentiality principles and relevant regulations, monitors, auditors, ethics committees, and drug regulatory authorities' inspectors may review the subject's original medical records to verify the clinical trial process and data.

(15) Confidentiality of subject-related identity verification records shall not be publicly used. If clinical trial results are published, the subject's identity information remains confidential.

(16) When new information that may affect the subject's continued participation in the trial arises, the subject or their guardian shall be promptly informed.

(17) When there are issues related to trial information and subject rights, or when trial-related harm occurs, the contact information of the researcher and ethics committee that the subject can reach out to shall be provided.

(18) Situations and reasons under which the subject may be terminated from the trial.

(19) The expected duration of the subject's participation in the trial.

(20) The expected number of subjects participating in the trial.

Article 25   Records and reports of the trial shall meet the following requirements:

(1) The researcher shall supervise data collection at the trial site and the performance of duties by all research personnel.

(2) The researcher shall ensure that all clinical trial data are obtained from the trial's source documents and records, and that they are accurate, complete, legible, and timely. Source data shall be attributable, legible, contemporaneous, original, accurate, complete, consistent, and durable. Modifications to source data shall be traceable, must not obscure the original data, and the reasons for modifications shall be recorded. For clinical trials involving patients as subjects, relevant medical records shall be entered into outpatient or inpatient medical record systems. When the clinical trial institution's information system supports establishing electronic clinical trial medical records, the researcher shall preferentially use it. The corresponding computerized system shall have comprehensive access control and audit trails, traceable to the creator or modifier of the records, ensuring the traceability of collected source data.

(3) The researcher shall fill out and modify case report forms according to the sponsor's provided instructions, ensuring that data in all case report forms and other reports are accurate, complete, clear, and timely. Data in case report forms shall be consistent with source documents; if inconsistencies exist, reasonable explanations shall be provided. Modifications to data in case report forms shall keep the original records clearly identifiable, retain modification trails, explain reasons if necessary, and be signed and dated by the modifier.

The sponsor shall have written procedures to ensure that changes to case report forms are necessary, recorded, and agreed upon by the researcher. The researcher shall retain relevant records of modifications and corrections.

(4) Researchers and clinical trial institutions shall properly preserve trial documents in accordance with " Essential Documents for Clinical Trials ” and the relevant requirements of drug regulatory authorities.

(5) During the processing of clinical trial information and subject information, attention shall be paid to avoiding illegal or unauthorized access, disclosure, dissemination, modification, destruction, or loss of information. The recording, processing, and storage of clinical trial data shall ensure the confidentiality of records and subject information.

(6) The sponsor shall clearly specify in the contract with the researcher and clinical trial institution the retention period, costs, and handling after expiration of essential documents.

(7) According to the requirements of monitors, auditors, ethics committees, or drug regulatory authorities, researchers and clinical trial institutions shall cooperate and provide necessary trial-related records.

Article 26   The researcher's safety reports shall meet the following requirements:

Except for serious adverse events that do not require immediate reporting as specified in the trial protocol or other documents (such as the investigator's brochure), the researcher shall immediately report all serious adverse events in writing to the sponsor and subsequently provide detailed written follow-up reports in a timely manner. Serious adverse event reports and follow-up reports shall indicate the subject's identification code in the clinical trial, rather than the subject's real name, citizen identification number, address, or other identity information. Adverse events and laboratory abnormalities important for safety evaluation as specified in the trial protocol shall be reported to the sponsor according to the protocol's requirements and timelines.

For reports involving death events, the researcher shall provide the sponsor and ethics committee with other required materials, such as autopsy reports and final medical reports.

After receiving relevant safety information about the clinical trial from the sponsor, the researcher shall promptly acknowledge receipt and review it, consider treatment adjustments for subjects if necessary, communicate with subjects as early as possible, and report suspected unexpected serious adverse reactions provided by the sponsor to the ethics committee.

Article 27   When a clinical trial is terminated or suspended early, the researcher shall promptly notify the subjects and provide appropriate treatment and follow-up. Additionally:

(1) If the researcher terminates or suspends the clinical trial without consulting the sponsor, the researcher shall immediately report to the clinical trial institution, sponsor, and ethics committee, providing a detailed written explanation.

(2) If the sponsor terminates or suspends the clinical trial, the researcher shall immediately report to the clinical trial institution and ethics committee, providing a detailed written explanation.

(3) If the ethics committee terminates or suspends an approved clinical trial, the researcher shall immediately report to the clinical trial institution and sponsor, providing a detailed written explanation.

Article 28   The researcher shall provide trial progress reports.

(1) The researcher shall submit an annual report of the clinical trial to the ethics committee or provide progress reports as required by the ethics committee.

(2) If situations arise that may significantly affect the implementation of the clinical trial or increase risks to subjects, the researcher shall promptly report in writing to the sponsor, ethics committee, and clinical trial institution.

(3) After the clinical trial is completed, the researcher shall report to the clinical trial institution; provide a summary of the clinical trial results to the ethics committee; and provide clinical trial-related reports required by the drug regulatory authorities to the sponsor.

 

Chapter 5  Sponsor

Article 29   The sponsor shall consider protecting the rights and safety of subjects and the authenticity and reliability of clinical trial results as fundamental considerations in clinical trials.

Article 30   The sponsor shall establish a quality management system for clinical trials.

The sponsor's quality management system for clinical trials shall cover the entire process of the clinical trial, including the design, implementation, recording, evaluation, result reporting, and document archiving of the clinical trial. Quality management includes effective trial protocol design, methods and processes for data collection, and the collection of information necessary for decision-making during the clinical trial.

Methods for quality assurance and quality control of clinical trials shall correspond to the inherent risks of the clinical trial and the importance of the information collected. The sponsor shall ensure the operability of each stage of the clinical trial, and the trial process and data collection should avoid excessive complexity. The trial protocol, case report forms, and other related documents shall be clear, concise, and consistent.

The sponsor shall fulfill management responsibilities. According to the needs of the clinical trial, a research and management team for the clinical trial may be established to guide and supervise the implementation of the clinical trial. Internal work within the research and management team shall be communicated in a timely manner. During inspections by the drug regulatory authority, members from both the research and management teams shall participate.

Article 31   The sponsor shall conduct quality management based on risk.

(1) When formulating the trial protocol, key aspects and data that protect the rights and safety of subjects and ensure the reliability of clinical trial results shall be clearly defined.

(2) Risks affecting key aspects and data of the clinical trial shall be identified. These risks shall be considered from two levels: the system level, such as facilities and equipment, standard operating procedures, computerized systems, personnel, suppliers; and the clinical trial level, such as investigational drugs, trial design, data collection and recording, informed consent process.

(3) Risk assessment shall consider the likelihood of errors occurring under existing risk controls; the impact of such errors on protecting subjects' rights and safety, as well as data reliability; and the extent to which such errors can be detected.

(4) Risks that can be reduced or accepted shall be identified. Risk reduction control measures shall be reflected in the design and implementation of the trial protocol, monitoring plans, contracts clarifying responsibilities of all parties, compliance with standard operating procedures, and various trainings.

When pre-setting the tolerance for quality risks, the medical and statistical characteristics of variables and statistical design shall be considered to identify systematic issues affecting subject safety and data reliability. If situations exceed the tolerance for quality risks, it shall be evaluated whether further measures are needed.

(5) During the clinical trial, quality management shall be documented and communicated promptly with relevant parties to promote risk assessment and continuous quality improvement.

(6) The sponsor shall regularly evaluate risk control measures by integrating new knowledge and experience gained during the clinical trial to ensure the effectiveness and applicability of the current quality management.

(7) The sponsor shall describe the quality management methods used in the clinical trial report and summarize events of serious deviations from quality risk tolerance and remedial measures.

Article 32   The sponsor's quality assurance and quality control shall meet the following requirements:

(1) The sponsor is responsible for formulating, implementing, and timely updating standard operating procedures for the quality assurance and quality control system of clinical trials to ensure that the implementation of clinical trials, data generation, recording, and reporting comply with the trial protocol, this standard, and relevant laws and regulations.

(2) The entire process of clinical trials and laboratory testing shall strictly follow quality management standard operating procedures. Quality control shall be applied at every stage of data processing to ensure all data are reliable and the data processing is correct.

(3) The sponsor shall sign contracts with investigators, clinical trial institutions, and all other relevant units participating in the clinical trial to clarify the responsibilities of all parties.

(4) Contracts signed by the sponsor with relevant units shall specify that the sponsor's monitoring and auditing, as well as inspections by the drug regulatory authority, may directly access the trial site to review source data, source documents, and reports.

Article 33   The sponsor's delegation to contract research organizations shall meet the following requirements:

(1) The sponsor may delegate part or all of the work and tasks of the clinical trial to a contract research organization, but the sponsor remains ultimately responsible for the quality and reliability of clinical trial data and shall supervise the work undertaken by the contract research organization. The contract research organization shall implement quality assurance and quality control.

(2) Work delegated to the contract research organization by the sponsor shall be governed by a contract. The contract shall specify the delegated specific work and corresponding standard operating procedures; the sponsor's right to verify the execution of standard operating procedures by the delegate; written requirements for the delegate; reporting requirements the delegate must submit to the sponsor; matters related to compensation for subject harm; and other matters related to the delegated work. If the contract research organization subcontracts tasks, it shall obtain the sponsor's written approval.

(3) Work and tasks not explicitly delegated to the contract research organization remain the responsibility of the sponsor.

(4) Requirements for the sponsor in this standard apply to contract research organizations undertaking related work and tasks of the sponsor.

Article 34   The sponsor shall appoint qualified medical experts to provide timely consultation on relevant medical issues of the clinical trial.

Article 35   The sponsor shall select qualified biostatisticians, clinical pharmacologists, and clinicians to participate in the trial, including designing the trial protocol and case report forms, formulating statistical analysis plans, analyzing data, and writing interim and final trial summary reports.

Article 36   The sponsor shall meet the following requirements in trial management, data processing, and record keeping:

(1) The sponsor shall select qualified personnel to supervise the implementation of the clinical trial, data processing, data verification, statistical analysis, and the writing of trial summary reports.

(2) The sponsor may establish an independent data monitoring committee to regularly evaluate the progress of the clinical trial, including safety data and important efficacy endpoint data. The independent data monitoring committee may advise the sponsor on whether to continue, modify, or stop the ongoing clinical trial. The independent data monitoring committee shall have written operating procedures and keep all relevant meeting records.

(3) The electronic data management system used by the sponsor shall undergo reliable system validation, meet pre-set technical performance criteria to ensure the completeness, accuracy, and reliability of trial data, and ensure the system remains in a validated and effective state throughout the trial.

(4) The electronic data management system shall have complete standard operating procedures covering the setup, installation, and use of electronic data management; the standard operating procedures shall specify system validation, functional testing, data collection and processing, system maintenance, system security testing, change control, data backup, recovery, system contingency plans, and software disposal; the standard operating procedures shall clarify the responsibilities of the sponsor, investigator, and clinical trial institution when using computerized systems. All personnel using computerized systems shall be trained.

(5) The methods for modifying computerized system data shall be predetermined, and the modification process shall be fully recorded; original data (such as retaining electronic data audit trails, data trails, and edit trails) shall be preserved; the integration, content, and structure of electronic data shall be clearly defined to ensure data integrity; when changes occur in the computerized system, such as software upgrades or data transfers, ensuring the integrity of electronic data is even more important.

If data conversion occurs during data processing, ensure that the converted data is consistent with the original data and that the data conversion process is visible.

(6) Ensure the security of the electronic data management system so that unauthorized personnel cannot access it; maintain a list of personnel authorized to modify data; electronic data shall be backed up in a timely manner; clinical trials with a blinded design shall always maintain the blind status, including data entry and processing.

(7) The sponsor shall use subject identification codes to identify all clinical trial data for each subject. After unblinding a blinded trial, the sponsor shall promptly inform the investigator in writing of the subject's trial medication status.

(8) The sponsor shall retain clinical trial data related to the sponsor; other data obtained by related units participating in the clinical trial shall also be retained as specific data of the sponsor in the essential clinical trial documents.

(9) If the sponsor suspends or prematurely terminates an ongoing clinical trial, all relevant investigators, clinical trial institutions, and drug regulatory authorities shall be notified.

(10) The transfer of ownership of trial data shall comply with relevant laws and regulations.

(11) The sponsor shall inform investigators and clinical trial institutions in writing of the requirements for retaining trial records; when trial-related records are no longer needed, the sponsor shall also inform investigators and clinical trial institutions in writing.

Article 37   The sponsor's selection of investigators shall meet the following requirements:

(1) The sponsor is responsible for selecting investigators and clinical trial institutions. Investigators shall have undergone clinical trial training, have clinical trial experience, and have sufficient medical resources to complete the clinical trial. For clinical trials involving multiple clinical trial institutions, if a lead unit needs to be selected, the sponsor is responsible.

(2) Sample testing laboratories involving medical judgment shall comply with relevant regulations and possess corresponding qualifications. The management, testing, transportation, and storage of specimens collected in clinical trials shall ensure quality. It is prohibited to conduct biological sample testing unrelated to the trial protocol approved by the ethics committee (such as genetics). After the clinical trial ends, the continued preservation or potential future use of remaining specimens shall be subject to the subject's informed consent, specifying the storage duration, data confidentiality issues, and under what circumstances data and samples may be shared with other researchers.

(3) The sponsor shall provide investigators and clinical trial institutions with the trial protocol and the latest investigator's brochure and shall allow sufficient time for investigators and clinical trial institutions to review the trial protocol and related materials.

Article 38   Before participating in the clinical trial, all parties involved shall have their responsibilities clearly defined by the sponsor and specified in the signed contract.

Article 39   The sponsor shall take appropriate measures to ensure compensation or indemnification can be provided to subjects and investigators.

(1) The sponsor shall provide investigators and clinical trial institutions with legal and financial insurance or guarantees related to the clinical trial, appropriate to the nature and degree of risk of the clinical trial. This does not include damages caused by the negligence of investigators and clinical trial institutions themselves.

(2) The sponsor shall bear the medical treatment costs and corresponding compensation for damages or death related to the clinical trial experienced by subjects. The sponsor and investigators shall promptly pay compensation or indemnification to subjects.

(3) The methods and means by which the sponsor provides compensation to subjects shall comply with relevant laws and regulations.

(4) The sponsor shall provide trial medications free of charge to subjects and pay for medical testing fees related to the clinical trial.

Article 40   Contracts signed between the sponsor, investigators, and clinical trial institutions shall clearly define the responsibilities, rights, and interests of all parties involved in the trial, as well as potential conflicts of interest to be avoided. The trial funding shall be reasonable and comply with market principles. The sponsor, investigators, and clinical trial institutions shall sign the contract to confirm.

The contract content shall include: compliance with this standard and relevant clinical trial laws and regulations during the implementation of the clinical trial; execution of the trial protocol agreed upon by the sponsor and investigators and approved by the ethics committee; adherence to data recording and reporting procedures; agreement to monitoring, auditing, and inspection; preservation and retention period of essential clinical trial documents; provisions regarding publication, intellectual property, etc.

Article 41   Before the clinical trial begins, the sponsor shall submit relevant clinical trial materials to the drug regulatory authority and obtain clinical trial approval or complete the filing. Submitted documents shall indicate version numbers and version dates.

Article 42   The sponsor shall obtain from investigators and clinical trial institutions the name and address of the ethics committee, the list of ethics committee members involved in project review, a statement of compliance with this standard and relevant laws and regulations, as well as ethics committee approval documents and other related materials.

Article 43   When drafting the clinical trial protocol, the sponsor shall have sufficient safety and efficacy data to support the route of administration, dosage, and duration of treatment. When important new information is obtained, the sponsor shall promptly update the investigator's brochure.

Article 44   The preparation, packaging, labeling, and coding of trial medications shall meet the following requirements:

(1) The preparation of investigational drugs shall comply with the relevant requirements of Good Manufacturing Practice for clinical trial drugs; the packaging labels of investigational drugs shall indicate that they are for clinical trial use only, including clinical trial information and investigational drug information; blinding shall be maintained in blinded trials.

(2) The sponsor shall clearly specify the storage temperature, transportation conditions (whether light protection is needed), storage duration, preparation methods and processes of drug solutions, and requirements for infusion devices of investigational drugs. The usage of investigational drugs shall be communicated to all personnel involved in the trial, including monitors, investigators, pharmacists, and drug custodians.

(3) The packaging of investigational drugs shall ensure that the drugs are not contaminated or deteriorated during transportation and storage.

(4) In blinded trials, the coding system of investigational drugs shall include emergency unblinding procedures to quickly identify the type of investigational drug in emergency medical situations without compromising the blinding of the clinical trial.

Article 45   The supply and management of investigational drugs shall meet the following requirements:

(1) The sponsor is responsible for providing investigational drugs to investigators and clinical trial institutions.

(2) Before obtaining approval from the ethics committee and permission or filing from the drug regulatory authority, the sponsor shall not provide investigational drugs to investigators and clinical trial institutions.

(3) The sponsor shall provide written instructions on the use, storage, and related records of investigational drugs to investigators and clinical trial institutions. The sponsor shall establish procedures for the supply and management of investigational drugs, including receipt, storage, distribution, use, and recovery. Investigational drugs recovered from subjects and unused by researchers shall be returned to the sponsor or destroyed by the clinical trial institution authorized by the sponsor.

(4) The sponsor shall ensure timely delivery of investigational drugs to investigators and clinical trial institutions to guarantee timely use by subjects; maintain records of transportation, receipt, distribution, recovery, and destruction of investigational drugs; establish a recovery management system for investigational drugs to ensure recall of defective products, recovery after trial completion, and recovery after expiration; establish a destruction system for unused investigational drugs. All management processes of investigational drugs shall have written records with accurate counts throughout.

(5) The sponsor shall take measures to ensure the stability of investigational drugs during the trial. Retained samples of investigational drugs shall be preserved within the storage period until the completion of clinical trial data analysis or the period required by relevant regulations, whichever is longer if the two differ.

Article 46   The sponsor shall clearly define the access rights to trial records.

(1) The sponsor shall specify in the trial protocol or contract that monitors, auditors, ethics committee reviewers, and drug regulatory inspectors are allowed to directly access the source data and source documents related to the clinical trial at the investigator and clinical trial institution.

(2) The sponsor shall confirm that each subject has given written consent for monitors, auditors, ethics committee reviewers, and drug regulatory inspectors to directly access their original medical records related to the clinical trial.

Article 47   The sponsor is responsible for the safety evaluation of investigational drugs during the drug trial. The sponsor shall promptly notify investigators, clinical trial institutions, and drug regulatory authorities of any issues discovered in the clinical trial that may affect subject safety, trial implementation, or alter the ethics committee's approval.

Article 48   The sponsor shall report adverse drug reactions according to requirements and deadlines.

(1) Upon receiving any safety-related information from any source, the sponsor shall immediately analyze and assess it, including severity, relevance to the investigational drug, and whether it is an expected event. The sponsor shall promptly report suspected unexpected serious adverse reactions to all investigators, clinical trial institutions, and ethics committees involved in the clinical trial; the sponsor shall also report these to the drug regulatory authorities and health administrative departments.

(2) The safety update reports provided by the sponsor during drug development shall include an assessment of the risks and benefits of the clinical trial, and relevant information shall be communicated to all investigators, clinical trial institutions, and ethics committees involved in the clinical trial.

Article 49   Monitoring of clinical trials shall meet the following requirements:

(1) The purpose of monitoring is to protect the rights and interests of subjects in clinical trials, ensure the accuracy and completeness of trial records and reports, and ensure compliance with the agreed protocol, this standard, and relevant regulations.

(2) Monitors appointed by the sponsor shall receive appropriate training and possess the knowledge required for clinical trial monitoring in medicine, pharmacy, etc., to effectively perform monitoring duties.

(3) The sponsor shall establish a systematic, prioritized, risk-based approach to monitor clinical trial implementation. The scope and nature of monitoring may be flexible, allowing different monitoring methods to improve efficiency and effectiveness. The sponsor shall document the rationale for selecting monitoring strategies in the monitoring plan.

(4) The sponsor shall develop a monitoring plan. The monitoring plan shall particularly emphasize protecting subjects' rights, ensuring data authenticity, and addressing various risks in clinical trials. The plan shall describe monitoring strategies, monitoring responsibilities of all trial parties, monitoring methods, and reasons for applying different monitoring methods. The plan shall emphasize monitoring of key data and processes and comply with relevant laws and regulations.

(5) The sponsor shall establish standard operating procedures for monitoring, which monitors shall follow during their work.

(6) The sponsor shall conduct clinical trial monitoring, with the scope and nature depending on the trial's purpose, design, complexity, blinding, sample size, and clinical trial endpoints.

(7) On-site monitoring and centralized monitoring should be conducted based on the risk associated with the clinical trial. On-site monitoring is performed at the clinical trial site and is usually conducted before the trial starts, during its implementation, and after it ends. Centralized monitoring involves timely remote assessment of ongoing clinical trials and remote evaluation of data collected from different clinical trial institutions. The process of centralized monitoring helps improve the effectiveness of clinical trial monitoring and serves as a supplement to on-site monitoring.

Statistical analysis applied in centralized monitoring can identify data trends, including the range and consistency of data within and between different clinical trial institutions, and analyze the characteristics and quality of the data, which helps in selecting monitoring sites and monitoring procedures.

(8) In special circumstances, the sponsor may combine monitoring with other trial activities, such as investigator training and meetings. During monitoring, statistical sampling methods can be used to verify data.

Article 50   The responsibilities of the monitor include:

(1) The monitor should be familiar with the investigational medicinal product, the trial protocol, the informed consent form, and other written materials provided to subjects, as well as the clinical trial standard operating procedures and this regulation and other relevant laws.

(2) The monitor should diligently perform monitoring duties according to the sponsor's requirements to ensure the clinical trial is conducted and recorded correctly according to the trial protocol.

(3) The monitor is the main contact between the sponsor and the investigator. Before the clinical trial, the monitor confirms that the investigator has sufficient qualifications and resources to complete the trial, and that the clinical trial institution has appropriate conditions to conduct the trial, including staffing and training, well-equipped and functioning laboratories, and all necessary inspection conditions related to the trial.

(4) The monitor should verify that during the clinical trial, the investigational medicinal product is within its validity period, stored under acceptable conditions, and supplied adequately; the investigational medicinal product is provided only to appropriate subjects at the doses specified in the trial protocol; subjects receive correct instructions on the use, handling, storage, and return of the investigational medicinal product; the clinical trial institution has proper control and records for receiving, using, and returning the investigational medicinal product; and the disposal of unused investigational medicinal products complies with relevant laws, regulations, and sponsor requirements.

(5) The monitor verifies the investigator's compliance with the trial protocol during the clinical trial; confirms that all subjects or their guardians signed the informed consent form before the trial; ensures the investigator has received the latest investigator's brochure, all trial-related documents, and necessary trial supplies, and implements the trial according to relevant laws and regulations; and ensures that the research staff have a thorough understanding of the clinical trial.

(6) The monitor verifies that the research staff fulfill the responsibilities stipulated in the trial protocol and contract, and whether these responsibilities are delegated to unauthorized personnel; confirms that enrolled subjects are qualified and reports enrollment rates and clinical trial progress; confirms that data recording and reporting are accurate and complete, and that trial records and documents are updated in real-time and well preserved; verifies that all medical reports, records, and documents provided by the investigator are traceable, clear, synchronously recorded, original, accurate, complete, and marked with dates and trial numbers.

(7) The monitor checks the accuracy and completeness of case report form entries and compares them with source documents. The monitor should pay attention to verifying that data required by the trial protocol are accurately recorded in the case report form and consistent with source documents; confirms that dose changes, treatment modifications, adverse events, concomitant medications, complications, lost to follow-up, and missed examinations are all recorded in the case report form; confirms that follow-ups not completed by the investigator, unimplemented trials, missed examinations, and corrections of errors or omissions are all recorded in the case report form; verifies that withdrawals and lost to follow-up of enrolled subjects are recorded and explained in the case report form.

(8) The monitor should notify the investigator of any errors, omissions, or illegible entries in the case report form; the monitor should ensure that corrections, additions, or deletions are made by the investigator or authorized personnel, with the modifier's signature, date, and, if necessary, an explanation for the change.

(9) The monitor confirms that adverse events are reported within the specified time frame according to relevant laws, regulations, the trial protocol, ethics committee, and sponsor requirements.

(10) The monitor confirms whether the investigator has preserved essential documents according to this regulation.

(11) The monitor should promptly communicate with the investigator about deviations from the trial protocol, standard operating procedures, or relevant laws and regulations, and take appropriate measures to prevent recurrence.

Article 51   After each monitoring visit, the monitor should promptly submit a written report to the sponsor; the report should include the monitoring date, location, monitor's name, names of investigators and other personnel contacted; the report should summarize the monitoring work, identify problems and factual statements found in the clinical trial, deviations and deficiencies from the trial protocol, and monitoring conclusions; the report should describe corrective actions taken or planned for issues found during monitoring and recommendations to ensure compliance with the trial protocol; the report should provide sufficient detail to review compliance with the monitoring plan. Centralized monitoring reports can be submitted separately from on-site monitoring reports. The sponsor should review and follow up on issues in the monitoring reports and keep documentation.

Article 52   Clinical trial audits should meet the following requirements:

(1) The sponsor may conduct audits beyond routine monitoring to assess the implementation of the clinical trial and compliance with laws and regulations.

(2) The sponsor selects personnel independent of the clinical trial to serve as auditors; auditors cannot concurrently serve as monitors. Auditors should receive appropriate training and have audit experience to effectively perform audit duties.

(3) The sponsor should establish audit procedures for the clinical trial and quality management system to ensure implementation of audit procedures during the clinical trial. These procedures should specify audit objectives, methods, frequency, and the format and content of audit reports. Auditors should document all observations and findings in writing during audits.

(4) When developing audit plans and procedures, the sponsor should consider the content of materials submitted to the drug regulatory authority, the number of subjects in the clinical trial, the type and complexity of the clinical trial, the risk level affecting subjects, and other known relevant issues.

(5) The drug regulatory authority may require the sponsor to provide audit reports as needed.

(6) The sponsor should provide audit certificates when necessary.

Article 53   The sponsor should ensure compliance with the clinical trial.

(1) When it is found that researchers, clinical trial institutions, or sponsors do not comply with the trial protocol, standard operating procedures, this specification, or relevant laws and regulations during the clinical trial, the sponsor shall immediately take measures to correct this and ensure good compliance with the clinical trial.

(2) When important compliance issues are found that may have a significant impact on the safety and rights of subjects or the reliability of clinical trial data, the sponsor shall promptly conduct root cause analysis and take appropriate corrective and preventive measures. If the violation of the trial protocol or this specification is serious, the sponsor may hold the responsible personnel accountable and report to the drug regulatory authority.

(3) When serious or uncorrected non-compliance issues are found with researchers or clinical trial institutions, the sponsor shall terminate the participation of the researcher or clinical trial institution in the clinical trial and promptly report in writing to the drug regulatory authority. At the same time, the sponsor and researchers shall take corresponding emergency safety measures to protect the safety and rights of the subjects.

Article 54   If the sponsor terminates or suspends the clinical trial in advance, they shall immediately inform the researchers, clinical trial institutions, and the drug regulatory authority, and explain the reasons.

Article 55   Upon completion or early termination of the clinical trial, the sponsor shall submit the clinical trial report to the drug regulatory authority in accordance with relevant laws and regulations. The clinical trial summary report shall comprehensively, completely, and accurately reflect the clinical trial results, and the safety and efficacy data in the summary report shall be consistent with the clinical trial source data.

Article 56   Sponsors conducting multicenter trials shall meet the following requirements:

(1) The sponsor shall ensure that all centers participating in the clinical trial comply with the trial protocol.

(2) The sponsor shall provide the same trial protocol to each center. Each center shall follow the protocol and comply with the unified evaluation standards for clinical and laboratory data and the instructions for filling out case report forms.

(3) Each center shall use the same case report form to record trial data obtained during the clinical trial. If the sponsor requires researchers to collect additional trial data, this should be stated in the trial protocol, and the sponsor shall provide additional case report forms to the researchers.

(4) Before the clinical trial begins, there shall be written documents clarifying the responsibilities of researchers at each participating center.

(5) The sponsor shall ensure communication among researchers at each center.

 

Chapter 6 Trial Protocol

Article 57   The trial protocol usually includes basic information, research background, trial objectives, trial design, implementation methods (methods, content, steps), and other content.

Article 58   Basic information in the trial protocol generally includes:

(1) Trial protocol title, number, version number, and date.

(2) Name and address of the sponsor.

(3) Names, positions, and units of persons authorized by the sponsor to sign and amend the trial protocol.

(4) Names, positions, unit addresses, and phone numbers of the sponsor's medical experts.

(5) Names, titles, positions of researchers, and addresses and phone numbers of clinical trial institutions.

(6) Names and addresses of units and related departments participating in the clinical trial.

Article 59   Research background in the trial protocol usually includes:

(1) Name and introduction of the investigational drug.

(2) Findings from non-clinical and clinical studies related to the clinical trial that have potential clinical significance.

(3) Known and potential risks and benefits to the subject population.

(4) Description of the route of administration, dosage, method of administration, and treatment duration of the investigational drug, with reasons explained.

(5) Emphasis that the clinical trial must be conducted in accordance with the trial protocol, this specification, and relevant laws and regulations.

(6) Target population of the clinical trial.

(7) Research background, references, and data sources related to the clinical trial.

Article 60   The trial protocol shall describe the objectives of the clinical trial in detail.

Article 61   The scientific validity of the clinical trial and the reliability of trial data mainly depend on the trial design, which usually includes:

(1) Clear definition of primary and secondary endpoints of the clinical trial.

(2) Reasons for the choice of control group and description of the trial design (e.g., double-blind, placebo-controlled, parallel group design), with research design, process, and different stages presented in flowchart form.

(3) Measures taken to reduce or control bias, including methods and processes of randomization and blinding. If single-blind or open-label trials are used, reasons and bias control measures must be explained.

(4) Treatment methods, dosage and administration plan of the investigational drug; dosage form, packaging, and labeling of the investigational drug.

(5) Expected duration and specific arrangements for subject participation in the clinical trial, including follow-up.

(6) Subjects, partial clinical trials, and entire clinical trials " Criteria for suspending the trial ”、 " Criteria for terminating the trial ”。

(7) Management process of the investigational drug.

(8) Procedures for maintaining the blind and unblinding.

(9) Clear specification of which trial data can be recorded directly as source data in the case report form.

Article 62   The trial protocol usually includes items for clinical and laboratory examinations.

Article 63   Subject selection and withdrawal usually include:

(1) Inclusion criteria for subjects.

(2) Exclusion criteria for subjects.

(3) Criteria and procedures for subjects withdrawing from the clinical trial.

Article 64   Subject treatment usually includes:

(1) Names of all investigational drugs used in each clinical trial group, dosage, administration regimen, route of administration, treatment duration, and follow-up period.

(2) Concomitant medications (including emergency treatment drugs) or therapies allowed before and during the clinical trial, and prohibited drugs or therapies.

(3) Methods for evaluating subject compliance.

Article 65   Develop clear visit and follow-up plans, including during the clinical trial, clinical trial endpoints, adverse event assessments, and follow-up and medical management after the trial ends.

Article 66   Efficacy evaluation usually includes:

(1) Detailed description of the clinical trial efficacy endpoints.

(2) Detailed description of the evaluation, recording, analysis methods, and time points for efficacy endpoints.

Article 67   Safety evaluation usually includes:

(1) Detailed description of the clinical trial safety endpoints.

(2) Detailed description of the evaluation, recording, analysis methods, and time points for safety endpoints.

(3) Procedures for recording and reporting adverse events and concomitant diseases.

(4) Methods and duration of adverse event follow-up.

Article 68   Statistics usually include:

(1) Determination of subject sample size, with reasons based on preliminary trials or literature data.

(2) Significance level, with explanation if adjustments are considered.

(3) Explanation of statistical hypotheses for primary endpoints, including null and alternative hypotheses, brief description of specific statistical methods and analysis software to be used. If interim analysis is needed, reasons, analysis timing, and procedures should be explained.

(4) Methods for handling missing data, unused data, and illogical data.

(5) Clear procedures for deviations from the original statistical analysis plan.

(6) Clear definitions of subject datasets used for statistical analysis, including all randomized subjects, all subjects who took investigational drugs, all eligible subjects, and subjects available for clinical trial outcome evaluation.

Article 69   The trial protocol should include implementation of clinical trial quality control and quality assurance.

Article 70   The trial protocol usually includes ethical considerations related to the trial.

Article 71   The trial protocol usually describes the processes for trial data collection and management, systems used for data management and collection, steps and tasks of data management, and quality assurance measures for data management.

Article 72   If not specified in contracts or agreements, the trial protocol usually includes direct access to source documents related to the clinical trial, data processing and record keeping, finance, and insurance.

 

Chapter 7  Investigator's Brochure

Article 73   The Investigator's Brochure provided by the sponsor is a compilation of pharmaceutical, non-clinical, and clinical information about the investigational drug. Its content includes chemical, pharmaceutical, toxicological, pharmacological, and clinical data and information about the investigational drug. The purpose of the Investigator's Brochure is to help investigators and other trial personnel better understand and comply with the trial protocol, assisting investigators in understanding many key fundamental elements of the protocol, including clinical trial dosage, dosing frequency, dosing intervals, administration methods, primary and secondary efficacy endpoints, and safety observation and monitoring.

Article 74   For marketed drugs undergoing clinical trials, when investigators have sufficient knowledge of pharmacology and related information, the Investigator's Brochure can be simplified. Parts of the Investigator's Brochure may be replaced by drug package inserts or other forms, only requiring provision of important, recent, comprehensive, and detailed clinical trial-related information about the investigational drug to investigators.

Article 75   The sponsor shall establish written procedures for revising the Investigator's Brochure. The Investigator's Brochure should be reviewed at least once a year during the clinical trial. Based on the clinical trial development steps and new drug safety and efficacy information obtained during the trial, the sponsor should inform investigators before updating the Investigator's Brochure and, if necessary, communicate with ethics committees and drug regulatory authorities. The sponsor is responsible for updating the Investigator's Brochure and promptly delivering it to investigators, who are responsible for submitting the updated brochure to the ethics committee.

Article 76   The cover page of the Investigator's Brochure should state the sponsor's name, investigational drug number or name, version number, release date, replacement version number, and replacement date.

Article 77   The Investigator's Brochure should include:

(1) Table of contents: confidentiality statement, signature page, table of contents, summary, preface, physical, chemical, pharmaceutical properties and structural formula of the investigational drug, non-clinical studies (non-clinical pharmacology, in vivo animal pharmacokinetics, toxicology), human effects (human pharmacokinetics, safety and efficacy, marketed use), data summary and investigator's guide, precautions, references (published literature, reports, listed at the end of each chapter).

(2) Summary: emphasizing important physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, and clinical information significant to the investigational drug development process.

(3) Preface: Briefly state the chemical name or approved generic name and approved trade name of the investigational drug; all active ingredients of the investigational drug, pharmacological classification, and its expected position among similar drugs (e.g., advantages); the rationale for conducting clinical trials of the investigational drug; the intended use of the investigational drug for disease prevention, diagnosis, and treatment. The preface should explain the conventional methods for evaluating the investigational drug.

(4) The investigator's brochure should clearly state the chemical formula and structural formula of the investigational drug, briefly describing its physicochemical and pharmaceutical properties. It should explain the storage and usage methods of the investigational drug. If the formulation information of the investigational drug may affect the clinical trial, the excipient components and formulation rationale should be explained to ensure necessary safety measures during the clinical trial.

(5) If the investigational drug has a structure similar to other known drugs, this should be stated.

(6) Introduction to non-clinical studies: Briefly describe the relevant findings from pharmacology, toxicology, and pharmacokinetics studies of the investigational drug in non-clinical research. Explain the methodologies and results of these non-clinical studies, discuss the implications of these findings for human clinical treatment, possible adverse effects on humans, and the relevance to unexpected effects in humans.

(7) The investigator's brochure should provide information from non-clinical studies: species of test animals, number and sex of animals per group, dosage units, dosing intervals, administration routes, duration of administration, systemic distribution data, and follow-up period after exposure. Study results should include characteristics and frequency of pharmacological and toxic effects of the investigational drug; severity or intensity of pharmacological and toxic effects; onset time; reversibility of pharmacological effects; duration of drug action and dose-response. Important findings in non-clinical studies should be discussed, such as dose-response relationships, possible relevance to humans, and various issues related to conducting human studies. If effective and non-toxic doses in the same animal species can be comparatively studied, these results may be used to discuss the therapeutic index and explain the relevance of study results to the proposed human dose. Comparative studies should be based on blood or organ tissue levels whenever possible.

(8) Introduction to non-clinical pharmacology studies: Should include a summary of the pharmacological aspects of the investigational drug, and if possible, important metabolic studies of the investigational drug in animals. The summary should include studies evaluating the potential therapeutic activity of the investigational drug (e.g., efficacy models, receptor binding and specificity), as well as studies evaluating the safety of the investigational drug (e.g., specialized studies evaluating pharmacological effects different from therapeutic effects).

(9) Introduction to animal pharmacokinetics: Should include a summary of the pharmacokinetics, biotransformation, and distribution of the investigational drug in the studied animal species. The discussion of findings should explain the absorption, local and systemic bioavailability, and metabolism of the investigational drug, as well as their relationship to pharmacological and toxicological findings in the animal species.

(10) Introduction to toxicology: A summary of toxicological effects found in relevant studies across different animal species should include single-dose administration, repeated dosing, carcinogenicity, special toxicology studies (e.g., irritation and sensitization), reproductive toxicity, genetic toxicity (mutagenicity), and other aspects.

(11) Effects in humans: The known effects of the investigational drug in humans should be fully discussed, including pharmacokinetics, pharmacodynamics, dose-response, safety, efficacy, and other pharmacological information. Summaries of all completed clinical trials of the investigational drug should be provided as much as possible. Usage of the investigational drug outside clinical trials, such as experience during marketing, should also be provided.

(12) Summary of pharmacokinetic information of the investigational drug in humans, including pharmacokinetics (absorption and metabolism, plasma protein binding, distribution, and elimination); bioavailability of a reference formulation of the investigational drug (absolute and relative bioavailability); population subgroups (e.g., gender, age, and organ dysfunction); interactions (e.g., drug - drug interactions and effects of food); other pharmacokinetic data (e.g., results of population studies completed during clinical trials).

(13) Safety and efficacy of the investigational drug: A summary and discussion of safety, pharmacodynamics, efficacy, and dose-response information obtained from prior human trials of the investigational drug (including metabolites) should be provided. If multiple clinical trials have been completed, safety and efficacy data from multiple studies and subgroups should be aggregated. Consideration may be given to clearly summarizing all adverse drug reactions from clinical trials (including all studied indications) in tabular form. Important differences in types and incidence of adverse drug reactions between indications or subgroups should be discussed.

(14) Marketing experience: The main countries and regions where the investigational drug has been marketed or approved should be stated. Important information obtained from marketing experience (e.g., prescriptions, dosages, administration routes, and adverse drug reactions) should be summarized. The main countries and regions where the investigational drug has not been approved for marketing or has been withdrawn should be stated.

(15) Data summary and investigator guidance: A comprehensive analysis and discussion of non-clinical and clinical data should be conducted, summarizing information from various sources about different aspects of the investigational drug to help investigators anticipate adverse drug reactions or other issues in clinical trials.

(16) The investigator's brochure should enable investigators to clearly understand the possible risks and adverse reactions of the clinical trial, as well as any special examinations, observation items, and preventive measures that may be required; this understanding is based on physical, chemical, pharmaceutical, pharmacological, toxicological, and clinical data obtained from the investigator's brochure. Based on prior human experience and the pharmacology of the investigational drug, guidance should also be provided to investigators on identifying and managing possible overdose and adverse drug reactions.

(17) The content of the investigator's brochure for traditional Chinese medicine and ethnic medicine research should be formulated with reference to the above requirements. It should also indicate the theoretical basis of the formulation, screening information, compatibility, functions, indications, existing human medication experience, medicinal material origin and production area; for traditional Chinese medicine compound preparations derived from ancient classical prescriptions, the source should be indicated; relevant medicinal materials and prescription information.

 

Chapter 8 Essential Document Management

Article 78   Essential documents for clinical trials refer to documents that assess the implementation of clinical trials and data quality, used to prove that investigators, sponsors, and monitors comply with this standard and relevant drug clinical trial laws and regulations during the clinical trial process.

Essential documents are important content for sponsor audits and drug regulatory authority inspections of clinical trials, and serve as the basis for confirming the authenticity of clinical trial implementation and the completeness of collected data.

Article 79   The sponsor, investigator, and clinical trial institution shall ensure that there are places and conditions for storing essential clinical trial documents. The storage equipment conditions should prevent direct exposure to light, be waterproof, fireproof, and conducive to long-term preservation of documents. Standard operating procedures for document management shall be established. Stored documents need to be easily identifiable, searchable, retrievable, and returnable. The media used for storing clinical trial data shall ensure that source data or its verified copies are kept complete and readable during the retention period, with regular testing or checks on the ability to restore and read, preventing intentional or unintentional alteration or loss.

Some documents generated during the implementation of clinical trials, if not listed in the essential clinical trial document management directory, may also be included in the essential document archives of the sponsor, investigator, and clinical trial institution based on necessity and relevance.

Article 80   For clinical trials used to apply for drug registration, essential documents shall be kept at least until the investigational drug is approved for marketing. 5 years; for clinical trials not used for drug registration applications, essential documents shall be kept at least until after the clinical trial is terminated. 5 years.

Article 81   The sponsor shall ensure that the investigator can always access and enter or correct data in the case report forms reported to the sponsor during the trial process; such data should not be controlled solely by the sponsor.

The sponsor shall ensure that the investigator can retain the case report form data submitted to the sponsor. Copies used as source documents shall meet the requirements of verified copies.

Article 82   At the start of the clinical trial, both the investigator and clinical trial institution, as well as the sponsor, shall establish archives for essential documents. At the end of the clinical trial, the monitor shall review and confirm the essential documents of the investigator, clinical trial institution, and sponsor, which shall be properly stored in their respective clinical trial archive files.

 

Chapter 9 Supplementary Provisions

Article 83   This regulation shall come into effect from 2020 year 7 month 1 day.