--- title_en: "Good Clinical Practice for Drugs (2020 Revision)" title_zh: "药物临床试验质量管理规范（2020修订）" abbreviation: "Drug GCP" hierarchy: "standard" issuing_body: "National Medical Products Administration; National Health Commission" adopted_date: 2020-04-23 effective_date: 2020-07-01 status: "effective" related_laws: ["rwd-guiding-principles", "drug-administration-law"] domains: ["health", "personal-information"] url: https://datacompliancechina.com/laws/drug-clinical-trial-qms/ summary: "Issued jointly by the NMPA and the National Health Commission (Announcement No. 57 of 2020) and effective July 1, 2020, this revised standard (Drug GCP) is the quality benchmark for the entire process of drug clinical trials — protocol design, organization and implementation, monitoring, audit, recording, analysis, summarization and reporting. It contains detailed requirements for trial-data management and integrity: source data must satisfy attributability, legibility, contemporaneousness, originality, accuracy, completeness, consistency and durability (ALCOA), changes must leave a trail, and electronic data-management/computerized systems must be validated with audit trails, access controls and data backup. The data-compliance touchpoints are extensive: protection of subject privacy and confidentiality of related information, use of a subject identification code in place of names, electronic-data and computerized-system controls, defined direct-access rights for monitors/auditors/the ethics committee/regulators, rules on transfer of data ownership, and long retention of essential documents." --- > **Source: Data Compliance China** — https://datacompliancechina.com/laws/drug-clinical-trial-qms/ · English rendering and annotations by DCC; the Chinese original governs. Cite as: Data Compliance China, "Good Clinical Practice for Drugs (2020 Revision)", https://datacompliancechina.com/laws/drug-clinical-trial-qms/ **Promulgated by:** National Medical Products Administration; National Health Commission. **Announcement No. 57 of 2020 of the National Medical Products Administration and the National Health Commission.** In order to deepen the reform of the drug review and approval system, encourage innovation, and further promote standardized research and the improvement of the quality 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 promulgated and shall come into force on July 1, 2020. This is hereby announced. **Attachment:** Good Clinical Practice for Drugs **National Medical Products Administration; National Health Commission** **April 23, 2020** --- ## Chapter 1 General Provisions **Article 1.** These Norms are formulated in accordance with the Drug Administration Law of the People's Republic of China, the Vaccine Administration Law of the People's Republic of China and the Regulation for the Implementation of the Drug Administration Law of the People's Republic of China in order to ensure that the process of drug clinical trials is well-regulated and that the data and results are scientific, authentic and reliable, and to protect the rights, interests and safety of trial subjects. These Norms apply to drug clinical trials conducted for the purpose of applying for drug registration. The activities relating to drug clinical trials shall comply with these Norms. **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, audit, recording, analysis, summarization and reporting. **Article 3.** Drug clinical trials shall comply with the principles of the Declaration of Helsinki of the World Medical Association and the relevant ethical requirements; the rights, interests and safety of trial subjects are the primary consideration and take precedence over the benefits to science and society. Ethical review and informed consent are important measures for safeguarding the rights and interests of trial subjects. **Article 4.** Drug clinical trials shall have a sufficient scientific basis. A clinical trial shall weigh the anticipated risks and benefits to the trial subjects and to society, and may be conducted or continued only when the anticipated benefits outweigh the risks. **Article 5.** The trial protocol shall be clear, detailed and operable. The trial protocol may be implemented only after the consent of the ethics committee has been obtained. **Article 6.** The investigator shall comply with the trial protocol in the course of the clinical trial; any matter involving a medical judgment or clinical decision shall be made by a clinical physician. The research personnel participating in the implementation of the clinical trial shall have the education, training and experience corresponding to undertaking the clinical trial work. **Article 7.** All paper or electronic materials of a clinical trial shall be properly recorded, handled and preserved, and shall be capable of being accurately reported, interpreted and confirmed. The privacy of trial subjects and the confidentiality of their related information shall be protected. **Article 8.** The preparation of the investigational drug shall comply with the relevant requirements of the good manufacturing practice for drugs used in clinical trials. The use of the investigational drug shall comply with the trial protocol. **Article 9.** The quality management system of a clinical trial shall cover the entire process of the clinical trial, with the focus on protection of the trial subjects, reliability of the trial results, and compliance with the relevant laws and regulations. **Article 10.** The implementation of a clinical trial shall comply with the principle of avoidance of conflicts of interest. ## Chapter 2 Terms and Their Definitions **Article 11.** The following terms used in these Norms have the meanings set out below: (I) Clinical trial means a systematic trial with human beings (patients or healthy subjects) as the object, intended to discover or verify the clinical, pharmacological or other pharmacodynamic effects and adverse reactions of an investigational drug, or the absorption, distribution, metabolism and excretion of the investigational drug, in order to determine the efficacy and safety of the drug. (II) Compliance of a clinical trial means the compliance of the parties participating in the clinical trial with the requirements relating to the clinical trial, these Norms and the relevant laws and regulations. (III) Non-clinical study means biomedical research not conducted on human beings. (IV) Independent data monitoring committee (data and safety monitoring committee, monitoring committee, data monitoring committee) means an independent data monitoring committee established by the sponsor to periodically evaluate the progress of the clinical trial, the safety data and the important efficacy endpoints, and to recommend to the sponsor whether to continue, adjust or stop the trial. (V) Ethics committee means a committee composed of personnel with medical, pharmaceutical and other backgrounds, whose duty is to ensure that the rights, interests and safety of trial subjects are protected by independently reviewing, consenting to and conducting follow-up review of the trial protocol and related documents, the methods and materials used to obtain and record the informed consent of trial subjects, and so on. (VI) Investigator means the person in charge of the trial site who conducts the clinical trial and is responsible for the quality of the clinical trial and the rights, interests and safety of the trial subjects. (VII) Sponsor means the individual, organization or institution responsible for initiating and managing a clinical trial and providing the funding for the clinical trial. (VIII) Contract research organization means a unit that, through a contractual authorization, performs certain duties and tasks of the sponsor or the investigator in a clinical trial. (IX) Trial subject means a person who participates in a clinical trial and serves as a recipient of the investigational drug, including patients and healthy subjects. (X) Vulnerable trial subject means a trial subject whose ability to safeguard his or her own wishes and rights is insufficient or lost, and whose willingness to voluntarily participate in a clinical trial may be unduly influenced by the anticipated benefits of the trial or by the fear of retaliation for refusing to participate. This includes: students and subordinates of the investigator, employees of the sponsor, military personnel, prisoners, patients with incurable diseases, patients in critical condition, persons living in welfare institutions, vagrants, minors, and persons unable to give informed consent. (XI) Informed consent means the process whereby a trial subject, after being informed of the various aspects that may affect his or her decision to participate in a clinical trial, confirms his or her consent to voluntarily participate in the clinical trial. This process shall be documented by a written informed consent form signed and dated. (XII) Impartial witness means an individual who is unrelated to the clinical trial and is not unfairly influenced by personnel related to the clinical trial, who, where a trial subject or his or her guardian lacks reading ability, acts as an impartial witness, reads the informed consent form and other written materials, and witnesses the informed consent. (XIII) Monitoring means the action of supervising the progress of a clinical trial and ensuring that the clinical trial is implemented, recorded and reported in accordance with the trial protocol, the standard operating procedures and the requirements of the relevant laws and regulations. (XIV) Monitoring plan means a document describing the monitoring strategy, methods, duties and requirements. (XV) Monitoring report means a written report submitted by the monitor to the sponsor after each on-site visit or other communication relating to the clinical trial, in accordance with the provisions of the sponsor's standard operating procedures. (XVI) Audit means the systematic and independent examination of the activities and documents relating to a clinical trial, in order to evaluate and determine whether the conduct of the activities relating to the clinical trial and the recording, analysis and reporting of trial data comply with the requirements of the trial protocol, the standard operating procedures and the relevant laws and regulations. (XVII) Audit report means a written evaluation report on the audit results, prepared by an auditor appointed by the sponsor. (XVIII) Inspection means the act of the drug administration department reviewing and inspecting the relevant documents, facilities, records and other aspects of a clinical trial. The inspection may be conducted at the trial site, the location of the sponsor or the contract research organization, and other places that the drug administration department considers necessary. (XIX) Direct access means the direct inspection, analysis, verification or copying, etc. of records and reports important for evaluating a drug clinical trial. Any party with direct access shall, in accordance with the relevant laws and regulations, take reasonable measures to protect the privacy of trial subjects and to avoid disclosing the proprietary information of the sponsor and other information that needs to be kept confidential. (XX) Trial protocol means a document explaining the objective, design, methodology, statistical considerations, and organization and implementation of a clinical trial. The trial protocol shall usually also include the background and rationale of the clinical trial, which content may also be set out in other reference documents. The trial protocol includes the protocol and its revised versions. (XXI) Investigator's brochure means a compilation of the clinical and non-clinical research materials relating to the investigational drug used in conducting a clinical trial. (XXII) Case report form means a paper or electronic document designed in accordance with the requirements of the trial protocol and reported to the sponsor, recording the relevant information of trial subjects. (XXIII) Standard operating procedure means a detailed written requirement formulated to ensure the consistency of a particular operation. (XXIV) Investigational drug means the investigational drug and the control drug used in a clinical trial. (XXV) Control drug means another research drug, marketed drug or placebo used in a clinical trial for comparison and control with the investigational drug. (XXVI) Adverse event means all untoward medical events occurring after a trial subject receives the investigational drug, which may manifest as symptoms and signs, illness or abnormal laboratory test results, but which do not necessarily have a causal relationship with the investigational drug. (XXVII) Serious adverse event means an untoward medical event such as death, life-threatening condition, permanent or serious disability or loss of function, the need for the trial subject to be hospitalized or to have hospitalization prolonged, as well as congenital anomaly or birth defect, occurring after a trial subject receives the investigational drug. (XXVIII) Adverse drug reaction means any harmful or unintended reaction to the human body, possibly related to the investigational drug, occurring in a clinical trial. There is at least one reasonable possibility of a causal relationship between the investigational drug and the adverse event, i.e. the relationship cannot be ruled out. (XXIX) Suspected and unexpected serious adverse reaction means a suspected and unexpected serious adverse reaction the nature and severity of whose clinical manifestation exceed the existing materials and information such as the investigator's brochure of the investigational drug, the package insert of a marketed drug or the summary of product characteristics. (XXX) Subject identification code means a unique code assigned to a trial subject in a clinical trial to identify his or her identity. When reporting the adverse events occurring in a trial subject and other data relating to the trial, the investigator uses this code in place of the trial subject's name to protect his or her privacy. (XXXI) Source document means the original records, documents and data generated in a clinical trial, such as hospital medical records, medical images, laboratory records, memoranda, trial subjects' diaries or evaluation forms, drug dispensing records, data automatically recorded by instruments, microfilm, photographic negatives, magnetic media, X-ray films, trial subject files, and the clinical-trial-related documents and records preserved by the pharmacy, laboratory and medical technology departments, including certified copies. Source documents include source data and may exist in the form of paper, electronic or other carriers. (XXXII) Source data means all the information recorded in the original records or certified copies of a clinical trial, including clinical findings, observation results and other relevant activity records needed for the reconstruction and evaluation of the clinical trial. (XXXIII) Essential documents means documents that, individually or after compilation, can be used to evaluate the implementation process of a clinical trial and the quality of the trial data. (XXXIV) Certified copy means a copy that has been reviewed and verified to confirm that its content, structure and the like are identical to those of the original, which copy is signed and dated by the reviewer, or is directly generated by a validated system, and may exist in the form of paper, electronic or other carriers. (XXXV) Quality assurance means the planned and systematic measures established in a clinical trial to ensure that the implementation of the clinical trial and the generation, recording and reporting of data comply with the trial protocol and the relevant laws and regulations. (XXXVI) Quality control means the techniques and activities implemented within the quality assurance system of a clinical trial to verify whether all the relevant activities of the clinical trial meet the quality requirements. (XXXVII) Trial site means the place where the activities relating to a clinical trial are conducted. (XXXVIII) Blinding means the procedure in a clinical trial whereby one or more parties are kept unaware of the treatment allocation of the trial subjects. Single blinding generally means that the trial subjects are unaware, and double blinding generally means that the trial subjects, the investigator, the monitors and the data analysts are all unaware of the treatment allocation. (XXXIX) Computerized system validation means the process of establishing and documenting that a computerized system, from its design to its discontinuation of use or conversion to another system, is able to meet specific requirements throughout its entire life cycle. The validation protocol shall be formulated on the basis of a risk assessment that takes into account factors such as the intended use of the system and the potential impact of the system on the protection of trial subjects and the reliability of the clinical trial results. (XL) Audit trail means a record that can trace and reconstruct the process of occurrence of an event. ## Chapter 3 Ethics Committee **Article 12.** The duty of the ethics committee is to protect the rights, interests and safety of trial subjects, and it shall pay particular attention to vulnerable trial subjects. (I) The documents that the ethics committee shall review include: the trial protocol and its revised versions; the informed consent form and its updated versions; the manner of and information for recruiting trial subjects; other written materials provided to trial subjects; the investigator's brochure; existing safety materials; documents containing information on subject compensation; documents proving the qualifications of the investigator; and other documents needed for the ethics committee to perform its duties. (II) The ethics committee shall review the scientific validity and ethicality of the clinical trial. (III) The ethics committee shall review the qualifications of the investigator. (IV) In order to better judge whether the rights, interests and safety of the trial subjects as well as basic medical care can be ensured in the clinical trial, the ethics committee may require the provision of materials and information beyond the content of the informed consent form. (V) When a non-therapeutic clinical trial (i.e. a trial with no anticipated direct clinical benefit to the trial subjects) is conducted, where the informed consent of the trial subjects is given on their behalf by their guardians, the ethics committee shall pay particular attention to whether the trial protocol has fully considered the corresponding ethical issues and the laws and regulations. (VI) Where the trial protocol clearly states that, in an emergency, the trial subject or his or her guardian is unable to sign the informed consent form before the trial, the ethics committee shall review whether the trial protocol has fully considered the corresponding ethical issues and the laws and regulations. (VII) The ethics committee shall review whether there is any improper influence, such as coercion or inducement, on trial subjects to participate in the clinical trial. The ethics committee shall review that the informed consent form may not adopt content that causes the trial subject or his or her guardian to waive lawful rights and interests, nor may it contain content that exempts the investigator, the clinical trial institution, the sponsor and its agency from the responsibilities they should bear. (VIII) The ethics committee shall ensure that the informed consent form and other written materials provided to the trial subjects explain the information on compensation to the trial subjects, including the method, amount and plan of compensation. (IX) The ethics committee shall complete the review or filing process of the materials relating to the clinical trial within a reasonable time limit and give a clear written review opinion. The review opinion shall include the name of the clinical trial reviewed, the documents (including version number) and the date. (X) The review opinions of the ethics committee are: approval; approval after necessary modifications; disapproval; termination or suspension of a research already consented to. The review opinion shall state the content required to be modified or the reasons for the denial. (XI) The ethics committee shall pay attention to and clearly require the investigator to promptly report: deviations from or modifications of the trial protocol made in the course of implementing the clinical trial to eliminate immediate hazards to trial subjects; changes that increase the risk to trial subjects or significantly affect the implementation of the clinical trial; all suspected and unexpected serious adverse reactions; and new information that may have an adverse impact on the safety of the trial subjects or the implementation of the clinical trial. (XII) The ethics committee has the right to suspend or terminate a clinical trial that has not been implemented in accordance with the relevant requirements or in which trial subjects have suffered unexpected serious injury. (XIII) The ethics committee shall conduct periodic follow-up review of the clinical trial in progress; the frequency of the review shall be determined according to the degree of risk to the trial subjects, but the review shall be conducted at least once a year. (XIV) The ethics committee shall accept and properly handle the relevant appeals of trial subjects. **Article 13.** The composition and operation of the ethics committee shall meet the following requirements: (I) The member composition and filing administration of the ethics committee shall meet the requirements of the health administration department. (II) The members of the ethics committee shall all receive training in ethical review and be able to review the ethical, scientific and other issues relating to the clinical trial. (III) The ethics committee shall perform its duties in accordance with its systems and standard operating procedures; the review shall have written records, indicating the meeting time and the content discussed. (IV) The voting members of the ethics committee meeting review opinion shall participate in the review and discussion at the meeting, including all categories of members, with a composition of different genders, and shall meet the prescribed number of persons. The meeting review opinion shall be formed into a written document. (V) The members voting or giving review opinions shall be independent of the clinical trial project under review. (VI) The ethics committee shall have detailed information on its members and ensure that its members possess the qualifications for ethical review. (VII) The ethics committee shall require the investigator to provide the various materials needed for the ethical review and answer the questions raised by the ethics committee. (VIII) The ethics committee may, as needed, invite relevant experts other than its members to participate in the review, but they may not participate in voting. **Article 14.** The ethics committee shall establish and implement the following written documents: (I) provisions on the composition, formation and filing of the ethics committee; (II) procedures for the meeting agenda, meeting notice and meeting review of the ethics committee; (III) procedures for the initial review and follow-up review of the ethics committee; (IV) procedures for the expedited review and consent to minor amendments to a trial protocol consented to by the ethics committee; (V) procedures for promptly notifying the investigator of the review opinion; (VI) procedures for the re-review of differing opinions on the ethical review opinion. **Article 15.** The ethics committee shall retain all records of the ethical review, including the written records of the ethical review, member information, submitted documents, meeting minutes and relevant correspondence records. All records shall be retained for at least 5 years after the conclusion of the clinical trial. The investigator, the sponsor or the drug administration department may require the ethics committee to provide its standard operating procedures and the list of ethical review members. ## Chapter 4 Investigators **Article 16.** The qualifications and requirements that the investigator and the clinical trial institution shall possess include: (I) having the practicing qualifications at the clinical trial institution; possessing the professional knowledge, training experience and competence required for the clinical trial; and being able to provide the latest work resume and relevant qualification documents at the request of the sponsor, the ethics committee and the drug administration department. (II) being familiar with the trial protocol, the investigator's brochure and the materials and information relating to the investigational drug provided by the sponsor. (III) being familiar with and complying with these Norms and the laws and regulations relating to the clinical trial. (IV) keeping a duty-division authorization form signed by the investigator. (V) the investigator and the clinical trial institution shall accept the monitoring and audit organized by the sponsor, as well as the inspection by the drug administration department. (VI) where the investigator and the clinical trial institution authorize an individual or unit to undertake duties and functions relating to the clinical trial, they shall ensure that the individual or unit possesses the corresponding qualifications, and shall establish complete procedures to ensure that it performs the duties and functions relating to the clinical trial and generates reliable data. The authorization by the investigator and the clinical trial institution of a unit outside the clinical trial institution to undertake duties and functions relating to the trial shall obtain the consent of the sponsor. **Article 17.** The investigator and the clinical trial institution shall have the necessary conditions for completing the clinical trial: (I) the investigator has the ability to enroll a sufficient number of trial subjects in accordance with the trial protocol within the time limit agreed for the clinical trial. (II) the investigator has sufficient time to implement and complete the clinical trial within the time limit agreed for the clinical trial. (III) the investigator has the authority to mobilize the personnel participating in the clinical trial during the clinical trial period and has the authority to use the medical facilities required for the clinical trial, so as to implement the clinical trial correctly and safely. (IV) the investigator ensures, during the clinical trial period, that all personnel participating in the clinical trial fully understand the trial protocol and the investigational drug, clarifies their respective divisions of work and duties in the trial, and ensures that the clinical trial data are authentic, complete and accurate. (V) the investigator supervises all research personnel in implementing the trial protocol and takes measures to implement the quality management of the clinical trial. (VI) the clinical trial institution shall set up a corresponding internal management department to undertake the management of the clinical trial. **Article 18.** The investigator shall give appropriate medical treatment to the trial subjects: (I) the investigator, being a clinical physician or an authorized clinical physician, shall bear the responsibility for all medical decisions relating to the clinical trial. (II) during the clinical trial and follow-up period, where a trial subject experiences an adverse event related to the trial, including a clinically significant laboratory abnormality, the investigator and the clinical trial institution shall ensure that the trial subject receives proper medical treatment, and shall truthfully inform the trial subject of the relevant circumstances. Where the investigator becomes aware that a trial subject has a concomitant illness requiring treatment, he or she shall inform the trial subject and pay attention to concomitant medication that may interfere with the clinical trial results or the safety of the trial subject. (III) with the consent of the trial subject, the investigator may inform the relevant clinical physician of the trial subject's participation in the trial. (IV) a trial subject may withdraw from the clinical trial without giving a reason. While respecting the personal rights of the trial subject, the investigator shall, as far as possible, ascertain the reasons for the withdrawal. **Article 19.** Communication between the investigator and the ethics committee includes: (I) before the implementation of the clinical trial, the investigator shall obtain the written consent of the ethics committee; trial subjects may not be screened before the written consent of the ethics committee has been obtained. (II) before the implementation of the clinical trial and during the course of the clinical trial, the investigator shall provide the ethics committee with all the documents needed for the ethical review. **Article 20.** The investigator shall comply with the trial protocol. (I) the investigator shall implement the clinical trial in accordance with the trial protocol consented to by the ethics committee. (II) without the consent of the sponsor and the ethics committee, the investigator shall not modify or deviate from the trial protocol, except for changes solely relating to the administrative aspects of the clinical trial, such as those made to promptly eliminate immediate hazards to the trial subjects, or the replacement of a monitor or a telephone number. (III) the investigator or the research personnel designated by him or her shall record and explain any deviation from the trial protocol. (IV) in order to eliminate immediate hazards to the trial subjects, where the investigator modifies or deviates from the trial protocol without obtaining the consent of the ethics committee, he or she shall promptly report to the ethics committee and the sponsor and explain the reasons, and report to the drug administration department where necessary. (V) the investigator shall take measures to avoid the use of concomitant medication prohibited by the trial protocol. **Article 21.** The investigator and the clinical trial institution have management responsibility for the investigational drug provided by the sponsor. (I) the investigator and the clinical trial institution shall assign a qualified pharmacist or other personnel to manage the investigational drug. (II) the management of the receipt, storage, dispensing, recovery, return and disposal of unused investigational drug at the clinical trial institution shall comply with the corresponding provisions and records shall be kept. The records of investigational drug management shall include the date, quantity, batch number/serial number, validity period, allocation code, signature and the like. The investigator shall keep records of the quantity and dosage of the investigational drug used by each trial subject. The quantity used and the remaining quantity of the investigational drug shall be consistent with the quantity provided by the sponsor. (III) the storage of the investigational drug shall comply with the corresponding storage conditions. (IV) the investigator shall ensure that the investigational drug is used in accordance with the trial protocol and shall explain to the trial subjects the correct method of using the investigational drug. (V) the investigator shall randomly take retained samples of the clinical trial drug for bioequivalence trials. The clinical trial institution shall retain the samples at least until 2 years after the drug is marketed. The clinical trial institution may entrust the retained samples to a qualified independent third party for preservation, but shall not return them to the sponsor or a third party with an interest in the sponsor. **Article 22.** The investigator shall comply with the randomization procedures of the clinical trial. A blinded trial shall be unblinded in accordance with the requirements of the trial protocol. Where the blinding is accidentally broken, or where emergency unblinding occurs due to a serious adverse event or other circumstances, the investigator shall provide a written explanation of the reasons to the sponsor. **Article 23.** When implementing informed consent, the investigator shall comply with the ethical principles of the Declaration of Helsinki and meet the following requirements: (I) the investigator shall use the latest version of the informed consent form and other information provided to the trial subjects that has been consented to by the ethics committee. Where necessary, the trial subjects shall sign the informed consent form again during the course of the clinical trial. (II) where the investigator obtains new information that may affect the continued participation of trial subjects in the trial, he or she shall promptly inform the trial subjects or their guardians and make corresponding records. (III) the research personnel shall not use improper means such as coercion or inducement to influence trial subjects to participate in or continue the clinical trial. (IV) the investigator or the designated research personnel shall fully inform the trial subjects of all matters relating to the clinical trial, including the written information and the consent opinion of the ethics committee. (V) the oral and written materials provided to the trial subjects, such as the informed consent form, shall all use plain and easily understandable language and expressions, so that the trial subjects or their guardians or witnesses can easily understand them. (VI) before signing the informed consent form, the investigator or the designated research personnel shall give the trial subjects or their guardians sufficient time and opportunity to understand the detailed circumstances of the clinical trial and shall answer in detail the questions raised by the trial subjects or their guardians relating to the clinical trial. (VII) the trial subject or his or her guardian, as well as the investigator who implements the informed consent, shall respectively sign and date the informed consent form; where it is not signed by the trial subject in person, the relationship shall be noted. (VIII) where the trial subject or his or her guardian lacks reading ability, an impartial witness shall witness the entire informed consent process. The investigator shall explain in detail to the trial subject or his or her guardian or the witness the content of the informed consent form and other written materials. Where the trial subject or his or her guardian orally consents to participate in the trial, the informed consent form shall be signed where possible, and the witness shall also sign and date the informed consent form to prove that the trial subject or his or her guardian received an accurate explanation of the informed consent form and other written materials from the investigator, understood the relevant content, and consented to participate in the clinical trial. (IX) the trial subject or his or her guardian shall obtain the original or a copy of the signed and dated informed consent form and other written materials provided to the trial subject, including the original or a copy of the updated informed consent form and the revised texts of other written materials provided to the trial subject. (X) where a trial subject is a person without civil capacity, the written informed consent of his or her guardian shall be obtained; where a trial subject is a person with limited civil capacity, the written informed consent of the person himself or herself and his or her guardian shall be obtained. Where the guardian gives informed consent on behalf of the trial subject, the relevant information on the clinical trial shall be informed to the trial subject within the scope understandable to the trial subject, and the trial subject shall, as far as possible, sign and date the informed consent form in person. (XI) in an emergency, where the informed consent of the trial subject cannot be obtained before participation in the clinical trial, his or her guardian may give informed consent on behalf of the trial subject; where the guardian is also not present, the manner of enrolling the trial subject shall be clearly stated in the trial protocol and other documents and obtain the written consent of the ethics committee; at the same time, the informed consent of the trial subject or his or her guardian to continue participating in the clinical trial shall be obtained as soon as possible. (XII) where a trial subject participates in a non-therapeutic clinical trial, the trial subject himself or herself shall sign and date the informed consent form to consent. A non-therapeutic clinical trial may have informed consent given by a guardian on behalf of the trial subject only where the following conditions are met: the clinical trial can be implemented only in trial subjects without the capacity for informed consent; the anticipated risk to the trial subjects is low; the negative impact on the health of the trial subjects has been minimized, and the laws and regulations do not prohibit the implementation of such a clinical trial; and the enrollment of such trial subjects has been reviewed and consented to by the ethics committee. In principle, such a clinical trial may be implemented only in patients suffering from the disease or condition to which the investigational drug applies. In the clinical trial, the trial subjects shall be closely observed; where a trial subject shows signs of excessive pain or discomfort, he or she shall be withdrawn from the trial, and necessary treatment shall be given to ensure the safety of the trial subject. (XIII) the specific time and personnel of the trial subject's informed consent shall be recorded in the medical history records. (XIV) where a child is a trial subject, the informed consent of his or her guardian shall be obtained and the informed consent form signed. Where the child is capable of making a decision to consent to participate in the clinical trial, his or her own consent shall also be obtained; where the child trial subject himself or herself does not consent to participate in the clinical trial or decides midway to withdraw from the clinical trial, the decision of the child trial subject himself or herself shall prevail, even if the guardian has consented to participate or is willing to continue participating, except in a therapeutic clinical trial for the treatment of a serious or life-threatening illness, where the investigator and his or her guardian consider that the life of the child trial subject would be endangered if he or she did not participate in the research, in which case the consent of his or her guardian is sufficient for the patient to continue participating in the research. In the course of the clinical trial, where a child trial subject reaches the conditions for signing informed consent, the trial may continue to be implemented only after the person himself or herself has signed the informed consent. **Article 24.** The informed consent form and other materials provided to the trial subjects shall include: (I) an overview of the clinical trial. (II) the trial objective. (III) the trial treatment and the possibility of random allocation to each group. (IV) the trial steps that the trial subject needs to comply with, including invasive medical procedures. (V) the obligations of the trial subject. (VI) the experimental content involved in the clinical trial. (VII) the risks or inconveniences that the trial may cause to the trial subject, especially where there is a risk of affecting the embryo, fetus or breastfeeding infant. (VIII) the anticipated benefits of the trial, as well as the possibility of not obtaining benefits. (IX) other alternative drugs and treatment methods, and their important potential benefits and risks. (X) the compensation and treatment that the trial subject may obtain in the event of injury related to the trial. (XI) the compensation that the trial subject may obtain for participating in the clinical trial. (XII) the anticipated expenses of the trial subject for participating in the clinical trial. (XIII) that the trial subject's participation in the trial is voluntary, that he or she may refuse to participate or has the right to withdraw from the trial at any stage of the trial at any time without being discriminated against or retaliated against, and that his or her medical treatment and rights and interests will not be affected. (XIV) that, without violating the principle of confidentiality and the relevant regulations, the monitor, auditor, ethics committee and the inspection personnel of the drug administration department may consult the trial subject's original medical records in order to verify the process and data of the clinical trial. (XV) the confidentiality of the trial subject's relevant identity identification records, which are not to be used publicly. Where the clinical trial results are published, the trial subject's identity information shall remain confidential. (XVI) that, where there is new information that may affect the continued participation of the trial subject in the trial, the trial subject or his or her guardian will be informed promptly. (XVII) the investigator and the ethics committee whom the trial subject may contact, and their contact information, when there are questions relating to the trial information and the rights and interests of the trial subject, and when injury related to the trial occurs. (XVIII) the circumstances and reasons under which the trial subject may be terminated from the trial. (XIX) the anticipated duration of the trial subject's participation in the trial. (XX) the estimated number of trial subjects participating in the trial. **Article 25.** The recording and reporting of the trial shall meet the following requirements: (I) the investigator shall supervise the data collection at the trial site and the performance of the work duties by each research personnel. (II) the investigator shall ensure that all clinical trial data are obtained from the source documents and trial records of the clinical trial and are accurate, complete, legible and timely. Source data shall be attributable, legible, contemporaneous, original, accurate, complete, consistent and durable. Modifications to source data shall leave a trail, shall not obscure the initial data, and the reasons for the modification shall be recorded. In a clinical trial with patients as trial subjects, the relevant medical records shall be entered into the outpatient or inpatient medical record system. Where the informatized system of the clinical trial institution has the conditions for establishing electronic medical records for the clinical trial, the investigator shall use it as the first choice; the corresponding computerized system shall have complete permission management and an audit trail, be traceable to the creator or modifier of the record, and ensure that the source data collected can be traced to their source. (III) the investigator shall, in accordance with the guidelines provided by the sponsor, complete and modify the case report forms, and ensure that the data in the various case report forms and other reports are accurate, complete, clear and timely. The data in the case report forms shall be consistent with the source documents; where there is any inconsistency, a reasonable explanation shall be given. Modifications to the data in the case report forms shall keep the initial records clear and identifiable, retain the modification trail, explain the reasons where necessary, and be signed and dated by the person making the modification. The sponsor shall have written procedures to ensure that its changes to the case report forms are necessary and recorded and have obtained the consent of the investigator. The investigator shall retain the relevant records of modifications and corrections. (IV) the investigator and the clinical trial institution shall properly preserve the trial documents in accordance with the "essential documents of clinical trials" and the relevant requirements of the drug administration department. (V) in the course of handling the clinical trial information and the trial subject information, care shall be taken to avoid the illegal or unauthorized access to, disclosure, dissemination, modification, destruction or loss of information. The recording, handling and preservation of clinical trial data shall ensure the confidentiality of the records and the trial subject information. (VI) the sponsor shall, in the contract, clarify with the investigator and the clinical trial institution the preservation period and expenses of the essential documents and the handling upon expiry. (VII) at the request of the monitor, auditor, ethics committee or drug administration department, the investigator and the clinical trial institution shall cooperate and provide the required records relating to the trial. **Article 26.** The safety reporting of the investigator shall meet the following requirements: Except for serious adverse events that are provided in the trial protocol or other documents (such as the investigator's brochure) as not needing to be reported immediately, the investigator shall immediately report all serious adverse events in writing to the sponsor, and shall subsequently promptly provide a detailed, written follow-up report. The serious adverse event report and the follow-up report shall indicate the trial subject's identification code in the clinical trial, rather than the trial subject's real name, citizen identity number, address and other identity information. The adverse events and abnormal laboratory values that are provided in the trial protocol and important for safety evaluation shall be reported to the sponsor in accordance with the requirements and time limits of the trial protocol. For a report involving a death event, the investigator shall provide the sponsor and the ethics committee with other required materials, such as the autopsy report and the final medical report. After the investigator receives the relevant safety information of the clinical trial provided by the sponsor, he or she shall promptly sign for and read it, consider whether the treatment of the trial subjects should be adjusted accordingly, communicate with the trial subjects as early as possible where necessary, and shall report to the ethics committee the suspected and unexpected serious adverse reactions provided by the sponsor. **Article 27.** When terminating or suspending a clinical trial early, the investigator shall promptly notify the trial subjects and give the trial subjects appropriate treatment and follow-up. In addition: (I) where the investigator terminates or suspends the clinical trial without consulting the sponsor, the investigator shall immediately report to the clinical trial institution, the sponsor and the ethics committee and provide a detailed written explanation. (II) where the sponsor terminates or suspends the clinical trial, the investigator shall immediately report to the clinical trial institution and the ethics committee and provide a detailed written explanation. (III) where the ethics committee terminates or suspends a clinical trial it has consented to, the investigator shall immediately report to the clinical trial institution and the sponsor and provide a detailed written explanation. **Article 28.** The investigator shall provide trial progress reports. (I) the investigator shall submit an annual report on the clinical trial to the ethics committee, or shall provide a progress report at the request of the ethics committee. (II) where a situation arises that may significantly affect the implementation of the clinical trial or increase the risk to trial subjects, the investigator shall report it in writing to the sponsor, the ethics committee and the clinical trial institution as soon as possible. (III) after the completion of the clinical trial, the investigator shall report to the clinical trial institution; the investigator shall provide the ethics committee with a summary of the clinical trial results and provide the sponsor with the clinical-trial-related reports required by the drug administration department. ## Chapter 5 Sponsors **Article 29.** The sponsor shall take the protection of the rights, interests and safety of the trial subjects and the authenticity and reliability of the clinical trial results as the basic consideration of the clinical trial. **Article 30.** The sponsor shall establish a quality management system for the clinical trial. The sponsor's quality management system for the clinical trial shall cover the entire process of the clinical trial, including the design, implementation, recording, evaluation, reporting of results and document filing of the clinical trial. Quality management includes effective trial protocol design, methods and processes for collecting data, and the collection of information necessary for making decisions in the clinical trial. The methods of quality assurance and quality control of the clinical trial shall be commensurate with the inherent risks of the clinical trial and the importance of the information collected. The sponsor shall ensure the operability of every part of the clinical trial, and the trial process and data collection shall avoid being overly complex. The trial protocol, case report forms and other relevant documents shall be clear, concise and internally consistent. The sponsor shall perform its management duties. 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. The internal work of the research and management team shall be communicated promptly. During an inspection by the drug administration department, the research and management team shall send personnel to participate. **Article 31.** The sponsor shall conduct quality management based on risk. (I) when formulating the trial protocol, the key parts and data for protecting the rights, interests and safety of the trial subjects and for ensuring the reliability of the clinical trial results shall be clarified. (II) the risks affecting the key parts and data of the clinical trial shall be identified. Such risks shall be considered at two levels: the system level, such as facilities and equipment, standard operating procedures, computerized systems, personnel and suppliers; and the clinical trial level, such as the investigational drug, the trial design, data collection and recording, and the informed consent process. (III) the risk assessment shall consider the likelihood of errors occurring under the existing risk controls; the impact of such errors on the protection of the rights, interests and safety of the trial subjects and on the reliability of the data; and the extent to which such errors can be detected. (IV) the risks that can be reduced or that are acceptable shall be identified. The control measures for reducing risks shall be reflected in the design and implementation of the trial protocol, the monitoring plan, the contract with the duties of all parties clarified, compliance with the standard operating procedures, and various types of training. When pre-setting the tolerance for quality risk, the medical and statistical characteristics of the variables and the statistical design shall be considered, so as to identify systemic problems affecting the safety of the trial subjects and the reliability of the data. When a situation arises that exceeds the tolerance for quality risk, an assessment shall be made of whether further measures need to be taken. (V) during the clinical trial period, the quality management shall be recorded and promptly communicated with the relevant parties, so as to promote risk assessment and continuous improvement of quality. (VI) the sponsor shall, in combination with the new knowledge and experience during the clinical trial period, periodically assess the risk control measures to ensure the effectiveness and applicability of the current quality management. (VII) the sponsor shall explain in the clinical trial report the quality management methods adopted, and summarize the events that seriously deviate from the tolerance for quality risk and the remedial measures. **Article 32.** The quality assurance and quality control of the sponsor shall meet the following requirements: (I) the sponsor is responsible for formulating, implementing and promptly updating the standard operating procedures relating to the quality assurance and quality control system of the clinical trial, so as to ensure that the implementation of the clinical trial and the generation, recording and reporting of data comply with the requirements of the trial protocol, these Norms and the relevant laws and regulations. (II) the entire process of the clinical trial and the laboratory tests shall be carried out in strict accordance with the standard operating procedures for quality management. Each stage of data handling shall have quality control to ensure that all data are reliable and that the data handling process is correct. (III) the sponsor shall conclude contracts with the investigator, the clinical trial institution and all other relevant units participating in the clinical trial, clarifying the duties of all parties. (IV) the contracts concluded by the sponsor with the relevant units shall indicate that the monitoring and audit of the sponsor and the inspection of the drug administration department may go directly to the trial site to consult the source data, source documents and reports. **Article 33.** Where the sponsor entrusts a contract research organization, the following requirements shall be met: (I) the sponsor may entrust part or all of the work and tasks of its clinical trial to a contract research organization, but the sponsor remains the ultimate responsible party for the quality and reliability of the clinical trial data and shall supervise the various tasks undertaken by the contract research organization. The contract research organization shall implement quality assurance and quality control. (II) the work entrusted by the sponsor to the contract research organization shall be the subject of a contract. The contract shall clarify the following: the specific work entrusted and the corresponding standard operating procedures; the sponsor's right to confirm the implementation of the standard operating procedures for the entrusted work; the written requirements for the entrusted party; the reporting requirements that the entrusted party needs to submit to the sponsor; the matters relating to the measures for compensation for trial subject injury; and other matters relating to the entrusted work. Where the contract research organization subcontracts any task, it shall obtain the written approval of the sponsor. (III) the duties for the work and tasks not expressly entrusted to the contract research organization shall remain the responsibility of the sponsor. (IV) the requirements for the sponsor in these Norms apply to the contract research organization undertaking the relevant work and tasks of the sponsor. **Article 34.** The sponsor shall designate a competent medical expert to promptly provide consultation on the relevant medical issues of the clinical trial. **Article 35.** The sponsor shall select qualified biostatisticians, clinical pharmacologists, clinical physicians and the like to participate in the trial, including designing the trial protocol and case report forms, formulating the statistical analysis plan, analyzing data, and writing the interim and final trial summary reports. **Article 36.** In trial management, data handling and record preservation, the sponsor shall meet the following requirements: (I) the sponsor shall select qualified personnel to supervise the implementation of the clinical trial, data handling, data verification, statistical analysis, and the writing of the trial summary report. (II) the sponsor may establish an independent data monitoring committee to periodically evaluate the progress of the clinical trial, including the safety data and the important efficacy endpoint data. The independent data monitoring committee may recommend to the sponsor whether the clinical trial in progress may be continued, modified or stopped. The independent data monitoring committee shall have a written work process and shall keep all relevant meeting records. (III) the electronic data-management system used by the sponsor shall pass reliable system validation and conform to the pre-set technical performance, so as to ensure the completeness, accuracy and reliability of the trial data and to ensure that the system remains in a validated and effective state throughout the entire trial process. (IV) the electronic data-management system shall have complete standard operating procedures covering the setup, installation and use of the electronic data management; the standard operating procedures shall explain the validation, functional testing, data collection and handling, system maintenance, system security testing, change control, data backup, recovery, system contingency plan and software retirement of the system; the standard operating procedures shall clarify the duties of the sponsor, the investigator and the clinical trial institution when using the computerized system. All personnel using the computerized system shall be trained. (V) the manner of modifying data in the computerized system shall be prescribed in advance, the modification process shall be completely recorded, and the original data (such as the retention of the electronic data audit trail, data trail and editing trail) shall be retained; the integration, content and structure of the electronic data shall be clearly prescribed to ensure the integrity of the electronic data; when a change occurs to the computerized system, such as a software upgrade or data migration, ensuring the integrity of the electronic data is even more important. Where data conversion occurs in the course of data handling, the consistency of the converted data with the original data, and the visibility of the data conversion process, shall be ensured. (VI) the security of the electronic data-management system shall be ensured, and unauthorized personnel shall not be able to access it; a list of the personnel authorized to modify data shall be kept; the electronic data shall be backed up promptly; for a blinded-design clinical trial, the blinded state shall be maintained throughout, including data entry and handling. (VII) the sponsor shall use a subject identification code to identify all clinical trial data of each trial subject. After a blinded trial is unblinded, the sponsor shall promptly inform the investigator in writing of the investigational drug situation of the trial subjects. (VIII) the sponsor shall preserve the clinical trial data relating to the sponsor; some other data obtained by the relevant units participating in the clinical trial shall also be retained in the essential documents of the clinical trial as the specific data of the sponsor. (IX) where the sponsor suspends or terminates early a clinical trial in progress, it shall notify all relevant investigators and clinical trial institutions and the drug administration department. (X) the transfer of ownership of trial data shall comply with the requirements of the relevant laws and regulations. (XI) the sponsor shall inform the investigator and the clinical trial institution in writing of the requirements for the preservation of trial records; when the relevant trial records are no longer needed, the sponsor shall also inform the investigator and the clinical trial institution in writing. **Article 37.** The sponsor's selection of the investigator shall meet the following requirements: (I) the sponsor is responsible for selecting the investigator and the clinical trial institution. The investigators shall all have undergone clinical trial training, have clinical trial experience, and have sufficient medical resources to complete the clinical trial. For a clinical trial in which multiple clinical trial institutions participate, where it is necessary to select a lead institution, the sponsor shall be responsible. (II) the laboratory for sample testing involving medical judgment shall comply with the relevant provisions and possess the corresponding qualifications. The management, testing, transport and storage of the specimens collected in the clinical trial shall ensure quality. Biological-sample testing (such as genetic testing) unrelated to the trial protocol consented to by the ethics committee is prohibited. After the conclusion of the clinical trial, where the remaining specimens are to continue to be preserved or may be used in the future, the trial subject shall sign an informed consent form, explaining the preservation period and the confidentiality of the data, as well as the circumstances under which the data and samples may be shared with other researchers. (III) the sponsor shall provide the investigator and the clinical trial institution with the trial protocol and the latest investigator's brochure, and shall provide the investigator and the clinical trial institution with sufficient time to review the trial protocol and the relevant materials. **Article 38.** Before all parties to the clinical trial participate in the clinical trial, the sponsor shall clarify their duties and indicate them in the concluded contract. **Article 39.** The sponsor shall, by appropriate means, ensure that it can provide compensation or indemnity to the trial subjects and the investigator. (I) the sponsor shall provide the investigator and the clinical trial institution with legal and economic insurance or guarantees relating to the clinical trial, commensurate with the nature and degree of risk of the clinical trial, but this shall not include injury caused by the fault of the investigator and the clinical trial institution themselves. (II) the sponsor shall bear the diagnosis and treatment expenses of the trial subjects for injury or death related to the clinical trial, as well as the corresponding compensation. The sponsor and the investigator shall promptly pay the compensation or indemnity given to the trial subjects. (III) the manner and method by which the sponsor provides compensation to the trial subjects shall comply with the relevant laws and regulations. (IV) the sponsor shall provide the investigational drug to the trial subjects free of charge and pay the medical testing expenses relating to the clinical trial. **Article 40.** The contract concluded by the sponsor with the investigator and the clinical trial institution shall clarify the responsibilities, rights and interests of all parties to the trial, as well as the possible conflicts of interest that all parties shall avoid. The trial funding in the contract shall be reasonable and conform to market rules. The sponsor, the investigator and the clinical trial institution shall sign the contract to confirm it. The contents of the contract shall include: compliance with these Norms and the relevant laws and regulations on the clinical trial in the course of implementing the clinical trial; implementation of the trial protocol determined through consultation between the sponsor and the investigator and consented to by the ethics committee; compliance with the data recording and reporting procedures; agreement to monitoring, audit and inspection; the preservation of and time limit for the essential documents relating to the clinical trial; and the stipulations on publishing articles, intellectual property rights and the like. **Article 41.** Before the clinical trial begins, the sponsor shall submit the relevant clinical trial materials to the drug administration department and obtain the permission for the clinical trial or complete the filing. The submitted document materials shall indicate the version number and version date. **Article 42.** The sponsor shall obtain from the investigator and the clinical trial institution the name and address of the ethics committee, the list of ethics committee members participating in the review of the project, the review statement conforming to these Norms and the relevant laws and regulations, as well as the documents consented to by the ethics committee upon review and other relevant materials. **Article 43.** When formulating the clinical trial protocol, the sponsor shall have sufficient safety and efficacy data to support its route of administration, dosage and duration of continuous medication. When important new information is obtained, the sponsor shall promptly update the investigator's brochure. **Article 44.** The preparation, packaging, labeling and coding of the investigational drug shall meet the following requirements: (I) the preparation of the investigational drug shall comply with the relevant requirements of the good manufacturing practice for drugs used in clinical trials; the packaging label of the investigational drug shall indicate that it is for clinical trial use only, the clinical trial information and the clinical trial drug information; and the blinded state shall be maintained in a blinded trial. (II) the sponsor shall clearly prescribe the storage temperature, transport conditions (whether protection from light is needed), storage time limit, the preparation method and process of the drug solution, and the requirements for the drug infusion device of the investigational drug. The method of use of the investigational drug shall be informed to all personnel relevant to the trial, including the monitor, investigator, pharmacist and drug custodian. (III) the packaging of the investigational drug shall be able to ensure that the drug is not contaminated or deteriorated during transport and storage. (IV) in a blinded trial, the coding system of the investigational drug shall include an emergency unblinding procedure, so that the type of investigational drug can be quickly identified in an emergency medical situation without breaking the blinded state of the clinical trial. **Article 45.** The supply and management of the investigational drug shall meet the following requirements: (I) the sponsor is responsible for providing the investigational drug to the investigator and the clinical trial institution. (II) the sponsor shall not provide the investigational drug to the investigator and the clinical trial institution before the clinical trial has obtained the consent of the ethics committee and the permission or filing of the drug administration department. (III) the sponsor shall provide the investigator and the clinical trial institution with a written instruction on the investigational drug, which shall clarify the use and storage of the investigational drug and the relevant records. The sponsor shall formulate procedures for the supply and management of the investigational drug, including the receipt, storage, dispensing, use and recovery of the investigational drug. The investigational drug recovered from the trial subjects and unused by the research personnel shall be returned to the sponsor, or destroyed by the clinical trial institution upon the authorization of the sponsor. (IV) the sponsor shall ensure that the investigational drug is delivered to the investigator and the clinical trial institution in a timely manner to ensure that the trial subjects can use it promptly; preserve the records of the transport, receipt, dispensing, recovery and destruction of the investigational drug; establish a recovery management system for the investigational drug to ensure the recall of defective products, the recovery after the conclusion of the trial, and the recovery after expiry; and establish a destruction system for unused investigational drug. The entire management process of the investigational drug shall have written records, with accurate counting throughout the entire process. (V) the sponsor shall take measures to ensure the stability of the investigational drug during the trial period. The preservation period of the retained samples of the investigational drug, within the storage time limit of the investigational drug, shall be until the conclusion of the clinical trial data analysis or the time limit required by the relevant regulations, whichever is longer where the two are inconsistent. **Article 46.** The sponsor shall clarify the access rights to the trial records. (I) the sponsor shall, in the trial protocol or contract, clarify that the investigator and the clinical trial institution permit the monitor, auditor, the reviewers of the ethics committee and the inspection personnel of the drug administration department to directly access the source data and source documents relating to the clinical trial. (II) the sponsor shall confirm that each trial subject has consented in writing that the monitor, auditor, the reviewers of the ethics committee and the inspection personnel of the drug administration department may directly access his or her original medical records relating to the clinical trial. **Article 47.** The sponsor is responsible for the safety evaluation of the investigational drug during the drug trial period. The sponsor shall promptly notify the investigator and the clinical trial institution and the drug administration department of the problems discovered in the clinical trial that may affect the safety of the trial subjects, may affect the implementation of the clinical trial, or may change the consent opinion of the ethics committee. **Article 48.** The sponsor shall report adverse drug reactions in accordance with the requirements and time limits. (I) after receiving safety-related information from any source, the sponsor shall immediately analyze and evaluate it, including its seriousness, its relevance to the investigational drug, and whether it is an expected event. The sponsor shall expeditiously report suspected and unexpected serious adverse reactions to all investigators and clinical trial institutions participating in the clinical trial and to the ethics committee; the sponsor shall report suspected and unexpected serious adverse reactions to the drug administration department and the health administration department. (II) the safety update report during the drug development period provided by the sponsor shall include an evaluation of the risks and benefits of the clinical trial, and the relevant information shall be communicated to all investigators and clinical trial institutions participating in the clinical trial and to the ethics committee. **Article 49.** The monitoring of the clinical trial shall meet the following requirements: (I) the purpose of monitoring is to ensure the rights and interests of the trial subjects in the clinical trial, to ensure that the trial records and the reported data are accurate and complete, and to ensure that the trial complies with the consented protocol, these Norms and the relevant regulations. (II) the monitor appointed by the sponsor shall have received corresponding training, possess the medical, pharmaceutical and other knowledge required for clinical trial monitoring, and be able to effectively perform monitoring duties. (III) the sponsor shall establish a systematic, prioritized, risk-assessment-based method for monitoring the implementation of the clinical trial. The scope and nature of the monitoring may be flexible, allowing the adoption of different monitoring methods to improve the efficiency and effectiveness of monitoring. The sponsor shall write the reasons for selecting the monitoring strategy in the monitoring plan. (IV) the sponsor shall formulate a monitoring plan. The monitoring plan shall particularly emphasize protecting the rights and interests of the trial subjects, ensuring the authenticity of the data, and ensuring the response to various risks in the clinical trial. The monitoring plan shall describe the monitoring strategy, the monitoring duties for all parties to the trial, the monitoring methods, and the reasons for applying different monitoring methods. The monitoring plan shall emphasize the monitoring of key data and processes. The monitoring plan shall comply with the relevant laws and regulations. (V) the sponsor shall formulate standard operating procedures for monitoring, and the monitor shall implement the standard operating procedures in the monitoring work. (VI) the sponsor shall implement the monitoring of the clinical trial; the scope and nature of the monitoring depend on the objective, design, complexity, blinding, sample size and clinical trial endpoints of the clinical trial. (VII) on-site monitoring and centralized monitoring shall be combined based on the risks of the clinical trial. On-site monitoring is monitoring conducted at the trial site, generally before, during and after the clinical trial. Centralized monitoring is the timely remote evaluation of the clinical trial in progress, as well as the remote evaluation of the data collected by aggregating data from different clinical trial institutions. The process of centralized monitoring helps to improve the monitoring effect of the clinical trial and is a supplement to on-site monitoring. The application of statistical analysis in centralized monitoring can determine data trends, including the range and consistency of data within and among different clinical trial institutions, and can analyze the characteristics and quality of the data, which helps in selecting monitoring sites and monitoring procedures. (VIII) in special circumstances, the sponsor may combine monitoring with other trial work, such as research personnel training and meetings. During monitoring, the method of statistical sampling survey may be adopted to verify data. **Article 50.** The duties of the monitor include: (I) the monitor shall be familiar with the relevant knowledge of the investigational drug, be familiar with the content of the trial protocol, the informed consent form and other written materials provided to the trial subjects, and be familiar with the standard operating procedures of the clinical trial, these Norms and other relevant regulations. (II) the monitor shall conscientiously perform monitoring duties in accordance with the requirements of the sponsor, ensuring that the clinical trial is correctly implemented and recorded in accordance with the trial protocol. (III) the monitor is the main liaison between the sponsor and the investigator. Before the clinical trial, the monitor confirms that the investigator possesses sufficient qualifications and resources to complete the trial and that the clinical trial institution possesses the appropriate conditions to complete the trial, including staffing and training, complete and well-functioning laboratory equipment, and the conditions for various trial-related examinations. (IV) the monitor shall verify that, in the course of the clinical trial, the investigational drug is within its validity period, the storage conditions are acceptable and the supply is sufficient; that the investigational drug is provided only to suitable trial subjects at the dosage prescribed in the trial protocol; that the trial subjects receive instructions on the correct use, handling, storage and return of the investigational drug; that the clinical trial institution has appropriate controls and records for the receipt, use and return of the investigational drug; and that the clinical trial institution's disposal of the unused investigational drug complies with the relevant laws and regulations and the requirements of the sponsor. (V) the monitor verifies the investigator's implementation of the trial protocol in the course of the clinical trial; confirms that all trial subjects or their guardians signed the informed consent form before the trial; ensures that the investigator receives the latest version of the investigator's brochure, all trial-related documents and trial-essential supplies, and implements them in accordance with the requirements of the relevant laws and regulations; and ensures that the research personnel have a full understanding of the clinical trial. (VI) the monitor verifies that the research personnel perform the duties prescribed in the trial protocol and contract and whether these duties are delegated to unauthorized personnel; confirms that the enrolled trial subjects are eligible and reports the enrollment rate and the progress of the clinical trial; confirms that the recording and reporting of data are correct and complete and that the trial records and documents are updated in real time and well preserved; and verifies that all medical reports, records and documents provided by the investigator are traceable, clear, contemporaneously recorded, original, accurate and complete, and dated and bear the trial number. (VII) the monitor checks the accuracy and completeness of the entries in the case report forms and compares them with the source documents. The monitor shall pay attention to checking that the data prescribed in the trial protocol are accurately recorded in the case report forms and are consistent with the source documents; confirms that the trial subjects' dosage changes, treatment changes, adverse events, concomitant medication, complications, loss to follow-up, missed examinations and the like are all recorded in the case report forms; confirms that the follow-ups not conducted, the trials not implemented and the examinations not done by the investigator, as well as whether corrections were made to errors and omissions, are all recorded in the case report forms; and verifies that the withdrawal and loss to follow-up of the enrolled trial subjects are all recorded and explained in the case report forms. (VIII) the monitor shall notify the investigator of filling-in errors, omissions or illegible handwriting in the case report forms; the monitor shall ensure that the corrections, additions or deletions made are operated by the investigator or an authorized person, and bear the signature and date of the person making the modification, with the reasons for the modification explained where necessary. (IX) the monitor confirms that adverse events have been reported within the prescribed time limit in accordance with the relevant laws and regulations, the trial protocol, the ethics committee and the requirements of the sponsor. (X) the monitor confirms whether the investigator has preserved the essential documents in accordance with these Norms. (XI) the monitor shall promptly communicate with the investigator on situations that deviate from the trial protocol, the standard operating procedures and the requirements of the relevant laws and regulations, and take appropriate measures to prevent recurrence. **Article 51.** After each monitoring, the monitor shall promptly report in writing to the sponsor; the report shall include the monitoring date, location, the name of the monitor, and the names of the investigator and other personnel whom the monitor contacted; the report shall include a summary of the monitoring work, a statement of the problems and facts discovered in the clinical trial, deviations from and deficiencies in the trial protocol, and the monitoring conclusion; the report shall explain the corrective measures already taken or to be adopted for the problems discovered during the monitoring, and the recommendations for ensuring that the trial is implemented in compliance with the trial protocol; and the report shall provide sufficient detail to enable a review of whether it complies with the monitoring plan. The centralized monitoring report may be submitted separately from the on-site monitoring report. The sponsor shall review and follow up on the problems in the monitoring report and form documents for preservation. **Article 52.** The audit of the clinical trial shall meet the following requirements: (I) in order to evaluate the implementation of the clinical trial and compliance with the laws and regulations, the sponsor may carry out an audit in addition to routine monitoring. (II) the sponsor shall select personnel independent of the clinical trial to serve as auditors, who shall not concurrently serve as monitoring personnel. The auditor shall have undergone corresponding training and have audit experience, and be able to effectively perform audit duties. (III) the sponsor shall formulate audit procedures for the clinical trial and the trial quality management system to ensure the implementation of the audit procedures in the clinical trial. These procedures shall set out the audit objective, audit methods, number of audits, and the format and content of the audit report. The problems observed and discovered by the auditor in the course of the audit shall all have written records. (IV) the sponsor shall formulate the audit plan and procedures on the basis of the content of the materials submitted to the drug administration department, the number of trial subjects in the clinical trial, the type and complexity of the clinical trial, the level of risk affecting the trial subjects, and other known relevant problems. (V) the drug administration department may, according to work needs, require the sponsor to provide the audit report. (VI) where necessary, the sponsor shall provide an audit certificate. **Article 53.** The sponsor shall ensure the compliance of the clinical trial. (I) where it is discovered that the personnel of the investigator, the clinical trial institution or the sponsor do not comply with the trial protocol, the standard operating procedures, these Norms or the relevant laws and regulations in the clinical trial, the sponsor shall immediately take measures to correct it, so as to ensure the good compliance of the clinical trial. (II) where an important compliance problem is discovered that may have a significant impact on the safety and rights and interests of the trial subjects, or on the reliability of the clinical trial data, the sponsor shall promptly conduct a root-cause analysis and take appropriate corrective and preventive measures. Where the problem of violating the trial protocol or these Norms is serious, the sponsor may pursue the responsibility of the relevant personnel and report to the drug administration department. (III) where it is discovered that the investigator or the clinical trial institution has a serious or persistent non-compliance problem that cannot be deterred, the sponsor shall terminate the continued participation of that investigator or clinical trial institution in the clinical trial and promptly report in writing to the drug administration department. At the same time, the sponsor and the investigator shall take corresponding emergency safety measures to protect the safety and rights and interests of the trial subjects. **Article 54.** Where the sponsor terminates or suspends a clinical trial early, it shall immediately inform the investigator and the clinical trial institution and the drug administration department and explain the reasons. **Article 55.** Upon the completion or early termination of the clinical trial, the sponsor shall submit the clinical trial report to the drug administration department in accordance with the requirements of the 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 of the clinical trial summary report shall be consistent with the source data of the clinical trial. **Article 56.** Where the sponsor conducts a multicenter trial, the following requirements shall be met: (I) the sponsor shall ensure that all centers participating in the clinical trial are able to comply with the trial protocol. (II) the sponsor shall provide all centers with the same trial protocol. Each center shall, in accordance with the protocol, comply with the same unified evaluation criteria for clinical and laboratory data and the same completion guidelines for the case report forms. (III) all centers shall use the same case report form to record the trial data obtained in the clinical trial. Where the sponsor needs the investigator to collect additional trial data, this content shall be indicated in the trial protocol, and the sponsor shall provide the investigator with additional case report forms. (IV) before the clinical trial begins, there shall be a written document clarifying the duties of the investigators at the centers participating in the clinical trial. (V) the sponsor shall ensure communication among the investigators at the centers. ## Chapter 6 Trial Protocol **Article 57.** The trial protocol usually includes basic information, research background materials, the trial objective, the trial design, the manner of implementation (methods, content, steps) and other contents. **Article 58.** The basic information in the trial protocol generally includes: (I) the title, number, version number and date of the trial protocol. (II) the name and address of the sponsor. (III) the name, position and unit of the personnel authorized by the sponsor to sign and modify the trial protocol. (IV) the name, position, unit address and telephone number of the sponsor's medical expert. (V) the name, professional title and position of the investigator, and the address and telephone number of the clinical trial institution. (VI) the names, addresses of the units and relevant departments participating in the clinical trial. **Article 59.** The research background materials in the trial protocol usually include: (I) the name and introduction of the investigational drug. (II) the findings in the non-clinical and clinical research of the investigational drug that are relevant to the clinical trial and have potential clinical significance. (III) the known and potential risks and benefits to the trial subject population. (IV) a description of the route of administration, dosage, method of administration and duration of treatment of the investigational drug, with reasons stated. (V) emphasis that the clinical trial needs to be implemented in accordance with the trial protocol, these Norms and the relevant laws and regulations. (VI) the target population of the clinical trial. (VII) the research background materials, references and data sources relating to the clinical trial. **Article 60.** The trial protocol shall describe in detail the objective of the clinical trial. **Article 61.** The scientific validity of the clinical trial and the reliability of the trial data mainly depend on the trial design, which usually includes: (I) clarifying the primary endpoints and secondary endpoints of the clinical trial. (II) the reasons for the selection of the control group and a description of the trial design (such as double-blind, placebo-controlled, parallel-group design), with the research design, processes and different stages represented in the form of a flowchart. (III) the measures taken to reduce or control bias, including the methods and processes of randomization and blinding. Where a single-blind or open-label trial is adopted, the reasons and the measures to control bias shall be explained. (IV) the treatment methods, the dosage and administration regimen of the investigational drug; the dosage form, packaging and labeling of the investigational drug. (V) the anticipated duration and specific arrangements of the trial subjects' participation in the clinical trial, including follow-up and the like. (VI) the "trial suspension criteria" and "trial termination criteria" for the trial subjects, part of the clinical trial and the entire clinical trial. (VII) the management process of the investigational drug. (VIII) the procedures for the preservation of the blinding code and for unblinding. (IX) clarifying what trial data may be directly recorded in the case report forms as source data. **Article 62.** The trial protocol usually includes the items of clinical and laboratory examinations. **Article 63.** The selection and withdrawal of trial subjects usually include: (I) the inclusion criteria for trial subjects. (II) the exclusion criteria for trial subjects. (III) the criteria and procedures for trial subjects to withdraw from the clinical trial. **Article 64.** The treatment of trial subjects usually includes: (I) the names, dosages, administration regimens, routes of administration, treatment times and follow-up periods of all investigational drugs used by the trial subjects in each group of the clinical trial. (II) the concomitant medication (including emergency treatment medication) or treatment permitted before and during the clinical trial, and the drugs or treatments prohibited from use. (III) the methods for evaluating the compliance of the trial subjects. **Article 65.** A clear visit and follow-up plan shall be formulated, including the follow-up and medical treatment during the clinical trial period, at the clinical trial endpoint, in the adverse event evaluation, and after the conclusion of the trial. **Article 66.** Efficacy evaluation usually includes: (I) a detailed description of the efficacy indicators of the clinical trial. (II) a detailed description of the evaluation, recording, analysis methods and time points of the efficacy indicators. **Article 67.** Safety evaluation usually includes: (I) a detailed description of the safety indicators of the clinical trial. (II) a detailed description of the evaluation, recording, analysis methods and time points of the safety indicators. (III) the procedures for recording and reporting adverse events and concomitant illnesses. (IV) the manner and period of follow-up of adverse events. **Article 68.** Statistics usually include: (I) determining the trial subject sample size and explaining the reasons based on earlier trial or literature data. (II) the significance level; where there is any adjustment, the consideration shall be explained. (III) explaining the statistical hypotheses of the primary evaluation indicator, including the null hypothesis and the alternative hypothesis, and briefly describing the specific statistical methods and statistical analysis software to be adopted. Where an interim analysis needs to be conducted, the reasons, the analysis time points and the operating procedures shall be explained. (IV) the methods for handling missing data, unused data and illogical data. (V) clarifying the procedures for modifications that deviate from the original statistical analysis plan. (VI) clearly defining the trial subject data sets used for statistical analysis, including all trial subjects who participated in randomization, all trial subjects who took the investigational drug, all trial subjects who met the inclusion criteria, and the trial subjects who can be used for the evaluation of the clinical trial results. **Article 69.** The trial protocol shall include the implementation of quality control and quality assurance of the clinical trial. **Article 70.** The trial protocol usually includes the consideration of the ethical issues relating to the trial. **Article 71.** The trial protocol usually explains the process for the collection and management of trial data, the system used for data management and collection, the steps and tasks of data management, and the quality assurance measures for data management. **Article 72.** If not stipulated in the contract or agreement, the trial protocol usually includes the direct access to source documents, data handling and record preservation, finance and insurance relating to the clinical trial. ## Chapter 7 Investigator's Brochure **Article 73.** The Investigator's Brochure provided by the sponsor is a compilation of the pharmaceutical, non-clinical and clinical materials on the investigational drug, the content of which includes the chemical, pharmaceutical, toxicological, pharmacological and clinical materials and data of the investigational drug. The purpose of the investigator's brochure is to help the investigator and the other personnel participating in the trial to better understand and comply with the trial protocol, and to help the investigator understand the many key basic elements in the trial protocol, including the dosage, frequency of administration, administration interval and mode of administration of the clinical trial, and the observation and monitoring of the primary and secondary efficacy indicators and safety. **Article 74.** Where a marketed drug undergoes a clinical trial and the investigator already fully understands its pharmacological and other relevant knowledge, the investigator's brochure may be simplified. The package insert and other forms may be used to replace part of the content of the investigator's brochure, and only the relevant, important and most recent comprehensive and detailed information on the clinical trial and the investigational drug needs to be provided to the investigator. **Article 75.** The sponsor shall formulate written procedures for the revision of the investigator's brochure. The investigator's brochure shall be reviewed at least once a year during the clinical trial period. The sponsor shall, based on the development steps of the clinical trial and the new information on the safety and efficacy of the relevant drug obtained in the course of the clinical trial, first inform the investigator before the investigator's brochure is updated, and communicate with the ethics committee and the drug administration department where necessary. The sponsor is responsible for updating the investigator's brochure and delivering it to the investigator promptly, and the investigator is responsible for submitting the updated brochure to the ethics committee. **Article 76.** The title page of the investigator's brochure shall state the name of the sponsor, the number or name of the investigational drug, the version number, the release date, the replaced version number and the replacement date. **Article 77.** The investigator's brochure shall include: (I) table of contents entries: confidentiality statement, signature page, table of contents, abstract, foreword, the physical, chemical and pharmaceutical properties and structural formula of the investigational drug, non-clinical research (non-clinical pharmacology, in vivo pharmacokinetics in animals, toxicology), effects in the human body (pharmacokinetics in the human body, safety and efficacy, marketing use situation), data summary and investigator guidance, precautions, and references (published literature and reports, listed at the end of each chapter). (II) abstract: emphasizing the physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic and clinical information of significant importance in the development of the investigational drug. (III) foreword: briefly explaining the chemical name or approved generic name and the approved trade name of the investigational drug; all active ingredients, the pharmacological classification of the investigational drug and its anticipated position (such as advantages) among similar drugs; the rationale for conducting a clinical trial of the investigational drug; and the proposed use of the investigational drug for the prevention, diagnosis and treatment of disease. The foreword shall explain the conventional methods for evaluating the investigational drug. (IV) the investigator's brochure shall clearly explain the chemical formula and structural formula of the investigational drug and briefly describe its physicochemical and pharmaceutical properties. It shall explain the storage method and method of use of the investigational drug. Where the formulation information of the investigational drug may affect the clinical trial, the excipient ingredients and the reasons for the formulation shall be explained, so as to ensure that the necessary safety measures are taken in the clinical trial. (V) where the investigational drug is structurally similar to other known drugs, this shall be explained. (VI) introduction to non-clinical research: briefly describing the relevant results found in the pharmacological, toxicological and pharmacokinetic research of the non-clinical research of the investigational drug. It shall explain the methodology and research results of these non-clinical studies and discuss the implications of these findings for human clinical treatment, the possible adverse effects on the human body, and the relevance of unexpected effects on the human body. (VII) the investigator's brochure shall provide the information in the non-clinical research: the species of test animals, the number and sex of animals in each group, the dosage unit, the dosage interval, the route of administration, the duration of administration, the systemic distribution data, and the follow-up period after exposure. The research results shall include the characteristics and frequency of the pharmacological and toxic effects of the investigational drug; the severity or intensity of the pharmacological and toxic effects; the time of onset of effect; the reversibility of the pharmacological effect; and the duration of drug action and the dose response. The most important findings in the non-clinical research, such as the dose-effect response, the possible relevance to the human body and the various aspects of possibly implementing human research, shall be discussed. Where the results of the effective dose and the non-toxic dose in the same species of animal can be compared for research, such results may be used for the discussion of the therapeutic index, and the relevance of the research results to the proposed human dose shall be explained. The comparative research shall be based, as far as possible, on blood or organ tissue levels. (VIII) introduction to non-clinical pharmacological research: shall include an abstract of the pharmacological aspects of the investigational drug and, where possible, important metabolism research of the investigational drug in animals. The abstract shall include research evaluating the potential therapeutic activity of the investigational drug (such as efficacy models, receptor binding and specificity), as well as research evaluating the safety of the investigational drug (such as specialized research on pharmacological effects different from the evaluation of therapeutic effects). (IX) introduction to pharmacokinetics in animals: shall include an abstract of the pharmacokinetics, biotransformation and distribution of the investigational drug in the animal species studied. The discussion of the findings shall explain the absorption, local and systemic bioavailability and metabolism of the investigational drug, and their relationship with the pharmacological and toxicological findings of the animal species. (X) introduction to toxicology: the abstract of the toxicological effects found in the relevant research in different animal species shall include single-dose administration, repeated-dose administration, carcinogenicity, special toxicological research (such as irritation and sensitization), reproductive toxicity, genetic toxicity (mutagenicity) and other aspects. (XI) effects in the human body: the known effects of the investigational drug in the human body shall be fully discussed, including pharmacokinetics, pharmacodynamics, dose response, safety, efficacy and information in other pharmacological fields. An abstract of all completed clinical trials of the investigational drug shall be provided as far as possible. The use of the investigational drug other than in clinical trials, such as experience during marketing, shall also be provided. (XII) an abstract of the pharmacokinetic information of the investigational drug in the human body, including pharmacokinetics (absorption and metabolism, plasma protein binding, distribution and elimination); the bioavailability (absolute and relative bioavailability) of a reference dosage form of the investigational drug; population subgroups (such as sex, age and impaired organ function); interactions (such as drug-drug interactions and the effect of food); and other pharmacokinetic data (such as the results of population research completed during the clinical trial period). (XIII) safety and efficacy of the investigational drug: an abstract and discussion of the information on the safety, pharmacodynamics, efficacy and dose response of the investigational drug (including metabolites) obtained from earlier human trials shall be provided. Where multiple clinical trials have been completed, the safety and efficacy data of multiple studies and subgroup populations shall be summarized. Consideration may be given to clearly summarizing, in tabular or other form, the adverse drug reactions of all clinical trials (including all indications studied). The important differences in the types and incidence of adverse drug reactions among indications or subgroups shall be discussed. (XIV) marketing use situation: the main countries and regions where the investigational drug has been marketed or approved shall be explained. The important information obtained from marketing use (such as the formulation, dosage, route of administration and adverse drug reactions) shall be summarized. The main countries and regions where the investigational drug has not been approved for marketing or has been withdrawn from the market shall be explained. (XV) data summary and investigator guidance: a comprehensive analysis and discussion of the non-clinical and clinical data shall be conducted, summarizing the information on different aspects of the investigational drug from various sources, so as to help the investigator anticipate adverse drug reactions or other problems in the clinical trial. (XVI) the investigator's brochure shall enable the investigator to clearly understand the possible risks and adverse reactions of the clinical trial, as well as the special examinations, observation items and preventive measures that may be required; this understanding is based on the physical, chemical, pharmaceutical, pharmacological, toxicological and clinical materials on the investigational drug obtained from the investigator's brochure. Based on the earlier human-use experience and the pharmacology of the investigational drug, the investigator shall also be provided with guidance on the identification and handling measures for possible overdose and adverse drug reactions. (XVII) the content of the investigator's brochure for traditional Chinese medicines and ethnic medicines shall be formulated with reference to the above requirements. It shall also indicate the theoretical basis of the formulation, screening information, compatibility, functions, indications, existing human-use medication experience, the original plant source and place of origin of the medicinal materials and the like; for compound traditional-Chinese-medicine preparations derived from ancient classic famous formulas, their source shall be indicated; and the materials such as the relevant medicinal materials and prescriptions shall be provided. ## Chapter 8 Management of Essential Documents **Article 78.** The essential documents of a clinical trial are documents for evaluating the implementation of the clinical trial and the quality of the data, used to prove that the investigator, the sponsor and the monitor complied with these Norms and the relevant laws and regulations on drug clinical trials in the course of the clinical trial. The essential documents are important content for the sponsor's audit and the drug administration department's inspection of the clinical trial, and serve as the basis for confirming the authenticity of the implementation of the clinical trial and the completeness of the data collected. **Article 79.** The sponsor, the investigator and the clinical trial institution shall confirm that they all have premises and conditions for preserving the essential documents of the clinical trial. The equipment and conditions for preserving the documents shall be able to prevent direct exposure to light, be waterproof and fireproof, and be conducive to the long-term preservation of the documents. Standard operating procedures for document management shall be formulated. The preserved documents shall be easy to identify, search, consult and return to place. The medium used to preserve the clinical trial materials shall ensure that the source data or their certified copies are preserved completely and remain readable during the retention period, and the ability to recover and read them shall be tested or checked periodically, so as to avoid intentional or unintentional alteration or loss. Where some documents generated in the course of the clinical trial are not listed in the management catalogue of essential documents of the clinical trial, the sponsor, the investigator and the clinical trial institution may also, based on necessity and relevance, include them in their respective essential-document archives for preservation. **Article 80.** For a clinical trial used to apply for drug registration, the essential documents shall be preserved at least until 5 years after the investigational drug is approved for marketing; for a clinical trial not used to apply for drug registration, the essential documents shall be preserved at least until 5 years after the termination of the clinical trial. **Article 81.** The sponsor shall ensure that the investigator can at all times consult and, in the course of the trial, enter and correct the data in the case report forms reported to the sponsor, and that such data are not controlled solely by the sponsor. The sponsor shall ensure that the investigator can retain the case report form data that have been submitted to the sponsor. Copies used as source documents shall meet the requirements for certified copies. **Article 82.** At the beginning of the clinical trial, both the investigator and the clinical trial institution and the sponsor shall establish the archive management of the essential documents. At the conclusion of the clinical trial, the monitor shall review and confirm the essential documents of the investigator and the clinical trial institution and the sponsor, and these documents shall be properly preserved in their respective clinical trial archive files. ## Chapter 9 Supplementary Provisions **Article 83.** These Norms shall come into force on July 1, 2020.