Promulgated by: National Medical Products Administration; National Health Commission. Announcement No. 28 of 2022 of the National Medical Products Administration and the National Health Commission.
In order to deepen the reform of the medical device review and approval system and strengthen the administration of medical device clinical trials, in accordance with the Regulation on the Supervision and Administration of Medical Devices (Order No. 739 of the State Council), the Measures for the Administration of Medical Device Registration and Filing (Order No. 47 of the State Administration for Market Regulation) and the Measures for the Administration of In-Vitro Diagnostic Reagent Registration and Filing (Order No. 48 of the State Administration for Market Regulation), the National Medical Products Administration, together with the National Health Commission, has organized the revision of the Good Clinical Practice for Medical Devices, which is hereby promulgated and shall come into force on May 1, 2022.
This is hereby announced.
Attachment: Good Clinical Practice for Medical Devices
National Medical Products Administration; National Health Commission March 24, 2022
Chapter 1 General Provisions
Article 1. These Norms are formulated in accordance with the Regulation on the Supervision and Administration of Medical Devices in order to strengthen the administration of medical device clinical trials, safeguard the rights, interests and safety of trial subjects, and ensure that the process of medical device clinical trials is well-regulated and that the results are authentic, accurate, complete and traceable.
Article 2. The activities relating to medical device clinical trials conducted within the territory of the People’s Republic of China for the purpose of applying for the registration of medical devices (including in-vitro diagnostic reagents, the same below) shall comply with these Norms.
These Norms cover the entire process of medical device clinical trials, including the protocol design, implementation, monitoring, audit and inspection of the medical device clinical trial, as well as the collection, recording, retention, analysis, summarization and reporting of data.
Article 3. Medical device clinical trials shall comply with the ethical principles of the Declaration of Helsinki of the World Medical Association and the relevant State norms on the ethics of biomedical research involving human beings. The parties participating in a medical device clinical trial shall bear the corresponding ethical responsibilities in accordance with their respective duties in the trial.
Article 4. The conduct of a medical device clinical trial shall have a sufficient scientific basis and a clear trial objective, and shall weigh the anticipated risks and benefits to the trial subjects and to society. A clinical trial may be conducted or continued only when the anticipated benefits outweigh the risks.
Article 5. A medical device clinical trial shall be conducted at a medical device clinical trial institution that possesses the corresponding conditions and has been filed in accordance with the provisions.
Article 6. A medical device clinical trial shall obtain the consent of the ethics committee. Where the device is included in the catalogue of Class III medical devices subject to clinical trial approval, the trial shall also obtain the approval of the National Medical Products Administration and be conducted at a Grade III Class A medical institution that meets the requirements.
Article 7. The sponsor of a medical device clinical trial shall establish a quality management system covering the entire process of the medical device clinical trial to ensure that the medical device clinical trial complies with the relevant laws and regulations and protects the rights, interests and safety of the trial subjects.
Chapter 2 Ethics Committee
Article 8. The duty of the ethics committee is to protect the lawful rights, interests and safety of trial subjects and to safeguard the dignity of trial subjects.
Article 9. The ethics committee shall comply with the ethical principles of the Declaration of Helsinki of the World Medical Association and the provisions of the relevant laws and regulations. The composition, operation and filing administration of the ethics committee shall meet the requirements of the health administration department.
Article 10. All members of the ethics committee shall receive training in ethics knowledge, these Norms and the relevant laws and regulations, be familiar with the ethical principles of medical device clinical trials and the provisions of the relevant laws and regulations, and comply with the working procedures of the ethics committee.
Article 11. Before a medical device clinical trial begins, the sponsor shall, through the principal investigator, submit the following documents to the ethics committee:
(I) the clinical trial protocol;
(II) the investigator’s brochure;
(III) the informed consent form text and any other written materials provided to the trial subjects;
(IV) procedural documents for recruiting trial subjects and for publicity directed at them (if applicable);
(V) the case report form text;
(VI) the product inspection report based on the product technical requirements;
(VII) materials relating to the preclinical research;
(VIII) the resume, professional expertise, competence, training received and other documents able to prove the qualifications of the principal investigator;
(IX) a statement that the development of the investigational medical device complies with the relevant requirements of the applicable medical device quality management system;
(X) other documents relating to the ethical review.
Article 12. The ethics committee shall review the ethicality and scientific validity of the medical device clinical trial, and shall focus on the following:
(I) the qualifications and experience of the principal investigator and whether he or she has sufficient time to participate in the clinical trial;
(II) whether the staffing, equipment and other conditions for the clinical trial meet the trial requirements;
(III) whether the degree of risk that the trial subjects may suffer is appropriate compared with the anticipated benefits of the trial;
(IV) whether the clinical trial protocol has fully considered the ethical principles and is scientifically valid, including whether the research objectives are appropriate, whether the rights, interests and safety of the trial subjects are safeguarded, and whether the risks that other personnel may suffer are fully protected;
(V) whether the information and materials about the trial provided to the trial subjects are complete, whether they clearly inform the subjects of the rights they are entitled to, whether the subjects can understand the contents of the informed consent form, and whether the method of obtaining informed consent is appropriate;
(VI) whether the inclusion and exclusion of trial subjects are scientific and fair;
(VII) whether the trial subjects obtain reasonable compensation for participating in the clinical trial, and whether the diagnosis, treatment and safeguard measures provided are sufficient in the event that a subject suffers injury or death related to the clinical trial;
(VIII) whether the protection of trial subjects from special populations, such as children, pregnant women, the elderly, persons with intellectual disabilities and patients with mental disorders, is sufficient.
Article 13. The review opinion of the ethics committee may be:
(I) approval;
(II) approval after necessary modifications;
(III) disapproval;
(IV) suspension or termination of an already-approved trial.
Where the review opinion requires modifications or constitutes a denial, the reasons shall be stated.
Article 14. The informed consent form shall generally include the following contents and explanations of relevant matters:
(I) the name of the principal investigator and relevant information;
(II) the name of the medical device clinical trial institution;
(III) the name, objective, methods and content of the clinical trial;
(IV) the process and duration of the clinical trial;
(V) the funding source of the clinical trial and possible conflicts of interest;
(VI) the anticipated possible benefits to the trial subjects and the known and foreseeable risks, as well as the adverse events that may occur;
(VII) information on the alternative diagnostic and treatment methods available to the trial subjects and their potential benefits and risks;
(VIII) where applicable, an explanation that the trial subjects may be allocated to different groups of the clinical trial;
(IX) that the trial subjects’ participation in the clinical trial is voluntary and that they have the right to withdraw at any stage of the clinical trial without being discriminated against or retaliated against, and that their medical treatment and rights and interests will not be affected;
(X) informing the trial subjects that their personal data relating to participation in the clinical trial are confidential, but that the administrative department of the medical device clinical trial institution, the ethics committee, the drug administration department, the health administration department, or the monitor or auditor may, where necessary for their work, consult the personal data of the trial subjects relating to participation in the clinical trial in accordance with prescribed procedures;
(XI) the free diagnostic and treatment items and other relevant compensation that the trial subjects may obtain during the clinical trial;
(XII) the treatment and/or compensation that the trial subjects may obtain in the event of injury related to the clinical trial;
(XIII) that the trial subjects may at any time during the clinical trial obtain information and materials relating to themselves.
The informed consent form shall indicate the version and date on which it was formulated, or the version and date after revision. The informed consent form shall use language and wording that the trial subjects can understand. The informed consent form shall not contain content that would cause the trial subjects to waive their lawful rights and interests or that would exempt the medical device clinical trial institution, the principal investigator or the sponsor from the responsibilities they should bear.
Article 15. Follow-up review by the ethics committee:
(I) the ethics committee shall conduct follow-up supervision of the medical device clinical trial, and where it discovers that the rights, interests and safety of the trial subjects cannot be safeguarded or other circumstances exist, it may at any time require in writing the suspension or termination of the clinical trial;
(II) the ethics committee shall review safety information such as serious adverse events occurring at the trial institution reported by the investigator, and review safety information such as serious adverse events relating to the investigational medical device reported by the sponsor. The ethics committee may require modifications to the clinical trial protocol, the informed consent form and other information provided to the trial subjects, and may suspend or terminate the clinical trial;
(III) the ethics committee shall review the possible impact of deviations from the clinical trial protocol on the rights, interests and safety of the trial subjects, or the possible impact on the scientific validity and integrity of the medical device clinical trial.
Article 16. In the course of a medical device clinical trial, the revision of documents such as the clinical trial protocol and the informed consent form, and the resumption of a suspended clinical trial, may be implemented only after the written consent of the ethics committee has again been obtained.
Article 17. The ethics committee shall preserve all records of the ethical review, including the written records of the ethical review, member information, submitted documents, meeting minutes and relevant correspondence records.
Chapter 3 Medical Device Clinical Trial Institutions
Article 18. A medical device clinical trial institution shall meet the filing conditions and establish a clinical trial management organizational structure and management system. A medical device clinical trial institution shall have a corresponding clinical trial management department to undertake the management of medical device clinical trials.
Article 19. The management department of a medical device clinical trial institution shall be responsible for filling in, managing and changing the filing information of the medical device clinical trial institution in the medical device clinical trial institution filing administration information system, including information on clinical trial specialties and principal investigators; for submitting online, in the filing system, the summary report on the medical device clinical trial work carried out in the previous year; and, before the ethics committee reviews the medical device clinical trial, for organizing the assessment of the qualifications of the principal investigator of the clinical trial and completing the filing thereof.
Article 20. A medical device clinical trial institution shall establish a quality management system covering the entire process of the implementation of medical device clinical trials, including systems for training and assessment, the implementation of clinical trials, the management of medical devices, the management of biological samples, the handling of adverse events and device defects and the reporting of safety information, recording, and quality control, so as to ensure that the principal investigator performs his or her duties relating to the clinical trial, that the trial subjects receive proper medical treatment, and that the authenticity of the data generated by the trial is ensured.
Article 21. Before accepting a medical device clinical trial, a medical device clinical trial institution shall, based on the characteristics of the investigational medical device, assess the relevant resources to ensure that it possesses matching qualifications, personnel, facilities and conditions.
Article 22. The medical device clinical trial institution and the investigators shall cooperate with the monitoring and audit organized by the sponsor, as well as the inspections carried out by the drug administration department and the health administration department.
Article 23. The medical device clinical trial institution shall properly preserve the clinical trial records and essential documents in accordance with the relevant laws and regulations and the contract with the sponsor.
Chapter 4 Investigators
Article 24. The principal investigator responsible for a medical device clinical trial shall meet the following conditions:
(I) having completed the filing as a principal investigator of medical device clinical trials;
(II) being familiar with these Norms and the relevant laws and regulations;
(III) possessing the professional knowledge and experience required for the use of the investigational medical device, having undergone training relating to clinical trials, having experience in clinical trials, and being familiar with the medical device clinical trial protocol, the investigator’s brochure and other materials provided by the sponsor;
(IV) having the ability to coordinate, mobilize and use the personnel and equipment for conducting the medical device clinical trial, and the ability to handle the adverse events and other associated events occurring in the medical device clinical trial.
Article 25. The principal investigator shall ensure that the medical device clinical trial complies with the latest version of the clinical trial protocol consented to by the ethics committee, and shall, within the agreed time limit, conduct the medical device clinical trial in accordance with the provisions of these Norms and the relevant laws and regulations.
Article 26. The principal investigator may, in accordance with the needs of the medical device clinical trial, authorize investigators who have undergone training relating to clinical trials to organize and carry out subject recruitment and informed consent, screening and follow-up; the management and use of the investigational medical device and the control medical device (if applicable); the management and use of biological samples (if applicable); the handling of adverse events and device defects; the recording of clinical trial data and the completion of case report forms; and so on.
Article 27. Investigators participating in a medical device clinical trial shall:
(I) possess the professional and technical qualifications, training experience and relevant experience corresponding to undertaking the medical device clinical trial;
(II) participate in the training relating to the medical device clinical trial organized by the sponsor, and participate in the medical device clinical trial within the scope authorized by the principal investigator;
(III) be familiar with the principles, scope of application or intended use, product performance, operating methods, installation requirements and technical indicators of the investigational medical device, and understand the materials relating to the preclinical research of the investigational medical device;
(IV) fully understand and comply with the clinical trial protocol, these Norms and the provisions of the relevant laws and regulations, as well as the duties relating to the medical device clinical trial;
(V) master the methods for preventing and handling on an emergency basis the risks that the clinical trial may give rise to.
Article 28. Investigators shall comply with the ethical principles of the Declaration of Helsinki of the World Medical Association and the relevant ethical requirements, and shall meet the following requirements:
(I) using 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;
(II) before the trial subjects participate in the clinical trial, explaining to the trial subjects the detailed circumstances relating to the investigational medical device and the clinical trial, and informing the trial subjects of the possible benefits and the known and foreseeable risks; after full and detailed explanation, the trial subject shall sign his or her name and the date on the informed consent form, and the investigator shall also sign his or her name and the date on the informed consent form;
(III) where a trial subject is a person without civil capacity or with limited civil capacity, the written informed consent of his or her guardian shall be obtained in accordance with the law; where a trial subject lacks reading ability, an impartial witness shall witness the entire informed consent process and sign and date the informed consent form;
(IV) not coercing or improperly inducing trial subjects by other means to participate in the clinical trial;
(V) ensuring that, after the informed consent form is updated and reviewed and consented to by the ethics committee, all affected subjects whose trial procedures have not yet concluded sign the newly revised informed consent form.
Article 29. Investigators have management responsibility for the investigational medical device and the control medical device (if applicable) provided by the sponsor, and shall ensure that they are used only for the trial subjects participating in the medical device clinical trial, store and keep them as required during the clinical trial, and dispose of them after the completion or termination of the clinical trial in accordance with the relevant laws and regulations and the contract with the sponsor.
Article 30. Investigators shall ensure that the collection, handling, preservation, transport and destruction of biological samples in the medical device clinical trial comply with the clinical trial protocol and the relevant laws and regulations.
Article 31. Where an adverse event occurs during a medical device clinical trial, the investigator shall provide the trial subject with sufficient and timely treatment and handling; where a trial subject develops a concomitant illness requiring treatment and handling, the investigator shall promptly inform the trial subject. The investigator shall record the adverse events occurring and the device defects discovered in the course of the medical device clinical trial.
Article 32. Investigators shall promptly report safety information in the medical device clinical trial:
(I) where a serious adverse event occurs during a medical device clinical trial, the investigator shall immediately take appropriate treatment measures for the trial subject; at the same time, the investigator shall, within 24 hours after becoming aware of the serious adverse event, report to the sponsor, the management department of the medical device clinical trial institution and the ethics committee; and shall follow up the serious adverse event in accordance with the provisions of the clinical trial protocol and submit a follow-up report on the serious adverse event;
(II) where it is discovered that the risks of the medical device clinical trial outweigh the possible benefits and the clinical trial needs to be suspended or terminated, the principal investigator shall report to the sponsor, the management department of the medical device clinical trial institution and the ethics committee, promptly notify the trial subjects, and ensure that the trial subjects receive appropriate treatment and follow-up.
Article 33. The principal investigator shall promptly handle the safety information received:
(I) upon receiving serious-adverse-event and other safety information relating to the investigational medical device 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, and communicate with the trial subjects as early as possible where necessary;
(II) upon receiving a notice from the sponsor or the ethics committee that the medical device clinical trial needs to be suspended or terminated, he or she shall promptly notify the trial subjects and ensure that the trial subjects receive appropriate treatment and follow-up.
Article 34. The principal investigator shall report to the ethics committee on the progress of the medical device clinical trial on time, and promptly report events affecting the rights, interests and safety of the trial subjects or deviations from the clinical trial protocol.
Article 35. Where the sponsor seriously or continuously violates these Norms and the relevant laws and regulations, or requires changes to the trial data or conclusions, the medical device clinical trial institution and the investigators shall report in writing to the drug administration department of the province, autonomous region or municipality directly under the Central Government where the sponsor is located.
Chapter 5 Sponsors
Article 36. The sponsor shall be responsible for the authenticity and compliance of the medical device clinical trial. Where the sponsor is an overseas institution, it shall, in accordance with the relevant laws and regulations, designate an enterprise legal person within the territory of China as its agent, who shall assist the sponsor in performing its duties.
Article 37. The sponsor’s quality management system shall cover the entire process of the medical device clinical trial, including the selection of the medical device clinical trial institution and the principal investigator, the design of the clinical trial protocol, the implementation of the medical device clinical trial, recording, the reporting of results, and document filing. The sponsor’s quality management measures shall be commensurate with the risks of the clinical trial.
Article 38. Before initiating a medical device clinical trial, the sponsor shall:
(I) ensure that the product design has been finalized and the preclinical research of the investigational medical device has been completed, including performance verification and validation, the product inspection report based on the product technical requirements, and the risk-benefit analysis, and that the results are able to support the medical device clinical trial;
(II) select, based on the characteristics of the investigational medical device, a filed medical device clinical trial institution, specialty and principal investigator;
(III) be responsible for organizing the formulation of the investigator’s brochure, the clinical trial protocol, the informed consent form, the case report form, the standard operating procedures and other relevant documents, and provide them to the medical device clinical trial institution and the principal investigator.
Article 39. The sponsor shall conclude a contract with the medical device clinical trial institution and the principal investigator, clarifying the rights and obligations of all parties in the medical device clinical trial.
Article 40. The sponsor shall, after the medical device clinical trial has passed ethical review and a contract has been concluded with the medical device clinical trial institution, file the clinical trial project with the drug administration department of the province, autonomous region or municipality directly under the Central Government where the sponsor is located.
After the filing of the medical device clinical trial has been completed, the medical device clinical trial institution may then begin the informed consent and screening of the first trial subject.
Article 41. Before a medical device clinical trial begins, the sponsor shall be responsible for organizing the training relating to the medical device clinical trial, such as the principles, scope of application, product performance, operating methods, installation requirements and technical indicators of the investigational medical device, as well as the clinical trial protocol, the standard operating procedures and other relevant documents.
Article 42. The sponsor shall provide the investigational medical device free of charge, and shall meet the following requirements:
(I) the investigational medical device shall be produced in accordance with the relevant requirements of the good manufacturing practice for medical devices and be of qualified quality;
(II) determining the transport conditions, storage conditions, storage time, validity period, etc. of the investigational medical device;
(III) the investigational medical device shall be appropriately packaged and preserved in accordance with the requirements of the clinical trial protocol; the packaging label shall indicate the product information, bear an easily identifiable and correctly coded mark, and indicate that it is for medical device clinical trial use only;
(IV) after the medical device clinical trial has been consented to by the ethics committee, the sponsor shall be responsible for transporting the investigational medical device to the medical device clinical trial institution under the prescribed conditions;
(V) for the investigational medical device recovered from the medical device clinical trial institution, the sponsor shall be responsible for keeping records of the recovery, disposal, etc.
Article 43. The sponsor shall pay the expenses relating to the medical device clinical trial for the trial subjects. Where a trial subject suffers injury or death related to the medical device clinical trial, the sponsor shall bear the corresponding treatment expenses, compensation or indemnity, but this shall not include injury caused by the fault of the investigator or the medical device clinical trial institution itself or by the progression of the trial subject’s own illness.
Article 44. The sponsor shall be responsible for the assessment and reporting of safety information during the medical device trial:
(I) the sponsor shall, within 7 days after becoming aware of a serious adverse event relating to the clinical trial medical device that is fatal or life-threatening, and within 15 days after becoming aware of a serious adverse event relating to the investigational medical device that is non-fatal or non-life-threatening and other serious safety risk information, report to the other medical device clinical trial institutions participating in the clinical trial, the ethics committee and the principal investigator, report to the drug administration department of the province, autonomous region or municipality directly under the Central Government where the sponsor is located, and report to the drug administration department and the health administration department of the province, autonomous region or municipality directly under the Central Government where the medical device clinical trial institution is located, and take risk control measures; where information arises that may affect the safety of the trial subjects, may affect the implementation of the medical device clinical trial, or may change the consent opinion of the ethics committee, the sponsor shall promptly organize the modification of the clinical trial protocol, the informed consent form and other information provided to the trial subjects, and other relevant documents, and submit them to the ethics committee for review;
(II) where a wide-ranging serious adverse event relating to the clinical trial medical device, or another major safety problem, occurs, the sponsor shall suspend or terminate the medical device clinical trial, and report to the management departments of all medical device clinical trial institutions, the ethics committee and the principal investigator, report to the drug administration department of the province, autonomous region or municipality directly under the Central Government where the sponsor is located, and report to the drug administration departments and the health administration departments of the provinces, autonomous regions or municipalities directly under the Central Government where all the medical device clinical trial institutions are located.
Article 45. The sponsor shall bear the responsibility for monitoring the medical device clinical trial, formulate standard operating procedures for monitoring, and select monitors who meet the requirements to perform monitoring duties:
(I) the number of monitors and the number of monitoring visits shall match the complexity of the medical device clinical trial and the number of medical device clinical trial institutions participating in the clinical trial;
(II) the monitors shall have received corresponding training, be familiar with these Norms and the relevant laws and regulations, possess relevant professional background knowledge, and be familiar with the research materials relating to the investigational medical device and the clinical information of similar products, the clinical trial protocol and its related documents, so as to be able to effectively perform monitoring duties;
(III) the monitors shall comply with the standard operating procedures for monitoring formulated by the sponsor and urge the medical device clinical trial to be conducted in accordance with the clinical trial protocol. The contents of monitoring include the compliance of the medical device clinical trial institution and the investigators with the clinical trial protocol, these Norms and the relevant laws and regulations in the course of implementing the clinical trial; the signing of the informed consent form, screening, follow-up, and safeguarding of the rights, interests and safety of the trial subjects; the management and use of the investigational medical device and the control medical device (if applicable); the management and use of biological samples (if applicable); the handling of adverse events and device defects; the reporting of safety information; the recording of clinical trial data and the completion of case report forms; and so on.
Article 46. To ensure the quality of the clinical trial, the sponsor may organize auditors who are independent of the medical device clinical trial and have corresponding training and experience to audit the implementation of the clinical trial and assess whether the clinical trial complies with the provisions of the clinical trial protocol, these Norms and the relevant laws and regulations.
Article 47. The sponsor shall ensure that the implementation of the medical device clinical trial complies with the clinical trial protocol; where it discovers that the medical device clinical trial institution and the investigators do not comply with the clinical trial protocol, these Norms and the relevant laws and regulations, it shall promptly point this out and rectify it; where the situation is serious or remains uncorrected, it shall terminate the continued participation of that clinical trial institution and those investigators in the clinical trial, and report in writing to the drug administration department of the province, autonomous region or municipality directly under the Central Government where the clinical trial institution is located.
Article 48. The sponsor shall, within 10 working days after the suspension, termination or completion of the medical device clinical trial, report in writing to all principal investigators, the management department of the medical device clinical trial institution and the ethics committee.
The sponsor shall, within 10 working days after the termination or completion of the medical device clinical trial, report to the drug administration department of the province, autonomous region or municipality directly under the Central Government where the sponsor is located.
Chapter 6 Clinical Trial Protocol and Trial Report
Article 49. To conduct a medical device clinical trial, the sponsor shall, based on the trial objective and taking into account the risks, technical characteristics, scope of application and intended use of the investigational medical device, organize the formulation of a scientific and reasonable clinical trial protocol.
Article 50. The clinical trial protocol generally includes the basic product information, basic clinical trial information, trial objective, risk-benefit analysis, trial design elements, justification of the reasonableness of the trial design, statistical considerations, manner of implementation (methods, content, steps), clinical trial endpoints, data management, provisions for amending the clinical trial protocol, provisions for defining and reporting adverse events and device defects, ethical considerations and other contents.
Article 51. The sponsor and the principal investigator shall conduct the medical device clinical trial in accordance with the clinical trial protocol and complete the clinical trial report. The clinical trial report shall comprehensively, completely and accurately reflect the results of the clinical trial, and the safety and effectiveness data in the clinical trial report shall be consistent with the source data of the clinical trial.
Article 52. The clinical trial report generally includes the basic information of the medical device clinical trial, the implementation situation, the statistical analysis methods, the trial results, the reporting of adverse events and device defects and their handling, the analysis and discussion of the trial results, the clinical trial conclusion, the ethical situation, problems and improvement suggestions, and other contents.
Article 53. The clinical trial protocol and the clinical trial report shall be signed and dated by the principal investigator and, after being reviewed, sealed and signed by the medical device clinical trial institution, delivered to the sponsor.
Chapter 7 Multicenter Clinical Trials
Article 54. A multicenter clinical trial refers to a clinical trial conducted at two or more (inclusive) medical device clinical trial institutions in accordance with the same clinical trial protocol.
Where a multicenter clinical trial is conducted in different countries or regions, it is a multi-regional clinical trial; a multi-regional medical device clinical trial conducted within the territory of China shall comply with the relevant requirements of these Norms.
Article 55. A sponsor conducting a multicenter medical device clinical trial shall meet the following requirements:
(I) the sponsor shall ensure that all centers participating in the medical device clinical trial are able to comply with the clinical trial protocol;
(II) the sponsor shall provide all centers with the same clinical trial protocol. After the ethicality and scientific validity of the clinical trial protocol have been reviewed and approved by the ethics committee of the lead institution, the ethics committees of the other medical device clinical trial institutions participating in the clinical trial shall not, as a general rule, propose modifications to the design of the clinical trial protocol, but shall have the right to disapprove the conduct of the trial at their own medical device clinical trial institution;
(III) all centers shall use the same case report form and completion guidelines to record the trial data obtained in the medical device clinical trial;
(IV) before the medical device clinical trial begins, there shall be a written document clarifying the duties of the principal investigators at the centers participating in the medical device clinical trial;
(V) the sponsor shall ensure communication among the principal investigators at the centers;
(VI) the sponsor shall be responsible for selecting and determining the coordinating investigator of the medical device clinical trial; the medical institution at which the coordinating investigator serves shall be the lead institution. The coordinating investigator shall undertake the coordination work among the centers in the multicenter clinical trial.
Article 56. The multicenter clinical trial report shall be signed and dated by the coordinating investigator and, after being reviewed, sealed and signed by the medical device clinical trial institution of the lead institution, delivered to the sponsor.
The clinical trial sub-summary of each sub-center shall be signed and dated by the principal investigator of that center and, after being reviewed, sealed and signed by the medical device clinical trial institution of that center, delivered to the sponsor. The clinical trial sub-summary of a sub-center mainly includes personnel information, information on the investigational medical device and the control medical device (if applicable), an overview of the trial, the case enrollment situation, the implementation of the clinical trial protocol, the summarization and descriptive analysis of the trial data, the quality management situation of the medical device clinical trial, the occurrence and handling of adverse events and device defects, an explanation of protocol deviations, and so on.
Chapter 8 Recording Requirements
Article 57. Medical device clinical trial data shall be authentic, accurate, complete and traceable. The source data of a medical device clinical trial shall be clear and identifiable and shall not be arbitrarily changed; where a change is truly necessary, the reason shall be explained, and the change shall be signed and dated.
Article 58. In a medical device clinical trial, the principal investigator shall ensure that any observations and findings are recorded correctly and completely. In a clinical trial with patients as trial subjects, the relevant medical records shall be entered into the outpatient or inpatient medical records.
Article 59. The principal 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 case report forms are accurate, complete, clear and timely. The data reported in the case report forms shall be consistent with the source documents. Modifications to the data in the case report forms shall ensure that the initial records remain clear and identifiable, retain the modification trail, and be signed and dated by the person making the modification.
Article 60. Where an electronic data-capture system is used in a medical device clinical trial, the system shall undergo reliable validation, have complete permission management and an audit trail, be traceable to the creator and time of creation or the modifier, time of modification and modification situation of the record, and ensure that the electronic data collected can be traced to their source.
Article 61. The essential documents of a medical device clinical trial are used to evaluate the implementation by the sponsor, the medical device clinical trial institution and the principal investigator of these Norms and the relevant requirements of the drug administration department. The drug administration department may inspect the essential documents of a medical device clinical trial and use them as the basis for confirming the authenticity of the implementation of the medical device clinical trial and the completeness of the data collected.
Article 62. The sponsor and the medical device clinical trial institution shall have premises and conditions for the preservation of the essential documents of the clinical trial, and shall establish an essential-document management system. The essential documents of a medical device clinical trial are divided, according to the stage of the clinical trial, into three parts: preparation-stage documents, conduct-stage documents, and post-completion-or-termination documents.
Article 63. The sponsor and the medical device clinical trial institution shall ensure the integrity of the essential documents of the clinical trial during the preservation period and avoid intentional or unintentional alteration or loss:
(I) the investigator shall properly preserve the essential documents of the clinical trial in the course of the medical device clinical trial;
(II) the medical device clinical trial institution shall preserve the essential documents of the clinical trial until 10 years after the completion or termination of the medical device clinical trial;
(III) the ethics committee shall preserve all records of the ethical review until 10 years after the completion or termination of the medical device clinical trial;
(IV) the sponsor shall preserve the essential documents of the clinical trial until such time as the medical device is no longer in use.
Chapter 9 Supplementary Provisions
Article 64. The following terms used in these Norms have the meanings set out below:
Medical device clinical trial means the process of confirming, at a medical device clinical trial institution that meets the conditions, the safety and effectiveness of a medical device (including in-vitro diagnostic reagents) for which registration is intended to be applied, under normal conditions of use.
Medical device clinical trial institution means an institution that possesses the corresponding conditions and conducts medical device clinical trials in accordance with these Norms and the relevant laws and regulations, including non-medical institutions such as blood centers and central blood banks, disease prevention and control institutions at or above the districted-city level, and drug rehabilitation centers that undertake clinical trials of in-vitro diagnostic reagents.
Clinical trial protocol means a document explaining the objective, design, methodology and organization and implementation of a medical device clinical trial. The clinical trial protocol includes the protocol and its revised versions.
Clinical trial report means a document describing the design, conduct, statistical analysis and results of a medical device clinical trial.
Case report form means a document designed in accordance with the provisions of the medical device clinical trial protocol, used to record all the information and data of each trial subject obtained in the course of the trial.
Investigator’s brochure means a compilation of materials provided by the sponsor to help the principal investigator and the other investigators participating in the clinical trial to better understand and comply with the clinical trial protocol, including but not limited to: basic information about the sponsor, a summary description of the investigational medical device, a summary and evaluation supporting the intended use of the investigational medical device and the rationale for the clinical trial design, possible risks, and recommended preventive and emergency handling methods.
Investigational medical device means the medical device, for which registration is intended to be applied, whose safety and effectiveness are confirmed in a medical device clinical trial.
Control medical device means a medical device already marketed within the territory of the People’s Republic of China that is used as a control in a medical device clinical trial.
Ethics committee means an independent committee composed of appropriate personnel, whose duty is to ensure that the rights, interests and safety of the trial subjects participating in a medical device clinical trial are protected.
Informed consent means the process whereby, after the various aspects of a medical device clinical trial have been disclosed to a trial subject, the trial subject confirms his or her voluntary participation in the medical device clinical trial, with a written informed consent form signed and dated serving as the documentary evidence.
Trial subject means an individual who voluntarily participates in a medical device clinical trial.
Impartial witness means an individual who is unrelated to the medical device clinical trial and is not unfairly influenced by personnel related to the clinical trial, who, where a trial subject lacks reading ability, acts as an impartial witness, reads the informed consent form and other information provided to the trial subject, and witnesses the informed consent.
Sponsor means the institution or organization that initiates, manages and provides financial support for a medical device clinical trial.
Investigator means the personnel who conduct a medical device clinical trial at a medical device clinical trial institution.
Principal investigator means the person in charge who conducts a medical device clinical trial at a medical device clinical trial institution.
Coordinating investigator means the investigator designated by the sponsor to carry out coordination work in a multicenter clinical trial, generally the principal investigator of the lead institution.
Monitoring means the activity whereby the sponsor, in order to ensure that a medical device clinical trial can comply with the clinical trial protocol, these Norms and the relevant laws and regulations, assigns dedicated personnel to evaluate and investigate the medical device clinical trial institution and the investigators, and to verify, record and report the data in the course of the medical device clinical trial.
Audit means the systematic and independent examination, organized by the sponsor, of the activities and documents relating to a medical device clinical trial, in order to determine whether the conduct of such activities and the recording, analysis and reporting of data comply with the clinical trial protocol, these Norms and the relevant laws and regulations.
Inspection means the supervision and administration activity carried out by the regulatory department with respect to the relevant documents, facilities, records and other aspects of a medical device clinical trial.
Deviation means the situation of intentional or unintentional non-compliance with the requirements of a medical device clinical trial protocol.
Adverse event means an untoward medical event occurring in the course of a medical device clinical trial, whether or not it is related to the investigational medical device.
Serious adverse event means an event occurring in the course of a medical device clinical trial that results in death or serious deterioration of health, including a fatal illness or injury, a permanent defect of body structure or body function, the need for hospitalization or prolongation of hospitalization, or the need to take medical measures to avoid a permanent defect of body structure or body function; or that results in fetal distress, fetal death or congenital anomaly or birth defect.
Device defect means an unreasonable risk that a medical device, under normal use, poses in the course of a clinical trial that may endanger human health and life safety, such as labeling errors, quality problems or malfunctions.
Source data means all the information in the original records and certified copies thereof of the clinical findings, observations and other activities in a medical device clinical trial, which can be used for the reconstruction and evaluation of the medical device clinical trial.
Source document means a printed, visual or electronic document, etc. that contains source data.
Article 65. Format templates for documents such as the medical device clinical trial protocol shall be separately formulated by the National Medical Products Administration.
Article 66. These Norms shall come into force on May 1, 2022.