Good Clinical Practice for Medical Devices

Good Clinical Practice for Medical Devices

Chapter I General Provisions

Article 1

This Practice is formulated in accordance with Regulations on the Supervision and   Administration of Medical Devices in order to strengthen the management of clinical trial of medical devices, safeguard the rights and interests of subjects during clinical trial of medical devices and ensure normative process of clinical trial of medical devices as well as true, scientific, reliable and traceable results.

Article 2

Clinical trial of medical devices implemented within the territory of the People’s Republic of China shall abide by this Practice.

This Practice covers the whole process of clinical trial of medical devices, including the design, implementation, supervision, verification and inspection of clinical trial protocol as well as data acquisition, recording, analysis summary and reporting.

Article 3

Clinical trial of medical devices as mentioned in this Practice refers to the process of confirming or verifying the safety and effectiveness of medical devices planned to be applied and registered under normal use in the clinical trial institutions of medical devices through qualification authentication.

Article 4

Clinical trial of medical devices shall abide by laws, ethical principles and scientific principles.

Article 5

Food and drug administration authorities at or above province level shall be responsible for the supervision and administration of clinical trial of medical devices.

Competent authorities of health to family planning shall strengthen the administration of clinical trial of medical devices within the scope of their duties.

Food and drug administration authorities and competent authorities of health to family planning shall establish reporting mechanism of quality management information for clinical trial of medical devices and strengthen information reporting of implementing examination and approval of clinical trials for Class III medical device and medical devices listed in the configuration management items of national large-scale medical equipments as well as corresponding supervision and management data of clinical trial.

Chapter II Preparation before Clinical Trial

Article 6

The implementation of clinical trial of medical devices shall have sufficient scientific basis and specific trial objectives and weigh the intended benefits and risks of the health of subjects and the public and the intended benefits shall exceed possible damages.

Article 7

Before clinical trial, sponsor shall finish preclinical study on investigational medical devices, including product design (structural composition, operating principle, mechanism of action, intended use, scope of application and applicable technical requirements), quality inspection, animal test and risk analysis, and the results shall support the clinical trial. The results of quality inspection shall include self-test report and qualified report on product registration inspection issued by qualified inspection agency within one year.

Article 8

Before clinical trial, sponsor shall prepare sufficient investigational medical devices. The development of investigational medical devices shall comply with relevant requirements of applicable quality management system for medical devices.

Article 9

Clinical trial of medical devices shall be implemented in two or more clinical trial institutions of medical devices.

The selected trial institutions shall be qualified clinical trial institutions of medical devices and their facilities and conditions shall meet the demands for implementing clinical trial safely and effectively. Investigators shall have professional skills, qualification and abilities to take this clinical trial and shall be trained.

Administrative measures for qualification accreditation for clinical trial institutions of medical devices shall be formulated by China Food and Drug Administration and National Health and Family Planning Commission of the People’s Republic of China.

Article 10

Before clinical trial, sponsor, clinical trial institutions and investigators shall conclude written agreement on trial design, trial quality control, assignment of responsibilities, relevant expenses of clinical trial taken by sponsor and treatment principles for possible injuries during trial.

Article 11

Clinical trial shall be agreed by ethics committee of the clinical trial institution of medical devices. For those listed in the catalogue of Class III medical devices that need examination and approval of clinical trial, it is required to be approved by China Food and Drug Administration.

Article 12

Before clinical trial, sponsor shall submit to food and drug administration authorities of province, autonomous region and municipality directly under the central government where it locates for filing.

Food and drug administration authorities who accept filing shall report the filing situation to the food and drug administration authority and competent authority of health to family planning at the same level where the clinical trial institution locates.

Chapter III Guarantee of Rights and Interests of Subjects

Article 13

Clinical trial of medical devices shall abide by the codes of ethics determined by World Medical Association Declaration of Helsinki.

Article 14

Ethical review and informed consent are main measures to guarantee the rights and interests of subjects.

All participants in clinical trial shall bear corresponding ethical responsibilities in accordance with their responsibilities in the trial.

Article 15

Sponsor shall avoid generating undue influence or misleading to participants, including subjects, clinical trial institutions and investigators, and relevant parties.

Clinical trial institutions and investigators shall avoid generating undue influence or misleading to participants, including subjects and sponsor, and relevant parties.

Article 16

Sponsor, clinical trial institutions and investigators shall not exaggerate indemnifying measure for participating in clinical trial to mislead subjects to participate in clinical trial.

Article 17

Before clinical trial, sponsor shall submit the following documents to ethics committee through investigator, administrative department for clinical trial of medical devices of clinical trial institution:

(I) Clinical trial protocol;

(II) Investigator’s brochure;

(III) Text of informed consent form and any other written material provided to subjects;

(IV) Procedural documents of recruiting subjects advertising to them;

(V) Text of case report form;

(VI) Self-test report and report on product registration and inspection;

(VII) Investigator's resume, professional skills, abilities, training accepted and other documents that can prove their qualification;

(VIII) Facilities and conditions of clinical trial institutions can meet the study review;

(IX) Statement that the development of investigational medical devices complies with relevant requirements of applicable quality management system for medical devices;

(X) Other documents relating to ethical review.

Ethics committee shall adhere to ethical and scientific principles to review and supervise the implementation of clinical trial.

Article 18

In case of one of the following situations during the process of clinical trial, investigators shall timely report to the administrative department for clinical trial of medical devices of clinical trial institution, through which timely notify sponsor and report to ethics committee:

(I) Serious adverse events;

(II) Progress report, including safety summary and deviation report;

(III) There is no need to report any amendment to the documents approved by ethics committee, which has no effects on subjects’ rights and interests, safety and health, or non-substantive changes irrelevant to the objectives or endpoint of clinical trial in advance, but it shall be notified in writing afterwards;

(IV) Suspension, termination or request recovery of clinical trial after suspension;

(V) Deviation of clinical trial protocol that affects subjects’ rights and interests, safety and health or scientificity of clinical trial, including request deviation and report deviation.

To protect subject rights and interests, safety and health, in case deviation occurred in emergency cannot be reported in time, it shall be reported afterwards in written form in accordance with relevant regulations as soon as possible.

Article 19

In case of revising clinical trial protocol and informed consent form, request deviation and recovery of the suspended clinical trial during the process of clinical trial, the implementation of them shall not be continued without written approval of ethics committee.

Article 20

It is required to try to avoid selecting juveniles, pregnant women, old people, mental retardation personnel and patients in life emergency as subjects; if necessary, it is required to abide by relevant additional requirements proposed by ethics committee, implement special design for their health status during clinical trial, and benefit their health.

Article 21

Before subjects participate in clinical trial, investigators shall fully explain the details of clinical trial for subjects or guardians of persons without capacity of civil conduct and persons with limited capacity for civil conduct, including the known, foreseeable risks and possible adverse events. Through full and detailed explanation, subjects and their guardians shall sign and data the informed consent form and investigators also need to sign and data the informed consent form.

Article 22

Informed consent form shall generally include the following content and instructions of matters:

(I) Investigator’s name and relevant information;

(II) Name of clinical trial institution;

(III) Trial name, objectives, methods and content;

(IV) Trial process and time limit;

(V) Capital source for trial and possible conflicts of interest;

(VI) Anticipate possible benefits for subjects, known and foreseeable risks and possible adverse events;

(VII) Alternative diagnosis and treatment methods available for subjects and the information of their potential benefits and risks;

(VIII) When needed, explain that subjects may be assigned to different groups of trial;

(IX) Subjects shall voluntarily participate in the trial, they shall have the right to withdraw from the trial at any phase without being discriminated or revenged, and their medical treatment, rights and interests shall not be affected;

(X) The personal information of subjects participating in the trial shall be confidential, but ethics committee, food and drug administration authorities, competent authorities of health to family planning or sponsor can consult personal information of subjects participating in the trial in accordance with established procedure due to work demands;

(XI) In case of injuries relating to trial, subjects can obtain treatment and economic compensation;

(XII) Subjects can be kept informed of information relating to them during the period of trial;

(XIII) Subjects can obtain free diagnosis and treatment items and other relevant allowances during the period of trial.

Informed consent form shall apply the language and words that can be understood by subjects or guardians. Informed consent form shall not contain the content that would cause subjects give up legitimate rights and interests and exempt the responsibilities of clinical trial institutions, investigators, sponsor or their agency.

Article 23

The obtaining of informed consent shall also comply with the following requirements:

(I) For subjects without disposing capacity, if ethics committee agrees in general and investigators consider that subjects’ participating in clinical trial comply with their own interests, they can also enter into clinical trial, but their guardians shall sign and date before trial.

(II) In case subjects or their guardians do not have reading ability, a witness is required to be on the scene during the process of informed consent. Through explaining informed consent form in details, the witness reads informed consent form in line with the content of verbal informed consent and the witness shall sign and date on informed consent form after verbal agreement of subjects and their guardians. The signature and date signed by the witness and investigator shall be on the same day.

(III) In case of juveniles as subjects, it is required to obtain informed consent of their guardians and sign informed consent form. In case juveniles can make intention for whether participating in the trial, it is required to obtain their own permission.

(IV) In case of finding important information involving investigational medical devices and clinical effects beyond anticipation, it is required to modify relevant content of informed consent form. The modified informed consent form shall be resigned and reconfirmed by subjects and their guardians after recognition of ethics committee.

Article 24

Informed consent form shall specify the formulation date or date of revised version. In case of revision of informed consent form during the process of trial, the revised informed consent form shall be agreed by ethics committee again before implementation. After the revised informed consent form reported to clinical trial institution, in case of affecting all subjects who do not finish trial process, they shall sign the newly revised informed consent form.

Article 25

Subjects shall have the right to withdraw from the trial at any phase without bearing any economic responsibility.

Chapter IV Clinical trial protocol

Article 26

In case of implementing clinical trial of medical devices, sponsor shall formulate scientific, and reasonable clinical trial protocol in accordance with the categories, risks and intended use of investigational medical devices.

Article 27

With regard to new products that are not approved for marketing at home and abroad, their safety and performance are not proved. It is required to firstly implement small sample feasibility test in the design of clinical trial protocol, then determine sample size to conduct follow-up clinical trials in accordance with the requirements of statistics after primarily confirming their safety.

Article 28

Clinical trial protocol for medical devices shall include the following content:

(I) General information;

(II) Background information of clinical trial;

(III) Trial objectives;

(IV) Trial design;

(V) Safety evaluation method;

(VI) Effectiveness evaluation method;

(VII) Statistical considerations;

(VIII) Provisions for the amendments to clinical trial protocol;

(IX) Provisions for report on adverse events and device defects;

(X) Direct access to source data and documents;

(XI) Texts of ethical issues involving in clinical trial, instructions and informed consent form;

(XII) Data processing and record retention;

(XIII) Financing and insurance

(XIV) Agreement on publication of trial results.

The above content can be included in other relevant documents of protocol, including investigator’s brochure. Specific information of clinical trial institution, agreement on publication of trial results, financing and insurance could be expressed in study protocol or stipulated in other stipulated agreement.

Article 29

Multicenter clinical trials shall be implemented by many investigators in different clinical trial institutions in accordance with the same study protocol. The design and implementation of the study protocol shall include but not limited to the following content:

(I) Study protocol shall be organized and formulated by sponsor and shall be discussed and designated by clinical trial institutions and investigators, specifying investigators of clinical trial institutions of leading unit as investigators;

(II) Coordinating investigators shall be responsible for the coordination of all clinical trial institutions during the process of clinical trial, organizing investigator meeting in the early, middle and late periods of clinical trial, and taking responsibility for the implementation of the whole trial together with sponsor;

(III) In general, all clinical trial institutions shall implement and finish clinical trials during the same period;

(IV) The sample size and allocation of all clinical trial institutions as well as reasons required for complying with statistical analysis;

(V) Requirements of sponsor and clinical trial institutions for plan of trial training and training records;

(VI) Establish transfer, management, verification and query programs of trial data, especially specify that information relating to trial data of all clinical trial institutions shall be intensively managed and analyzed by leading unit;

(VII) After the completion of multicenter clinical trial, the investigators of all clinical trial institutions shall issue clinical trial summary separately and submit it after being approved in accordance with provisions together with case report form to coordinating investigators to finish the final report.

Chapter V Responsibilities of Ethics Committee

Article 30

Ethics committee of clinical trial institution of medical devices shall be composed by at least 5 committee members, including medical professionals, non-medical professionals, with different genders. Non-medical committee members shall include at least one legal professional and one person beyond the clinical trial institution. The members of ethics committee shall have qualification or experiences in assessing and evaluating the scientific, medical and ethnical aspects of this clinical trial. All committee members shall be familiar with codes of ethics and relevant provisions of clinical trial of medical devices and abide by the constitution of ethics committee.

Article 31

Ethics committee of medical devices shall abide by the codes of ethics of World Medical Association Declaration of Helsinki and provisions of food and drug administration authorities, establish corresponding working procedures and form document, and fulfill responsibilities in accordance with working procedures.

Committee members independent of investigators and sponsor in ethics committee shall be entitled to give opinions and take part in the voting of relevant trial.

Article 32

In case of holding a meeting, ethics committee shall give prior notice, the people participating in review and voting shall be not less than 5 persons, and any decision shall be adopted by half or more members of ethics committee.

Investigators can provide information of any aspect relating to the trial, but they shall not participate in review, voting or giving opinions.

In case of reviewing some special trials, ethics committee can invite experts in relevant fields.

Article 33

Ethics committee shall strictly review study protocol and relevant documents from the perspective of safeguarding rights and interests of subjects and pay attention to the following content:

(I) Investigator’s qualification and experience as well as whether the investigator has sufficient time to take part in this clinical trial.

(II) Whether personnel allocation and equipment conditions of clinical trial institutions comply with the requirements for the trial.

(III) Whether the degree of possible risks suffered by subjects is suitable by comparing with intended benefits of the trial.

(IV) Whether study protocol gives full consideration to ethical principles and complies with scientificity, including whether research objectives are suitable, whether subject rights and interests are safeguarded, whether it is scientific for protecting other personnel free from suffering possible risks and the inclusion method of subjects.

(V) Whether inclusion method of subjects and information relating to this trial provided to subjects or their guardians are complete, whether subjects could understand, and whether the method of obtaining informed consent form is suitable. If necessary, ethics committee shall organize representatives of subject population to test the level of understanding for the information, whether informed consent is suitable. The evaluation results shall be recorded in writing and kept for 10 years after the end of clinical trial.

(VI) In case injuries or death of subjects occur relating to clinical trial, whether the given treatment and insurance measures are sufficient or not.

(VII) Whether the amendments to study protocol are acceptable.

(VIII) Whether the possible harms of subjects can be analyzed and evaluated periodically during the implementation of clinical trial.

(IX) Deviation of study protocol may affect rights and interests of subjects, safety and health, or the scientificity and integrity. Whether it is acceptable.

Article 34

The ethics committee of leading unit shall be responsible for establishing review procedures for ethical review of multicenter clinical trial to ensure the consistency and timeliness of review.

Before all clinical trial institutions start the trials, the ethics committee of leading unit shall be responsible for review the ethical rationality and scientificity of study protocol. On the premise of accepting the review opinions from ethics committee of the leading unit, the ethics committees of all other clinical trial institutions participating in the trial can apply the forms of meeting review or document review to review the feasibility of this trial in this clinical trial institution, including qualification and experience of investigators, facilities and conditions. In general, they will not put forward revision opinions for the design of study protocol, but have the right to not approve the trial implemented in their clinical trial institution.

Article 35

After receiving the application for clinical trial of medical devices, ethics committee shall convene a meeting to review, discuss, sign and seal written opinions, attach the name list, major and signature of personnel participating in the meeting. The opinions of ethics committee can be:

(I) Agree;

(II) Agree after necessary revision;

(III) Disagree;

(IV) Suspend or terminate the approved trial.

Article 36

Ethics committee shall trace and supervise the clinical trial of this clinical trial institution. In case rights and interests of subjects cannot be guaranteed, ethics committee can ask for suspending or terminating this clinical trial in writing at any time.

The suspended clinical trial shall not be recovered without consent of ethics committee.

Article 37

Ethics committee shall keep all relevant records for at least 10 years after the completion of clinical trial.

Chapter VI Responsibilities of Sponsor

Article 38

Sponsor shall be responsible for launching, applying, organizing and supervising clinical trial as well as the authenticity and reliability of clinical trial. Sponsor is manufacturing enterprise of medical device in general. In case the sponsor is overseas agency, it shall designate agent in China in accordance with provisions.

Article 39

Sponsor shall be responsible for organizing, formulating and revising investigator’s brochure, clinical trial protocol, informed consent form, case report form, relevant standard operating procedures and other relevant documents as well as organizing and implementing necessary training for clinical trial.

Article 40

Sponsor shall select trial institution and investigators from qualified clinical trial institutions of medical devices in accordance with the characteristics of investigational medical devices. Before signing clinical trial agreement with clinical trial institutions, sponsor shall provide the latest investigator’s brochure and other relevant documents to clinical trial institutions and investigators to determine whether bear this clinical trial.

Article 41

Investigator’s brochure shall mainly include the following content:

(I) Basic information of sponsor and investigators;

(II) Summary of investigational medical devices;

(III) Summary and evaluation of reasons that support the intended use and clinical trial design of investigational medical devices;

(IV) The manufacturing of investigational medical devices shall comply with the statement required by applicable quality management system for medical devices.

Article 42

Sponsor shall not ballyhoo the mechanism and efficacy of investigational medical devices during the formulation clinical trial protocol.

Article 43

In case of obtaining important information that affects clinical trial during clinical trial, sponsor shall revise investigator’s brochure and relevant documents timely and submit to ethics committee for examination and approval through administrative department for clinical trial of medical devices of clinical trial institution.

Article 44

Sponsor shall conclude written agreement on the following items with clinical trial institution and investigators:

(I) Implement clinical trial, accept supervision, verification and inspection in accordance with relevant laws and regulations and clinical trial protocol;

(II) Abide by data record and reporting procedure;

(III) Keep basic documents relating to the trial for not less than the legal time until the sponsor informs clinical trial institutions and investigators of no more need of such documents;

(IV) After obtaining approval of ethics committee, sponsor shall be responsible for providing investigational medical devices to clinical trial institutions and investigators and ensuring their transportation conditions, storage conditions, storage time and period of validity;

(V) Investigational medical devices shall qualified quality as well as easily identifiable and correct code, with labeled special marking of “investigational”, and shall be packaged and stored properly in accordance with the requirements of clinical trial protocol;

(VI) Sponsor shall formulate standard operating procedure relating to quality control of clinical trial for clinical trial institutions and investigators, such as transportation, reception, storage, distribution, treatment and recycle of investigational medical devices.

Article 45

Sponsor shall be responsible for the safety of investigational medical devices during clinical trial. In case it is found to affect the safety of subjects or the implementation of trial may change the approval of ethics committee for the continuous trial, sponsor shall notify all clinical trial institutions and investigators immediately and make corresponding treatment.

Article 46

In case sponsor decides to suspend or terminate clinical trial, it is required to notify the administrative departments of clinical trial of medical devices of all clinical trial institutions within 55 days and give reasons in written form. Administrative departments of clinical trial of medical devices of clinical trial institutions shall notify corresponding investigators and ethics committees in time. The suspended clinical trial shall not be recovered without the consent of ethics committee. After the end of clinical trial, sponsor shall notify the food and drug administration authorities of province, autonomous region and municipality directly under the central government where it locates in written form.

Article 47

Sponsor shall ensure all investigators who implement clinical trials strictly abide by clinical trial protocol. In case clinical trial institutions and investigators fail to observe relevant laws and regulations, this Practice and clinical trial protocol, it is required to be pointed out and corrected. In case of serious conditions or continuous failure to correct, it is required to terminate the trial and report to food and drug administration authorities of province, autonomous region and municipality directly under the central government where it locates as well as China Food and Drug Administration.

Article 48

Sponsor shall bear treatment expenses and corresponding economic compensation for injuries or death of subjects relating to the clinical trial, except for the injuries caused by errors of clinical institutions and their medical staff during diagnosis activity.

Article 49

Sponsor shall bear supervision responsibility for clinical trial and select satisfactory supervisors to fulfill supervision responsibility.

The number of supervisors and the time of supervision depend on the complexity of clinical trial and the number of clinical trial institutions participated in the trial.

Article 50

Supervisors shall have corresponding professional background of clinical medicine, pharmacy, biomedical engineering and statistics, pass necessary training, be familiar with relevant regulations and this Practice, and be familiar with non-clinical information of investigational medical devices, clinical information of product of the same kind, clinical trial protocol and relevant documents.

Article 51

Supervisors shall abide by the standard operating procedure for the supervision of clinical trial of investigational medical devices formulated by sponsor to supervise and urge the implement of clinical trial in accordance with protocol. The specific responsibilities shall include:

(I) Before trial, confirm that clinical trial institution has had proper conditions, including personnel allocation and training comply with requirements, lab is well equipped and in good conditions, there are sufficient subjects as expected, and study participants are familiar with the trial requirements.

(II) In early, middle and late periods of the trial, supervise whether clinical trial institutions and investigators abide by relevant regulations, this Practice and clinical trial protocol.

(III) Make sure that each subject has signed informed consent form before participating in the clinical trial, understand the inclusion of subjects and progress of trial. Clearly and faithfully record the undone follow-up of investigators, undone trial, undone examination and whether errors and omissions are corrected. The revised informed consent form shall be resigned by subjects who are confirmed not to finish clinical trial procedure and are affected.

(IV) Confirm that all case report forms are filled correctly and remain in line with the original data. All errors and omissions are corrected or marked, signed and dated by investigators. Disease categories, total cases, gender and age of cases and efficacy of each trial shall be confirmed and recorded.

(V) Make sure the records of subjects’ withdrawing from clinical trial or noncompliance of the provisions required by informed consent form and discuss such situations with investigators.

(VI) Make sure that all adverse events, complication and other device defects are recorded, serious adverse events and device defects that may cause serious adverse events are reported and recorded within stipulated time.

(VII) Supervise and inspect the supply, utilization, maintenance, transportation, reception, storage, distribution, treatment and recycle of investigational medical devices.

(VIII) Supervise scheduled maintenance and calibration of relevant devices during the process of clinical trial.

(IX) Make sure that all documents relating to clinical trial received by investigators are the latest versions.

(X) Written report shall be submitted to sponsor after each supervision and inspection and the report shall include the name of supervisor, inspection data, inspection time, inspection place, inspection content, name of investigator, completion situations, existing problems, conclusion and correction for errors and omissions.

Article 52

Sponsor shall ensure the quality of clinical trial and organize inspectors independent of clinical trial with corresponding training and experience to implement inspection and evaluate whether clinical trial complies with the requirements of study protocol.

As a part of routine work of good clinical practice of the sponsor, inspection can also be used for evaluating the effectiveness of inspection or implement verification for serious or repeated deviation and alleged counterfeiting of clinical trial protocol.

Article 53

Inspector shall formulate inspection plan and inspection procedure in accordance with the importance of clinical trial, quantity of subjects, types and complexity of clinical trial and risk level of subjects.

Article 54

With regard to serious adverse events and device defects that may cause serious adverse events, sponsor shall report to the registered food and drug administration authority and competent authority of health to family planning at the same level within 5 working days after learning, notify to other clinical trial institutions and investigators participated in the trial at the same time, and timely inform ethics committee of the clinical trial institution through administrative departments of clinical trial of medical devices.

Article 55

In case of applying electronic clinical database or remote electronic clinical data system, sponsor shall make sure that clinical data are controlled or true and form complete verification documents.

Article 56

With regard to multicenter clinical trial, sponsor shall ensure that documents are formulated before clinical trial and specify assignment of responsibilities of coordinating investigators and other investigators.

Article 57

With regard to multicenter clinical trial, sponsor shall organize and formulate standard operating procedure in accordance with clinical trial protocol, organize training for the utilization and maintenance of clinical trial protocol and investigational medical devices for all investigators participated in the trial, and ensure the consistency in the implementation of clinical trial protocol and the utilization of investigational medical devices.

Article 58

In multicenter clinical trial, the sponsor shall ensure the rigorous and rational design of case report form and make coordinating investigator obtain all data of all sub-center clinical trial institutions.

Chapter VII Responsibilities of Clinical Trial Institutions and Investigators

Article 59

Before accepting clinical trial, clinical trial institutions shall evaluate relevant resources to decide whether accept this clinical trial in accordance with the characteristics of investigational medical devices.

Article 60

Clinical trial institutions shall properly keep clinical trial record and basic documents as agreed with sponsor.

Article 61

Investigators who are in charge of clinical trial shall meet the following conditions:

(I) Professional title and qualification above associate professor, such as associate chief physician, associate professor and associate researcher in the clinical trial institutions;

(II) Professional knowledge and experience required for investigational medical devices and passing relevant trainings if necessary;

(III) Familiar with the data and literatures relating to clinical trial required and provided by sponsor;

(IV) Capacity to coordinate, dominate and use personnel and devices of this trial, and handle the adverse events and other correlating events of investigational medical devices;

(V) Familiar with relevant national laws, regulations and this Practice.

Article 62

Before clinical trial, administrative department for clinical trial of medical devices of clinical trial institution shall coordinate sponsor to file an application to ethics committee and submit relevant documents in accordance with provisions.

Article 63

Investigators shall ensure that the staff participated in the trial is familiar with the principles, scope of application, product performance, operating methods, installation requirements and technical indexes of investigational medical devices, understands preclinical research data and safety data of investigational medical devices, and masters precautions and emergency treatment for possible risks in clinical trial.

Article 64

Investigators shall ensure all participants of clinical trial fully understand clinical trial protocol, relevant provisions, characteristics of investigational medical devices and relevant responsibilities of clinical trial, make sure that enough subjects comply with the inclusion criteria of clinical trial protocol and enter into clinical trial, ensure enough time in the agreed trial period, and implement and finish clinical trial safely according relevant regulations.

Article 65

The investigator shall ensure that the investigational medical devices are only used for subjects of the clinical trial for free.

Article 66

Investigators shall strictly abide by clinical trial protocol. Without consent of sponsor and ethics committee or approval of China Food and Drug Administration in accordance with regulations, investigators shall not deviate the protocol or substantially change the protocol. However, in case of an emergency that subjects face direct danger that needs to be eliminated immediately, it can be reported in writing afterwards.

Article 67

Investigators shall be responsible for recruiting subjects and talking with subjects or their guardians. Investigators are responsible to specify the details relating to investigational medical devices and clinical trial for subjects, inform subjects of possible benefits and known and foreseeable risks, and obtain the signature of subjects and their guardians and dated informed consent form.

Article 68

Investigators and other personnel participated in the trial shall not force or induce subjects in unjustifiable way to take part in the trial.

Article 69

In case of finding unexpected adverse events of investigational medical devices during clinical trial, investigators shall revise relevant content of informed consent form together with the sponsor. After being reviewed and approved by ethics committee in accordance with relevant working procedure, the affected subjects and their guardians shall resign the revised informed consent form for confirmation.

Article 70

Investigators shall be responsible for making decisions relating to clinical trial. In case of adverse events relating to clinical trial, clinical trial institutions and investigators shall provide sufficient and timely treatment and disposal for subjects. In case subjects have complications and need treatment and disposal, investigators shall timely notify subjects.

Article 71

In case of serious adverse events during clinical trial, investigators shall take proper treatment measures for subjects immediately, report to administrative departments of clinical trial of medical devices of clinical trial institutions where they belongs, and notify sponsor in writing through them. Administrative departments of clinical trial of medical devices shall report to corresponding ethics committee and food and drug administration authorities of province, autonomous region and municipality directly under the central government and competent authorities of health to family planning where the clinical trial institution locates in written form within 24 hours. For death event, clinical trial institutions and investigators shall provide all necessary data to ethics committee and sponsor.

Article 72

Investigators shall record all adverse events and device defects occurred during the process of clinical trial, analyze event cases together with sponsor, form written analysis report, put forward opinions of continuing, suspending or terminating trial, and report to ethics committee for review through administrative departments of clinical trial of medical devices of clinical trial institutions.

Article 73

Investigators shall ensure that clinical trial data are loaded in case report form accurately, completely, clearly and timely. Case report form shall be signed by investigators. Any change in data shall be signed and dated by investigator and kept original record, which shall be clear and recognizable.

Article 74

Clinical trial institutions and investigators shall ensure authenticity, accuracy, clarity and safety of data and documents formed in clinical trial.

Article 75

Clinical trial institutions and investigators shall accept the inspection and verification of sponsor as well as supervision of ethics committee, and provide all required records relating to the trial. In case food and drug administration authorities and competent authorities of health to family planning send inspectors to implement inspection, clinical trial institutions and investigators shall cooperate with them.

Article 76

In case clinical trial institutions and investigators find risks exceed possible benefits or have obtained the results that is enough to judge the safety and effectiveness of investigational medical devices, and need to suspend or terminate clinical trial, it is required to notify subjects and ensure subjects obtain proper treatment and follow-up, report in accordance with regulations and provide detailed written explanation at the same time. If necessary, report to food and drug administration authorities of province, autonomous region and municipality directly under the central government where it locates.

In case of receiving the notice of sponsor or ethics committee on the need of suspending or terminating clinical trial, investigators shall timely notify subjects and ensure subjects obtain proper treatment and follow-up.

Article 77

In case sponsor violates relevant regulations or require to change the trial data and conclusion, clinical trial institutions and investigators shall report to food and drug administration authorities of province, autonomous region and municipality directly under the central government where sponsor locates or China Food and Drug Administration.

Article 78

At the end of clinical trial, investigators shall ensure the completion of all records and reports. Meanwhile, investigators shall ensure the received investigational medical devices remain the same with the used, discarded or returned quantity and ensure that the rest investigational medical devices are disposed properly and recorded for filing.

Article 79

Investigators can authorize corresponding personnel to recruit subjects, continuously communicate with subjects and manage investigational medical devices in accordance with the demands of clinical trial. Investigators shall implement relevant training for the authorized personnel and form corresponding documents.

Chapter VIII Recording and Reporting

Article 80

In the clinical trials, investigators shall ensure that any observation and finding is recorded accurately and completely and fill in the case report form seriously.

Record shall at least include:

(I) The used information of investigational medical devices, including name, model, specifications, receipt date, batch number or serial number;

(II) Medical record and nursing record of relevant medical history and disease progress of every subject;

(III) Record of using investigational medical devices for every subject, including utilization date, time and status of investigational medical devices of every time;

(IV) Signature and date of recorder.

Article 81

As original data, clinical trial record cannot be changed arbitrarily. Where change is really needed, it is required to give reasons, sign and mark the date.

Clinical trial protocol with significant deviation or data beyond the acceptable clinical range shall be verified and given necessary explanation of investigators

Article 82

Sponsor shall record information relating to clinical trial accurately and completely and the content shall include:

(I) Transporting and handling record of investigational medical devices, including name, model, specifications, batch number or serial number, name, address and delivery date of recipient, returned for repair or recycling and handling date of samples, reasons and handling methods of medical devices after clinical trial;

(II) Agreement signed with clinical trial institutions;

(III) Inspection report and verification report;

(IV) Record and report on serious adverse events and device defects that may cause serious adverse events.

Article 83

Investigators shall verify and confirm the safety and effectiveness of investigational medical devices in accordance with design requirements of clinical trial protocol and finish clinical trial report. Clinical trial report of multicenter clinical trial shall contain clinical trial summary of each branch center.

Article 84

For the multicenter clinical trial, clinical trial summary of each branch center shall at least include overview of clinical trial, general clinical information, information description of investigational medical devices and control medical devices, dataset of safety and effectiveness, occurrence rate and treatment of adverse events and protocol deviation, attached with case report form.

Article 85

The clinical trial report shall be in line with clinical trial protocol, mainly including:

(I) General information;

(II) Abstract;

(III) Brief introduction;

(IV) Clinical trial objectives;

(V) Clinical trial methods;

(VI) Content of clinical trial;

(VII) General clinical information;

(VIII)  Investigational medical devices and control medical devices or control diagnosis and treatment methods;

(IX) Applied statistical analysis method and evaluation method;

(X) Clinical evaluation standards;

(XI) Organization structure of clinical trial;

(XII) Statement of ethnical situation;

(XIII) Clinical trial results;

(XIV) Adverse events found in clinical trial and their treatment;

(XV) Analysis and discussion of clinical trial results, especially indications, scope of application, contraindications and precautions;

(XVI) Clinical trial conclusion;

(XVII) Problems and improvement and suggestions;

(XVIII) Name list of test personnel;

(XIX) Other situations need to be explained.

Article 86

Clinical trial report shall be signed and dated by investigators, provided opinions after being examined and approved by administrative departments of clinical trial of medical devices of clinical trial institutions, and submitted to sponsor after being dated and sealed by clinical trial institutions.

In multicenter clinical trial, the summary of each branch center shall be signed and dated by investigators of the center, approved by the administrative department of clinical trial of medical devices of the center, and submitted the leading unit after being dated and sealed by clinical trial institutions.

Chapter IX Management of Investigational medical devices

Article 87

Sponsor shall refer to the provisions of China Food and Drug Administration on administration of instructions for use and labels of medical devices to make proper identification for investigational medical devices and mark with “investigational”.

Article 88

The record of investigational medical devices shall include record relating to manufacturing data, batch number and serial number of products, inspection record relating to product quality and stability, record of transporting, maintaining and delivering to all clinical trial institutions for use, information on recovery after trial and handling data

Article 89

Clinical trial institutions and investigators shall be responsible for the utilization of investigational medical devices. Investigators shall ensure that all investigational medical devices are only used for subjects of this clinical trial and shall store and take care of investigational medical devices during trial period in accordance with requirements and handle investigational medical devices after clinical trial in accordance with relevant national provisions and agreement with sponsor. The above process shall be in the charge of specially-assigned person and recorded. Investigators shall not deliver investigational medical devices to any non-participant of clinical trial.

Chapter X Management of Basic Documents

Article 90

Clinical trial institutions, investigators and sponsor shall establish preservation system of basic documents. The basic documents of clinical trial shall be divided into three parts in accordance with clinical trial phases, namely documents of preparation phase, documents of implementation phase and documents after termination or completion.

Article 91

Clinical trial institutions shall keep clinical trial data for 10 years after the end of clinical trial. Sponsor shall keep clinical trial data until no such medical device is used.

Article 92

Basic documents of clinical trial can be used to evaluate the implementation of This Practice and relevant requirements of food and drug administration authorities by sponsor, clinical trial institutions and investigators. Food and drug administration authorities can implement inspection for basic documents of clinical trial.

Chapter XI Supplementary Provisions

Article 93 Meanings of the following terms in This Practice:

Clinical trial institutions of medical devices refer to medical institutions designated by China Food and Drug Administration and National Health and Family Planning Commission of the People’s Republic of China to undertake clinical trial of medical devices. Unless otherwise specified, “clinical trial institutions”in This Practice refer to “clinical trial institutions of medical devices”.

Investigational medical devices refer to medical devices planned to be applied and registered, whose safety and effectiveness are confirmed and verified in clinical trial.

Sponsor refers to institution or organization who launches and manages clinical trial and provides financial support.

Investigator refers to the person in charge of implementing clinical trial in clinical trial institution. In case trial is implemented by a group of personnel in clinical trial institution, investigator refers to the person in charge of the group, also known as principal investigator.

Ethics committee refers to the independent institution set by clinical trial institution to review the scientificity and ethicality of the items of clinical trial of medical devices.

Administrative department of clinical trial of medical devices refers to the division or department set in clinical trial institutions to take charge of organization, management and quality control of clinical trial of medical devices.

Multicenter clinical trial refers to clinical trial implemented in three or more clinical trial institutions in accordance with the same clinical trial protocol.

Subject refers to individual person who is recruited to accept clinical trial of medical devices.

Informed consent refers to the process for subjects to confirm to participate in this clinical trial voluntarily after subjects are informed of all situations of clinical trial, for which an informed consent form shall be signed and dated as documentary evidence.

Informed consent form refers to the documentary evidence signed subjects to indicate that they participate in clinical trial voluntarily.

Supervision refers to the activity that sponsor assigns special personnel to evaluate and investigate clinical trial institutions and investigators, verify, record and report the data during clinical trial in order to ensure that clinical trials are implemented in accordance with clinical trial protocol, standard operating procedure, This Practice and relevant applicant management requirements.

Supervisor refers to special person assigned by sponsor to supervise the items of clinical trial of medical devices.

Verification refers to systematic independent inspection for relevant activities and documents of clinical trial organized by sponsor so as to confirm whether the implementation of such activity, data recording, analyzing and reporting comply with clinical trial protocol, standard operating procedure, This Practice and relevant applicable management requirements.

Checker refers to person entrusted by sponsor to implement verification for the items of clinical trial of medical devices.

Inspection refers to the supervision and administration activities for relevant documents, facilities, records and other aspects by supervision department.

Inspector refer to person assigned by supervision department to inspect the items of clinical trial of medical devices.

Deviation refers to the situation of failure to abide by the requirements of clinical trial protocol intentionally or unintentionally.

Case report form refers to the document stipulated and designed in accordance with clinical trial protocol to record all information and data of each subject obtained during the trial process.

Endpoint refers to the index used to assess clinical trial hypothesis.

Source data refers to the original record of activities found and observed during clinical trial and other activities as well as all approved information in the copies, which can be used for the reconstruction and evaluation of clinical trial.

Source document refers to printing document, visual document or electronic document that contain source data.

Adverse events refer to adverse medical events occurred during the process of clinical trial, no matter they are relevant to investigational medical devices or not.

Serious adverse events refer to events occurred during the process of clinical trial that cause death or serious deterioration of health condition, including fatal diseases or injuries, permanent defects of body structure or body functions, demands of hospitalization or extending the duration of hospital stays, demands of medical or surgical intervention so as to avoid causing permanent defects to body structure or body functions, and events leading to fetal distress, fetal death or

congenital anomaly and congenital defect.

Device defects refer to unreasonable risks of medical devices under normal use during the process of clinical trial that may endanger human health and life safety, such as label error, quality problem and fault.

Standard operating procedure refers to the standards and detailed written specifications drafted to effectively implement and finish each work during clinical trial.

Clinical data refers to the information of safety and performance obtained from relevant literatures or clinical utilization of medical devices.

Article 94

Format model of documents, including application and approval form for ethnical review of clinical trial of medical devices, shall be separately formulated by China Food and Drug Administration.

Article 95

This Practice is not applicable to in vitro diagnostic reagent managed in accordance with medical devices.

Article 96

This Practice shall come into force as of June 1, 2016. Provisions for Clinical Trials of Medical Devices (Order No. 5 of China Food and Drug Administration) issued on January 17, 2004 shall be repealed simultaneously.