Key Points and Judgment Principles for Clinical Trials of Medical Devices Issued by the National Medical Products Administration
2019-09-12
Notice on Inspection Points and Judgment Principles for Clinical Trials of Medical Devices by the National Medical Products Administration
Drug Administration Comprehensive Medical Device Note [2018] No. 45
The Food and Drug Administration (FDA) of each province, autonomous region, and municipality directly under the Central Government, Verification Center: In order to strengthen the supervision and management of the clinical trial process of medical devices, guide regulatory departments to carry out supervision and inspection of clinical trials of medical devices, and in accordance with the requirements of the "Measures for the Administration of Medical Device Registration" and the "Quality Management Standards for Clinical Trials of Medical Devices", the National Medical Products Administration has organized the formulation of the "Key Points and Judgment Principles for Clinical Trials of Medical Devices", which is now released.
Comprehensive Department of the National Medical Products Administration
19-Nov-18
Key points and judgment principles for clinical trial inspection of medical devices
According to the requirements of the "Regulations on the Administration of Medical Device Registration" and the "Quality Management Standards for Clinical Trials of Medical Devices", this inspection checklist and judgment principle are formulated to guide the on-site inspection work of medical device clinical trials.
1、 Key inspection points
| serial number | Key points of on-site inspection | Inspection content |
| 1 | Preparation before clinical trials | |
| 1.1 | Clinical trial institutions should have the qualifications to conduct clinical trials of relevant medical device products | Check the qualification certificate of drug clinical trial institutions or the filing certificate of medical device clinical trial institutions |
| 1.2 | The third category of medical devices that require clinical trial approval should be approved | Check the clinical trial approval documents for medical devices, and ensure that the approval date is no later than the start date of the clinical trial |
| 1.3 | Clinical trial projects shall be filed in accordance with relevant regulations | Check the "Medical Device Clinical Trial Filing Form" issued by the provincial bureau, with the filing date no later than the start date of the clinical trial |
| 1.4 | Clinical trials should obtain approval from the ethics committee of the clinical trial institution | Check the ethical review approval documents, with the approval date no later than the start date of the clinical trial enrollment |
| 1.5 | The development of experimental medical devices complies with the relevant requirements of the applicable medical device quality management system | Declaration that the development of medical devices for inspection and testing complies with the relevant requirements of the applicable medical device quality management system |
| 1.6 | The experimental medical devices have self inspection reports and product registration inspection qualification reports issued by qualified inspection agencies within one year | Check the corresponding inspection report |
| 1.7 | The facilities and conditions of the clinical trial institution are suitable for the clinical trial project | Check the main instruments, equipment, and facility conditions involved in the experimental plan |
| 1.8 | Clinical trial institutions have quality control certificates for medical or laboratory operations (if any) | The clinical laboratory carries out quality control in the clinical laboratory and inspects effective certificates of quality evaluation between clinical laboratories |
| 1.9 | Test related instruments and equipment should be regularly maintained and calibrated | Check the maintenance and calibration records of testing related instruments and equipment |
| 1.10 | Researchers should possess professional qualifications, clinical trial expertise, qualifications, and abilities | Check the professional qualifications, professional title certificates, resumes, etc. of the researchers. The researchers responsible for clinical trials should have relevant professional and technical titles and qualifications at or above the associate professor level in the clinical trial institution |
| 1.11 | Researchers have received training on clinical trial protocols and the use and maintenance of experimental medical devices | Check the clinical trial protocol and training records for the use and maintenance of medical devices used in the trial, with the training date no later than the start date of the clinical trial |
| 1.12 | Clinical trial signing clinical trial agreement/contract | Check the agreement/contract signed between the sponsor/agent and the clinical trial institution, specifying their respective responsibilities |
| 1.13 | The content of the agreement/contract matches the information of the medical device used in the experiment | Check the agreement/contract and clinical trial protocol for consistency in relevant information |
| 2 | Protection of subjects' rights and interests | |
| 2.1 | Ethical Review | |
| 2.1.1 | Ethics committee members have received training | Check the training records or certificates of ethics committee members |
| 2.1.2 | The content of ethical review complies with relevant norms, guiding principles, and SOP requirements | The content of ethical review should comply with Articles 17 and 33 of the Good Clinical Practice for Medical Devices (GCP), relevant guiding principles, and hospital ethical SOP requirements |
| 2.1.3 | Ethical review records should be complete | The integrity of the materials kept by the ethics committee should include the review materials, review forms, attendance sheets, voting tickets, meeting minutes, review approvals, and other documents specified in the SOP |
| 2.1.4 | The ethics committee's vote complies with relevant norms, guiding principles, and SOP requirements | The inspection of ethical review opinions, composition of ethics committee members, and voting records should comply with the requirements of Articles 30, 32, and 35 of the Medical Device GCP, guiding principles, and SOP |
| 2.1.5 | The revision, request for deviation, and resumption of suspended clinical trials in clinical trial protocols, informed consent forms, and other documents should obtain written approval from the ethics committee | Review the approval documents of the ethics committee regarding the relevant situation |
| 2.1.6 | The ethics committee tracks and supervises approved clinical trials | Check the tracking records of clinical trials |
| 2.2 | informed consent | |
| 2.2.1 | The content of the informed consent form complies with relevant standards, guiding principles, and SOP requirements | The content of the informed consent form should comply with the requirements of Article 22, Guiding Principles, and SOP of the Medical Device GCP |
| 2.2.2 | Prior to clinical trials, participants or their guardians and researchers shall sign their names and dates on the informed consent form, in compliance with relevant standards, guidelines, and SOP requirements | Check the subject screening form and signed informed consent form, the number of participants should be consistent, and they should be signed by the subjects themselves or their guardians/witnesses and researchers before participating in the clinical trial |
| 2.2.3 | The signed version of the informed consent form is consistent with the version approved by ethical review | Check the version and content of the informed consent form, and the signed informed consent form should be consistent with the version and content approved by ethical review |
| 2.2.4 | The content of the informed consent form should be updated, and the informed consent of the affected subjects or their guardians in the clinical trial should be obtained again | Check the updated version of the informed consent form. After the update, the affected subjects or their guardians in the trial should sign a new version of the informed consent form |
| 3 | Clinical trial protocol | |
| 3.1 | The clinical trial protocol has been confirmed by all center researchers and sponsors | Check the confirmation status of researchers in the clinical trial protocol. The clinical trial protocol should be signed by all center researchers and sponsors, and stamped with the official seal of the clinical trial institution |
| 3.2 | The content of the executed clinical trial protocol is consistent with the content of the ethical review clinical trial protocol | Check that the clinical trial protocol is consistent with the version and content of the clinical trial protocol kept by the ethics committee |
| 3.3 | The trial protocol executed by each center in a multicenter clinical trial is of the same version | Check that the clinical trial protocol versions saved and executed by each clinical trial center should be the same version |
| 3.4 | The clinical trial protocol submitted for registration application should be consistent with the clinical trial protocol stored by the clinical trial institution | Check that the clinical trial protocol submitted for registration application and the clinical trial protocol saved by the clinical trial institution are consistent in version and content |
| 4 | Clinical trial process | |
| 4.1 | Clinical trial personnel should obtain authorization from the principal investigator and relevant training | Check the division of labor authorization form, researcher training records, and signatures |
| 4.2 | Medical decisions related to clinical trials should be the responsibility of the researchers | Check personnel resumes and personnel division tables. The personnel authorization in the division table should be reasonable, and the medical decisions in the original documents should be signed by the researchers |
| 4.3 | Having case screening and selection records | Check the selection records of case screening, and clearly record the reasons for the failure of subject screening in the selection records. Researchers can provide subject identification documents |
| 4.4 | Subject identification documents or original records of screening selection, physical examination, etc. cover subject identification information | Check the subject identification documents or original records such as screening, physical examination, etc., which contain the subject's ID number, name, and other identification information |
| 4.5 | Researchers should follow the randomization procedure of clinical trials (if applicable) | The allocation of subject selection and randomization numbers should comply with the clinical trial protocol |
| 4.6 | The physical examination of subjects and auxiliary laboratory tests should be consistent with the trial protocol | The physical examination and laboratory auxiliary examination items in the original medical record should be consistent with the requirements of the clinical trial protocol, and any deviations from the protocol should be recorded |
| 4.7 | Are laboratory and other auxiliary checks conducted within the time frame specified in the plan | The auxiliary examination time of the laboratory should be within the time range specified in the clinical trial protocol, and any deviation from the time range should be recorded |
| 4.8 | The subjects were enrolled according to the inclusion and exclusion criteria of the experimental protocol | Check the medical history, medication history, laboratory tests, diagnosis, etc. in the original medical record. The subjects should meet all the inclusion and exclusion criteria in the clinical trial protocol |
| 4.9 | There are original records of the use of experimental medical devices | Check the original medical records, device usage records, and subject diary cards, and record the use of experimental medical devices |
| 4.10 | The product name, specifications, and usage method (such as date, time, status, etc.) of the experimental medical device are consistent with the clinical trial protocol, researcher manual, and instructions | The name, specifications, and usage methods (such as date, time, status, etc.) of the experimental medical device recorded in the original medical records, device usage records, and subject diary cards should be consistent with the clinical trial protocol, researcher manual, and instructions |
| 4.11 | The observation follow-up points should be consistent with the plan, and any follow-up visits, experiments, or examinations that were not conducted should be recorded truthfully | Check the follow-up records in the original medical records to ensure consistency with the data in the Case Report Form (CRF). Any deviations from the protocol should be recorded |
| 4.12 | Deviation from the plan in emergency situations should be reported in writing | There should be records of deviations from the protocol in emergency situations, and reports submitted to the sponsor, ethics committee, and clinical trial management department of the medical device clinical trial institution should be checked |
| 4.13 | Participants who withdraw or are lost to follow-up for any reason should be recorded and explained in detail | Check the completion status of subjects in the selection form, original medical records, CRF, or sub center clinical trial summary, and record and provide detailed explanations for withdrawal and loss to follow-up |
| 4.14 | The safety and effectiveness evaluation should comply with the requirements of the test plan | The safety and effectiveness evaluation methods in the original medical records should be carried out in accordance with the requirements of the clinical trial protocol, and the original data should be consistent with the CRF |
| 4.15 | Researchers should verify data that deviates significantly from the clinical trial protocol or is outside the clinically acceptable range | Check the inspection report form, and the researcher should determine the abnormal values in it |
| 4.16 | The combined use of drugs and medical devices should be recorded according to the experimental protocol, and there should be no combined drugs or medical devices that violate the requirements of the experimental protocol (if applicable) | Check the original medical records and hospital HIS system. Researchers should record the combined use of drugs and medical devices, and ensure consistency with the data in CRF and clinical trial statistical databases |
| 4.17 | Adverse events, complications, and device defects should be recorded | Check the original medical records and hospital HIS system. Researchers should record adverse events, complications, and device defects, and ensure consistency with the data in CRF and clinical trial statistical databases |
| 4.18 | Timely treatment and management of serious adverse events/adverse events (SAE/AE), tracking and follow-up | Check the original medical records or serious adverse event/adverse event report forms. The handling of serious adverse events/adverse events should be timely and tracked for follow-up |
| 4.19 | Check the original medical records or serious adverse event/adverse event report forms. The handling of serious adverse events/adverse events should be timely and tracked for follow-up | Check the serious adverse event report form, the records should be complete, and prove that the researcher reported in writing to the corresponding ethics committee and the drug supervision and management department and health and family planning department of the province, autonomous region, or municipality where the clinical trial institution is located within 24 hours. Check the report of device defects and prove that the device defects have been reported to the ethics committee for review by the medical device clinical trial management department of the clinical trial institution |
| 4.20 | When suspending or terminating clinical trials, subjects should receive appropriate treatment and follow-up | Check the original medical records and ensure that the subjects receive appropriate treatment and follow-up |
| 4.21 | Blind trial shall be conducted according to the requirements of the trial protocol for unblinding (if any) | Check the unblinding records and verify that unblinding complies with the protocol requirements |
| 4.22 | The sponsor supervises the implementation of clinical trials | Check the monitoring records of the inspectors, and the researchers should take timely corrective measures for the problems found during the monitoring |
| 5 | Record and Report | |
| 5.1 | Clinical trial records | |
| 5.1.1 | Accurate, complete, clear, and timely filling of clinical trial records | Check the original medical records CRF， Records should be accurate, complete, clear, and timely |
| 5.1.2 | Make corrections to errors and omissions | Check the modification records, data query forms, and response records in the original medical records, and correct any errors or omissions |
| 5.1.3 | The modification of clinical trial records should be explained with reasons, signed and dated by the modifier, and the original records should be kept clear and legible | Check the original medical record modification records, ensure that the modifications meet the requirements, and record the reasons for the modifications |
| 5.1.4 | The inspection results of the laboratory, imaging department, electrocardiogram room, endoscopy room, etc. can be traced back | Check the hospital's LIS, PACS and other systems, and the relevant auxiliary examination data should be traceable in the system |
| 5.1.5 | The data in CRF is consistent with the original medical records | Check CRF and original medical records, data should be consistent |
| 5.1.6 | Electronic clinical databases or remote electronic clinical data systems should ensure that clinical data is controlled, authentic, and has complete validation documents (if applicable) | When checking electronic clinical databases or remote electronic clinical data systems, there should be training records, independent accounts, usage permissions, data review, verification documents, and audit tracking functions |
| 5.2 | Clinical trial report | |
| 5.2.1 | After the completion of a multicenter clinical trial, each sub center has a clinical trial summary or clinical trial report | The clinical trial summary or clinical trial report of each sub center should be kept intact |
| 5.2.2 | The clinical trial summary or clinical trial report should have the signature of the researcher, indicate the date, have the review opinion of the clinical trial institution, indicate the date, and be stamped with the seal of the clinical trial institution | The clinical trial summary or clinical trial report should be signed by the researcher, dated, reviewed by the clinical trial institution, dated, and stamped with the clinical trial institution seal |
| 5.2.3 | The database data or sub center clinical trial summary data used for statistics is consistent with CRF | Randomly check the statistics of CRF clinical trials and the data in the database, and ensure that the data is consistent |
| 5.2.4 | The clinical trial report or statistical analysis report is consistent with the database data or sub center clinical trial summary data used for statistics | Check the clinical trial report or statistical analysis report for consistency with the clinical trial statistical database or sub center clinical trial summary data |
| 5.2.5 | The content of the clinical trial report submitted for registration application is consistent with the content of the clinical trial report kept by the clinical trial institution | Check that the clinical trial report submitted for registration application and the clinical trial report kept by the clinical trial institution have consistent versions and contents |
| 6 | Management of experimental medical devices | |
| 6.1 | Save information including name, model, specifications, receiving date, production date, product batch number or serial number, etc | The handover form or other relevant records for medical devices used in inspection and testing should include information such as name, model, specifications, receipt date, production date, product batch number or serial number, quantity, etc |
| 6.2 | Consistent with the product name, specifications and models in the testing report and clinical trial report | Check the specifications and models of the medical devices used in clinical practice, testing reports, and clinical trial reports, and ensure that the information is consistent |
| 6.3 | The records of transportation, reception, storage, distribution, recycling, and disposal should be complete | Check the records of transportation, receiving, storage, distribution, recycling, and disposal, which should be complete in content, and identify the reasons for inconsistent quantities in the records |
| 6.4 | Whether the transportation conditions, storage conditions, storage time, expiration date, etc. meet the requirements | Check the transportation, receiving, and storage records, and ensure that the transportation conditions, storage conditions, storage time, expiration date, etc. meet the requirements |
| 6.5 | The quantity used, discarded, or returned is consistent with the quantity provided by the applicant | Check the records of receipt, use, disposal, and recycling, and the quantity should be consistent with the data provided by the applicant |
| 6.6 | The storage and use of special medical devices are consistent with the content of the summary report | Medical devices with special storage requirements (such as radiation protection, low-temperature refrigeration, etc.) should be inspected, and the storage conditions and usage should be consistent with the content of the summary report |
