NMPA: Key Inspection Points for Medical Device Clinical Trial Projects

No.

On-site Inspection Points

Inspection Content

1

Clinical Trial Conditions and Compliance

1.1

Medical device clinical trials shall be conducted in medical device clinical trial institutions that have appropriate conditions and have completed the required filing procedures.

Check the medical device clinical trial institution filing management information system. The relevant specialties and principal investigator shall have completed filing, and the filing date shall be earlier than the date of ethical review for the project. The trial site shall be consistent with the filed site.

1.2

Medical devices listed in the catalog of Class III medical devices requiring clinical trial approval shall obtain approval from the NMPA, and the clinical trials shall be conducted in qualified Class III Grade A medical institutions.

Check the clinical trial approval opinion document. The announcement date shall not be later than the date of informed consent for the first subject. The undertaking institution shall be a Class III Grade A medical institution.

1.3

The principal investigator shall meet the filing requirements. For innovative medical devices or Class III medical devices requiring clinical trial approval, the principal investigator shall have a senior professional title and have participated in more than three medical device or drug clinical trials.

Check the innovative medical device certification document or clinical trial approval opinion document. Check the principal investigator's practicing qualifications, professional title certificates, resume, etc. Check relevant materials proving the principal investigator's participation in more than three medical device or drug clinical trials, such as attendance sheets for initiation meeting training, subject screening records, center summaries, authorization forms, outpatient or inpatient medical records, quality control records, etc., from completed clinical trials.

1.4

The clinical trial shall obtain approval from the ethics committee of the clinical trial institution.

Check the ethical review approval document. The approval date shall be before the informed consent or screening of the first subject.

1.5

Clinical trials shall be filed with the provincial-level medical device regulatory department where the sponsor is located.

Check the medical device clinical trial filing document issued by the provincial-level medical device regulatory department. The filing date shall not be earlier than the date of the ethical approval and contract signing, and shall be before the informed consent or screening of the first subject.

1.6

The trial medical device shall be produced in accordance with the relevant requirements of the Medical Device Quality Management规范 (Specifications) and shall be of qualified quality.

Check the declaration of conformity with the applicable medical device quality management system requirements and the qualification certificate for the trial medical device.

1.7

The trial medical device shall have a product inspection report based on the product technical requirements.

Check the self-inspection report from the enterprise or the product inspection report issued by a qualified inspection agency. The inspection items shall cover all clauses of the product technical requirements, and the conclusion shall be qualified.

1.8

The facilities and conditions of the clinical trial institution shall be suitable for the clinical trial project. Trial-related instruments and equipment shall be regularly maintained and calibrated.

Check that the main instruments, equipment, and facilities involved in the clinical trial comply with the trial protocol or relevant requirements. Check the maintenance, calibration, and verification records or certificates for trial-related instruments and equipment during use, and ensure they are within the validity period.

1.9

The hospital's clinical laboratory shall have internal quality control. Clinical trial-related testing items shall have a valid external quality assessment certificate issued by an organization recognized by the health authority (if applicable).

Check the relevant system for internal quality control of clinical testing in the clinical laboratory and quality control records. Check the valid external quality assessment certificate for clinical testing.

1.10

Investigators shall have the corresponding professional technical qualifications, training experience, and relevant experience to undertake medical device clinical trials, and shall be authorized by the principal investigator.

Check the investigators' practicing qualifications, professional title certificates, resumes, training records or certificates, etc. Check the authorization form. The responsibilities shall be clear and the division of labor reasonable.

1.11

Investigators shall receive training on the clinical trial protocol and the use and maintenance of the trial medical device.

Check the investigators' training records, which should include training related to medical device clinical trials, such as the principle, intended use, product performance, operation method, installation requirements, and technical indicators of the trial medical device, as well as the clinical trial protocol, standard operating procedures (SOPs), and other relevant documents. Training shall be completed before performing the duties specified in the authorization form.

1.12

Before the trial begins, the sponsor shall sign 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.

Check the clinical trial agreement/contract. The rights and obligations of all parties shall be clearly defined and signed/stamped. The information on the trial medical device in the contract shall be consistent with the clinical trial protocol.

1.13

The sponsor shall provide the medical device clinical trial institution and the principal investigator with trial-related documents and materials such as the trial medical device.

Check the handover records of relevant documents such as the investigator's brochure, clinical trial protocol, informed consent form, case report form (CRF), SOPs, etc., and the handover records of materials such as the trial medical device. The supply and handover of materials and trial medical devices shall meet trial requirements, with accurate quantities and versions.

2

Protection of Subjects' Rights and Interests

2.1

Ethical Review

2.1.1

The content and opinions of the ethical review shall comply with relevant regulations, GCP, guiding principles, and SOP requirements.

Check that the ethical review documents, review content, and review opinions comply with the requirements of relevant regulations, GCP, guiding principles, and SOPs.

2.1.2

The ethics committee shall retain all records of the ethical review.

Check the documents retained by the ethics committee, including written records of ethical reviews, committee member information, submitted documents, meeting minutes, and relevant correspondence records, or documents specified in the ethics committee's SOPs. The content shall be complete and accurate and consistent with the ethical review opinions.

2.1.3

Revisions to the clinical trial protocol, informed consent form, and other documents, and the resumption of a suspended clinical trial, shall be implemented only after re-obtaining written approval from the ethics committee.

Check the approval documents from the ethics committee for the relevant situations and the implementation status. The implementation time shall not be earlier than the ethical approval time.

2.1.4

The ethics committee shall conduct ongoing review of the clinical trial and shall review safety information, protocol deviations, etc.

Check the ethics committee's ongoing review documents, review records, etc. The process shall comply with the ethics committee's relevant systems and SOPs. Review safety information such as serious adverse events (SAEs) occurring at the institution and sponsor-reported trial medical device-related SAEs. Review the potential impact of deviations from the clinical trial protocol on subjects' rights and safety, or on the科学性 (scientificity) and integrity of the medical device clinical trial.

2.2

Informed Consent

2.2.1

The content of the informed consent form shall comply with GCP, relevant regulations, and SOP requirements.

Check the specific content of the informed consent form. It shall comply with GCP, relevant regulations, and SOP requirements.

2.2.2

Before screening and enrollment in the clinical trial, the subject and/or guardian (if required), and the investigator, and an impartial witness (if required) shall all sign their names and dates on the latest version of the informed consent form approved by the ethics committee.

Check the subject screening form and the signed informed consent forms. The numbers should be consistent. The signatory names and signing dates shall meet the requirements.

2.2.3

Investigators shall use the latest version of the informed consent form and other written materials provided to subjects that have been approved by the ethics committee.

Check the version and content of the signed informed consent forms. They shall be consistent with the latest version and content approved by the ethical review.

2.2.4

The signing time of the informed consent form shall not be earlier than the ethical approval time. The screening time shall, in principle, not be earlier than the signing time of the informed consent form.

Check the informed consent signing time, ethical approval time, and screening time.

2.2.5

After the informed consent form is updated and reviewed and approved by the ethics committee, all affected subjects whose trial procedures have not ended shall be re-obtained informed consent.

Check the updated version of the informed consent form. Affected subjects in the trial whose procedures have not ended and/or their guardians/impartial witnesses (if required) shall re-sign the newly revised informed consent form.

3

Clinical Trial Protocol

3.1

The clinical trial protocol shall be signed and dated by the principal investigator and reviewed and stamped by the medical device clinical trial institution.

Check the clinical trial protocol. It shall be signed by the principal investigator and the sponsor's responsible person, and stamped with the seals of the clinical trial institution and the sponsor.

3.2

The medical device clinical trial shall comply with the latest version of the clinical trial protocol approved by the ethics committee.

Check all previous versions of the clinical trial protocol and those retained by the ethics committee. The versions and content shall be consistent.

3.3

For multicenter clinical trials, the trial protocol executed by each center shall be the same version.

Check the version of the clinical trial protocol saved and executed by each clinical trial center. In principle, it should be the same version with consistent content.

3.4

The content of the clinical trial protocol submitted for registration application shall be consistent with the content of the clinical trial protocol retained by the clinical trial institution.

Check the clinical trial protocol submitted for registration application and the clinical trial protocol retained by the clinical trial institution. The versions and content shall be consistent.

4

Clinical Trial Implementation Process

4.1

Subject Screening and Enrollment

4.1.1

There shall be records of subject screening and enrollment.

Check the subject screening and enrollment records. The screening and enrollment criteria shall be consistent with the trial protocol. Reasons for screen failure shall be clearly recorded.

4.1.2

Original records such as subject identification documents or screening/enrollment documents shall contain subject identity verification information.

Check original records such as subject identification documents or screening/enrollment documents. They shall contain subject identity verification information such as ID number, name, gender, age, etc.

4.1.3

Investigators shall comply with the randomization procedures specified in the clinical trial protocol (if applicable).

Check the assignment of subject enrollment numbers and random numbers. It shall comply with the trial protocol requirements. The time of randomization shall be after the subject screening process is completed and all criteria are met.

4.1.4

Subject enrollment shall meet the inclusion criteria specified in the trial protocol and shall not meet the exclusion criteria.

Check the present illness history, past history, medication history, laboratory tests, diagnosis, etc., in the hospital's HIS system (inpatient/outpatient medical records). The subject shall meet all inclusion criteria in the clinical trial protocol and shall not meet the exclusion criteria. Sufficient supporting evidence shall be retained for enrolled subjects.

4.2

Clinical Trial Protocol Execution

4.2.1

Trial procedures such as physical examinations, laboratory tests, and follow-up records for subjects shall be consistent with the trial protocol and within the time range specified in the protocol.

Check that the trial process in the original medical records is consistent with the requirements of the clinical trial protocol. Follow-ups shall be conducted within the time range specified in the clinical trial protocol. Failure to perform follow-ups, unperformed trial procedures, and omitted examinations shall be truthfully recorded.

4.2.2

Deviations from the clinical trial protocol shall be reported to the ethics committee.

Check the protocol deviation reports submitted to the ethics committee. The content shall be comprehensive and complete.

4.2.3

Subject withdrawal and loss to follow-up for any reason shall be recorded and explained in detail.

Check the subject completion status in the screening/enrollment form, original medical records, CRF, or center summary. Withdrawal and loss to follow-up shall be recorded in detail.

4.2.4

Safety and efficacy evaluation methods shall comply with the trial protocol requirements.

Check that the safety and efficacy evaluation methods in the source documents are executed according to the clinical trial protocol requirements.

4.2.5

Concomitant use of drugs and medical devices, and concomitant treatments shall be recorded according to the trial protocol.

Check original medical records, the hospital HIS system, subject diary cards (if any). Concomitant use of drugs and medical devices, and concomitant treatments shall be recorded. Any protocol violations shall be recorded, handled, and reported promptly.

4.2.6

For blinded trials (if involved), blinding, maintenance of blinding, and unblinding shall be performed according to the trial protocol requirements. In case of accidental unblinding or emergency unblinding required for SAEs, the investigator shall operate according to the emergency unblinding procedure and provide a written explanation.

Check blinding implementation records and unblinding records. Blinding maintenance and unblinding shall comply with protocol规定 (stipulations). Check the emergency unblinding operating procedures and related records.

4.2.7

Monitors shall monitor the implementation of the clinical trial.

Check relevant records of monitoring conducted by the monitor, such as monitoring reports, email correspondence, or communication records. Investigators shall promptly take corrective measures for issues found during monitoring.

4.3

Safety Information Handling and Reporting

4.3.1

Clinical trial-related medical decisions shall be the responsibility of an investigator at the institution who has a practicing physician qualification.

Check personnel resumes and the authorization form. Medical decisions in source documents shall be signed by an investigator at the institution who has a practicing physician qualification and is authorized.

4.3.2

Investigators shall verify abnormal laboratory values or abnormal reports.

Check laboratory test reports. Investigators shall evaluate abnormal values therein.

4.3.3

When adverse events or serious adverse events occur, investigators shall provide sufficient and timely treatment and management for the subjects.

Check the original medical records for the treatment and management of adverse events and serious adverse events by the investigator.

4.3.4

Investigators shall record adverse events, serious adverse events, and device defects discovered during the medical device clinical trial process.

Check original medical records, the hospital HIS system, adverse event records, SAE report forms, and device defect record forms. There should be no concealment, omission, misjudgment, or misrecording. The criteria for judging association with the medical device shall comply with the trial protocol规定 (stipulations) and medical practice. The basis for judgment shall be recorded in the source documents.

4.3.5

Investigators shall report to the sponsor, the management department of the medical device clinical trial institution, and the ethics committee within 24 hours of becoming aware of a serious adverse event. They shall also follow up on the serious adverse event as required and submit follow-up and summary reports.

Check the original medical records and the serious adverse event report form. Reporting shall be within the time limit, and the report content shall be complete and accurate. Follow-up shall be conducted, and follow-up and summary reports shall be submitted.

4.3.6

Trial medical device-related serious adverse events shall be reported by the sponsor to the designated department within the specified time. If widespread trial medical device-related serious adverse events or other major safety issues occur, the sponsor shall suspend or terminate the medical device clinical trial and report as required.

Check the serious adverse event report forms reported by the sponsor. The content shall be filled out according to the template format, and risk control measures shall be taken. The reporting time limit and scope shall comply with GCP regulations. If the judgment of association with the medical device is inconsistent with the investigator's, there shall be a reasonable explanation.

4.3.7

When it is found that the risks of the medical device clinical trial outweigh the potential benefits, and the trial needs to be suspended or terminated, the principal investigator shall report as required, promptly notify the subjects, and ensure that the subjects receive appropriate treatment and follow-up.

Check the original medical records and the serious adverse event report form. Subjects shall receive appropriate treatment and follow-up. If risks are found to outweigh benefits, the clinical trial shall be suspended or terminated as required, and reported to the sponsor, institutional management department, and ethics committee.

4.3.8

The principal investigator shall promptly handle received safety information.

Check trial medical device-related serious adverse events and other safety information. The principal investigator shall promptly acknowledge receipt and read it. If the subject's treatment needs adjustment, it should be communicated with the subject and recorded in the source documents.

4.3.9

The principal investigator shall report the progress of the medical device clinical trial to the ethics committee as required and promptly report events affecting subjects' rights and safety.

Check the progress reports of the medical device clinical trial.

5

Clinical Trial Data Recording, Traceability, and Reporting

5.1

Clinical Trial Records

5.1.1

In medical device clinical trials, any observations and findings shall be recorded correctly and completely.

Check that the records in clinical trial documents such as original medical records are accurate, complete, clear, and timely. If paper records (notebooks, record sheets) are used, they shall be controlled, and forms shall be version-controlled.

5.1.2

Medical device clinical trial data shall be authentic, accurate, complete, and traceable.

Check the data in the original medical records. It shall meet the general standards for clinical trial data quality (ALCOA+): Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, and Available.

5.1.3

For clinical trials with patients as subjects, relevant medical records shall be recorded in the outpatient or inpatient medical records. Institutions that already use electronic medical record systems for daily diagnosis and treatment shall also use electronic medical records for clinical trials.

Check outpatient or inpatient medical records. They shall cover relevant medical records such as basic subject information (gender, age, etc.), informed consent process, enrollment time, clinical diagnosis and treatment information, etc. The management of clinical trial source documents shall comply with medical management requirements.

5.1.4

Source data for medical device clinical trials shall be clear and identifiable and shall not be altered arbitrarily. If alteration is necessary, the reason shall be stated, signed, and dated.

Check the source data. If there are modifications, the reason for modification shall be indicated, and the initial record shall remain clear and identifiable, retaining the modification trail/trace. The modifier shall sign and date.

5.1.5

The completion and modification of the case report form (CRF) shall comply with GCP requirements and the guidelines provided by the sponsor.

Check that the data in the CRF is accurate, complete, clear, and timely. For data modifications, the initial record shall be clear and identifiable, retaining the modification trail/trace, stating the reason for modification, and the modifier shall sign and date.

5.1.6

For electronic data capture (EDC) systems, they shall be reliably validated, have完善的 (comprehensive)权限管理 (permission management) and audit trails, and can trace the creator of the record, creation time, or modifier, modification time, modification circumstances. The collected electronic data shall be traceable (if applicable).

Check the EDC system. It shall have user management, role management, and permission management. Different personnel or roles shall have unique login permissions, independent accounts, audit trails, data review, and validation documents.

5.1.7

If the source data of trial results are in the form of electronic photos, images, or electronic documents, the source files and key process files shall be completely saved.

Check the form of source data storage. Source files and key process files shall be completely saved, including files in various formats. Final data alone should not be retained. In special circumstances, backup files can be saved, and the backup files shall be checked.

5.2

Clinical Trial Data Traceability

5.2.1

Information in the case report form, such as informed consent, medical history or concomitant diseases, enrollment, visits, device usage records, and condition records, shall be consistent with the trial source data.

Spot-check data in the case report form. It shall be consistent with the source data.

5.2.2

Data in the registration application database, such as primary efficacy endpoints, safety endpoints, inclusion/exclusion criteria, shall be consistent with the source data.

Spot-check data in the database. It shall be consistent with the source data.

5.2.3

Relevant data and reporting status recorded in the center summary or clinical trial report shall be consistent with the source data.

Spot-check relevant data or trial status recorded in the center summary or clinical trial report. It shall be consistent with the source data. There shall be no concealment, omission, or misrecording.

5.2.4

Concomitant medications, concomitant medical devices, concomitant treatments, etc., recorded in the case report form, database, center summary, or clinical trial report shall be traceable in the HIS system, medical records, or subject diary cards.

Spot-check concomitant medications, concomitant medical devices, concomitant treatments, etc. They shall be traceable in the original records, and there shall be no omissions.

5.2.5

Examination and test results from departments such as the laboratory, radiology, ECG, and endoscopy shall be traceable.

Check hospital LIS, PACS systems, or related instruments and equipment. Auxiliary examination data shall be traceable in the systems or instruments/equipment.

5.2.6

If subject self-assessment results are used as efficacy and safety data, they shall be traceable to the original assessment records confirmed by the subject's signature.

Check subject diary cards, subject self-assessment reports, etc. Efficacy and safety indicators shall be recorded in detail and confirmed by the subject's signature.

5.3

Clinical Trial Report

5.3.1

For multicenter clinical trials, the clinical trial report shall be signed and dated by the coordinating investigator and reviewed and stamped by the lead unit institution. Each center shall have a clinical trial summary, which shall be signed and dated by the principal investigator of that center and reviewed and stamped by the medical device clinical trial institution of that center.

Check the clinical trial summary of each center or the clinical trial report. It shall comply with Articles 52 and 56 of GCP.

5.3.2

Data among source data, case report forms, the registration application database, center summaries, clinical trial reports, and other application materials shall be consistent.

Spot-check data among source data, case report forms, the registration application database, center summaries, clinical trial reports, and other application materials. They shall be consistent.

5.3.3

The content of the clinical trial report and center summary submitted for registration application shall be consistent with the content of the clinical trial report retained by the clinical trial institution.

Check the clinical trial report and center summary submitted for registration application and those retained by the clinical trial institution. The versions and content shall be consistent.

5.3.4

The conditions and procedures for database locking shall comply with the SOP for database locking (if any).

Check the SOP for database locking and related records. The database locking process and time shall have clear documentation. For blinded clinical trials, unblinding shall occur only after database locking.

6

Trial Medical Device Management

6.1

The trial medical device shall be used only for subjects participating in that medical device clinical trial.

Check the trial medical device usage records. It shall not be used for subjects outside the clinical trial.

6.2

There shall be original records of the use of the trial medical device and the control medical device (if any).

Check original medical records, device usage records, subject diary cards (if any). The usage of the trial medical device and control medical device (if any) shall be recorded, including name, batch number, specification, quantity, etc.

6.3

The product name, specification model, and operation procedure of the trial medical device and control medical device (if any) shall be consistent with the clinical trial protocol, investigator's brochure, and instructions for use.

Check the product name, specification model, and operation procedure of the trial medical device and control device (if any) recorded in the original medical records, device usage records, and subject diary cards (if any). They shall be consistent with the clinical trial protocol, investigator's brochure, and instructions for use.

6.4

The storage information for the trial medical device and control medical device (if any) shall include name, model, specification, receipt date, production date, product batch number or serial number, etc.

Check the handover form or other relevant records for the trial medical device and control medical device (if any). It shall include information such as name, model, specification, receipt date, production date, product batch number or serial number, quantity, validity period, signature, manufacturer (if any), etc.

6.5

The device name, specification model, batch number, or serial number in various device management records shall be consistent with those in the inspection report, center summary, clinical trial report, and other application materials.

Check that information such as the name, specification model, batch number, or serial number of the medical device used clinically, in the inspection report, center summary, and clinical trial report is consistent. Or provide relevant materials for model coverage, such as a statement of typicality, analysis of differences between the covered model/configuration and the main tested model/configuration, etc.

6.6

Records shall be kept for the transportation, receipt, storage, distribution, use, recovery, and disposal of the trial medical device and control medical device (if any).

Check records of transportation, receipt, storage, distribution, use, recovery, and disposal. The content shall be complete. Abnormalities in each环节 (link) shall be promptly assessed, handled, and recorded.

6.7

Transportation conditions, storage conditions, storage time, validity period, etc., shall meet the requirements.

Check transportation and storage records. Transportation conditions, storage conditions, storage time, validity period, etc., shall comply with the requirements of the investigator's brochure, trial protocol, instructions for use, etc.

6.8

The quantity used, remaining quantity, and other circumstances (e.g., loss, authorized destruction, etc.) of the trial and control medical devices (if any) shall be consistent with the quantity provided by the sponsor.

Check the receipt, use, destruction, and recovery records. The quantities shall be consistent with the data provided by the sponsor. Reasons for quantity discrepancies in any环节 (link) shall be recorded.

6.9

The storage and usage of special medical devices shall be consistent with the content of the trial protocol and the summary report.

Check medical devices with special storage requirements (e.g., requiring radiation protection, low-temperature refrigeration, etc.). The storage conditions and usage shall be consistent with the trial protocol, instructions for use, and summary report content.