According to “Guideline on Acceptance of Overseas Clinical Trial Data of Medical Devices” issued on January 11, 2018, Overseas Clinical Trial Data package should include three parts:
1. Clinical trial protocol
3. Clinical study report
The study report shall include the analysis and conclusion for the complete clinical trial data.
According to “Guideline on Acceptance of Overseas Clinical Trial Data of Medical Devices” issued on January 11, 2018, there are three principles:
1. Ethics principle
2. Scientific principle, in terms of clinical trial design, clinical trial outcomes, and benefits and risks of participants.
3. Compliance principle. The overseas trial must comply with “Regulation of Medical Device Clinical Trial Quality Management” issued on March 1, 2016. If not comply, the difference must be demonstrated in detail.
1. Difference in Technical Review Requirements
2. Difference in Subjects (internal factors and external factors)
3. Difference in Clinical Trial Conditions
For multi-center or clinical trials, the following points should be followed:
– The study design should meet the requirements of the multi-center clinical trial in the “Medical Device Clinical Trial Quality Management Practice” (China Medical Device GCP), published on March 1, 2016.
– One clinical trial site should be identified as the lead site. All the sites should use same clinical protocol and conduct the clinical trial in the same period of time, to ensure the consistency of trial implementation and administration of study medical device.
– Statistical analysis principles and methods can follow those of multi-center clinical trial.
– The lead site should compile the clinical trial summaries from other sites and complete the clinical study report (CSR). The CSR should be stamped by all sites.
After signing an agreement or contract with each clinical trial site, the sponsor can file with the provincial drug administration department where the sponsor/agent is located. After the record is filed, clinical trials can be conducted.
When the same clinical trial project was filed for multiple times, the sponsor shall provide all the records obtained previously. The provincial drug administration department shall indicate in the “recording number” column of the “Medical Device Clinical Trial Record Form”, so that the clinical trial record number of the same project can be consistent.
Based on our previous experience, it is very likely that the reviewer only accepts one predicate device for the justification for clinical trial exemption. That is to say, you need to have a NMPA approved product that is very similar to your product structure design.
Simple CER is only a comparison table following NMPA’ s format requirements.
NMPA has a specific requirement for the comprehensive CER format and contents (16 sections). Comprehensive CER could be 50 or more pages long.
In China, all medical devices are divided into three classes (Class I, Class II, Class III) by their risk levels. Clinical trials are not required for Class I medical devices. For Class II and Class III medical devices, clinical trials are not required only if the products are included in the clinical trial exemption catalog or their efficacy and safety can be proved through comparison and analysis of predicates.
In China, local type testing is required before a medical device clinical trial can begin. Clinical trials for medical devices and IVDs must comply with China’s Good Clinical Practice (GCP) regulations and should be conducted in at least three qualified clinical trial organization. These clinical trials should also be registered with the NMPA (CFDA) branch at province, autonomous region or multiplicity level where the applicant is located. The applicant should submit a clinical trial protocol and report during the registration submission.
For IVDs and Class II medical devices, clinical trial approval or application is not needed in China. Only ethics committee approval/Institutional Review Board (IRB) is required instead. However, for Class III medical devices, which are at the higher risk level, NMPA (CFDA) does require an application for conducting clinical trials in China.
For the purpose of encouraging the development of globally synchronous R&D, NMPA (CFDA) accepts overseas clinical trials data that meet the requirements of NMPA clinical trial data registration management.
NMPA holds these 3 fundamental principles for overseas clinical data acceptance:
1. Ethical principle
2. Legal principle
3. Scientific principle
In addition, NMPA reviewers will evaluate the differences between overseas clinical data and China’s domestic conditions when deciding whether to accept the overseas clinical data or not. The top three major differences in consideration are:
1. Regulatory technical review differences
2. Ethnical differences
3. Clinical environment differences
Last but not least, overseas medical device clinical trial data submitted by the applicant should be authentic, scientific, reliable and traceable. Your overseas clinical data shall at least include the following:
1. Clinical trial protocol
2. Opinions of the ethics; and
3. The clinical trial report which includes the analysis of the complete clinical trial data and the conclusions.
Over the recent years, NMPA have significantly strengthened China’s clinical trial requirements. Not only NMPA now audits clinical trials for registration, it also inspects trial data for conditional approvals (for devices already approved but more clinical research is needed). In 2018 alone, NMPA published several draft guidelines addressing inspection of medical devices clinical studies.
From its medical device clinical trial audits. NMPA identified some comment issues and mistakes made by applicants. The list includes:
1. A clinical trial site is not listed on the NMPA (CFDA) filed institutions.
2. Some clinical trial personnel are not from the clinical trial institution.
3. The clinical trials protocol is not in accordance with the intended use of medical device.
4. Instruction of reused samples is not provided
5. In the multi-center test, the reference reagents are different.
6. The clinical trial procedures are inconsistent with the clinical trial protocol.
7. The records in the original medical records are incomplete.
8. The clinical data are inconsistent with the statistical analysis data provided on site.