Pre-registration clinical evaluation is the most critical link in the medical device registration application stage. The way of clinical evaluation will directly determine the registration period and cost of medical devices.
For medical device products that have already undergone clinical trials overseas, the NMPA issued the "Technical Guiding Principles for Accepting Overseas Clinical Trial Data for Medical Devices" to guide how overseas clinical trial data can be used to register medical devices in China. This article mainly introduces the data requirements for accepting clinical trial data of overseas medical devices.
I. Scope of overseas clinical trial data acceptance
Research data generated in the process of confirming the safety and effectiveness of medical devices to be registered in China under normal use conditions in all or at the same time in overseas clinical trials institutions that have the requirements of the country (region) where the clinical trial is conducted.
Overseas clinical trials need to comply with the relevant regulations of overseas clinical trials and are carried out in countries (regions) with clinical trial quality management.
II. Follow the basic principle - the principle of law
The overseas clinical trials should meet the regulatory requirements for clinical trials of medical devices (including in vitro diagnostic reagents) in China.
If the clinical trial quality management document that the clinical trial meets is different from the "GCP", the content of the difference should be explained in detail, and it should be fully proved that the difference does not affect the authenticity, scientificity, reliability and traceability of the research results.
For example: In addition to the IRB-IEC approval, the clinical trial plan in Korea also needs to be approved by MFDS and accept their inspection. Registration projects in China only need to file the clinical trial plan, informed consent and other documents in the local provincial bureau. This content does not affect the research results, and can protect the rights and interests of the subjects.
The applicant and the clinical trial institution shall accept the supervision and inspection of the NMPA.
III. Data and material requirements for overseas clinical trials
The overseas clinical trial materials submitted by the applicant shall include at least: clinical trial protocol, ethical opinions, and clinical trial report. The clinical trial report should include analysis and conclusions of the complete clinical trial data.
When some additional information is needed according to the relevant technical requirements for registration in China, supplementary clinical trials may be carried out in China or abroad. After the comprehensive evaluation of the supplementary test data and the original overseas trial data meets the relevant technical requirements for registration in China, it will be accepted.
If the applicant uses the data of multi-center clinical trials carried out in China and abroad at the same time as the registration application information, it should also clarify the distribution basis of the number of subjects undertaken in China to facilitate further evaluation of whether it meets the relevant registration requirements in China.
IV. Considerations and technical requirements when accepting overseas clinical trial data
1. Differences in technical review requirements
Such as the design of the protocol and the difference in the requirements of the endpoint criteria, etc., it is necessary to follow the relevant requirements for clinical trials in the "Guidelines for Technical Evaluation of Medical Devices" issued by the NMPA; when there is inconsistency, sufficient and reasonable reasons and basis should be provided.
Judging from the study of Remdesivir in the United States and China, the difference in the setting of the endpoint criteria will directly affect the success of the trial. For example: since there is no unified guiding principle for the endpoint criteria of the facial implant PPDO, we will refer to the effectiveness and safety criteria set in the “Guidelines for Technical Review of Absorbable Surgical Suture Registration” (to improve the efficiency of surgery, postoperative complications and adverse events, etc.).
2. Differences in the subject population
Differences caused by ethnic differences. If the genotype of the diagnostic reagent is different, the detection rate of the diagnostic reagent is different. Facial lifting surgery is applicable to the Asian population, so there is no racial heterogeneity in clinical trials of lifting surgery.
3. Differences in clinical trial conditions
Differences in test conditions include: differences in medical environment, medical facilities, investigator capabilities (learning curve), diagnosis concepts or guidelines, etc. For example, different concepts or standards of diagnosis and treatment, different methods of operation, different levels of doctor's operation or different levels of medical equipment, etc.
For example, due to the earlier and more mature facial lifting surgery in Korea, there may be new procedures that have not been carried out in China. Whether it can be applied to the registration of clinical trials in China needs further evaluation.Applicants should clarify the methods used to reduce or eliminate the impact of various differences, such as subgroup design of the test population, or subgroup analysis of existing clinical trial data, if necessary.