The SAIC released the technical guidelines for accepting data on overseas clinical trials of medical devices

Pharmaceutical Network January 12 hearing in order to implement the General Office of the CPC Central Committee and the General Office of the State Council "on deepening the reform review and approval system to encourage innovation in medical devices," (Office word 〔2017〕 42), to strengthen the registration of medical device products To further improve the quality of registration examination and encourage the innovation of medical device research and development, the State Food and Drug Administration has formulated the technical guidelines for accepting the data of overseas clinical trials of medical devices (see Annex) and is hereby promulgated.

announce.

Annex: technical guidelines for accepting clinical data from overseas clinical trials of medical devices

food drug Regulatory Authority

January 10, 2018

In order to better meet the public right medical instruments According to the Opinions of the General Office of the CPC Central Committee and the General Office of the State Council on the Opinions on Deepening the Innovation of Medical Device Innovation in the Examination and Approval System of Examination and Approval (Office Word [2017] No. 42) and the registration of medical device registration in our country The guidelines set out in this guideline are intended to provide applicants with technical guidance on the registration of overseas clinical trial data of medical devices and the regulatory authorities' review of such clinical trial data to avoid or reduce repetitive clinical trials and accelerate medical treatment Instruments in the process of listing in China.

This guideline is applicable to guide the medical devices (including in vitro diagnostic reagents) to apply for the clinical evaluation data when they apply for registration in China.

The clinical trial data related to this guideline refer to the clinical trial organizations that have the required conditions of the countries (or regions) where the clinical trial is carried out in whole or in the same period, Safety and effectiveness of the confirmation process generated by the research data.

Overseas clinical trials should follow the ethical guidelines set forth in the Helsinki Declaration of the World Medical Congress.Applicants also need to describe the clinical trial used to carry out the ethics, law, Regulations The norms and standards formulated standard , Or international norms and standards.

Overseas clinical trials should be conducted in countries (regions) that have quality control of clinical trials and meet the regulatory requirements for clinical trials of medical devices (including in vitro diagnostic reagents) in our country. If clinical trial compliance with clinical trial quality management documents and the Clinical Trial of Medical Devices Differences in Quality Management Practices (GCPs) should be specified, and the differences should be explained in detail, and the differences are not enough to prove the authenticity, scientificity, reliability and traceability of the research results and can protect the rights and interests of the subjects. Clinical trial agencies should receive the supervision and inspection of the State Food and Drug Administration.

Data from clinical trials abroad should be truthful, scientific, reliable and traceable. Applicants should provide complete experimental data and may not screen them.

Applicants should ensure that the purpose of the clinical trial abroad is appropriate, the experimental design is scientific and reasonable, the experimental conclusion is clear, the rights and interests of the subject are protected, and the risks of other personnel may be protected.

The clinical trial data submitted by the applicant should at least include: clinical trial plan, ethical opinions and clinical trial report, which should include the analysis and conclusion of the complete clinical trial data.

Based on the clinical evaluation path selected in the applicant's application for registration, the clinical trial data from overseas can be used as clinical trial data, and can also be used as verification data to prove that the difference with the same type of instruments does not adversely affect the safety and efficacy of the product. The latter clinical trial The data generation process includes: data generated from clinical trials carried out abroad for differences from the same variety of instruments; and the applicant's existing overseas clinical trial data can cover the content of the differences required for comparison with the same variety of instruments.

The data from abroad are in accordance with the registration requirements of our country and the data are scientific, complete and sufficient to be accepted.The data from abroad are in accordance with the basic requirements set forth in Article 2 of these Guidelines. However, according to the relevant technical requirements of registration in our country, Complementary clinical trials conducted in China or abroad should be accepted after the supplementary test data and the original overseas experimental data are comprehensively evaluated and meet the technical requirements of registration in China.

Applicants who use multicenter clinical trial data carried out in China and overseas during the same period as the registration declaration data should also clarify the basis for the distribution of the number of cases borne in China so as to further evaluate whether they meet the relevant requirements for registration in our country.

Medical devices listed as "the third category of medical devices requiring clinical trial approval" may also submit overseas clinical trial data according to these guidelines.

Clinical trials conducted abroad may meet the technical review requirements of the countries (or regions) where the tests are conducted but may not be in full compliance with the relevant review and assessment requirements of our country. For example, in clinical trial design, some countries only require clinical trials to obtain the mechanical performance The conclusion of an observation point; However, in our country to declare the registration, the performance of the device may require multiple endpoints to confirm its effectiveness, and the safety of medical devices with appropriate evidence support.If the State Food and Drug Administration The technical guidelines for the release of a specific medical device contain the relevant requirements for its clinical trial. The overseas clinical trial of the device should take into account the relevant requirements. Where there is an inconsistency, sufficient and reasonable grounds and basis shall be provided.

Due to the mechanism of the medical device acting on the human body, the way and time of contact with the human body and the expected clinical effects, the safety effect and the intervention level of some instruments used in different populations are different. Applicants should confirm that the study population Data can be extrapolated to the use of our population.

1. Internal factors: refers to factors based on human genetic characteristics or demographic characteristics, including race, race, age, gender and so on.

2. External factors: refers to the social environment, the natural environment, cultural factors, including eating habits, religious beliefs, the exposed environment, smoking, drinking, disease Incidence, rare or regional comorbidity, obesity, treatment philosophy, socio-economic conditions, education, medical compliance and so on.

Some of these factors can be based on both internal and external factors, such as racial differences.

Overseas clinical trials need to consider the impact of the differences in test conditions between our country and the experimental population on the expected population of our country.The differences in test conditions include: medical environment, medical facilities, researchers' abilities (learning curves), treatment concepts or guidelines Differences, etc. Some factors may have a significant impact on the test results, for example, due to the concept of treatment or different standards, clinical practice may not meet the relevant clinical practice guidelines. In addition, the differences in the level of medical facilities and researchers will produce test data Influence, high operational requirements of equipment, researchers on the use of equipment may have a direct impact on test conclusions.

The above three aspects of the differences arising from the impact of factors in a medical device clinical trial data may exist a single, may also be a number of coexistence, although these factors are known to exist objectively and will have a certain impact on clinical trials, However, the determination of the extent of the impact of various factors should be combined with the characteristics of the device to be declared, the purpose of clinical trials, etc. According to the status quo of medical devices, clinical experience, as well as related diseases and treatment methods of cognitive, most of the medical devices Of the clinical trial data to determine the impact of non-clinical significance, may not require proof of one by one.Is able to determine the impact of certain factors on clinical trial data have a clinically significant effect, or difficult to determine some of the factors on clinical trial data When having a clinically significant impact, applicants should clarify the approaches used to reduce or eliminate the effects of variances, such as designing subgroups of the study population as needed or subgrouping existing clinical trial data analysis.

For clearly defined factors that have clinically significant impact on the test data, applicants may conduct supplementary tests on the basis of different factors in our country. Combined with the original data from overseas clinical trials, the applicants may confirm that the device is under normal use in our country Safe and effective.

It is recommended that applicants fully communicate with the medical device reviewing department before submitting the data of clinical trials in foreign countries so as to facilitate scientific, complete and full consensus on the clinical evaluation of the medical device to be declared.

Examples of products that can be clinically meaningful for the clinical data that can be defined by different factors are as follows:

Example 1: A pulse oximeter device that utilizes pulsatile blood flow to cause a time-dependent change in tissue optical properties through the interaction of optical signals with tissue for noninvasive measurement of SpO2 and pulse rate (PR) , That is, Pluse Rate) .Because the working principle involves the interaction of optical signals and tissue, the problem of skin melanin deposition should be considered, the color difference between the overseas population and the Chinese population should be considered, and corresponding clinical research should be carried out.

Example 2: In vitro diagnostic reagents for gene detection of genetic diseases, if there is a difference in genetic genes of different ethnic groups, the detection genes of overseas products based on the selection of overseas populations may be different from the genetic genes of our population, and the genetic diseases of related diseases in our population should be considered Of the mutation sites, mutation frequency and other influencing factors, the corresponding clinical research.

Example 3: In vitro diagnostic reagents for pathogen detection are different in domestic and foreign genotypes, such as hepatitis B virus genotype distribution in different parts of the world, our common type is B, C, D, the world currently There are 9 genotypes of AI found in the genotypes.Hepatitis B virus genotyping detection reagent should be clinically evaluated to prove its genotype coverage and detection ability.