To strengthen the administration of registration of medical devices and products, further enhance the quality of registration review, and encourage the research and development of medical devices used in the prevention and treatment of rare diseases, the National Medical Products Administration (the “NMPA”) prescribed and promulgated the Guidelines for the Registration Review of Medical Devices Used in the Prevention and Treatment of Rare Diseases (the “Guidelines”) on October 12, 2018. The Guidelines mainly include provisions concerning the scope of application, communications, clinical trials, market approval, etc., as detailed below.
1. Scope of application
Pursuant to the Guidelines, the Guidelines are only applicable to the application for registering medical devices (including in vitro diagnostic reagents) used in the prevention and treatment of rare diseases, and any changes to relevant approved matters. The rare diseases referred to in the Guidelines are diseases contained in the Catalogue of Rare Diseases jointly released by the National Health and Wellness Committee, the Ministry of Science and Technology, the Ministry of Industry and Information Technology, the NMPA, and the State Administration of Traditional Chinese Medicine.
2. Communications and exchanges
An applicant may apply for a communications exchange with the relevant product technical review department for confirming the applicability of the Guidelines and the clinical evaluation path to be adopted before filing the registration application. If necessary, an applicant may apply for further communications sessions with the technical review department regarding major technical issues, major safety issues and clinical trial programs.
Meanwhile, the Guidelines point out that there needs to be corresponding records to communications between an applicant and the technical review department, with the contents of such communications confirmed by the parties in writing. When filing registration application materials, an applicant shall provide in the registration materials the records of the preliminary communications for the product and explain the status of the work in resolving the relevant issues as filed.
3. Clinical trials
With respect to issues in clinical trials, the Guidelines primarily put forward basic principles for pre-clinical studies, clinical trial exemptions, and clinical trials per se.
As far as pre-clinical studies are concerned, the Guidelines require an applicant to fully explain the functional mechanisms of the declared product, clarify the potential risks, and conduct a thorough pre-clinical evaluation. The pre-clinical study of the product should be able to confirm that the product risks are with an acceptable range. Meanwhile, the Guidelines also pointed out that an applicant should provide a thorough set of comparative research data between the declared product and the existing diagnostic and therapeutic methods (if any) as well as with similar products (if any) in the market, and clearly state the advantages of the declared product and the benefits to the patients.
For clinical trials exemptions, for medical devices used to treat rare diseases if sufficient pre-clinical studies have been conducted, or if there is other evidence showing that benefits to the patients are significantly greater than the risks, the device may be exempted from clinical trials pursuant the opinions of the technical review department on condition that there have been communications with the technical review department. Meanwhile, for overseas medical devices which have been marketed and used in the prevention and treatment of rare diseases, if the overseas clinical trial data can meet the Technical Guidelines for Accepting Overseas Clinical Trial Data for Medical Devices, such data may be used as the clinical trial data at the time of registration. If the review department believes, in the course of technical review, that it is not necessary to supplement domestic clinical trials before the products are launched in the market, the device may be exempt from clinical trials.
For clinical trials itself, the Guidelines hold that for medical devices used in the prevention and treatment of rare diseases, if preclinical studies cannot prove that the benefits of the clinical application of the product to patients are significantly greater than the risks, clinical trials must be conducted. In clinical trials, the safety and efficacy evaluation requirements shall be established according to the product characteristics. In addition, attention should also be paid to the patients’ level of acceptance of the medical device used in the trials, the potential harm to the patients and the usage variations between different medical institutions.
4. Approval for Market Launch
Regarding the approval for market launch, the Guidelines indicate that a conditional approval for market launch may be issued for medical devices based on its benefits and risks assessment, its expected clinical applications, preclinical studies, as well as in consideration of the following circumstances: (1) limitation on the scope of medical institutions that can legally use the product; (2) identification of the key points of focus in the benefits/risks assessment during the clinical application process; (3) studies required after the launch of the product on the market, e.g., follow-up study of clinical trials cases and clinical use after product launch; and (4) time limit on post-market product evaluation. In the meantime, the registrant shall work according to the contents of the registration certificate and report the assessment results to the relevant registration administration department. The registration administration department shall reduce or cancel the conditions imposed on the product at the time of registration based on the product studies before and after its launch.
Other than the above, the Guidelines also provide detailed regulations on the background materials for preclinical studies, the clinical trial institutions, the clinical trial requirements, the clinical trial cases, and the importation of clinical trial data, thereby giving clearer guidance for the registration review of medical devices used to treat rare diseases. Enterprises involved in the manufacture or sale of medical devices for rare diseases may keep an eye on the Guidelines.