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Following the implement of new Drug Registration Regulation in July 2020, the clinical trial registration system will have some major changes in China.
This article is mainly to introduce the basic information and requirements regarding clinical trial registration in China. Following the implement of new Drug Registration Regulation in July, 2020, the clinical trial registration system will have some major changes, this article will also introduce some key points for clinical trial registration in China.
The Declaration of Helsinki says that every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject.1Currently many global authorities also require that clinical trials conducted in their countries or regions should be registered in their official websites or database, such as the clinicaltrials.gov in United States and EudraCT (EU Clinical Trials Register as the public version) in European Union member states and the European Economic Area.]
In China, the Center for Drug Evaluation (CDE), affiliated to the former China Food and Drug Administration (CFDA), currently the National Medical Products Administration (NMPA, a subordinate agency of the State Administration for Market Regulation) launched a pilot database of Registration and Publicity for Drug Clinical Trials (hereinafter referred to as China Register) for the first time on its official website in November, 2012. China Register was in trial run since then and clinical trials authorized by CFDA since the 1st January, 2012 could be registered in this database.2 The completion guidance and instruction were also available on the website at the same time and updated as required accordingly.
On the 6th September, 2013, CFDA officially released the Notice of the Register for Drug Clinical Trial Information(, No. 28)ï¼stipulating that the holders with clinical trial approvals (also named as applicants) should register and have the clinical trials information public in China Register that are approved by CFDA and to be conducted in China, including bioequivalence(BE), pharmacokinetics (PK), phase I, II, III and IV studies. 3The notice also set deadlines for updating the information for each milestone during clinical trials. In November of the same year, the exclusive website was finally launched.
Since the December 1, 2015, BE studies for chemical products were managed on filing instead of review and approval process. Applicants should get a filing number firstly, then complete the registration of trial information.4 In the light of this policy, the module for BE trials filing was also built and added into China Register together for convenience.
The holders with clinical trial approvals in valid should complete the registration within 3 months since the release of the Notice No. 28. Therefore, the number of registered clinical trials surged quickly since its first launch in 2012 and reached more than 3056 cases (counted based on CTR, the same below) in 2013. In following 3 years, the quantity of annual registered trials remained 800 to 1000 cases. Besides, due to releases of the Opinions on Reforming the Review & Approval System for Drugs and Medical Devices(the State Council  , No. 44) by the State Councilin August 20155and the Opinions on Deepening the Reform of Review & Approval System to Encourage Innovation in Drugs and Medical Devices(General Office , No. 42) by the General Office of Central Committee of the Communist Party of China and the State Councilin October 2017 6, the review and approval process for clinical trial application was optimized and accelerated. Therefore, the annual number of registered trials was more than before in recent years and reached 1685, 2570, and 2756 cases in 2017, 2018 and 2019 separately. Till to the first quarter of 2020, China Register has more than 4200 primary accounts and the total number of registered trials amounts to 13,504 cases. See Figure 1 for the whole picture with the annual data.
Currently, China Register can assort the registration based on drug categories, i.e. chemicals, biologics, Chinese and natural medicinesand the territory where the trials are conducted, i.e. domestic and global trials (or multi-regional clinical trials, MRCTs). Till now, chemicals and domestic trials still dominate the main parts for China Register and there is no significant change according to the statistics since 2012. See the Figure 2 and 3 for the percentage separately in the end of 2019.
According to the Opinions No. 42 mentioned above, NMPA issued the Notice of Optimizing the Review and Approval Processes for Drug Clinical Trial Application(NMPA , No. 50).7The notice states that applicants can conduct clinical trials in China as to the protocols in application packages if they have NOT received any negative comments or queries from the authority within 60 working days since the date of application. Besides, the requirement for clinical trial registration is also highlighted again in this notice.
Revised and adopted by the Twelfth Session of the Standing Committee of the 13th National People's Congress on August 26, 2019, the newly revised Drug Administration Law of the People's Republic of China (hereinafter referred to as DAL) has been enforced since December 1, 2019, marking the second systematically and structurally major revision of the Law since its initial promulgation in 1984. The practical and effective experience of reforms in pharmaceutical industry were transformed into laws.8
In accordance with the new DAL, NMPA is now working in an orderly fashion on the development, formulation and revision of matching regulations, normative documents and technical guidelines. The Drug Registration Regulation (Decree No. 27 of State Administration for Market Regulation, hereinafter referred to as DRR) was released in March, 2020 and shall be in practice as from July 1, 2020.9 The requirement of registration of clinical trial is also involved in this new DRR for the first time, which stipulates that applicants should register protocols and related information on the official database prior to initiating clinical trials. Besides, applicants should persistently update the information and also need to upload the results when clinical trials are completed. The clinical trial information will be disclosed for public after it is reviewed by authority and applicants should be responsible for its authenticity.
As the newly revised DAL has already in practice now and the new DRR will be effective in July 1, 2020, CDE is now drafting the implementation guidance regarding clinical trial registration, which will underline MAH’s obligations and clearly define the scope of trial registration, the nature and standard of trial information review, the deadline for information submission, update and review, etc.
The new DRR further requires that study results also need to be submitted in China Register, which is also the requirement of the Declaration of Helsinki, so the current registry system also need to be upgraded for this and will be optimized for convenient use. Meanwhile, the completion guidance for registration will be updated based on new regulations and new system and will also be available on China Register for downloading.
In order to enhance the supervision of drug safety in the period of clinical trial and gradually improve the life cycle management, the registration information in China Register would be incorporated into the pharmacovigilance system step by step as a whole for drug safety supervision. Therefore, it is also very important for MAHs to ensure the trial information in China Register is authentic and well quality controlled, besides completing and updating the registration in a timely manner.
Zhuxing Yao, Clerk, Office of Clinical Trial Management, CDE, NMPA. E-mail: firstname.lastname@example.org Haixue Wang, Director, Office of Clinical Trial Management, CDE, NMPA. E-mail: email@example.com
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