Objective: To study the regulatory requirements and implementation of the change management during the clinical research of drugs in Japan, and compare it with the current construction and implementation status of relevant regulatory regulations in China, in order to provide reference for improving the regulatory system of the change management of sponsors and production sites during the clinical research of drugs in China. Methods: A systematic review and study of regulatory regulations on the change of sponsors and production sites during the clinical research in Japan was conducted. Suggestions were provided based on the current situation of change management during the clinical research in China. Results and Conclusion: In Japan, the clinical trial sponsors and clinical trial drug production sites are allowed to apply for registration and change of clinical trials both domestically and internationally. The regulatory measures in the Japanese regulatory system are of reference value to China, such as "domestic agent system for fulfilling responsibilities and obligations, comprehensive and efficient advisory services, and worldwide regulatory inspections covering the whole process".

Objective: To provide reference through comparative research and analysis of regulations, for improving China's drug clinical trials and change management during clinical trials, especially for the sponsor change or production site change, and their change management during clinical trials. Methods: The regulatory requirements and implementation of European Union(EU) drug clinical trial applications and change management during clinical trials were collected and studied. Suggestions were provided by comparing them with the present regulatory framework and situation of China. Results and Conclusion: In EU, the clinical trial sponsors and clinical trial drug production sites are allowed to apply for registration and change of clinical trials both domestically and internationally. The EU clinical trial regulatory system is relatively mature and complete which are of reference value to China, such as a unified clinical trial application portal website and clinical trial information database, an integrated system of scientific and ethical in parallel review procedures, the qualification and responsibility for the sponsors and their legally designated representatives, and measures of supervision and risk control for production sites of investigational drugs as well as their changes.

Objective: To study the regulatory requirements and implementation of the change management during the clinical research of drugs in the United States, and compare it with the current construction and implementation status of relevant regulatory regulations in China, in order to provide reference for improving the regulatory system of the change management of sponsors and production sites during the clinical research of drugs in China. Methods: A systematic review and study of regulatory regulations on the change of sponsors and production sites during the clinical research in the United States was conducted. Suggestions were provided based on the current situation of change management during the clinical research in China. Results and Conclusion: The regulatory system for drug clinical trials in the United States adopts a combination of approval and inspection, and allows sponsors and production sites to exist in different countries (cross-border) under the premise of controllable risks by strengthening the sponsor responsibility system. In recent years, China's drug review and approval reform has been continuously deepening, and a regulatory system for changes during clinical trials has been initially established. In the future, the relevant requirements for changes during clinical trials in China can be refined in stages to support industrial development.

Objective: To provide reference for improving the regulatory system of drug clinical trials and change management during clinical trials by reviewing the corresponding regulatory requirements in China and investigating the current situation of the industry. Methods: Literature research on the regulatory requirements for clinical trials and their changes in China, as well as survey on the status quo of the industry, were conducted to provide reference suggestions for the subsequent improvement of the regulatory system of drug clinical trials and change management during clinical trials in China. Results and Conclusion: The reform of drug evaluation and approval in China has been continuously improved in recent years, and there are demands for “cross-border” and changes in sponsors and production sites along with the development of the industry. Considering the practical needs of innovative development and current regulations, under controllable risk conditions, China has a certain foundation to support the "cross-border" and "cross-border changes" of sponsors and clinical trial drug production sites.

Objective: To conduct risk assessment and risk control research on different combinations of domestic and overseas sponsors and clinical trial drug production sites during the clinical trial phase of new drugs, and in order to provide reference for further improving the cross-border management of sponsors and production sites during the clinical trial phase in China. Methods: Failure Mode and Effect Analysis and Risk Priority Number were used to identify, analyze, and assess the risks of different combinations of domestic and overseas sponsors and production sites. Results and Conclusion: During the clinical trial phase of new drugs, "the sponsor is in China while the production site is overseas (for global supply)" and "the sponsor is overseas while the production site is in China" are two low-risk cross-border situations, and potential risks can be controlled through appropriate measures. It is recommended to prioritize the registration path for these two cross-border situations.

Objective: To evaluate and analyze the risk changes of cross-border changes in sponsors or production sites, and provide reference for the management of cross-border changes in sponsors and production sites. Methods: Based on the initial risk assessment results of different combination modes of the sponsors and production sites, and the risk re-evaluation results after implementing risk control measures, a comparative analysis was conducted on the changes in the "risk index level" before and after the changes occur between different combination modes. Results and Conclusion: Based on the results of the initial risk evaluation, the risk index levels of two change scenarios were lower after the change than before the change, and based on the results of the risk re-evaluation, the risk index levels of four change scenarios were lower after the change than before the change.

Objective: To propose management strategies for sponsors, production sites, and their changes during the clinical research phase of new drugs in China, to provide reference for adapting to the new situation of drug research and development and improving China's drug regulatory policies. Methods: This study analyzed the current issues in the management of sponsors and production sites in the clinical research phase in China, drew on the management experience of foreign regulatory agencies, conducted comprehensive assessment and judgment based on risk principles, and proposed relevant management countermeasures and suggestions suitable for China's national conditions. Results and Conclusion: With the core of ensuring the safety of subjects and the goal of encouraging innovation and improving the accessibility and availability of public medication, this study proposes specific management suggestions on strengthening the responsibility of sponsors as the main body, strengthening the quality management of clinical trial drug preparation, the pilot situation of moderately relaxing the cross- border and cross-border changes of applicants/sponsors and clinical trial drug production sites.