In the past, China only approved drugs and medical devices that had been tested on participants in China, and foreign applicants could start testing in China only after they had demonstrated the safety of their drugs and medical devices with tests conducted overseas. This meant that Chinese people gained access to innovative new drugs or medical devices years after they had been approved overseas.
The Opinions propose that certain qualified clinical trial data obtained from foreign centres may be used to support drug and medical device applications in China, which provides a promising prospect for drug and medical device manufacturers to avoid duplicating clinical studies in China and to accelerate their approval timelines in China.
Overseas clinical trial data of medical devices
In January 2018, the former CDFA announced the implementation of the Technical Guidelines for the Acceptance of the Overseas Clinical Trial Data of Medical Devices (“Medical Devices Guidelines”). The Medical Devices Guidelines explain the principles, acceptance criteria, technical requirements and considerations for accepting overseas clinical trial data in support of marketing approval for medical devices.
Pursuant to the Medical Devices Guidelines, any overseas clinical trial data must comply with three basic principles as follows:
principle of ethics: the overseas clinical trial must follow the ethics rules stipulated by the Declaration of Helsinki;
principle of legitimacy: the overseas clinical trial must be conducted in accordance with Good Clinical Practices, and the medical device applicant and clinical trial institutions must subject themselves to the competent regulatory authorities’ inspections; and
principle of scientific study: the overseas clinical trial data must be authentic, scientific, reliable and traceable, and the applicant must provide complete trial data without any selection.
Overseas clinical trial data submitted by the applicant shall include at least the ethics committee’s opinions, the clinical trial protocol, and the clinical trial report, which includes the analysis of the complete clinical trial data and the conclusions. If the review agency finds any overseas clinical trial data to be inadequate under the applicable technical requirements, the applicant may need to conduct a supplementary trial, which may be conducted in or outside China following the relevant technical requirements.
In addition, the Medical Devices Guidelines further specify three special considerations to be considered in the technical review process concerning whether, and to what extent, overseas clinical trial data can support the marketing approval of a medical device application, including:
differences in technical review requirements – a clinical trial conducted overseas may meet the technical review standards in the country of origin, but not necessarily all the technical requirements in China;
differences in trial subjects – the applicant shall confirm that the clinical data can be extrapolated using Chinese subjects, but internal and external differences in subjects may influence the results of clinical trials; and
differences in clinical conditions – variations in trial conditions include medical environment, medical facilities, diagnosis and treatment concepts, etc.
Where such differences may have clinical significance, the applicant may conduct a supplementary trial in China to address the relevant differences. Such data can then be used to validate the safety and efficacy of the medical device under ‘normal’ Chinese conditions, and may be submitted in conjunction with overseas clinical study data to support the registration application.
Overseas clinical trial data of drugs
Following the issuance of the Medical Device Guidelines in January, the NMPA issued the Technical Guidelines for the Acceptance of the Overseas Clinical Trial Data of Drugs (“Drugs Guidelines”) on July 10, 2018. The Drugs Guidelines apply to overseas clinical data submitted by applicants for both new drugs and generic drugs. Structured similarly to the Medical Device Guidelines, the Drugs Guidelines set forth the basic principles and requirements on the acceptance of overseas clinical trial data, and specify different levels of acceptance based on the quality of the data itself and different circumstances.
As stipulated under the Drugs Guidelines, overseas clinical data of drugs shall be submitted based on the basic principles of authenticity, completeness, accuracy and traceability. By “completeness”, the Drugs Guidelines emphasise that clinical trial data of the proposed drug shall be provided in full in order to qualify, rather than provided selectively. During the application for drug registration, both the domestic and the overseas clinical trial data shall be submitted in accordance with the Administrative Measures for Drug Registration, and shall be compiled into a complete data package. In specific, such data package shall contain biopharmaceutical, clinical pharmacology, efficacy and safety data.
The Drugs Guidelines categorise the acceptance of overseas clinical trial data into three levels: (1) fully accepted, (2) partially accepted, and (3) not accepted. Specifically, overseas clinical trial data can be “fully accepted” if it is authentic and reliable and complies with ICH GCP standards and the examination requirements for drug registration, and if it is equipped with clinical research data supporting the relevant effectiveness and safety evaluation of target indications, and without any ethnic-sensitive factors that may affect the effectiveness and safety.
Overseas clinical trial data will be “partially accepted” if there are ethnically sensitive factors that may affect the efficacy and safety of the drugs, although they are authentic, reliable, in line with ICH GCP standards and Chinese drug approval standards and equipped with clinical research data supporting the relevant effectiveness and safety evaluation of target indications. If such data is highly questionable in terms of its authenticity, completeness, accuracy and traceability, it will not be accepted.
Regarding registration applications for drugs treating significant illnesses, rare diseases, pediatrics, and for which there is a lack of effective treatment methods, after evaluating the data for clinical trials carried out outside of China and obtaining a "partially accepted" recognition, it is acceptable to use conditional clinical trial data to collect further validity and safety data for post-acceptance evaluation.