On January 11, 2018, the China Food and Drug Administration released the “Technical Guidelines for Accepting Data on Overseas Clinical Trials of Medical Devices”.
These guidelines aim to provide technical guidance for applicants to declare the registration of overseas clinical trial data of medical devices and to supervise the review of such clinical trial data, so as to avoid or reduce repetitive clinical trials and speed up the launching of medical devices in China.
SCOPE OF APPLICATION
This guideline is applicable to the guidance of the process of accepting applicants to use clinical data from overseas as clinical evaluation materials when a medical device (including in vitro diagnostic reagents) is in the process of applying for registration in China. Medical devices listed as “Class Ⅲ of Medical Devices Requiring Clinical Trial Approval” may also submit overseas clinical trial data according to these guidelines.
The guidelines are drafted by the Center for Medical Device Evaluation of the China Food and Drug Administration.
All registered applicants of medical devices (including in vitro diagnostic reagents) to have clinical trials conducted wholly or concurrently abroad.
These guidelines are divided into four parts, which are the scope, the basic principles of accepting data from overseas clinical trials, the submission and acceptance of data from overseas clinical trials, and the considerations and technical requirements when accepting data from overseas clinical trials.
Overseas clinical trials should follow the principles of ethics, law, and science. Applicants who submit clinical trial information should at least include: clinical trial program, ethical advice, and clinical trial reports. The clinical trial report should include an analysis of the complete clinical trial data and conclusions.
If the data of overseas clinical trials complies with the relevant requirements of China registration, and are scientific, complete and sufficient, then they shall be accepted. If the overseas trial data are in line with the basic requirements of Article 2 of these guidelines, but supplementary data are required according to the relevant technical requirements of registration in China, supplementary clinical trials may be carried out in or outside of China. If the supplementary trial data and the original overseas trial data are in line with the relevant technical requirements of registration in China, they shall be accepted.
Applicants who use clinical trial data from multiple centers both in China and overseas during the same period as the registration 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 China.
Ethical Principle: International clinical trials shall follow the Declaration of Helsinki for ethical standards.
Legal Principle: International clinical trials shall meet the Chinese clinical trial regulatory requirements. If differences exist between the GCP used in the international clinical trials and China GCP, it shall be specified and explained that the differences will not affect the research outcome’s authenticity, reliability, and traceability.
Scientific Principle: The international clinical trial shall be authentic, reliable, and traceable. The applicant shall provide complete trial data, not selective data.
CFDA requires foreign clinical trial dossiers to at least contain:
- Clinical trial protocol
- Ethical opinions
- Clinical trial report (shall include the analysis and conclusions on the complete clinical trial data)
Applicants for registration application could make use of the international clinical trial data as clinical trial material, or as the validation material to justify that the difference between the submitted device and similar medical devices has no impact on the product’s safety and effectiveness.
CFDA will only accept registration of applications with complete and sufficient international trial data that meet relevant CFDA requirements. In the event that the international trial data meet basic requirements specified in Section II of the CFDA guideline but require additional items based on relevant technical requirements of registration, supplementary clinical trials may be conducted in China or internationally. Application will be accepted if the supplementary trial data and the previous international trial data meet relevant technical requirements under a comprehensive evaluation.
Variations in Technical and Clinical Information
Technical Requirements: If the technical review guideline of a specific medical device issued by the CFDA specified relevant requirements for the clinical trial of the medical device, such requirements shall be considered for the international clinical trial. In the event of any inconsistency, sufficient and reasonable grounds and basis shall be provided.
Variations in Clinical subject population: The applicant shall confirm that the data obtained from the international subjects are applicable to the Chinese population. Subject factors that may impact the clinical trial data include:
– Internal factors: refers to the factors based on human genetic characteristics or demographic characteristics, including race, ethnicity, age, gender, etc.
– External factors: refers to the factors that affect the social environment, natural environment, and culture, including life habits, incidence of disease, rare or regional comorbidity, obesity, treatment philosophy, socioeconomic situation, education level, medical compliance, etc.
Variations in Clinical Trial Conditions: The applicant shall consider the impact of clinical trial conditions on clinical data. Differences in clinical trial conditions include:
– medical environment
– investigator capabilities (accounting for a learning curve)
– treatment philosophy
The applicant shall evaluate the practical impact of the above-mentioned differences in clinical trials. When it is affirmed that some factors have practical impact on the result of clinical trials, the applicant shall explain the methods to be adopted to eliminate the impact. It is recommended that the applicant shall, before submitting international clinical trial data, have thorough communications with the Center of Medical Device Evaluation to reach an agreement on the completeness and sufficiency of the applicant’s clinical trial materials.