On January 11, 2018, the CFDA issued a guideline for accepting medical device international clinical trial data. This new guideline could benefit foreign medical device manufacturers by facilitating their clinical trial preparation for CFDA registration. Although the CFDA is becoming more open to international data, there are a list of considerations to keep in mind, such as the differences of GCP, technical review requirements, trial subjects, and clinical trial conditions between China and foreign countries. This article summarizes CFDA’s guideline for accepting international clinical trial data.
The guideline aims to provide guidance to applicants who seek to register their international medical device clinical trial data and to regulatory authorities who evaluate and review clinical trial data; to avoid or reduce redundant clinical trials and accelerate the premarket approval process in China.
I. Scope
The Guidelines are applicable to the registration of a medical device (including IVD), specifically on acceptance of the international clinical trial data submitted by the applicant, as the clinical evaluation data in China.
The international clinical trial data refer to the study data generated for the validation of the safety and effectiveness of the medical device specified for CFDA registration, under the normal service condition by qualified clinical trial institutions in the host country/region where the clinical trial is conducted for the corresponding period.
II. Basic Principles for the Acceptance of International Clinical Trial Data
1. Ethical Principle
International clinical trials shall follow the Declaration of Helsinki for ethical standards.
2. 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.
3. Scientific Principle
The international clinical trial shall be authentic, reliable, and traceable. The applicant shall provide complete trial data, not selective data.
III. Submission of international clinical trial data and acceptance criteria
International clinical trial documents submitted by the applicant shall at least include: clinical trial protocol, ethical opinions, and clinical trial report. The clinical trial report shall include the analysis and conclusions on the complete clinical trial data.
Based on the clinical evaluation pathway selected by the applicant for registration application, the international clinical trial data could be used as clinical trial materials, or as the validation materials to prove that the difference between the submitted device and similar medical devices has no impact on the product’s safety and effectiveness.
Only the scientific, complete and sufficient international trial data that meet relevant CFDA requirements for the registration in China will be accepted. If the international trial data meet the basic requirements specified in Section II of this guideline, but additional items are required according to relevant technical requirements of registration, a supplementary clinical trial may be conducted in China or internationally. If the supplementary trial data and the previous international trial data meet relevant technical requirements under a comprehensive evaluation, the data would be accepted.
For medical devices in the List of Class III Medical Devices Requiring Clinical Trial Approval, the international clinical trial data may also be submitted according to this guideline.
IV. Considerations & technical requirements for the acceptance of international clinical trial data
1. Difference in technical evaluation requirements
A clinical trial conducted internationally may meet the technical review requirements of the country (region) where it has been conducted, but not necessarily fully meet the relevant technical review requirements in China. For example, for the design of a clinical trial, the requirement in some countries is that the clinical trial can reach the conclusion that the performance of a medical device achieves one observation endpoint. Yet, the requirement for a registration application in China is that the effectiveness can only be verified when the performance of a medical device achieves multiple observation endpoints; and there is appropriate evidence supporting the safety of the medical device. 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.
2. Difference in clinical subjects
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.
3. Difference 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, facilities, investigator capabilities (accounting for a learning curve), treatment philosophy and standards.
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.
