NMPA (CFDA) issued Guideline for Acceptance of Overseas Clinical Trial Data of Medical Devices on January 11th, 2018. A year later, we revisit this important guideline to remind foreign medical device and IVD manufacturers how it impacts clinical trial data submissions.
This guideline pertains to the acceptance of overseas clinical trial and evaluation data that are submitted by medical device and IVD registration applicants in China. It is expected that Good Clinical Trial Practice (GCP), NMPA Registration Regulations and Clinical Evaluation Report (CER) Guidance will be modified to align with the above guideline.
Highlights from the guideline:
I Three Principles & Acceptance Criteria
To submit qualified overseas clinical data, manufacturers have to meet the three principles:
1) Ethical principle. It includes the gap analysis of ethical standards between China and countries where the overseas clinical trials were conducted.
2) Legal principle. It includes the GCP and regulatory requirements gap analysis between China and countries where the overseas clinical trials were conducted.
3) Scientific principle. It includes the analysis of study design, objectives, endpoints, conclusion, etc. Evaluate if the study is properly designed, if the study objectives are reasonable, and if the study conclusion is clear and scientific.
On the basis of being authentic, scientific, reliable and traceable, overseas medical device clinical trial data submitted by the applicant shall at least include:
1) clinical trial protocol;
2) opinions of the ethics; and
3) the clinical trial report which includes the analysis of the complete clinical trial data and the conclusions
Clinical trial data may be submitted to meet the requirements of clinical trial materials, or as the validation materials, to prove that a similar medical device brings no adverse effects to product safety and efficacy.
Where overseas trial data requires supplemental or partial data, a supplementary clinical trial may be conducted in China or overseas following the relevant technical requirements for Chinese registration. If both the supplemental and overseas trial data meet relevant Chinese technical requirements for comprehensive evaluation, the data shall be accepted.
In the case of multi-center (China and overseas) clinical trial data submission, the applicant shall justify the distribution of the cases undertaken by Chinese institutions to further evaluate whether such data meet relevant requirements for Chinese registration. (For medical devices in the List of Class III Medical Devices Requiring Clinical Trial Review and Approval, the overseas clinical trial data may also be submitted according to the technical guidelines.)
II Considerations for the Acceptance of Overseas Clinical Trial Data & Technical Requirements
Difference in Technical Review Requirements
A clinical trial conducted overseas may meet the technical review requirements in the country (region) of clinical study origin, but not necessarily fully meet the relevant guidelines in China.
For example, in some global territories, the intended performance of a medical device can be determined through a single observation endpoint. However, in China, medical device efficacy can only be verified when device performance achieves multiple observation endpoints. As such, territory-specific requirements shall be considered for the overseas clinical trial data; if there is clinical trial data inconsistency, sufficient and reasonable grounds and basis shall be provided by the manufacturer.
Difference in Subjects
The registration applicant shall confirm that the data of any study population can be extrapolated using Chinese subjects. However, there may be differences in subjects that may influence the clinical trial data, including:
1) Internal factors: the influence factors based on human genetic characteristics or demographic characteristics, such as race, ethnic lines, age and gender.
2) External factors: the influence factors based on social environment, natural environment and culture, such as dietary habit, religious beliefs, incidence of diseases, rare or regional comorbidity, treatment concept, social and economic conditions and educational background.
Difference in Clinical Trial Conditions
1) When conducting an overseas clinical trial, it is necessary to consider the influence on trial data and relevance of the intended target population related to trial condition differences. Noteworthy variances in trial conditions include medical environment, medical facilities, investigator ability, and the diagnosis and treatment concepts, as an example.
2) Device manufacturers with clinical trial factors that can be clearly defined as significantly influential have the option to conduct a supplementary Chinese-run trial addressing these factors. This data can then be used to validate the safety and effectiveness of the device under ‘normal’ Chinese service conditions, and may be submitted in conjunction with overseas clinical study data.
3) Should a manufacturer select the above route, it is highly recommended that the applicant conduct sound communication with the medical device evaluation authority in China prior to the submission of overseas clinical trial data. This process will assist all parties in reaching consensus of the scientific approach, completeness and sufficiency of the clinical evaluation data for the medical device under application.
For English version of Guideline for Acceptance of Overseas Clinical Trial Data of Medical Devices, please email info@ChinaMedDevice.com. We charge nominal fees for the translation.
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About ChinaMed Device, LLC
ChinaMed Device, LLC (www.ChinaMedDevice.com), a Boston headquartered company, provides regulatory and commercialization turnkey solutions for western medical device, IVD, CDx and combination products to enter China. Our NMPA (CFDA) regulatory services include: RA, regulatory strategy, regulatory submissions, clinical evaluation reports (CER), clinical trials, QA, GMP and post-market compliance. Our commercialization services include: market assessment research, reimbursement, partnership strategies, and distribution qualification. We are a NMPA (CFDA) certified legal agent with offices in Boston and Beijing enabling us to service our clients 24/7.