On January 11, 2018, the China Food and Drug Administration (CFDA) issued “Technical Guidelines for the Acceptance of Overseas Clinical Trial Data of Medical Devices.” These guidelines pertain to the acceptance of overseas clinical trial and evaluation data that are submitted by medical device and In Vitro Diagnostics (IVD) registration applicants in China.
It is expected that Good Clinical Trial Practice (GCP), CFDA Registration Regulations and Clinical Evaluation Report (CER) Guidance will be modified to align with the above technical guidelines following the approval of the China State Council Order No. 680, “Regulations for the Supervision and Administration of Medical Devices,” which is currently under the ‘call for comments’ period. (Read NAMSA’s blog post on the Regulations for the Supervision and Administration of Medical Devices here.)
Highlighted below are the most significant requirements for the CFDA’s recently-released technical guidelines and how they may impact clinical trial data submissions for medical device and IVD registration applicants.
I. Submission of Overseas Clinical Trial Data & Acceptance Criteria
On the basis of being authentic, scientific, reliable and traceable, overseas medical device clinical trial data submitted by the applicant shall at least include:
- clinical trial protocol;
- opinions of the ethics; and
- 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
a. 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.
b. 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:
- Internal factors: the influence factors based on human genetic characteristics or demographic characteristics, such as race, ethnic lines, age and gender.
- 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.
c. Difference in Clinical Trial Conditions
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.
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.
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.
Following are examples where it may be determined that different factors have clinically significant influence on clinical trial data:
|Device||Pulse oximeter device that uses a time-dependent change in the tissue optical properties caused by pulsatile blood flow through the interaction of optical signals with tissue for noninvasive measurement of pulse oxygen saturation (SpO2) and pulse rate (PR).|
|Situation||Because the operating principle involves the interaction between optical signals and tissues, the issue of skin melanin deposition shall be considered. There is a difference in the skin color between the overseas population and the Chinese population, and the corresponding clinical study shall be carried out.|
|Device||An IVD reagent for gene detection of genetic disease.|
|Situation||If there is a difference in genetic genes for various ethnic groups, the detection genes selected for foreign products based on the overseas population may differ from those in general Chinese population. It is then necessary to conduct a corresponding clinical study based on such influence factors as the mutation site, mutation frequency of genetic genes of relevant diseases in the Chinese population.|
How Can NAMSA Help?
The above considerations for Chinese medical device manufacturers are just a few that must be carefully managed when submitting overseas clinical trial data for registration applications in China.
NAMSA invites you to contact us at firstname.lastname@example.org to discuss you medical device development efforts in China, including regulatory impacts that may impact your intended commercialization strategies.