Medical device regulations in China are often likened to the European Union (EU)’s MDR, with a vital prerequisite of Clinical Evaluation Reports (CERs), as required by China’s National Medical Products Administration NMPA (formerly CFDA). Although both the aforementioned regulatory frameworks permit the use of equivalent devices as a basis for clinical data for a new device, the ensuing steps to compliance and documentation differ between the EU and China.
Analogous to EU requirements, Clinical data requirements in China are broken down by device classes, with Class II and III devices requiring clinical data and Class I devices requiring only a basic clinical description. In China, the process begins with a review of the New Device Clinical Trial Exemption Catalogues which contain a list of product types that do not require clinical trial data or a CER. For such products, documentation of two comparisons is required:
1) A basic comparison of the product under evaluation with a similar product type listed in the catalog
2) A comparison of the device under evaluation with an equivalent device approved in China.
Equivalent Devices in China
Devices which satisfy equivalence requirements should have a clinically exempt CER, which has similar literature search and reporting requirements as listed in MEDDEV 2.7/1 Rev 4. A Product Technical Requirement (PTR) document must be created to set up required testing for performance and safety (verification and validation) at approved facilities in China.
If there are no differences with equivalent devices, the manufacturer/applicant should collect & analyze clinical literature &/or experience data of the equivalent medical device and generate a CER. Equivalence should be supported by nonclinical studies, and/or clinical literature data, and/or clinical experience data, and/or clinical trial data conducted in China. If differences exist, the applicant should aim to prove that the differences do not affect the safety and effectiveness based on the above. In the event that this is not possible, an analysis or evaluation cannot be conducted based on the clinical application or trials data of the equivalent device. Here the applicant should submit corresponding clinical trial material in line with relevant regulations. In case an equivalent device cannot be identified, a clinical trial is required.
Reviews are conducted on a case-by-case basis for medical devices which need a clinical trial and rely on data generated outside of China. It is estimated that 30% of these devices will require a clinical trial, which must be initiated in the form of a request from the sponsor to the local/provincial NMPA office. Such clinical trials require a clinical research coordinator and the implementation of Helsinki ethical principles.
Key Differences Between EU MDR and Chinese Regulations
Post Market Clinical Follow-up (PMCF): Unlike China where PMCF is not required, the EU requires continuous updates to the clinical evaluation documentation throughout a device’s lifetime in the form of PMCF. However, in China, a design change submission requires an update to the CER. Also, Chinese language literature sources and clinical data from the Chinese population should be provided.
It is mandatory for the equivalent device to be approved in China. A detailed description of the similarities and differences between the two products should be provided including, but not limited to, the qualitative and quantitative data, and verification and validation results.
MDR guidelines state that in order to demonstrate equivalence, clinical, technical and biological characteristics shall be taken into consideration. The only relevant clinical data considered is the data obtained when the equivalent device is a CE-marked medical device, used in accordance with its intended purpose as documented in the IFU.
Evaluation Approach & Strategy:
Unlike the clinical evaluation approach in China which is primarily related to device equivalence, the EU MDR requires the clinical evaluation plan, clinical development plan, and clinical evaluation report to be submitted as part of the technical documentation. Under the MDR, a clinical evaluation requires consideration of currently available alternative treatment options for the same clinical purpose and should be updated throughout the lifecycle of the device.
In China, however, there is no channel to update the CER standalone, as the clinical evaluation needs to be submitted as part of new registration or change registration. Thus, it is recommended that manufacturers/applicants write or update the CER with the submission.
Guiding principles on Literature Search and Screening describe the requirements of the search database, search means, search terms and the logical relationship of search terms, procedures and criteria of literature screening, and the output of literature search and screening results.
Analysis & Evaluation
The NMPA guidelines require that both a device under evaluation and an equivalent device be analyzed using pertinent data. Based on the analytical results of different data sets, the applicant should evaluate whether the device under evaluation could reach the expected performance in normal conditions of use, and whether the risks are acceptable when weighed against the expected benefits.
The goal of the analysis as per EU MDR is to collectively demonstrate compliance with each of the general safety and performance requirements pertaining to the clinical performance and clinical safety of the device, when the device is used according to its intended purpose.
Our Thoughts on China’s Clinical Evaluation Process for Medical Devices
So far, the industry has attempted to use the EU guidance with slight alterations for CER submissions in China. Ostensibly, requirements in the MDR and NMPA guidelines look similar, but CERs for China, written using EU guidance, are frequently rejected by Chinese authorities.
If care is taken to add the necessary additional NMPA requirements, it is possible to convert and submit existing EU CERs for NMPA. In order to achieve this, an in-depth literature search must be conducted to identify clinical studies, complaints and adverse events, and corrective measures associated with clinical risks. A comprehensive evaluation of multiple data sets and other supporting documents relevant to the Chinese population, data of clinical trials conducted in China is required for a successful clinical evaluation.
Thus, a holistic approach to clinical evaluation, which considers the specific requirements outlined above, while learning from international experience, will help ease entry into the Chinese market for aspiring applicants.