Medical device regulations in China are often similar 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 forgoing regulatory frameworks permit 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, Device classes break down clinical data requirements in China. Class II and III devices requiring clinical data, and Class I devices require only a basic clinical description.
In China, the process begins with reviewing 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 necessary:
A.) basic comparison of the product under evaluation with a similar product type listed in the catalog
B.) comparison of the device under evaluation with an equivalent device approved in China.
Equivalent Devices in China
Devices that satisfy equivalence requirements should have a clinically exempt CER, which has similar literature search and reporting requirements listed in MEDDEV 2.7/1 Rev 4.
Manufacturers must create a Product Technical Requirement (PTR) document. They must set up necessary testing for performance and safety (verification and validation) at approved facilities in China.
Let’s suppose there is no difference with equivalent devices. The manufacturer/applicant should collect & analyze clinical literature &/or experience data of the equivalent medical device and generate a CER.
Nonclinical studies should support equivalence, and/or clinical literature data, and/or clinical experience data, and/or clinical trial data conducted in China. If differences exist, the applicant should prove that the differences do not affect the safety and effectiveness based on the above.
One cannon conduct analysis or evaluation based on the equivalent device’s clinical application or trials data if this is not possible. Here the applicant should submit corresponding clinical trial material in line with relevant regulations. In case we cannot identify an equivalent device, a clinical trial is a must.
Must conduct reviews on a case-by-case basis for medical devices which need a clinical trial and rely on data generated outside of China.
Under research, the estimation of 30% of these devices will require a clinical trial, which the manufacturer must initiate 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’s ethical principles.
Key Differences Between EU MDR and Chinese Regulations
Post Market Clinical Follow-up (PMCF):
Unlike China, where PMCF is not necessary, 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, they should provide Chinese language literature sources and clinical data from the Chinese population.
The equivalent device must be approved in China. One should provide a detailed description of the similarities and differences between the two products. Including, but not limited to, the qualitative and quantitative data and verification and validation results.
MDR guidelines state that to demonstrate equivalence, clinical, technical, and biological characteristics shall be considered. The only relevant clinical data is the data, where the equivalent device is a CE-marked medical device, used following its intended purpose as documented in the IFU.
Evaluation Approach & Strategy:
Unlike the clinical evaluation approach in China, which primarily relates to device equivalence. The EU MDR requires the clinical evaluation plan, clinical development plan, and clinical evaluation report to submit as a part of the technical documentation.
Under the MDR, a clinical evaluation requires considering currently available alternative treatment options for the same clinical purpose and ought to update throughout the device’s lifecycle.
In China, however, there is no channel to update the CER standalone, as the clinical evaluation ought to submit as part of a new registration or change registration. Thus, it is put forward that manufacturers/applicants write or update the CER with the submission.
Guiding principles on Literature Search and Screening describes the search database requirements, search terms, and the logical relationship of search terms, the procedures and criteria of literature screening, and the output of literature search and screening results.
Analysis & Evaluation
The NMPA guidelines require analysis using pertinent data of both a device under evaluation and an equivalent device. Based on the analytical results of different data sets. The applicant should evaluate whether the device under evaluation passes the performance result in normal conditions of use; or 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 about the device’s clinical performance and clinical safety 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 Chinese authorities decide to reject CERs for China, written using EU guidance. Proper Care to add the necessary additional NMPA requirements, converting and submitting existing EU CERs for NMPA is a must. To achieve this, the manufacturer must conduct an in-depth literature search 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 necessary 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.