Medical devices and In Vitro Diagnostics (IVDs) in China are regulated by the National Medical Products Association (NMPA). All manufacturers of devices and diagnostics must register their products with the NMPA and obtain a Medical Device Registration Certificate (MDRC) before products can legally be placed within the Chinese marketplace.
As in most other major markets of the world, devices in this APAC region are regulated by risk classification: Class I, Class II and Class III. However, it is important to note that the risk classification of a particular device may not correspond directly to an EU or U.S. class, but one commonality is that regulatory oversight increases with each progressive classification level.
Additionally, Class II and III devices, in most cases, require local testing, unless a device meets the NMPA definition of a ‘predicate device,’ already on the market in China. In this instance, a local or overseas clinical study may be required, both of which must meet Chinese Good Clinical Practices (GCP).
With offices in Beijing and Shanghai, and a consulting team of more than 20 Associates, NAMSA can help guide you through the nuances of the Chinese medical device marketplace.
Chinese Regulatory Strategy
Irrespective of device risk classification, foreign manufacturers must demonstrate Home Country Approval (typically via a Certificate of Free Sale) prior to submitting an application to the Chinese NMPA. In addition, device Sponsors can submit an Innovative Device Application without the approval from a manufacturer’s home country. However, the device must satisfy NMPA “innovative” characteristics with the recommendation that overseas companies synchronize access of products, at least in the country of origin and in China.
Class I medical devices in China can be registered in four to six weeks, but the NMPA review timeframe for Class II and III devices may take as long as 12-24 months. Therefore, it is critical to ensure that the best regulatory strategy is adopted to minimize development timelines.
NAMSA’s service offerings in China can assist with the above process by:
- Accurately classifying technology according to NMPA’s classification guidelines outlined in Decree 15
- Assessing whether existing testing data is likely to be accepted by the NMPA; if not, determining what additional testing may be required
- Assessing whether a Clinical Evaluation Report (CER), or an existing overseas clinical study, will suffice or whether a local clinical investigation will be necessary (Note that this is one of, if not the largest, issue faced by foreign manufacturers when beginning the registration process in China)
- Evaluating the registration processes, timelines and overall costs
NAMSA has significant experience with additional regulatory affairs areas in China and can provide additional services such as:
- Product Technical Requirement (PTR) development which would be approved as an appendix of MDRC
- Any tests required to be performed in China test facility
- Change Submission if there is device change after approval
- Extension Submission as the expired date of MDRC is 5 years
- Innovative Device application in China
- Clinical trial approval application in China for specific devices required by NMPA
NMPA Technical File Compilation and Submission
NMPA regulatory submissions must be submitted in a manufacturer’s original language and also in Chinese. The structure of a submission is based on the RPS ToC content issued by NMPA in November of 2021. It’s also important to note that since 2019, the majority of submissions are submitted via the Electronic Regulated Product Submission System (e-RPS), which allows manufacturers to track the status of a submission and exchange feedback with NMPA reviewers throughout the process.
Class II and Class III technical files in China often require the inclusion of clinical data stemming from clinical literature evaluation or clinical investigations conducted either in China or overseas. Any strategic decision regarding the clinical evaluation pathway should be carefully made to minimize the registration timeframe. Clinical evaluations based on MEDDEV 2.7.1 (rev4) and MDR 2017/745 will be rejected by the NMPA on the basis that clinical evaluation regulations in China, while similar to the aforementioned guidance and regulation, differ in some key areas.
Some fundamental differences surround the NMPA requirement of including CERs in Chinese literature sources and selection of NMPA-approved equivalent device(s). These and other differences can be accounted for when working with NAMSA for CER development in China.
All CERs prepared by NAMSA also incorporate clinical evaluation guidance updates, issued by the NMPA in September 2021.
Below are just some of the medical writing services NAMSA offers in the China region:
- Clinical evaluation strategy and feasibility assessment
- Clinical evaluation report (CER)
- Clinical evaluation based on overseas clinical trial
- Literature retrieval, screening, appraisal and evaluation
Clinical Study Management
If a device isn’t on the Chinese clinical trial exempt list, and if there is no clinical data from equivalent devices, it is likely that a clinical investigation in China will be necessary. To help meet these needs, NAMSA provides significant expertise and knowledge within clinical research through the following services:
- Protocol development and study design
- Investigators brochure (IB)
- Inform Consent Form (ICF)
- CRF design
- Site selection and qualification
- Ethical Committee (EC) submissions
- HGRAC applications
- Site management
- On-site monitors
- Remote monitors
- Quality Control (QC) visits
- Database management
- Data review and data cleaning
- Sample size calculations
- Randomization design
- Biostatistics support
- Statistical analysis reports
- Clinical study reports
- Audit support
The NMPA has their own Quality Management System in place: the China GMP. The requirements within are similar to those of ISO 13485:2016 with most manufacturers submitting ISO 13485 certificates as demonstration of compliance.
However, Chinese device regulations change frequently and one such significant change surrounds the guidance issued in March 2020 covering random inspection regimens with regards to manufacturing processes, distribution and management of medical devices marketed in China. These audits, conducted by the NMPA, are comparable to undergoing an MDSAP or U.S. FDA inspection. These types of inspections pose potential risks to any foreign manufacturer if they are not aware of the subtle differences between the NMPA QMS (GMP) requirements as compared to ISO 13485 or 21 CFR Part 820. Any major non-conformities identified by the NMPA during these audits can lead to certificate suspension or cancellation.
NAMSA can assist Sponsors with these requirements and set them up for success in the region through the following services:
- Conducting gap analyses of quality systems, utilizing NMPA requirements as a benchmark
- Conducting mock audits
- Creating and offering training
Pre- and Post-Market Support
In June 2021, the new Regulation for Medical Device Administration and Supervision (State Council Order 739) came into effect. One of the fundamental changes introduced by the new regulation was emphasis on control of the device lifecycle instead of focusing solely on pre-market approval.
Consequently, the NMPA now takes additional measures to monitor the performance of devices after they have obtained regulatory approval, including the requirement for annual risk evaluation reports, AE monitoring and product recalls. As a result, manufacturers must ensure they have appropriate Post-Market Surveillance (PMS) procedures in place. They must also work to confirm that their QMS include procedures for product traceability, recall systems and control of third party subcontractors and distributors.
NAMSA can assist with pre- and post-market processes in China through:
- Updating China QMS to include all appropriate procedures
- Conducting Post-Market Clinical Research
- Auditing subcontractors and distributors