During the whole process of medical device lifecycle, the standards will be updated periodically. For example, GB 9706.1-2020 Medical electrical equipment—Part 1: General requirements for basic safety and essential performance (IEC 60601-1: 2012, MOD) was published in April, 2020, but will take effect since May 1, 2023.
How to handle such standard update during the registration? BradyKnows has helped overseas manufacturers conduct the test under new standard for new registration and certificate modification.
Below is the case study for different scenarios.
Scenario 1: Standard (e.g., GB 9706.1-2020) update during registration or modification
If the standard has been released, but not effective, as per recommendations from NMPA, the manufacturers submit the test report as per new standard. For more cautious practice, our clients are doing the two tests as per the old and new standard. The purpose for this practice is to avoid the test failure based on new standard. If fails in new standard, we can submit the test report based on old standard.
Scenario 2: Standard (e.g., GB 9706.1-2020) update during renewal
It is not very clearly how to handle standard update during renewal as per regulations. As per BradyKnows experiences, if the manufacturer has done substantial changes on product in order to comply the mandatory standard update, such as replacing critical components (Type A components), such changes are the scenario requiring certificate modification. Then, the manufacturer should apply the certificate modification first, followed by renewal. Some of our clients has experiences such scenarios that NMPA did not accept the renewal, so they should do modification first. If the mandatary standard updates will not make any substantial change on product, as per standard comparison and justification or new test, the product is in compliance with new mandatory standard, then during the renewal, a scenario statement and proof documents (such as standard justification or new test report) can be provided, rather than additional certificate modification first.
On March 31, 2022, NMPA officially released China new GCP (Medical Device Clinical Trial Quality Management Provisions, i.e., Medical Device Good Clinical Practice). The new GCP will take effective since May 1, 2022.
Key points in China new GCP are listed as below:
- Reorganize the framework of GCP
- Clarify the responsibilities of each party involved in clinical trial
- Sponsor is a major role in clinical trial, including risk management into clinical trial
- Enhance the requirement of clinical trial site
- Enhance the responsibility of investigators
- Clarify the responsibilities of each party involved in clinical trial
- IVD clinical trial regulated by GCP similar as medical device
- Adjust the safety information reporting process (SAE reporting)
- Simplify and optimize some requirement
- Delete the requirement of Medical device clinical trial shall be conducted in two and above clinical trial institutions, solving the issue of some medical devices difficult and not necessary to conduct clinical trial in two sites.
- Delete the requirement on test report with 1-year validity (one important dossier for IRB/EC application), beneficial to clinical trial.
- Reflect the requirement of latest international regulatory system (IMDRF MDCE WG/N57 FINAL:2019)
- Introducing the concept of conducting multi-region clinical trial in different countries or regions
- Beneficial to global innovative device conducting medical device clinical trial in China in parallel
On March 22, 2022, NMPA published the updated version of China GMP (Good Manufacturing Practice) and GSP (Good Supply Practice). The new GMP and GSP will take effective since May 1st, 2022. BradyKnows QA team made assessment and summarized key updates in new version of China GMP compared with old version as below:
1.Fully implement the medical device registrant filing entity system, and strictly implement the main responsibility of the enterprise. The following impacts are mainly aimed at enterprises that entrust production.
- Allow the entrusted production enterprise to apply for the production license with the registration certificate of the registrant.
- Abolish the restriction of entrusted production filing and the restriction that only one enterprise can be entrusted to produce the same product at the same period.
- Clarify the responsibilities and obligations of both the registrant and the entrusted manufacturer, stipulate that the registrant is responsible for the quality and safety of medical devices, and the entrusted manufacturer is responsible for the production behavior. The registrant is responsible for listing release.
- Clarify the registrant’s inspection responsibilities, inspection methods, results handling, investigation and evidence collection and other regulatory requirements in the case of cross-provincial entrusted production.
2.Simplify relevant application materials and procedural requirements. The following impacts are mainly aimed at production enterprises.
- Abolish the “copy of business license” required to apply for a medical device production license and apply for Class I medical device production filing.
- The review time limit for medical device production license applications has been adjusted from 30 working days to 20 working days.
- If the medical device filing entity produces the Class I medical device by itself, it can go through the production filing together with the product filing.
3.Enrich and improve supervision means, improve operability, and solve practical problems in supervision.
- Establish a medical device reporting system. Four forms of reporting, annual report, production product variety report, production condition change report and re-production report are stipulated; as perspective of self-inspection report system, for import medical device registrants and filing entities, their legal agent shall submit self-inspection report to local NMPA at the location of legal agent before March 31 of the following year.
- Diversify inspection methods: supervision inspection, key inspection, follow-up inspection, causal inspection and special inspection and other forms of supervision and inspection.
- Refine and clarify information disclosure and responsibility interview system: If medical device registrants, filing entities and entrusted manufacturers fail to take effective measures to eliminate the existing medical device quality and safety risks, the drug regulatory department may conduct a responsibility interview on the registrant, filing party, the legal representative of the entrusted production enterprise.
- Strengthen the informatization construction of medical device production supervision.
4.Strengthen risk management and increase penalties for illegal acts.
On April 22, 2022, NMPA published a Communication Procedure for Medical Device Real World Data Application Projects in Hainan Boao Lecheng Medical Tourism Pilot Zone. As per this Procedure, NMPA will enhance the guide on medical device pilot program in Hainan to help apply RWD for China registration.
Hainan Medical Tourism Pilot Zone
Urgent Use Policy & RWD
- The foreign-approved medical devices, IVDs and drugs for urgent Chinese clinical needs, without predicates approved in China, can be imported to Hainan via the policy dated back to April 2018.
- The real-world data generated in the Hainan pilot zone can support the registration with NMPA.
What Products are Qualified ?
- NMPA unapproved products
- No predicates or better than predicates in China
- Clinically significant
- Expanded scope of overseas imported medical devices allowed to enter the Pilot Zone; Imported and inventoried products in Hainan are considered duty-free.
- Greater access to urgently needed medical devices entering Hainan via the emergency review pathways, and devices can be stored in bonded warehouses in Pilot Zones before approval is obtained; and
- More leeway given to enterprises to collect and apply real-world clinical data for medical devices, to expedite approval processes and shorten time of marketing.
- The urgent use approved products by Hainan can be promoted outside of Hainan throughout China. Patients can come from anywhere in China. However, treatments need to be done in Hainan, but follow-up can be done outside of Hainan.
- Generating revenue immediately while collecting Real-World data (RWD). Products can be sold directly to hospitals from overseas manufacturers.
Hainan Pilot Zone Benefits: Commercial & Regulatory
- NMPA un-approved devices but with major country-of-origin approval can be used and sold in real clinical setting
- No local type testing required before commercial use
- Save money and time for national NMPA regulatory approval
- Revenue generating clinical data can be used as real-world evidence (RWE) to support China NMPA regulatory approval
- Duty free with local warehouse
- Overseas clinicians can practice and perform surgeries
Real World Data Application
- providing clinical evidence for the CER based on equivalence route;
- supporting device registration, alongside existing clinical evidence;
- supporting product registration by using the real-world data generated after special approval of clinically urgently needed foreign medical devices;
- as the external control for a single arm study;
- providing clinical data for the establishment of the objective performance criteria for a single arm study;
- supporting an amendment to existing medical device registration in terms of scope of application, intended use, and contraindications;
- supporting an amendment to the clinical values claimed in IFU;
- supporting post-market studies on products with a conditional approval;
- for use in the evaluation of long-term safety and effectiveness of high-risk implants;
- for use in the clinical evaluation of medical devices for treatment of rare diseases throughout the full life cycle to expedite the product registration; and
- post-market surveillance.
NOTE: Currently, real world data cannot be used as sole clinical evidence; however, it can be used to support product registration as a supplement to existing evidence.
- Guidelines For Stability Studies Of Non-active Implantable Medical Devices (March 16, 2022 Revision)
- Medical Device Software Registration Review Guideline（March 9, 2022)
- Medical Device Clinical Trial Institution Conditions And Record Management Measures (March 9, 2022)
- Notice Of NMPA On Expanding The Pilot Work Of The Medical Device Registrant System
- Notice of Shanghai Drug Administration, Jiangsu Provincial Drug Administration, Zhejiang Provincial Drug Administration, Anhui Provincial Drug Administration on Issuing the “Measures for Cross-regional Supervision of the Medical Device Registrant Systemin the Yangtze River Delta Region (Trial)” (March 10, 2020)
- Medical Device Cybersecurity Registration Review Guidelines (Revised 2022)