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Significant product change

Significant changes of medical device in China, EU, MDSAP countries

Background

The authority of most important countries of medical device has similar regulations guiding manufacturer to handle product changes. The famous one is “Deciding When to Submit a 510(k) for a Change to an Existing Device” at FDA.


Compared to different significant changes of medical device among diverse countries, the common aspects to consider is related to production, material, supplier, intended use, labelling and design specification. If it goes deeper in details, the changes can be extremely country specific different to analyse. The key is to make a risk analysis to see whether there is a new risk deriving from the new change, to analyse the impact on safety and performance requirement, whether clinical – and usability data extra are needed to verify the change.


In term of action after analysing product change, manufacturer can file the change in quality management or notify the authority or make a new change registration.


Comparison of significant change in China, EU, MDSAP countries

It is quite interesting to compare different significant change guidance worldwide. There is normally complex deciding tree, description of each change terms, even examples from best of practise and examples of non-significant change.

In China the binding regulation of product change is at Medical device registration and filing management methods in 2021.


Article 79 The registrant shall take the initiative to conduct post-marketing studies on medical devices to further confirm the safety, effectiveness and quality control of medical devices and strengthen the continuous management of listed medical devices.


Registered Class II and Class III medical device products, their design, raw materials, production processes, scope of application, methods of use and other substantive changes that may affect the safety and effectiveness of the medical device, the registrant shall apply to the original registration department for changes in registration procedures; other changes shall be filed with the original registration department within 30 days of the date of change.


The product name, model, specification, structure and composition, scope of application, technical requirements of the product, the address of the manufacturer of the imported medical device, etc., as set forth in the registration certificate, belong to the matters requiring change of registration as stipulated in the preceding paragraph. The name and residence of the registrant, the name and residence of the agent, etc., belong to the matters required to be filed under the preceding paragraph. Domestic medical device production address change, the registrant shall be for the record after the corresponding change in production license.


If other changes occur, the registrant shall do the relevant work in accordance with the requirements of the quality management system and report to the drug regulatory authority in accordance with the regulations.


Note: so far there is no change notification to NMPA prior to implementation!


"New: There are some changes below which is extra to list in new annual quality management report"

·Change of design, material, critical components, critical production process, quality control

Below we just summarise the main comparison of significant/substantial changes of medical device between China, EU and MDSAP countries. The details of product changes in EU and MDSAP countries must be analysed based on original guidance. 

China EU MDSAP countries
Significant change registration (I): design, raw materials, production processes, scope of application, methods of use and other substantive changes Significant change registration on certificate (II): The product name, model, specification, structure and composition, scope of application, technical requirements of the product, the address of the manufacturer of the imported medical device administrative change registration: The name and residence of the registrant, the name and residence of the agent intended use; Performance specifications; mechanism of operation, operation principle; Shelf life; sterilization method; material; packaging; intended use; warning, contraindication, precaution; Performance specifications; mechanism of operation, operation principle; Shelf life; sterilization method; material; critical supplier; packaging; manufacturing process

How different of Chinese significant change of medical device?


Common product changes

As like change of name and address of manufacturers in Japan and Brazil, in China you need an administrative change which is approved briefly.


As software changes in EU, China has its own guidance “Guidelines for the technical review of medical device software registration” and “Guidelines for technical review of medical device network security registration“ regulating which changes of software triggers a new registration. In general major software updates depending on software naming rule and major cybersecurity update are in scope of significant change registration.


International are the changes of medical device which trigger new registration same as in China:

  • design
  • raw materials
  • production processes
  • scope of application
  • methods of use
  • specification
  • structure and composition
  • technical requirements of the product

 

What is different?


In China the name and residence of the Chinese agent belong to administrative change too. So the process of changing Chinese agent is not a big deal.


Quite special is significant change registration on product certificate (see. Significant change registration on certificate II above in table) in China. In our article we name product certificate so called Chinese ID. If the essential information (Address of production, product name, model, variant, composition and intended use) was changed on certificate and its annex PTR (technical parameter), significant change registration is needed as well.


Please consider all change notification letters issued by NMPA after each change registration.


Besides updating certificate number and revision date of Chinese instruction for use after product approval, manufacturers shouldn’t change any contents for the version of IFU which was submitted at registration dossier to NMPA. Once the content was changed, an brief application at NMPA must be made.


Chinese obligatory standards triggers also change registration before renewal, only if the applicable items in standard apply to your product, however not if

  • the applicable items unchanged in new obligatory standards


What is not binding changes, but need to be paid attention?


Leaning from worldwide changes, manufacturers have to consider following un-binding changes too. By uncertainness consult Chinese authority in time.


Intended use: It will be an issue if you extend or shorten intended use. If it was in scope of defined product code in China, it is fine. Otherwise take a careful change consideration.


Shelf life, sterilization method, packaging; material: We experience strengthened requirements of shelf life - (real time and acceleration), sterilization, packaging testing and documents of raw material at medical device registration in China. It is not unimportant if you shorten shelf life, impair sterility or packaging and change especially material contacting patient. In this case, risk management and assessment of safety and performance requirement always help. 

Outlook


At new regulation “Medical device registration and filing management methods” in 2021, NMPA stipulates that manufacturer should notify all non-significant changes of medical device and IVD within 30 days of the date of change to NMPA. It is more speculation how manufacturers, Chinese agent, NMPA communicate tones of non-significant changes of medical device. However we suggest you to record non-significant changes of medical device and IVD. As above mentioned in annual QM report there are also some QM-changes to report.


For sure is that manufacturer should have own procedure assessing product changes in quality system for their approved medical device and for upcoming or running registration in China. It could be interesting that manufacture should define the role with Chinese agent in contract how to analysis and document of product significant and non-significant changes.


Please make sure that many design changes trigger firstly at least a new equivalent summary assessment or a testing, either outsourced testing, internal tesing or local testing in China.


Manufacturers have to decide whether to notify authority after accessing the product changes or make a change registration or freeze this change in China and bundle all essential changes in next registration of medical device.

On demand workshop of design control Template of design control Change registration
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