Comply with NMPA requirements from the beginning
LINAC is the most commonly used machine for giving external radiation therapy. It delivers high-energy x-rays and/or electrons to a particular part of the body. It can be used to treat cancer at any part of the body.
There are different techniques used when giving external radiation therapy. Some of these techniques can also be used together to deliver precise radiation therapy. Besides standard external radiation therapy, there are also 3-dimensional conformal radiation therapy (3D-CRT), Intensity-modulated radiation therapy (IMRT), Volumetric-modulated arc therapy (VMAT), Image-guided radiation therapy (IGRT), Stereotactic radiosurgery (SRS), Stereotactic body radiation therapy (SBRT), etc., these techniques will require Linac integrated with other accessories or components to perform accurate patient positioning and precise dose delivery.
As the LINAC system is one of the most complex medical devices, classified as high risk (Class III medical device) in China, with many standards and requirements for regulatory affairs, an oversight could cause big trouble during NMPA registration.
REGULATIONS & REQUIREMENTS
Unlike the other medical devices, LINAC does not have official registration guidance yet, it must comply with all applicable general requirements. For the general pre-market approval procedure, besides the generic regulations or requirements need to be considered, specifically for LINAC, there are other guidelines or standards that also need to pay special attention to, such as electrical systems verification, SW verification and validation, cybersecurity validation, usability/human factors validation, as well as packaging, transportation, and expected lifetime validation
The Product Technical Requirement (PTR) is needed for type testing and will be submitted to NMPA for technical review. PTR consists of product name, model, category, performance & safety requirements, and their relevant test methods. The key components, specification summary could be also required.
To prepare a proper PTR, a bunch of Chinese standards have to be referenced. Unlike other regions’ regulatory requirements, the manufacturer can follow the harmonized standards or other state-of-the-art standards/specifications, or reasonable rationale to show their product’s safety and effectiveness. The Chinese regulatory requirements on the standards are very strict, the manufacturer has to fully reference all the applicable standards (GB and/or YY), some of which are translated directly from IEC or ISO, and sometimes there might be minor deviations. While there are also standards that are completely the Chinese version. So, medical device manufacturers have to carefully consider these Chinese standards during the design and development stage, if they will sell the product to China.
The type testing will be conducted according to the PTR which refers to all the applicable standards. For example, if the LINAC integrated with X-ray positioning modules, the X-ray device related standards, such as GB 9706.3, GB 9706.14… will be referenced, while if the LINAC is MR guided, the MR standards, such as YY 0319-2008 and YY/T 0482-2010 should be considered.
Due to the complexity of the system, the inspectors may not perform the full test items, but they will put more effort to the GB 15213 tests, manufacturers could use some existing verification data to demonstrate the compliance so that to shorten the type testing process.
The most important thing is the system design that must comply with the Chinese standards, due to that there are some deviations in the standards (for example GB 15213 and IEC 60976 are not equivalent on some topics), or sometimes there is no IEC standard at all for some specific requirements (for example YY/T 0106, YY/T 0888-2013, and so on), the design input must include all these “special requirements”.
The accompanying documents also have to fully comply with the standard requirements, all the technical information has to be provided. If there are specifications that are not applicable to the system, a rationale shall be indicated.
If the manufacturer for the first time produced a LINAC system, or it is their first time register in China, it is recommended to perform a clinical trial in China, or if the system already did the clinical trial outside of China (either it is pre-approval study or post-market follow up study), if the study is compliance to the local GCP (or ISO 14155), and can explain there will be no impact due to the differences of race or healthcare conditions, the overseas clinical trial report may also be accepted.
If the manufacturer already has previously approved LINAC systems on the Chinese market, the new product (or an updated design) can go through a clinical evaluation pathway by comparing it with the equivalent product(s) that approved in China. The clinical evaluation report (CER) has to strictly follow the NMPA guidance on clinical evaluation.
NMPA now accept e-Submission with their eRPS system, which has to be done by the manufacturer’s China Legal Agent (China Representative) with the CA certificate (a USB drive) that can perform the e-Sign process.
The submission has to follow the eRPS documentation structure, with both English and Chinese version documentation, or only the Chinese documentation.
The e-Submission will be roughly checked by the technical reviewer based on their checklist to see if all the documentation and the description are sufficient and correct. A good quality dossier can move forward to the next step for in-depth technical review, during which a deficiency letter can be issued, applicant has to complete all the additional requirements and submit through eRPS system, there is only one chance to submit, before that, a pre-review can be applied to ensure everything can be accepted after final submission.
Once the system is approved, the design change must be very careful, as NMPA regulation requires change submission of information in the certificate is changed, while the PTR is part of the certificate, any significant changes such as components, software updates, or other design changes may trigger a change submission, although these kinds of change will not need submission but documented in the manufacturer’s quality system in other regions. Most importantly, before making the changes, make sure to have the assessment from the China regulatory team.
The certificate has to be renewed before it’s expired (the license is valid for 5 years), the system that applies for renewing submission must be the one has not changed compared to the latest approval, this requirement could cause some troubles for the manufacturer’s strategy due to the planned design change, the regulatory timeline must to properly scheduled for such a complex system.
Please go to Download for more information about the strategy and other resources.