FAQ-Clinical Evaluation Report

Question: which of the requirements are obligatory regulation only? or all the standards?
Answer: Order 739 is the regulation, and all technical guidance were authored by CMDE reviewers. So, when you submit documents for review, you need to follow all the technical requirements stated in the technical guidance.
Question: Is there a recommended number of subjects (or % of the Pivotal Study) needed for registration in China? For a class 3 drug device combination product for a rare disease.
Answer: For the pivotal study, it depends on whether you have conducted studies in overseas. If you have already had it, you may need a small bridging study of 20-50 patients to be conducted in China. If you do not have any overseas clinical data and you want to conduct a pivotal study in China to support a submission for class 3 devices, you may need somewhere around 150 or 200 patients.
Question: How often do you expect NMPA to require the periodic required clinical evaluations (e.g. 1x/year, 1x/5 years)?
Answer: As discussed, this is not clarified in the current technical guidance. We believe, however, the updating frequency may be similar to that of EU CERs. This is something we are hypothesizing. Stay tuned for the upcoming final released guidance. It may contain some interpretations or clarifications on this regard.
Question: Do these periodic evaluations need to be submitted to NMPA, similar to a normal regulatory new product or change market submission?
Answer: As of today, we don’t know the answer. But we believe, for periodic updates, this is the process you must follow the new regulation. In our best understanding, you may not need to submit the periodic clinical evaluation report. But in the future, if the agency wants to audit it, you should have these documents already in place. You should have the procedure and documentation in place. But definitely, for the registration of new products or making significant changes to existing products, you need to submit the clinical evaluation report.
Question: What is expected for clinical evaluations during the design phase?
Answer: We believe the clinical evaluation is a process. The output of this process serves as the internal documents for you to decide on whether you need additional clinical evidence, whether you need clinical trial for the clinical evaluation and obligation. So, this is the step where you need to collect all existing evidence and try to identify whether you need any additional information.
Question: clinical data on the device/equivalent/ comparable device and also no state-of-the-art too?
Answer: This question is not very clear. As we mentioned in the presentation, the clinical data can be generated from subject device, equivalent device or comparable device. If you want to use a comparable device as well, you must summarize the clinical data for all devices to compose your CER.
Question: Which is the example of some exemption for the China CER?
Answer: Please refer to the clinical evaluation exemption catalog. From the excel table, you can find the class II or III devices exempted from clinical evaluation.
Question: China vs EU comparison: the chart says Clinical Evaluation Exemption Catalog: Is the Clinical Trial Exemption Catalog meant? Is it the same?
Answer: Under Order 680, clinical trial exemption catalog was used. However, this catalog was converted to clinical evaluation exemption catalog. The content of these two catalogs is essentially the same.
Question: The regulation (annex I) mentions that ‘During the design development phase, clinical evaluation is required to determine the clinical data needed for premarket product evaluation, to determine whether a clinical trial is needed and the clinical endpoints that need to be observed’ Is that not very similar to the EU Clinical Evaluation Plan? How should it be documented?
Answer: They are different from EU CEP. CEP (clinical evaluation plan) is just a planning document which contains the scoping and methodology of clinical evaluation. However, during the design development phase, you have to do the actual clinical evaluation. This is the process you use to determine whether you have sufficient amount of clinical evidence. How should it be documented? This should be documented internally. I don’t think you need to submit this document to the agency.
Question: Are clinical evaluations required for products already approved or is this requirement only for new products?
Answer: I believe the clinical evaluation is required for all products including products that have been approved in China.
Question: When will the new CER guidance come into force?
Answer: Probably in few weeks, according to the previous experiences. Every time the agency collects industry’s feedback and then uses a few weeks to update or clarify guidance, and eventually release the final guidance.
Question: We’ve been told to take a “wait & see” approach with regards to the new NMPA guidelines to bypass full clinical investigations for a new ventilator. Are you also in line with a more “relaxed” stance for CER coming from the latest NMPA guidelines?
Answer: I would encourage you to use the decision-making process flowchart, then you will be super clear where you are. You can make your own decision.
Question: You mentioned effectiveness in some slides, but then focused on Performance and also mentioned patient benefit for CER; could you please clarify what the key requirements are?
Answer: They belong to the same category. The benefit of your device generally refers to the effectiveness data or clinical performance data. And on the other hand, the risk of your device generally is related to the safety side.
Question: Chinese CER did not used to need state of art, you mean now they do? like the EU CER?
Answer: Yes.
Question: Is there a requirement for the clinical evaluation to assess comparable or similar devices even if you do not plan to utilize equivalency as a route to conformity?
Answer: if you plan to use your own clinical study data, you do not need to demonstrate equivalency.
Question: What is exactly meant by intended clinical superiority for state of the art- China CER?
Answer: This refers to the advantage of your product. This should be based on existing evidence. Basically, you claim that your device is better than the competitors’ devices or alternative treatment modalities in some ways.
Question: Just wondering if you have one equivalent and enough data do you need a fully appraised state-of the art report?
Answer: I would say this is one section required to be included in the CER; you don’t need to create a stand-alone report. You still need the state of the art.
Question: Can you explain the strategy of oversea clinical data for medical device registration in China?
Answer: For the overseas clinical data, let us say, if you have done a pivotal study in the US or in other markets, you wanted to use the collected data to seek NMPA approval, you definitely can use these data. However, always keep in mind, one of the key requirements to make this strategy successful to write a report proving that your data collected from overseas can be extrapolated to Chinese patients. This is the key to submit the overseas clinical data.
Question: To go thru the CER simple route and compare with the equivalent device in terms of clinical data, what resources is available to get equivalent devices ’clinical report?
Answer：If you are using for own device as equivalent device, you definitely have the access to the clinical report. If you use competitor’s device, you will need to find their publicly available resources. In the new technical guidance, the requirement of comparing manufacturing processes is gone and this is good news for us.