Products that are easier to market by taking the CER path are roughly: imported products converted to domestic ones; similar products that have been on the market for a long time and preferably from the same company; stable production processes with no major changes; and low risk.
The State Food and Drug Administration's release of the draft Technical Guidelines for the Clinical Evaluation of Medical Devices for comment drew widespread attention, opening a new path for new products to be marketed in China.In June 2015, the guidelines came into effect.
Clinical Evaluation or Clinical Trial
Currently, a clearer path has been formed for new medical device products to be marketed in China: Class I devices are filed, and most Class III devices require clinical trials, especially those in the Catalog of Class III Medical Devices Requiring Clinical Trial Approval. For Class II devices and some Class III devices, the two options are clinical evaluation or clinical trials.
Most companies want to choose clinical evaluation over clinical trials. Cost is one of the major reasons. Clinical trials are costly, and the results are unknown, making them a risky investment; a clinical evaluation report (CER) is not cheap, and most of the quotes from clinical contracting organizations (CROs) are around 200,000 to 300,000 yuan, but they are still low compared to the investment in clinical trials. Time-consuming is another important reason. Clinical trials counting the time for pre-preparation and start-up, often a project can be completed in 2-3 years is already a good result. While clinical evaluation reports are usually completed in about 3-4 months, advancing the time to market for new products by at least 1-2 years. Considering the rapid renewal and short life cycle of medical device products, this shortened 1-2 years is valuable to manufacturers.
For these reasons, many companies have high hopes for clinical evaluation, so much so that the price of clinical evaluation reports has risen. However, a careful reading of the "Technical Guidelines for Clinical Evaluation of Medical Devices", combined with an analysis of the current situation of the Center for Device Evaluation (CMDE), it is not difficult to find that the drug regulatory authorities issued the guidelines are not intended to give manufacturers a fast track to the rapid listing of a large number of new products, but rather in order to "differentiate between the different clinical evaluation of the situation, and reasonably set up the corresponding requirements to improve the clinical evaluation of targeted, scientific, and reduce the number of clinical evaluations. The evaluation of the targeted, scientific, reduce the burden of management relative."
Difficulty in marketing through CER
For products with low risk, stable manufacturing process, no major changes in product design, and a large amount of safety and efficacy data already accumulated in the past, it is a waste of resources and time to require manufacturers to conduct another clinical trial to provide data, and CER provides a way to utilize the existing data to complete the assessment of the safety and efficacy of the product. assessment. However, for innovative, risky devices, it is difficult to complete a listing through CER.
Difficulty #1: Difficulty in finding suitable analogs. The ideal comparator product is one that is not too different from the product being applied for and is already on the market in China. Not many products meet this requirement, especially those with technological innovations. In addition, a hidden condition is that the comparison product should preferably be the previous generation product of your own company. This requirement mainly comes from the comparison in terms of production process. If it is not your own company's product, it is difficult to get the information and parameters of production. Currently, CMDE requires proof of the legal source of the data, and in Article 6 of the Notice of the Food and Drug Administration on Relevant Issues Concerning the Implementation of the Registration and Management Measures for Medical Devices and In Vitro Diagnostic Reagents, issued on November 4, 2015, it is emphasized that "where clinical evaluation is carried out in accordance with Article 6 of the Technical Guidelines for the Clinical Evaluation of Medical Devices, such as the use of the same varieties of In the sixth article, it is emphasized that "if the clinical evaluation is carried out in accordance with the sixth principle of the Technical Guidelines for Clinical Evaluation of Medical Devices, and if the same variety of medical devices is used, the applicant should submit the authorization for the use of the same variety of medical device production process, clinical data and other information," which eliminates the possibility of obtaining the other company's information through non-public means.
Difficulty No. 2: Inability to find sufficient clinical literature. For completely innovative products, it is difficult to take the CER route because of the lack of previous literature and data, and CMDE will carefully consider approving innovative products to be marketed through CER due to risk considerations. For completely domestically produced products, there is less foreign data; for imported products, if they are listed without clinical trials in foreign countries in Class II and have not been on the market for long enough, there is also less literature. Therefore, considering the requirements of this article, the CER route is more appropriate for products with a long time on the market (relatively more clinical literature), no major improvements in the production process (no difference or very small difference in comparison), and a very low degree of risk.
Difficulty #3: Inconsistent results in the clinical literature and insufficient strength of evidence. Although a large amount of clinical literature can be found for some products, CER has a requirement for quantitative analysis, which requires the introduction of META analysis. Although there is a large amount of literature, if the final conclusions of this literature are not consistent, it may still not be possible to obtain clinical evidence of sufficient strength. In a certain CER training, someone had asked how many clinical documents are needed for CER, and the speaker's answer was that it ultimately depends on the strength of the evidence, if the documents are very persuasive and the conclusions are consistent, maybe a few documents are enough; on the contrary, if the persuasive power is weak, let's say they are all case reports, the number of cases is only a few cases and the conclusions of the different documents are still inconsistent, it is very likely that hundreds of documents will not be able to provide the adequate evidence for the review.
Difficulty No. 4: The Chinese subset of data is harder to obtain. In the clinical dataset section, there is a requirement for a subset of Chinese data, which is often a hindrance for imported products. On the one hand, in the trials in Europe and the United States, there are not many Chinese/Asian ethnicities involved, and the Caucasian ethnicity is dominant; on the other hand, due to certain considerations, quite a number of trials in Europe and the United States do not explicitly collect ethnicity data, which makes it difficult to extract the Chinese/Asian ethnicity data out of the trial results. If data on Chinese ethnicity cannot be provided in the CER, the CMDE will likely require a small clinical trial to simply prove the point that ethnicity does not make a difference. However even a small trial will cost a lot of time and money. If the outcome of the CER results in a clinical trial rather than marketing approval, then the preceding effort is close to failure.
In addition, if the product is relatively innovative and risky, even if a certain amount of data and clinical literature can be obtained to generate a CER, the CMED is still likely to ask for more data out of concern for the product's safety.
Which products are suitable for CERs
Till now, companies have submitted a number of CERs to the CMDE, including those that have been withdrawn from review, those that have requested additional data, and those that have been approved. Combining the requirements of CER and the feedback from CMDE, the products that are more likely to go through CER are:
1. Imported products are converted to domestic ones;
2. Similar products have been on the market for a long time and preferably from the same company;
3. Stable production process with no major changes;
4. Low risk.
The Technical Guideline for Clinical Evaluation of Medical Devices opens up a new way for medical devices to be marketed in China, saving manufacturers time and cost and avoiding meaningless repetition of existing data, which is a positive step forward for regulators, manufacturers and patients alike. How to further interpret the guiding principles, through the CER pathway as soon as possible to let the device to the market, but also need to be all parties of the *** with efforts.