Which medical device products are eligible for market approval through clinical evaluation?

2020-09-01

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Pharmaceutical News, November 26: The National Medical Products Administration has released a draft of the “Technical Guidance Principles for Clinical Evaluation of Medical Devices,” which has attracted widespread attention and opened a new pathway for bringing new products to market in China. The guidance officially came into effect in June 2015. Clinical Evaluation or Clinical Trials? Currently, the process for launching new medical devices in China is fairly well-defined: Class I devices require only filing, while most Class III devices mandate clinical trials—particularly those listed in the “Catalogue of Class III Medical Devices Requiring Clinical Trial Approval.” For Class II devices, as well as certain Class III devices, manufacturers face a choice between clinical evaluation and clinical trials. Most companies prefer clinical evaluation over clinical trials. Cost is a major factor: clinical trials are extremely expensive, with uncertain outcomes, making them a high-risk investment. While a clinical evaluation report (CER) is not inexpensive—typically priced around RMB 200,000–300,000 by contract research organizations (CROs)—it remains far less costly than conducting full-scale clinical trials. Another significant advantage is time savings. Including preparatory and initiation phases, completing a clinical trial often takes two to three years—a lengthy timeline. In contrast, a CER can usually be finalized within three to four months, shortening the time-to-market by at least one to two years. Given the rapid pace of innovation and short product lifecycles in the medical device industry, this reduction in time is highly valuable for manufacturers. For these reasons, many companies place great hopes on clinical evaluation, driving up pricing for such services. However, a careful reading of the “Technical Guidance Principles for Clinical Evaluation of Medical Devices,” combined with an analysis of the current situation at the Center for Medical Device Evaluation (CMDE), reveals that the regulatory authorities did not issue these guidelines primarily to create a fast-track route for mass-market entry of new products. Instead, the aim is “to differentiate among various clinical evaluation scenarios, appropriately set corresponding requirements, enhance the relevance and scientific rigor of clinical evaluations, and reduce the administrative burden on stakeholders.” Challenges in Using CERs for Market Entry For low-risk devices with stable manufacturing processes, minimal design changes, and substantial prior safety and efficacy data, requiring manufacturers to conduct another clinical trial is both wasteful of resources and time. A CER offers an alternative approach, leveraging existing data to assess product safety and effectiveness. Nevertheless, for innovative or higher-risk devices, achieving market approval via CER remains challenging. First, finding suitable comparator products is difficult. Ideally, the comparison should involve a product similar to the one under review that has already been approved domestically. Such options are rare, especially for devices featuring technological innovations. Additionally, there’s an implicit requirement: the comparator should ideally be the manufacturer’s own previous-generation product. This preference stems largely from production‑process comparisons; without access to proprietary manufacturing information, obtaining relevant technical details becomes nearly impossible. Currently, the CMDE mandates proof of legitimate data sources. In Article 6 of the “Notice of the State Food and Drug Administration on Issues Related to the Implementation of the Regulations on Registration Management of Medical Devices and In Vitro Diagnostic Reagents” issued on November 4, 2015, it is emphasized that “when conducting clinical evaluations pursuant to Article 6 of the Technical Guidance Principles for Clinical Evaluation of Medical Devices, if the applicant uses production processes, clinical data, or other materials from the same type of medical device, they must submit authorization documents confirming the use of such materials.” This measure effectively prevents unauthorized acquisition of third-party data. Second, securing sufficient clinical literature poses another challenge. For truly innovative products, the CER route is particularly difficult due to the lack of prior studies and data. Out of caution, the CMDE may hesitate to approve innovative products through CER. Domestically produced devices typically have limited international data, while imported products that entered the market without clinical trials abroad—and whose overseas presence is relatively brief—often lack robust clinical evidence. Therefore, products that meet the following criteria are more likely to succeed via CER: long market history (providing ample clinical literature), stable manufacturing processes (with little or no significant change compared to previous versions), and low risk levels. Third, inconsistencies in clinical study results and insufficient evidence strength further complicate matters. Even when abundant clinical literature exists, quantitative analyses required by the CER necessitate meta-analysis. If the conclusions drawn from these studies remain divergent, adequate clinical evidence may still elude researchers. During a recent CER training session, someone asked how many clinical papers would be needed. The instructor replied that the final decision hinges on the strength of the evidence: if the studies are highly persuasive and reach consistent conclusions, just a few papers might suffice; conversely, if the evidence is weak—such as case reports involving only a handful of cases with conflicting findings—even hundreds of papers may fail to provide the necessary support for regulatory approval. Fourth, obtaining reliable Chinese-subgroup data presents additional hurdles. The CER requires inclusion of Chinese-specific data subsets, which can be particularly problematic for imported products. On one hand, clinical trials conducted in Europe and the U.S. often include very few Chinese or Asian participants, with Caucasian subjects predominating. On the other hand, some studies deliberately avoid collecting detailed ethnic data, making it difficult to extract Chinese or Asian subpopulation information from the results. Without such data, the CMDE may demand a small-scale clinical trial solely to confirm the absence of ethnic disparities. Yet even a modest trial entails considerable time and expense. If the outcome of the CER ultimately leads to a clinical trial rather than market approval, all prior efforts could prove futile. Moreover, for highly innovative products carrying certain risks, even after assembling sufficient data and clinical literature to prepare a CER, the CMDE may still request additional evidence to ensure product safety. Which Products Are Suitable for CER? To date, numerous companies have submitted CERs to the CMDE. Some have been rejected, others requested supplementary data, while a few have received approval. Based on the requirements outlined in the guidance and feedback from the CMDE, products best suited for the CER pathway generally exhibit the following characteristics: 1. Imported products transitioning to domestic production; 2. Long-standing market presence, preferably from the same manufacturer; 3. Stable manufacturing processes with no major modifications; 4. Low risk profile. The “Technical Guidance Principles for Clinical Evaluation of Medical Devices” have indeed opened a new avenue for medical device registration in China, saving manufacturers time and costs while avoiding redundant duplication of existing data. This represents a positive step forward for regulators, manufacturers, and patients alike. Further interpretation of these guidelines and concerted efforts across all stakeholders will be essential to accelerate the market introduction of medical devices through the CER pathway.

On November 26, according to the Pharmaceutical Network, the National Medical Products Administration released a draft of the “Technical Guidance Principles for Clinical Evaluation of Medical Devices,” which has attracted widespread attention and paved a new pathway for the market launch of new products in China. The guidance officially came into effect in June 2015.

　　Clinical evaluation or clinical trial

　　At present, a relatively clear pathway has emerged for the market approval of new medical devices in China: Class I devices are subject to filing, while most Class III devices require clinical trials, particularly those listed in the “Catalogue of Class III Medical Devices Requiring Clinical Trial Approval.” For Class II devices, as well as certain Class III devices, manufacturers must choose between conducting a clinical evaluation or performing a clinical trial.

　　The vast majority of companies prefer to opt for a clinical evaluation rather than a clinical trial. Cost is a key factor: clinical trials are extremely expensive, their outcomes remain uncertain, and they represent a high‑risk investment. While a clinical evaluation report (CER) is not inexpensive—current quotes from clinical research organizations (CROs) typically range from RMB 200,000 to 300,000—it is still far lower than the costs associated with a full‑scale clinical trial. Another significant consideration is the time required: factoring in preliminary preparation and initiation, completing a clinical trial within two to three years is already considered a commendable achievement. By contrast, a clinical evaluation report can usually be finalized in about three to four months, shortening the time to market by at least one to two years. Given the rapid pace of innovation and the relatively short lifecycles of medical devices, this one‑to‑two‑year advantage is highly valuable for manufacturers.

　　For the reasons outlined above, many companies place great expectations on clinical evaluation, driving up the costs of clinical evaluation reports. However, a careful reading of the “Technical Guidance for Clinical Evaluation of Medical Devices,” combined with an analysis of the current situation at the Center for Medical Device Evaluation (CMDE), reveals that the regulatory authorities did not issue this guidance to create a fast-track pathway enabling manufacturers to bring large numbers of new products to market quickly. Rather, the aim is “to differentiate among various clinical evaluation scenarios, establish appropriate requirements accordingly, enhance the relevance and scientific rigor of clinical evaluations, and reduce the administrative burden on regulated entities.”

　　Listing via CER is challenging.

　　For products that carry low risk, have stable manufacturing processes, involve no major changes to their design, and for which substantial safety and efficacy data have already been accumulated, requiring manufacturers to conduct another clinical trial to generate new data represents a waste of resources and time. The Comparative Effectiveness Review (CER) offers a pathway to leverage existing data to assess product safety and efficacy. However, for innovative devices that entail higher risks, relying on CER to secure market approval remains challenging.

　　One difficulty is finding a suitable comparator product. Ideally, the comparator should be a product that is not substantially different from the applicant’s device and is already on the Chinese market. Such products are relatively scarce, especially for devices with technological innovations. There is also an implicit preference that the comparator be the applicant’s own previous‑generation product, mainly because comparisons of manufacturing processes are required: if the comparator is not the applicant’s product, it is very difficult to obtain production‑related information and parameters. Currently, the CMDE (Center for Medical Device Evaluation) requires proof of the lawful origin of supporting data. In its November 4, 2015 Notice on Issues Related to the Implementation of the Measures for the Registration Administration of Medical Devices and In Vitro Diagnostic Reagents, the China Food and Drug Administration stated: “When conducting clinical evaluation in accordance with Article 6 of the Technical Guidance Principles for Clinical Evaluation of Medical Devices, if the applicant uses production processes, clinical data, or other materials of the same type of medical device, the applicant shall submit an authorization letter permitting the use of such production processes, clinical data, and related materials.” This provision effectively rules out obtaining another company’s proprietary information through non‑public channels.

　　Challenge No. 2: Insufficient clinical literature can be found. For entirely novel products, it is difficult to pursue the CER pathway, as there is a lack of prior literature and data. Out of risk‑based considerations, the CMDE will also exercise caution when approving innovative products for market entry via CER. Fully domestically developed products typically have limited international data; for imported products that were marketed abroad as Class II devices without conducting clinical trials, or whose post‑market experience is still too brief, relevant literature is likewise scarce. Therefore, to meet this criterion, products that have been on the market for an extended period (and thus possess relatively abundant clinical evidence), whose manufacturing processes have not undergone substantial modifications (showing no meaningful differences compared with earlier versions), and which carry low risk levels are best suited to the CER pathway.

　　Challenge No. 3: Inconsistent findings across clinical literature and insufficient evidence strength. Although some products may be supported by a large body of clinical studies, CER assessments require quantitative analysis, necessitating the use of meta‑analysis. Even when the number of studies is substantial, if their conclusions are not consistent, it may still be impossible to establish clinically robust evidence. During one CER training session, someone asked how many clinical studies would be required. The instructor replied that the answer ultimately depends on the strength of the evidence: if the studies are highly persuasive and reach uniform conclusions, just a few may suffice; conversely, if the evidence is weak—such as case reports involving only a handful of cases—and the findings vary across studies, even hundreds of papers might fail to provide the level of evidence needed for regulatory review.

　　Challenge No. 4: Data on the Chinese subpopulation are relatively difficult to obtain. In the clinical dataset requirements, there is a stipulation for a Chinese‑specific data subset, which often poses a significant hurdle for imported products. On the one hand, in clinical trials conducted in Europe and the United States, the proportion of Chinese or other Asian participants is typically low, with Caucasian subjects predominating. On the other hand, for various reasons, many such trials do not explicitly collect information on racial/ethnic groups, making it challenging to extract Chinese or Asian data from the trial results. If Chinese‑specific data cannot be provided in the CER, the CMDE may require a small‑scale clinical trial solely to demonstrate that there are no race‑related differences. However, even a modest trial would entail substantial time and financial resources. Should the CER ultimately lead to the need for a full clinical trial rather than direct marketing approval, the preceding efforts could effectively be rendered futile.

　　Furthermore, if a product is highly innovative and entails a certain level of risk, even with available data and clinical literature to support a CER, the CMDE may still require additional data, given its concerns about the product’s safety.

　　Which products are suitable for CER?

　　To date, various companies have submitted numerous CERs to the CMDE. Some have been returned for reconsideration, others have been requested to provide additional data, and still others have been approved. Based on the CER requirements and the CMDE’s feedback, products that are relatively easier to navigate through the CER process generally include:

　　1. Conversion of imported products to domestic production;

　　2. The product should have been on the market for a long time, and ideally be from the same company.

　　3. The production process is stable, with no major changes;

　　4. Low risk.

　　The “Technical Guidance for Clinical Evaluation of Medical Devices” has opened a new pathway for the market approval of medical devices in China, saving manufacturers time and costs while preventing the unnecessary duplication of existing data. This represents a significant advancement for regulatory authorities, manufacturers, and patients alike. Further interpretation of the guidance and concerted efforts across all stakeholders will be essential to expedite the market entry of devices through the CER framework.