Medical device registration management is one of the most crucial links in the entire lifecycle management of medical devices. It plays a connecting role between the research and development and production of medical devices, and is not only an important means to determine the safety and effectiveness of medical device products, but also a basic prerequisite for strengthening the quality management of medical devices after they are launched. Therefore, how to continuously innovate this important system and promote the healthy development of the industry is an important issue that medical device management departments and industry practitioners should consider. This article studies the development of China's medical device registration management system in different periods since 1996, analyzes the new problems encountered by the system in practice, and explores the paths and methods for innovating China's medical device registration management system.
What changes have occurred in China's medical device registration management system?
01. Changes in Management Methods for Class I Medical Devices
As is well known, China implements classified management of medical devices based on the level of risk. The 2000 version of the "Regulations" uniformly implements registration management for all categories of medical devices. The revised "Regulations" in 2014 changed the first category of medical devices to record management. The original intention of this change is to implement the concept of risk management and improve regulatory efficiency. This change has been recognized by the industry in practice, not only simplifying the registration process for first class medical devices, but also improving the efficiency of regulatory resources to a certain extent. It is a major progress in China's medical device registration management system.
02. The appearance of continued registration of medical devices
The 2014 version of the Regulations correctly distinguished between continued registration and re registration, replacing re registration with continued registration. Continuing registration refers to when the product registration certificate of a medical device is about to expire, the registrant can submit application materials to the relevant department to apply for extending the validity period of the registration certificate. It can be seen that the effectiveness and validity period of the registration certificate have been extended, but there have been no substantial changes in the structural characteristics, technical principles, etc. of the corresponding products, which is also the basic starting point for continuing registration. The requirement for re registration is that regardless of whether the product has undergone any substantial changes, as long as the certificate expires, the registration process needs to be repeated. Re-registering products that have not undergone substantial changes in safety and effectiveness will clearly result in resource waste and increase enterprise costs. In contrast, the proposal to continue registration has to some extent simplified the cumbersome re registration process and is an important progress in streamlining and improving the medical device registration management system.
03. Changes in Innovative Medical Device Registration Management
Innovation is an important driving force for promoting the development of things. In this era of "keeping up with the times, keeping up with the times, and keeping up with the times", innovative medical devices hold a special position in registration management. In 2014, the national drug regulatory department issued and implemented the "Special Approval Procedure for Innovative Medical Devices (Trial)" (hereinafter referred to as the "Special Approval Procedure (Trial)"), which proposed special approval for innovative medical devices for the first time. Subsequently, in 2018, it was revised to the "Special Review Procedure for Innovative Medical Devices" (hereinafter referred to as the "Special Review Procedure"). There are two main changes after the revision: (1) For products that have obtained invention patent rights or their usage rights in China through legal transfer, it is required that the application time for special examination of innovative medical devices should not exceed 5 years from the date of patent authorization announcement; (2) For products whose applications for core technology invention patents have been disclosed by the patent administration department under the State Council, the Patent Search Consulting Center of the China National Intellectual Property Administration is required to issue a search report, which indicates that the core technology scheme of the product is novel and creative. The changes in these two aspects mainly emphasize the novelty of patents. The promulgation of the "Special Approval Procedure (Trial)" is equivalent to opening up a "shortcut" for innovative medical device registration, which not only enhances the innovation enthusiasm of research and development institutions and enterprises, but also promotes the promotion and application of new medical device technologies. But at the same time, stricter requirements have been put forward for the core technological innovation and quality management system of medical device enterprises. However, in the long run, there is still great room for development in China's innovative medical device market. In addition, the "Special Review Procedure (Trial)" is only a normative document for government departments. Compared with the relevant laws of the United States' innovation plan, China's medical device innovation policy should also strengthen the protection of innovation actions.
04. Emergency approval and priority approval of medical devices
The "Emergency Approval Procedure for Medical Devices" released in 2009 strengthened the response to public health emergencies, providing a legal basis for approving medical device products in emergency situations. On this basis, in 2016, China issued the "Priority Approval Procedure for Medical Devices", which implements priority approval for medical devices specifically designed for the treatment of rare diseases, malignant tumors, elderly diseases, and children, as well as those that are urgently needed in clinical practice and included in major national scientific and technological projects or key research and development plans, through a process of first reviewing and then processing. The release and implementation of the "Emergency Approval Procedure for Medical Devices" and "Priority Approval Procedure for Medical Devices" have further improved China's medical device registration management system, which is greatly beneficial for deepening the reform of medical device review and approval and ensuring the clinical use needs of medical devices.
What are the problems with the current medical device registration management system?
Practice is the foundation of theory and the ultimate goal of proposing it. The establishment of the medical device registration management system is to better promote the supervision and development of the medical device industry, thereby serving the general public and promoting public health. Therefore, it is necessary to handle the problems in the medical device registration management system with caution.
01. The registration and approval standards for Class II medical devices vary
China has a vast territory and significant differences in regional economic and technological levels. The development of industries in different provinces is uneven, and the capabilities of medical device review and approval teams in different provinces also vary to some extent. According to regulations, all 31 provincial-level drug regulatory departments in China have the approval authority for Class II medical devices. In principle, these regulatory departments should apply regulations equally to similar products and make consistent evaluation results. However, due to various factors, there are varying degrees of differences in the perception of product risk, product category attribution, and clinical evaluation pathways among different review departments. Even for the same type of product, different approval authorities (even within the same approval authority) often have some differences in the severity of review and approval, as well as the scope of application, instructions, product standards, and other aspects of the approved product. Through the efforts of the National Drug Administration to organize multiple evaluation business training, evaluation capability checks, and develop corresponding registration guidelines, the differences in evaluation and approval capabilities among different provinces are continuously narrowing. Under long-term efforts, the phenomenon of "high class, low batch" or "low class, high batch" that had previously occurred in some regions has been significantly reduced. However, in order to fundamentally solve the problem of inconsistent evaluation standards, further improvement of the system is still needed.
02. Low authenticity and compliance of clinical trial data for medical devices
Clinical trials of medical devices are one of the main methods of clinical evaluation, and the authenticity and compliance of clinical trial data directly affect the verification of product safety and effectiveness. In 2017, the Supreme People's Court and the Supreme People's Procuratorate jointly issued the "Interpretation on Several Issues Concerning the Application of Laws in Criminal Cases of Falsification of Application Materials for Drug and Medical Device Registration", punishing illegal and criminal acts of data falsification during the registration process of drugs and medical devices in accordance with the law. According to the results of several clinical trial supervision and spot checks conducted by regulatory authorities from 2016 to 2019 (see Table 1), the phenomenon of low authenticity of clinical trial data of medical devices has significantly decreased after 2017, but the problem of low data compliance has become increasingly prominent year by year, exposing issues worth noting such as the need to strengthen the legal and responsibility awareness of applicants and clinical trial institutions, and the urgent need to improve clinical trial quality management capabilities.
The cause of the problem
01. The unified scientific concept lacks support for the review and approval of medical devices
The medical device review and approval department in China has always been committed to the standardization of product review standards and has taken various ways to enhance the professionalism of the review team. However, the numerous categories of medical devices, strong interdisciplinary nature, and rapid technological updates pose challenges to the professional capabilities of the evaluation team. At present, professionals engaged in the review and approval of medical devices are limited to their professional background and knowledge structure, and their understanding of the same product is different. Therefore, the focus and scale of the review may sometimes vary. With the accelerated application of new technologies such as 3D printing technology, artificial intelligence technology, and big data in the field of medical devices, there is an urgent need for unified scientific concepts to guide practice in the review and approval of medical devices. The proposal of scientific regulation of medical devices precisely meets the above needs. Personnel engaged in supervision need to master the basic theories and knowledge of regulatory science in order to be competent for the review and approval of new technologies and products. Medical device reviewers and inspectors need to be very familiar with industry laws, regulations, and technical knowledge in order to make a correct judgment on the safety and effectiveness of medical device products based on the information submitted by the applicant. Therefore, this places high demands on the professional abilities, work experience, and educational background of auditors and inspectors. However, the reality is that the improvement of the professional abilities of reviewers and inspectors is often achieved through "fragmented" training, and it is urgent to form a unified concept for medical device review and approval at the national level. This depends on the promotion of scientific medical device regulation, and the formation of a unified scientific connotation in product review principles, review concepts, review methods and means, and review supervision.
02. Inadequate demand for clinical trials of medical devices
Clinical trials of medical devices often exist as a pre registration and application process, so the progress of clinical trials to a certain extent determines the progress of the entire medical device registration and application. However, the constraints of multiple factors make the clinical trial needs unsatisfied, mainly manifested in three aspects: (1) the number of clinical trial institutions is small, and the degree of specialization is low. In addition, compared with relatively standardized and specialized drug clinical trials, the development time of medical device clinical trials in China is short and still in the stage of improvement; (2) The low treatment of personnel engaged in clinical trial activities in medical institutions, coupled with the verification action of the authenticity and compliance of medical device clinical trial data initiated by the National Drug Administration, has led to a decrease in the willingness and enthusiasm of some medical institutions to conduct clinical trials after weighing their risk benefit ratio. The phenomenon of delayed clinical trial queues is severe, and the industry's clinical trial needs are more difficult to meet in a timely manner; (3) Clinical trial applicants have weak professional abilities, which makes it difficult for the entire clinical trial process to proceed smoothly. For example, many production enterprises are unclear about the product registration process, and the personnel responsible for registration do not have a deep understanding of the registration approval process and specific requirements for registration materials. Due to these factors, clinical trials of medical devices have become the main reason for affecting the efficiency of medical device registration and review.
03. Unclear definition of quality management responsibilities for medical device registration
The issues found in the authenticity and compliance verification of clinical trial data of medical devices have exposed the fact that the quality and safety responsibilities in medical device registration management are not clearly defined. Some medical device research and development institutions and registration applicants use shortcuts to push their products to the market, but ignore their responsibilities after the products are launched; Many production and business enterprises, after producing and selling their products, rarely consider the quality management after the product is launched. This leads to each subject taking on segmented responsibilities at a certain stage, while no subject is willing to actively take on the ultimate responsibility throughout the entire product lifecycle. This result is not conducive to the implementation of quality and safety responsibilities under the medical device registration management system, so it is necessary to re-examine the legal relationships between various entities under the current segmented management of the entire product lifecycle.
Suggestions for Improving the Medical Device Registration Management System in China
01. Establish the medical device registrant system as the basic industry management system
Since December 2017, the medical device registration system has been piloted and implemented in Shanghai, and has now expanded to 21 provinces (districts, cities) nationwide. The key content of this system includes that medical device registrants with corresponding production qualifications can either produce medical devices themselves or entrust production, breaking the binding model of medical device registration license and production license, and innovating the entrusted production management method after medical device registrants hold certificates, which has been welcomed by the industry. It is recommended to establish the medical device registrant system as the basic management system for the medical device industry on the basis of pilot projects. The second paragraph of Article 8 of the 2018 Amendment to the Regulations on the Supervision and Administration of Medical Devices (Draft for Review) by the Ministry of Justice mentions a new term - the holder of the medical device marketing license, which is actually completely consistent with the meaning of the medical device registrant. As the rights and obligations of the medical device registrant run through all aspects of the entire life cycle of the medical device product, Establishing the medical device registrant system as the basic management system of the industry is conducive to solving problems in registration management practice. In addition, in the Draft Regulations for Review, it is no longer stipulated that the food and drug supervision and management departments of provinces, autonomous regions, and municipalities directly under the central government are responsible for the review and approval of Class II medical devices, but directly review and approve them by the drug supervision and management department of the State Council. If this is ultimately implemented, it will actually eliminate the provincial-level management of the second type of medical devices, which is conducive to solving the problem of inconsistent standards of medical device registration review and approval caused by differences in technology, economy, and other aspects among approval agencies in different regions.
02. Clarify the relationship between the review and approval system related to medical devices. In China's medical device review and approval system, it includes various forms such as special approval for innovative medical devices, priority approval for medical devices, emergency approval for medical devices, and conditional approval for medical devices. According to Article 13, Paragraph 2 of the "Draft Regulations for Review", for medical devices used to treat rare diseases, serious life-threatening diseases without effective treatment methods, and urgent needs in response to public health emergencies, the drug regulatory department may approve them with conditions and specify relevant matters in the medical device registration certificate. This is the first time that conditional approval has been proposed as an important type of medical device registration management in the legislative draft, in order to prepare institutional reserves to address the urgent need for medical devices in certain emergency situations. The special approval for innovative medical devices is applicable to innovative medical devices that meet the conditions, while the priority approval for medical devices is applicable to medical devices used for rare diseases, frequently occurring diseases in the elderly or children, certain serious life-threatening diseases without effective treatment methods, or medical devices supported by major national scientific and technological projects. The "Emergency Approval Procedure for Medical Devices" issued in 2009 in China is applicable to the approval of products that are required for emergency response to public health emergencies and have not yet been launched in China, or products that cannot meet the emergency response needs of public health emergencies even though similar products have already been launched in China. These review and approval systems are applicable to different targets, but there are also intersections. Both conditional approval and emergency approval for medical devices are targeted at sudden public health events, and priority approval and conditional approval for medical devices are also targeted at medical devices that are seriously life-threatening and have no effective treatment methods for diseases. In the future, it is necessary to further clarify their applicable objects, procedures, and requirements from a institutional perspective.
03. Expand the exemption scope for clinical evaluation of Class II medical devices
Article 17 of the 2014 version of the Regulations stipulates that eligible Class II and Class III medical devices can be exempted from clinical trials, while Article 19 (2) of the Draft Regulations proposes that in principle, Class II medical device registration and application will not undergo clinical evaluation, which is a significant improvement compared to previous regulations. One is that the new regulations use the concept of "clinical evaluation", noting the difference between clinical evaluation and clinical trials. The first paragraph of Article 19 of the Draft Regulations for Review clarifies the definition of clinical evaluation of medical devices for the first time, which means that "clinical evaluation of medical devices refers to the process in which the applicant confirms whether the product meets the clinical application scope and usage requirements through clinical literature, clinical experience data, clinical trials, and other information. This definition clarifies the correct relationship between clinical evaluation and clinical trials, pointing out that clinical trials are a primary form of clinical evaluation and are not completely equivalent to clinical evaluation. Secondly, it is proposed that the second type of medical devices should not undergo clinical evaluation in principle, which deepens the understanding of low-risk medical devices and is conducive to the correct implementation of risk management principles. Thirdly, in the face of a serious shortage of clinical trial institutions and professional talents, the reduction of clinical evaluation activities for the second type of medical devices is conducive to alleviating the shortage of talent resources in the entire industry. Therefore, for low-risk medical devices, constructing a new clinical evaluation system with exemption from clinical evaluation as the norm and the need for clinical evaluation as the exception is undoubtedly very effective in improving the efficiency of medical device review and approval and truly implementing risk management. Indeed, the principle of not conducting clinical evaluation for the second type of medical device does not mean that there are no requirements for its safety and effectiveness. Before the product is launched, the applicant still needs to provide sufficient information to prove the safety and effectiveness of the product; After the product is launched, regulatory authorities must also strengthen quality management after the product is launched.
04. Strengthen the cultivation of clinical trial and registration talents for medical devices
In the medical device industry, there is a shortage of professional medical device clinical trial and registration specialists. Medical device clinical trial institutions have little or no separate training on the "Quality Management Standards for Medical Device Clinical Trials". This has to some extent affected the efficiency of clinical trials of medical devices and the smooth progress of registration and application. Therefore, various medical device clinical trial institutions should take the implementation of the "Management Measures for the Conditions and Filing of Medical Device Clinical Trial Institutions" as an opportunity to increase the reserve of clinical trial personnel, improve the work benefits of clinical trial personnel, and establish a professional team of medical device clinical trial talents. The country should elevate the training of specialized medical device clinical trials and registration specialists to the same level as the training of professional medical device inspectors, and provide corresponding support policies and guidance. In addition, medical device related enterprises should attach importance to and strengthen the internal training of clinical trial personnel and registration specialists. Enterprises should be proactive and attach importance to the study of laws, regulations, and standards. A dedicated person should be responsible for collecting, organizing, and guiding the application of policies, regulations, standards, and related review guidelines to ensure that products comply with regulatory requirements during the design and development process. In addition, enterprises can also enhance the professional abilities and comprehensive qualities of relevant personnel through various methods such as pre job training, on-the-job guidance, and continuing education. The medical device industry has a very broad prospect, and it will rapidly develop in the driving force of market demand and technological innovation. This article only explores the improvement of the medical device regulatory system from the perspective of "registration management", and there are more areas that are worthy of in-depth consideration and exploration. From the perspective of "registration", I believe that with the revision and improvement of the "Regulations" and "Measures", the medical device registration management system that has been implemented for more than 20 years will inevitably bring forth new ideas and constantly radiate new vitality.
Source: China Food and Drug Network
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