Overview of US and China's Medical Device Regulations

In October 2017, the General Office of the CPC Central Committee and the General Office of the State Council issued the Opinions on Deepening the Reform of the Review and Approval System and Encouraging Innovation in Drugs and Medical Devices. This is another guiding document for deepening the reform of the review and approval system for drugs and medical devices, following the Opinions of the State Council on Reforming the Review and Approval System for Drugs and Medical Devices issued in August 2015. It provides greater support for scientific and technological innovation in drugs and medical devices in China and has milestone significance for the innovative development of China's pharmaceutical industry. This article summarizes the regulatory situations of innovative medical devices by drug regulatory authorities in China and the United States, providing a reference for further improvement of China's innovative medical device regulatory model. First,

To ensure the safety and effectiveness of medical devices, encourage research and innovation in medical devices, promote the promotion and application of new medical device technologies, and promote the development of the medical device industry, in accordance with the relevant requirements of the Medical Device Supervision and Administration Regulations and the Medical Device Registration Management Measures, the former State Food and Drug Administrationformulated and issued the Special Approval Procedures for Innovative Medical Devices (Trial) on February 7, 2014, clarifying the definition, application process, and review and approval requirements for innovative medical devices. On December 1, 2018, the National Medical Products Administration issued the newly revised Special Review Procedures for Innovative Medical Devices (hereinafter referred to as the "Review Procedures"), improving the applicable situations, detailing the application process, enhancing the effectiveness of innovative reviews, improving the review methods and notification formats, and clarifying that priority will be given to changes in the licensing matters of innovative medical devices.

According to the Review Procedures, innovative medical devices should meet the following conditions: legally owning the core technology invention patent rights of the product in China, or legally obtaining the invention patent rights or its usage rights in China through assignment, or the patent application has been disclosed by the State Intellectual Property Office; the main working principleThe mechanism of action is the first of its kind in China, there are no similar products on the market in China, the performance or safety has fundamental improvements compared with similar products, the technology is internationally leading, and it has significant clinical application value; it has a basically finalized product, the research process is real and controlled, and the research data is complete and traceable. At the same time, the newly revised Review Procedures further limit the patent authorization period, patent novelty, and creativity.

Innovative medical devices generally need to go through two steps to be listed according to the Review Procedures: First, domestic or foreign applicants submit an application for special approval of innovative medical devices, and the Medical Device Technical Review Center (hereinafter referred to as"Device Review Center") Innovative Medical Device Review Office organizes experts to conduct a review to confirm whether it meets the definition of innovative medical devices in this procedure; Second, applicants can continue to submit product registration applications through the special review channel for innovative medical devices. From the provincial to the national drug regulatory departments, from quality system verification, registration inspection, and review and approval at various stages, the principle of "early intervention, dedicated personnel, and scientific approval" will be followed. Priority will be given to innovative medical devices without lowering standards or reducing procedures, and communication and exchanges with applicants will be strengthened.

Sincethe innovative channel was opened in 2014, up to the first quarter of this year, the Device Review Center has received 1135 applications for special review of innovative products, and 216 have been approved. 78 have entered the review procedure, accounting for 36% of the approved projects. The first review time for innovative products has been greatly reduced, shortening the review time limit by nearly 60% compared with conventional products, effectively promoting the registration and listing process of innovative medical devices, promoting the development of the innovative medical device industry, and achieving good social effects.

In 2016, the former State Food and Drug Administration issued the Priority Approval Procedures for Medical Devices, clarifying the conditions, review and approval procedures, and regulatory requirements for priority approval products. It stipulates that medical devices that meet one of the following situations can be included in the priority approval procedure: 1. Diagnosis or treatment of rare diseases with obvious clinical advantages; 2. Diagnosis or treatment of malignant tumors with obvious clinical advantages; 3. Diagnosis or treatment of diseases unique to and prevalent among the elderly, and there are currently no effective diagnostic or treatment methods; 4. Exclusively for children, and with obvious clinical advantages; 5. Clinically urgent, and there are no similar products approved for registration in China. In addition, medical devices included in major national science and technology projects or national key research and development plans, as well as other medical devices that should be given priority approval, can also be included in the priority approval procedure.

It should be noted that there are slight differences between the priority approval procedure and the special review channel for innovative medical devicesAfter the application product is identified for priority approval, it can be directly transferred to the review and approval process, sorted separately according to the receiving time, and given priority for technical review.

As an important part of the innovation of the medical device industry, regulatory departments are the link between promoting research and development, production, and clinical application. In order to fully utilize professional capabilities, effectively integrate high-quality resources in the health industry, provide positive guidance for industrial development, and promote the normative and healthy development of the industry, regulatory departments represented by the Device Review Center are also actively involved in national key research and development plans, creatinga full-chain research project of "production, learning, research, medicine, and management", including both horizontal technology service platform research and vertical professional research targeting a certain type of product.

Among them,the "Development and Application Research of Intelligent Medical Device Industry Technological Innovation Service Platform" project aims to build an industry service platform based on technical interpretation and technical guidance systems, fully utilize the professional advantages of technical review, establish various service approaches, methods, and platforms, and provide technical and regulatory aspects for product research and development innovation. Full-dimensional guidance and services; the "Research on the Scientific Basis of New Medical Metal Material Standards and Their Review" project focuses on the key common problems existing in new medical metal materials and their implanted devices urgently needed for current industry development, such as new low-modulus titanium alloys, shape memory alloys, degradable magnesium alloys, and 3D-printed metal materials and implanted devices, and establishes a series of review guidelines and evaluation methods to ensure product safety and effectiveness, providing important support and institutional guarantees for industrial development and scientific supervision.

In addition to the above review and approval paths and national key research and development plans, regulatory departments are also actively studying how to address the regulatory challenges brought about by technological innovation. As a frontier position for technical review, the Device Review Center undertakes the regulatory science research projects of the National Medical Products Administration, includingthe "Regulatory Science Research on New Materials for Medical Devices" project. This project will establish innovative regulatory theories, systems, technologies, and methods for innovative medical devices using new materials based on the existing medical device evaluation system, enhance the scientific nature of regulatory measures and decisions, further improve the effectiveness and accuracy of China's medical device regulation, and achieve mutual promotion and positive interaction between government regulation and medical device innovation, providing institutional, technological, and theoretical guarantees for promoting China's medical devices to catch up with and even lead the world.

Medical devices are clinically oriented, and clinical evaluation is an important means of evaluating the risks and benefits of medical devices. China, as a member of the International Medical Device Regulators Forum (As the leading country in the "Clinical Evaluation of Medical Devices" project group within the IMDRF, China is benchmarking its medical device regulatory experience against international standards, actively absorbing international coordination experience, and further transforming it into regulatory requirements suitable for China. II. The Innovative Regulatory Situation of Medical Devices in the United States

` ` ` ` ` `The United States Food and Drug Administration (FDA) supports and guides medical device innovation in two ways. First, it optimizes and establishes new medical device review and approval pathways to accelerate the market entry of innovative medical devices; second, it develops and publishes application tools and strategic plans to aid in review decision-making in a timely manner, reasonably allocates internal and external resources to regulatory agencies, and promotes the development of innovative regulatory science to promote industry innovation.

` ` ` ` (I) Optimization and establishment of product review and approval pathways

` ` ` ` ` `On May 17, 2013, the FDA released a priority review pathway for medical device marketing applications (Priority Review). These products are applicable to "treating or diagnosing life-threatening, irreversible, debilitating diseases or conditions," and at least one of the following conditions should also be met: 1. The device's breakthrough technology is superior to existing technologies and brings clinical advantages; 2. There is no approved alternative treatment or diagnostic method available; 3. The device has outstanding clinical advantages superior to existing approved products; 4. The utilization rate of the device is most in the interests of patients.

` ` ` ` ` `Applications granted priority review will be at the front of the review application queue, with rapid review in premarket approval (PMA), premarket notification (510k), and de novo classification applications. It may also receive additional review resources, such as team review and expert panel review.

` ` ` ` (II) Expedited Access Pathway

` ` ` ` ` `On April 13, 2015, the FDA launched an expedited access pathway for medical devices (Expedited Access Pathway), aimed at accelerating the market entry of medical devices that treat or diagnose life-threatening or irreversibly debilitating diseases (such as chronic or positive hepatitis, myocardial infarction, cancer, stroke, etc.). Products entering the expedited pathway enjoy the preferential policies mentioned in the "Priority Review Pathway" above. At the same time, applicants can discuss with the staff of the Center for Devices and Radiological Health (CDRH) under the FDA to develop a Data Development Plan, which identifies the clinical and non-clinical data that the applicant needs to collect, and the time schedule for the development and marketing of the device, guiding the applicant during the R&D stage.

` ` ` ` ` `(III) Humanitarian Use Device Approval Pathway

` ` ` ` ` `The FDA proposed the criteria for identifying Humanitarian Use Devices (HUDs) and the exemption approval pathway in the 1990 Medical Device Safety Act to encourage companies to develop medical devices for the treatment or diagnosis of rare diseases. Such medical devices must meet the following conditions: 1. Used to treat or diagnose extremely low-prevalence diseases that affect fewer than 4,000 people annually in the United States; 2. There are no other marketed devices that can treat the disease; 3. The use of the device will not cause serious and unreasonable risks to patients; 4. The potential benefits to patients outweigh the risks of disease or injury.

` ` ` ` ` `Once a medical device is identified as a humanitarian use device, it can apply for a Humanitarian Device Exemption (Humanitarian Device Exemption) pathway. Specifically, applicants should at least demonstrate to the FDA that the use of the device does not pose a significant unreasonable risk to patients, and that the potential benefits to patients' health outweigh the risks, protecting patient interests.

` ` ` ` ` `In December 2016, the US Congress passed the 21st Century Cures Act, revising the definition of humanitarian use devices, changing the previous rare disease population limit from "fewer than 4,000 people" to "no more than 8,000 people." III. Regulatory Science Development Plan

` ` ` ` ` `The FDA first proposed the Critical Path Initiative in March 2004 to encourage scientific innovation in the research, evaluation, and production processes of medical devices. In 2006, the FDA also released a list of Critical Path opportunities, listing 76 specific scientific opportunities to help address scientific issues related to the regulation of medical products, including pharmaceuticals and medical devices. These 76 specific contents can be summarized into six aspects: better evaluation tools; improving the efficiency of clinical trials; utilization of bioinformatics; shifting to 21st-century manufacturing methods; developing products to address urgent public health needs; and addressing special risk groups.

` ` ` ` ` `The FDA first proposed the Medical Device Innovation Initiative in February 2011. Priority review is given to new and groundbreaking medical devices, aiming to provide patients with timely access to safe, breakthrough new medical device products by reducing the time and cost of medical device development, evaluation, and review. The "expedited access pathway" mentioned above is one of the outcomes of the Innovation Initiative. At the same time, the Innovation Initiative also seeks to enhance the FDA's regulatory capabilities, including using multiple media and tools to deepen understanding of products or technologies, developing application guidelines to establish a "risk-benefit" framework, and increasing the transparency of approval decisions.

` ` ` ` ` `To improve review capabilities and enhance service quality and efficiency,CDRH began developing and releasing Regulatory Science Priorities in 2013. CDRH defines regulatory science as the science in regulatory service. It helps ensure the reliability of regulatory decisions and, through the development and application of tools, standards, and methods, studies the anticipated public health effects of safety, effectiveness, quality, and performance throughout the product lifecycle; regulatory science priorities serve as a catalyst to improve the safety, effectiveness, performance, and quality of medical device products and to facilitate the market entry of innovative medical devices; to provide reference for the agency's annual plans and budgets; to regularly evaluate the research progress of regulatory science to better serve registration decisions; to release regulatory science priorities to guide the research and work of external agencies, and strengthen cooperation to maximize resource utilization.

` ` ` ` ` `From July 25th to 27th, 2019, iiMedia Research will host the "GIIS 2019 4th China Greater Health Industry Upgrading Summit." The summit will focus on the topic of "Yanqi Healthy Talk - Medical Transformation from Scale to Value" and will discuss market environments, investment hotspots, and industrial transformations in four sub-sectors: medical big data, pharmaceutical innovation, private medical services, and technological medical services.