Source: China Journal of Food and Drug Regulation

Citation

Wang Guang-Ji, WANG Yue, LI Jie, CHANG Gui-Hong, Zhou Xin-Teng, LI Fu-Ying, CAO Feng-chao, Yu Bing, LIAN Yun-Fei, Chen Yu-Jie, WANG Jing, LIU Juan, WANG Yun, HAN Liang. Introduction of foreign cell therapy product regulatory system and its implications for China [J]. China Food and Drug Regulation,2023(9):6-13. (in Chinese)

Introduction to the Regulatory System of Cell Therapy Products Abroad and Its Enlightenment for China

Wang Guangji

China Pharmaceutical University

WANG Yue

Professional Committee for Cell and Gene Therapies of China Society for Drug Regulation

LI Jie

Professional Committee for Cell and Gene Therapies of China Society for Drug Regulation Overland Pharmaceutical (Shanghai) Co., Ltd.

CHANG Gui-hong

CARsgen Therapeutics Holdings Limited

ZHOU Xin-teng

Fosun Kite Biotechnology Co., Ltd.

LI Fu-ying

BRL Medicine Inc.

CAO Feng-chao

Beijing Shangzhihegui Technology Co., Ltd.

YU Bing

China Association of Enterprises with Foreign Investment, R&D-based Pharmaceutical Association Committee

LIAN Yun-fei

Jiangsu Topcel-KH Pharmaceutical Co., Ltd.

CHEN Yu-jie

Overland Pharmaceutical (Shanghai) Co., Ltd.

WANG Jing

Jiangsu Renocell Biotech Co., Ltd.

LIU Juan

Juventas Cell Therapy Ltd.

WANG Yun

China Association of Enterprises with Foreign Investment, R&D-based Pharmaceutical Association Committee

HAN Liang

Beijing Shangzhihegui Technology Co., Ltd.

Abstract

With strong support from national policies, China has initially established a regulatory system for cell therapy products that covers the entire lifecycle, covering research and development, registration, production, and post-marketing. However, compared to mature regulatory systems for other biological products and the regulatory systems in developed countries or regions, there is still significant room for improvement. This article comprehensively reviews the current status of China's cell therapy industry and regulatory system, analyzes the regulatory system for cell therapy products abroad, and explores the enlightenment for building China's regulatory system. The aim is to propose a scientifically sound and practical plan to further improve China's regulatory system for cell therapy in a comprehensive manner.

Key words

cell therapy; industrial development status; overseas supervision system; enlightenment

With the continuous development and breakthrough of cell therapy technology, cell therapy has become an important frontier in the field of life science and medicine. Cell therapy products show great application potential in the face of many serious or refractory diseases that are ineffective in traditional treatments, such as cancer, genetic diseases and organ damage. Global enterprises have accelerated the layout and investment in this field, and increased the research and development and commercialization of this field; At the same time, governments all over the world attach great importance to and provide policy support. At present, cell therapy has become a key support and development direction in the field of biomedicine at home and abroad.

The Outline of the 14th Five-Year Plan for National Economic and Social Development and the 2035 Vision Goal of the People's Republic of China pointed out that China should accelerate the development and expansion of strategic emerging industries, including the biomedical industry, including cell and gene therapy drugs. Since 2021, Beijing, Shanghai, Tianjin and Shenzhen have successively issued the Development and Construction Plan for Zhongguancun National Independent Innovation Demonstration Zone during the 14th Five-Year Plan Period, Regulations on Promoting the Construction of Zhangjiang Biomedical Industry Innovation Highland in Shanghai Pudong New Area, Measures to Encourage the high-quality development of Cell and gene therapy Industry in Tianjin Binhai High-tech Zone, and Regulations on the promotion of cell and gene Industry in Shenzhen Special Economic Zone Local policies, such as ", strongly support the development of the cell therapy industry.

Cell therapy products have the characteristics of rapid technological development, large differences, and complex mechanism of action of products, and their regulation is more complex than that of other biological products or chemicals, which brings different degrees of risk to patients, and also brings unprecedented challenges to researchers and regulatory authorities. Therefore, the rapid development of a scientific and perfect cell therapy product regulatory system is the cornerstone of the development of the industry, and the challenges brought by the rapid and high-quality development of the industry will continue to promote the improvement of industry regulation. Although China clearly encourages the development of the cell therapy industry, and is making continuous progress in the construction of the system, but compared with the mature regulatory system of other biological products and the cell therapy regulatory system of developed countries or regions, there is still no systematic standardized laws, regulations and guiding principles of the three-level system. With the strong support of the China Drug Regulatory and Administration Research Society, the Cell and Gene therapy product Regulatory Research Committee officially set up the topic "Research on the Development status of China's cell therapy industry and regulatory proposals - Exploration and Establishment of a druggability evaluation system", starting from a comprehensive review of the status quo of China's cell therapy industry and regulatory system, combined with the regulatory experience of Europe, America and Japan and other countries or regions. Some suggestions were put forward to further improve the regulatory system of cell therapy products in China.

01 Status of cell therapy industry and regulatory system in China

1.1 Industry status

China's cell therapy industry is in a similar stage of explosive growth as other parts of the world. From the perspective of research and development, Citeline's Trialtrove database shows that if the start time of clinical trials is calculated before December 31, 2022, there are a total of 10,223 clinical trial projects of cell therapy products worldwide, and 2,253 clinical trial projects of cell therapy products in China. About 22% of the global clinical trials of cell therapy products, the number of clinical trials in China and the United States accounted for about 60% of the global clinical trials of cell therapy products, and the research showed a pattern of "two strong competition" to lead the world. The cell therapy clinical studies carried out in China and the United States mainly focus on phase I and Phase II, mainly on CAR T cells, and the target selection is also relatively similar, especially in the field of lymphatic and hematopoietic malignancies. At the same time, some Chinese enterprises have also carried out active research and development activities in the field of solid tumor and general CAR-T.

With the gradual development and maturity of the technology, the global cell therapy products entered the harvest period after 2010. As of November 2022, according to the Insight database, a total of 48 cell therapy products [1] have been approved worldwide, including 22 stem cell therapy products, 8 CAR T products, 2 T cell products, and 16 separate types of products calculated as "other". The approved cell therapy products are mainly used in the field of genetic diseases and rare diseases at first, and then gradually promoted to malignant tumors, infectious diseases, cardiovascular diseases and autoimmune diseases, among which the target of CAR-T products is more concentrated on CD19.

At the same time, with the encouragement of the government, Chinese enterprises are also actively promoting the industrialization of the field of cell therapy. 2021 is known as the "first year of cell therapy" in China: two autologous CD19-targeting CAR-T products, Akilencel injection from Fosun Kette Biotechnology Co., Ltd. and Rechiolencel injection from Shanghai Yaoming Juno Biotechnology Co., Ltd. were approved by the State Drug Administration. China's third CAR-T product, Nanjing Reindeer Biomedicine Co., Ltd. of Ikiolencel injection, targeting B-cell maturation antigen (BCMA) autologous CAR-T, was also conditionally approved by the State Drug Administration in June 2023. At present, there are a number of enterprises have or plan to apply for domestic listing. In addition, some leading biotechnology companies have stepped out of the development path of focusing on the global, domestic and foreign layout. Nanjing Legend Biotechnology Co., Ltd. signed a global cooperative development agreement with Xi 'an Janssen Pharmaceutical Co., Ltd. for Sidagiolencel in 2017, and in February 2022, Sidagiolencel was approved for marketing by the U.S. Food and Drug Administration (FDA).

The global cell therapy research and development is active, and the development prospect of cell therapy is very broad. Since 2015, a large amount of capital has entered the field of cell therapy research and development to become the driving force for the accelerated development of the cell therapy industry, while the successive approval of cell therapy drugs has also enhanced the confidence of investors to continue to invest. At the same time, large pharmaceutical companies have set off a wave of mergers and acquisitions in the field of cell therapy. Gilead, Bristol-Myers Squibb, Novartis, Bayer, Roche, Takeda and other pharmaceutical giants have acquired mature cell therapy technologies or products through mergers and acquisitions to quickly supplement or enhance their research and development capabilities and product pipelines, and win the first-mover advantage in the "battle" for cell therapy. At the same time, it also vigorously promotes the transformation of relevant technologies from research and development to market application. As a result, with the continuous emergence of new cell therapy, gene therapy and RNA therapy technologies, the global cell therapy industry has entered a stage of rapid development, and with the breakthrough of new technologies and the advent of new products, the global market size will continue to rise. The market size of China's cell therapy industry will also grow rapidly under the background of favorable policies and increased R&D investment, and the compound annual growth rate may be higher than the global average.

Overall, although the number of approved products for cell therapy in China is lower than that of leading countries, and the product types and treatment areas are more concentrated, the number of R&D pipelines has ranked among the first echelon with considerable potential. As far as technology is concerned, although there are still some technical card points in China, the gap in front-end research and development capacity is small compared with foreign countries, and even at the international leading level in some fields.

1.2 Status of the regulatory system

At present, China's cell therapy supervision is divided into the following two forms: one is for the purpose of listing therapeutic products need to be developed and registered in accordance with the relevant laws and regulations of drug management, through the State Drug Administration drug evaluation Center (hereinafter referred to as the drug evaluation center) technical review, and then approved by the State drug Administration after listing; The other is that cell therapy technologies that are not marketed for clinical research can be carried out by medical institutions as the responsible subjects, which need to follow the relevant regulations of the National Health Commission and its subordinate agencies.

In 2019, the State Medical Products Administration launched the Scientific Action Plan for Drug Regulation in China, and "Research on the Technical evaluation and regulatory system of Cell and gene therapy Products" as the first key task was included in the scope of the first batch of research projects. It fully reflects the State Drug Administration's emphasis on the development of strategic biomedical industries such as cell and gene therapy and its determination to establish a scientific regulatory system. Since 2020, the Center has closely responded to the demands of the industry, led the industry standards, and issued 31 guidelines related to cell and gene therapy products (including drafts for comment), accounting for more than 60% of the total number of its releases. From the guidelines issued by the Center, the focus is on quality, safety and efficacy, which relate to product quality, non-clinical and clinical studies, as well as post-marketing pharmacovigilance and risk management.

In 2015, the Administrative Measures for Stem Cell Clinical Research (Trial) was issued, which promoted exploratory research on cell therapy technology mainly in clinical institutions. In 2023, based on the model and experience of stem cell clinical research management, the Guidelines for Somatic Cell Clinical Research Work (Trial) will be released, which will strengthen the guidance for medical institutions to carry out somatic cell clinical research in a similar way to stem cell clinical research management, so as to promote the healthy development of somatic cell clinical research initiated by researchers in medical institutions.

With the improvement of scientific cognition and industrial policy support, China's cell therapy product supervision has basically formed a regulatory framework from research and development, registration, production and marketing, making China's cell therapy research and transformation of results continue to expand.

02 Foreign cell therapy product regulatory system

According to the project plan, this research group sorted out the regulatory system of cell therapy products in the United States, the European Union and Japan and other countries or regions, including relevant definitions, regulatory frameworks, regulatory systems, regulatory paths and marketing authorization procedures, sorted out the published technical guidelines, and compared them with China's regulatory system accordingly. This paper mainly introduces the research results related to the regulatory system and regulatory path.

Cell therapy or regenerative therapy technology or product is an emerging technology or therapy developed in recent years, which has both technical and pharmaceutical properties. There are still many unclear aspects in the global understanding of the clinical application of such technology or product, and there are also challenges and disputes in the development and regulation of technology or product. And the functions of health and drug regulatory systems are different in different countries or regions. Therefore, the regulation of cell therapy products has not yet formed a unified, coordinated and perfect regulatory system on a global scale. Countries or regions are exploring the establishment of a regulatory framework system suitable for their own countries or regions according to their own conditions, and there are different regulatory methods for cell therapy products.

Although the regulatory system functions of countries or regions are different, from the perspective of supervision and approval, cell therapy products and clinical applications are mainly divided into two paths: the first is regulated by drug regulatory authorities according to drugs, such as the United States and the European Union; The second is to adopt a "dual-track system", in which medical technology is regulated by the health department, and the clinical application is directly carried out in the hospital, while the marketed products are managed as pharmaceuticals, as in Japan. In general, for cell therapy products for marketing purposes, the prevailing international management model is to supervise them according to drugs.

2.1 The United States

For drugs, the United States uses a three-tier structure of laws, regulations and guidelines to form its regulatory system. The FDA regulates cell therapy products based on 21 CFR, which was updated in 2005. Added Part 1271 "Human Cells, Tissues, andCellular and Tissue-Based Products" (HCT/Ps); The regulatory level is regulated by FDA according to product risk categories in accordance with sections 361, 351, and 21 CFR 1271.10 of the Public Health Service Act (PHS). Low-risk products can follow the 361 path and only need to be registered with the FDA, without submitting a new drug clinical trial application (IND) and without premarket review approval. High-risk products are regulated as drugs or biological products under the 351 pathway of the U.S. Food, Drug, and Cosmetic Act and Section 351 of the PHS Act. These products are subject to clinical trials through an IND, submission of a biologics Marketing Authorization application (BLA) and premarket approval, as well as post-market regulation. In addition to HCT/Ps compliance, human cells, tissues, and cell and tissue based products must also comply with the relevant regulations for biologics and pharmaceuticals, such as 21 CFR Parts 600s, Part 312, and Parts 210 & 211. In order to regulate and guide the development of cell therapy products, the FDA has also issued a series of guidelines related to cell therapy.

Cell therapy products are regulated by the Office of Therapeutic Products (OTP) of the FDA's Center for Biologics Evaluation and Research (CBER). In response to the exponential growth of cell therapy products, in 2022 FDA established the Office of Organization and Advanced Therapeutics (OTAT), building on the organization and Office of Advanced Therapeutics (OTAT) established in 2016, and the OTP is composed of six offices responsible for 14 divisions and 33 branches. The OTP currently has 300 employees and plans to hire 100 more reviewers over the next five years [2-3].

2.2 European Union

The EU uses a three-tier regulatory system consisting of laws, regulations and guidelines. The European Union has set up the Committee on Advanced Therapies (CAT), which is responsible for the technical review of new technologies, new therapies and new products, and stipulates that advanced therapeutic products (ATMP) must carry out centralized review procedures. Considering the particularity of this kind of product, it is necessary to submit the product classification application before the formal listing review; Provide review comments on the submitted ATMP; These comments are submitted to the Committee for Medicinal Products for Human Use (CHMP), which makes a recommendation for marketing authorization; The European Commission (EC) then makes the final decision which is binding on all member States [4-5]. For unmet medical needs, patients are in urgent need of ATMP treatment, and can continue to benefit from ongoing clinical research, ATMP can be used without obtaining marketing authorization under the circumstances of meeting some conditions, that is, the so-called "hospital exemption" provisions. However, the European Medicines Agency (EMA) is very cautious about such products, stressing that it does not recommend a "hospital exemption" as the preferred route for ATMP to supply the market [6].

To support the development of ATMP, EMA offers a range of advisory services and incentives, providing formal support to developers through: scientific advice and programme assistance [7]; Rare disease drug identification [8]; Office of micro, small and medium-sized enterprises [9]; ATMP classification support [10]; Certification of quality and non-clinical data for micro, small and medium-sized enterprises [11] and a series of fee reduction measures.

2.3 Japan

Japan also uses a three-tier regulatory system consisting of laws, regulations and guidelines. In May 2013, Japan promulgated the Regenerative Medicine Promotion Law, which established the direction of safe and effective basic development of regenerative medicine [12]. Based on this law, the Law on Quality, Efficacy and Safety Assurance of Pharmaceuticals and Medical Devices and the Law on Safety of Regenerative Medicine were implemented in November 2014, and the regulatory system of regenerative medicine was reformed [13]. The Law on Quality, Efficacy and Safety Assurance of Pharmaceuticals and Medical Devices replaces the Law on Pharmaceutical Affairs, and establishes a special classification of regenerative medicine products on the basis of the original drug classification, determines the definition of "regenerative medicine products", and regulates the commercialization of regenerative medicine products, including the marketing application, production, circulation, use and post-marketing monitoring and other multi-link management. Clinical trials of regenerative medicine products for the purpose of marketing should be carried out in accordance with the relevant requirements of the Law on Quality, Efficacy and safety Assurance of Pharmaceuticals and medical Devices, etc., by the Cell and Tissue Product Approval Office under the Japanese Pharmaceutical and Medical Device General Agency (PMDA) is responsible for regulatory review, and the Ministry of Health, Labor and Welfare makes the final approval of marketing authorization. Clinical research on regenerative medicine that is not intended for listing is conducted in accordance with the requirements of the Regenerative Medicine Safety Law, and the Ministry of Health, Labor and Welfare is responsible for certification/filing supervision [13-17]. That is, Japan implements a "dual-track" regulatory model for regenerative medicine.

03 Enlightenment on constructing our country's supervisory system

Representative countries or regions such as the United States, the European Union and Japan have clarified the definition of cell therapy products from a legal perspective, and have continuously improved and improved them from the level of regulations and technical guidelines, establishing a three-level regulatory system of laws, regulations and guidelines, and systematically implementing hierarchical supervision from top to bottom. There is a relatively clear definition, classification and management process for a variety of advanced therapies, including cell therapy products, and a lot of regulatory resources have been invested in this field through the establishment of the organization and Advanced Therapy office, the establishment of the Advanced Therapy Committee, and the establishment of a special cell and tissue product approval office, providing strong regulatory support for cell therapy products. With the rapid development of the industry and technology, the regulatory agencies of these representative countries or regions have prospectively invested more regulatory resources to promote their own development, improve their regulatory capabilities, provide timely technical advice and suggestions for the industry, and further accelerate the transformation and utilization of new technologies and new research, thus promoting the healthy and rapid development of the industry. The different characteristics of its regulatory system and regulatory path have positive reference for China to improve the regulatory system of cell therapy.

3.1 Introduce national encouragement policies to promote the approval of new products and the introduction of new technologies

The National Development and Reform Commission released the "14th Five-Year Plan for Bioeconomy Development" in 2021, but there is no clear specific plan for the cell therapy industry. It is suggested that on the basis of the "14th Five-Year Plan" bioeconomy Development Plan, the specific path and implementation plan to promote the development of cell therapy industry should be formulated.

After decades of efforts, especially since 2017, the drug approval Center has issued more than 30 technical guidelines, and China has initially formed a technical support system for the whole life cycle from research and development, registration, production to the market, which has laid a certain foundation for the transformation of cell therapy research results and the healthy development of the industry in China. However, at the operational level, such innovative products still need to pass the review of relevant data and after determining their innovation and clinical value, they may be given priority for review and approval. It is suggested that the definition and interpretation of cell therapy products should be clearly defined in relevant laws and regulations, and innovative cell therapy products should be included in the priority review and approval process with reference to children's drugs and drugs for rare diseases.

Although China has made some progress in cell therapy technology, some key technologies in this field still need to apply international patent technology. It is suggested to formulate policies to encourage foreign investment in relevant fields and the introduction of related technologies, and appropriately adjust and revise the relevant provisions of "prohibiting investment in the development and application of human stem cells, genetic diagnosis and treatment technologies" in the "Special Administrative Measures for Foreign Investment Access (Negative List) (2021 edition)".

3.2 Allocate sufficient regulatory resources to optimize and upgrade the regulatory system

Different from traditional chemicals and macromolecular drugs, emerging cell therapy products involve a wide range of technologies, rapid iteration, complex production process, and high potential safety risks. For regulatory agencies in various countries, how to scientifically regulate cell therapy products and how to formulate and establish regulatory policies and systems that are constantly optimized and upgraded to match the rapid development of the industry is a subject that needs long-term exploration.

Under the combined force of multiple factors, the field of cell therapy in China has developed rapidly in recent years, and the drug approval center accepted more than 50 clinical applications in the first half of 2023 alone. In recent years, the drug testing Center has fully mobilized internal resources, actively discussed with applicants on the difficulties and key issues of research and development projects through various communication meetings, and provided technical guidance. However, at present, the evaluation resources of the Drug approval Center for cell therapy products are relatively scattered. The Department of Biological Products Medicine is responsible for biological products, vaccines and cell and gene therapy products at the same time; the Clinical Department of biological products is responsible for vaccines, blood products and cell and gene therapy products at the same time; and the Department of Pharmacology and Toxicology and the Department of Statistical and Clinical Pharmacology are responsible for all registration applications of the drug approval Center. The review and communication work is quite heavy. The situation at the verification Centre is similar. In this case, the current communication and exchange of cell therapy products and the review and verification need to follow the same procedures and time as other products. Therefore, it is a challenge to allocate the corresponding review resources according to the rapid technological progress, continuously optimize the review standards and systems of cell therapy products, further improve the regulatory efficiency in this field, and provide timely guidance to the industry. It is suggested that the national drug regulatory authorities should increase the allocation of regulatory resources for cell therapy products, or add additional human resources specifically for the supervision of cell therapy products, or on the basis of existing regulatory human resources, tilt existing resources towards cell therapy products through the optimization or adjustment of the structure of relevant regulatory departments, so as to further improve the efficiency and refinement of regulation. On the basis of optimizing the allocation of regulatory resources, it is proposed to manage the communication and exchange meetings related to cell therapy products in accordance with Class I meetings, and strengthen timely technical guidance to applicants, so as to meet the challenges that may be brought about by the explosive growth of China's cell therapy industry.

The research and development and production of cell therapy products involve the application of a large number of new technologies and new models, and the scientific cognition of related products is in the process of rapid accumulation. It is suggested that the national drug regulatory authorities should follow the principle of encouraging innovation and explore innovative regulatory models for cell therapy products, such as establishing a fault-tolerant and error-correcting mechanism and implementing scientific, inclusive and prudent supervision. To provide guarantee for the establishment of regulatory system and legal system in line with the scientific law of cell therapy product research and development.

The relevant guidelines put forward general requirements for the common problems of cell therapy products, but in the specific research and development practice, there will be individual issues that cannot be covered by the guidelines, and even the speed of technology development is faster than the speed of the guidelines. Therefore, in order to improve the efficiency of research and development, technical requirements need to be updated in a timely manner, and industry and regulatory authorities need to reach a timely consensus on major issues. It is suggested that the relevant regulatory departments should set up a special advisory committee of cell therapy products experts in accordance with the Management Measures for External Experts of the Drug Evaluation Center to attract top experts in pharmaceutical, non-clinical, translational medicine and clinical and other related fields at home and abroad to exchange and discuss new technologies, new processes and new research and development models involved in cell therapy products, and make decisions on major issues. Consult on major regulatory decisions.

On the basis of the increase and optimization of regulatory resources, it is recommended that the relevant regulatory departments open a column on the implementation of technical guidelines for cell therapy products on their official websites, and it is recommended that industry associations release relevant industry consensus to collect and solve problems encountered in the implementation of existing or new regulations and technical guidelines in this field.

For key quality control projects unique to cell therapy products with large investment in laboratory construction and high requirements for technical and personnel qualifications, it is recommended that relevant departments support qualified verification institutions or laboratories to establish or coordinate relevant resources to solve the internal control and testing problems unique to cell therapy products.

3.3 Do a good job in training, introducing and reserving regulatory and industrial talents in the field of cell therapy products

Both regulatory and industrial talents in the field of cell therapy products are in a state of shortage. It is recommended to formulate a strategy for the cultivation, introduction and reserve of regulatory and industrial talents in this field at the national level, encourage national or local drug regulatory authorities to establish a system for the cultivation, retention and evaluation of relevant talents, and incorporate relevant policies into government support plans.

3.4 Continue to optimize and improve the management of investigator-initiated clinical studies (Iits) to further promote the development of cell therapy products

The purpose of IIT research for cell therapy products is to quickly obtain clinical safety and efficacy data of drugs in the early stage of product development, complete the proof-of-concept of products, so as to understand product candidates faster, improve the efficiency of product trial and error iteration, and accelerate the development of cell therapy products. The "Management Measures for Stem Cell Clinical Research (Trial)" and "Guidelines for Somatic Cell Clinical Research (Trial)" have been successively issued, which has played a positive role in standardizing IIT research. It is suggested that the national health authorities should further strengthen the role of new technology and new materials, academic and ethical committees in medical institutions in the review of IIT research.

On June 21, 2023, the Drug Approval Center issued the Technical Guidelines for Clinical Trials of Human Stem Cells and their derived cell Therapeutic Products (Trial), which clearly defined the requirements for IIT research of stem cell products to be applied to drug registration review, and played a positive guiding role in promoting the transformation of stem cell clinical technology. It is recommended to introduce relevant applicable guidelines for somatic cell therapy products as soon as possible to clarify the technical requirements for transforming medical technology into products.

For those with the same target and the same mechanism of action, it is recommended that the national health authorities restrict the approval of IIT research of similar medical technologies or products to avoid confusion caused by different regulatory paths.

3.5 We will actively participate in the relevant work of the International Technical Coordination Committee for the Registration of Drugs for Human Use (ICH), and strengthen the power of our country in the formulation of international standards

In June 2023, ICH announced the formation of the Cell and Gene Therapy Discussion Group (CGTDG), tasked with developing a coordinated roadmap for the field. The international unification and coordination of cell therapy technical standards will help China's cell therapy industry avoid wasting human and material resources in research and development. If calculated according to the time of the first approval of the product, the gap between China's cell therapy products and the international community is only 4 years, which is at the same development stage with the international representative countries. Although the number of approved cell therapy products in China is lower than that of leading countries, and the product types and treatment areas are also more concentrated, the number of R&D pipelines has ranked among the first echelon with considerable potential. In 2018, the State Drug Administration was elected as a member of the ICH Management Committee. These advantages provide a rare opportunity for our country to strengthen the interaction with drug regulatory authorities all over the world, improve our country's discourse power in the formulation of international standards, promote the international coordination of standards, and ensure the predictability and efficiency of cell therapy product supervision.

04 Conclusion

Cell therapy is an innovative and disruptive therapeutic approach that is now in a rapid development stage. With the support of relevant policies, China's cell therapy industry has been developing rapidly since 2021, there are three new CAR-T drugs approved for listing, another three new CAR-T drugs have completed the listing application, and China's self-developed CAR-T products are listed in internationally representative countries. It shows that China's cell therapy industry has been realized and run on the international stage.

There are many challenges in the development and supervision of cell therapy products because of the variety of raw materials used in the production of cell therapy products, rapid technological iteration, complex production process, and large variability of starting raw materials, processes and quality. In order to enhance China's overall innovation ability and international influence in frontier fields, and realize the leap-forward of China's cell therapy industry from running to leading, it is necessary to learn from the regulatory concepts, new technologies and new methods of internationally representative countries or regions in a timely manner on the basis of China's existing regulatory system, actively promote the coordination of international standards, and constantly optimize China's cell therapy product regulatory system. Make the regulatory system, regulatory policy and the progress and breakthrough of innovative technology achieve the same frequency resonance.

First Author Profile

Wang Guangji Ph.D., Academician and Professor of Chinese Academy of Engineering, China Pharmaceutical University. Major directions: Innovative research on key technologies of preclinical pharmacokinetics of innovative drugs, research on the basis of substances acting in Chinese traditional medicine complex systems and integrated pharmacokinetics, integrated research on metabolomics and pharmacokinetics