Shanghai Action Plan for Promoting Gene-Therapy-Related Scientific and Technological Innovation and Industrial Development (2023-2025)

Cell and gene therapy is an important "new track" for global technology and industry competition. This Action Plan is formulated in order to implement the "14th Five-Year" Plan of Shanghai Municipality for Building a Science and Technology Innovation Center with Global Influence, to further implement the Shanghai Action Plan for Promoting Cell-Therapy-Related Scientific and Technological Innovation and Industrial Development (2022-2024), to promote the coordinated development of gene therapy and cell therapy, and to accelerate the creation of a mechanism that brings forth a new surge of biomedical scientific and technological innovations and the creation of a cluster area for industrial development.

I. Guiding Ideology

Guided by Xi Jinping Thought on Socialism with Chinese Characteristics for a New Era, we shall thoroughly carry out the spirit of the 20th National Congress of the Communist Party of China based on the new development stage, completely, accurately and comprehensively implement the new development philosophy, build the new development paradigm, and promote high-quality development, always adhere to the "Four Aspects". In view of the characteristics of gene therapy, such as wide interdisciplinary scope, high technical development barriers, many clinical application challenges and great industrial development potential, we shall pay equal attention to R&D and transformation, and go hand in hand with innovation and service, make breakthroughs in key core technologies, improve clinical research and transformation capabilities, promote advancement in industrial processing technology, optimize industrial development ecology, and comprehensively improve the capability in breeding innovations and industrial development of Shanghai's gene therapy science and technology.

II. Basic Principles

- Adhering to pioneering innovation breeding and consolidating the strategic layout. We shall face the forefront of world science and technology, consolidate the forward-looking layout of basic research, and promote the innovation of basic theories and methods, so as to enhance the original innovation ability; we shall face the whole industrial chain, consolidate the layout of key core technologies, and strive to break through a number of underlying technologies, so as to provide support for the birth of a number of groundbreaking innovative products.

- Adhering to the development of the whole chain and strengthening the integration of the "four chains". We shall establish a full-chain resource allocation mechanism to promote the deep integration of innovation chain, industrial chain, capital chain and talent chain; we shall strengthen cooperation between industry, university, research and medical industry, dredge the two-way link between the basic research, applied research and industrialization, promote the transformation and industrialization of innovation achievements, and build a new pattern of gene-therapy-related scientific and technological innovation and industrial development.

- Adhering to industrial orientation and strengthening policy guarantee. We shall innovate a system and mechanism to promote the innovation breeding and industrial development; we shall improve the policy guarantee system to promote the organic combination of effective market and   effective government, accelerate the agglomeration of innovative elements such as talents, technology and capital, and create an excellent industrial development ecology.

III. Main Objectives

By 2025, Shanghai's capability in breeding innovation in gene-therapy-related science and technology shall be further enhanced, its clinical research and transformation and application capabilities shall be further enhanced, its innovation system shall be further improved, and its industrial ecology shall be further optimized. Shanghai shall be an important source of gene-therapy-related science and technology innovation and provide new impetus for the high-quality development of the industry.

- Capability in breeding innovation shall be continuously improved. More than 20 innovation bases and platforms (key laboratories, technology innovation centers, etc.) related to gene therapy shall be built and upgraded, and an independent and controllable gene therapy technology innovation system shall be basically formed; a number of innovations shall emerge, and a number of key core technologies with independent intellectual property rights shall be formed in the fields of gene editing and drug delivery.

- Capability in clinical transformation shall be continuously enhanced. More than five clinical medical research centers and demonstration research wards in gene therapy and related fields shall be constructed; research hospitals with gene therapy characteristics shall be attempted and constructed and; more than five new clinical trials shall be approved.

- Industrial vitality shall continuously escalate. Public service platforms such as research and development, preparation, testing, pilot test and production in gene therapy related fields shall be constructed and promoted; more than 15 leading and backbone enterprises in gene therapy industry shall be introduced and cultivated and; 1-2 innovative products shall be expected to apply for marketing.

IV. Major Tasks

1. Enhancing the Capability in Breeding Innovation

(1) Planning a Forward-looking Layout of Basic Research

Strengthen basic research in the fields of disease genetics and pathogenesis, gene editing, drug delivery, etc., explore new targets of gene therapy, explore new paths of gene expression and regulation, study new strategies of targeted delivery, develop new methods of gene therapy for complex polygenic diseases such as tumors, nervous system diseases and cardiovascular diseases, so as to consolidate the scientific foundation of drug innovation in gene therapy.

(2) Making Breakthroughs in Key Core Technology

Strengthen research on new tools for gene manipulation, such as nucleic acid sequence design and synthesis, gene editing, etc., and new carriers for drug delivery, promote the cross-integration of the cutting-edge technologies such as artificial intelligence and synthetic biology with the gene therapy-related technologies, break through core key technologies, and build an autonomous and controllable gene therapy technology innovation system, so as to support high-quality industrial development.

(3) Carrying out Independent Research and Development of Key Equipment and Materials

Strengthen the research of core equipment such as tangential flow filtration system, liposome high-pressure homogenizer and disposable bioreactor, key biomaterial and materials such as virus, nuclease and small guide ribonucleic acid, and key consumables such as serum-free culture medium and filter membrane, to promote the research and development of gene therapy and the independent control of production supply chain.

2. Enhancing the Capability in Clinical Research Transformation

(4) Strengthening the Capacity of Clinical Research

A number of clinical medical research centers in gene therapy and related fields shall be built in accordance with the international top standards, thus accelerating clinical research and transformation; characteristic research hospitals and demonstration research wards for gene therapy shall be constructed, thus promoting clinical trials and product development of gene therapy drugs; special disease cohorts for major diseases such as tumors, nervous system diseases and cardiovascular diseases shall be established, and an open sharing platform for the cohorts shall be built, thus promoting the development of gene therapy products and technical research and; medical institutions shall be encouraged to form some relevant regulations, to facilitate the standardization of clinical research.

(5) Encouraging Medical Institutions to Carry out Clinical Research

Encourage medical institutions in this Municipality to undertake clinical trials of new drugs by the enterprises in this Municipality and independently carry out the investigator-initiated trial (IIT) in accordance with relevant provisions in the field of gene therapy. Upon completion of relevant research work, funding shall be granted to medical institutions on a merit basis according to the standard of RMB 50,000 per person based on the number of people enrolled in the project, with the total amount of funding for each project not exceeding RMB 500,000 yuan, and the cumulative funding for each medical institution not exceeding RMB 5 million yuan per year.

(6) Optimizing Ethical Review and Human Genetic Resources Approval Services

Give full play to the role of the alliance of the municipal hospital ethics committees in studying and formulating working rules and standards such as rapid ethical review, and in establishing a mutual recognition mechanism for ethical review results of municipal hospitals;  give full play to the role of the Shanghai Medical Ethics Expert Committee and the Shanghai Clinical Research Ethics Committee, in organizing research, consultation, service and training on related ethics in the field of gene therapy, thus improving the ethical review ability of medical institutions. Give full play to the role of the Shanghai Pudong Human Genetic Resources Management Service Station, in strengthening the dissemination and implementation of the Detailed Rules for the Implementation of the Regulations on the Administration of Human Genetic Resources, to push gene therapy-related enterprises to strengthen the team construction of human genetic resources specialists, so as to improve service quality.

3. Enhancing the Capability in Public Service

(7) Strengthening the Construction of Systematic Scientific and Technological Innovation Bases

Build a Shanghai Frontier Biotechnology Research Institute, strengthen frontier biological basic research and technical research, and explore and practice new research paradigms such as artificial intelligence empowerment and Trial Ready Cohort (TRC); build and upgrade key laboratories, technology innovation centers, enterprise technology centers and other innovation bases in the field of gene therapy, so as to improve the capability in breeding innovation and the application level of achievements transformation in the fields of gene therapy.

(8) Strengthening the Construction of Professional "Incubators" and Innovation Platforms

Build and upgrade a number of high-quality professional "incubators" to incubate new technologies and enterprises; build smart process research and development platforms, automatic testing platforms, modular enlarged pilot scale platforms and other functional platforms, establish a service system of gene therapy and engineering functional platforms in related fields in line with the Good Manufacturing Practice (GMP), accelerate concept verification, product testing and pilot scale, shorten the R&D, clinical and production cycles, and further optimize the innovation and entrepreneurship ecology.

(9) Strengthening the Capacity in Building of Industrial Development Services

Encourage market players such as CRO/CDMO to build and optimize third-party service platforms such as drug carrier library screening, agent filling and product evaluation to serve the needs of gene therapy drug enterprises, and provide services such as virus database establishment and storage, preparation development and production, and quality evaluation of gene therapy products for relevant units to enhance industrial service capabilities.

4. Upgrading the Level of Industrial Development

(10) Strengthening the Spatial Layout of "1+1" Industries

With the Zhangjiang Cell and Gene Industrial Park in Pudong New Area as the core, build an international landmark of gene industry and create a gathering area for gene therapy technology innovation and industrial development; relying on the Pujiang Gene Future Valley in Minhang District and other parks, build a demonstration zone of the gene therapy industry chain integrating R&D, testing and manufacturing; combined with the needs of the gene therapy industry, strengthen the construction of public facilities and comprehensive service system in industrial bases.

(11) Optimizing the ecology of enterprise development

Guide the upstream and downstream industrial chain enterprises such as raw materials and reagents, delivery carriers, facilities and equipment, and research and development services to gather and develop, so as to create a comprehensive and convenient industrial chain supply system; establish the Industry-University-Research and investment alliance; accelerate the formulation of standards in key raw materials, production preparation, quality inspection, storage and transportation and other fields, and actively promote their use to improve the standardization of the industrial chain; promote the construction of the Shanghai Innovative Biological Products Quality Inspection and Testing Center to enhance the testing capacity of related products.

(12) Promoting the Internationalization of Enterprises

Under the premise of risk control, support qualified diversified investors to carry out research and development of human cell and gene technology and promote industrialization process in accordance with relevant laws, rules and regulations, and promote the coordinated development and deep integration of the industrial chain and the capital chain; support the international exchanges and cooperation, deeply integrate into the international advanced technology and supervision system, so as to improve the international development level of gene therapy enterprises.

V. Safeguard Measures

1. Establishing the 'Shanghai Gene Therapy Science and Technology Innovation Major Project'

While facing the frontier biotechnology fields such as gene therapy, organize and implement innovative projects, promote basic research, clinical transformation and product development, innovate scientific theories and methods, and form a number of key core technologies and innovative products with independent intellectual property rights.

2. Accelerating Product Evaluation and Application

Give full play to the role of the Yangtze River Delta Center for Medical Device Evaluation and Inspection of NMPA, guidance and service shall be positioned before and during the registration application of key gene therapy products in this Municipality; explore and establish a scientific research base for gene therapy supervision to provide support for improving the level of product supervision and; encourage real-world research and explore the application of real-world data to clinical evaluation of gene therapy drugs for rare diseases.

3. Strengthening the Protection and Application of Intellectual Property Rights

For international invention patents in the field of gene therapy that have been applied to foreign countries through the PCT channel and have been examined by the relevant patent examination institutions and authorized, fundings shall be provided according to 50% of the official expenses such as registration fees and examination fees, and such funding for each patent may not exceed RMB 20,000 yuan, and for each PCT international application to no more than five countries or regions; support key enterprises to apply for fast pre-examination service of Shanghai Intellectual Property Protection Center, so as to improve the quality of patent application and speed up the evaluation, and strengthen the ability of enterprises in intellectual property protection and risk prevention.

4. Strengthening Fiscal and Taxation Policy Support

For gene therapy products of which clinical trials have been conducted in China and marketing licenses obtained by registered enterprises in this Municipality and which are manufactured in this Municipality, financial support of up to 30 million yuan shall be provided, with the cumulative amount of support not exceeding 100 million yuan per year for each unit;  gene therapy products in this Municipality shall be introduced into the "List of Anti-Cancer Drugs and Rare Disease Drugs Subject to VAT Policy", so as to effectively guarantee the demand of patients for such drugs.

5. Improving Insurance Support Measures

Gene therapy innovative products shall be encouraged to enter the national health insurance drug catalog, and multiple and composite payment methods are expected; the inclusion of gene therapy drugs in rare diseases and other fields into the scope of the "Huhuibao Medical Insurance" and other people-oriented commercial medical insurance coverage shall be supported; multi-level commercial medical insurance shall be further explored, and new innovative payment modes such as installment payment and payment according to the efficacy of treatment shall be explored by enterprises, commercial insurers, and medical institutions in this Municipality and; the medical institutions and enterprises are encouraged to buy liability insurance related to human clinical trials, and a financial subsidy of 50% of premiums shall be granted to eligible entities, and the subsidy for a single policy may not exceed 500,000 yuan.

6. Strengthening the Financial Support

Make good use of government guidance funds, biomedical industry equity investment funds, etc., and guide social capital to jointly increase support for gene therapy enterprises in the initial stage and growth stage; for gene therapy enterprises that have successfully introduced equity financing of more than 50 million yuan (calculated by the actual amount in place), a government subsidy of up to 2% of the funding shall be granted according to the actual amount of equity financing, and the total shall not exceed 10 million yuan per year for each enterprise; encourage banks in Shanghai to launch more financial service products and support the application of "new drug loan" in gene therapy; deepen the "Pujiang Light Action" program and support gene therapy-related enterprises to be listed in the science and technology innovation board and other domestic and foreign capital markets; strengthen the listing service of financial institutions such as brokers for high-quality gene therapy enterprises and; promote outstanding gene therapy enterprises and other technology enterprises listed overseas to return to the science and technology innovation board of Shanghai Stock Exchange.

7. Strengthening the Introduction of Innovative Talents

Exert the brand influence of "Hai Ju Ying Cai" and introduce more high-end talents; implement the evaluation project of high-end technical talents in gene therapy industry, and recommend key units in the field of gene therapy to be included in the list of key institutions for talent introduction; increase the support of special projects such as the Morning Star Project, Academic/Technical Leaders Project and Industrial Elites Project for gene-therapy-related talents; pilot the training program of engineering master and doctor in the field of gene therapy, and explore the new mode of training engineering masters and doctors in enterprises; encourage enterprises and public institutions in the field of gene therapy to set up Post-Doctoral Research Centre or herein-stationed postdoctoral innovation internship bases, support postdoctoral students to apply for the Shanghai Super Post-doctor Project, and cultivate scientific research talents that meet the needs of industrial development; and strengthen personnel training and improve the construction of professional and technical personnel in enterprises relying on the relevant industrial platforms in the field of gene therapy.

8. Promoting the Facilitation of Customs Clearance for Research and Development Items and Special Goods

Promote the pilot import of research and development items in the field of gene therapy, and support related enterprises and research and development items to be included in the "white list"; promote the pilot work of the joint supervision mechanism for the entry and exit of special goods in the field of gene therapy, support key enterprises to apply for the pilot units of the joint supervision mechanism, optimize the approval process for key biomaterial and materials related to gene therapy research and development and production, and speed up customs clearance procedures.