干细胞、基因诊断与治疗外资限制放开，产业迎来发展新机遇

9月8日，商务部、国家卫生健康委、国家药监局共同发布了《关于在医疗领域开展扩大开放试点工作的通知》（下称“《通知》”），宣布自即日起在北京、上海、广东、海南四地的自由贸易区（港）试点，允许外商投资企业从事人体干细胞、基因诊断与治疗技术开发和技术应用。所有经过注册上市和批准生产的产品，可在全国范围使用。

涉及到的疗法和应用包括iPSC（诱导性多能干细胞）疗法、CAR-T(嵌合抗原受体T细胞）疗法、TCR-T（T细胞受体基因工程化T细胞）疗法、CAR-NK（嵌合抗原受体NK细胞）疗法、TILs（肿瘤浸润淋巴细胞）疗法、mRNA、基因测序和体外诊断（IVD）等。

背景

国家发改委和商务部发布的《外商投资产业指导目录（2007年修订）》首次将“人体干细胞、基因诊断与治疗技术开发和应用”列为禁止外商投资领域，此后的《外商投资准入负面清单》始终未作放宽。由于“禁止投资人体干细胞、基因诊断与治疗技术开发和应用”的内容过于宽泛，缺乏细化的定义和解释，一定程度影响了细胞与基因治疗行业发展。

此前，为应对负面清单对外国投资的监管和限制，有不少从事人体干细胞、基因诊断与治疗技术开发和应用的企业采用了VIE架构。《通知》实施后，外商独资企业（WFOE）或合资企业（Joint Venture）即可在试点地区从事相关研发和应用。相关国内企业可以根据具体需要调整架构，在取得境外投资、深化国际合作的同时，避免VIE架构带来的不确定性。

此前，多方不断呼吁在保障生物安全的前提下，适度放宽外商投资干细胞及基因诊断与治疗技术开发与应用的政策限制，一些地方政府也在探索政策试点。自2019年以来，上海、北京、深圳、天津等多地监管部门发布文件，鼓励外资企业在当地开展人体干细胞，或基因诊断与治疗技术的开发与应用试点。

近年来，全球范围内针对细胞与基因治疗企业的投资和融资出现下降。美元基金曾是国内生物医药行业的投资主力，但近两年由于种种原因，不少撤离了中国市场。试点开放后，松绑了国内细胞与基因治疗企业获得外资技术和资金的限制，国际合作将助推相关产业的快速发展。

展望

据悉，中国的人类遗传资源监管也正酝酿变革。2024年7月，国家卫健委公布了2024年部门规章立法工作计划，《人类遗传资源管理实施细则》的修订列入其中。虽然目前《外商投资准入负面清单（2024年版）》仍保留“禁止外商投资人体干细胞、基因诊断与治疗技术开发和应用”的规定，未来在试点地区积累经验后，很可能有望进一步放开限制。

由于细胞与基因诊断/治疗产品研发成本高昂，相关产品的定价相对较高，因此创新疗法的普及需要支付体系的创新，特别是商业健康险和支付模式的进一步发展。以CART-T产品为例，国内已获批上市的CAR-T免疫细胞药品，定价普遍超过100万元/支。未来上市的细胞和基因治疗产品，需要被更多商业健康险和普惠性医疗保险纳入，并探索新的付费模式，才能助力更多患者走上可及可愈之路。

On 7 September, the Ministry of Commerce (MOFCOM), National Health Commission (NHC), and National Medical Products Administration (NMPA) jointly issued the Notice on the Pilot Work of Expanding Openness in the Medical Industry ("Notice"). The Notice allows foreign-invested enterprises to immediately engage in the development and application of human stem cell and gene diagnostics and therapies in four pilot free trade zones in Beijing, Shanghai, Guangdong, and Hainan. Products registered and approved within these zones are permitted for use nationwide.

This includes therapies such as induced pluripotent stem cell (iPSC) therapy, Chimeric Antigen Receptor T-Cell (CAR-T) therapy, T-cell Receptor T-cell (TCR-T) therapy, Chimeric Antigen Receptor Engineered Natural Killer Cell (CAR-NK) therapy, Tumor-Infiltrating Lymphocytes (TILs) therapy, mRNA, gene sequencing, and In Vitro Diagnostics (IVD).

Background

The Catalogue of Industries Encouraging Foreign Investment (2007 Revision), issued by the National Development and Reform Commission (NDRC) and MOFCOM, initially categorised the "development and application of human stem cell and gene diagnostic and therapy technologies" as prohibited for foreign investment. The subsequent Special Management Measures for the Market Entry of Foreign Investment ("Negative List") maintained these restrictions. However, the vague terminology used in the prohibition has left industries uncertain about its scope, hindering the growth of China's cell and gene therapy (CGT) industry.

Previously, many enterprises involved in the development and application of cellular and gene diagnostics and therapies used Variable Interest Entity (VIE) structures to navigate the restrictions on foreign investment under the Negative List. With the release of the Notice, Wholly Foreign-Owned Enterprises (WFOEs) and Joint Ventures (JVs) can now engage in R&D and applications of CGTs within the pilot zones. This allows relevant enterprises to adjust their structures as needed to attract offshore investment and deepen international cooperation, while avoiding the uncertainties associated with VIE structures.

While policy restrictions on foreign investment in CGT R&D were implemented to safeguard China’s biosafety, industry stakeholders have continuously called for their relaxation. In response, since 2019, major cities like Shanghai, Beijing, Shenzhen, and Tianjin have issued documents encouraging foreign investment in CGT R&D.

In recent years, global financing for CGT companies has declined. Dollar funds, once the mainstay of investment in China's biomedical industry, have largely withdrawn from the market over the past two years. The Notice eases restrictions on domestic CGT companies' access to foreign-funded technology and capital, enabling international cooperation that is expected to drive the rapid growth of China’s CGT industry.

Outlook

Changes are also underway in China’s regulation of human genetic resources. In July, NHC included a revision of the Implementing Rules for the Management of Human Genetic Resources in its 2024 legislative agenda. Currently, the 2024 Edition of the Negative List still prohibits foreign investment in the biotechnology areas discussed earlier. However, as experience is gained in the pilot zones, restrictions are likely to be further relaxed.

Due to high R&D costs, CGT product prices remain high. For instance, CAR-T immune cell drugs in China typically exceed CNY 1 million per unit. Enhancing access to these innovative therapies requires further development of commercial health insurance (CHI) to include more CGT products in both CHI and Supplementary Medical Insurance, along with the exploration of new payment methods.