CGT领域外资准入开放试点——机遇与挑战并存

9月8日，国家发展改革委、商务部发布《外商投资准入特别管理措施（负面清单）（2024年版）》（“ 《外商投资准入负面清单》 ”），自2024年11月1日起施行。同日，商务部、国家卫生健康委和国家药监局联合发布了《关于在医疗领域开展扩大开放试点工作的通知》（“ 《医疗领域开放通知》 ”），允许外商投资企业在北上广三地自贸区和海南自贸港从事人体干细胞、基因诊断与治疗技术开发和技术应用。这一政策红利无疑为跨国药企带来了新的机遇，但同时也伴随着诸多挑战。基于我们为多家跨国公司在CGT准入、IIT、注册临床试验、产品生产、注册、海关等各环节提供了全方位的合规咨询，本文将聚焦跨国公司在投资细胞与基因治疗技术（CGT）过程中可能面临的风险，包括人类遗传资源管理、临床试验合规、知识产权保护和数据安全等方面的问题。此外，我们还将探讨原有VIE架构拆除过程中的复杂性，以及在开展研究者发起的临床试验（IIT）和产品注册时的关注点。

On September 8, the National Development and Reform Commission and the Ministry of Commerce issued the "Special Administrative Measures for Foreign Investment Access (Negative List) (2024 Edition)" (" Foreign Investment Access Negative List "), which will come into effect on November 1, 2024. On the same day, the Ministry of Commerce, the National Health Commission, and the National Medical Products Administration jointly issued the "Notice on Carrying Out Pilot Work for Expanding Opening-up in the Medical Field" (" CGT Opening Notice "), allowing foreign-invested enterprises to engage in human stem cell, gene diagnosis, and treatment technology development and application in the free trade zones of Beijing, Shanghai, Guangzhou, and Hainan Free Trade Port. While this policy dividend undoubtedly brings new opportunities for multinational pharmaceutical companies, it also comes with many challenges. Drawing on our extensive experience providing compliance consulting to multinational companies across aspects of CGT, from market entry and IITs to registered clinical trials, manufacturing, product registration, and customs clearance, this article will focus on the risks that multinational companies may face in investing in Cell and Gene Therapy (CGT) technology, including issues related to human genetic resource management, clinical trial compliance, intellectual property protection, and data security. In addition, we will explore the complexities of dismantling existing VIE structures, as well as key points to consider when conducting investigator-initiated trials (IIT) and product registration.

《医疗领域开放通知》拟在医疗领域开展如下两项扩大开放试点工作：

The “CGT Opening Notice” proposes to carry out the following two pilot projects to expand opening-up in the medical field:

（一）生物技术领域 （ Biotechnology Field）

自2024年9月7日起， 在北京自贸区、上海自贸区、广东自贸区和海南自由贸易港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，以用于产品注册上市和生产。所有经过注册上市和批准生产的产品，可在全国范围使用。

Starting from September 7, 2024, foreign-invested enterprises are allowed to engage in human stem cell, gene diagnosis, and treatment technology development and application for product registration, marketing, and production in the free trade zones of Beijing, Shanghai, Guangdong, and Hainan Free Trade Port. All registered, marketed, and approved products can be used nationwide.

（二）独资医院领域 （ Wholly Foreign-Owned Hospital Sector）

拟允许在北京、天津、上海、南京、苏州、福州、广州、深圳和海南全岛设立外商独资医院（中医类除外，不含并购公立医院）。

It is proposed to allow the establishment of wholly foreign-owned hospitals (excluding traditional Chinese medicine and the acquisition of public hospitals) in Beijing, Tianjin, Shanghai, Nanjing, Suzhou, Fuzhou, Guangzhou, Shenzhen, and the entire Hainan Island.

尽管中国政府放宽了外资在生物技术领域的准入限制，但跨国公司在中国开展人体干细胞、基因诊断与治疗技术的研发和应用时，仍需面对以下方面的挑战：

Although the Chinese government has relaxed restrictions on foreign investment in the biotechnology field, multinational companies still face the following challenges when conducting research, development and application of human stem cells, gene diagnosis, and treatment technologies in China:

1、人类遗传资源管理（Human Genetic Resource Management）

跨国公司在中国开展基因治疗临床试验时，可能会遇到人类遗传资源管理方面的挑战。特别在与中国合作方共享相关人类遗传资源，以及可能需要将部分样本送往海外研究中心进行分析的复杂场景下，如何确保符合《中华人民共和国人类遗传资源管理条例》的严格规定？公司需要建立完善的内部审核机制，确保每一步操作都符合中国的法规要求。此外，如何在保证研究进度的同时，及时获得相关部门对人类遗传资源出境的审批，也是一个需要慎重考虑的问题。

Multinational companies may encounter challenges in managing human genetic resources when conducting gene therapy clinical trials in China. Particularly in complex scenarios where relevant human genetic resources are shared with Chinese partners and some samples may need to be sent to overseas research centers for analysis, how can companies ensure compliance with the strict regulations of the "Regulations of the People's Republic of China on the Management of Human Genetic Resources"? Companies need to establish a comprehensive internal audit mechanism to ensure that every step of operation complies with Chinese regulations. At the same time, there is also an issue that needs to be carefully considered: how to obtain timely approval from relevant departments for the export of human genetic resources while ensuring research progress.

2、临床试验（Clinical Trials）

在开展CGT的国际多中心临床试验时，如何平衡中国与其他国家的监管要求差异是一个重大挑战。跨国公司可能会发现，按照FDA或EMA标准设计的CGT产品试验方案可能无法直接满足中国NMPA的要求。这不仅涉及试验设计，还包括细胞制备、基因编辑、质量控制以及长期随访等CGT特有环节的差异处理。例如，在细胞来源管理、基因编辑安全性评估、治疗效果的评估标准、长期不良反应监测机制等方面，中国可能有其特殊规定。如何确保所有参与试验的中国医疗机构严格遵守针对CGT产品的特殊GCP要求，同时保证跨国数据的一致性和可比性，是跨国公司需要深入考虑的问题。此外，由于CGT产品的独特性，如何在不同监管体系下统一定义产品特性和质量标准，也是一个需要谨慎应对的挑战。

Balancing the regulatory requirements of China and other countries is a major challenge when conducting international multi-center clinical trials for CGT. Multinational companies may find that CGT product trial protocols designed according to FDA or EMA standards may not directly meet the requirements of China's NMPA. This involves not only trial design but also differences in handling CGT-specific aspects such as cell preparation, gene editing, quality control, and long-term follow-up. For example, China may have special regulations on cell source management, gene editing safety assessment, treatment efficacy evaluation standards, and long-term adverse reaction monitoring mechanisms. How to ensure that all participating Chinese medical institutions strictly comply with the special GCP requirements for CGT products while ensuring the consistency and comparability of transnational data is an issue that multinational companies need to consider deeply. In addition, due to the uniqueness of CGT products, how to uniformly define product characteristics and quality standards under different regulatory systems is also a challenge that needs to be carefully addressed.

3、知识产权保护（Intellectual Property Protection）

在中国开展CGT的研发时，知识产权保护面临着独特的挑战。跨国公司在与中国研究机构或企业合作开发CGT新技术时，如何清晰界定基因编辑工具、细胞处理方法、载体设计等关键技术的知识产权归属和使用权限？在技术交流过程中，如何平衡信息共享和核心CGT技术保护，特别是涉及基因序列、细胞培养配方等敏感信息时？此外，由于CGT领域技术迭代快速，中国的专利申请流程和时间要求可能影响技术保护的及时性，公司需要制定适应中国环境的CGT专利策略，以确保关键的基因编辑、细胞治疗方法等发明能够及时在中国获得保护。同时，鉴于CGT领域专利界定的复杂性，在面对潜在的知识产权侵权行为时，如何在中国的法律框架下有效维护CGT相关专利权也是一个重要考量。特别是对于涉及人类胚胎基因编辑等敏感技术领域，如何在道德伦理和知识产权保护之间找到平衡，更是跨国公司需要审慎考虑的问题。

Intellectual property protection faces unique challenges when conducting CGT research and development in China. How can multinational companies clearly define the ownership and usage rights of key technologies such as gene editing tools, cell processing methods, and vector designs when cooperating with Chinese research institutions or companies to develop new CGT technologies? How to balance information sharing and core CGT technology protection during technical exchanges, especially when involving sensitive information such as gene sequences and cell culture formulas? Moreover, due to the rapid iteration of technology in the CGT field, China's patent application process and time requirements may affect the timeliness of technology protection. Companies need to formulate CGT patent strategies adapted to the Chinese environment to ensure that key inventions in gene editing and cell therapy methods can be protected in China in a timely manner. At the same time, given the complexity of patent definition in the CGT field, how to effectively protect CGT-related patent rights under the Chinese legal framework when facing potential intellectual property infringement is also an important consideration. Especially for sensitive technological areas such as human embryo gene editing, how to find a balance between ethical considerations and intellectual property protection is an issue that multinational companies need to consider carefully.

4、数据安全和个人信息保护（Data Security and Personal Information Protection）

CGT研究和治疗过程中涉及的人体基因组数据、细胞信息等属于敏感个人信息，其管理必须严格遵守《数据安全法》和《个人信息保护法》的要求。跨国公司如何在确保患者隐私的同时，有效利用这些数据进行跨国研究和产品开发？中国法律对人类遗传资源信息的管理有特殊规定，跨国公司如何在保证全球CGT数据分析能力的同时，满足中国的数据本地化要求？此外，在进行CGT相关的跨境数据传输时，如何完成必要的安全评估和备案程序，特别是涉及基因编辑、干细胞治疗等前沿领域的数据？当发生涉及CGT数据的安全事件时，如何按照中国的法规要求及时报告和处理，同时最大限度地保护患者的遗传隐私？这些都是CGT领域的跨国公司需要提前考虑和准备的重要问题。

Human genome data and cell information involved in CGT research and treatment processes are considered sensitive personal information, and their management must strictly comply with the requirements of the "Data Security Law" and the "Personal Information Protection Law". How can multinational companies effectively utilize this data for transnational research and product development while ensuring patient privacy? Chinese law has special provisions for the management of human genetic resource information. How can multinational companies meet China's data localization requirements while ensuring global CGT data analysis capabilities? Furthermore, how to complete the necessary security assessments and filing procedures when conducting cross-border data transfers related to CGT, especially data involving cutting-edge fields such as gene editing and stem cell therapy? When CGT data security incidents occur, how to report and handle them in a timely manner according to Chinese regulatory requirements while maximizing the protection of patients' genetic privacy? These are important issues that multinational companies in the CGT field need to consider and prepare for in advance.

CGT行业的外商投资准入限制放宽，为原本通过VIE架构运营的企业提供了直接进入中国市场的机会。然而，VIE架构的拆除并非易事，企业需要关注以下几个关键方面：

The relaxation of foreign investment access restrictions in the CGT industry provides opportunities for companies originally operating through VIE structures to directly enter the Chinese market. However, dismantling VIE structures is not easy, and companies need to pay attention to the following key aspects:

首先，资产重组的复杂性不容忽视。企业需要制定周密的重组方案，确保原VIE架构下的资产和业务能够平稳过渡。其次，税务影响需要全面评估，包括可能产生的税务成本和潜在风险，并据此制定相应的税务筹划策略。

First, the complexity of asset restructuring cannot be ignored. Companies need to formulate meticulous restructuring plans to ensure a smooth transition of assets and businesses under the original VIE structure. Second, the tax impact needs to be comprehensively assessed, including potential tax costs and risks, and corresponding tax planning strategies should be formulated accordingly.

监管审批是另一个关键挑战。企业应提前与相关部门沟通，了解审批要求和流程，为顺利获得架构调整的批准做好准备。同时，在这个过程中，平衡各方股东（特别是境内外股东）的利益至关重要，需要通过充分沟通来寻求共识。此外，企业还需要关注合规风险、融资影响、人员和业务过渡，以及知识产权保护等问题。考虑到CGT行业的特殊性，确保合规经营、维护核心技术优势尤为重要。

Regulatory approval is another key challenge. Companies should communicate with relevant departments in advance to understand approval requirements and processes, and prepare for obtaining approval for structural adjustments. At the same time, balancing the interests of various shareholders (especially domestic and foreign shareholders) is crucial in this process and requires thorough communication to seek consensus. In addition, companies need to pay attention to compliance risks, financing impacts, personnel and business transitions, and intellectual property protection issues. Given the special nature of the CGT industry, ensuring compliant operations and maintaining core technological advantages are particularly important.

为应对这些挑战，CGT企业在拆除VIE架构时应采取全面的策略：制定详细的重组方案，聘请专业顾问，与监管机构保持良好沟通，做好风险评估和管理。

To address these challenges, CGT companies should adopt comprehensive strategies when dismantling VIE structures: formulate detailed restructuring plans, engage professional advisors, maintain good communication with regulatory authorities, and conduct thorough risk assessments and management.

《医疗领域开放通知》允许外商投资企业以“用于产品注册上市和生产”为目的从事人体干细胞、基因诊断与治疗技术开发和技术应用，对于仅提供资金支持研究者发起CGT临床试验（IIT）的外资企业而言，仍需谨慎应对潜在的合规挑战。外资企业需要重点关注如何界定其资助行为，在资助协议中明确界定各方责任和权限。同时，企业还需要建立有效的机制，确保被资助的研究项目严格遵守中国的人类遗传资源管理、个人信息保护和数据安全法规。

The "CGT Opening Notice" allows foreign-invested enterprises to engage in human stem cell, gene diagnosis, and treatment technology development and application for the purpose of "product registration, marketing, and production". For foreign companies that only provide financial support for investigator-initiated CGT clinical trials (IIT), they still need to carefully address potential compliance challenges. Foreign companies need to focus on how to define their funding activities and clearly delineate responsibilities and authorities in funding agreements. At the same time, companies need to establish effective mechanisms to ensure that funded research projects strictly comply with Chinese regulations on human genetic resource management, personal information protection, and data security.

另一个关键问题是如何在提供资金支持的同时，避免对研究的独立性产生不当影响。这涉及到利益冲突的管理，特别是在研究结果发布和潜在知识产权分配方面。外资企业需要在资助协议中明确规定相关限制，确保研究的客观性和科学性不受资金来源的影响。

Another key issue is how to avoid improperly influencing the independence of research while providing financial support. This involves managing conflicts of interest, especially in terms of publishing research results and potential intellectual property allocation. Foreign companies need to clearly stipulate relevant restrictions in funding agreements to ensure that the objectivity and scientific nature of the research are not affected by the source of funding.

此外，考虑到CGT研究的敏感性，外资企业还需要特别关注如何在不直接参与研究的情况下，确保研究者获得受试者的有效知情同意，尤其是涉及基因编辑、干细胞治疗等前沿技术时。

Furthermore, considering the sensitivity of CGT research, foreign companies need to pay special attention to ensuring that researchers obtain effective informed consent from subjects, especially when involving cutting-edge technologies such as gene editing and stem cell therapy, without directly participating in the research.

为有效应对这些挑战，外资企业应当建立专门的合规审查机制，制定详细的资助指南，并与中国监管部门保持良好沟通。定期的合规培训和审核也是必不可少的，以确保企业员工充分理解中国特殊的监管环境，并能够及时调整资助策略以适应政策变化。

To effectively address these challenges, foreign companies should establish dedicated compliance review mechanisms, develop detailed funding guidelines, and maintain good communication with Chinese regulatory authorities. Regular compliance training and audits are also essential to ensure that company employees fully understand China's special regulatory environment and can adjust funding strategies in a timely manner to adapt to policy changes.

在政策开放带来的利好背景下，CGT产品的注册过程仍面临着一系列独特的挑战。首先，政策开放虽然为外资企业进入中国CGT市场提供了可能，但产品注册分类的问题仍然存在。现有的注册分类体系可能难以准确定位一些创新性产品，这就要求监管机构在开放政策的同时，考虑建立更加灵活和包容的分类标准。其次，在审评过程中，CGT产品的复杂性可能导致审评周期延长。虽然政策开放为更多企业带来了机会，但如何在保证审评质量的同时提高效率，避免创新产品因审评延迟而失去市场机会，是值得认真考虑的问题。此外，开放政策可能带来更多国际多中心临床试验的机会，但同时需要考虑如何设计既符合国际标准又满足中国特殊要求的试验方案，以及如何处理跨文化背景下的伦理问题。

Against the backdrop of favorable policy openings, the registration process for CGT products still faces a series of unique challenges. Firstly, although policy openings provide opportunities for foreign companies to enter the Chinese CGT market, product registration classification issues still exist. The existing registration classification system may have difficulty accurately positioning some innovative products, which requires regulatory authorities to consider establishing more flexible and inclusive classification standards while opening up policies. Secondly, in the review process, the complexity of CGT products may lead to extended review cycles. Although policy openings bring opportunities for more companies, how to improve efficiency while ensuring review quality and avoid innovative products losing market opportunities due to review delays is a question worth serious consideration. In addition, open policies may bring more opportunities for international multi-center clinical trials, but how to design trial protocols that meet both international standards and China's special requirements, and how to handle ethical issues in cross-cultural contexts?

面对这些挑战，企业需要积极与监管机构沟通，深入理解中国市场的特殊需求，并在产品开发过程中充分考虑这些因素。同时，建议监管机构也继续完善相关政策，在鼓励创新的同时，确保CGT产品的安全性和有效性。

Facing these challenges, companies need to actively communicate with regulatory authorities, deeply understand the special needs of the Chinese market, and fully consider these factors in the product development process. At the same time, it is recommended that regulatory authorities continue to improve relevant policies to ensure the safety and effectiveness of CGT products while encouraging innovation.

基于我们以往为CGT行业提供的业务合规、公司架构、临床及注册、知识产权保护等方面的服务经验，建议CGT企业尽快寻求高质量法律服务以应对合规挑战。我们坚信，通过政府、企业、律师等专业组织的共同努力，这些挑战最终将转化为推动行业进步的动力，为中国CGT产业的发展铺平道路。

Based on our past experience providing services in areas such as business compliance, corporate structuring, clinical and regulatory matters, and intellectual property protection for the CGT industry, we recommend that CGT companies seek high-quality legal services promptly to address compliance challenges. We firmly believe that through the combined efforts of the government, enterprises, and professional organizations like law firms, these challenges will ultimately become drivers of progress, paving the way for the development of China's CGT industry.