汉坤 • 观点 | 重磅：《生物制品分段生产试点工作方案》要点评析（中英双语）

作者：汉坤律师事务所 顾泱 | 尤鹏飞 | 郑杜之韵 | 张玉臻 | 于逢祺 | 王乐怡 | 孙舒闻

Authors: Han Kun Law Offices Aaron Gu | Pengfei You | Duzhiyun Zheng | Matt Zhang | Franky Yu | Leyi Wang | Shuwen Sun

近日，国家药监局印发《生物制品分段生产试点工作方案》（“《试点方案》”），对试点开放生物制品分段生产的工作做了介绍。这是生物制品分段生产监管的突破，是业界期待已久的成果。这一突破预示着生物制品分段生产跨省、跨境生产的可能性，对于优化资源配置、降低生产成本、提高生产效率具有重要意义，并将推动我国生物医药产业融入全球市场，增强国际竞争力。本文将围绕《试点方案》提出的试点品种、试点企业要求、国际/跨境合作、监管强化等重点内容，分析其对行业的影响，供业界参考、讨论。

Recently, the National Medical Products Administration (the “NMPA”) issued the “Pilot Work Plan for Segmented Production of Biological Products” (the “Pilot Plan”), introducing the pilot initiative for the segmented production of biological products. This represents a breakthrough in the regulation of segmented production of biological products, a long-awaited achievement in the industry. This breakthrough suggests the possibility of cross-provincial and even cross-border production of biological products, which marks the significant progress in optimizing resource allocation, reducing production costs, and improving production efficiency, and will promote the integration of China’s biopharmaceutical industry into the global market, enhancing international competitiveness. This article will analyze the impact of the Pilot Plan including the types of pilot products, requirements for pilot enterprises, international/cross-border collaboration, and tightened regulatory requirement. In this article, we hope to share our insights from these aspects and provide a reference for the industry.

在本次《试点方案》印发之前，《药品管理法》并未完全禁止生物制品分段生产^[1]。在2022年发布的《药品管理法实施条例》的修订草案征求意见稿中，首次提出了对有特殊要求的创新或临床急需药品，经批准可以分段生产^[2]；2022年发布的《疫苗生产流通管理规定》也明确经国家药监局同意后疫苗原液或者制剂可分开委托生产^[3]。在实践层面，2021年以来，苏州、上海等地已经开始了相关实践和政策探索^[4]。这些先行探索为本次试点方案的出台积累了宝贵的经验。本次国家药监局发布的《试点方案》，是首次从国家层面推动生物制品分段生产工作。

Prior to the issuance of the Pilot Plan, China had not explicitly prohibited the exploration of the segmented production of biological products at the legislative level, thereby leaving flexibility to explore future practices in this area. As the primary legislation governing drug regulation, the Drug Administration Law did not specifically prohibit the segmented production of biological products. The draft amendment to the Regulations for Implementation of the Drug Administration Law, published in 2022, first proposed that innovative drugs or urgently needed drugs in clinical practice with special requirements could be approved for segmented production. In addition, the Regulations on the Production and Distribution Management of Vaccines, published in 2022, also clarified that, with the consent of the NMPA, the vaccine raw liquid (in Chinese: 原液) and formulation (in Chinese: 制剂) could be manufactured separately through contract manufacturing. In practice, since 2021, regions such as Suzhou and Shanghai have begun relevant practices and policy explorations. These preliminary explorations have accumulated valuable experience for the issuance of this Pilot Plan, which is the first official national-level initiative to promote the segmented production of biological products.

《试点方案》涵盖了几款市场上非常热门的生物制品^[5]，包括PD-1抑制剂、GLP-1激动剂产品、ADC产品等，目前细胞和基因治疗产品未明确包含在内，有待与监管部门的进一步澄清或沟通。《试点方案》同时规定，试点品种亦包括国家药监局规定的其他生物制品，这为细胞和基因治疗产品参加试点留有空间。此外，《试点方案》还遵循了“一品一策”的原则，即针对不同的产品制定不同的政策和管理措施，这说明《试点方案》在制定的过程中，考虑到了不同的生物制品的特点以及监管的特定需求，对于不同品种的分段生产管理措施，或呈现多样性的特点。

The Pilot Plan covers several popular biological products available in the market, including PD-1 inhibitors, GLP-1 agonists, and antibody-drug conjugate (ADC) products. As of now, cell and gene therapy (CGT) products are not explicitly included, pending further clarification and guidance from regulatory authorities. The Pilot Plan also stipulates that pilot products may include other biological products as specified by the NMPA, potentially allowing CGT products to fall within the scope of the pilot products. Additionally, the Pilot Plan adopts the principle of “Each Product has its Own Policy (in Chinese: 一品一策)”, i.e., distinct policies and measures will be developed for different biological products. It has shown that the establishment of Pilot Plan has taken into account the characteristics of different biological products and their specific regulatory needs, providing diverse measures for segmented production across different product types.

值得注意的是，近期发布的《关于在医疗领域开展扩大开放试点工作的通知》同样以试点的方式，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（关于此通知中规定的要点，请详见我们的解读文章：《外资限制终放开，中国干细胞与基因治疗（CGT）和基因诊断行业迎来新机遇》）。我们期待看到两项试点工作在未来的联合，在细胞和基因治疗方面，允许开展分段生产的试点工作，以降低生产成本，提高研发效率。

It is noteworthy that in the recently issued Notice on Carrying Out Pilot Programs to Expand Opening-Up in the Healthcare Sector, foreign-invested enterprises in such pilot initiative are also permitted to engage in the development and application of human stem cells, gene diagnostic and therapy technologies (For key takeaways of such notice, please refer to our article: China Pilots Lifting Restrictions on Foreign Investment in Stem Cell, Gene Therapy, and Genetic Diagnosis Sectors in Four Free Trade Zones). We look forward to the potential synergy between these two pilot initiatives in the future, which may facilitate segmented production of CGT products to reduce production costs and enhance R&D efficiency.

《试点方案》中，对试点企业的要求依然十分严格。首先，试点企业应以其自研品种^[6]进行申请。此处对于自研品种的解释仍待进一步澄清，如企业与其他方合作研发创新生物制品，或企业通过许可交易的方式引入生物制品并成为持有人，是否属于此处的“自主研发”，这将影响着《试点方案》在许可交易以及合作研发的产品中的适用性，须在后续的监管实践中保持关注。

In the Pilot Plan, the requirements for qualified pilot enterprises are stringent. Notably, pilot enterprises must apply with their originally-developed products. However, further clarification is needed regarding the definition of “originally-developed products”, particularly in cases involving collaborative R&D or licensed-in projects for innovative biological products. The interpretation of this requirement will significantly impact the Pilot Plan’s applicability to biological products in licensing and co-development projects, requiring close attention in future regulatory practices.

此外，受托生产企业应当执行与委托人统一的质量管理体系，且应当具有三年以上生物制品商业化生产经验。且须选派两名以上适格的技术人员驻厂确保标准统一、有效衔接。这相较于一般委托生产中仅要求对受托方质量管理体系进行现场审计、确保衔接的要求更进一步。体现了在生物制品分段生产中，对于企业间合作、协调能力以及质量管理有更高的要求。

Additionally, the entrusted manufacturing enterprises must implement a unified quality management system with the entrusting enterprises and must have at least three years of commercial production experience in biological products. The entrusting enterprises must designate at least two qualified technical personnel to be stationed on-site to ensure unified standards and seamless coordination. This requirement goes beyond conventional contract manufacturing requirements, which typically only mandate the entrusting enterprises to conduct on-site audits on the entrusted manufacturing enterprises’ quality management system. This tightened requirement reflects higher standards for inter-company collaboration, operational coordination, and quality management necessary in the segmented production of biological products.

《试点方案》支持生物制品跨省分段生产。对于委托生产双方位于不同省份的情况，《试点方案》提出要求，两地监管部门应共同研究制定监管方案。此外，新政下，进口药品的境外申请人/持有人也可以申请试点分段生产，这说明《试点方案》还将支持生物制品的跨境分段生产。在我国进口药品只能在境外生产的长期要求下，这无疑是一项重大利好。但未来可能出现更灵活的生产安排，例如进口药品的原液在中国境内生产，而制剂在境外完成，这也是《试点方案》中“一品一策”工作思路的体现。

The Pilot Plan supports cross-provincial segmented production of biological products. For cases where the contracting parties are located in different provinces, the Pilot Plan requires the regulatory authorities from both provinces to collaboratively develop and formulate regulatory plans. Furthermore, the Pilot Plan allows foreign applicants/holders of imported drugs to participate in the pilot program, signaling support for cross-border segmented production of biological products. This represents a significant breakthrough, particularly considering China’s historical requirement that imported drugs shall be produced overseas. Looking ahead, more flexible manufacturing arrangements may emerge, such as producing the raw liquid within China while completing formulation production abroad—an arrangement that exemplifies the “Each Product has its own Policy”, the regulatory approach outlined in the Pilot Plan.

《试点方案》下，试点企业和试点品种势必面临更严格的监管。省级药监局将对试点品种实施年度全覆盖检查和抽检，积极接受企业的委托检验。定期的GMP符合性检查和飞行检查也可能成为常态，以确保分段生产产品的质量。此外，跨省监管协调始终是一大挑战。不同省份协调经验和监管资源差异，可能影响跨省分段生产的监管有效性。随着试点工作深入，我们期待监管部门积累经验，建立成熟有效的跨省监管方案。

Under the Pilot Plan, pilot enterprises and pilot products are bound to face stricter regulation. Provincial Medical Products Administrations will implement annual comprehensive inspections and sampling inspections on pilot products, and will actively accept entrusted inspections from enterprises. Regular GMP compliance inspections and unannounced inspections are also likely to become a routine to ensure the quality of products in segmented production. Additionally, cross-provincial regulatory coordination has always been a major challenge. Differences in regulatory experience and resources among provinces may affect the effectiveness of supervision over cross-provincial segmented production. As the pilot work progresses, we anticipate that regulatory authorities will accumulate experience and establish effective cross-provincial regulatory plans.

就试点地区，包括国家战略提出探索新政的省级行政区域，以及具备产业基础、项目需求和强监管能力的省级行政区域。预计将包括今年3月提出推进生物制品分段生产试点政策的上海。我们也期待未来有更多地区执行试点。

The pilot regions include provincial administrative areas that according to the national strategy has been proposed to explore this new initiative, and those provincial administrative areas with real project needs, industrial foundations and strong regulatory capabilities. It is expected that this will include Shanghai, where the policy to promote pilot work on segmented production of biological products was proposed in March this year. We also look forward to more regions implementing Pilot Plan in the future.

关于试点时间，企业需在2025年12月31日前提交试点申请，试点工作将于2026年12月31日结束。我们期待经过两年试点的经验积累，能够为此后正式实施生物制品分段生产奠定基础。

As for the timeline, enterprises must submit pilot applications by December 31, 2025, and the pilot work will conclude by December 31, 2026. We hope that the experience accumulated over two years of pilot work will lay a foundation for the subsequent official implementation of segmented production of biological products.

生物制品分段生产新政对我国生物制药行业意义重大。新政的开展有望为行业带来重要机遇，包括优化生产分工、提高产业效率，以及加强区域和国际间的合作。但在实施过程中，如何在分段生产模式下确保产品质量、实现有效监管及协调跨区域乃至跨境监管合作等问题，仍需进一步探索。我们期待行业参与者和监管机构携手并进，共同完善这一政策的执行细节。通过稳步推进和经验积累，克服潜在的挑战，充分释放生物制品分段生产的政策活力，推动我国生物制药行业的高质量发展。

The Pilot Plan is of great significance for China’s biopharmaceutical industry. The implementation of this Pilot Plan is expected to bring important opportunities to the industry, including optimizing production division, improving industrial efficiency, and strengthening regional and international cooperation. However, during the implementation of the Pilot Plan, how to ensure product quality, achieve effective regulation, and coordinate cross-regional and cross-border regulatory cooperation under the segmented production model remains to be further explored. We believe that the industry participants and regulatory agencies may work together to refine the details of this Pilot Plan. Through steady advancement and experience accumulation, the regulatory authorities may overcome potential challenges, stimulate the vitality of the market participants and promote the high-quality development of China’s biopharmaceutical industry.