2024年11月13日，国家药品监督管理局印发《境外药品上市许可持有人指定境内责任人管理暂行规定》（以下简称" 《境内责任人新规》"）。该新规将于2025年7月1日正式生效，引起了业界广泛关注。《境内责任人新规》的出台是我国药品上市许可持有人（MAH）制度（以下简称" MAH制度"）建设取得的关键性进展。新规将进一步落实进口药品的MAH与境内责任人责任，保障公众用药安全。对此，本文将从实践角度出发，围绕《境内责任人新规》的核心要点进行分析，供行业参考、交流。
On November 13, 2024, the National Medical Products Administration (the "NMPA") issued the Interim Provisions on the Management of Domestic Responsible Entity Designated by Overseas Marketing Authorization Holders (hereinafter referred to as the "Regulations on Domestic Responsible Entities"). This regulation will officially take effect on July 1, 2025 and has garnered significant attention from the industry. The introduction of the Regulations on Domestic Responsible Entities represents a major milestone in the evolution of China's Marketing Authorization Holder (MAH) regulations. The new regulation aims to clarify and reinforce the responsibilities of MAH and domestic responsible entities for imported drugs, thereby enhancing the safety of public medication use. In this article, we analyze several key points of the Regulations on Domestic Responsible Entities from a practical perspective, with the aim of offering valuable insights and encouraging discussion within the industry.
一、要点解读
Interpretation of key points
（一）境内责任人与境内代理人
Domestic Responsible Entities vs. Domestic Agents
此前，我国监管法规主要将境外持有人指定的在中国境内履行持有人义务的企业法人称为"境内代理人" 1。本次，《境内责任人新规》进行了概念更新，将"境内代理人"的角色称谓更新为"境内责任人"。2024年11月发布的《医药代表管理办法（征求意见稿）》同样规定由进口药品MAH指定的"境内责任人"履行MAH义务。这一身份称谓的变化，不仅标志着境内主体责任的强化，也体现了监管理念和要求的革新。
Previously, the entity designated by overseas MAH to fulfill MAH's obligations in China is referred to as the "domestic agent" in China's regulatory regulation. This time, the Regulation on Domestic Responsible Entities has updated the concept of "domestic agent" to "domestic responsible entities". Similarly, the Draft Measures for the Administration of Pharmaceutical Representatives issued in November 2024 specifies that the "domestic responsible entity" designated by the MAH for imported drugs is responsible for fulfilling MAH obligations. The change in terminology not only underscores the responsibilities of domestic entities but also reflects innovative developments in regulatory concepts and requirements.
值得提示的是，境内责任人仍需遵循监管框架下对境内代理人的监管要求，包括需要根据《药品召回管理办法》实施药品召回，以及根据《医药代表备案管理办法（试行）》对医药代表的备案和管理负责等。
It is worth noting that domestic responsible entities must still adhere to the regulatory requirements previously applicable to domestic agents. These responsibilities include implementing drug recalls in accordance with the Drug Recall Management Measures and overseeing the filing and management of pharmaceutical representatives under the Provisional Measures for the Filing of Pharmaceutical Representatives.
（二）境内责任人的指定阶段
Designation for Domestic Responsible Entities
境内责任人和注册代理是两个不同的角色。《境内责任人新规》规定，境外MAH应在药品首次进口销售前指定境内责任人，且目前没有明确规定要求在药品临床试验或注册申请阶段就指定境内责任人 2。而注册代理则是在药品注册申请阶段，受MAH委托，负责处理与药品注册相关事务的中国境内企业法人 3。因此，境内责任人和注册代理是不同角色，各自承担不同主体职责。
The roles of domestic responsible entities and registration agents are distinct. According to the Regulations on Domestic Responsible Entities, overseas MAHs are required to designate a domestic responsible entity before the initial importation and sale of the drug. However, there is currently no explicit requirement to designate a domestic responsible entity during the clinical trial or registration application stages. In contrast, a registration agent is a domestic legal entity authorized by the MAH during the drug registration application phase to handle matters related to drug registration. Thus, domestic responsible entities and registration agents serve separate functions, each with its own set of responsibilities.
此外，在实际操作中，境内责任人和注册代理通常可以由不同主体担任。例如，根据我们的项目经验，如果境外企业对通过国内合作方递交注册资料存在保密性顾虑，则可以由经销商等合作方担任境内责任人，而将注册代理的职责委托给CRO或其他专业机构，并由律所提供合规支持。这种灵活安排不仅有助于满足企业的保密性需求，还能帮助企业更好地应对复杂的市场环境及日益严格的监管要求。
In practice, domestic responsible entities and registration agents can be different entities. For instance, based on our project experiences, if an overseas company has confidentiality concerns about submitting registration materials through a domestic partner, the domestic responsible entity role can be assigned to a distributor or other partner, while registration agent responsibilities can be entrusted to a CRO or other specialized service provider, with assistance from lawyers. This flexible arrangement not only helps safeguard confidentiality but also enables companies to navigate complex market dynamics and increasingly stringent regulatory requirements more effectively.
（三）药品说明书的编写：境内责任人与境内联系人
Drug Insert Sheet: Domestic Responsible Entities and Domestic Contact Entities
根据《境内责任人新规》的要求，境内责任人的名称、地址和联系方式应当在药品说明书中明确列出 4。与此同时，按照现行《化学药品及生物制品说明书通用格式和撰写指南》的规定，境外生产的药品还需在说明书中列明境外MAH指定的中国 境内联系人的相关信息，包括其名称、注册地址、邮政编码、电话和传真号码等。
In accordance with the requirements of the Regulations on Domestic Responsible Entities, the name, address, and contact information of the domestic responsible entities must be clearly listed in the drug insert sheet. Additionally, under the current General Format and Writing Guidelines for Drug Insert Sheet of Chemical Drugs and Biological Products, imported drugs must also include in their drug insert sheet the relevant information of the domestic contact entities in China designated by the overseas MAHs. Such information should include the name, registered address, postal code, telephone number, fax number, and other details.
鉴于《境内责任人新规》即将生效，而《化学药品及生物制品说明书通用格式和撰写指南》现行有效，境内责任人与境内联系人之间的关系尚未明确。是否需要在药品说明书中同时列出二者的信息，以及它们各自的具体职责，仍有待后续细则进一步明确。而这些问题也将对药品说明书的编写构成新的挑战，并同时对企业合规和信息披露提出更高要求。
The Regulations on Domestic Responsible Entities are set to take effect, and the current General Format and Writing Guidelines for Drug Insert Sheet of Chemical Drugs and Biological Products remains in force. Therefore, the relationship between the domestic responsible entity and the domestic contact entity has yet to be clarified. It remains uncertain whether the information of both entities will need to be listed in the drug insert sheet, along with their respective responsibilities, which are likely to be further clarified in subsequent regulations. Moreover, these uncertainties will also present new challenges for the drafting of drug insert sheets and impose higher requirements on corporate compliance and information disclosure.
（四）境内责任人的选定与条件
Selection and Requirements for Domestic Responsible Entities
《境内责任人新规》明确了境内责任人的资质要求，规定境外MAH在指定境内责任人时需要充分考量相关主体的质量管理体系、人员配置、场所条件以及是否具有履行相关共同义务的能力等，强调境内责任人的资质条件要高度对标境外MAH的资质条件，然而上述条件的具体判断标准和要求仍有待进一步探索。例如，劳动关系在集团内其他主体的员工为境内责任人开展工作是否能够满足"有专门人员独立负责药品质量管理活动"这一条件，有待监管规则的细化、明确。由于《境内责任人新规》第十七条明确了地方药监部门可以进一步制定实施细则，建议境外MAH密切关注境内责任人所在地的省级药监部门相关实施细则的出台，以适时做出应对、调整措施。
The Regulations on Domestic Responsible Entities specifies the requirements for domestic responsible entities, mandating that overseas MAHs carefully consider relevant entities' quality management systems, personnels, facilities, and capabilities to fulfill relevant joint obligations when designating domestic responsible entities. The Regulations on Domestic Responsible Entities also emphasizes the requirements of the domestic responsible entities should closely align with those of overseas MAHs. However, the specific criteria and qualifications for these requirements still need further clarification. For instance, it remains unclear whether employees with labor relations in other entities within the same group as the domestic responsible entities can meet the requirement of "having dedicated personnel solely responsible for drug quality management". Considering the Article 17 of the Regulations on Domestic Responsible Entities authorizes local drug regulatory authorities to issue further implementation rules, it is recommended that overseas MAHs closely monitor the issuance of the rules by the provincial drug regulatory authorities where the domestic responsible entities are located, in order to make timely adjustments and responses.
我们特别提示，境外MAH在选择境内责任人时需要谨慎评估，以确保其指定的境内责任人能够满足《境内责任人新规》及相关法律法规的要求。同时，境内企业在接受境外MAH指定时也需谨慎考虑其现有条件和能力，以确保双方在履行共同义务时能够有效配合，避免潜在的法律风险。
We particularly advise that overseas MAHs carefully evaluate their selection of domestic responsible entities to comply with the Regulations on Domestic Responsible Entities and relevant laws and regulations. Similarly, domestic responsible entities should thoroughly assess their existing conditions and capabilities, ensuring that both parties can effectively cooperate in fulfilling joint obligations and avoid potential legal risks.
（五）境外MAH的授权工作与责任分配
Authorization and Responsibility Allocation for Overseas MAHs
我们建议境外MAH在《境内责任人新规》正式实施前，尽早选择符合《境内责任人新规》要求的境内责任人，并提前准备并公证授权责任清单。据我们了解，部分跨国药企已开始在实践中自行制定相关文件，企业可密切关注后续细则的出台或官方提供的文件模板。与此同时，境外MAH应尽快完成境内责任人的授权及系统报告工作，并及时修订说明书，以免在过渡期结束后，因说明书不符合要求而受到处罚。如果在2025年4月30日（药品年度报告截止时间 [5]）前，境外MAH仍未完成境内责任人报告事项，则仍可按照原渠道继续填报上一年度报告信息。此外，考虑到境外MAH需与境内责任人承担连带责任，我们建议境外MAH通过内部协议明确双方的职责分工和责任分配。
We recommend that overseas MAHs select entities that meet the requirements of the Regulations on Domestic Responsible Entities before its official implementation and prepare and notarize the authorization responsibility list in advance. Based on our observation, many multinational pharmaceutical companies have already begun drafting authorization responsibility list. It is also advisable to closely monitor the issuance of detailed regulations or official document templates. Meanwhile, overseas MAHs should promptly complete the authorization and system reporting for the domestic responsible entities and timely revise the drug insert sheets to avoid penalties resulting from non-compliance once the transition period ends. If overseas MAHs have not completed the system reporting for the domestic responsible entities by April 30, 2025 (the deadline for the annual drug reporting), they may still submit information for the previous year through the original channels. Furthermore, considering that overseas MAHs and domestic responsible entities bear joint liability, we recommend that overseas MAHs clearly define responsibilities and distribute obligations through internal agreements.
同时，我们特别提示，未来MAH和境内责任人之间的责任如何区分认定，以及公证的责任清单和内部协议能否在监管执法时有效作为切断风险的防火墙，仍需进一步观察。但总体而言，责任分配越清晰，越有助于监管部门在执法过程中准确区分责任，并有效降低潜在的法律风险。
At the same time, we would like to emphasize that the differentiation and determination of responsibilities between the MAH and the domestic responsible entity is still an area that requires careful observation. Specifically, it remains to be seen whether authorization responsibility list and internal agreements can effectively serve as "firewall" to mitigate risks during regulatory enforcement. However, overall, the clearer the allocation of responsibilities, the better it will assist regulatory authorities in accurately distinguishing responsibilities during enforcement and reducing ambiguity.
二、结语
Conclusion
《境内责任人新规》的出台标志着中国医药监管在规范化进程中迈出了重要一步，然而，相关要求的具体标准仍有待行业和监管机构共同探索和逐步落实。与此同时，随着全球医药市场的不断开放，中国医药行业将面临着前所未有的发展机遇，不仅可以推动创新药品"走出去"，亦能够吸引创新药品"走进来"，并进一步引进国际先进技术和资源，为国内医药市场注入新的活力。未来，我们期待看到一个更加规范、开放且充满活力的中国医药市场，并在《境内责任人新规》等日益完善的监管框架下，为国内外患者提供更高质量的医疗产品和服务。
The issuance of the Regulations on Domestic Responsible Entities marks a significant step in the normalization of China's pharmaceutical regulatory framework. However, the specific standards for the relevant requirements are still being explored and will be gradually implemented by medical industry and regulatory authorities. As the global pharmaceutical market continues to open, China's pharmaceutical industry is poised to encounter unprecedented development opportunities. This will not only promote the export and import of innovative drugs, but also facilitate the introduction of advanced international technologies and resources, injecting new energy into the domestic pharmaceutical market. In the future, we anticipate that a more regulated, open, and dynamic Chinese pharmaceutical market, supported by an increasingly refined regulatory framework, and as exemplified by the Regulations on Domestic Responsible Entities, will be able to provide higher quality medical products and services to both domestic and overseas patients.
Footnotes
1. 药品召回管理办法》第二十条、《医药代表备案管理办法（试行）》第四条、《境外药品上市许可持有人境内代理人管理暂行规定（征求意见稿）》第二条、《中华人民共和国药品管理法实施条例（修订草案征求意见稿）》第四十四条。
1. The Article 20 of theDrug Recall Management Measures, the Article 4 of the Provisional Measures for the Filing of Pharmaceutical Representatives, the Article 2 of the Draft Interim Provisions on the Management of Domestic Agents for Overseas Marketing Authorization Holders, and the Article 44 of the Draft for Comments on the Implementing Regulations of the Drug Administration Law of the People's Republic of China.
2. 《境内责任人新规》第五条："境外持有人应当在药品首次进口销售前，通过国家药品业务应用系统向所在地省、自治区、直辖市药品监督管理部门报告其指定的境内责任人，并上传指定境内责任人的授权材料。"
2. The Article 5 of the Regulations on Domestic Responsible Entities: "Before the initial importation and sale of a drug, overseas holders shall report their designated domestic responsible entity to the drug regulatory authority of the province, autonomous region, or municipality where the domestic responsible entity is located via the National Drug Business Application System and upload the authorization materials for the designated domestic responsible entity."
3.《药品注册管理办法（2020）》第九条："申请人应当为能够承担相应法律责任的企业或者药品研制机构等。境外申请人应当指定中国境内的企业法人办理相关药品注册事项。"
3. The Article 9 of the Drug Registration Administration Measures (2020): "Applicants shall be enterprises or drug research institutions capable of assuming corresponding legal responsibilities. Overseas applicants shall designate a domestic legal entity in China to handle matters related to drug registration."
4. 《境内责任人新规》第七条："...境内责任人名称、地址、联系方式应当在药品说明书中列出。"
The Article 7 of the Regulations on Domestic Responsible Entities: "
4. The name, address, and contact information of the domestic responsible entity should be listed in the drug insert sheet."
5. 《药品年度报告管理规定》："...2021年度报告信息填报时间截止为2022年8月31日；从明年开始，每年4月30日之前填报上一年度报告信息。
5. The Regulations on the Annual Reporting Management for Drugs: "... The deadline for submitting the 2021 annual reporting information is August 31, 2022; starting from next year, the deadline for submitting the previous year's report information will be April 30 of each year."
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