Navigating the Latest Changes in China’s Regulation of Human Genetic Resources 应对中国人类遗传资源监管的最新变化

Multinational companies have been required to obtain pre-approval from, or complete record-filing with, the Human Genetic Resources Administration of China (HGRAC) before they initiate clinical trials or research projects in China, on the grounds that these activities involve China’s human genetic resources (HGR). Some of the regulatory requirements on HGR will or have recently changed in certain situations. This article will discuss the latest changes to assist companies in navigating the HGRAC regulatory landscape.
跨国公司在中国启动临床试验或研究项目前，如果涉及利用中国人类遗传资源，必须取得中国人类遗传资源管理办公室（“人遗办”）的事先审批或备案。中国人类遗传资源的监管措施日益推陈出新。本文将聚焦新的监管要求，帮助企业了解中国人类遗传资源监管的新图景。

On March 21, 2022, the Ministry of Science and Technology (MOST) proposed for public comment the Implementing Rule for Regulation on the Administration of Human Genetic Resources (the Proposed Rule). In March and April, 2022, MOST also issued two sets of Q&As to announce its new interpretations and requirements, and began to implement them.
2022年3月21日，科技部公布了《人类遗传资源管理条例实施细则（征求意见稿）》（“《征求意见稿》”）。此前，科技部于2022年3月和4月通过问答的方式（“《问答》”），发布了关于人类遗传资源管理的新解读和新要求，并已经开始实施。

The Proposed Rule and the Q&As will and have changed the implementation of several provisions in the 2019 Regulation on the Administration of Human Genetic Resources (the Regulation), substantially impacting multinational pharmaceutical companies conducting clinical trials and human research in China. Companies should be aware of the latest changes, and adjust their strategies and practices in order to prepare for and comply with the new requirements.
《征求意见稿》和《问答》即将或已经改变2019年《人类遗传资源管理条例》（“《人遗条例》”）的诸多规定的实施，对于在中国开展临床试验和人类研究项目的跨国医药企业有着重要影响。企业应持续关注这些最新变化，调整实践策略，以符合这些新要求。

This article will focus on the following five aspects of the changes: (1) narrower scope of HGR information, (2) clearer definition of foreign parties, (3) more clinical trials eligible for record-filing, (4) exemptions from foreign ethics committee review, and (5) amendments to pre-approval or record-filing.
我们将在本文中聚焦讨论以下五个方面：（1）缩限的人类遗传资源信息的范围、（2）更清晰的外方单位的定义、（3）更多符合备案资格的临床试验、（4）外方伦理审查的豁免，以及（5）国际合作审批及备案的变更。

Narrower Scope of HGR Information
缩限的人类遗传资源信息的范围

The current Regulation defines HGR broadly to include HGR materials and HGR information. Among these interpretations, (1) HGR materials are genetic materials, including organs, tissues and cells containing human genomes, genes and other genetic substances, and (2) HGR information refers to information such as data generated from HGR materials. Accordingly, as long as the information is derived from HGR materials (e.g., blood), even if the information (e.g., routine blood test report) does not have genetic properties, it is considered HGR information and falls within the scope of the Regulation.
“人类遗传资源”在《人遗条例》中的定义十分宽泛，包括人类遗传资源的“材料”和“信息”。其中，（1）“人类遗传资源材料”是指含有人体基因组、基因等遗传物质的器官、组织、细胞等遗传材料，（2）“人类遗传资源信息”指利用人类遗传资源材料产生的数据等信息材料。据此，只要信息来源于人类遗传资源材料（例如：血液），即使该信息（例如：血常规报告）不反映遗传信息，也会落入人类遗传资源的范围，受到《条例》监管。

The Proposed Rule, in comparison, narrows down the scope of HGR information to “information such as human genetic data and genomic data generated from HGR materials.” Accordingly, if the testing information of HGR materials does not have genetic properties, it would not be considered HGR information.
相较而言，《征求意见稿》将“人类遗传资源信息”的范围缩限解释为“利用人类遗传资源材料产生的人类基因、基因组数据等信息资料”。据此，如果人类遗传材料的检测信息不反映遗传属性，就不属于人类遗传资源信息。

Furthermore, the Q&As list some examples that the agency has already carved out from the scope of HGR information, including (1) clinical image data (e.g., image data in ultrasound, CT, PET-CT, NMR, X-ray, interventional treatments, fundoscopy, endoscopy, dermoscopy, and pathology), and (2) clinical data not involving population genetics research (e.g., information on general laboratory tests, such as routine blood tests, urine tests, liver and kidney function tests, and blood biochemistry tests; individual growth and development indicators, such as height and weight; questionnaire information; and data in medical imaging results).
此外，《问答》中列举了不被主管部门视为人类遗传资源的部分实例，包括（1）临床图像数据（例如：B超、CT、PET-CT、核磁共振、X射线等影像数据，介入、眼底镜、内窥镜、皮肤镜、病理诊断等图片数据），和（2）不涉及人群基因研究的临床数据（例如：血常规、尿常规、肝肾功、血生化等一般实验室检查信息，身高、体重等生长发育指标，问卷信息，影像学/图片结果数据等）。

The narrower scope of HGR information is great news to many companies, since it will now exempt human research information that does not include genetic or genomic data from recording-filing before provision or open access of this information to foreign parties. The record-filing requirement has been particularly challenging for companies to comply with, especially in situations such as simultaneous electronic data capture and transmission, journal article publication, conference presentation, and regulatory submission outside China, as we have discussed in an earlier article.
人类遗传资源信息范围的缩限对于许多公司来说是个好消息，因为这使得向外方单位提供或开放使用不包括基因或基因组数据的人类研究项目的信息前，将无需进行备案。正如我们在之前文章中所述的，在电子数据同步采集和传输、期刊文章发表、会议演讲和向境外监管机构提交信息等情况下，这一备案要求对公司来说尤其具有挑战性。

Clearer Definition of Foreign Parties
更清晰的外方单位的定义

The current Regulation defines “foreign parties” as (1) foreign organizations, and (2) China-domiciled institutions established or actually controlled by foreign organizations or individuals. The meaning of “control” is not explained, however, and it is unclear whether foreign parties include China-domiciled companies with foreign investment in any amount, or companies without any foreign investment but which are controlled by foreign enterprises and individuals through contractual arrangements such as VIE structure.
《人遗条例》将“外方单位”定义为（1）外国组织，及（2）外国组织、个人设立或者实际控制的机构，但未界定“控制”的含义。不明确的是，外方单位是否包括含有任何比例外资成分的公司，以及境外企业和个人通过协议控制（如VIE架构）的无外资成分的中国企业。

The Proposed Rule clarifies the meaning of “control” to include the following situations:
《征求意见稿》明确了“控制”的含义，包括以下情形：

• Foreign organizations or individuals holding or indirectly holding more than 50% of the shares, equity, voting rights, property shares or other similar interests in the entity;
  境外组织、个人持有或者间接持有机构50%以上的股份、股权、表决权、财产份额或者其他类似权益；
• Foreign organizations or individuals holding voting rights or other interests in decision-making which are sufficient to exert significant influence on the resolution of the entity or on the decision-making and internal management of the entity;
  境外组织、个人所享有的决策机构表决权或其他权益足以对该机构的决议或对该机构的决策、内部管理产生重大影响；
• Foreign organizations or individuals, through agreements or other arrangements, sufficient to exert significant influence on the entity’s decision-making, business management and other major matters; and
  境外组织、个人通过协议或者其他安排，足以对机构的决策、经营管理等重大事项施加重大影响；和
• Other circumstances as determined by MOST.
  科技部认定的其他情形。

Accordingly, the scope of “foreign parties” will include China-domiciled companies with VIE structures, but not companies with less than 50% of foreign investment if the foreign investor’s voting or other decision-making rights will not exert significant influence on the entity.
据此，VIE架构的中国企业将被明确视为“外方单位”。但是，境外投资者持股未达到50%且对企业的决策、内部管理不产生重大影响的机构，将不再属于“外方单位”。

This is a positive development for foreign invested companies in China that do not fall within the scope of “foreign parties.” They will be able to engage in sampling and preservation of HGR in China and will no longer be restricted to use HGR only when collaborating with Chinese entities.
这对不落入“外方单位”范围的在华外商投资企业来说是个好消息。这些企业将突破《人遗条例》的限制，可以在中国采集和保藏人类遗传资源，利用中国人类遗传资源时也不再需要与中方单位开展合作研究。

More Clinical Trials Eligible for Record-Filing
更多符合备案资格的临床试验

The Regulation allows foreign parties to receive and use HGR in human research, including clinical trials, but restricts such activities to international collaborations with Chinese entities.  Multinational companies must therefore collaborate with Chinese hospitals and clinical testing laboratories when conducting clinical trials in China.
《人遗条例》允许外方单位在人类研究项目中，包括临床试验中，获取和使用人类遗传资源，但此类研究活动必须与中方单位合作开展。因此，跨国公司在中国开展临床试验时必须与中国的医院和临床检验实验室合作。

The Regulation requires pre-approval from or record-filing with HGRAC before initiating HGR-related clinical trials. Record-filing is simper and faster, but limited to when the clinical trial (1) is for the purpose of obtaining a marketing authorization of drugs or medical devices in China, (2) does not involve the export of HGR materials, and (3) is conducted “within the clinical sites” in China.
《条例》要求在开展涉及人类遗传资源的临床试验前，需要取得人遗办的审批。相较而言，备案程序更加简便快捷，但其仅限于符合以下条件的临床试验：（1）旨在获得药品或医疗器械在中国上市许可，（2）不涉及人类遗传资源材料出境，且（3）临床试验在中国的临床机构开展。

In order to meet the requirement of “within the clinical sites,” HGRAC has been requiring the following:
为满足“临床试验在临床机构开展”的条件，人遗办有如下要求：

• The HGR are sampled, tested, analyzed and the residual samples are processed in the clinical sites; or
  所涉及的人类遗传资源仅在临床机构内采集、检测、分析和剩余样本处理等；或

• The HGR are sampled within the clinical sites, and the third-party laboratories are contracted by the clinical sites for testing, analyzing and residual sample processing.
  所涉及的人类遗传资源在临床机构内采集，由临床机构委托的单位进行检测、分析和剩余样本处理等。

In practice, these requirements are difficult to meet because most third-party laboratories are contracted by sponsors, rather than clinical sites.
上述要求通常难以得到满足，因为在实践中，第三方实验室大多由申办者而不是临床机构委托。

The Proposed Rule relaxes those requirements. As long as the HGR are sampled within the clinical sites and the testing, analysis and residual sample processing are performed by a domestic third party designated by the clinical trial protocol, the record-filing procedures would apply. In other words, the third-party laboratory is no longer required to be contracted by clinical sites, making it possible for most clinical trials to be eligible for record-filing, which is simpler and faster than pre-approval.
《征求意见稿》放宽了备案的要求，即只要所涉及的人类遗传资源在临床机构内采集，并由相关临床试验方案指定的境内单位进行检测、分析和剩余样本处理，就可以适用备案程序。换而言之，第三方实验室不再必须由临床机构委托。据此，大多数的临床试验将可以适用更简便和快捷的备案程序。

Moreover, according to the Q&As, pre-approval is not required in the implementation: (1) if the foreign party provides funding without substantial participation, does not receive research-related data, and does not share research results (e.g., foreign-owned pharmaceutical companies provide clinical sites with clinical research drugs or research funding only); or (2) if in clinical trials, the sponsors, contract research organizations, and other collaborators are all Chinese parties, and only the provider of the electronic data capture (EDC) system is a foreign party.
《问答》还规定了在实践中不需要人遗办审批的情形：（1）如果外方单位提供资助但无实质性参与，不获取研究相关数据信息，并且研究成果与外方不共享（例如：外资制药企业仅为医疗机构提供临床研究用药或研究经费资助），则不需要取得人遗办的审批；或者（2）临床试验中，申办方、合同研究组织等合作各方均为中方单位，只有电子数据采集系统（EDC）的供应商是外方单位，也无需人遗办审批。

Furthermore, record-filing has become simpler and faster, according to the Q&As. After submitting record-filing application for clinical trials, and after being approved under the formality review, the system will automatically generate a filing number for that record which shows the record-filing is successful, then parties can start clinical trials.
此外，根据《问答》，备案程序已变得更加简便和快捷：提交临床试验备案申请后，经形式审查通过，系统自动生成备案号即备案成功，双方即可开展临床试验。

Exemptions from Foreign Ethics Committee Review
外方伦理审查豁免

The Regulation requires collaborating parties to obtain ethics committee review and approval in their home countries. Under certain circumstances, however, some foreign parties have found it difficult, if not impossible, to obtain ethics committee review in their home countries because the human research is to be conducted in China.
《人遗条例》要求合作方在各自所在国进行伦理审查。但是，在一些情况下，外方单位因人类研究在中国进行而无法或者难以获得所在国的伦理审批。

The Proposed Rule provides an exemption for foreign parties from ethics committee review, when Chinese ethics committee finds that (1) the international collaboration does not involve major ethical issues, and (2) foreign ethics committee review indeed cannot be provided. Such exemption will accelerate the HGRAC pre-approval or record-filing process.
《征求意见稿》增加了外方豁免伦理审查的情形，即经中方合作机构伦理委员会审查，认为国际合作不涉及重大伦理问题，且确实无法提供外方伦理审查的，可以豁免外方伦理审查，从而有利于加速取得人遗办的审批或备案。

Amendments to Pre-Approval or Record-Filing
国际合作审批及备案的变更

The Regulation requires submitting an amendment and obtaining an approval of the amendment submission before implementing any major changes to research projects or clinical trials cleared under the pre-approval process, such as a change of collaborator, research purpose, research content, or duration of collaboration. It is not clear, however, whether any changes to collaborator, research purpose, content, or duration would constitute a “major change”.
《人遗条例》规定，在利用中国人类遗传资源开展研究项目或临床试验过程中，经事先审批的合作方、研究目的、研究内容、合作期限等重大事项发生变更的，应当在实施变更前办理变更审批手续。但是，规定未明确，是否合作方、研究目的、研究内容、合作期限的任何变化都属于“重大变更”。

The Proposed Rule clarifies that the following matters are not major changes:
《征求意见稿》对此予以明确，以下事项属于非重大变更：

• The research protocol remains unchanged, and there is only a 10% or less change to the cumulative number of cases compared to the previously approved quantity;
  研究方案不变，仅涉及例数累计不超过获批数量10%以内的变更；
• Changes of the collaborating parties other than the sponsor, leading entity of the clinical trial, contract research organization, or third-party laboratory, or changes of the entity names of any of the collaborating parties; and
  除申办方、组长单位、合同研究组织、第三方实验室之外的参与单位，以及合作各方的法人单位名称发生变更的；和
• The research protocol has been changed, but the change does not involve any change to the types, quantity or use of HGR or the change does not exceed the previously approved scope.
  研究方案变更，但不涉及人类遗传资源种类、数量、用途的变化或变更后的内容不超出已批准范围的情况。

For non-major changes, collaborators can proceed with such changes by submitting an amendment, without having to wait and obtain approval of amendment submission.
对于非重大变更，向监管机构作出说明和进行报备即可，无需等待和取得监管机构对此的审批。

According to the Regulation, any entity that provides or offers open access of HGR information to foreign parties must submit the information to MOST for backup and make a record-filing with HGRAC; however, the Regulation is silent as to whether an amendment submission is required for any change to (1) provision or open access of HGR information to foreign parties or (2) clinical trials which are regulated under the record-filing process.
根据《人遗条例》，将人类遗传资源信息向外方单位提供或者开放使用的，应当向科技部提交信息备份并在遗传办进行备案。但是，《人遗条例》没有规定信息对外提供、开放使用备案或临床试验国际合作备案完成后，涉及人类遗传资源的事项发生变更的，是否需要变更备案。

The Proposed Rule clarifies that:
《征求意见稿》对此予以明确：

• As to record-filing of providing HGR information to foreign parties or offering open access of HGR information, if changes relate to the use of HGR or other significant matters, the collaborating parties are required to timely submit an amendment and complete the record-filing process for the amendment submission; and
  对于对外提供或开放使用备案而言，发生用途变化等重大事项变更，合作方应及时进行备案变更；和
• As to record-filing of clinical trials, changes in the type, quantity or use of HGR are major changes, and the collaborating parties are required to submit an amendment and complete the record-filing process for the amendment submission before making such major changes; for changes not involving any of the above matters, collaborating parties are only required to submit a statement describing these changes before any change is made.
  对于临床试验备案而言，发生人类遗传资源种类、数量、用途等变化的，属于重大变更，合作方应进行备案变更；不涉及上述事项的，在变更活动开始前提交变更说明即可。

Conclusion
结语

The Proposed Rule and Q&As will or have changed the requirements under the Regulation, reflecting new interpretations and trends of Chinese authorities in regulating HGR. The Proposed Rule, once implemented, will have significant impact on pharmaceutical companies conducting clinical trials in China. Companies should continue to monitor this regulatory development, consider submitting comments on the Proposed Rule, and adjust their strategies and practices in order to prepare for and comply with the new requirements.

《征求意见稿》和《问答》在诸多方面厘清了《人遗条例》的要求，体现了中国监管机构在人类遗传资源管理中的新解读和新动向。《征求意见稿》一旦实施，将对医药企业在中国开展临床试验有重大影响。企业应持续关注，考虑提交反馈意见，并调整其实践策略，以应对和符合这些新要求。

If you have any questions about the above topics, please feel free to contact us.
若您对上述话题有任何疑问，欢迎随时联系我们。

*Thanks for the contributions by interns Jessica Gao and Shway Liu.

感谢实习生高思遥和刘水行云对本文的贡献。

© Arnold & Porter Kaye Scholer LLP 2022 All Rights Reserved. This Advisory is intended to be a general summary of the law and does not constitute legal advice. You should consult with counsel to determine applicable legal requirements in a specific fact situation.