On June 1, 2023, the Ministry of Science and Technology (MOST) issued the Implementation Rule for the Regulation on the Administration of Human Genetic Resources (the Implementation Rule) which will come into effect on July 1, 2023. Following the promulgation of the 2019 Regulation on the Administration of Human Genetic Resources (the Regulation), the Implementation Rule marks a significant milestone in China's regulation of human genetic resources. The Implementation Rule clarifies many requirements of the Regulation, creating both opportunities and challenges on multinational pharmaceutical companies conducting clinical trials and human research in China. It is therefore critical for companies to fully understand these newly clarified requirements, take appropriate measures to mitigate risks, and take advantage of the opportunities created by the Implementation Rule.
2023年6月1日，科技部公布了《人类遗传资源管理条例实施细则》（“《实施细则》”），并将于2023年7月1日起正式实施。《实施细则》是自2019年《人类遗传资源管理条例》（“《人遗条例》”）出台以来，中国人类遗传资源监管的新里程碑，厘清了《人遗条例》中的诸多监管要求。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而言，既是机会也是挑战。了解《实施细则》的新要求并采取适当的措施以降低风险、把握机遇是至关重要的。

This article will discuss the latest changes brought by the Implementation Rule focusing on the following five topics: (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.
本文关注《实施细则》带来的新变化，聚焦以下五个方面：（1）人类遗传资源信息缩限范围；（2）更清晰的外方单位的定义；（3）更多临床试验符合备案资格；（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。

1. Narrower Scope of HGR Information
人类遗传资源信息缩限范围

The current Regulation defines HGR broadly to include HGR materials and HGR information, stating that (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, the information could be interpreted to be within the scope of HGR information under 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”。具体而言，（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《人遗条例》监管。

The Implementation Rule, in comparison, narrows the scope of HGR information to be “information such as human genetic data and genomic data generated from HGR materials.” Moreover, the Implementation Rule makes it clear that HGR information does not include “clinical data, image data, protein data, and metabolome data.” Accordingly, if the clinical laboratory testing information of HGR materials does not have genetic properties, it would not be considered HGR information under the Implementation Rule.
相较而言，《实施细则》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”，并且，《实施细则》明确说明人类遗传资源信息不包括“临床数据、影像数据、蛋白质数据和代谢数据”。据此，如果人类遗传材料的临床实验室检测信息不反映遗传属性，就不属于《实施细则》所规范的人类遗传资源信息。

Furthermore, according to the Q&As issued by the MOST on March 2 and April 15, 2022 (the Q&As), 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，根据科技部于2022年3月2日及4月15日发布的问答（“《问答》”），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 creates opportunities for many companies, which can now exclude human research information that does not include genetic or genomic data from record-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一个良好的机遇，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。

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

The current Regulation defines “foreign parties” broadly 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 a VIE structure.
《人遗条例》将“外方单位”宽泛地定义为（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 Implementation Rule clarifies the meaning of “control” to include the following situations:
《实施细则》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 which are sufficient to control or exert significant influence on the decision-making, management, and other actions of the entity
    境外组织、个人所享有的表决权或者其他权益足以对机构的决策、管理等行为进行支配或者施加产生重大影响
  • Foreign organizations or individuals, through investment, agreements, or other arrangements, sufficient to control or exert significant influence on the entity's decision-making, management, and other actions
    境外组织、个人通过投资关系、协议或者其他安排，足以对机构的决策、管理等行为进行支配或者施加重大影响
  • Other circumstances as stipulated by laws, regulations, and rules
    法律、行政法规、规章规定的其他情形

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 does not have significant influence on the company's decision-making or management.
据此，VIE架构的中国内资企业将被明确视为“外方单位”。但是，境外投资者持股未达到50%且对企业的决策、管理不产生重大影响的机构，将不再属于“外方单位”。

In addition, all entities established in Hong Kong and Macau were previously regarded as foreign parties under the Regulation. According to the Implementation Rule, Chinese-controlled entities established in Hong Kong and Macau are treated as Chinese parties, which further narrows the scope of foreign parties.
此外，根据《人遗条例》，在香港和澳门设立的机构原先一般被视为外方单位。《实施细则》阐明，设在香港和澳门的内资实控机构视为中方单位，这一规定进一步缩小了外方单位的范围。

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 utilizing 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。

3. More Clinical Trials Eligible for Record-Filing
更多临床试验符合备案资格

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 medical institutions 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疗机构和临床检验实验室合作。

The Regulation requires pre-approval from or record-filing with the Human Genetic Resources Administration of China (HGRAC) before initiating HGR-related clinical trials. Record-filing is simper and faster, but applicable only 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.
《人遗条例》要求在开展涉及人类遗传资源的临床试验前，需要取得人类遗传资源管理办公室（“人遗办”）的审批或备案。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 above third requirement of “within the clinical sites,” HGRAC requires the following:
为满足上述第三项“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, and analyzed and the residual samples are processed in the clinical sites
    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
  • 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 Implementation 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.
《实施细则》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 a 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. Parties can then 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。

4. 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 Implementation Rule provides an exemption for foreign parties from ethics committee review. If the foreign party is unable to provide ethics review materials from the country or region where it is located, the foreign party can submit materials indicting its acceptance of the ethics review opinions of the Chinese party.
《实施细则》增加了外方豁免伦理审查的情形，即外方单位确无法提供所在国或地区伦理审查证明材料的，可以提交外方单位认可中方单位伦理审查意见的证明材料。

5. 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 approved 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，是否涉及合作方、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 Implementation Rule clarifies that the following matters are not major changes:
《实施细则》对此予以明确，以下事项属于非重大变更：

  • The research content or protocol remains unchanged and there is only a 10% or less change to the total number of cases compared to the previously approved quantity
    研究内容或者研究方案不变，仅涉及总量累计不超过获批数量10%变更的
  • 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
    除申办方、组长单位、合同研究组织、第三方实验室以外的参与单位，以及合作方法人单位名称发生变更的
  • The research content or 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
    研究内容或者研究方案发生变更，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

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，向监管机构提交事项变更的书面说明及相应材料即可，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 the 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（《实施细则》中改称为“事先报告”）。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 Implementation Rule clarifies that:
《实施细则》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 or recipients of HGR, it is required to submit an amendment and complete the record-filing process for the amendment submission before any change is made.
    对于对外提供或开放使用事先报告而言，用途、接收方等事项发生变更的，应当在变更事项实施前向科技部提交事项变更报告.
  • As to record-filing of clinical trials, if changes relate to the type, quantity, or use of HGR, or the collaborator, research protocol, research content, or research purpose, the party who made the record-filing is required to submit an amendment and complete the record-filing process for the amendment submission; for changes not involving any of the above matters, it is only required to submit a written statement describing these changes before any change is made.
    对于临床试验备案而言，人类遗传资源种类、数量、用途发生变更，或者合作方、研究方案、研究内容、研究目的等重大事项发生变更的，备案人应办理备案变更；不涉及上述事项的，在变更活动开始前提交变更的书面说明及相应材料即可。

Conclusion
结语

With the promulgation of the Implementation Rule, China's regulation of HGR has reached a new milestone, which will have significant impact on multinational pharmaceutical companies operating 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.
随着《实施细则》的出台，中国人类遗传资源监管迎来了一个新的里程碑，对于在中国开展活动的跨国医药企业有着重要影响。企业应持续关注最新变化，调整实践策略，以符合新的监管要求。

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