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.
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.
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.
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.
Narrower Scope of HGR Information
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.
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.
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).
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.
Clearer Definition of Foreign Parties
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.
The Proposed Rule clarifies the meaning of “control” to include the following situations:
- 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;
- 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;
- 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
- Other circumstances as determined by MOST.
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.
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.
More Clinical Trials Eligible for Record-Filing
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.
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.
In order to meet the requirement of “within the clinical sites,” HGRAC has been requiring the following:
- The HGR are sampled, tested, analyzed and the residual samples are processed in the clinical sites; or
- 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.
In practice, these requirements are difficult to meet because most third-party laboratories are contracted by sponsors, rather than clinical sites.
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.
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.
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.
Exemptions from Foreign Ethics Committee Review
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.
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.
Amendments to Pre-Approval or Record-Filing
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”.
The Proposed Rule clarifies that the following matters are not major changes:
- 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;
- 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
- 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.
For non-major changes, collaborators can proceed with such changes by submitting an amendment, without having to wait and obtain approval of amendment submission.
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.
The Proposed Rule clarifies that:
- 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
- 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.
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.
If you have any questions about the above topics, please feel free to contact us.
*Thanks for the contributions by interns Jessica Gao and Shway Liu.
© 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.