Challenges, Rewards, and Digital Aspects in Establishing Macau’s First Regional Biobank

Macau (also known as Macao), is one of two Special Administrative Regions (SAR) of China—the other being Hong Kong SAR—which maintains a separate government and economic system from those of mainland China under the principle of “one country, two systems.” With a population of approximately 690,000, Macau enjoys a high degree of autonomy by having its own legislation, immigration, customs control, currency, taxation, and public health laws. Though the central government in China remains responsible for its defense and foreign affairs.^[1]

Macau has one of the highest per capita gross domestic product (GDP) in the world (USD 30.12 billion in 2021, indicatively more than the entire country of Cambodia (USD 29.95 billion in 2021). However, this income is mostly exclusively derived from its well-known gaming industry.^[2,3] In recent years, both the central government of China and Macau have been setting goals to diversify the latter’s economy and, therefore, enhance its development and resilience in the longer term. This initiative forms an integral part of the Guangdong-Hong Kong-Macau Greater Bay Area master plan, that is, the Chinese central government’s umbrella development plan to build a world-class city cluster for cooperation in the areas of innovation, cross-boundary infrastructure development, and tourism. Therefore, the urban areas of Guangzhou, Shenzhen/Hong Kong, and Macau, create a geographic triangle contributing to the emergence of the megacity-cluster of the Greater Bay Area with an estimated resident population of 87.6 million.^[4,5]

Thus, aligned with the above, the development of four new major industries was proposed for Macau in 2021, with an investment benchmark set in the annual GDP for the next 10 years. The new major industries include the following: one health; modern finance; new, innovative high-tech; and sports/Cultural industries.^[6] These four industries reflect both the local government’s priorities as well as the position of Macau, emerging as an increasingly important global interface between mainland China and the rest of the world. As this is a new and ambitious task for Macau, it has attracted scientific interest in understanding the requirements for emerging new infrastructures within the “one country, two systems” framework. Without an established framework to support highly competitive, international research or scalable research infrastructure capacity in Macau, the government is looking at different approaches to further Macau’s progress and prioritization of its one health sector. One such solution is the establishment of biobanks for collected biological and clinical samples and associated data. This article discusses the infrastructure required for developing the one health and new innovative high-tech industries in Macau from a healthcare research perspective, using biobanking as a specific example while considering existing challenges and opportunities. This narrative review article presents operational infrastructure and associated requirements and builds upon our previous findings regarding the positive professional perception of the potential of developing digital research infrastructure in Macau for a biobank.^[7]

For the Macau high-tech industries and their overlap with healthcare, the authors used the PubMed and Google Scholar databases for articles identified as of March 2024, searching from 1997 to date, to identify relevant sources, using specific queries with the search terms in combination including always the terms “Macao” and/or “Macau” and alternately the terms “economic,” “development,” “diversification,” “history,” “science,” “healthcare,” and “medicine.” As this paper aimed to provide a broad overview of Macau’s already established systems and upcoming policies, we manually identified relevant sources specific to the topic from the retrieved articles as opposed to a systematic review approach.

The authors used the same approach, focusing on introducing the framework needed to establish a functional biobank in Macau. The authors considered the overall environment, with the constant search terms “biobank*” and “Macao” and/or “Macau” and alternately added search words of “added-value,” “effective,” “operation,” “function,” and “frameworks.” Articles were manually reviewed for their relevance through their titles and abstracts.

For the regulatory challenges and data and digital challenges, comprehensive information was identified through liaising with local expertise on relevant regulations through communicating with the Lawyer Manuela António and respective local agencies, as well as from communicating with available local professional experts who participated in providing comments to our prior feasibility study.^[7]

Despite its high GDP, the sole reliance of Macau’s prosperity on a single industry creates a systemic vulnerability, which the local government appreciates, hence the significance of the drive to diversify its economy in the last decade.^[8] This view is shared by the central Chinese government, which has honored several core policies since the handover of Macau’s sovereignty to China in 1999.^[9] For example, the central Chinese government has honored the provision of land from the neighboring city Zhuhai (China) to Macau to expand the University of Macau. Additionally, tax exemptions and concession policies were provided at the jointly managed nearby Hengqin (Zhuhai) district. The Hengqin district was designed to cater to high-tech enterprises, including but not limited to developments for traditional Chinese medicine, financial services, and international trade events.

However, if one compares the Hengqin development zone with other similar development zones in China, the progress remains comparatively slow. For example, the Taizhou National Medical High-Tech Development Zone (Zhejiang province, China) established a biobank as a support mechanism for biomedical research in 2007.^[10] The Taizhou biobank housed over 200,000 biological samples from the general population in its first 7 years of operation. It provided samples for research that resulted in numerous publications and supported local academic and pharmaceutical operations. Some of the local operations requesting samples included local disease epidemiology projects that provided the evidence for public health policies. The indirect impact on the local economy was the gain of additional high-value skilled staff, expanding healthcare research, and the integration of a platform into existing structures for academic concepts to be tested and translated. The strong growth of the Taizhou National Medical High-Tech Development Zone has meant that Zhejiang province has remained one of the fastest-growing regions of China during that period (GDP growth of 10.1% in 2021).^[10]

By comparison, studies in Macau’s population have been sporadic and focused on piloting new approaches rather than integrating facilities and skills into routine operations. One example is the population-wide genetic risk prediction of complex diseases to inform precision public healthcare planning.^[11] One health studies are even rarer, with Macau being one of the many study sites included but not as the main site of study.^[12] Furthermore, the overall increase in Macau’s scientific output is the lowest within the Guangdong-Hong Kong-Macau Greater Bay Area.^[13] Considering Taizhou’s success, the creation of research platforms in Macau that can support future activities has come into focus with biobanking as one of those highlighted platforms. Biobanks are essential infrastructures for biomedical research, providing high-quality, research-ready samples at scale.^[14] Biobanks have a crucial role in public health surveillance in more established healthcare systems and provide precise evidence for policy decision-making.^[15,16] Successful examples include the UK Biobank, which serves as a global research hub,^[17] and the China National GeneBank in Shenzhen (China), which houses one of the largest biospecimen and data collections in the world.^[18] Thus, in the interest of the Macau SAR self-development, a biobank in Macau, can be considered an infrastructure that can service both the one health and new high-tech industries and provide the foundation for further digital integration of processes within healthcare research.

Biobanks take considerable investment to set up, sustain, and generate economic value in the long term.^[19] As with other infrastructures (e.g., genomics facilities, imaging facilities, etc.) a biobank needs to have its role and market identified to succeed.^[20] The main specificities of Macau’s market and governance mean that Macau has the advantage of a relatively easy-to-regulate and monitor market because of its small size. Using the same reasoning, follow-up to legal requests and records would be easier to obtain than in mainland China, where additional layers of administration exist. One of the challenges Macau faces is the lack of representative sample sizes for most diseases because of its small size. However, the large, diverse population is characterized by one of the highest life expectancies in the world, consistently attracting research questions on geriatrics and comorbidities.

The original legislation on biological samples was not designed with modern biomedical research in mind (such as one supporting one health and new high-tech industries). For example, the law for importing and exporting biological samples for research purposes is not fully defined, as the law was originally designed and intended for clinical practice (e.g., organ transplant or diagnostic purposes).^[21] Having said that, the relatively small number of administrative layers means that the importation and exportation of biological specimens is easier than in mainland China. Therefore, biobanks that might be created in Macau can potentially counterbalance its small market size with administrative flexibility, as the latter can allow it to look outward and service neighboring regions in Southeast Asia, where resource availability might be prohibitive for creating such facilities. Investing in these new opportunities is likely to bring high-value new skills to the local economy, promoting the intended diversification. An initial survey with relevant stakeholders from Macau on the potential creation of a biobank has reported a very positive reception of the idea and demonstrates an overall positive inclination to consider such a development.^[7]

Despite the potential positive impact of investing in biobanking as part of the wider investment in healthcare research and technologies, a few challenges need to be addressed. Existing challenges are the legal and operational frameworks relating to biomedical research, as most biological samples are informationally valuable, while they require cold-chain storage and dedicated logistics. Such practice requires a very defined and efficient legal framework to guarantee smooth operations and scalability. With the support of Lawyer Manuela António, we understand that the regulatory framework for importing biological materials to Macau dates back to the 1990s and is designed for the purpose of organ transplant. Some of these laws were later updated to accommodate the importation of biological reagents and therapeutic blood products. According to current regulations, the importation of such products continues to be allowed. Specifically, the importation of human and animal blood, glands, and organs for therapeutic use is covered by import Schedule B. The key question is wheather research samples are covered in general or only if they are intended for therapeutic purposes. In addition, order 47/SS/2009 from the Macau Health Bureau may have additional requirements (e.g., providing evidence that blood products are HIV-1 negative). Therefore, a more defined legal framework is recommended to regulate research samples. In addition to the regulation from the Macau Health Bureau, importation of certain blood products will require approval from the Pharmaceutical Administration Bureau, in which a panel of infectious diseases needs to be tested, and a Good Manufacturing Practice certificate from the manufacturer should be provided as applicable. While these regulations are very suitable and operate well for clinical therapeutic purposes, they are not entirely aligned with biomedical research requirements. A summary of these laws is shown in Supplementary Material A.

Another essential set of elements for biomedical research is reagent consumables. Under Chief Executive’s Decision Number 209/2021, laboratory consumables’ importation is classified in group B1 and granted by the Pharmaceutical Administration Bureau. Applications for importing such materials must be submitted in person and processed in working days. Each reagent will be inspected on-site by the Pharmaceutical Administration Bureau. The system has been working well thus far but is not designed to cater to any potential rapid biomedical research development and the pressures that scaling up activities may impose. For example, in response to public health emergencies, an immediate response to generate scientific data will require a sudden increase in the importation of reagents. Macau can consider the reference system operated in Singapore for medicine through the Medicinal Products as Clinical Research Materials Regulations of 2016^[22] or in its neighbor, Hong Kong SAR, in which authorized entities will only need special approval for short-listed controlled items. Such systems were evolved for efficiency in catering to rapid biomedical research development, with common, harmless, and conventional reagents only requiring a fast, digital registration in the system to clear customs.

The data derived from using biological samples and reagents plays an equally important role in biomedical development. For example, genetic information can be used for diagnostic purposes for hereditary conditions, while epidemiologic data linked to information, such as sex, date of birth, education, and social aspects, can inform public health policies. Social data, such as average income and number of visits to the clinic, are also important to understand, for example, the accessibility of public healthcare services within a particular group. Thus, data protection laws supporting access to such data and its use for further research are important. The data protection legislation in Macau is the Personal Data Protection Act (Law No. 8/2005), which was significantly influenced by the European data protection legislation, including Portugal’s Law Number 68/98 on the Protection of Personal Data, which was implemented under the EU Directive 95/46/EC. The law applies only to data collected within Macau but not outside. On the other hand, on May 28, 2019, the Regulation of the People’s Republic of China on Human Genetic Resources Management (the Regulation on Human Genetic Resources) was passed.^[23] This new regulation places more emphasis on protecting the privacy and rights of data subjects, focuses more on safeguarding public health, national security, and social public interests, and states that collecting and using consumers’ genetic data without their informed consent is not allowed.^[24] Therefore, Macau has the potential to act as a bridge between those two distinctly different legal frameworks.

Regarding ethics in Macau, the ethics are governed by the Comissão de Ética para as Ciências da Vida (Commission of Ethics and Life Science), supervised by the Secretariat for Social Affairs and Culture, while the Macau Health Bureau acts as an advisory body to the commission. The commission was founded by legislation in 1996, overlooking mainly blood and organ transplants, while there is no defined legislation relating to the practices of modern biomedical research.

As a considerable number of biological samples collected and stored in biobanks are used in pharmaceutical research,^[25] another challenge regarding legal frameworks is the licensing of self-funded pharmaceutical laboratories, clinical diagnostic laboratories, which are solely used for clinical purposes, and academic research laboratories, which operate under an educational license. With the support of Lawyer Manuela António, the current legislation relating to this matter was reviewed. Their team has examined Decree-Law Number 55/97/M of December 9, Decree-Law Number 11/99/M of March 22, Chief Executive’s Notice Number 28/2003, and the Commercial Code of Macau. Under the current legislation, setting up a private laboratory with a purpose related to scientific research is not subject to government approval and/or licensing. In fact, unless the laboratory is responsible for manufacturing some type of product under the mentioned Decree-Law Number 11/99/M of March 22, there is no need for an industrial license. While most countries also have regulations to manage biosafety aspects according to the materials handled in their laboratories (beyond the licensing aspects mentioned above), this is not the case in Macau. Thus, Macau needs to develop a legal framework and regulate the biosafety and biosecurity aspects of such laboratories.

At the same time, Macau is one of the urban areas with the highest digital information integration globally, both for private businesses and education.^[26,27] The digital security is particularly strongly safeguarded because of the highly developed gaming business. As such, the foundational digital infrastructure is extant, even though never applied at scale toward infrastructures for medical research and innovation. Thus, provided the legal framework is further clarified, implementing medical research infrastructures, such as biobanks, and their digital integration within the regional ecosystem is indeed possible.

As described throughout this section and shown in Figure 1, the framework to address many of these challenges is to educate and build on the frameworks that are in existence; however, they are not well defined or lack clarity about biobanking. Conversations with the appropriate government bodies coalesce toward convening committees to determine what is needed to establish well-defined, quality biobanks in Macau. The established committees would work together with researchers and international biobanking experts in developing biobanking and biosecurity laws and clarify existing regulations, such as Schedule B, which defines the importing of research samples with consideration of Chinese and Macau laws. This group would also recommend updates to the general biosafety guidelines used, introduce the best practices reference for biobanks, establish requirements for high-risk biological samples collected and/or used in Macau, and communicate with import agencies to better institute a system toward accessing basic laboratory reagents with green light imports, especially those that require rapid turnover and/or necessitate temperature regulations.

Understandably, this will not happen overnight. The good news is that it does not have to be reinvented, as there are many templates from other successful Asian regional biobanks that the Macau government can follow. With the revised and updated policies and procedures in place, facing these challenges can be manageable and thus result in a win-win scenario for all stakeholders.

While Macau has been trying to diversify its economies over the past 20 years, compared with relevant regional developments, its development is hampered by the lack of core research infrastructures. Given Macau’s SAR status, a biobank in Macau supports the central government’s umbrella development plan to build a world-class city cluster for cooperation in the areas of innovation and cross-boundary infrastructure development without many of the restrictions that are placed in other regions of China. It can be an infrastructure that can support both the one health and new high-tech industries and provide the foundation for future digital integration of processes within healthcare research. A biobank in Macau is likely to attract biotech businesses to use the facilities based in Macau while generating local, high-skilled employment and supporting local academic entities. Thus, establishing a biobank in Macau that is digitally integrated can contribute toward a positive ecosystem in the medical research field, promoting sustainable growth.

Macau can further strengthen its regional biobanking capabilities by serving as a bridge between China and the rest of Southeast Asia. This can be accomplished by forming collaborations, leveraging technology, and standardizing practices along with collective efforts and partnerships with experts and stakeholders that play a vital role in shaping policies, guidelines, and regulations to support growth and sustainability across the region. Embracing these opportunities will contribute to advancing scientific research and medical diagnosis, enhancing public healthcare, improving innovative technologies, and contributing to global scientific endeavors.

To accomplish this, and taking the creation of a biobank as a specific example, certain challenges need to be addressed. These challenges relate to the existing regulatory frameworks, the data protection policies, and the digital integration of such infrastructure into the existing ecosystem. The current work provides a detailed view of the above challenges and opportunities. This endeavor opens the door for collaborations from global scientific research teams and multinational pharmaceutical companies while supporting the central government’s plan to expand in innovation and cross-border development areas.

The authors thank Advogada Manuela António, Esteves Wong, and António Camacho Coelho from the firm Manuela António – Lawyers and Notaries for their professional legal advice provided pro bono for the purposes of this study. They also thank Jasper HC Luong (Smoke-free & Healthy Life Association of Macau, Macau SAR, China) for his input and edits to the finalized manuscript.