In an interaction with BioPharma APAC, Raymond Chow, Vice President of Commercial for Asia-Pacific at Cytiva, shares his insights on the rapidly evolving landscape of cell and gene therapy manufacturing in the Asia-Pacific region. With a focus on the unique opportunities and challenges presented by the region, Raymond discusses the role of innovation in genomic medicine, the impact of government support, and the strategic measures Cytiva is implementing to enhance local production capabilities. He also delves into the critical role of regulatory bodies, the complexities of scaling up manufacturing processes, and the exciting collaborations between local biotech companies and global entities that are shaping the future of cancer therapeutics in Asia.

How would you describe the current landscape of cell and gene therapy manufacturing in the Asia-Pacific region, and what distinguishes it from other global regions?

The current landscape of cell and gene therapies manufacturing in Asia Pacific is looking promising for two reasons – innovation in mRNA and government support.

Firstly, the Asia Pacific region is showing bright spots in innovation in genomic medicines, especially mRNA. For example, in 2022, a Singapore-based A*STAR-led team of scientists represented the only group in Asia to be awarded contract from Wellcome Leap R3 program for their ability to manufacture circular RNA for mRNA vaccines. In South Korea, Samyang Holdings and LG Chem have established a strategic partnership agreement for the development of novel mRNA-based cancer therapeutics. In India, Gennova developed an mRNA Covid vaccine with favorable storage condition  for the developing world.

Secondly, governments are funding and driving mRNA vaccine development locally. For example, in Singapore last year, the Ministry of Health in Singapore announced its funding for mRNA-based cancer vaccine development in the country. In South Korea, the government has aimed for the development of at least one homegrown mRNA vaccine as part of their ambitions to become a global vaccine production hub. They have allocated a budget of about US$1.92b over a five-year period to achieve this. The Australian government is ramping up to build the sovereign vaccine manufacturing capability by establishing the first large-scale mRNA vaccine manufacturing facility at Monash University in Melbourne  as well its  first dedicated mRNA medicines manufacturing workforce training centre.

I see two factors that set Asia Pacific’s genomic medicine landscape apart from other global regions – population diversity and cost efficiency.

The genetic diversity in Asia Pacific provides unique opportunities for developing therapies tailored to specific genetic backgrounds. This diversity can also facilitate broader clinical trials and research. In addition, the large and growing patient populations in Asia Pacific provide a robust local industry for cell and gene therapies. Furthermore, approximately half of global cancer cases are found in Asia Pacific. mRNA has shown promise in managing virus-related cancers, which account for 20% of cancers.

Secondly, Asian countries are increasingly adopting advanced manufacturing technologies, including automation and digitalization, to enhance production efficiency and quality control. In addition, in some countries, lower labour costs and operational expenses can be a significant advantage for large-scale production.

Altogether, these factors make it economically viable to set up manufacturing facilities here.

What role do regulatory bodies in Asia play in the growth of the cell and gene therapy sector, and how are these regulations evolving to support innovation and commercialization?

Regulatory bodies in Asia play a crucial role in shaping the landscape for the cell and gene therapy sector. Their influence extends from ensuring the efficacy and safety of therapies to fostering innovation and commercialization. 

Firstly, various regulatory agencies in Asia establish stringent guidelines to ensure that cell and gene therapies are safe and effective for patients such as HSA in Singapore  and Pharmaceuticals and Medical Devices Agency (PMDA) in Japan. These guidelines include rigorous clinical trial requirements, quality control measures, and surveillance.

Secondly, they are responsible for the approval and licensing of new therapies. They review comprehensive data from clinical trials can fast-track approval processes for therapies that address unmet medical needs or show significant promise. In addition, initiatives like Japan’s Sakigake designation and China’s priority review system help to accelerate the development and approval of breakthrough therapies.

Thirdly, Asian regulatory bodies often collaborate with international counterparts to harmonize standards and facilitate global clinical trials. Organizations like the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) play a key role in this process.

According to data from the 2023 Global Biopharma Resilience Index, to support innovation and commercialisation, the biopharma industry must work in closer collaboration with both government policymakers and regulatory-agency leadership to ensure regulatory processes are adapted to suit emerging technologies and therapies. This is because although there has been progress on facilitating faster drug approvals, while continuing to ensure safety and efficacy, that is just the last of a number of regulatory barriers that new products must overcome to reach the market.

Given the complex and personalized nature of cell and gene therapies, what are the primary challenges faced in scaling up manufacturing processes within the APAC region?

The first challenge for developing and scaling up manufacturing processes for cell and gene therapies in Asia Pacific is talent.

Compared to big biopharma companies, biotech startups developing genomic medicines in Asia struggle to compete for mature talent, and to train new associates.

To mitigate this pain point, which takes a high stake in their R&D budget, Cytiva has established the Fast Trak Education and Training Programme, available at six centres globally – three of which are based in Asia Pacific region - Korea, China, and India. For example, both Songdo and Shanghai Fast Trak centres have the capability to train more than 300 people every year for the biotechnology industry. The India centre collaborates with Bangalore BioInnovation Centre to set up a world class incubation centre to provide bioprocessing training programmes to support the startup ecosystem in India.

To nurture talent in Southeast Asia, where cell therapy and mRNA innovation is emerging, Cytiva established the Cytiva Experience Learning Lab (CELL). Located in Singapore, this learning facility provides education and training on the latest bioprocessing and production techniques to develop advanced therapeutics to tertiary academics and research institutes.

Secondly, cell and gene therapies are highly personalized, making process standardization difficult. Developing scalable, reproducible, and robust manufacturing processes is a significant technical challenge. In addition to that, ensuring consistent quality and safety across large-scale production is critical. Implementing rigorous quality control measures that can adapt to scalable manufacturing is complex. In addition, there are relatively few specialized manufacturing facilities in the APAC region. This can lead to bottlenecks and limited production capacity. Our enterprise solutions, consisting of FlexFactory™ production platforms and process design services, provide customers with options to achieve their goals at every level of biomanufacturing. FlexFactory™ is our scalable, integrated upstream and downstream single-use or hybrid platform that gives customers rapid access to a cGMP manufacturing capacity while providing flexibility in their production process when their needs change

Thirdly, we need to address access, navigating the diverse healthcare systems and reimbursement policies across the APAC region. Addressing these challenges requires a coordinated effort involving stakeholders from industry, government, academia, and healthcare providers. 

How is Cytiva positioning itself to address the manufacturing capacity constraints in the Asia-Pacific region, and what strategies are being implemented to enhance local production capabilities?

In my view, capacity constraints in Asia Pacific can be focused on two areas - talent and domain knowledge challenges as well as manufacturing capacity constraints. To enhance local production capabilities, we’ll continue to nurture talent and give customers access to flexible and scalable manufacturing solutions.

Earlier, I’ve elaborated on how we’re addressing domain knowledge and talent constraints through our Fast Trak Bioprocess Training and Education offering, where we train the next generation of talent, and reinforce specialist knowledge in bioprocessing skills and in the field.

Secondly, our enterprise solutions, consisting of FlexFactory™ production platforms and process design services, provide customers with options to achieve their goals at every level of biomanufacturing — process, capacity, equipment, automation, and human competencies.

FlexFactory™ is our scalable, integrated upstream and downstream single-use or hybrid platform. It gives customers rapid access to a cGMP manufacturing capacity while providing flexibility in their production process when their needs change. We have approximately 150 FlexFactories globally, 45% of which are in Asia Pacific.

That said, the industry will see an increasing demand for access to CDMO facilities across the landscape, as companies working across the full range of therapeutic modalities will continue to seek external capacity for the manufacture of their products, both during clinical development and post-approval. 

In India, Cytiva has launched a manufacturing facility equipped with a customer experience centre in Pune last year, to support local demand for the development of biologics and biosimilars, as well as the talent training required for it.

What opportunities do you see in the Asia-Pacific region for expanding cell and gene therapy manufacturing, particularly in terms of collaboration between local biotech companies and global entities?

Asia Pacific presents great opportunities for global companies and local biotech companies to work closely together to advance cell and gene therapy manufacturing. Cytiva offers the technology, innovation support and training to help biotechs advance their pursuits faster.

Firstly, Cytiva’s manufacturing technologies have enabled 5 out of 6 approved CAR-T therapies from development through to commercial production globally. With our FlexFactory biomanufacturing platform, we’ve helped Thai-based Genepeutic Bio establish the first GMP-certified cell therapy manufacturing facility in the country so it can deliver chimeric antigen receptor-T (CAR T) cell therapies to a few hundred patients with relapsed and refractory blood cancers such as acute lymphoid leukemia (ALL) in Thailand and Southeast Asia by 2025.   

Beyond Thailand, in Australia, for example, Cytiva and the University of Adelaide worked together with BioCina, an Australian-based contract development and manufacturing organization (CDMO), to expand its facility in Adelaide to manufacture mRNA-based vaccines and therapies. Both facilities are GMP-certified.

Secondly, and as outlined in Cytiva’s 2023 Global Biopharma Resilience Index, on one hand economies such as Singapore, South Korea, Japan and Australia, are able to put in place favorable ecosystems for biotechs to set up, develop therapies and scale up manufacturing. Their contributions have made Asia Pacific the second largest region for Advanced Therapy Medicinal Product (ATMP) trials, surpassing Europe. Other countries within Asia are at an earlier developmental stage in their journey to nurture biotech innovation. To address this, Cytiva provided flexible access to bioprocess development and technology verification to biotech startups to advance their projects from molecule to market. This initiative is called BioChallenge, and it has expanded its impact across China, South Korea, Southeast Asia, and Australia and New Zealand. In the 2023 Southeast Asia BioChallenge, two winners – Singapore-based BetaLife and Thailand-based BGF Plantrix emerged as winners.

Thirdly, the shortage of talent remains one of the factors holding back Asia’s potential to become a biotech hub – with some countries facing stiffer competition than others. In 2023, for example, Cytiva added another training centre in India – the Cytiva Customer Experience Center in Pune. This centre conducts immersive trainings and technology demonstrations needed to accelerate the development of novel therapeutics and help India deliver on its ambition to be a global biomanufacturing hub.

Looking ahead, what are the key trends and advancements in cell and gene therapy manufacturing that you believe will shape the industry in Asia over the next 5-10 years?

Artificial intelligence is becoming increasingly widespread, but uncertainties in regulations are making cell and gene therapy providers cautious, especially in adopting AI-driven analytical technologies in clinical and manufacturing settings.  Additionally, some analytical technology developers mentioned that they often miscalculate development costs because they underestimate the expense of acquiring training data.

Secondly, the shift towards decentralized manufacturing is a trending subject for cell and gene therapy providers. Analytical technologies must be adjusted to a non-traditional user base and environment.  User-friendly interfaces and tool robustness, especially for data management, extraction and interpretation, are essential as standardization and validation across multiple sites continue to be a challenge.

Thirdly, developments in health IT and adoption of electronic health records across APAC have paved the way for a more comprehensive storage of data on a patient’s health history including genetic history, which can accelerate and be integrated into research and clinical settings.