Building Sustainable Vaccine Manufacturing Practices in Lower-Resourced Settings

Vaccines are inherently labile biologicals that require complex manufacturing and handling processes. Vaccine manufacturing requires multiple considerations, such as technical expertise, production capabilities, market demand, and stringent regulatory requirements. Underpinning these considerations is the need for sustainable funding. Vaccine manufacturing is a capital-intensive endeavor with facilities and equipment costing up to $700 million. This excludes the costs of product development, licensing, regulatory, and overhead costs, clubbed with a significant risk of development failure and unprofitability. Because of the high investments needed, there are often conflicting interests between commercial drivers and public health needs. The COVAX manufacturing task force highlighted key prerequisites for vaccine manufacturing to address future pandemic responses. These include a wide range of efforts, including upgrading manufacturing facilities to international standards, expanding the vaccine manufacturing workforce and regulatory capabilities, and enabling technology transfer.

Maintaining quality throughout the process of vaccine production to delivery is paramount. As it involves many upstream and downstream processes, vaccine manufacturing demands a robust quality management system to ensure an uninterrupted supply of raw materials, consumables, current Good Manufacturing Practice-compliant facilities, and state-of-the-art equipment. Optimizing the scale-up of production, validation, and prompt resolution of technical issues are important to address when expanding the production capacity. The complexity of production is further constrained by vaccine lability, with many vaccines requiring cold chain maintenance during transportation and storage, some at very low temperatures. In addition, supply chain networks for manufacturing and packaging processes spread across different countries add to the complexity of producing consistently good quality batches of these susceptible biological products.

From an economic perspective, investing in or scaling up vaccine manufacturing capacity has limited utility without sustainable demand. Overall vaccine demand depends on several factors: (i) private, public, and donor market demands; (ii) disease prevalence; (iii) vaccine effectiveness and safety; (iv) trust in the government and health system; and (v) social norms, such as social influence, vaccination decisions of peers and vaccine free-riding behavior. For example, Gavi, the Global Vaccine Alliance, provides data on forecasting vaccine demand to assist stakeholders in understanding the vaccine market needs. On the supply side, health systems must also have adequate facility readiness to effectively deliver the vaccines.

During the COVID-19 pandemic, expedited regulatory approvals were crucial for the rapid development, manufacturing, and delivery of vaccines. However, prior to the pandemic, fragmented regulatory requirements, complex quality control standards, and the lack of a central monitoring and coordinating system to manage capacity had hampered vaccine manufacturing efforts.

Setting up sustainable vaccine manufacturing capabilities also depends on issues around intellectual property rights of the vaccines. The current Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) established by the World Trade Organization grants disproportionate market power to the bigger developers and manufacturers and leads to market oligopoly, further increasing the barrier of entry for smaller manufacturers. While technology transfer as a method of collaboration is proposed to improve efficiency in manufacturing, it requires extensive and transparent knowledge sharing and active support from the original manufacturers to reproduce the original vaccines with acceptable variations. This entire technology transfer process may take from 18 months up to 30 months as it involves a wide range of activities and expertise, including specialized skills, documentation, laboratory technicians, and regulation registration. In public health emergencies where it is essential to ramp up vaccine production, this timeline delays access to life-saving vaccines.

Vaccine manufacturing also has a profound impact on the environment. Vaccine packaging material, which is essential for transport and storage, can raise costs including disposal expenses. There is a significant increase in glass, plastic, and rubber residues from vaccine containers as well. Combined with the added waste from the process of vaccination, such as needles and syringes that are often non-biodegradable, vaccine manufacturing greatly affects the environment.

The increasing vaccine inequity due to limited diversity in regional manufacturing, rising costs of vaccine manufacturing facilities and equipment, complex and fragmented regulatory frameworks, and market oligopoly of vaccine manufacturing due to intellectual property rights threaten to derail the progress and lives saved by immunization. Below are recommendations to ensure the sustainability of vaccine manufacturing.

• Conduct feasibility assessments and demand forecasting to understand vaccine demand and choose appropriate technology platforms and vaccine candidates.
• Direct public investments in manufacturing facilities, including funding in national budgets.
• Employ a life-course approach to vaccination. This includes providing immunization schedules and access to vaccination for individuals of all ages with national disease burden consideration, individual phase of life, lifestyle preferences, and risk factors for infectious disease.
• Improve regulatory pathways and standards using regulatory reliance and strengthen regulatory capacity by training and upskilling the regulatory workforce.
• Promote greater collaboration and cooperation among countries to address systemic issues around intellectual property rights, technology transfer, and data sharing.
• Implement optimization of packaging materials and sustainable manufacturing practices to maintain ecological sustainability.

NOTE: The ADB-CoRE Vaccine Regulation Project aims to inform the ADB Human and Social Development Sector Group on the vaccine regulatory landscape in Asia and the Pacific, focusing on Bangladesh, India, Indonesia, Republic of Korea, and Singapore. Initiated in 2022, it has facilitated public-private vaccine stakeholder engagements among ADB developing member countries and produced country-specific and regional vaccine landscape analysis and recommendations.

This article reflects a collaborative effort, with insights from Assistant Professor Tan-Koi Wei Chuen, Professor Silke Vogel, and Professor John Lim of Duke-NUS Medical School; and Dr. Ben Coghlan, Dr. Jae Kyoun Kim, and Dr. Patrick Osewe of Asian Development Bank.

A. Farlow et al. 2023. The Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs. Vaccines (Basel). 11 (3).

D. E. Phillips et al. 2017. Determinants of Effective Vaccine Coverage in Low and Middle-Income Countries: A Systematic Review and Interpretive Synthesis. BMC Health Services Research. 17 (1). 681.

H.C. Turner, G.E. Thwaites, and H.E. Clapham. 2018. Vaccine-Preventable Diseases in Lower-Middle-Income Countries. The Lancet Infectious Diseases. 18 (9). pp. 937–939.

N. Sood et al. 2022. Shifting the Demand for Vaccines: A Review of Strategies. Annual Review of Public Health. 43. pp. 541–557.

R. Phadke et al. 2021. Eco-Friendly Vaccination: Tackling an Unforeseen Adverse Effect. The Journal of Climate Change and Health. 1:100005.

S. Plotkin et al. 2021. The Complexity and Cost of Vaccine Manufacturing—An Overview. Vaccine. 35 (33). pp. 4064–71.

World Health Organization. 2023. Global Vaccine Market Report 2022: A Shared Understanding for Equitable Access to Vaccines. WHO.