Vaccine Manufacturing Capacity Research Articles

'Our project, your problem?' A case study of the WHO's mRNA technology transfer programme in South Africa.

In June 2021 the World Health Organization (WHO) and the Medicines Patent Pool (MPP) launched an mRNA technology transfer programme. With a South African consortium serving as the hub, the programme aimed to increase vaccine manufacturing capacity in low- and middle-income countries (LMICs) in view of the "vaccine apartheid" that was observed during COVID-19. Following Clarke's "situational analysis," the present study assessed whether the mRNA programme differs from the approach and practices that comprise current biopharmaceutical production. Numerous documentary sources, including legal agreements underpinning the programme, funding agreements, and patent filings, were reviewed. Semi-structured interviews with 35 individuals, ranging from the programme's architects and university scientists to representatives from LMIC vaccine manufacturers taking part in the programme were also conducted. While the mRNA programme may improve the sharing of knowledge, other design features, in particular, weak conditionalities around product affordability, participants' freedom to contract with third parties, and acceptance of market-based competition, are in line with the status quo. Further, WHO and MPP's tight control over the programme evokes the dynamics that are often in play in global health, to the detriment of empowering LMIC-based manufacturers to generate mRNA products in response to local health needs.

Advancing Vaccinology Capacity: Education and Efforts in Vaccine Development and Manufacturing across Africa.

Africa, home to the world's second-largest population of approximately 1.3 billion, grapples with significant challenges in meeting its medical needs, particularly in accessing quality healthcare services and products. The continent faces a continuous onslaught of emerging infectious diseases, exacerbating the strain on its already fragile public health infrastructure. The COVID-19 crisis highlighted the urgency to build local vaccine production capacity and strengthen the health infrastructure in general. The risks associated with a heavy reliance on imported vaccines were exposed during the COVID-19 pandemic, necessitating the need to nurture and strengthen the local manufacturing of vaccines and therapeutic biologics. Various initiatives addressing training, manufacturing, and regulatory affairs are underway, and these require increasing dedicated and purposeful financial investment. Building vaccine manufacturing capacity requires substantial investment in training and infrastructure. This manuscript examines the current state of education in vaccinology and related sciences in Africa. It also provides an overview of the continent's efforts to address educational needs in vaccine development and manufacturing. Additionally, it evaluates the initiatives aimed at strengthening vaccine education and literacy, highlighting successful approaches and ongoing challenges. By assessing the progress made and identifying the remaining obstacles, this review offers insights into how Africa can enhance its vaccine manufacturing capacity to respond to vaccine-preventable disease challenges.

The Value of Flexible Vaccine Manufacturing Capacity: Value Drivers, Estimation Methods, and Approaches to Value Recognition in Health Technology Assessment.

Expanding flexible vaccine manufacturing capacity (FVMC) for routine vaccines could facilitate more timely access to novel vaccines during future pandemics. Vaccine manufacturing capacity is 'flexible' if it is built on a technology platform that allows rapid adaption to new infectious agents. The added value of routine vaccines produced using a flexible platform for pandemic preparedness is not currently recognised in conventional health technology assessment (HTA) methods. We start by examining the current state of play of incentives for FVMC and exploring the relation between flexible and spare capacity. We then establish the key factors for estimating FVMC and draw from established frameworks to identify relevant value drivers. The role of FVMC as a countermeasure against pandemic risks is deemed an additional value attribute that should be recognised. Next, we address the gap in the vaccine-valuation literature between the conceptual understanding of the value of additional FVMC and the availability of accurate and reliable tools for its estimation to facilitate integration into HTA. Three practical approaches for estimating the value of additional FVMC are discussed: stated and revealed preference studies, macroeconomic modelling, and benefit-cost analysis. Lastly, we review how value recognition of additional FVMC can be realised within the HTA process for routine vaccines manufactured on flexible platforms. We argue that, while the value of additional FVMC is uncertain and further research is needed to help to better estimate it, the value of increased pandemic preparedness is likely to be too large to be ignored.

An mRNA technology transfer programme and economic sustainability in health care.

The World Health Organization (WHO) set up the messenger ribonucleic acid (mRNA) technology transfer programme in June 2021 with a development hub in South Africa and 15 partner vaccine producers in middle-income countries. The goal was to support the sustainable development of and access to life-saving vaccines for people in these countries as a means to enhance epidemic preparedness and global public health. This initiative aims to build resilience and strengthen local vaccine research, and development and manufacturing capacity in different regions of the world, especially those areas that could not access coronavirus disease 2019 (COVID-19) vaccines in a timely way. This paper outlines the current global vaccine market and summarizes the findings of a case study on the mRNA technology transfer programme conducted from November 2022 to May 2023. The study was guided by the vision of the WHO Council on the Economics of Health for All to build an economy for health using its four work streams of value, finance, innovation and capacity. Based on the findings of the study, we offer a mission-oriented policy framework to support the mRNA technology transfer programme as a pilot for transformative change towards an ecosystem for health innovation for the common good. Parts of this vision have already been incorporated into the governance of the mRNA technology transfer programme, while other aspects, especially the common good approach, still need to be applied to achieve the goals of the programme.

The role of hesitancy and infrastructure in the equity and efficiency of COVID-19 vaccine administration.

After the first COVID-19 vaccines received emergency use authorization from the U.S. FDA in December 2020, U.S. states employed vaccine eligibility and administration plans (VEAPs) that determined when subgroups of residents would become eligible to receive the vaccine while the vaccine supply was still limited. During the implementation of these plans, public concern grew over whether the VEAPs and vaccine allocations from the federal government were resulting in an equitable and efficient vaccine distribution. In this study, we collected data on five states' VEAPs, federal vaccine allocations, vaccine administration, and vaccine hesitancy to assess the equity of vaccine access and vaccine administration efficiency that manifested during the campaign. Our results suggest that residents in states which opened eligibility to the vaccine sooner had more competition among residents to receive the vaccine than occurred in other states. Regardless of states' VEAPs, there was a consistent inefficiency in vaccine administration among all five states that could be attributed to both state and federal infrastructure deficits. A closer examination revealed a misalignment between federal vaccine allocations and the total eligible population in the states throughout the campaign, even when accounting for hesitancy. We conclude that in order to maximize the efficiency of future mass-vaccination campaigns, the federal and state governments should design adaptable allocation policies and eligibility plans that better match the true, real-time supply and demand for vaccines by accounting for vaccine hesitancy and manufacturing capacity. Further, we discuss the challenges of implementing such strategies.

Key considerations for the development of novel mRNA candidate vaccines in LMICs: A WHO/MPP mRNA Technology Transfer Programme meeting report

The WHO/MPP mRNA Technology Transfer Programme, initiated in 2021, focuses on establishing mRNA vaccine manufacturing capacity in LMICs. On 17–21 April 2023, Programme partners were convened to review technology transfer progress, discuss sustainability aspects and promote mRNA product development for diseases relevant to LMICs. To help guide product development, this report introduces key considerations for for understanding the likelihood of technical and regulatory success and of policy development and procurement for mRNA vaccines to be developed and manufactured in LMICs. The report underscores the potential for LMICs to establish sustainable mRNA R&D pipelines.

Expanding global vaccine manufacturing capacity: Strategic prioritization in small countries.

The COVID-19 pandemic highlighted significant gaps in equitable access to essential medical countermeasures such as vaccines. Manufacturing capacity for pandemic vaccines, therapeutics, and diagnostics is concentrated in too few countries. One of the major hurdles to equitable vaccine distribution was "vaccine nationalism", countries hoarded vaccines to vaccinate their own populations first which significantly reduced global vaccine supply, leaving significant parts of the world vulnerable to the virus. As part of equitably building global capacity, one proposal to potentially counter vaccine nationalism is to identify small population countries with vaccine manufacturing capacity, as these countries could fulfill their domestic obligations quickly, and then contribute to global vaccine supplies. This cross-sectional study is the first to assesses global vaccine manufacturing capacity and identifies countries with small populations, in each WHO region, with the capacity and capability to manufacture vaccines using various manufacturing platforms. Twelve countries were identified to have both small populations and vaccine manufacturing capacity. 75% of these countries were in the European region; none were identified in the African Region and South-East Asia Region. Six countries have facilities producing subunit vaccines, a platform where existing facilities can be repurposed for COVID-19 vaccine production, while three countries have facilities to produce COVID-19 mRNA vaccines. Although this study identified candidate countries to serve as key vaccine manufacturing hubs for future health emergencies, regional representation is severely limited. Current negotiations to draft a Pandemic Treaty present a unique opportunity to address vaccine nationalism by building regional capacities in small population countries for vaccine research, development, and manufacturing.

Leveraging the positives from the pandemic to strengthen infectious disease care in low-income and middle-income countries

Leveraging the positives from the pandemic to strengthen infectious disease care in low-income and middle-income countries

Upscaling vaccine manufacturing capacity - key bottlenecks and lessons learned

The COVID-19 pandemic put enormous pressure on the vaccine production chain as billions of vaccines had to be produced in the shortest timeframe possible. Vaccine production chains struggled to keep up with demand, resulting in disruptions and production delays. This study aimed to make an inventory of challenges and opportunities that occurred in the production chain of the COVID-19 vaccine. Insights derived through approximately 80 interviews and roundtable discussions were combined with findings from a scoping literature review. Data were analysed through an inductive process where barriers and opportunities were linked to specific facets of the production chain. Key bottlenecks identified include a lack of manufacturing facilities, a lack of tech-transfer personnel, inefficient arrangement of production stakeholders, critical shortages in raw materials, and restricting protectionist measures. A need for a central governing body to map out shortages and to coordinate allocation of available resource became evident. Other suggested solutions were to repurpose existing facilities and to build in more flexibility in the production process by making materials interchangeable. Also, simplification of the production chain could be achieved through geographical reengagement of processes. Three overarching themes were identified, impacting overall functioning of the vaccine production chain: regulatory and visibility, collaboration and communication, and funding and policy. The results in this study showed a multitude of interdependent processes underlying the vaccine production chain, executed by diverse stakeholders with differing objectives. It characterizes the global complexity of the pharmaceutical production chain and highlights its extreme vulnerability to disruptions. More resilience and robustness must be integrated into the vaccine production chain, and low-middle income countries should be empowered to manufacture vaccines themselves. In conclusion, there’s a need to rethink the production system for vaccines and other essential medicines in order to become better prepared for future health crises.

COVID-19 as a catalyst for vaccine manufacturing: A South African experience

COVID-19 highlighted inequitable vaccine distribution and the urgent need for vaccine manufacturing capacity on the African continent. This resulted in a burst of scientific engagement and international funding to augment capacity on the continent. However, short-term investment needs to be reinforced by a robust, strategic long-term plan to ensure sustainability.

Building global vaccine manufacturing capacity: Spotlight on Africa

Africa is set to experience a three-fold increase in vaccine demand by 2040, yet the continent possesses few domestic capabilities for vaccine production. This lack of production capacity, heavy reliance on foreign aid, disruptions of hard-won immunization progress due to the effects of the COVID-19 pandemic, and fluctuating vaccine market dynamics threaten to hinder ongoing efforts to increase vaccination rates on the continent. In order meet the vaccine demands of a rapidly growing population, and to be able to provide novel vaccines to its population in the future, the African continent must develop a sustainable vaccine manufacturing infrastructure. The African Union, in partnership with the Africa Centres for Disease Control and Prevention, recently set forth its Program for African Vaccine Manufacturing Framework for Action, which sets the goal of Africa producing 60 % of its vaccine needs by 2040. To meet these goals, African governments and their multinational, philanthropic, and private sector partners must work to secure low-cost financing and provide a favourable regulatory environment for nascent African vaccine manufacturers. Doing so will save lives, safeguard the health of the continent’s current and future citizens, and contribute to economic growth through the development of local bioeconomies.

Placing a value on increased flexible vaccine manufacturing capacity for future pandemics.

Placing a value on increased flexible vaccine manufacturing capacity for future pandemics.

COVID-19 and Malaria Vaccine Advanced Market Commitments: Opportunities to Incentivize Investment in Africa’s Vaccine Manufacturing Industry

Introduction Using push dynamics to drive the purchase of commodities with forecasted demand, the advanced market commitment (AMC) model has been applied to the development of vaccines catering to low-income countries in Africa and the globe. This model is currently the driving force behind both the delivery of COVID-19 vaccines to countries unable to afford open market prices and the roll out of the RTS,S/AS01 (Mosquirix) malaria vaccine in the WHO Africa region. Methods This literature review instills a comprehensive understanding of the costs associated with vaccine manufacturing development in the Africa region and draws particular focus to the prices paid by African national governments for the recently rolled out COVID-19 vaccines through the COMAX AMC as well as the estimated costs (based on birth cohort data and DPT vaccination coverage data) of the recently WHO recommended malaria vaccine program. Results Ethiopia, a GAVI supported country, is projected to pay between 4.2 and 9.9 million USD annually to vaccinate its target population with RTS,S/AS01b. GAVI ineligible countries such as South Africa and Egypt are projected to spend approximately 15.5 million and 43.3 million USD respectively. Of the GAVI ineligible and self financing countries, those with COVID-19 vaccine manufacturing capacity such as South Africa are able to access vaccine costs at 10 USD/dose compared to the 37 USD/dose spent by the 8 countries without manufacturing capacity. Results Investment in existing vaccine manufacturing companies in Eastern and Western Africa has projected growth with CAGR as high as 37% within 10 years. By purchasing and procuring vaccines from local regional manufacturing hubs, a number of donor un-supported self-financing countries in Africa have the potential to save up to 10 USD per vaccine dose.

Techno-Economic Evaluation of Novel SARS-CoV-2 Vaccine Manufacturing in the Insect Cell Baculovirus Platform

The need to increase the COVID-19 vaccine manufacturing capacity at low to middle-income countries (LMIC) led to a growing focus on Novavax (NVX-CoV2373), a thermostable protein subunit vaccine manufactured using a baculovirus and insect cell system (BICS) platform. This study aimed to conduct a techno-economic analysis to assess the BICS platform of vaccine manufacturing and compare it to the mRNA and the saRNA platform. The data from the Novavax patent for the COVID-19 vaccine formulation and the manufacturing steps were used to simulate the BICS vaccine production in SuperPro Designer. From the techno-economic analysis, the productivity of all platforms was compared in terms of doses/day per L production scale. The saRNA platform’s productivity is about 1,000-fold of the BICS platform and 20-fold of the mRNA platform. BICS is a feasible option for LMIC to produce vaccines because the cost per dose is like the saRNA platform, while the mRNA platform’s cost per dose is 7 times higher than the BICS and saRNA platforms. However, further optimization is necessary to improve the productivity of the BICS platform to match saRNA’s platform.

Breaking the cycle: building vaccine manufacturing capacity in Africa

The COVID-19 pandemic had brought inequities in access to vaccines into sharp relief and highlighted the importance of manufacturing vaccines within low and middle-income countries. The road ahead has many challenges but with optimism and perseverance, I believe we can build a more sustainable vaccine ecosystem in Africa.On November 8, 2002, Charlotte Barker, Editor, Vaccine Insights, spoke to Patrick Tippoo about building vaccine manufacturing capacity in Africa. This article has been written based on that interview.

Strengthening pandemic preparedness: Build the vaccine manufacturing capacity in low- and middle-income countries

Strengthening pandemic preparedness: Build the vaccine manufacturing capacity in low- and middle-income countries

First International Conference on Public Health in Africa (CPHIA 2021)

The first international Conference on Public Health in Africa (CPHIA 2021) was hosted virtually by the African Union (AU) and Africa Centres for Disease Control and Prevention (Africa CDC) from 14-16 December 2021. This historic three-day conference focused on the need to address long-standing health challenges on the continent, including vaccine inequity and manufacturing capacity, the ongoing COVID-19 pandemic, and the need to build resilient health systems.

Closing the global vaccine equity gap: equitably distributed manufacturing

Closing the global vaccine equity gap: equitably distributed manufacturing

Transforming or tinkering: the world remains unprepared for the next pandemic threat

Transforming or tinkering: the world remains unprepared for the next pandemic threat

Vaccine apartheid: global cooperation and equity

Vaccine apartheid: global cooperation and equity