Containers for vaccine manufacturing might tackle local outbreaks and prevent future pandemics

Disease and treatment 17. nov 2022 4 min Associate Professor Seyed Soheil Mansouri Written by Morten Busch

Almost 3 years into the COVID-19 pandemic and nearly 2 years after the first COVID-19 vaccine was approved, bottlenecks in production and supply chain infrastructure continue to delay vaccination campaigns in low- and middle-income countries. Now researchers have designed mobile on-demand vaccine manufacturing units that can produce nearly 10,000 vaccine doses daily near the end-users. Since the new setup can accommodate various types of production from food to biopharmaceuticals, it can become an important tool to prevent or combat not just pandemics but also food shortages and famine.

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When the COVID-19 pandemic peaked and almost shut down the entire world and thus world trade, many countries had to start producing various basic necessities locally. This became even more significant when the COVID-19 vaccines appeared. The competition for the tools that could open society up again was intense. At the back of the queue came those who did not have the skills to produce or did not have the money to pay. However, the lack of vaccines in low- and middle-income countries created not only a more uncertain world but also fertile ground for developing new SARS-CoV-2 variants, which ultimately plagued the whole world again.

“One lesson learned from a quality viewpoint during this pandemic was that everybody realised that diseases spreading even in the poorest country in the world can also make life miserable for affluent people. In this work, we designed two mobile on-demand (MOD) vaccine manufacturing units based on a protein antigen expressed in yeast and in vitro transcription of mRNA – each comprising three shipping containers. The moderate increase in production costs for these smaller units is outweighed by reduced waste and the earlier protection of vulnerable populations,” explains co-author Seyed Soheil Mansouri, Associate Professor, Department of Chemical and Biochemical Engineering, Technical University of Denmark, Kongens Lyngby.

Idea of modularity and flexibility

The project initially started as a competition for European students. A team of BSc students at the RWTH Aachen University, DTU and Technologico de Monterrey also started investigating. After the competition, the students reached out to Seyed Soheil Mansouri.

“They asked me whether I could help them, since they were interested in continuing. The idea was to set up MOD vaccine manufacturing production, which could enable local production of vaccines in the regions in which they are needed the most. Thus, MOD vaccine manufacturing may help to quickly ramp up production volume while bypassing infrastructure bottlenecks such as the inadequate capacity of planes and airports to ship and receive cooled vaccine doses via air freight,” says Seyed Soheil Mansouri.

Even before the COVID-19 pandemic, WHO estimated that 50% of vaccine doses may be wasted worldwide because of shipping and storage problems. So new solutions are needed to guarantee reliable global supply and rapid distribution of vaccines while being flexible enough to respond to local outbreaks and new SARS-CoV-2 variants emerging in the future.

“MOD vaccine production provides a solution that contrasts with the conventional approach of centralised production in a few unique large-scale plants. This implements the ideas of modularity and flexibility. The MOD plants can be moved between severely affected areas to quickly tackle local outbreaks,” explains Seyed Soheil Mansouri.

Production costs per dose considerably higher

Despite the apparent technical challenges of producing viral proteins such as the COVID-19 spike protein and in vitro production of the new mRNA vaccine technology, the researchers managed to design a container concept that enables all the many small-scale processes needed for production. The real challenge of the project, however was quite different.

“The human capacity and the resources needed for these modular units then also become an issue. So fully implementing this also requires substantial automation. Collaborative robots can actually make all this, and eventually these units could be basically operated from a central global operation hub,” says Seyed Soheil Mansouri.

To determine whether the container setup was economically feasible, the costs per vaccine dose in the MOD container setups were analysed and compared with a centralised production scenario. Finally, the researchers optimised the facility location for a vaccination campaign in Nigeria as an application example.

“Despite our efforts to obtain accurate cost estimates for individual cost factors, we ended up with considerable uncertainty of the final costs. Establishing a pilot plant can narrow this uncertainty since we can determine the production costs more precisely. However, the production costs per dose were definitely considerably higher than the estimated costs for centralised production,” explains Seyed Soheil Mansouri.

Fitting into different types of production

Nevertheless, the researchers think that the MOD containers may ultimately justify the extra costs, because they may help to provide much-needed vaccine doses more rapidly than centralised production. Further, eliminating interregional transport and regional intermediate storage hubs from the distribution network reduces storage temperature anomalies.

“The loss of doses will be greatly reduced, and this represents a very strong economic incentive. But support will be needed at the beginning, either subsidies from governments or donations from private and public organisations until the capacity is created locally and the production becomes self-sufficient. So MOD vaccine production might be feasible and potentially attractive, but future work will have to determine the practical implementation of the approach,” says Seyed Soheil Mansouri.

The researchers strongly believe that decentralised small-scale factories can help tip the scales in the battle against COVID-19 and future pandemics. Afterwards, the plants can be collected and restocked for a new campaign in another region.

“So, experts on the ships transporting them could reprogramme them on the way from, for example, Africa to Asia. And the time elapsed in ocean transport could be sufficient for them to start to produce a new vaccine,” adds Seyed Soheil Mansouri.

More resilient to famine

For now, the MOD container concept is still on the drawing board but might be used in the current pandemic against COVID-19.

“Even though some high-income countries might be approaching herd immunity, the vaccination campaigns worldwide have just begun, and the lack of supply chain infrastructure in low- and middle-income countries is a major limitation to distributing vaccines in these regions. Further, SARS-CoV-2 will not disappear, and new variants or even new pandemics will emerge. With the MOD units, we can help to create a better response,” explains Seyed Soheil Mansouri.

Alternatively, if the containers are designed intelligently, they can even be adapted for different types of production, including food and biopharmaceuticals.

“What we have done here is actually the beginning of some sort of conceptual way of thinking. For example, the MOD production units can be used to cultivate novel types of protein such as microalgae or the like, to rapidly provide some source of food, making communities more resilient to famine, or they can even be repurposed for small-scale production of cancer vaccines,” concludes Seyed Soheil Mansouri.

Mobile on demand COVID-19 vaccine production units for developing countries” has been published in Industrial & Engineering Chemistry Research. Earlier results of this research were presented as part of the European Committee for the Use of Computers in Chemical Engineering Education (EURECHA) Student Contest 2020. The Novo Nordisk Foundation has supported the research through a grant for the project Accelerated Innovation in Manufacturing Biologics (AIMBio).

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