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Bioreactors – How Reduced Bioreactor Footprint Can Improve Global Vaccine Delivery

The global distribution of vaccines is vital to eradicating deadly diseases such as smallpox, Sars-Cov-2 and polio. There was an intensive vaccination campaign back in 1980 which the Who Health Organisation declared that smallpox was eradicated. Due to mass vaccination, there is also fewer than 500 cases of polio a year.

The United States is one of the countries with the ability to implement extensive vaccination campaigns and has nearly eliminated 14 deadly diseases such as diphtheria and measles. Unfortunately, there are more deadly diseases prevalent in countries that are unable to afford a rigorous vaccination campaign.

The high cost of vaccines is what is the main issue when it comes to carrying out nationwide vaccinations. Vaccines that are manufactured at a cheaper price can be distributed globally at lower costs which contributes to the elimination of once deadly diseases.

Bioreactor Footprint Correlates Closely with Manufacturing Costs:

Reducing bioreactor and various instruments footprint can be very beneficial when it comes to the distribution of vaccines as space is a precious commodity in these plants. Reducing the footprint of bioreactors will reduce the overall cost of the goods, leading to a more efficient and cost-effective setup.

The footprint of bioreactors can be greatly reduced with engineering innovative methods to increase cell density. This results in greater yields from the same setup and more doses of the vaccine can be produced without the need to increase costs.

Increasing Productivity with Reduced Equipment Usage:

The goal of process intensification is to increase productivity while reducing necessary plant size. This means there is lower capital investment needed when setting up new facilities, lower lifetime overhead costs, and the overall cost of goods – while maintaining or possibly increasing the output of goods from the plants.

When using bioreactors, the process intensification is achieved by increasing the cell density in the reactors medium. Cell cultures are grown on 2D surfaces, and scale-up is simple as it requires increasing the amount of surface area available for the cells to adhere to.

This method can achieve a cell density of 20 million cells/mL and requires a large manufacturing footprint: the number of incubators and biosafety cabinets needs to scale with the culture size. Skilled operators are needed to monitor such cultures.

Microcarriers are a newer technology that enable scientists and manufacturers to reach significantly higher cell densities using a smaller footprint. In 2014, the Pall iCELLis achieved 100 million cells/mL, and this keeps increasing. Currently, Univercells is using a grant from the Gates Foundation to increase the density up to an impressive 250 million cells/mL – with the goal of lowering vaccine manufacturing cost enough that they can deliver polio vaccines to low and middle income countries at a cost of only $0.15 per dose.

Scaling Out and How It Can Maximise Efficiency in Existing Facilities:

Scaling out bioreactor facilities refers to expanding the product of smaller bioreactors without needing to scale up to production-scale reactors. This can be achieved by simply increasing numbers of smaller bioreactors or expanding the cell density in a single, smaller reactor.

It is often easier and more feasible to scale out rather than up from 2,000 litre bioreactors to 10-20,000 litre bioreactors. This allows for large scale culture growth along with vaccine production without needing to facilitate larger scale bioreactors.

The key advantage to scaling out this process means that single-use bioreactors can still be used. SUBs are cheaper, more flexible, and can achieve significantly more uptime than multiuse reactors – but they generally have a maximum capacity of about 2,000 L. Being able to increase the number of SUBs in a facility while also increasing the achievable cell density can bridge the 10x gap between a SUB and a production-scale bioreactor.

Scaling-up reduces the necessary footprint in commercial scale bioreactors and can be useful in phase 3 of vaccine trials that require a production of many doses yet still have uncertain outcomes. Plants will be able to meet production needs for clinical trials without needing a huge level of expenditures which may allow a greater number of biologics to make it to the clinic trials. This would result in a great number of new vaccines making it to the worldwide marketing quicker and allow us to combat new diseases, like Sars-Cov-2, more effectively than we would have in the past.

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