Biopharma Visions – Features

David Gemmell examines possible biopharmaceutical facilities of the future

IN THE final article of our biopharmaceutical series, we will briefly discuss the conceptual designs of the facilities of the future. Over the last four articles, we have evaluated different key technologies used in traditional and new biotherapeutic manufacturing processes. TEC number 972 discussed the rise of continuous bioprocessing. Many of these next-generation technologies will be essential to meet future bioprocess requirements.

Many large biomanufacturers are investing in large capacity stainless steel facilities with large 20,000 L bioreactors.1 There will likely always be a place for large-scale traditional manufacturing, especially for older molecules or those with very large patient populations or markets. This article will focus on expected trends for advanced manufacturing processes focused on small batch volumes with higher throughputs.

Facilities of the future

Significant changes are expected with regard to next-generation bioprocesses. The industry is actively seeking manufacturing capabilities that can be deployed in developing countries so that a “made in
country-for-country strategy could be applied.2

By creating simplified designs and incorporating some of the closed processing concepts we’ve talked about in previous articles (ECT numbers 971–972), a much smaller facility could be achieved that does not rely heavily on traditional steam and water services for sterilization and cleaning purposes.

By using pre-sterilized single-use components such as filters, bags, transfer sets, etc., turnaround time is greatly reduced and cross-contamination risks are mitigated. These benefits have been discussed before, but one benefit that has yet to be highlighted is the sheer mobility of these technologies. By using smaller, skid-based unit operations with higher flow rates but overall smaller batch volumes, plant designers can create highly flexible concepts that have a modest physical footprint and dramatically cleanroom HVAC requirements. reduced. This can lead to huge savings, as HVAC systems are typically the most expensive utility systems to operate.

Ballroom concept

One of the key concepts is to create a large space that can be arranged in different ways. This is called the “ballroom” concept.3 Depending on the physical hardware selected, this could be separated into fixed upstream stainless steel capacities followed by flexible downstream single-use or fully single-use (SU) purification operations. According to the manufacturing philosophy, the upstream could be cycled so that a bioreactor was always harvested and fed into a purification train. This allows unit operations to be organized upstream and downstream as needed.

Using smaller unit operations designed for continuous purification can provide high throughputs. A facility operating connected, single-use, continuous-flow processes could manufacture different products and purify them quickly. Once the batch is processed, the entire part would be disassembled, refitted with different unit operations, and configured for the next separate product. This kind of flexibility is very valuable. It allows manufacturers to quickly adapt to market demands and emerging disease outbreaks around the world.

Modular installations

Designing modular facilities that can be shipped anywhere and assembled immediately can provide much-needed local manufacturing capabilities to support immunization programs near viral outbreaks. These could take the form of self-contained units the size of a shipping container, as noted earlier, or they could be individual modules designed to be assembled into a much larger facility. This concept is particularly useful for deployment in developing countries that are less likely to have sophisticated manufacturing facilities to deploy the vaccines. In theory, the ability to quickly build identical facilities in different locations would minimize the difficulty of transferring technology products to/from different sites and allow manufacturers to move between sites in the wake of pandemics.

Automation and robotics

Another key facet of the facility of the future is the integration of automated systems, robotics and fully digital working methods. Automated receipt and storage of raw materials along with digital quality certificates, sent in advance, allow for minimal on-site quality control labs to test incoming materials. Connected digital inventory control, robotic handling and automated manufacturing schedules will increase facility productivity and reduce processing time. Operators and engineers using mobile digital technologies such as augmented reality glasses and other digital tools will minimize setup issues and enable better control of processes that will be undertaken on a holistic basis. Unit operations will no longer be controlled individually; a connected process will be key to maximizing process efficiency.

Biopharmaceutical vendors have already launched software suites designed to improve processing by enabling the digital connection of different unit operations and the collection and display of critical information in meaningful ways.4

Science fiction or distant future?

The industry’s ultimate goal is to shift to a “personalized medicine” approach. The basis of this concept is very simple, if not extraordinarily expensive with current technology. A patient would be subjected to some form of analysis from a blood sample or other quantitative assessment. The sample would be fed into an analytics platform and, using artificial intelligence, ratings would be generated. A bespoke biological therapy would be conceptualized, verified and manufactured by a small stand-alone biological treatment unit. Analytics is certainly beyond any real-world technology at the moment, but manufacturing may be a little closer to reality.

This device would contain a miniature upstream and downstream manufacturing process that would generate single doses of the drug product, using next-level automation, AI-based analysis or drug development and drawing from a digital library conditions, biological information and medical records.

While this level of technology is a staple of the sci-fi genre, there are promising signs that it could one day be a real-life capability. Vaccine manufacturing processes using mRNA are being miniaturized; this has huge potential beyond making vaccines.5 One could argue that this concept would have limited utility, as economies of scale will still apply and most people will not need individual treatments. While this is true, there are unique use cases such as remote or mobile deployment options such as future space stations, remote colonies on distant planets, or perhaps more terrestrial options such as deployment on large ships or submarines. While the humble beginnings of it are currently being conceptualized, the reality of this automatic medicine dispenser is still a long way off.

We are critical

Chemical engineers are, and always have been, at the forefront of technological development. Whether it’s distilling crude oil into lighter and more useful fractions, splitting the atom and harnessing the energy produced or separating drinking water from pollutants. In the last century, you could say that some of the greatest technological developments have been biological. Before the 1940s, a simple cut could have life-threatening ramifications, but when Alexander Fleming discovered penicillin and it was developed and industrialized, that changed dramatically. Today, it is produced in large-scale fermentation processes designed and controlled by chemical engineers.

The biopharmaceutical industry has given diabetics synthetic human insulin and specific therapies to treat chronic diseases and genetic disorders. Biofuels reduce the environmental impact of the fossil fuel industry. Biological organisms such as fungi are being researched to potentially degrade waste stored in landfills or floating in our oceans. Biological computing systems have the potential to greatly exceed the performance of conventional systems.

Nature has always developed remarkably elegant ways to solve problems. We, as a species, as technology developers, are in our infancy compared to the millennia of iterative evolution imposed by the natural world. However, scientists and engineers working closely together, drawing inspiration from biological systems, will bring advanced technologies closer to the future every day.

The UK invests millions in research and development in biotechnology. Many foreign companies are also investing in the UK. one such example is the mRNA vaccine development center.6 The opportunities for chemical engineers have never been greater. There are also more university courses in bio-processing in UK institutions than ever before. Now is the time to leverage our existing experience in bioindustry and the wonders of the natural world and apply these techniques in controllable and repeatable ways for the betterment of society.

References

1.Fujifilm, Fujifilm will invest USD 1.6 billion to improve and expand its global cell culture manufacturing service offering (2022), https://bit.ly/3JHZAKa
2. Adepoju, P, New initiatives to advance mRNA vaccine production in Africa (2022); Nature, https://go.nature.com/3QxgL3u
3. PSI, Biopharmaceutical Plant Design: Lessons Learned on the Dance Floor, https://bit.ly/3QejMpk
4. Merck, Merck accelerates the preparation of the bioprocessing plant of the future (2020), https://bit.ly/3BTFUkK
5. Blankenship, K, Tesla partners with CureVac to create ‘micro RNA factories’ for COVID-19 vaccine, says Musk, (2020), https://bit.ly/3vOdXqI
6. Department of Health and Social Affairs, Moderna will open a vaccine research and manufacturing center in the UK (2022), https://bit.ly/3A9twM4


Acknowledgements: Michael Burns, Paul Beckett, Stuart Rolfe and Carole Inglevert for their help in writing this article.


This is the fifth and final article in a series discussing the contribution of chemical engineers to the biopharmaceutical industry. To read the full series, visit: https://www.thechemicalengineer.com/tags/chemical-engineers-and-the-biopharmaceuticals-industry/

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