The COVID-19 crisis has cast the vaccines industry into scrutiny; an industry that has been silently beleaguered for decades, according to an opinion piece proposing a new way forward, published in Trends in Biotechnology.
The authors, based at Imperial College, London, UK, the IPQ, Gothenburg, Sweden and the Directorate for Science, Technology and Innovation, OECD, Paris, France, say the vaccines industry has not changed appreciably in decades regarding technology, and has struggled to remain viable, with large companies withdrawing from production.
They referenced a 2003 publication from the US National Academy of Sciences that concluded the amount that the nation spent on vaccines “appears to be insignificant compared with that spent on other medical and social interventions that may have lesser social benefits.”
Moreover, the reviewers, citing a report from the WHO, noted that the numbers of companies supplying vaccines have steadily reduced: some 80% of vaccines arise from five multinationals. “At the heart of the problem is a tension between relatively poor financial returns to the vaccine industry and the high costs in production and R&D.”
And, compared to small molecule pharmaceuticals, centralized vaccine production facilities are capital intensive. Fixed costs are high, especially for new vaccines, they said. “For example, the need for eggs for production is at least 70 years old, is expensive and time-consuming, but difficult to replace.”
In the past, high-income countries have paid a higher price until the fixed costs are amortized, said the authors. Then lower-income countries have adopted vaccines as the price has dropped after paying the fixed costs. “However, there is now tremendous pressure for a COVID-19 vaccine to be available for all who need it, effectively everyone.”
The long distribution chains of centralized vaccine production are patchy, resulting in incomplete geographical coverage, they argue.
The solution: Marrying biofoundries and distributed manufacturing
While centralization of labor and production has been the norm in many industries, the World Economic Forum (WEF), back in 2015, put distributed manufacturing in its top ten emerging technologies for the year. In essence, production is done close to the final customer, and much of the material supply chain is replaced by information, explained the authors.
In summary, the authors say that a combination of biofoundries and the distributed manufacturing model offers solutions to the troubled vaccines manufacturing industry as:
- Biofoundries incorporate high levels of automation that implement complex workflows in order to increase the reliability and reproducibility of biotechnology.
- Biofoundries in different locations can communicate via digital data to complete design/build/test/learn operations.
- Distributed manufacturing attempts to bring small-scale manufacturing to many locations, directly in contradiction to the centralized mass production paradigm.
- Biofoundries are suited to the design of certain types of vaccines that do not require whole cells.
- The design and prototyping of vaccines in biofoundries with final manufacture in small-scale facilities offers the possibility to bring manufacturing close to the point of care.
Economically, locating production close to the end user has the highest potential to capture value, particularly for emergency preparedness and response, stressed the authors.
“The need for a cold chain, prone to logistics malfunctions and temperature excursions, is almost completely removed. Most importantly, a small production facility situated close to an outbreak site can, potentially, fill the gap between routine production and precipitous need at the onset of outbreak creating a stockpile in a short timeframe.”
The combination of biodesign tools (BioCAD) and biofoundries is rapidly producing a new type of biology – digital biology – that could revolutionize the production of vaccines and many other areas of biomedicine, they said.
“The approach chimes with the distributed supply chains and distributed manufacturing that could be transformative in dealing with COVID-19 and future pandemics throughout the world.”
The potential of the approach was demonstrated by Crone and co-workers who showed that an automated SARS-CoV-2 clinical diagnostics platform designed and developed in a biofoundry can be quickly deployed and scaled, commented the authors.
"While many nonbiological drugs are produced using standardised chemical engineering processes, vaccine production, especially with whole cells, has been less amenable to standardisation and is thus less predictable. To break the economies-of-scale model for vaccine manufacturing, cost savings have to be made through strain engineering and molecular design. This is fertile breeding ground for the emerging synthetic biology industry. Vaccine production would benefit from the systematic workflow approach of synthetic biology. The technology of mRNA is amenable to optimisation through almost limitless combinations of derivatives. Likewise, the biofoundry is an obvious vehicle for generation of these combinations."
Systematic workflow increasingly involves the use of biofoundries, they said.
Biofoundries are based on information infrastructures that allow the robots and other equipment within the biofoundries to be programmed to follow detailed, complex workflows. They are highly automated facilities that comprise the extensive and coordinated use of laboratory robots that are programmed to perform specific tasks according to a workflow. "Typically, different platforms within the biofoundries perform different tasks; for example, liquid handling, genetic assembly, characterisation functions."
There are also sustainability wins from this approach.
“In terms of environmental footprint, there is evidence that the pharmaceutical industry is significantly more emissions-intensive than the automotive industry. The biofoundries, where design and initial vaccine selection and build (prototype) is performed, can be anywhere, and certainly separated from manufacturing. In this case it is not vaccine that is transported, but information. Replacing material transfer by information transfer saves money and emissions, lowers risk due to cold chain failures and speeds the innovation process.”
Talent and Education
In such a vaccine production model, with convergence of artificial intelligence, machine learning, and robotics, there would be a need for a new kind of graduate, biologists would be required with greater knowledge of computer science and IT systems as biofoundries take over the laborious liquid handling functions, stressed the team.
As it is, the need for a specially trained workforce for the synthetic biology sector is considered by many in industry to be a key pinch point for the industrial development of the area, they said.
“It is entirely feasible that apprenticeships and day-release education will play a prominent part in developing this workforce. Higher education is rising to the challenges with a range of solutions from technician training, undergraduate degrees, Masters and interdisciplinary PhD programs, massive open online courses (MOOCs) and business management courses.”
In concluding, the authors said that biofoundries and distributed manufacturing have the potential to open up a new era of biomanufacturing, one based on digital biology and information systems. “This seems a better model for tackling future outbreaks and pandemics.”
Source: Trends in Biotechnology.
Title: Build a Sustainable Vaccines Industry with Synthetic Biology
Authors: RI Kitney, J Bell, J Philp