In 2020, as part of the fight against COVID-19, we have witnessed incredible collaborations between biotech, big pharma, academia and not-for-profit organizations, all working together to develop treatments and vaccines at record speed. Global demand for products treating and preventing infection with the virus presents huge opportunities for the biomanufacturing sector, along with challenges in managing limited global bioreactor capacity, maximizing manufacturing efficiencies, and adopting facilities to work with new and innovative technologies.

Vaccines, monoclonal antibodies, cytokines and other ‘biopharmaceuticals’ all make use of biomanufactured products. Their creation involves the use of scalable, validated biotech processes that use biological organisms, or parts of biological organisms, to produce useful products, naturally or through advanced genetic engineering techniques. The first bio pharma products approved for therapeutic use was biosynthetic human insulin made via recombinant DNA. It was developed by Genentech, but licensed to Eli Lilly & Co, who manufactured and marketed it in 1982, under the trade name Humulin. Dominated by small biotechs, R&D investment in new medicines by the biopharma industry stood at $102 billion in 2018, and the sector had been predicted to grow at a rate of around 10% per year over the next four to five years.

That was before COVID.

About 75% of COVID-19 treatments – at various stages of development – are produced in mammalian cell culture. Even if only a fraction of these products reach the market, a significant proportion of people requiring treatment for the symptoms of COVID are going to be using products manufactured in this way. In itself, this might not seem to be a challenge – after all, in 2019, the top 10 biopharma products were produced in mammalian cell culture. The biopharma market has long been dominated by monoclonal antibodies, so the equipment exists to deliver on those demands. However, as explained by Patti Seymour (Managing Director, BDO USA) in a recent webinar hosted by CPhI, in order to treat 25 million patients (the number of people believed to have contracted the virus so far), about 150 x 10,000L bioreactors would be required. This represents the entire world’s current capacity for mammalian systems. Therefore, in a worst-case scenario, if existing bioreactors were given over to the production of COVID-19 treatments, there would be limited capacity for others, including those needed for some types of cancer. In other words, with the world’s current capacity for biomanufacturing, demand for COVID-19 treatments has the potential to severely disrupt the production of other important medicines.

This situation presents tremendous opportunities for urgent investment in increased bioreactor capacity. Current estimates suggest that only about 20% of biomanufacturing capacity is provided by CMOs. With demand looking fairly certain to exceed current capacity, this would appear to be an obvious area for good return on investment.

Decisions surrounding new investments in capacity for biomanufacturing should consider the impact of continuous bioprocessing, which is becoming more mainstream technology. As pointed out by Eric Langer (President and Managing Partner, BioPlan Associates), biomanufacturing productivity and efficiency have never been more important, and continuous bioprocessing is providing an increasingly common answer to these challenges. In particular, the industry has been looking at continuous perfusion, purification/chromatography, bioprocess control and monitoring. CMOs are often on the cutting edge of these innovative technologies, and are in a prime position to provide high-value, competitive services.

The COVID-19 pandemic has also been a driving factor in changing the way that the industry produces vaccines. Traditional approaches, using eggs or blood plasma to grow the virus and develop antigens, are simply not quick enough. On average, it takes 12 to 36 months to manufacture a vaccine before it is ready for distribution, but countries (and their economies) can’t wait that long for a vaccine to control COVID-19. Therefore, the industry has turned to more innovative approaches, such as recombinant antigen, DNA and mRNA-based solutions.

At the time of writing this blog, the three front-runners are the Oxford and AstraZenca, Moderna, and Pfizer and BioBTech vaccines. The Oxford vaccine works like a traditional inoculation – a spike protein of the virus is injected and triggers an immune response, so if the real virus enters the body an immunity will already exist. However, both the Pfizer and Moderna vaccines use mRNA-based solutions, which introduce genetic instructions for the vaccinated person's own cells to produce antigens and generate an immune response. In less than a year, all three vaccines have completed a process that normally takes at least a decade. Manufacturing began ‘a(chǎn)t risk’ back in the summer – before the results of trials were known – at facilities located as far afield as the USA, the UK and Australia. In a truly unprecedented move, governments across the world have pre-ordered millions of doses of all three vaccines, although none has yet been approved by the regulatory authorities. The rapidity with which these vaccines have been developed, manufactured and sold has been truly mind-blowing.

In summary, pre-COVID-19 predictions of 10% growth per year now seem modest. Thanks for the global necessity for treatments and vaccines for the virus, it seems that demand for facilities is going to outstrip capacity for a while to come, and a rush of investment in new bioreactor capacity, potentially including the latest continuous technologies, should probably be encouraged over the next few years. There are obvious challenges to setting up such facilities – the extremely high financial cost being just one – but for those who can afford to do it, return on investment seems almost guaranteed.

Author biography

Sarah Harding, PhD

Sarah Harding worked as a medical writer and consultant in the pharmaceutical industry for 15 years, for the last 10 years of which she owned and ran her own medical communications agency that provided a range of services to blue-chip Pharma companies. She subsequently began a new career in publishing as Editor of Speciality Chemicals Magazine, and then Editorial Director at Chemicals Knowledge. She now focusses on providing independent writing and consultancy services to the pharmaceutical and speciality chemicals industry.

-----------------------------------------------------------------------
Editor's Note:

To become a freelance writer of En-CPhI.CN,

welcome to send your CV and sample works to us,

Email: Julia.Zhang@ubmsinoexpo.com.