The US Food and Drug Administration (FDA) approved the first two SARS-CoV-2 vaccines less than one year after COVID-19 first broke out in the country, and it is no coincidence that both front-runner vaccines were mRNA-based. mRNA platforms provide the biopharmaceutical industry with the flexibility needed to respond to novel outbreaks quickly.
Before COVID-19, mRNA-based platforms were still in early stages of development, but as the urgency and impact of the pandemic started to become clear, academic researchers, biopharmaceutical companies and regulators took unprecedented steps to work together to bring mRNA-based vaccines to market.
How academic researchers, the biopharma industry and regulators came together
Academic researchers published their data about the virus’s genetic code only weeks after the virus was first identified. Meanwhile, vaccine developers reprioritized their pipelines and put SARS-CoV-2 on top. Companies that had established mRNA or viral vector platforms prior to 2020, such as Moderna, BioNtech and Johnson & Johnson, were able to rapidly accelerate the development of their vaccine candidates. Amid this effort, smaller players partnered with legacy vaccine manufacturers to test their vaccines in clinical trials. To bring vaccines to the population as quickly as possible, regulators expedited emergency use authorizations (EUA) for several vaccine candidates and gave manufacturers authority to rapidly scale up vaccine manufacturing to meet demands for billions of doses.
In this article, we will explore the manufacturing strategies and tools that the biopharmaceutical industry adopted to make such efficient vaccine production possible.
The value of mRNA platforms
As the pandemic began to unfold, the biopharmaceutical industry was faced with a decision. It had to weigh the risks associated with investing in a novel vaccine platform against its potential to yield a safe and effective vaccine quickly. On the one hand, mRNA technologies have not been widely adopted commercially, but on the other, they had already been tested in several Phase I and II trials for infectious disease and cancer, so the industry was aware of its potential.
mRNA platforms provide the industry with flexibility that enables faster vaccine development in several ways. First, it is easier to produce mRNAs in the laboratory than it is to produce proteins or viruses, making the development process easier to scale up. Second, the same basic components can be used to develop an mRNA vaccine against any virus, making this technology a truly versatile platform.
All mRNA vaccines essentially work the same way. Manufacturers generate mRNA that encodes one of the virus’ protein antigens through a chemical reaction called in vitro transcription. The mRNAs are then purified and inserted into lipid nanoparticles that can fuse with cells in the human body. Once inside the body, our cells’ own machinery translates the mRNA into the designated protein antigen, against which the body mounts an immune response to provide us with long-term immunity against the SARS-CoV-2 virus.
From a manufacturing perspective, mRNA-based vaccines offer the most efficient response to a viral outbreak; manufacturers just need to adjust the platform with the new antigen sequence.
Single-use technologies: Another key to flexible manufacturing
mRNA platforms are just one set of tools for increasing flexibility in vaccine manufacturing; another tool that can increase agility is single-use technologies. Single-use technologies are manufacturing products that use sterile fluid containment bags in place of stainless steel vessels. The bags can be disposed of after each use, removing the need for costly, time-consuming and hazardous cleaning protocols. Single-use technologies increase flexibility because they can be implemented faster than stainless steel technologies can. The emergence of new vaccine platforms creates an opportunity to adopt stainless steel more widely.
Traditionally, manufacturing a novel vaccine relied on the production of the pathogen itself (such as a virus), which then had to be inactivated or weakened. This meant that companies needed to develop the process from scratch for each pathogen. Single-use technologies didn’t exist when these processes were originally developed, and as a result, many legacy vaccine manufacturers are relying on stainless steel in facilities designed to only produce one vaccine.
But today, newer platforms, such as recombinant proteins, viral vectors and mRNA, which don’t require the growth of a pathogen, allow manufacturers to shift from one process to the other in the same facility. Single-use technologies make this possible, providing the needed flexibility.
According to McKinsey, the industry must produce 14 billion vaccine doses to immunize the global population.2 Many biopharmaceutical manufacturers were not ready to face this demand when the pandemic started; they lacked the capacity to manufacture vaccines on such a large scale in so little time. Fortunately, contract development and manufacturing organizations (CDMOs) had already widely adopted single-use technologies before the pandemic to become flexible, meaning they could repurpose their facilities to manufacture mRNA, recombinant protein- and viral vector-based vaccines and vastly increase supply.
Preparing for the next pandemic
To mitigate the spread of future viral outbreaks as efficiently as possible, biopharmaceutical companies must continue investing in tools, strategies and expertise that expand their vaccine manufacturing capabilities. This not only means expanding their current vaccine pipelines but also investing in flexible tools such as mRNA platforms and single-use technologies to speed up production. If this pandemic taught us anything, it is that viruses overload healthcare systems and destroy economies, and the biopharmaceutical industry plays a critical role in limiting the damage. As companies in the biopharmaceutical industry take stock of their processes and build a plan to better equip themselves to face emerging health threats, flexibility must be a central focus. If the industry centers its future plans on flexibility, pandemic response can be more effective and timelier.
About the author
Amélie Boulais is the Head of Market Entry Strategy, Virus Based Therapeutics at Sartorius.
1. Pardi N, Hogan M, Porter F. et al. mRNA vaccines — a new era in vaccinology. Nat Rev Drug Discov 2018;17: 261–279. https://doi.org/10.1038/nrd.2017.243
2. Agrawal G, Conway M, Heller J, et al. How accessible and effective will COVID-19 vaccines be? On pins and needles: Tracking COVID-19 vaccines and therapeutics. McKinsey. February 28, 2021. Accessed March 22, 2021. https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/on-pins-and-needles-will-covid-19-vaccines-save-the-world