By Henrik Ihre, Ph.D., Director, Strategic Technologies, Cytiva
Inventing, developing, testing, and distributing two “new” mRNA vaccines within a year is nothing less than a remarkable achievement. Work with mRNA technology by companies such as Moderna and Pfizer-BioNTech may allow us to return to our normal lives soon. In some ways, you could argue that the Covid-19 pandemic has accelerated the ideaa/growth of mRNA-based pharmaceuticals — the seeds of which were planted in the 1970’s. The often-overlooked angle is the behind-the-scenes work that helps manufacture mRNA at scale and deliver it securely around the world. Discussions 50 years ago were scientifically interesting but didn’t have “business legs.” There was no immediate need, and the mRNA molecule could not yet be delivered efficiently or with reliability since the methods and technologies hadn’t been invented yet.
Now, the mRNA technology has proven itself as a flexible and versatile route for some prophylactic vaccines. The time is right to address the long list of what could be achieved with this molecule – including personalized cancer vaccines, regenerative therapies, and even systemic treatments of diseases now handled by daily injections of recombinant proteins manufactured outside the body.
The fact that new mRNA-based vaccines could be brought to the market quickly during 2020 is attributed to several factors such as: immediate need; decades of research within the field of mRNA therapeutics; and the ability of Life Science companies like Cytiva to support the biopharmaceutical industry with the required tools, equipment and processes for developing and manufacturing these new molecules.
Manufacturing mRNA-based pharmaceuticals is a rather complex. The process is made up of key elements such as design and manufacture of a plasmid containing the required genetic information for the mRNA pharmaceutical. These plasmids are typically manufactured in an E.coli based fermentation process then harvested, purified, and used as templates for the enzymatic In Vitro Transcription (IVT) process yielding the desired mRNA molecule. Once the mRNA molecules have been formed, they a need to be purified from a variety of side products and impurities before it can safely be formulated into a carrier such as a lipid nanoparticle (LNP) and administrated to patients.
It is safe to say that everyone has been surprised by how quickly the mRNA pharmaceuticals entered the market. One consequence of the speed is that currently, several of the developed processes and protocols are far from optimized. It was mission-critical to bring these first mRNA vaccines to the world. Several of the processes were developed based on existing tools and equipment, which were not necessarily designed or optimized for an ideal mRNA manufacturing process.
Now that this technology is showing its effectiveness in prophylactic vaccines, the next steps will be to explore other therapeutic areas where perhaps cancer vaccines may be the next viable target. As one could imagine, the need for a pandemic prophylactic vaccine, given in billions of doses, may differ rather significantly from a personalized cancer vaccine given to few individuals in terms of how the mRNA is manufactured and what the required timelines and quantities look like.
mRNA technology as well as the people and products enabling these inventions and manufacturing processes have indeed helped us to turn this into a better world again. The future of mRNA looks bright and will clearly offer new tools in the pharmaceutical toolbox, but it will also require development of novel and dedicated products and processes to meet the different needs for scale and time to market.