mRNA & The Next Pandemic
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Overview
Scientists have attempted to develop RNA-based drugs for decades, but prior efforts have been limited in success. The COVID-19 pandemic ushered mRNA vaccine technology onto the world stage, increasing the number of patients receiving this technology from thousands to millions. A core application of mRNA vaccine technology is in the prevention and treatment of future pandemics. Here, we highlight the scientific potential of mRNA vaccine technology in pandemic prevention and the operational changes that need to occur in order for mRNA technology to be leveraged again for future pandemics.
The ‘Pandemic Era’
First, what’s the likelihood of another pandemic occurring in our lifetimes, or even in the next decade? Infectious disease experts and epidemiologists, including Dr. Anthony Fauci, believe that COVID-19 is only the beginning of a ‘pandemic era’. The increasing emergence of zoonotic viruses is the result of a human-dominant ecosystem. To prevent future pandemics, we must not only learn to live more harmoniously with our ecosystem, but also leverage science to prepare for the worst.
mRNA Technology is Ready for Prime Time
Decades of research in academic and industry labs focused on tuning mRNA manufacturing, design and delivery to rectify problems like mRNA instability, immunogenicity, and cellular uptake set the stage for their clinical use in infectious diseases like influenza and Zika virus, as well as cancer. These efforts were most strikingly brought to bear in 2020, when the COVID-19 pandemic spurred Moderna and Pfizer-BioNTech to rapidly develop and deploy safe and efficacious mRNA vaccines, with projected impact of 1 billion shots and $50B in revenue for 2021.
The validation of mRNA as a platform opens the door for a wave of innovation in mRNA based vaccines and therapeutics. mRNA’s rapid scalability and high customizability make the platform uniquely poised to address future pandemics. mRNA vaccines are rapidly scalable because the ingredients to make an mRNA vaccine such as plasmid DNA, phage polymerase and other components, are readily available at GMP level quality. Furthermore, unlike other vaccines such as the influenza vaccine, which uses chicken eggs or other mammalian cell lines to generate viral proteins, mRNA vaccines rely on the recipient’s cells to produce the antigen. Removing a reliance on exogenous cell lines makes the production process less expensive and more efficient. mRNA vaccines are also highly customizable, an important quality to have as viruses evolve to escape existing therapies.
Nevertheless, serious practical concerns around mRNA vaccines remain to be addressed. Perhaps the largest barrier to the scalable clinical application of mRNA vaccines is their inherent instability, which necessitates ultra-cold chain storage and complicates distribution. Population-scale manufacturing represents another key bottleneck for rapid mRNA vaccine deployment. Continued efforts in engineering mRNA and excipient formulations will improve the stability and accessibility of mRNA vaccines — however, supply chain infrastructure must also be updated to enable efficient distribution to address COVID-19 and emerging infectious diseases.
To Prepare for the Next Pandemic, Strengthen Manufacturing, & Distribution
Operationalizing the manufacturing and distribution of the COVID mRNA vaccine in a pandemic is a historical achievement. For perspective, ~150 million doses of influenza vaccine are delivered every year. With the COVID vaccine, ~190 million doses have already been delivered in less than half a year. Despite this achievement, the U.S. still faced significant barriers in operationalizing its national vaccination strategy. These barriers include: manufacturing deficiencies, lack of specialized cold storage equipment and lack of a centralized information technology system.
Build Manufacturing Infrastructure
Manufacturing deficiencies have been a key rate-limiting factor in the rapid deployment of the COVID-19 mRNA vaccines. In March 2021, Pfizer-BioNTech and Moderna were manufacturing combined totals upwards of 20M doses per week, thanks in part to partnerships with contract drugmakers like Catalent. By the end of 2021, Pfizer expects to manufacture 2.5B doses of its vaccine, and Moderna is scaling its own efforts with initiatives like a 500M dose supply agreement with Gavi. Notably, new waves of manufacturing-focused innovation from firms like National Resilience, started in 2021 by Rob Nelsen and ARCH Venture Partners, aim to galvanize manufacturing capabilities through integration and partnerships to deliver up to 1B doses on day one of future pandemics.
Bolster Rural America’s Cold Chain
A key barrier to operationalizing vaccine distribution is the special cold storage equipment needed to store mRNA vaccines. While both Moderna and Pfizer-BioNTech vaccines require cold storage, the latter requires ultra-cold freezers chilled to -70C. This equipment requirement limits the distribution of the Pfizer-BioNTech to wealthy hospitals and facilities with the right equipment; which tend to be academic centers in urban areas. For most rural hospitals, many of which were already struggling financially due to the pandemic, spending $10-$15k on an ultra-cold freezer is unfathomable. Fortunately, other vaccines with less stringent cold storage requirements received EUA shortly after Pfizer-BioNTech became available. Moreover, given that Moderna’s vaccine does not require ultra-cold storage, Pfizer-BioNTech is looking into submitting new data to enable vaccine storage at a similar, higher temperature as its competitor. However, if it were not for the availability of multiple vaccines with different storage requirements, rural America would have been wholly left to fend for itself in the vaccine rollout. In addition to improvements in stability technologies (as discussed above), it is our hope that a centralized network, such as the federal government or the American Hospital Association, could stockpile cold storage freezers and distribute them fairly to the areas of highest medical need if a national vaccination effort were to occur again.
Centralize Information Technology Systems
Another distribution barrier in the COVID-19 national vaccine strategy is the lack of a centralized information technology system. Centralized information technology systems are crucial to streamlining the communication, scheduling, documentation and reporting of vaccinations. Currently, there is little interoperability between vaccine appointment websites such that one individual can register for multiple appointments. This can result in redundancy within the registration system, leading to wasted doses if some appointments are left unattended. Moreover, vaccination records administered outside a health system are still being recorded on a paper card, making the records difficult to track down if the card were lost. It is astonishing that in an age where private enterprises can track online purchases to the last temporal and spatial detail, that vaccination records are still being kept on paper cards. In preparation for the next pandemic, we need to develop a public health infrastructure that can be readily deployed for national vaccination registration, and where individual vaccines can be tracked to individual patients.
Conclusion
Of the stages of vaccine development that we have seen unfold in the last year, the rate limiting step was not research and clinical development, but rather manufacturing and distribution. Given that the COVID-19 pandemic is likely not the last pandemic of this generation, it is critical for industry leaders to begin thinking about how to prepare our healthcare system for the next pandemic. While biopharma companies such as Pfizer have already pledged to double down on R&D capabilities in preparation for future pandemics, we believe that it is equally, if not more important for the industry to invest in developing manufacturing and supply chain infrastructure that supports the rapid deployment of hundreds of millions of vaccines across the country.
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❤️ HUGE thanks to Jessica Chao, Jingyi Liu, & Eric Dai, for putting this together :)
Alix Ventures, by way of BIOS Community, is providing this content for general information purposes only. Reference to any specific product or entity does not constitute an endorsement or recommendation by Alix Ventures, BIOS Community, or its affiliates. The views expressed by guests are their own and their appearance on the program does not imply an endorsement of them or any entity they represent. Views and opinions expressed by Alix Ventures employees are those of the employees and do not necessarily reflect the view of Alix Ventures, BIOS Community, affiliates, and content sponsors.
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