Changing the Status Quo of Vaccine Production

The rapid onset and spread of SARS-CoV-2 resulting in the global COVID-19 pandemic has had devastating effects on global health, education, and economies. The long-term fallout of this truly catastrophic event has yet to be fully realized as many countries are still battling rising infection rates, the emergence of more infectious variants, vaccine supply and distribution issues, and more.

COVID-19 has enhanced existing disparities in wealth and resources where high-income countries have over 200% population coverage of vaccine doses, leaving developing countries struggling to gain access to supply even with efforts by the COVID-19 Vaccines Global Access Facility (COVAX Facility) to facilitate equitable global distribution.¹ The focus on self-recovery has overshadowed the need for global immunization to overcome this pandemic.

Despite the admitted early failures in the response to SARS-CoV-2, retrospective reports applaud the unprecedented speed at which COVID-19 vaccines were developed and deployed—speed to clinic had never been more important. The Moderna vaccine (mRNA-1273) went from sequence selection to preclinical evaluation in 63 days and was in commercial production in just 10 months.² By comparison, the development of the mumps vaccine, which previously held the fastest record, took four years from the initial isolation of the virus to regulatory approval in 1967.^2,3

Lessons learned during the development of COVID-19 vaccines underscore the need to reimagine the current paradigm of vaccine production from design to manufacturing methods, which has lagged severely behind. Reinvigorated investment in the vaccine industry to replace outdated technologies and embrace new innovations can help better prepare the world for future pandemics and democratize global access to vaccines.

The mRNA technology behind COVID-19 vaccines is poised to disrupt the status quo where speed, versatility, and flexible platform production represent significant advantages to improve global vaccine manufacturing capabilities.

Convergence of innovative technologies

Decades of mRNA research have been brought to fruition by the Moderna and BioNTech/Pfizer COVID-19 vaccines, which rely on mRNA to deliver the genetic instructions encoding the SARS-CoV-2 spike protein to cells.⁴ In contrast to classical vaccines, RNA technology leverages the cells’ own translational machinery to produce the viral proteins that will activate the immune system.

A critical technology that was essential to the successes of the mRNA vaccines is the lipid nanoparticle (LNP) delivery system used to get the mRNA inside cells. LNPs encapsulate and protect the mRNA to facilitate its entry into cells where it is translated and presented as a membrane-bound spike protein antigen that can elicit an immune response.

The modularity of mRNA and LNP technologies can provide the agility for rapid, iterative prototyping of vaccine variants without the need for process modification or revalidation since common manufacturing processes can be leveraged.⁵ The disease-agnostic platform can be easily adapted to produce a wide range of RNA-based treatments that can expand the scope of the technology beyond infectious diseases to broader disease targets, which could make alternate manufacturing models more economically feasible.

As RNA-LNP technology continues to mature, better mRNA constructs and modifications to the LNP carrier system to improve stability, increase in vivo efficacy, and reduce dosing requirements will undoubtedly benefit next-generation RNA-based vaccines and provide efficiencies that will allow for more flexible manufacturing designs.

The success of mRNA vaccines has driven an acceleration of other RNA-enabled treatments that will only exacerbate the already strained capacity to produce the COVID-19 vaccines; therefore, new solutions to address bottlenecks in development and manufacturing are needed. A manufacturing technology that scales easily and practically from the bench to commercial manufacturing is a critical issue in translating RNA medicines.

Next-generation microfluidic mixing devices that easily integrate into existing workflows and rapidly scale across all stages of development and manufacturing are improving vaccine time to market, formulation robustness, and repeatability. Innovative technologies like these are helping address uncertainties related to both the development and operation of large-scale production processes as RNA-LNP technology becomes more widespread and readily adopted.

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