Development of mRNA manufacturing for vaccines and therapeutics: mRNA platform requirements and development of a scalable production process to support early phase clinical trials

Abstract

The remarkable success of SARS CoV-2 mRNA-based vaccines and the ensuing interest in mRNA vaccines and therapeutics have highlighted the need for a scalable clinical-enabling manufacturing process to produce such products, and robust analytical methods to demonstrate safety, potency, and purity. To date, production processes have either not been disclosed or are bench-scale in nature and cannot be readily adapted to clinical and commercial scale production. To address these needs, we have advanced an aqueous-based scalable process that is readily adaptable to GMP-compliant manufacturing, and developed the required analytical methods for product characterization, quality control release and stability testing. We also have demonstrated the products produced at manufacturing scale under such approaches display good potency and protection in relevant animal models with mRNA products encoding both vaccine immunogens and antibodies. Finally, we discuss continued challenges in raw material identification, sourcing and supply, and the cold chain requirements for mRNA therapeutic and vaccine products. While ultimate solutions have yet to be elucidated, we discuss approaches that can be taken that are aligned with regulatory guidance.

Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies

“…Finally, the production of multicomponent protein vaccines will be challenging owing to both the difficulty and time necessary to produce multiple proteins by GMP and the cost of such a vaccine. The modified mRNA and LNP technology that has been so successful for COVID-19 vaccines 182,183 may be more amenable for the production of multicomponent vaccines compared to protein-based vaccines 127,[184][185][186][187][188][189] .…”

Robust Recombinant Expression of Human Placental Ribonuclease Inhibitor in Insect Cells

“…The addition of RI at local administration of naked self-replicating mRNA significantly improved its repeatability and efficacy [ 29 ]. We should emphasize that RI expressed in High Five cells is per se endotoxin-free, which is a high priority in vaccine development [ 30 , 31 ].…”

Universal Flu mRNA Vaccine: Promises, Prospects, and Problems

“…At the same time, it should be noted that the difficulty of scaling up mRNA vaccine production is of particular concern [ 79 ]. This problem remains the subject of active research [ 80 , 81 ].…”