Document Type

Working Paper

Date of this Version

4-20-2021

Abstract

mRNA vaccines are a new frontier of medicine. Unlike pre-existing vaccine technologies, mRNA vaccines present the human body with the genetic information to make a protein whose production incites a natural immune response. In this manner, mRNA vaccines create antibodies and build immunity towards pathogens resulting in the same protection as traditional vaccines yet without presenting the body with the foreign virus. Among the many advantages of this new technology is that the manufacturing process, rather than being specific to a virus or recombinant protein, is specific to mRNA. In this manner, the process is independent of the actual disease the vaccine targets and is only dependent on the biological properties of an mRNA strand. This is tremendously advantageous since the same manufacturing process can be used for the mRNA strand of any genetic mutation of a virus or even for a completely different pathogen.

This proposal is for a manufacturing process to produce 200 million sterile doses of an mRNA vaccine against SARS-CoV-2 in a 13-week period thereby vaccinating 100 million people. The process uses Pfizer's pharmaceutical formulation and starts with a plasmid DNA that contains the genetic code for the entire viral spike (S) glycoprotein. The pDNA is fed to a WAVE bioreactor for an in vitro transcription (IVT) reaction that produces mRNA through phage T7 RNA polymerase. The mRNA is purified through two diafiltration steps with an 100 kDa MWCO, a chromatography column to remove undesired dsRNA and a sterile filter to remove biological impurities. The purified mRNA is then diluted in 50 mM sodium acetate and fed to one of the twenty-five 16X microfluidics devices along with a mixture of lipids in an ethanol buffer. With a flowrate ratio of 3:1, the mRNA is encapsulated into the lipid mixture in the microfluidics devices to make lipid nanoparticles (LNPs). This step is key since the lipid-based capsule serves as an envelope for the mRNA, when injected in the human body, to enter the cell's cytoplasm with high stability and without disintegration. The LNPs are purified through a 100 kDa MWCO diafilter in a third tangential flow filtration device and a sterile filter. These purified LNPs are diluted with 1X PBS and sucrose to meet the desired concentration of all components in the pharmaceutical formulation and the mRNA concentration of 0.5 mg/mL. Each week this continuous manufacturing process will fully produce 15.4 sterile million doses that will be packaged into 2 million vials. The vials will be sent out in thermal containers following the regulatory storage and freezer conditions. Throughout the process, the quality of the product will be ensured through the use of sterile and FDA approved equipment, the control of the length of the mRNA produced from the IVT reactor and an endotoxin level test. The proposed process has an internal rate of return of 449%, a return on investment of 475% and a net present value of $19.6 billion dollars. Beyond its application in the strategy to address the current COVID-19 global pandemic, this proposed process will be part of pushing the frontiers of medicine with the novel use of mRNA vaccines.

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Date Posted: 11 May 2021