Course Description:
mRNA market in 2021 grew exponentially due to the success of COVID-19 vaccines by BioNTech, Johnson and Johnson and Moderna. As this technology shows promise, manufacturers are looking for modern approaches to scale production to meet overwhelming demand. This webinar will focus on current manufacturing processes for producing mRNA for vaccines.
1- RNA Active Substance Manufacturing
In-vitro transcription is the main method of mRNA manufacturing. Begins from a DNA template and the mRNA is assembled from this DNA template by using the T7 RNA polymerase enzyme.
2- Enzymatic Capping
Enzymatic capping of the mRNA product is required to facilitate translation in vivo. Either polyadenylated tails can be added using the vaccinia capping enzyme or cap analogues can be added. This is followed by addition of the DNAse I enzyme to digest any remaining template DNA.
3- Downstream Purification / Polishing
Tangential flow filtration is the primary method for isolating the mRNA based on size. Following this initial capture step, additional chromatography steps (anion exchange, hydrophobic interaction, and reverse phase) are used to further purify and isolate the mRNA to be encapsulated into lipid nanoparticles. Lastly, the purified mRNA is concentrated and diafiltered using UFDF and followed by sterile filtration.
4- Lipid Nanoparticle (LNP) Formulation and Purification
For in vivo administration of mRNA, the mRNA must be encapsulated in lipid nanoparticle. The lipid nanoparticle encapsulation provides stability to the mRNA construct and aids in delivery by rendering the overall formulation more stable and decreases the potential for an immune response. The mRNA encapsulation in LNPs is a self-assembly process promoted by rapid mixing of two solutions: an aqueous acidic buffer containing mRNA and an ethanol solution containing lipids for conjugation.
Who should participate:
Drug manufacturing, pharmaceutical manufacturing, biomanufacturing, biologics organizations; Job function: process design, quality assurance (QA), quality control (QC), operations managers, quality management, pharmaceutical quality directors, MHA, MPH.
Though this course is being made available on USP’s Education site, the course content was developed by Pharmatech Associates, a USP company. USP has not independently reviewed or verified the accuracy of the course content.