2024 - Quality by Design in mRNA Manufacturing

The COVID-19 pandemic triggered an unprecedented surge in the development of messenger ribonucleic acid (mRNA)-based vaccines and other therapeutics such as protein replacement therapies.
mRNAs are produced by a cell-free process based on the in vitro transcription (IVT) reaction, a RNA-polymerase-catalyzed polycondensation of nucleoside triphosphates (NTPs) into a nascent mRNA chain guided by the deoxyribonucleic acid (DNA) template. The mRNA production workflow is adaptable to production from milligram to multigram scale, supported by the high-pressure liquid chromatography (HPLC) monitoring of the consumption of NTPs with the concomitant production of mRNA. It also integrates quality by design (QbD) principles to ensure robustness and scalability.
A data-driven model of process yield (in g/L), including the impact of NTP concentration and Mg:NTP ratio on the reaction yield can be derived to optimize the reaction cost drivers (e.g. RNA polymerase and DNA template) while minimizing the dsRNA formation, a critical quality attribute in mRNA products.
mRNA purification can be achieved with affinity chromatography selective for polyadenylated mRNA (Oligo dT) coupled with reverse-phase chromatography, which is used to remove IVT components (NTPs, DNA and T7) and IVT by-products. The elimination of dsRNA improves translation and minimizes the activation of innate immune response. For the development of personalized, mRNA-based therapies, such as neoantigen mRNA vaccines, the minimization of the innate immune response may be critical to the clinical success of mRNA therapeutics.
Register for this webinar today to gain insights into the technological advancements and operational considerations for ensuring the quality by design approach in developing mRNA-based vaccines and therapeutics.
Keywords: Vaccine, Regulatory, Vaccine Development, mRNA Vaccines, mRNA Therapeutics, mRNA Technology, Cell & Gene Therapies, CDMO/CMO, Quality