Merck

mRNA Vaccine Process Manufacturing

Process Train for mRNA Vaccines

Process Train for mRNA Vaccines

Delivery of an mRNA into the cytosol of a cell can induce production of a target protein to trigger an immune response for vaccination purposes. The power and promise of mRNA technology were demonstrated by the development of COVID-19 vaccines with unprecedented speed and efficacy.

Development and manufacturing of mRNA vaccines is comparatively simple, scalable and extremely rapid. mRNA is produced by in vitro synthesis through an enzymatic process and there is no need to remove cells or host cell proteins. This simplified manufacturing process allows GMP facilities to switch to a new protein target within a very short period of time, with minimal adaptation to process and formulation.


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Optimise Production of Plasmid DNA

Given the central role of the DNA Template in mRNA vaccine production, its design and purity are important factors for optimizing the mRNA product. Different technologies can be used. The traditional method is based on a plasmid DNA that is amplified within bacterial cells, and subsequent purification steps must be designed to yield a pure, concentrated, circular pDNA, which is then linearized. Our differentiated polymerase chain reaction (PCR)-based technology for DNA Template generation, has shown to have advantages over other technologies for mRNA manufacturing.

Maximize Recovery of the mRNA

The purity of the mRNA is a crucial determinant of yields and efficiency. Impurities removal reduces innate immune responses and result in significantly higher levels of reporter protein expression. Following in vitro transcription, products and process impurities must be removed including eventual endotoxins, immunogenic double stranded RNA (dsRNA), residual DNA template, RNA polymerase, RNA-DNA hybrids, secondary RNA structures (hairpin contaminants), elemental impurities. Such impurities can induce strong inflammatory reactions and side effects and need to be closely controlled prior product releasing.

Ensure Efficient Purity of the mRNA

Several options are available for mRNA purification including tangential flow filtration (TFF), reverse-phase ion-pair, anion exchange (AEX), hydrophobic interaction chromatography (HIC), and affinity chromatography using poly(dT) capture. Following the chromatography steps, a final concentration and diafiltration is performed to maximize purity and to transfer the mRNA into the appropriate buffer for formulation or storage.

Optimize Delivery of the Vaccine

The purified mRNA must be formulated into the delivery particle. Lipid nanoparticles (LNP) are commonly used for this purpose and to protect the mRNA from degradation. Lipids must be chosen based on the desired delivery route to achieve maximum efficacy and optimal biodistribution. Additional aspects to be considered when selecting the lipid include the type, source and quality.