The Role of Separation Techniques in the Analysis of mRNA Therapeutic Drug Substances and Drug Products

ABSTRACT

Messenger ribonucleic acids (mRNA) therapeutics are becoming more widespread pharmaceutical tools to treat a wide range of diseases or infections, as highlighted by regulatory approval of two vaccines for SARS-CoV-2. Alongside their use as vaccines, they also play a role in protein replacement therapy to ensure therapeutic protein is synthesized within the patient. Structural elements, such as the 5' cap, UTR regions, reading frame, and poly A tail are considered as critical quality attributes (CQAs) that are subject to a range of analytical techniques. However, chromatography and other separation methods are commonly used for characterization and quantification of the drug substance and drug product. This article reviews a range of techniques available for separative analysis of mRNA therapeutics, their associated impurities, and delivery vehicles.