The impact of chemical reactivity on the quality and stability of RNA-LNP pharmaceuticals.

Lipid nanoparticles (LNPs) are the most established platform for delivery of mRNA payloads. Their tunability and streamlined manufacturing facilitated an unprecedentedly rapid scale-up during the COVID-19 pandemic. However, being multicomponent, complex systems also poses a challenge of controlling their quality and safety. Analytical checkpoints need to be established to characterize LNPs on multiple levels during development and commercialization. This Perspective centres on the chemical reactivity and purity of mRNA-LNP components, which need to be addressed as raw materials, drug substance, excipients, and the fully formed and stored product. Herein, we describe such appropriate orthogonal analytics to design and analyse LNP formulations. For such novel biopharmaceuticals, better controls that go beyond the current analytical workflow and address the nuanced chemical stability, which helps ensure reproducibility, stability and safety, need to be established.