A Novel Mass Spectrometry Paradigm to Analyze Classical and New Biotherapeutic Modalities

Abstract

Next-generation biotherapeutics are on the rise to address diseases in new and promising ways, and gene-based vaccines offer fast development timelines for combating future pandemics rapidly. At the same time, classical biologics (such as monoclonal antibodies [mAbs]) and new protein modalities continue to be developed to combat diseases such as cancer and chronic inflammatory disease. However, these new biopharmaceutical modalities are introducing unique analytical challenges in the detection and characterization of impurities in lipid nanoparticles (LNPs) for gene therapy and gene-based vaccine products, host-cell proteins (HCPs) in viral vector-based therapies, and post-translational modifications (PTMs) in protein therapeutics. These irregularities could impair the safety and efficacy of novel therapeutics. A new fragmentation approach—tunable electron-activated dissociation (EAD) tandem mass spectrometry (MS/MS)—offers a solution. The tunable energy enables detailed characterization, in an intuitive manner, of lipid impurities, glycopeptides, and other PTMs.