Relevant factors to guarantee quality of oligonucleotide-based products

In recent years, oligonucleotides have rapidly made their way into the market. Their development and clinical potential have made them strong candidates for addressing a variety of diseases. Oligonucleotides are synthetic chemical entities carrying unique characteristics that often require a different approach to preclinical assessment compared to small molecules. However, their unique chemical complexity presents significant challenges for both pharmaceutical development and regulatory evaluation. In this light, the work aims to review the features and current regulatory landscape of oligonucleotides and discuss the key points for assessing the quality profiles of the medicinal products containing oligonucleotides; to this end, a comprehensive review of all oligonucleotide-based medicines was conducted based on information on regulatory authorization portals such as EMA and FDA with particular focus on quality aspects. The results highlight that these complexities lie in the characterization of the active substance and drug product, especially impurity profiles, and the sterilization of these products. Current regulatory guidelines need to be routinely updated to support developers in addressing these complexities and it is crucial to understand the critical quality attributes of oligonucleotides and their control strategies for researchers in the initial stages of R&D.