Development of advanced analytical methods for the characterization of complex generics

Advanced analytical methods for characterization and comparative analysis of complex products, which help to link product attributes to product quality, safety and efficacy, are useful for facilitating the development of generic complex products. The purpose of this study is to develop advanced analytical methods for analyzing the diastereomer compositions in phosphorothioate (PS) oligonucleotides using either TEGSEDI (inotersen) or SPINRAZA (Nusinersen) as the model product. The proposed studies will focus on 1) understanding the diastereomer composition in TEGSEDI or SPINRAZA (Nusinersen), and 2) determining whether and how the manufacturing process may affect the diastereomeric distributions in the drug product. Methods developed through this research may also be applied in cases of other synthetic oligonucleotides, and could greatly facilitate the development and assessment of generic oligonucleotide drug products. Knowledge gained from this research may also contribute to quality control of oligonucleotide drugs.