Monday, March 25 2024 12:30 pm US EDT
This presentation focuses on the control of starting material (SM) quality in the manufacture of oligonucleotide therapeutics. It delves into the process for synthesis of phosphoramidites, emphasizing the importance of chemistry knowledge and control of quality attributes to justify their designation as RSMs in alignment with ICH Q7 and Q11 guidelines. The general approach for categorization of phosphoramidite impurities according to their potential impact on API integrity and drug safety is presented, with a focus on so-called ‘critical, reactive’ impurities that can have a theoretical impact on API quality. The analytical techniques for purity and impurities characterization and measurement are discussed, and exemplary data for amidites typically used for in N=1 oligonucleotides is shown.
David Butler, PhD, is the Chief Technology Officer at Hongene Biotech Corporation, a vertically
integrated raw materials supplier and CDMO services provider that is focused on the RNA manufacturing space, the scope of which includes mRNA, vaccines, oligonucleotides, gene editing, and gene therapy. Prior to Hongene, he led organizations driving drug discovery and development of oligonucleotide therapeutics as VP and Head of Medicinal Chemistry at Wave Life Sciences, VP and Head of Therapeutics Development at Alltrna, and VP and Head of Chemistry at Korro Bio. He also spent time as a Principal Scientist at Alnylam Pharmaceuticals developing early LNP technologies for siRNA delivery that were the progenitors of those used for mRNA related products today. He is passionate about team building, working with individuals and companies to help them succeed, and leveraging novel technologies to advance RNA medicines more efficiently and safely.