Challenges of Generic Oligonucleotide Drug Substance Development

Michael Tikhonov, R&D, TAPI, Netnya, Israel (Michael.tikhonov@teva.co.il)

In 2022 FDA issued a product-specific guidance for Nusinersen advocating for the establishment of diastereomeric composition sameness between generic API and the Reference Listed Drug (RLD). This recommendation presents a formidable challenge for generic industry as Nusinersen drug substance, with its intricate structure, is a mixture of about 130,000 stereoisomers. TAPI approaches for development of generic Nusinersen drug substance manufacturing process, analytical characterization and sameness assessment will be presented