Course Description:
Traditional phosphorothioate oligonucleotide synthesis methods generate stereoisomeric mixtures composed of thousands of PS-modified molecules. Wave Life Sciences is pioneering the development and manufacture of multiple stereospecific oligonucleotide modalities for a wide range of genetically defined diseases. The stereospecific platform chemistry enables the controlled placement of Sp and Rp linkages in the backbone, thereby generating a single stereodefined molecule. With the commercialization of several products within the oligonucleotide class, some common themes are emerging in overall oligonucleotide CMC control strategy, but there is elevated interest in CMC aspects pertaining to stereochemistry. In this presentation, we outline the variety of analytical tools that have been deployed as part of our overall CMC strategy to characterize the platform processes that generate stereopure oligonucleotides, and to provide detailed unambiguous determination of the structural composition, identity and stability of stereopure oligonucleotides.
Examples of stereochemistry and related control analytics that will be presented include:
1) Critical raw material characterization and control using LC-MS, NMR, Optical Rotation
2) Intact oligonucleotide NMR studies of closely related diastereomers and overall structural characterization
3) Selected studies on model system coupling and stereochemical stability
4) Cleavage/digestion assays for API structural confirmation
Who should participate:
- QA Manager
- QA Staff
- QC Chemist
- QC Manager
- R&D
- Regulatory
- Student
The live version of this recording took place on during the USP Workshop on Therapeutic Peptides and Oligonucleotides:
Regulations and Quality Standards on March 2, 2022
Access Duration:
Access to this course expires 60 days from the date of registration or until you mark the course ‘Complete’ – whichever occurs first.
Speaker:
Philip Ross, Ph.D.
Senior Director, Analytical/QC – CMC
Wave Life Sciences