Course Description:
Synthetic oligonucleotides are short nucleic acid chains produced by chemical synthesis that can control gene expression in a sequence specific manner. They can target different diseases by interfering with RNA functions at the cellular level. As a new class of therapeutics, synthetic oligonucleotides have shown a great promise in the treatment of neurological disorders, metabolic diseases, cancers, and other diseases with unmet medical needs. Over the past twenty years, the U.S. Food and Drug Administration (FDA) has approved over 10 synthetic oligonucleotide drugs. Among them, several contain synthetic modifications to the phosphate linkage and carbohydrate groups, such as phosphorothioate (PS) and phosphorodiamidate morpholino oligonucleotides (PMOs). While these synthetic oligonucleotides offer exciting opportunities in fighting various diseases, they also pose a new set of significant scientific and regulatory challenges, especially for generic drug development. A PS oligonucleotide or a PMO typically has numerous potential drug substance diastereomers. This, along with other synthesis and purification aspects, gives rise to huge numbers of structurally similar products and related impurities which are difficult to identify, quantify, and control. Moreover, there are currently no guidelines and guidances from regulatory agencies on quality control of oligonucleotide drugs, including control of product-related impurities. To facilitate the development of generic synthetic oligonucleotides, FDA is developing product-
specific guidances on oligonucleotide drug products. A product-specific guidance represents FDA’s current thinking and expectations on how to develop generic products therapeutically equivalent to the reference listed drugs (RLDs). Using SPINRAZA (nusinersen) as an example, we will discuss our current thinking on developing generic synthetic oligonucleotides and how to demonstrate therapeutical equivalence to the RLD.
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 February 28, 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.
Speakers:
Deyi Zhang, Ph.D.
Senior Chemist
Center for Drug Evaluation and Research (CDER)
US FDA