Biocatalysis has transformed small molecule API chemical synthesis by shortening routes, lowering waste & reducing costs. Enzyme applications are now being exploited in oligo synthesis. This presentation showcases enzymes used in single & double-stranded oligo synthesis. This technology base can be applied to develop enzymatic methods for oligo synthesis resulting in improved yields & purity profiles compared to traditional methods.

Limited platform knowledge, complex relationships, and accelerated speed to market are just a few of the reasons why process development of oligonucleotides, like other cell and gene therapy products, is so challenging.  The advantages of designed experiments (DOE) instead of One Factor at A time (OFAT) experimentation in such situations is well recognized, gaining significant popularity over the past decade. Control strategies developed using designed experiments result in robust processes, reducing risk not only in early process development, but across the product lifecycle. But do you know there are recent developments in the science of designed experiments?  Computational advancements have led to new classes of designs with desirable properties such as reduction in the number of experiments, flexibility to assign varying focus to factors and adequate precision, even in the presence of second order terms. In this talk, examples of the advantages of these designs over classical designs will be shown, along with common mistakes made for all classes of designed experiments. 

ICH guidance M4Q (the Quality section of the Common Technical Document), although initially not intended to include oligonucleotides within its scope, is now applied routinely to regulatory submissions for oligonucleotides from initial clinical trial applications to marketing applications.  This presentation will provide some suggestions on organizing the effort to prepare a clinical trial application and maintaining that dossier through to the marketing application.  The presentation also will provide some insight into certain sections of M4Q to aid in understanding the content expected in those sections.  

This presentation will provide an overview about the regulatory landscape for oligonucleotides. Issues related to the pharmaceutical quality of oligonucleotides are highlighted and experiences from recent regulatory submissions will be discussed.

There is an increasing number of oligonucleotides reaching late-stage clinical development or already approved. Synthetic oligonucleotides, due to similarities in manufacturing and analysis, offer a unique opportunity to accelerate the development of both drug substance and drug product – compared to small molecules for instance. And a good understanding of the regulatory guidelines is important to achieve this goal. Leveraging on real-world cases, this presentation will provide possible strategies for the management of CMC operations towards successful global development/registration of oligonucleotide therapeutics and for addressing the regulatory expectations for assuring quality and performance in a phase appropriate way.