Main Conference Day 2Wednesday, 4 November 2026 - Europe/Amsterdam

This presentation will review the recent evolution of global regulatory guidance for synthetic oligonucleotides, assess areas of convergence and divergence, and explore future opportunities for harmonisation and efficiency.

CMC regulatory strategies and health authority interactions for oligonucleotide programs will be discussed, with a focus on recent ASO commercial applications in the US and ex-US regions. Similarities and differences in submission content, filing strategies, regulatory expectations, and health authority requests will be highlighted, supported by recent filing experiences and case studies. Perspectives on emerging hot topics and practical learnings from recent submissions will be discussed, along with potential future areas for regulatory engagement.

The presentation will provide an update on the main principles and current status of guidelines and the expected timelines for implementation. It will summarise key feedback received during the public consultation of two draft guidelines, with a focus on the main scientific and regulatory challenges for stakeholders. The presentation will also provide an overview of the most common issues encountered during Marketing Authorisation Application procedures in recent years.

Regulators increasing expect terminal sterilization for ASO drug products by steam/autoclave as a process that offers high sterility assurance levels (≤10^-6). Aseptic processing is only allowed if steam sterilization is not feasible. Published ASO data to date (DeCollibus et al 2023) largely focus on molecule-centric, concentration-based chemical degradation, such as depurination and backbone cleavage/hydrolysis, with limited evaluation of the formulation aspects. EMA draft guidance (EMA/CHMP/CVMP/QWP/262313/2024) states that moderate degradation, even above qualification limits, is not enough to reject terminal sterilization. Instead, the guideline encourages optimizing formulation factors (pH, buffer system, and osmolality), and container-closure to enable its use. With advancements in ASO chemical modifications and molecule designs, formulation composition may emerge as a potentially limiting factor. This presentation will illustrate some case studies under such circumstances to help make informed decisions on feasibility of steam sterilization during early phases of ASO drug product development.