Oligonucleotide Chemistry, Manufacturing & Controls (CMC): From Process Design to Commercial Scale

High-quality nucleoside and nucleoside analogue building blocks are fundamental to successful oligonucleotide drug development. As therapeutic pipelines diversify, manufacturers are evolving synthetic routes to improve efficiency, scalability, and access to novel chemical space. Carbohydrate-free and alternative synthesis strategies are increasingly being used to enable faster, more flexible production of next-generation oligonucleotide APIs as programs move toward clinical and commercial development.

Why this matters now:
Leading pharma and CDMOs are adopting these approaches to remove early CMC bottlenecks and future-proof their oligonucleotide manufacturing platforms as programs move rapidly toward clinical and commercial scale.

Key Session to Attend:
Carbohydrate-Free Synthesis of Nucleosides and Nucleoside Analogues - Gain insights into modern synthetic strategies that streamline building block production while supporting scalable oligonucleotide CMC development.

Enzymatic oligonucleotide synthesis is emerging as a transformative approach for improving manufacturing efficiency, selectivity, and sustainability. Central to this shift is the reliable production of modified nucleoside 5′-triphosphates (5′-NTPs), which enable enzymatic and hybrid manufacturing platforms designed to overcome the limitations of traditional solid-phase synthesis.

Why this matters now:
As oligonucleotide modalities expand and scale requirements increase, pharma and biotech teams are actively evaluating enzymatic and hybrid approaches to reduce solvent use, improve stereochemical control, and build more flexible CMC platforms for next-generation RNA and antisense therapies.

Key Session to Attend:
Biomanufacturing of Modified 5′-NTP Building Blocks for Enzymatic Assembly - Explore how enzymatic production methods are reshaping oligonucleotide CMC and supporting next-generation RNA and antisense therapies.

Oligonucleotide therapeutics often incorporate complex chemical modifications that introduce significant analytical and manufacturing challenges, particularly during process scale-up. Robust CMC control strategies are essential to ensure product quality, batch-to-batch consistency, and regulatory readiness - especially for stereochemically complex molecules such as phosphorothioate-modified oligonucleotides.

Why this matters now:
Regulatory expectations for analytical characterisation are increasing as oligonucleotide programs advance, placing greater emphasis on impurity control, stereochemical consistency, and validated analytical methods that can support late-stage development and commercial supply.

Key Session to Attend:
Controlling Phosphorothioate Stereochemistry: Challenges and Innovations in Oligonucleotide Manufacturing - Understand emerging analytical and process solutions for managing complexity in oligonucleotide CMC programs.

As oligonucleotide therapeutics progress toward late-stage development and commercialization, manufacturers are under growing pressure to scale production while reducing environmental impact and cost. Sustainable CMC strategies, including solvent reduction, process intensification, and platform innovation, are becoming core requirements for regulatory-ready and commercially viable oligonucleotide manufacturing.

Why this matters now:
Sustainability is no longer a future goal but a present-day constraint, with manufacturing leaders redesigning processes to meet internal ESG targets, regulatory expectations, and long-term supply demands as oligonucleotide pipelines mature.

Key Session to Attend:
Advancing Sustainability through Innovation in Oligonucleotide Manufacturing - Learn how leading organizations are implementing greener, more scalable manufacturing solutions for oligonucleotide drug substances.