Many RNA programs accelerate through discovery only to encounter systemic bottlenecks during GLP tox studies and clinical scale-up. For example, microbially derived templates introduce inherent sequence instabilities – such as poly(A) truncations – that frequently surface as CQA failures at larger scales. Furthermore, suboptimal IVT CPPs often lead to poor process productivity and elevated dsRNA loads, and reliance on research grade process enzymes without cGMP equivalents creates regulatory and supply-chain dead ends. These missteps in early-stage development – from template architecture to reaction conditions – result in comparability hurdles and delays at critical clinical transitions.
This webinar focuses on the high-impact decisions that determine whether an RNA program advances or stalls during tech transfer. We will explore how template design and process optimization influence purity, reproducibility, and overall development performance. A key focus will be the role of cell-free enzymatic DNA platforms in bypassing the limitations of traditional microbial upstream processes to reduce host cell components while significantly compressing development timelines.
Crucially we will discuss how to ensure a high-velocity path to the clinic by aligning research-stage methods with cGMP-grade ancillary materials and an analytically sound foundation. Attendees will gain actionable decision guides and best-practice frameworks designed to improve reproducibility, comparability, and readiness for clinical manufacturing. Join us to learn how to scale with confidence and move quickly without exposing your program to avoidable regulatory risks.
Key Learning Objectives
- Identify early-stage pitfalls specific to mRNA, including: template quality, IVT variability, dsRNA formation, capping and poly(A) control.
- Apply phase-appropriate material selection for linear DNA templates, including when and how to transition from research grade to cGMP materials while preserving comparability.
- Design fit-for-purpose QC and analytical strategies for mRNA (e.g., integrity, dsRNA, 5′ cap, poly(A) tail, residual DNA and enzymes) to maintain consistent product quality as batches scale.
- Plan for supply-chain and process scalability, including evaluation of enzymatic, cell-free linear DNA synthesis technologies to reduce lead times and variability from research through cGMP.
