This presentation introduces an integrated framework combining experimental validation and mechanistic modeling to evaluate process transferability between axial flow chromatography (AFC) and radial flow chromatography (RFC). Under strictly harmonized conditions, AFC protocols were successfully applied to RFC without re-optimization, achieving equivalent performance metrics, including dynamic binding capacity, purity, and yield. Geometric scale-up from 2 L to 21 L RFC confirmed predictability and highlighted substantial footprint advantages compared to AFC. Additionally, the RFC process was modeled in GoSilico to simulate hydrodynamic behavior, elution profiles, and scale-up scenarios. This synergy of empirical validation and in-silico simulation provides a scientifically sound basis for GMP-compliant, efficient, and sustainable process development. It addresses a critical challenge in downstream processing in industrial biotechnology: enabling rapid, low-risk migration of chromatographic methods across different column geometries.