Digital-Assisted Workflow for Organic Solvent Nanofiltration: Accelerating Process Development in Pharmaceutical Manufacturing

Abstract Organic solvents contribute more than 80% of total process mass intensity (PMI) in pharmaceutical manufacturing. Although organic solvent nanofiltration (OSN) diafiltration processes can improve sustainability, achieving high product yield typically requires large solvent volume to operate. Here, we present a digital-assisted workflow, built on the OSN Designer framework, that enables rapid screening of OSN process configurations to identify architectures that minimize solvent consumption while maintaining API recovery. The framework integrates a solution-diffusion transport model, film theory for concentration polarization, and non-steady-state mass balances, calibrated from crossflow experiments with compound A on the Borsig oNF-3 membrane in 2-methyltetrahydrofuran. Validated with average concordance correlation coefficient (ccc) of 0.72 across steady-state and dynamic operating regimes, the model was applied without recalibration to evaluate four process configurations. A two-stage membrane cascade with closed-loop permeate recycling achieved a process mass intensity (PMI) of 7.76─a 92.4% reduction relative to the single-stage constant-volume diafiltration baseline (PMI 101.5). The formalized four-phase workflow reduces experimental effort to approximately 3 weeks from more than 6–8 months and is directly transferable to other pharmaceutical OSN systems.