By Dogan Ornek, Nida Sayed, Jiangshan Zhou, Justin Lin, and Philip J. Ramsey
Volume 24, Open Access (October 2025)
Efficient bioprocess characterization is essential for both regulatory compliance and commercial viability of biologics. Traditional approaches using resolution III/IV screening designs followed by response surface methodology are time-consuming, costly, and not always effective in identifying the important experimental effects. Definitive screening designs (DSDs) represent a novel class of three-level screening designs that can simultaneously evaluate main effects and quadratic relationships. While DSDs are increasingly used in bioprocess development, practical implementation guidelines remain limited. This case study bridges this gap by introducing a model-based framework to identify critical process parameters (CPPs) and optimize operating ranges for robust biologics production using plasmid DNA (pDNA). Minimal 14-run DSDs evaluated six input parameters and successfully identified CPPs and optimal operating ranges. This approach reduces experimental requirement by >50% compared to traditional designs, providing an efficient and economical strategy for bioprocess characterization and optimization…
Citation: Ornek, D; Sayed, N; Zhou, J; Lin, J; Ramsey, P. J. Breaking the DoE bottleneck: how definitive screening designs enable faster, cheaper biologics process development. BioProcess J, 2025; 24. DOI:Â 10.12665/J24OA-Ornek-BIB
Posted online October 22, 2025