Characterization and Optimization of Biologics Manufacturing Using Space-Filling Designs and Machine Learning

By Dogan Ornek, Nida Sayed, Matthew Sousa, Connor Crue, Ravi Chari, Stephanie Delzell, Adalia Cardoso, Roy Lin, and Philip J. Ramsey

Volume 24, Open Access (September 2025)

This study assessed a novel statistical approach using space-filling designs (SFDs) and self-validating ensemble modeling (SVEM) machine learning to efficiently identify key process factors using recombinant adeno-associated virus type 9 (rAAV9) gene therapy manufacturing as a case study. Based on risk assessment of parameters that may impact rAAV9 production, we have evaluated six process parameters using 24-run SFDs generated by the JMP statistical software. SFDs are a new class of design of experiment (DoE) created with the objective of covering the entire design space as completely as possible; this in turn allows more accurate modeling of complex response surface behavior typically found in bioprocesses…

Citation: Ornek, D; Sayed, N; Sousa, M; Crue, C; Chari, R; Delzell, S; Cardoso, A; Lin, R; Ramsey, PJ. Characterization and optimization of biologics manufacturing using space-filling designs and machine learning. BioProcess J, 2025; 24. http://dx.doi.org/10.12665/J24OA-Ornek

Posted online September 8, 2025