Optimization Of AAV Production Using New Statistical Design Of Experiment: Space Filling Designs

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

Low titer and limited scalability remain persistent problems in AAV manufacturing, and the usual response surface designs may be part of the difficulty. They place most design points near the boundary of the experimental region, leaving interior kinetic behavior largely unmeasured. Developed with statistician Philip J. Ramsey of the University of New Hampshire, this work applies a 24-run space filling design to six process parameters in suspended HEK293 cells, run in a high-throughput microbioreactor platform with integrated analytics. It tracks effects on titer, capsid, and transfection efficiency, and considers what fuller coverage of the design space means for setting critical process parameters.

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