Characterization of a pDNA Biomanufacturing Fermentation Process Using Definitive Screening Designs and JMP® 10 Software
Dogan Ornek, PhD, Senior Scientist, Lonza Biologics
Philip Ramsey, PhD, Professor, University of New Hampshire
Novel antiviral and cancer fighting vaccines based on naked plasmid DNA (pDNA) are heading toward FDA approval. The long-term viability of these vaccines partly depends upon the development of efficient and robust pDNA biomanufacturing processes. Traditionally, this type of characterization has been accomplished via a two-step procedure utilizing a combination of Resolution III or IV screening designs and response surface designs (often Box-Behnken). This two-step process is time-consuming and costly. Jones and Nachtscheim (2011) introduced definitive screening designs, a new class of efficient experimental designs that can allow factor screening as well as the estimation of quadratic effects and two-way interactions within a single experiment. The designs are implemented in JMP 10. In this talk we show how the use of a single five-factor, 15-run definitive screening design resulted in the successful characterization and modeling of a fermentation step of a pDNA biomanufacturing process. In addition, the 15-run definitive screening design was evaluated against a 31-run, 2^(5-1) fractional factorial design augmented with axial points to accommodate quadratic effects. Both designs were used on the same process with the same factors. The 15-run definitive screening design process characterization was equivalent to that provided by the much larger augmented fractional factorial, including the identification of two important quadratic effects. The successful comparison validates the use of definitive screening designs for biomanufacturing process characterization with substantial cost and time savings. The talk will cover details of the design comparison, model selection and process characterization. In addition, a brief tutorial on pDNA manufacturing and vaccines will be provided.