From Industrial Biotech (Biofuels/chemicals) to Cell Therapies (Stem Cells): Delivering the Next Generation of Products and Processes Using Design of Experiments (DoE), Quality by Design (QbD) and Scale-up/Scale Down Methods
April 16th, 2012, SC 5326 3:00 p.m.
Tiffany D. Rau, PhD.
Global Biotechnology Consultant
The ability to quickly and cost effectively develop and manufacture the next generation of products which include therapeutic proteins, vaccines, enzymes, biochemicals and biofuels is key to delivering the pipelines of today and tomorrow to the clinic and to the market place. Today’s organizations are not just developing products using one expression platform but many, for example, bacteria, yeast, CHO, fungi and even stem cells. It is beneficial to have controlled scale-up/scale-down tools that are flexible enough to be used to explore and develop a variety of expression platforms each having opportunities and challenges. DoE experiments are often used to define the multivariate design space of fermentation processes and this is done with greater efficiency using high-throughput systems that model large scale unit operations thus allowing the scientist and engineer to obtain QbD (Quality by Design) data earlier for process robustness, cost of goods analysis as well as information for future regulatory filings. An overview of the biotechnology industry with respect to process development and scale-up will be presented and this will include examples of rapid cell line selection and process development in both microbial and mammalian expression systems. The data will also show the importance of identifying critical parameters early in development and then having the confidence in the models to scale up those findings. Next generation work in the area of human embryonic stem cells (hESC) and small scale bioreactors will also be presented where a hESC Mixl reporter line will undergo differentiation towards a cardiac line in small scale bioreactors. One of the critical parameters that was explored for the hESC work was dissolved oxygen level and how it impacts growth and differentiation.