Monday, November 9, 2009 - 9:15 AM
S10

Process Characterization of a Fermentation Process

Thomas Harrington, Process Developement, Lonza Microbial Biopharmaceuticals, CA

An integrated Design of Experiments study was performed to determine Critical Process Parameters using a fermentation scale down model.  The central design was a 16-batch full factorial study to investigate four parameters at two levels (Dissolved Oxygen, Induction Temperature, Induction Wet Cell Weight, and Feed Rate).  The secondary design was a 4-batch fractional factorial study consisting of three parameters at two levels (Feed Rate, Dissolved Oxygen, and Dithiothreitol Concentration in the extraction pool).  These two studies shared four center point batches to allow the entire CPP study to be performed with only 24 fermentations.  Responses from the fermentations, capture column partial purifications, and full-process purifications were analyzed for statistical significance at the 95% confidence level.  None of the fermentation parameters had an effect on the purified drug substance quality attributes.  Proven Acceptable Ranges were established and optimum conditions were determined.