(597b) Match-Maker's Dilemma: Developing a Novel Cell Culture Process for a Late-Stage Program for Which Every Parameter Changes, But Product Quality Remains Unchanged

Following the acquisition of a late-stage program with clearly defined product quality attributes, we were tasked with developing an entirely new cell culture process from cell line to harvest capable of meeting a pre-defined increase in productivity
(> 5-fold) while still matching existing product quality attributes (purity, glycosylation patterns and enzyme activity).  Initially, we mapped out a series of experiments across multiple scales evaluating many different clones.  As we proceeded to distinguish -clones from each other on the basis of productivity and product quality, we began to identify limitations in our existing cell culture platform process.  For instance, necessary co-factors for the desired product were at low levels in the basal media with respect to the product concentration, and supplementation of these co-factors was found to be beneficial to productivity. The timing and exact amount of supplementation was determined experimentally along with modifications to the feeding strategy.  Once the production clone was selected, additional experiments were performed to fine tune operating conditions with both product quality and scale-up in mind.  Of particular interest were glycosylation patterns and maintaining similar sialylation levels.  Ultimately, modifications to feed delivery lines, timing of supplementation, feed composition, gassing strategy and harvest criteria led to a successful program capable of meeting all pre-defined criteria.