Accelerating Fed-Batch Process Development Using Rationally Designed Feed Media

摘要

Rational design of culture media for fed-batch production of recombi-nant therapeutics can be used to dramatically improve product yields in a short time frame. A fed-batch process including a feed medium, hydrolysate supplement, and easy-to-implement fed-batch process can be designed in less than six months using this methodology. Feed media are designed using a combined bottom-up and top-down approach that involves spent media analysis and previous experience. Hydrolysate supplements are quickly developed using survey experiments followed by statistically designed mixtures experiments. The optimal method of combining (he feed and hydrolysate supplement are then determined followed by process development experiments to determine the best overall feeding strategy. In keeping with the rational design approach, development of each media component and the feeding strategy are conducted concurrently. A case study is presented with example data given from each step of a fed-batch development project for a recombinant CHO cell line. Overall production in the developed fed-batch process was increased six fold when compared to batch culture in a project conducted over a five month period.