Efforts are being focused to streamline process development timelines to move products quickly into different stages of clinical trails. Consequently, more efficient methods for process development have become increasingly important for accelerating process optimization and reducing costs. Techniques such as high throughput screening and the leveraging of automation have been used to improve process development efficiency. In addition, mathematical tools such as DOE, mathematical models and MultiSimplex algorithms can also be used to increase efficiency during process development.

Here we present two case studies in which these mathematical tools were utilized to quickly and efficiently establish operating conditions for the purification of antibody-derived fusion proteins. The first involves the development of elution conditions for a Protein-A chromatography operation in which the goal was to achieve a high step yield and reduce product related aggregate. The second concerns the use of a multimodal anion exchange resin for the reduction of product related impurities through the use of an intermediate wash. By using these methods, an optimal elution condition was achieved after only 8 experiments for the Protein-A unit operation, resulting in an 85% process yield with a reduction of product related aggregate from ~20% to less than 2%. These tools also enabled the rapid development of optimal intermediate wash conditions for the multimodal ion exchange process which were found to be robust, scalable and resulted in the removal of the product related impurities while maintaining > 80% step yields.