During the early phase development, a phase-appropriate approach often focuses on development speed rather than on process performance. As a program heads toward phase 3/registration, in addition to the process performance qualification exercise, companies may seek opportunities to improve the process economics and increase supply without changing production scale or the host cell line. In this case study, a process improvement project was undertaken starting with media and feed screening with a goal of increasing the titer by up to two fold while maintaining comparable product quality. The ambr®15 microbioreactor was used as a scale down model to execute the initial media and feed screens. The top performing media and feed combination that maintained the desired product profile was then taken into a second round of ambr screens for fed-batch process development. A methodology for modulating the product profile was identified during the second round of ambr screens, in which optimization of the ratio of multiple commercially available basal media resulted in the ability to either increase or decrease the overall percentage of a key product quality attribute in the molecule’s product profile while maintaining high titer. Further experiments were conducted at the 10L scale to demonstrate successful scale up, increase robustness and determine the process parameter ranges for the improved media process. This improved process was then confirmed at the 10L scale and executed at the 2000L.

Late-phase process improvement: Methods to increase titer while maintaining product quality

255th National Meeting (2018)

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