Process development for the recovery and purification of a recombinant HSA-fusion protein expressed in <i>saccharomyces cerevisiae</i> was successfully performed under accelerated timelines. The work presented in this poster focuses on challenges encountered during the scale-up for pre-clinical and clinical bulk drug substance manufacturing. While the manufactured drug substance exhibited the required quality and stability profiles during initial scale-up demonstration runs, high endotoxin levels were detected owing to the significant endotoxin-binding properties of HSA. Subsequent measures were taken to control endotoxin levels and successfully deliver acceptable toxicology material, including an evaluation of endotoxin removal approaches through filtration, as well as the use of closed harvest operations and single-use downstream equipment. Further scale-up had an impact on product quality and stability, which was attributed to an increase in proteolytic activity. Studies focused on identification and characterization of specific proteases are discussed. For harvest operations, an evaluation of process and operational differences and related risks across lab- and pilot-scale, and the resulting potential effect on protease activity, are also discussed.

Understanding endotoxin control and protease degradation during scale-up and technology transfer for an HSA-fusion protein

2019 Spring National Meeting

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