The emergence of precision medicine and the need to increase speed to the clinic pose challenges for conventional centralized, large-scale biomanufacturing platforms. The ability to rapidly produce new products with high-quality and at a small-scale using minimal expert knowledge could meet this challenge. To this end, we have demonstrated a bench-scale, integrated, and automated end-to-end biologics manufacturing system capable of producing, purifying, and formulating high-quality products in less than 80 hours without human intervention. Our flexible system includes separate modules for cultivation, multi-stage chromatography, and tangential filtration, which are all controlled using a single integrated control software. The multi- stage chromatography module employs straight-through processing to increase throughput and minimize complexity. To realize the utility of such a system for precision medicine, or rapid material production during early clinical stages, we have developed a complementary, integrated approach for process development to make new, non-platform products on the system in 3-6 months. For novel purification processes we have taken advantage of the low and consistent host cell protein burden of our host organism, Pichia pastoris. Based on a one-time analysis of the host cell proteins, along with knowledge of chromatographic behavior for a few target products, we have developed a universal starter process for purifying proteins produced in Pichia. To date, more than four unique proteins, including growth hormones, nanobodies, and recombinant vaccines, have successfully been purified from Pichia based on this integrated, two-column process with minimal modifications. We believe that our end-to-end biologics manufacturing system coupled with rapid process development enabled by this universal starter process for purification could minimize the time and expertise required to produce a new drug with high-quality at a small- scale. This may also help increase access to these drugs where and when patients need them.

Rapid, end-to-end manufacturing of biologics enabled by a universal starter process for purification of proteins produced in Pichia pastoris

2019 Spring National Meeting

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