Separation and Purification Technology, Vol.77, No.3, 355-366, 2011
Systematic downstream process development for purification of baccatin III with key performance indicators
Performance and cost-efficiency of biotechnological processes largely depend on decisions made in early phases of process development. Experimental investigation of process alternatives, unit operations, mass separating agents and operating conditions should therefore follow a systematic approach. Results should be evaluated and alternatives benchmarked with the aim of designing the most cost-efficient total process. Key performance indicators can meet this demand prior to availability of complete process concepts or mass balances. In this paper utilization and benefit of purification performance index (PPI), purification fingerprints and separation cost indicator (SCI) are demonstrated for the example of an experimentally-based downstream process development. Adsorption is investigated as a first purification step to separate baccatin III, a precursor of the anti-cancer drug paclitaxel, from the supernatant of a plant cell culture of Taxus baccata. Nine sorbents and 11 solvents (desorbents) are screened at different phase ratios. Concentration changes of the target substance and 13 major contaminants are evaluated and rated by costs with key performance indicators to find an optimal process concept. As a result, 94% pure baccatin III can be obtained from filtered fermentation broth by a simple low-cost downstream process consisting of three steps only: adsorption, washing and desorption. (C) 2011 Published by Elsevier B.V.