(372s) Alternative Generation and Evaluation Using a Design Framework: Case Study on Drug Substance Manufacturing Processes of Biopharmaceuticals
In this work, we present a case study of alternative generation and evaluation for drug substance manufacturing processes of biopharmaceuticals. The basis of the work is the design framework that can systematically generate alternatives at four decision layers that are product specifications, process flowsheet, equipment, and operating conditions . The framework, previously applied to a sterile filling that is a process after drug substance manufacturing, is applied to standard drug substance manufacturing processes of mAbs. If only the choice between batch or continuous operation mode is considered for each of the six unit operations in the involved process, 64 process alternatives can be generated. However, to realize continuous operation, there are further process options available, e.g., alternating tangential flow (ATF) or tangential flow filtration (TFF) system for perfusion, and simulated moving bed (SMB) chromatography or continuous countercurrent tangential chromatography (CCTC) for purification. Combining all of these options generates more than 60,000 process alternatives. A comprehensive set of the alternatives will be automatically generated and evaluated with respect to process production time and costs to select the preferred combination of process alternatives.
The application of the design framework to drug substance manufacturing enables the systematic and comprehensive generation of alternatives to achieve a more holistic approach for process design of biopharmaceuticals.
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