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Increased interest in the pharmaceutical industry to transition from batch to continuouos manufacturing motivates the use of digital frameworks that allow systematic comparison of candidate process configurations. This article evaluates the technical and economic feasibility of different end‐to‐end optimal process configurations, namely, batch, hybrid and continuous, for small‐scale manufacturing of an active pharmaceutical ingredient. Production campaigns were analyzed for those configurations containing continuous equipment, where significant start‐up effects are expected given the relatively short campaign times considered. Hybrid operating mode was found to be the most attractive process configuration at intermediate and large annual production targets, which stems from combining continuous reactors and semi‐batch vaporization equipment. Continuous operation was found to be more costly, due to long stabilization times of continuous crystallization, and thermodynamic limitations of flash vaporization. Our work reveals the benefits of systematic digital evaluation of process configurations that operate under feasible conditions and compliant product quality attributes.

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