Design Space Visualization and Technoeconomic Evaluation of a Batch Manufacturing Process for the Green Production of an Anti-cancer Drug (Adavosertib) Precursor

The development of cost-effective and sustainable manufacturing processes is a growing priority in the pharmaceutical industry, with many companies turning to computational modeling to reduce reliance on experimental campaigns. Established simulation frameworks must however support in silico pharma R&D, especially for detailed process design and optimization. This paper introduces a robust but simple and flebible modeling framework for simulating and optimizing batch manufacturing processes, applying it to the production of AZD1775 HMS (a small-molecule intermediate required for the synthesis of the experimental anti-cancer drug Adavosertib). The entire design space is mapped using high-fidelity submodels for batch reactors and liquid–liquid extraction (LLE) units. The impact of solvent selection, reagent concentration, separation solvent ratio, operating temperature, and equipment size on process viability has also been evaluated, towards identification of a cost-optimal and environmentally friendly LLE solvent system (water–acetonitrile–toluene) and process conditions. Drug development can thus be streamlined by this systematic pathway for sustainable manufacturing, achieving economic and environmental goals simultaneously.