From direct energy calculation to the life cycle assessment of a drug synthesis process: comparative case study of antibiotic intermediate synthesis at different development stages

This study conducts a Life Cycle Assessment (LCA) of the production of an intermediate in the synthesis of zosurabalpin, a novel antibiotic under clinical investigation, with a focus on direct energy consumption. The assessment examines two chemical processes: the Suzuki reaction and hydrolysis, evaluating their environmental impact across three production stages based on process descriptions and inventory data from Hoffmann-La Roche. The process was first implemented at an industrial scale in 2020, followed by laboratory-scale development in 2023, leading to process optimization and re-implementation on an industrial scale in 2024. The study assesses the extent to which optimizations have reduced environmental impact. A key finding is that material consumption is the dominant driver of environmental impact, whereas direct energy consumption plays a minor role. The study highlights the importance of industrial data collection, enabling an LCA primarily based on primary data. Additionally, it explores the applicability of lab-scale LCA as a predictive tool for industrial-scale impact, demonstrating its reliability when cleaning processes are separately accounted for. The study also examines the relationship between LCA results and Process Mass Intensity (PMI), a green chemistry metric for mass efficiency. The findings indicate that PMI reductions align with decreases in LCA impact, as process optimization focused on solvent consumption. However, since LCA captures factors beyond material efficiency, PMI alone does not provide a fully comprehensive environmental assessment. This study underscores LCA’s role in incorporating sustainability in pharmaceutical process development and its usefulness for early-stage decision-making.