Environmental impact of upstream processing strategies for E. coli-based antibody fragment production: A case study of green metrics versus life cycle assessment.

The positive impact of pharmaceuticals on society is accompanied by environmental issues associated with resource use and production emissions. This study evaluates the environmental footprint of a microbial recombinant fragment antigen-binding (Fab) production process using Escherichia coli at the laboratory scale under the different upstream process strategies fed-batch, repetitive fed-batch, Chemostat and cascaded setup. Simplified green metrics were applied to assess mass and energy efficiency, followed by a cradle-to-gate life-cycle assessment (LCA) to account for emissions associated with raw-material supply. The comparison of both approaches, supported by correlation analysis, identified energy demand as the key driver of the environmental impact of the process itself. In addition, the LCA revealed that the carbon source is a major contributor not captured by green metrics alone. Continuous cultivations reduced the global warming potential (GWP) by up to 40% and water consumption by 12%. A sensitivity analysis of internal, external, and scale-dependent parameters confirmed the robustness of these findings. Transitioning to renewable electricity can further reduce GWP by 35-42%, reflecting the high energy intensity of biopharmaceutical manufacturing. This study addresses an important gap in the environmental assessment of microbial biopharmaceutical production and highlights process intensification as a critical path to improve energy efficiency.