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Enhancing the biochemical supply chain towards sustainable development requires more efforts to boost technology innovation at early design phases and avoid delays in industrial biotechnology growth. Such a transformation requires a comprehensive step-wise procedure to guide bioprocess development from laboratory protocols to commercialization. This study introduces a process design framework to guide research and development (R&D) through this journey, bearing in mind the particular challenges of bioprocess modeling. The method combines sustainability assessment and process optimization based on process efficiency indicators, technical indicators, Life Cycle Assessment (LCA), and process optimization via Water Regeneration Networks (WRN). Since many bioprocesses remain at low Technology Readiness Levels (TRLs), the process simulation module was examined in detail to account for uncertainties, providing strategies for successful guidance. The sus-tainability assessment was performed using the geometric mean-based sustainability footprint metric. A case study based on Chitosan production from shrimp exoskeletons was evaluated to demonstrate the method’s applicability and its advantages in product optimization. An optimized scenario was generated through a WRN to improve water management, then compared with the case study. The results confirm the existence of a possible configuration with better sustainability performance for the optimized case with a sustainability footprint of 0.33, compared with the performance of the base case (1.00).