Considering the capital intensive nature of the chemical industry, redesign of existing production plants is a strategic decision. In this study, retrofitting is performed using a systematic path flow decomposition method, enriching it with hazard assessment and life cycle analysis path flow indicators and proposing a classification scheme for coupling these new path flow indicators with relevant heuristics for process alternative generation. The developed methodology is applied in a batch production plant from the pharmaceutical industry. The method highlights solvent recovery or substitution as important retrofitting actions, generates diverse process layout structures to achieve this task and evaluates them from cost, hazard and life cycle assessment point of view. Extractive distillation using glycol as an entrainer is identified as the multiobjective optimal option for separating the THF/Water azeotrope with improvement up to 40% for the various objectives compared with a base case where the waste solvent is incinerated. (c) 2015 American Institute of Chemical Engineers AIChE J, 61: 3423-3440, 2015