In biopharmaceutical manufacturing, single-use equipment is becoming popular for small-scale production schemes instead of stainless steel equipment. In this work, a decision support framework is presented to systematically generate alternatives at multiple decision layers. The framework includes decision layers for product specifications, the process flowsheet, equipment material, and operating conditions. Generated alternatives are evaluated on their economic and environmental impacts in addition to the risks regarding product quality and supply robustness. A case study was performed, where a comprehensive set of alternatives for equipment material was investigated with representative elements from other layers for the sterile filling of biopharmaceuticals. The results confirmed the preference for single-use equipment for small-scale and short-term production. Results also showed a preference for using fixed equipment for large-scale and long-term production. Generated hybrid alternatives outperformed empirically generated alternatives and provided a compromise between the competing environmental and economic indicators. (C) 2018 Published by Elsevier Ltd.