End-to-end continuous bioprocessing: Impact on facility design, cost of goods, and cost of development for monoclonal antibodies.

This article presents a systematic approach to evaluate the business case for continuous processing that captures trade-offs between manufacturing and development costs for monoclonal antibodies (mAbs). A decisional tool was built that integrated cost of goods (COG) with the cost of development models and new equipment sizing equations tailored to batch, hybrid, and end-to-end continuous processes. The COG analysis predicted that single-use continuous facilities (sized using a dedicated downstream processing train per bioreactor) offer more significant commercial COG savings over stainless steel batch facilities at annual demands of 100-500 kg (35%), compared to tonnage demands of 1-3 tons (±10%) that required multiple parallel continuous trains. Single-use batch facilities were found to compete with continuous options on COG only at 100 kg/year. For the scenarios where batch and continuous facilities offered similar COG, the analysis identified the windows of operation required to reach different COG savings with thresholds for the perfusion rate, volumetric productivity, and media cost. When considering the project lifecycle cost, the analysis indicated that while end-to-end continuous facilities may struggle to compete on development costs, they become more cost-effective than stainless steel batch facilities when considering the total out-of-pocket cost across both drug development and commercial activities.