A simplified techno‐economic model for the molecular pharming of antibodies

Abstract

By the end of 2017, the Food and Drug Administration had approved a total of 77 therapeutic monoclonal antibodies (mAbs), most of which are still manufactured today. Furthermore, global sales of mAbs topped $90 billion in 2017 and are projected to reach $125 billion by 2020. The mAbs approved for human therapy are mostly produced using Chinese hamster ovary (CHO) cells, which require expensive infrastructure for production and purification. Molecular pharming in plants is an alternative approach with the benefits of lower costs, greater scalability, and intrinsic safety. For some platforms, the production cycle is also much quicker. But do these advantages really stack up in economic terms? Earlier techno-economic evaluations have focused on specific platforms or processes and have used different methods, making direct comparisons challenging and the overall benefits of molecular pharming difficult to gauge. Here, we present a simplified techno-economic model for the manufacturing of mAbs, which can be applied to any production platform by focusing on the most important factors that determine the efficiency and cost of bulk drug manufacturing. This model develops economic concepts to identify variables that can be used to achieve cost savings by simultaneously modeling the dynamic costs of upstream production at different scales and the corresponding downstream processing costs for different manufacturing modes (sequential, serial, and continuous). The use of simplified models will help to achieve meaningful comparisons between diverse manufacturing technologies. K E Y W O R D Sdownstream processing, protein manufacturing, techno-economic analysis, therapeutic antibodies, upstream production

Development of an intensified fed-batch production platform with doubled titers using N-1 perfusion seed for cell culture manufacturing

“…The intensified platform fed-batch Process C developed in this study is very effective for mAb manufacturing. Since cell culture titer and production scale are two of the most important parameters to determine manufacturing costs (Kelley 2009;Mir-Artigues et al 2019), Process C with much higher titers (Table 2) and successful scale up in large-scale manufacturing makes the manufacturing costs lower than in the fed-batch Process A and Process B. Effective mAb manufacturing with higher titer and volumetric productivity, better robustness and lower costs has been a goal for both academia and the biopharmaceutical industry for the last 3 decades.…”

High Level Production of Monoclonal Antibodies Using an Optimized Plant Expression System

“…Furthermore, plant systems do not need to be grown in sterile conditions and, as plants lack animal pathogens, plant-based biotechnology has improved intrinsic safety over mammalian expression systems (Sack et al, 2015b). These factors allow highly scalable production of biopharmaceutical proteins with substantially reduced costs (Tusé et al, 2014;Walwyn et al, 2015;Nandi et al, 2016;Alam et al, 2018;Mir-Artigues et al, 2019). The cost-effectiveness of plant-based systems may especially benefit developing countries (Ma et al, 2013).…”

Structural and In Vitro Functional Analyses of Novel Plant-Produced Anti-Human PD1 Antibody

“…Comparing to current antibody production platforms, plants offer several advantages for producing antibodies over others. Plants have significantly lower infrastructure and raw material cost for upstream production compared to mammalian cells 4,5 . Plants-based system can do greater scalability because there is no restriction on the fermenter size.…”