Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost Advantages for Continuous Methods for a Broad Range of Manufacturing Scales

Abstract

The biopharmaceutical industry is evolving in response to changing market conditions, including increasing competition and growing pressures to reduce costs. Single-use (SU) technologies and continuous bioprocessing have attracted attention as potential facilitators of cost-optimized manufacturing for monoclonal antibodies. While disposable bioprocessing has been adopted at many scales of manufacturing, continuous bioprocessing has yet to reach the same level of implementation. In this study, the cost of goods of Pall Life Science's integrated, continuous bioprocessing (ICB) platform is modeled, along with that of purification processes in stainless-steel and SU batch formats. All three models include costs associated with downstream processing only. Evaluation of the models across a broad range of clinical and commercial scenarios reveal that the cost savings gained by switching from stainless-steel to SU batch processing are often amplified by continuous operation. The continuous platform exhibits the lowest cost of goods across 78% of all scenarios modeled here, with the SU batch process having the lowest costs in the rest of the cases. The relative savings demonstrated by the continuous process are greatest at the highest feed titers and volumes. These findings indicate that existing and imminent continuous technologies and equipment can become key enablers for more cost effective manufacturing of biopharmaceuticals.

Implementation of Fully Integrated Continuous Antibody Processing: Effects on Productivity and COGm

“…Increasing culture duration beyond 42 days yielded diminishing returns but remained advantageous compared to the batch scenario. This model was specific to the process derived for the experimentally tested monoclonal antibody, but the conclusions were in line with other cost modeling exercises …”

“…This model was specific to the process derived for the experimentally tested monoclonal antibody, but the conclusions were in line with other cost modeling exercises. [17][18][19]30,31]…”

Truly continuous low pH viral inactivation for biopharmaceutical process integration

“…The biopharmaceutical industry is following other industries in moving from discrete batch operation to integrated continuous manufacturing, especially for high demand products, such as monoclonal antibodies (MAbs; Shukla, Wolfe, Mostafa, & Norman, 2017; Walsh, 2018). The drivers for continuous processing are many‐fold; process intensification and cost savings (Baur, Angarita, Müller‐Späth, Steinebach, & Morbidelli, 2016; Hummel et al, 2018; Pagkaliwangan, Hummel, Gjoka, Bisschops, & Schofield, 2018; Pollock, Coffman, Ho, & Farid, 2017) might emerge as the most obvious ones but steady‐state operation and thus better, more reproducible quality have also been associated with continuous biomanufacturing (Karst et al, 2017; Kaufman, Wasley, & Dorner, 1988; Walther et al, 2019). While upstream processing is ahead in this transition, where chemostat and perfusion reactors are commonly employed at the manufacturing scale (Arathoon & Birch, 1986; Shukla et al, 2017; Warnock & Al‐Rubeai, 2006), downstream operations have only in recent years started this transition.…”

Process‐wide control and automation of an integrated continuous manufacturing platform for antibodies

“…Significant efforts have been made to successfully develop unit operations capable to handle continuous streams both for upstream and downstream processing (Angarita et al, 2015; Jungbauer, 2013; Rathore, Agarwal, Sharma, Pathak, & Muthukumar, 2015; Rathore, Kateja, & Agarwal, 2017; Steinebach, Müller‐Späth, & Morbidelli, 2016; Rathore et al, 2017; Wolf et al, 2018). Primary drivers are economic benefits as discussed in different studies (Arnold, Lee, Rucker‐Pezzini, & Lee, 2019; Hummel et al, 2019; Pollock, Coffman, Ho, & Farid, 2017; Walther et al, 2015), higher efficiency of counter‐current chromatographic purification units (Pfister, Nicoud, & Morbidelli, 2018) as well as more homogeneous product quality through uniformity of the microenvironment and reduced residence time in continuous bioreactors (Karst et al, 2018; Karst, Steinebach, Soos, & Morbidelli, 2017; Liu, Gaza‐Bulseco, Faldu, Chumsae, & Sun, 2008; Pacis, Yu, Autsen, Bayer, & Li, 2011; Zydney, 2015). Furthermore, by integrating all unit operations in a single manufacturing platform, processing time, production efficiency, and equipment footprint can be further optimized (Arnold et al, 2019; Karst et al, 2017).…”

“…. Primary drivers are economic benefits as discussed in different studies (Arnold, Lee, Rucker-Pezzini, & Lee, 2019;Hummel et al, 2019;Pollock, Coffman, Ho, & Farid, 2017;Walther et al, 2015), higher efficiency of counter-current chromatographic purification units (Pfister, Nicoud, & Morbidelli, 2018) as well as more homogeneous product quality through uniformity of the microenvironment and reduced residence time in continuous bioreactors Karst, Steinebach, Soos, & Morbidelli, 2017;Liu, Gaza-Bulseco, Faldu, Chumsae, & Sun, 2008;Pacis, Yu, Autsen, Bayer, & Li, 2011;Zydney, 2015). Furthermore, by integrating all unit operations in a single manufacturing platform, processing time, production efficiency, and equipment footprint can be further optimized (Arnold et al, 2019;Karst et al, 2017).…”