The business impact of an integrated continuous biomanufacturing platform for recombinant protein production

Walther, Johannes; Godawat, Rahul; Hwang, Chris; Abe, Yuki; Sinclair, Andrew H.; Konstantinov, Konstantin

doi:10.1016/j.jbiotec.2015.05.010

Cited by 212 publications

(171 citation statements)

References 20 publications

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“…More recently, however, changes in the industry landscape have challenged this approach. Patent expirations have led to growing competition from biosimilars, creating a strong need to reduce manufacturing costs . Furthermore, producers of orphan drugs and personalized medicines require increased operational flexibility to maintain a diverse molecule pipeline in multiproduct facilities .…”

Section: Introductionmentioning

confidence: 99%

Investigating the combination of single‐pass tangential flow filtration and anion exchange chromatography for intensified mAb polishing

Elich¹,

Goodrich²,

Lutz³

et al. 2019

Biotechnology Progress

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There is growing interest within the biopharmaceutical industry to improve manufacturing efficiency through process intensification, with the goal of generating more product in less time with smaller equipment. In monoclonal antibody (mAb) purification, a unit operation that can benefit from intensification is anion exchange (AEX) polishing chromatography. Single‐pass tangential flow filtration (SPTFF) technology offers an opportunity for process intensification by reducing intermediate pool volumes and increasing product concentration without recirculation. This study evaluated the performance of an AEX resin, both in terms of host cell protein (HCP) purification and viral clearance, following concentration of a mAb feed using SPTFF. Results show that preconcentration of AEX feed material improved isotherm conditions for HCP binding, resulting in a fourfold increase in resin mAb loading at the target HCP clearance level. Excellent clearance of minute virus of mouse and xenotropic murine virus was maintained at this higher load level. The increased mAb loading enabled by SPTFF preconcentration effectively reduced AEX column volume and buffer requirements, shrinking the overall size of the polishing step. In addition, the suitability of SPTFF for extended processing time operation was demonstrated, indicating that this approach can be implemented for continuous biomanufacturing. The combination of SPTFF concentration and AEX chromatography for an intensified mAb polishing step which improves both manufacturing flexibility and process productivity is supported.

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Section: Introductionmentioning

confidence: 99%

Investigating the combination of single‐pass tangential flow filtration and anion exchange chromatography for intensified mAb polishing

Elich¹,

Goodrich²,

Lutz³

et al. 2019

Biotechnology Progress

View full text Add to dashboard Cite

show abstract

“…Cost modeling studies that focus on continuous mAb purification often compare processes that use different upstream formats to target the same mAb demand . Studies that do compare different downstream modes at the same feed scale either do so in detail for a few cases, or do not consider a continuous downstream in which all unit operations after the bioreactor occur in parallel …”

Section: Introductionmentioning

confidence: 99%

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

Hummel

Pagkaliwangan

Gjoka

et al. 2018

Biotechnology Journal

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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.

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“…Continuous manufacturing is currently evaluated as an alternative production technology for various biopharmaceuticals at different stages of industrial development. Improved economics, higher volumetric productivity and flexibility, as well as enhanced controllability of product quality are main drivers toward continuous production platforms . Mammalian cell perfusion cultures are well‐known and have regained attraction in this context .…”

Section: Introductionmentioning

confidence: 99%

Improved Performance in Mammalian Cell Perfusion Cultures by Growth Inhibition

Wolf¹,

Closet²,

Bzowska

et al. 2018

Biotechnology Journal

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Mammalian cell perfusion cultures represent a promising alternative to the current fed-batch technology for the production of various biopharmaceuticals. Long-term operation at a fixed viable cell density (VCD) requires a viable culture and a constant removal of excessive cells. Product loss in the cell removing bleed stream deteriorates the process yield. In this study, the authors investigate the use of chemical and environmental growth inhibition on culture performance by either adding valeric acid (VA) to the production media or by reducing the culture temperature (33.0 °C) with respect to control conditions (36.5 °C, no VA). Low temperature significantly reduces cellular growth, thus, resulting in lower bleed rates accompanied by a reduced product loss of 11% compared to 26% under control conditions. Additionally, the cell specific productivity of the target protein improves and maintained stable leading to media savings per mass of product. VA shows initially an inhibitory effect on cellular growth. However, cells seemed to adapt to the presence of the inhibitor resulting in a recovery of the cellular growth. Cell cycle and Western blot analyses support the observed results. This work underlines the role of temperature as a key operating variable for the optimization of perfusion cultures.

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The business impact of an integrated continuous biomanufacturing platform for recombinant protein production

Cited by 212 publications

References 20 publications

Investigating the combination of single‐pass tangential flow filtration and anion exchange chromatography for intensified mAb polishing

Investigating the combination of single‐pass tangential flow filtration and anion exchange chromatography for intensified mAb polishing

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

Improved Performance in Mammalian Cell Perfusion Cultures by Growth Inhibition

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