A new, integrated, continuous purification process template for monoclonal antibodies: Process modeling and cost of goods studies

Xenopoulos, Alex

doi:10.1016/j.jbiotec.2015.04.020

Cited by 116 publications

(89 citation statements)

References 21 publications

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“…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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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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“…Two flow-through purification/polishing chromatography steps were successfully combined in a single operation with a pool-less concept without intermediate product hold tanks [6]. Adoption of flow-through polishing with replacement of bind/elute chromatography can significantly reduce the cost of unit operations [8]. The resulting process time achieved from an entire flow-through purification process was estimated to be less than the batch chromatography train itself [7].…”

Section: Introductionmentioning

confidence: 99%

Polishing approach with fully connected flow‐through purification for therapeutic monoclonal antibody

Ichihara

Ito

Gillespie³

2018

Engineering in Life Sciences

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The biopharmaceutical industry is evolving toward process intensification that can offer increased productivity and improved economics without sacrificing process robustness. A semi‐continuous downstream process linking purification/polishing unit operations in series can reduce or eliminate intermediate holding tanks and reduce overall processing time. Accordingly, we have developed a therapeutic monoclonal antibody polishing template comprised of a connected flow‐through polishing technologies that include activated carbon, cation exchange, and anion‐exchange chromatography. In this report, we evaluated fully‐connected pool‐less polishing with three flow‐through technologies, operating as a single skid to streamline and improve an mAb purification platform. Laboratory‐scale pool‐less processing was achieved without utilizing in‐line pH adjustment and conductivity dilution based on the previously optimized single process parameter. Two connected flow‐through configurations of polishing steps were evaluated: a two‐step process using anion exchange and cation exchange and a three step process using activated carbon, anion exchange and cation exchange chromatography. Laboratory‐scale proof of concept studies showed comparable performance between the batch purification process and the pool‐less process configuration. Three step polishing highly intensified the processes and provided higher process loading and achieved bulk drug specification with higher impurity clearance (>95%) and high overall mAb yield (>95%).

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“…This last constraint enabled straight-through, integrated bioprocesses to be identified using our tool, addressing a major objective in industrial downstream bioprocessing (Ghose, Jin, Liu, & Hickey, 2009;Klutz et al, 2015;Walther et al, 2015;Warikoo et al, 2012;Xenopoulos, 2015;Zydney, 2015). The software was constrained to search for three-step purification processes that contained a single flowthrough step.…”

Section: Purification Process Synthesis Using An In Silico Toolmentioning

confidence: 99%

An impurity characterization based approach for the rapid development of integrated downstream purification processes

Timmick

Vecchiarello

Goodwine

et al. 2018

Biotech & Bioengineering

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In this study, we describe a new approach for the characterization of process-related impurities along with an in silico tool to generate orthogonal, integrated downstream purification processes for biological products. A one-time characterization of process-related impurities from product expression in Pichia pastoris was first carried out using linear salt and pH gradients on a library of multimodal, salt-tolerant, and hydrophobic charge induction chromatographic resins. The Reversed-phase ultra-performance liquid chromatography (UPLC) analysis of the fractions from these gradients was then used to generate large data sets of impurity profiles. A retention database of the biological product was also generated using the same linear salt and pH gradients on these resins, without fraction collection. The resulting two data sets were then analyzed using an in silico tool, which incorporated integrated manufacturing constraints to generate and rank potential three-step purification sequences based on their predicted purification performance as well as whole-process "orthogonality" for impurity removal. Highly ranked sequences were further examined to identify templates for process development. The efficacy of this approach was successfully demonstrated for the rapid development of robust integrated processes for human growth hormone and granulocyte-colony stimulating factor.

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A new, integrated, continuous purification process template for monoclonal antibodies: Process modeling and cost of goods studies

Cited by 116 publications

References 21 publications

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

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

Polishing approach with fully connected flow‐through purification for therapeutic monoclonal antibody

An impurity characterization based approach for the rapid development of integrated downstream purification processes

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