Evolving trends in mAb production processes

Shukla, Abhinav A.; Wolfe, Leslie S.; Mostafa, Sigma S.; Norman, Carnley

doi:10.1002/btm2.10061

Cited by 194 publications

(128 citation statements)

References 64 publications

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“…Three downstream processes were modeled using BioSolve Process for direct cost of goods (CoGs) and net present cost (NPC) comparison. The three processes: stainless steel (SS) batch, SU batch, and an integrated, continuous bioprocessing (ICB) platform were analogous in that they followed what is more or less an established set of downstream unit operations for mAb purification . Downstream costs were evaluated for the three processes across an array of scenarios relevant to clinical and commercial manufacturing.…”

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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“…Flow‐through mode of operation for the second step was fixed in order to ensure that the charge variant resolution obtained by the CEX column remained unaltered after the product passes through the second column. Multimodal chromatography was selected as the method of choice over HIC and AEX modes of chromatography for clearance of aggregates based on its superior performance and also the ability to remove HMWI even at low conductivity in the feed …”

Section: Resultsmentioning

confidence: 99%

“…A variety of such process platforms for mAb therapeutics have been reported in the literature . A platform process that utilizes multimodal anion and cation exchange resins in place of traditional anion and cation exchange has also been reported recently . This platform has been shown to perform consistently for multiple mAbs, delivering product containing high molecular weight impurities (HMWI) of <1% and HCP of <50 ppm.…”

Section: Introductionmentioning

confidence: 99%

Integrated Chromatographic Platform for Simultaneous Separation of Charge Variants and Aggregates from Monoclonal Antibody Therapeutic Products

Kateja

Kumar

Godara

et al. 2017

Biotechnology Journal

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Achieving consistent product quality of a biotherapeutic is a major target for any biopharmaceutical manufacturer, even more for a biosimilar producer as comparability with the innovator product is a regulatory expectation. The complexity of biotherapeutic products and their tedious manufacturing processes, however, make this a non-trivial exercise. The primary motivation of this work is to develop an integrated chromatographic platform for purification of monoclonal antibody (mAb) therapeutics that can deliver the desired separation of both charge variants and aggregates, in addition to the process related impurities like host cell proteins (HCP) and host cell DNA. To achieve the same, an integrated two-stage chromatographic process platform consisting of cation exchange chromatography and multimodal chromatography is being proposed. The versatility of the proposed platform has been successfully demonstrated for three different mAbs. It have been shown that in each case charge variant separation is achieved with the required clearance of aggregates (<1%), HCP (<10 ppm), and DNA (<5 ppb). Moreover, the proposed platform is conducive to use for development of a continuous process and offers smaller process time, lower buffer utilization, and decreased operational costs when compared to the conventional purification platforms.

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“…In order to provide demonstrated clearance of viruses, a combination of purification unit operations is used . These most often include a combination of chemical inactivation, filtration, and chromatography unit operations . Because many mAbs have conserved properties that make them highly similar, such as a constant domain, similar sized variable domains, and in most cases basic isoelectric points—the design of these unit operations for different antibodies can be maintained.…”

Section: Scientific and Technology Considerationsmentioning

confidence: 99%

Suitability of a generic virus safety evaluation for monoclonal antibody investigational new drug applications

Sipple

Nguyen

Patel

et al. 2019

Biotechnology Progress

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Biologics produced from CHO cell lines with endogenous virus DNA can produce retrovirus‐like particles in cell culture at high titers, and other adventitious viruses can find their way through raw materials into the process to make a product. Therefore, it is the industry standard to have controls to avoid introduction of viruses into the production process, to test for the presence of viral particles in unclarified cell culture, and to develop purification procedures to ensure that manufacturing processes are robust for viral clearance. Data have been accumulated over the past four decades on unit operations that can inactivate and clear adventitious virus and provide a high degree of assurance for patient safety. During clinical development, biological products are traditionally tested at process set points for viral clearance. However, the widespread implementation of platform production processes to produce highly similar IgG antibodies for many indications makes it possible to leverage historical data and knowledge from representative molecules to allow for better understanding and control of virus safety. More recently, individualized viral clearance studies are becoming the rate‐limiting step in getting new antibody molecules to clinic, particularly in Phase 0 and eIND situations. Here, we explore considerations for application of a generic platform virus clearance strategy that can be applied for relevant investigational antibodies within defined operational parameters in order to increase speed to the clinic and reduce validation costs while providing a better understanding and assurance of process virus safety.

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Evolving trends in mAb production processes

Cited by 194 publications

References 64 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

Integrated Chromatographic Platform for Simultaneous Separation of Charge Variants and Aggregates from Monoclonal Antibody Therapeutic Products

Suitability of a generic virus safety evaluation for monoclonal antibody investigational new drug applications

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