Upstream cell culture process characterization and in-process control strategy development at pandemic speed

Xu, Jinying; Ou, Jianfa; McHugh, Kyle P.; Borys, Michael; Khetan, Anurag

doi:10.1080/19420862.2022.2060724

Cited by 14 publications

(11 citation statements)

References 34 publications

(40 reference statements)

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“…This concept provides a simple and robust scale-up approach to implement robust processes across multiple production sites. A systematic scale-up strategy could facilitate the development of scale down models which helps to enable fast CMC and product development timelines (Xu et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…This concept provides a simple and robust scale‐up approach to implement robust processes across multiple production sites. A systematic scale‐up strategy could facilitate the development of scale down models which helps to enable fast CMC and product development timelines (Xu et al, 2022). Nevertheless, it needs to be mentioned that the impact of mechanical on cell metabolism was clearly different between the impact of and osmotic stress and should be further explored in future studies.…”

Section: Discussionmentioning

confidence: 99%

“…Chinese hamster ovary (CHO) cells are well characterized and widely used as an expression system for the synthesis of complex glycosylated therapeutic proteins (Palomares et al, 2004; Tejwani et al, 2018; Zhu, 2012), including monoclonal antibodies (mAb) (Niklas & Heinzle, 2012; Parau et al, 2022; Schulze et al, 2022; Sidoli et al, 2004), viral vaccines (Vester et al, 2010), and hormones (Nottorf et al, 2007). The most commonly used production mode in the field is still the fed‐batch process (Ben Yahia et al, 2021; Ghaffari, 2015; Romanova et al, 2021; Xu et al, 2022; Zhang, 2010). Nevertheless, biopharmaceutical companies are facing more constraints, as the years progress, to further increase productivity, while reducing production costs (Farid et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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“Organized stress” for robust scale‐up of intensified production process with fed‐batch seed bioreactor

Yahia

Piednoir

Dahomais

et al. 2023

Biotech & Bioengineering

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Process intensification has been widely used for many years in the mammalian biomanufacturing industry to increase productivity, agility and flexibility while reducing production costs. The most commonly used intensified processes are operated using a perfusion or fed‐batch seed bioreactor enabling a higher than usual seeding density in the fed‐batch production bioreactor. Hence, as part of the growth phase is shifted to the seed bioreactor, there is a lower split ratio, which increases the criticality of the seed bioreactor and could impact production performance. Therefore, such intensified processes should be designed and characterized for robust process scale‐up. This research work is focused on intensified processes with high seeding density inoculated from seed bioreactor in fed‐batch mode. The impact of the feeding strategy and specific power input (P/V) in the seed bioreactor and on the production step with two different cell lines (CL1 and CL2) producing two different monoclonal antibodies was investigated. Cell culture performance in the production bioreactor has been improved due to more stressful conditions for the cells in the seed bioreactor and the impact of the production bioreactor P/V on the production performance was limited. This is the first reported study highlighting a positive impact of cellular stress in seed bioreactors on intensified production bioreactor with the introduction of the “organized stress” concept.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

“Organized stress” for robust scale‐up of intensified production process with fed‐batch seed bioreactor

Yahia

Piednoir

Dahomais

et al. 2023

Biotech & Bioengineering

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“…For instance, Agostinetto et al used non‐clonal cell banks for manufacturing of a SARS‐CoV‐2‐neutralizing mAb at 200‐L and 2,000‐L scales to rapidly provide clinical trial materials within 4.5 months (Agostinetto et al, 2022 ). On the other hand, Xu et al reported the completion of late‐stage cell culture process characterization of two SARS‐CoV‐2‐neutralizing mAbs within 4 months, in comparison to a typical 12‐month timeline (J. Xu et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Rapidly accelerated development of neutralizing COVID‐19 antibodies by reducing cell line and CMC development timelines

Tan

Qian

et al. 2022

Biotech & Bioengineering

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Since the Coronavirus Disease 2019 (COVID‐19) outbreak, unconventional cell line development (CLD) strategies have been taken to enable development of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐neutralizing antibodies at expedited speed. We previously reported a novel chemistry, manufacturing, and control (CMC) workflow and demonstrated a much‐shortened timeline of 3–6 months from DNA to investigational new drug (IND) application. Hereafter, we have incorporated this CMC strategy for many SARS‐CoV‐2‐neutralizing antibody programs at WuXi Biologics. In this paper, we summarize the accelerated development of a total of seven antibody programs, some of which have received emergency use authorization approval in less than 2 years. Stable pools generated under good manufacturing practice (GMP) conditions consistently exhibited similar productivity and product quality at different scales and batches, enabling rapid initiation of phase I clinical trials. Clones with comparable product quality as parental pools were subsequently screened and selected for late‐stage development and manufacturing. Moreover, a preliminary stability study plan was devised to greatly reduce the time required for final clone determination and next‐generation sequencing‐based viral testing was implemented to support rapid conditional release of the master cell bank for GMP production. The successful execution of these COVID‐19 programs relies on our robust, fit for purpose, and continuously improving CLD platform. The speed achieved for pandemic‐related biologics development may innovate typical biologics development timelines and become a new standard in the industry.

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“… 5 While monoclonal antibodies (mAbs) have been developed to treat infectious diseases previously, 6–9 the coronavirus disease 2019 (COVID-19) pandemic has created renewed interest in using antibody-based biotherapeutics as a treatment option for infectious diseases. 10–12 In 2021, the global antibody market was valued at 217.3 billion USD and is projected to exhibit an annual growth rate of approximately 15% in the next decade. 13–15 Considering the scale at which antibody-based biotherapeutics are now being discovered and developed, it is apparent that the industrialization of mAbs has come of age.…”

Section: Introductionmentioning

confidence: 99%

Trends in industrialization of biotherapeutics: a survey of product characteristics of 89 antibody-based biotherapeutics

Martin

Grimaldi

Grempler

et al. 2023

mAbs

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There is considerable interest in the pharmaceutical industry toward development of antibody-based biotherapeutics because they can selectively bind diverse receptors and often possess desirable pharmacology. Here, we studied product characteristics of 89 marketed antibody-based biotherapeutics that were approved from 1986 to mid-2020 by gathering publicly available information. Our analyses revealed major trends in their emergence as the best-selling class of pharmaceuticals. Early on, most therapeutic monoclonal antibodies were developed to treat cancer, with CD20 being the most common target. Thanks to industrialization of antibody manufacturing technologies, their use has now blossomed to include 15 different therapeutic areas and nearly 60 targets, and the field is still growing! Drug manufacturers are solidifying their choices regarding types of antibodies and their molecular formats. IgG1 kappa continues to be the most common molecular format among marketed antibody-based biotherapeutics. Most antibody-based biotherapeutics approved since 2015 are either humanized or fully human, but the data we collected do not show a direct correlation between humanness and reported incidence of anti-drug antibodies. Furthermore, there have also been improvements in terms of drug product stability and high concentration liquid formulations suitable for subcutaneous route of administration, which are being approved more often in recent years. These improvements, however, have not been uniformly adopted across all therapeutic areas, suggesting that multiple options for drug product development are being used to serve diverse therapeutic purposes. Insights gained from this analysis may help us devise better end-to-end antibody-based biotherapeutic drug discovery and development strategies.

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Upstream cell culture process characterization and in-process control strategy development at pandemic speed

Cited by 14 publications

References 34 publications

“Organized stress” for robust scale‐up of intensified production process with fed‐batch seed bioreactor

“Organized stress” for robust scale‐up of intensified production process with fed‐batch seed bioreactor

Rapidly accelerated development of neutralizing COVID‐19 antibodies by reducing cell line and CMC development timelines

Trends in industrialization of biotherapeutics: a survey of product characteristics of 89 antibody-based biotherapeutics

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