Are automated disposable small-scale reactors set to dominate the future of pharmaceutical bioprocess development?

Pollard, David

doi:10.4155/pbp.13.62

Cited by 7 publications

(4 citation statements)

References 13 publications

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“…There is a commercial and clinical need to expedite cell therapy process development; small‐scale, high‐throughput platforms provide a means to achieve this. Such technologies can improve efficiency, reduce costs, and accelerate time to market while minimizing development resources (Bareither and Pollard, ; Pollard, ; Rafiq and Hewitt, ). Moreover, the high‐throughput nature of these technologies are amenable for Quality by Design (QbD) tools such as factorial design of experiments (DoE) which have become an integral part of modern process development and manufacture.…”

Section: Introductionmentioning

confidence: 99%

Process development of human multipotent stromal cell microcarrier culture using an automated high‐throughput microbioreactor

Rafiq

Hanga

Heathman

et al. 2017

Biotech & Bioengineering

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Microbioreactors play a critical role in process development as they reduce reagent requirements and can facilitate high‐throughput screening of process parameters and culture conditions. Here, we have demonstrated and explained in detail, for the first time, the amenability of the automated ambr15 cell culture microbioreactor system for the development of scalable adherent human mesenchymal multipotent stromal/stem cell (hMSC) microcarrier culture processes. This was achieved by first improving suspension and mixing of the microcarriers and then improving cell attachment thereby reducing the initial growth lag phase. The latter was achieved by using only 50% of the final working volume of medium for the first 24 h and using an intermittent agitation strategy. These changes resulted in >150% increase in viable cell density after 24 h compared to the original process (no agitation for 24 h and 100% working volume). Using the same methodology as in the ambr15, similar improvements were obtained with larger scale spinner flask studies. Finally, this improved bioprocess methodology based on a serum‐based medium was applied to a serum‐free process in the ambr15, resulting in >250% increase in yield compared to the serum‐based process. At both scales, the agitation used during culture was the minimum required for microcarrier suspension, NJS. The use of the ambr15, with its improved control compared to the spinner flask, reduced the coefficient of variation on viable cell density in the serum containing medium from 7.65% to 4.08%, and the switch to serum free further reduced these to 1.06–0.54%, respectively. The combination of both serum‐free and automated processing improved the reproducibility more than 10‐fold compared to the serum‐based, manual spinner flask process. The findings of this study demonstrate that the ambr15 microbioreactor is an effective tool for bioprocess development of hMSC microcarrier cultures and that a combination of serum‐free medium, control, and automation improves both process yield and consistency. Biotechnol. Bioeng. 2017;114: 2253–2266. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

Process development of human multipotent stromal cell microcarrier culture using an automated high‐throughput microbioreactor

Rafiq

Hanga

Heathman

et al. 2017

Biotech & Bioengineering

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“…The recent development of single use disposable bioreactors from TAP Biosystems that can operate either 24 bioreactors in parallel at 250 ml volumes or 48 bioreactors at 15 ml has greatly increased the throughput and accuracy with which scale-down bioreactors can be run [21][22][23][24]. Resin slurry plates or micropipette tips that can be run in a 96-well format could prove to be crucial techniques for providing rapid quality assessments of material generated in these disposable bioreactors.…”

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confidence: 99%

Pushing the limits of high-throughput chromatography process development: current state and future directions

Welsh¹

2015

Pharmaceutical Bioprocessing

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“…For example, smallscale stirred-tank bioreactor platforms are more reliable predictors of large-scale performance than traditional shake-flask models, reducing time to market and cost of goods [55]. Moreover, translational researchers should employ quality tools such as risk assessments and process maps to break down each process step to its constituent components and ensure that each process platform is scalable, and identify what process steps, if any, can be eliminated entirely or replaced with an alternative, more readily scalable step.…”

Section: Consider Scale From the Outsetmentioning

confidence: 99%

The Early Career Researcher’s Toolkit: Translating Tissue Engineering, Regenerative Medicine and Cell Therapy Products

et al. 2015

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Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization.

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Are automated disposable small-scale reactors set to dominate the future of pharmaceutical bioprocess development?

Cited by 7 publications

References 13 publications

Process development of human multipotent stromal cell microcarrier culture using an automated high‐throughput microbioreactor

Process development of human multipotent stromal cell microcarrier culture using an automated high‐throughput microbioreactor

Pushing the limits of high-throughput chromatography process development: current state and future directions

The Early Career Researcher’s Toolkit: Translating Tissue Engineering, Regenerative Medicine and Cell Therapy Products

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