The Current Scientific and Regulatory Landscape in Advancing Integrated Continuous Biopharmaceutical Manufacturing
Abstract
There is a trend across the pharmaceutical sector toward process intensification and continuous manufacturing to produce small-molecule drugs or biotechnology products. For biotechnology products, advancing the manufacturing technology behind upstream and downstream processes has the potential to reduce product shortages and variability, allow for production flexibility, simplify scale-up procedures, improve product quality, reduce facility footprints, increase productivity, and reduce production costs. On the upstream side of biotechnology manufacturing, continuous perfusion cell cultures are fairly well established. However, truly integrated continuous biomanufacturing requires the uninterrupted connection of continuous unit operations (upstream and downstream) with no isolated intermediate or hold steps occurring between them. This work examines the current scientific and regulatory landscape surrounding the implementation of integrated continuous biomanufacturing.
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Fully integrated continuous manufacturing provides advantages by reducing costs, improving quality, and speeding up product release.
“A fully integrated continuous manufacturing provides advantages by reducing the costs, improving the quality while speeding up the product release [24, 26]”
From Current PAT Landscape in the Downstream Processing of Biopharmaceuticals (2025) · cites this paper as [26]
Implementation of PAT in downstream processing has been somewhat limited due to various difficulties associated with it.
“Implementation of PAT in DSP has been somewhat limited due to various difficulties associated with it [26].”
From Current PAT Landscape in the Downstream Processing of Biopharmaceuticals (2025) · cites this paper as [26]
Comprehensive monitoring of all critical quality attributes cannot be achieved with a single analytical technology; an integrated approach combining multiple techniques, sensors, and control systems is essential for effective process monitoring and control.
“The comprehensive monitoring of all critical quality attributes (CQAs) cannot be achieved with a single analytical technology; instead, an integrated approach combining multiple techniques, sensors and control systems is essential for effective process monitoring and control [20, 26].”
From Current PAT Landscape in the Downstream Processing of Biopharmaceuticals (2025) · cites this paper as [26]
Cites
Bhatia, H., Mehdizadeh, H., Drapeau, D., & Yoon, S. (2018) · Engineering in Life Sciences · doi:10.1002/elsc.201700084 · Cited by 87 · see citing works
Self-citationShaw, A. D., Kaderbhai, N., Jones, A., Woodward, A. M., Goodacre, R., Rowland, J. J., & Kell, D. B. (1999) · Applied Spectroscopy · doi:10.1366/0003702991945777 · Cited by 84 · see citing works
Balakrishnan, S., Suma, M. S., Raju, S. R., Bhargav, S. D. B., Arunima, S., Das, S., & Ananthasuresh, G. K. (2015) · BioResearch open access · doi:10.1089/biores.2015.0024 · Cited by 20 · see citing works
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mRNA vaccines manufacturing: challenges and bottlenecks
Rosa, S. S., Prazeres, D. M. F., Azevedo, A. M., & Marques, M. P. C. (2021) · Vaccine · doi:10.1016/j.vaccine.2021.03.038 · Cited by 545 · see citing works
Perfusion culture of Chinese Hamster Ovary cells for bioprocessing applications
MacDonald, M. A., Nöbel, M., Roche Recinos, D., Martínez, V. S., Schulz, B. L., Howard, C. B., Baker, K., Shave, E., Lee, Y. Y., Marcellin, E., et al. (2022) · Critical Reviews in Biotechnology · doi:10.1080/07388551.2021.1998821 · Cited by 55 · see citing works
Yilmaz, D., Mehdizadeh, H., Navarro, D., Shehzad, A., O'Connor, M., & McCormick, P. (2020) · Biotechnology Progress · doi:10.1002/btpr.2947 · Cited by 51 · see citing works
Current PAT Landscape in the Downstream Processing of Biopharmaceuticals
Sathiyapriyan, P., Mukherjee, S., Vogel, T., Essen, L., Boerema, D., Vey, M., & Kalina, U. (2025) · Analytical Science Advances · doi:10.1002/ansa.70013 · Cited by 45 · see citing works
Continuous integrated manufacturing for biopharmaceuticals: A new paradigm or an empty promise?
Rathore, A. S., Thakur, G., & Kateja, N. (2023) · Biotechnology and Bioengineering · doi:10.1002/bit.28235 · Cited by 41 · see citing works
- Authors
- Fisher, A. C., Kamga, M.-H., Agarabi, C., Brorson, K., Lee, S. L., & Yoon, S.
- Venue
- Trends in Biotechnology
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 37
- Issue
- 3
- Pages
- 253-267
- ISSN
- 0167-7799
- Cited by
- 158
- References
- 3
- Language
- en
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