Bioprocess Engineering: Advances in Cell Culture Systems, Reactor Design, Scale-up Strategies, and Intensification Processes for the Production of Biological and Bioactive Compounds
DOI:
https://doi.org/10.56294/evk2025149Keywords:
Bioprocesses, Cell Culture, Bioreactors, EngineeringAbstract
Bioprocess engineering is undergoing an unprecedented transformation, driven by the growing demand for complex and bioactive biological products across diverse industries, from pharmaceuticals to food and energy. Recent advances have redefined the efficiency, scalability, and sustainability of biomanufacturing. Key elements of this evolution include the widespread adoption of single-use systems, the integration of automation and artificial intelligence (AI) for precise control and predictive optimization, and the fundamental shift toward continuous bioprocessing. These innovations not only reduce costs and production times but also improve product quality and consistency, enabling the manufacturing of personalized therapies and high-value compounds. Scaling strategies have diversified to include both scale-up and parallel expansion (scale-out), tailored to specific product needs. Together, these developments are laying the foundation for more agile, cost-effective, and environmentally responsible biomanufacturing, preparing the industry to address global challenges in health and sustainability.
References
1. Leadvent Group. The Future of Bioprocessing: Emerging Trends and Technologies. https://www.leadventgrp.com/blog/the-future-of-bioprocessing-emerging-trends-and-technologies
2. EBSCO. Bioprocess Engineering. https://www.ebsco.com/research-starters/engineering/bioprocess-engineering
3. PharmaFocus America. Bioprocessing & Bioproduction In-Depth Focus 2025. https://www.pharmafocusamerica.com/articles/bioprocessing-bioproduction-in-depth-focus-2025
4. Single-Use Bioreactors Market Sizing. Towards Healthcare; 2025 May 09. https://www.towardshealthcare.com/insights/single-use-bioreactors-market-sizing
5. Towards Healthcare. Single-Use Bioreactors Market Challenges & Solution in Biomanufacturing. 2025 May 09. https://www.towardshealthcare.com/insights/single-use-bioreactors-market-sizing
6. Green Elephant Biotech. Scale-Up vs. Scale-Out in Bioprocessing. https://www.greenelephantbiotech.com/post/scale-up-vs-scale-out-in-bioprocessing
7. Extrapolate. Bioprocess Technology Powering Innovation. 2024 Mar 14. https://www.extrapolate.com/blog/bioprocess-technology-powering-innovation
8. Taylor & Francis. Bioprocess engineering. https://taylorandfrancis.com/knowledge/Engineering_and_technology/Biomedical_engineering/Bioprocess_engineering/
9. Demcon Life Sciences Health. Cell culture equipment. https://lifescienceshealth.demcon.com/showcases/cell-culture-equipment
10. BCC Research. Bioprocess Optimization and Digital Bio-Manufacturing: Transforming the Industry.; 2025 Jan 10. https://blog.bccresearch.com/bioprocess-optimization-and-digital-bio-manufacturing-transforming-the-industry
11. Bioprocessing Summit. The Bioprocessing Summit. Cell Culture. https://www.bioprocessingsummit.com/24/cell-culture
12. IDBS. Enhancing Process Performance with AI in Bioprocessing. 2025 May 22. https://www.idbs.com/knowledge-base/enhancing-process-performance-with-ai-in-bioprocessing/
13. Bordeaux, M., de Girval, D., Rullaud, R., Subileau, M., Dubreucq, E., Drone, J. (2014). High-cell-density cultivation of recombinant Escherichia coli, purification and characterization of a self-sufficient biosynthetic octane -hydroxylase. Applied Microbiology and Biotechnology, 98(14),6275-6283. DOI: 10.1007/s00253-014-5671-1 DOI: https://doi.org/10.1007/s00253-014-5671-1
14. SUSupport. Seed Train Intensification: Next Step Biopharma. 2024 Nov 28. https://www.susupport.com/knowledge/manufacturing-processes/bioprocessing/seed-train-intensification-next-step-biopharma
15. Repligen. Process Intensification. 2025. https://www.repligen.com/solutions/process-intensification
16. Eppendorf. Batch, Fed-Batch, and Continuous Culture. https://www.eppendorf.com/hu-en/lab-academy/applied-industries/bioprocessing/introduction-to-bioprocessing/batch-fed-batch-and-continuous-culture/
17. Muiznieks L. Perfusion for Live Cell Imaging: A Review. Elveflow. https://www.elveflow.com/microfluidic-reviews/perfusion-for-live-cell-imaging-a-review/
18. Gupta P, Kateja N, Mishra S, Kaur H, Rathore AS. Economic assessment of continuous processing for manufacturing of biotherapeutics. Biotechnol Prog. 2021 Mar;37(2):e3108. doi: 10.1002/btpr.3108. DOI: https://doi.org/10.1002/btpr.3108
19. Mendes AR, Spínola MP, Lordelo M, Prates JAM. Advances in Bioprocess Engineering for Optimising Chlorella vulgaris Fermentation: Biotechnological Innovations and Applications. Foods. 2024; 13(24):4154. https://doi.org/10.3390/foods13244154 DOI: https://doi.org/10.3390/foods13244154
20. FasterCapital. Bioreactor design: Enhancing Bioreactor Performance through Innovative Design Approaches. 2025 Apr 08. https://www.fastercapital.com/content/Bioreactor-design--Enhancing-Bioreactor-Performance-through-Innovative-Design-Approaches.html
21. Mabion. Bioprocess Operation Modes and Advanced Bioreactor Technology. https://www.mabion.eu/science-hub/articles/bioprocess-operation-modes-and-advanced-bioreactor-technology/
22. IDBS. Challenges in Scaling Up Bioprocesses in Bioprocessing. 2025 May 22. https://www.idbs.com/knowledge-base/challenges-in-scaling-up-bioprocesses-in-bioprocessing/
23. Eppendorf. Bioprocessing Scale-Up. https://www.eppendorf.com/id-en/lab-academy/applied-industries/bioprocessing/introduction-to-bioprocessing/bioprocessing-scale-up/
24. Key Considerations for Industrial Bioprocess Scale-Up. CRB Group. https://www.crbgroup.com/insights/biotechnology/industrial-biotechnology
25. Bioprocessing Summit. Digital Transformation and AI in Bioprocess. https://www.bioprocessingsummit.com/digital-transformation
26. Eppendorf. Cell Culture in Bioreactors. https://www.eppendorf.com/us-en/lab-academy/applied-industries/bioprocessing/introduction-to-bioprocessing/cell-culture-in-bioreactors/
27. Process Intensification. Sartorius. https://www.sartorius.com/en/applications/biopharmaceutical-manufacturing/process-intensification
28. Xu J, Xu X, Huang C, Angelo J, Oliveira CL, Xu M, Xu X, Temel D, Ding J, Ghose S, Borys MC, Li ZJ. Biomanufacturing evolution from conventional to intensified processes for productivity improvement: a case study. MAbs. 2020 Jan 1;12(1):1770669. doi: 10.1080/19420862.2020.1770669. DOI: https://doi.org/10.1080/19420862.2020.1770669
29. Evotec. The Promise of Continuous Processing to Advance Biopharmaceutical Production. https://www.evotec.com/en/sciencepool/the-promise-of-continuous-processing-to-advance-biopharmaceutical-production
30. Sridhar K, Inbaraj BS, Sharma M. Advancing Natural Bioactive Formulations: Innovations in Agri-Food-Pharma for Enhanced Health and Sustainability. Bioengineering (Basel). 2025 Apr 11;12(4):405. doi: 10.3390/bioengineering12040405. https://pmc.ncbi.nlm.nih.gov/articles/PMC12024521/ DOI: https://doi.org/10.3390/bioengineering12040405
31. SUSupport. Introduction to Therapeutic Proteins. 2024 Apr 10. https://www.susupport.com/knowledge/biopharmaceutical-products/vaccines/introduction-therapeutic-proteins
32. TECNIC. What is Upstream and Downstream Bioprocess?. https://www.tecnic.eu/what-is-upstream-and-downstream-bioprocess/
33. Argonne National Laboratory. Bioprocess Engineering. https://www.anl.gov/topic/science-technology/bioprocess-engineering.
Published
Issue
Section
License
Copyright (c) 2025 Freddy Ednildon Bautista-Vanegas , Jose Luis Diaz-Guerrero , Ingrid Neysa Cabezas-Soliz , Blas Apaza-Huanca, Estefannie Eunice Valverde Fernández, Jhossmar Cristians Auza-Santivañez , Themis Karim Ocampo Gamboa, Rebeca Rocio Gomez Rosales, Luis Mariano Tecuatl Gómez , Pablo Carías, Ruben Marco Antonio Soliz-Mendoza (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
The article is distributed under the Creative Commons Attribution 4.0 License. Unless otherwise stated, associated published material is distributed under the same licence.
