Process intensification in the biopharma industry: Improving efficiency of protein manufacturing processes from development to production scale using synergistic approaches

• Published in: Chemical engineering and processing Vol. 171; p. 108727
• Main Authors: Müller, Dirk, Klein, Lukas, Lemke, Johannes, Schulze, Markus, Kruse, Thomas, Saballus, Martin, Matuszczyk, Jens, Kampmann, Markus, Zijlstra, Gerben
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.01.2022
• Subjects: Biopharma; Continuous processes; Optimization; Perfusion; Process intensification; Scale-down models; Scale-down models; Process intensification; Continuous processes; Biopharma; Perfusion; Optimization
• ISSN: 0255-2701; 1873-3204
• DOI: 10.1016/j.cep.2021.108727

•Implemented examples demonstrate synergistic process intensification from perfusion clone selection to production process.•Predictive scale-down models are crucial to rapidly establish scalable intensified processes.•Multi-step intensification delivers up to tenfold gain in space-time yield for mAb processes.•The presented approach may facilitate wider adoption of process intensification in biopharma. Process intensification strives for more efficient conversion of raw materials into products while minimizing resource usage. In the biopharma industry, typical intensification gains include increased plant capacities, reduced raw material costs, smaller facilities and improved sustainability. Rapid growth combined with increasingly diverse and challenging molecule formats in the biopharma sector necessitate strategies for fast development of highly productive and cost-efficient processes. Using monoclonal antibody production in CHO cells as example, we present intensification techniques and process sequences that deliver synergistic benefits like increasing space-time yields up to 10-fold, shortening production runs by 30%, or saving numerous days in cell expansion. Combining highly productive perfusion with continuous downstream purification promises improved yields and production economics, especially for advanced, often labile molecules. Predictive scale-down models demonstrated here for selecting intensification-ready cell lines and for rapid setup of intensified processes are essential to realize such benefits broadly in the industry. They enable testing and quick tailoring of intensification alternatives like high-inoculation fed-batch or perfusion to suit molecule needs, facility space, and financial conditions. Since many techniques also readily extend to other protein biotherapeutics, intensification can be regarded as key pillar enabling fast, cost-efficient development and production of biopharma products in the coming years. [Display omitted]