Think continuous, think small.
Continuous bioprocessing allows the constant and uninterrupted processing of materials in parallel production lines.
The explosive growth in mAb-based biologics, the globalization of biomanufacturing, and the economic pressures to reduce capital investment, cost of development and cost of goods all point to changes in how biopharmaceutical manufacturing plants are designed, built and operated. The benefits of continuous processing when applied to biologics production can be paradigm-changing.
When converting to continuous processing, the volumetric productivity of the process increases while the size and volume of equipment decreases. A facility running a continuous process will be significantly smaller than a large-scale batch facility, thus reducing capital expenses.
Benefits of continuous processing include:
- Reduced capital cost and time
- Reduced equipment size
- Deployment of single-use technology
- Streamlined process flow
- Low cycle times
- Steady state operation
- Consistent product quality
- Increased productivity
Perfusion, or upstream continuous processing, has been used since the 1980s. High cell density perfusion, or XCell™ ATF perfusion, delivers higher cell concentration and cell viability.
N-1 perfusion refers to the intensification of cell growth in the step prior to the production bioreactor (N). This process intensification is done using perfusion in the N-1 bioreactor for high cell density seeding of the production bioreactor (N), or removal of the N-1 bioreactor if the N-2 bioreactor can provide enough cells for the production bioreactor (N).
High density (HD) cell banking
High density (HD) cell banking is a novel method for seed train optimization using perfusion to intensify cell density and reduce the number of early-stage expansion steps.
A continuous capture chromatography process is the next big challenge for modern bioproduction. Multi-column chromatography operates in continuous mode, balancing downstream productivity with upstream titers.
Integrated upstream and downstream continuous bioprocesses have the potential to revolutionize bioprocessing, leading to significant improvements in process efficiencies, manufacturing footprint, productivity and cost of goods.
The opinions expressed in this book are those of the authors and not of Repligen Corporation.
- Introduction to Continuous Manufacturing:Technology Landscape and Trends
Eric S. Langer & Ronald A. Rader, BioPlan Associates
- A Brief History of Perfusion Biomanufacturing
Jerry Shevitz and John Bonham-Carter
- Bioreactor Configuration and Operation
Christel Fenge, Jörg Weyand, Gerhard Greller, Thorsten Adams,
Sartorius Stedim Biotech
- How to Develop a Perfusion Process
Véronique Chotteau, Royal Technical University, KTH
- Case Study: Optimized Perfusion
Shaun Eckerle, Gallus BioPharmaceuticals
- Process Intensification Approaches for Cost Sensitive Protein Applications
Willem Adriaan de Jongh, Expres2ion Biotechnologies
- Impact of Single-use Technology on Continuous Bioprocessing
William G. Whitford, Thermo Fisher Scientific
- Continuous Multicolumn Chromatography Processes
Marc Bisschops, Tarpon Biosystems
- Continuous Processes: Economic Evaluation
Andrew Sinclair & Andrew Brown, BioPharm Services
- Vision: Integrating Upstream and Downstream in a Fully Continuous Facility
Tim Johnson, Genzyme
Selected Third Party references