Solutions
Perfusion Cell Culture
Increase output, reduce cost per gram, and improve flexibility with upstream process intensification through perfusion cell culture, without expanding your facility footprint.
How Perfusion Cell Culture Works
Perfusion cell culture is a continuous upstream bioprocessing strategy in which cells are maintained in a bioreactor for an extended period (typically weeks) while fresh culture medium is continuously supplied and spent medium, metabolic waste products, and harvested product are continuously removed.
At the core of every perfusion system is a cell retention device, which keeps viable cells inside the bioreactor while allowing continuous media exchange. By maintaining cells in a nutrient-rich, low-waste environment, perfusion cultures sustain high viable cell densities (VCD) and high viability over long run durations that are not achievable in traditional fed-batch.
Perfusion enables 10X VCD and 10X product than Fed-Batch
While optimized fed-batch processes typically reach 10–20×10⁶ cells/mL, perfusion cultures routinely sustain 100×10⁶ cells/mL or higher, driving volumetric productivities of 2 g/L/day or more.
Figure A
Figure B
Perfusion achieved 100-130 million viable cell density (VCD) compared to 13 million for Fed-Batch. Perfusion culture viability was maintained above 90% over a period of 17 days. Fed-Batch viability began to drop after day 9 to approximately 70% at days 14-15. Higher VCD and viability of perfusion cultures translated to an increase in total product yield. The perfusion process yielded approximately 30-35 g, while the Fed-Batch process achieved 3 g in approximately 15 days.
Why You Should Move to Perfusion
Perfusion cell culture offers greater productivity, more operational flexibility, and improved sustainability over traditional fed-batch.
Higher Productivity, Smaller Footprint
Achieve 10X or higher volumetric productivity using smaller bioreactor volumes and fewer production runs. Reduce CAPEX, facility footprint, and costs on a per-gram basis while meeting or exceeding output targets.
Greater Operational Flexibility
Perfusion supports three scaling strategies: scale-up, scale-out, and scale-on that give multiproduct facilities and CDMOs the agility to respond to demand without capital investment or process redesign.
Sustainability
Smaller equipment footprints, fewer production runs, and greater process efficiency drive meaningful sustainability impact reductions compared to fed-batch, based on published modeling data.
Higher Productivity, Smaller Footprint
Achieve 10X or higher volumetric productivity using smaller bioreactor volumes and fewer production runs. Reduce CAPEX, facility footprint, and costs on a per-gram basis while meeting or exceeding output targets.
Greater Operational Flexibility
Perfusion supports three scaling strategies: scale-up, scale-out, and scale-on that give multiproduct facilities and CDMOs the agility to respond to demand without capital investment or process redesign.
Sustainability
Smaller equipment footprints, fewer production runs, and greater process efficiency drive meaningful sustainability impact reductions compared to fed-batch, based on published modeling data.
Boost Upstream Productivity with N-1 and N-Stage Perfusion
Biologics demand is outpacing upstream capacity, and teams need practical, low-risk strategies to increase output within existing fed-batch facilities. Perfusion-based process intensification offers two proven strategies to increase productivity and lower COGs.
- N-stage perfusion maximizes productivity and reduces upstream COG
- N-1 perfusion accelerates fed-batch timelines with higher-density inoculation
- Both approaches are scalable and widely adopted across leading upstream cell culture processes at all scales
Scaling Strategies for Perfusion Cell Culture
One of the most important advantages of perfusion is the flexibility it provides in how manufacturers respond to growing or variable demand. Three distinct scaling approaches are available, each with trade-offs.
Scale-Up | Increase Bioreactor Volume
Increase bioreactor size to achieve higher total output per run. Provides economies of scale and is the most familiar approach for teams transitioning from fed-batch.
- Economies of scale at high volumes
- Familiar operational model
- Fewer campaigns required
Requires capital investment and facility build time.
Scale-Out | Parallel Bioreactor Operations
Run multiple smaller bioreactors in parallel to increase aggregate output while maintaining operational flexibility. Well-suited for multiproduct manufacturing environments.
- No single point of failure
- Supports simultaneous campaigns
- Flexible allocation across products
Increases operational complexity and consumable usage.
Scale-On (Scale-by-Time) | Extend Run Duration
PERFUSION ONLY
Increase total output by extending the duration of a continuous run using existing equipment with no additional capital investment.
- No capital investment required
- Leverages existing equipment
- Ideal for variable demand scenarios
Not achievable in fed-batch; run duration is fixed.
Cell Retention Technology Considerations
Repligen is the only provider with differentiated, scalable solutions across ATF, TFF, and TFDF filters covering the full spectrum of upstream process intensification needs. The appropriate choice depends on cell type, shear sensitivity, and process requirements.
XCell® ATF System | Alternating Tangential Flow
- Lowest shear
- Proven scalability
- Long, continuous process duration
- Single use and stainless-steel formats
KrosFlo® KPS Tangential Flow Filtration (TFF) Systems | Tangential Flow Filtration
- Broadest size range
- Multiple chemistries
- Configurable systems
- Built-in Redundancy
KrosFlo® TFDF® Systems | Tangential Flow Depth
- No wetting
- Single technology workflow
- Rapid media exchange
- Large molecule clarification
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