High Productivity Harvest

High Productivity Harvest for Fed-Batch processes simplifies primary recovery and boosts production, eliminates centrifuge and depth filtration steps, and harvests material ready for processing on a capture column.

High Productivity Harvest

An innovative application of a cell retention device in the clarification step developed by Repligen, High Productivity Harvest for Fed-Batch processes has both productivity and process benefits.

Traditional Clarification

A traditional clarification process typically includes multi-stage harvest steps that are equipment-intensive and known to have high variability in processing. Because of the materials of construction used, extensive rinsing is needed causing large usage of buffer/WFI.

During centrifugation, there are no true linear scaling tools making it very labor-intensive. Lastly, traditional clarification processes are usually performed in an open system that is inherently non-sterile and not aligned with the industry trend to manufacture in closed system facilities.  

Step A
The fed-batch process is started inthe same way.  

Step B
Once the peak cell density is achieved, start to pump fresh media in at a set flow rate between 0.1 and 1 vvd.  As fresh media is pumped in, the harvesting of the product is initiated. In this example, the media exchange was started on Day 10, but this is flexible depending on the process.  

Step C
On the last day of the run, end addition of fresh media and start to draw down the volume in the reactor at 1-2 vvd.   Operating at 20LMH for a 1000L reactor, the reactor will be harvested in approximately 4 hours.  If a 2000L reactor it will take approximately 8 hours.

Step D
High Productivity Harvest is completed to match the original fed batch production timing.
 

Typical Fed-Batch process

Start of High Productivity Harvest
~ 0.1 – 1 vvd

Start of Draw Down
~ 1 – 2 vvd
~ 20 LMH

Finish High Productivity Harvest and
Clarification

Matching typical Fed-Batch
Production Timing

Harvest ready for purification

• 2x total accumulated IgG
• Harvested product is 0.2µm filtered and ready for purification, no centrifugation and no depth filtration required 
   

Higher viable cell density and viability

• Viable cell density increased by more than 3-fold in fed-batch cultures using High Productivity Harvest compared to traditional FB
• Viability in fed-batch cultures using High Productivity Harvest remained at >90% throughout run, a healthier environment for the cells and the product of interest
   

Higher product quality

• HCP per mg of IgG is lower in both HP Harvest FB conditions compared to traditional FB harvest
• Requirement for depth filtration eliminated