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.
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.
High Productivity Harvest uses an XCell™ ATF Cell Retention Device after peak density is achieved in a typical Fed-Batch process. Fresh media is added in a set flow rate while the harvesting of the product is initiated. This results in significant productivity and process gains.
The fed-batch process is started inthe same way.
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.
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.
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
Matching typical Fed-Batch
Harvest ready for purification
Higher viable cell density and viability
Higher product quality
Alternating Tangential Flow (ATF) Filtration
An award-winning technology, ATF allows the removal of spent media while keeping cells in culture. Applied using an XCell™ ATF device attached to a bioreactor, ATF minimizes cell shear and keeps cells in constant equilibrium with bioreactor contents. This results in faster cell growth at higher densities with higher productivity. Today, the XCell™ ATF device, in single-use or reusable format, is the leading perfusion device for mAb and rProtein production.