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.
HPH generates the same product titer in half the time or twice the product compared to traditional Fed-Batch at no additional time. Leverage the combination of HPH and N-1 Perfusion to obtain up to twice the product in half the time. Transition to a single-step, closed system and eliminate centrifugation, which involves high CAPEX, non-linear scaling, and is unsuitable for shear sensitive applications, and depth filtration, which is low flux, low capacity, and has a messy and cumbersome setup process. Whether your intended application is mAb, rProteins, lentivirus, enzymes, or vaccines, HPH can boost productivity and deliver more product, faster.
HPH increases productivity and throughput while maintaining a fed batch process. No perfusion or media exchange of the N bioreactor is required, allowing the N bioreactor to maintain a single and discreet fed batch harvest point.
HPH achieves 20 million VCD compared to 4 million for Fed-Batch. HPH viability maintained above 100% over a period of 8 days. Fed-Batch viability begins to drop after day 3 to approximately 75% at days 8-9. Higher VCD and viability translates to an increase in total product yield. HPH process yields approximately 1500 mg/day. Fed-Batch process achieves 800-1000 mg/day in approximately 8-10 days.
Higher viable cell density (VCD) and viability with HPH
Higher product titer with High Productivity Harvest
Traditional Fed-Batch achieves a VCD of approximately 10 million cells over the course of 14 days with viabilities dropping from day 8 to day 14 to approximately 80%. HPH at 0.25, 0.5 and 1 VVD produced similar viable cell densities until day 10. At day 10, HPH process begins and achieves up to 40 million VCD compared to 10 million VCD for traditional Fed-Batch. HPH viability maintained above 90% throughout the run. Higher VCD and healthier cultures in HPH deliver a 200% IgG yield increase. HCP levels were significantly reduced with 80-100 ug (per mg of IgG) of host cell protein (HCP) in HPH process compared to 150 ug (per mg of IgG) of HCP in traditional Fed-Batch. A 0.2 µm filtered clarified stream with lower impurity levels removes centrifugation and depth filtration unit operations further increasing efficiency.
Higher viable cell density and higher product yield
Clarified harvest ready for purification
High Productivity Harvest (HPH) is a novel application developed by Repligen that enables you to harvest a fed batch bioreactor in a fully sterile manner while eliminating both centrifugation and depth filtration. A 0.2µm filtered, closed system and single step process using the XCell™ ATF System, HPH can significantly increase yields above industry standards and generate a sterile clarified batch harvest ready for either batch or continuous chromatography. This webinar will demonstrate how HPH works, present initial results of up to a two-fold increase in protein production, and how you can apply HPH specific to your product need or facility design.
A representative example of an HPH process is shown below. It consists of three main steps: start of Fed-Batch process, attachment of a Cell Retention Device for High Productivity Harvest, followed by bioreactor draw down. HPH start date is flexible and depends on the process. Harvest can be completed in the same timeframe as traditional Fed-Batch or the bioreactor run can be extended for further yield increase depending on process and facility constraints.
Step A: Process start
Start the fed-batch process as usual.
Step B: CRD attachment and High Productivity Harvest
Once the peak cell density is achieved, attach the cell retention device (CRD) and start to pump in fresh media at a low flow rate. As fresh media is pumped in, product harvesting is slowly initiated.
Step C: Draw down
On the last day of the run, stop the addition of fresh media and start to draw down the volume in the bioreactor.
Step D: Process finish
HPH Fed-Batch can be completed in the same timeframe as traditional Fed-Batch or the production run extended to further improve yield.
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.
High Productivity Harvest: A Novel Approach to Fed-batch Process Intensification
Intensified Seed Expansion and High Productivity Harvest of Fed-batch Cultures Using the XCell ATF® System