Novel periodic alternating tangential filtration harvest approach provides incresed volumetric productivity
October 6-10, 2019
Perfusion cell culture processes provide opportunities to increase product yield through improved cell growth, increased productivity and extended process duration. Most commonly, perfusion cell culture also leads to a continuous harvest operation and collection of harvested cell culture fluid to be processed downstream.
As an alternative to continuous harvest, we evaluated instead a periodic harvest approach applied to a non-steady state perfusion cell culture process using alternative tangential flow (ATF). In this ATF perfusion process, product is first accumulated in the bioreactor using ultrafiltration for 15 days with the product then being harvested by microfiltration at end of the process. To further extend the culture time beyond 15 days and maximize productivity, we investigated a sequence of five periodic harvests from a single upstream bioreactor run. The periodic harvests were achieved using an ATF configuration in which ultrafiltration and microfiltration hollow fiber filters were stacked in series (Figure 1). The ultrafiltration hollow fiber retains the product while the microfiltration filter allows product to be collected in the permeate. Permeate was only drawn from the microfiltration filter during the periodic harvest cycles while the permeate was drawn from the ultrafiltration filter during the none harvest cycle periods. This allowed for the accumulation of product in the bioreactor between the periodic harvests. Five harvest cycles were conducted over a 24-day perfusion process. Each harvest cycle was collected for a day with the first harvest cycle starting on day 11.
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Sean Cole, Johanna Mullen, Chetan Goudar, and Natalia Gomez, "Novel periodic alternating tangential filtration harvest approach provides incresed volumetric productivity" in "Integrated Continuous Biomanufacturing IV", Veena Warikoo, Roche, USA Alois Jungbauer, BOKU, Austria Jon Coffman, Boehringer Ingelheim, USA Jason Walther, Sanofi, USA Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/biomanufact_iv/39