September 23-26, 2018
Improvements in single-use systems have allowed implementation of high-density cultures in emerging bioprocess workflows while progressive advances in media optimization and improved clone genetic selection have underscored the perceived performance limitations of single-use bioreactors (S.U.B.s). This study presents how strategic enhancements to the sparge and agitation systems of Thermo Scientific™ HyPerforma™ S.U.B.s have revealed the potential for a three- to four-fold improvement of mixing and mass transfer performance compared to legacy SUB designs. This study investigates the following:
- Bioreactor characterization, TruBio™ DeltaV™ controller optimization, online process analytics, and scalability analysis of the S.U.B. when targeting perfusion applications from 50 L pilot scale to 500 L production scale working volumes.
- High-density culture results (>260E06 cells/mL) while maintaining proper operating parameters. New data reveal how a 50 L S.U.B. – equipped with a specialized precision drilled-hole sparger (DHS), single-use foam probe, and oversized impeller – is able to improve overall S.U.B. operating efficiency. Results also include specific suggestions on how to maintain a nearly ideal dissolved carbon dioxide environment, reduce headspace foam generation, and produce lower overall shear levels, thus yielding excellent cell viability.
- The work also demonstrates best practices and the desirable process benefits that can be achieved through reduced technical risk, lower labor, and simplified technical transfer of a completely disposable processing assembly. Further evidence is presented on the advantages of continuous processing when used in high-density seed train intensification or as a compact production-scale bioreactor system operating at reasonable media exchange rates of one to two vessel volumes per day (VVD).
Please click Additional Files below to see the full abstract.
Ben Madsen, Jordan Cobia, Nephi Jones, and Kevin Mullen, "Continuous Process Performance Enhancements for 50-500 L S.U.B.s" in "Single-Use Technologies III: Scientific and Technological Advancements", Weibing Ding, Amgen Martina Micheletti, University College London Robert Repetto, Pfizer Eds, ECI Symposium Series, (2018). http://dc.engconfintl.org/sut_iii/46