Dr. Weichang Zhou, Senior Vice President of Bioprocess Development, of WuXi Biologics will be speaking at Cell Culture Engineering XV in Greater Palm Springs Area, California on Tuesday May 10th from 12:10 AM – 12:35 PM. In addition, Dr. Jimmy Li, Executive Director of Cell Culture Development, will present a poster. See below for titles and summaries.
Scale-up and scale-down challenges for a high density long-term perfusion suspension cell culture in large-scale single use bioreactors
Weichang Zhou and Hang Zhou, Biologics and Bioprocess, WuXi Biologics
Weichang Zhou, Ph.D.
Senior Vice President of Bioprocess Development
As part of efforts to develop a continuous processing platform for biologics manufacturing using single use bioreactors, we have been focusing on development of several initial unit operations: high density perfusion suspension cell cultures and early product capture steps, in order to realize its potentials of being flexible, improving product quality and lowering costs. These initial unit operations require large volumes and represent the most important part of this processing platform. By integrating these steps into a continuous operation, we can deliver the largest benefits of this processing platform. In this presentation, we will discuss our efforts towards continuous biologics manufacturing using a case study focusing on direct scale-up of an ATF (Alternating Tangential Flow) based high density perfusion cell culture, from 2L scale coupled with ATF2 to large single use bioreactors coupled with ATF6 or ATF10. Appropriate considerations of agitation and aeration rates, ATF operation parameters as well as bioreactor processing conditions resulted in successful scale-up of more than 100 folds. This high density long-term perfusion suspension cell culture was successfully implemented in large scale single use bioreactors. Results of large-scale manufacturing batches indicate highly consistent process performance, productivity and quality of directly captured products. Furthermore, a representative scale-down model based on ATF2 was established for manufacturing support and further process optimization.
Challenges of scale down model for disposable bioreactors: case studies on growth & product quality impacts
Jincai Li, Guangming Zhang, Huilin Zhu & Weichang Zhou, Bioprocess Development, WuXi Biologics
Jimmy Li, Ph.D.
Executive Director of Cell Culture Development
Despite wide-spread use of disposable bioreactors, there is a lack of well-established scale-down model for larger scale SUBs. Here we report a case of NS0 cell culture process transfer from 2000L stainless steel bioreactor (SST) to 2000L disposable bioreactor (SUB). Initial attempts in trying to grow the NS0 cells in the small scale 2D bags yielded non-satisfactory results, as growth was impacted by bag material type as well as by suppliers of the same bag material type. However, 3D bags of 50L and above proved to be supportive of the NS0 cell line growth.
Even for cell lines that do not have growth issues in SUBs, surprising product quality difference between SUBs and traditional bench top glass bioreactors are still being observed, thus making the bench top glass bioreactors non-ideal as scale down models. We report two cases where glycan profiles of the expressed antibody products show such dramatic differences. In one case, extensive testing of glass bioreactors from various suppliers led to a particular type being able to mimic the glycan profiles from the SUB, whereas in the other case, alternative scale down model had to be identified and the process had to be modified to maintain the glycan profiles when scaling up to the 200L SUB.