(457o) Operational Challenges of Large Scale Monoclonal Antibody Bulk Production for Clinical Trial Delivery

In support of early phase clinical trials, a monoclonal antibody production process was executed at pilot plant scale (2000-L) to generate clinical material using a reduced manufacturing cycle time and resource sparing staffing model. Since this was first therapeutic protein process run in the facility, the campaign required implementation of several novel operational and staffing strategies to ensure delivery of clinical supplies for a fast-track clinical program.

Operational improvements that were successfully implemented during the campaign included turnaround of the production bioreactor in less than 24 hours and use of 500-L media totes to reduce the number of media containers and aseptic connections to the bioreactor by more than 50%. Additional efficiencies were gained through implementation of improved oxygen manifolds to enhance oxygen supply capacity four-fold and increased working volume of the production bioreactor to increase volumetric productivity by 8%. The resource utilization strategy adopted during this campaign involved cross-training of staff on both upstream and downstream operations, thus permitting a 24-hour turnaround between batches while ultimately reducing staffing requirements by 35% from previous campaign batches.

The successful execution of the operational and resource utilization strategies permitted the required number of bulk runs to be completed on schedule with 100% success rate. In addition, these efficiencies will allow the area to have greater flexibility and will provide for additional capacity to support future simultaneous multi-product processing.