Integration of CHO cell culture process improvements with continued process verification
May 6-11, 2018
Continued verification of the manufacturing process is a key component of the process validation lifecycle. It provides assurance that the process remains in a state of control during commercial manufacturing through ongoing process and product monitoring and review of quality system elements, such as change control, deviation management. Continuous improvement of cell culture process and operations is an important aspect of routine commercial manufacturing. This is driven by factors such as increased health authority requirements, advanced technology, emerging knowledge on mammalian cell culture process and product quality, and cost benefit. Most operational improvements, when implemented, are assumed not to impact culture performance and/or critical quality attributes. However, unintended consequences have been encountered during the continuous improvement of CHO cell culture processes in Vacaville facility. Through the continued process verification (CPV), the impact to process performance and product quality is able to be detected and corrected when needed. A few examples shared in this poster will focus on the areas easily overlooked during implementation of a change, and the cumulative impact of multiple changes through life cycle of the products. Cell culture process A uses depth filter as part of medium filtration, and it has been known that depth filter can impact the glycosylation pattern as part of the effort to evaluate depth filter removal during lab scale. Due to a vendor initiated change (VIC) for the depth filter manufacturing process, intensive studies were conducted in lab scale to understand the potential impact to product quality. However, when utilizing the post VIC change filter in large scale, an unexpected shift in glycosylation profile was observed. Troubleshooting studies were performed to better understand the change, and further process changes were implemented to revert the product quality back to pre VIC level. A second case study will discuss the impact pH control related changes implemented to cell culture process B, and their impact to culture performance and product quality. The result from the interaction of those changes will be discussed. This poster will shed some light on the need to integrate CPV into the implementation of ongoing process and operational improvements.
Jun Luo, Bunyada Kwong, Jesse Bergevin, and Lisa Vulliet, "Integration of CHO cell culture process improvements with continued process verification" in "Cell Culture Engineering XVI", A. Robinson, PhD, Tulane University R. Venkat, PhD, MedImmune E. Schaefer, ScD, J&J Janssen Eds, ECI Symposium Series, (2018). https://dc.engconfintl.org/ccexvi/28