(661b) Case-Studies of Enhancing Manufacturing Flexibility for a Commercial Biologic

During the manufacturing process of a commercial recombinant molecule, CHO cells are cultured through the inoculum expansion in shake-flasks and seed bioreactors followed by inoculation of the production bioreactor. During primary recovery, cell culture is centrifuged and the centrate is passed through a series of depth filters and sterile filters prior to transfer to downstream operations. Three case-studies will be presented to illustrate typical study workflows carried out to support the manufacturing of a commercial biologic moiety. The first case-study entails the validation of three optional, additional passages during inoculum expansion. Evaluation of process parameters against acceptance criteria derived from the in-process control strategy for inoculum expansion will be described. The second case-study details how a selective pressure agent used in inoculum expansion, and originating from an alternate vendor, was evaluated by comparison to the same compound originating from the primary approved vendor. The third case-study discusses a process qualification study for changing out a depth filter and a membrane filter during primary recovery. These case-studies successfully improved manufacturing flexibility allowing full utilization of capacity while handling several multi-product campaigns.