To initiate the manufacturing process of a recombinant molecule, CHO cells are cultured through the inoculum expansion steps in shake-flasks followed by the seed bioreactor steps to inoculate the production bioreactor. A typical inoculum expansion process comprises 5 passages, however, from cell line stability studies, more passages are often acceptable. For example, in the present case, typical processing utilizes 5 passages and cell line stability studies allow up to 3 additional passages setting the maximum allowable 8 passages. This case-study describes how we established the in-process limits and demonstrated acceptable performance of the cell line in the full-scale production process, following inoculum expansion for the maximum allowable passages. Acceptance of this study and the maximum number of passages was based on a three level evaluation. First, a full-scale lot was purposely extended to test the maximum number of passages (the extended passages lot), and the other process parameters were evaluated against acceptance criteria defined in the in-process control (IPC) strategy for the inoculum, seed and production bioreactor steps. Second, drug substance made from the extended passages lot was compared to drug substance release specifications. Thirdly, a retrospective comparison against manufacturing history was completed demonstrating that the IPC strategy process parameters for the extended passages lot were within an acceptable tolerance range. The extended passaging was therefore qualified for commercial production, allowing manufacturing flexibility during multi-product campaigns.

Evaluation of extended passaging during inoculum expansion of a CHO cell line: a case-study of improving manufacturing flexibility

249th National Meeting (2015)

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