Since the biopharmaceutical industry is highly competitive, the main purpose of cell culture process development is to develop a highly productive and robust process within a tight clinical development timeline. Thus, sufficient drug substance with a high quality standard can be delivered for clinical trials and unmet patient need. CHO cell line creation and lead clone selection, which often require significant time investment, are critical for cell culture process development and biomanufacturing. Different CHO cell clones show heterogeneity, resulting in different cell characteristics, culture productivity, and protein quality attribute profiles. This can occur even when the clones were created using the same protocol or were subcloned from the same master well. In addition, there are many culture conditions to be optimized for late phase process development and different clones may require different conditions to achieve their high productivity specifically. Therefore, the cell line specific conditions further increase the complexity and timeline for lead clone selection. An additional challenge arises when attempting to change cell line during clinical stages after the FIH campaign. The drug substance quality attributes during the late phase are required to be comparable to the early phase product. In this study, we developed an effective lead clone selection strategy integrated with late phase process development using both high throughput technology and lab bioreactors. After data evaluation of cell culture performance, quality attributes, and genetic testing, we successfully selected a lead clone with favorable titer and quality attributes during late phase process development. In this presentation, we will show two case studies using this strategy for mAb production in a tight timeline.

Effective CHO lead clone selection for late phase process development in a tight timeline

255th National Meeting (2018)

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