The transition from batch to continuous manufacturing is imminent for the production of biotherapeutics like mAb due to the distinct advantages offered by the latter such as increased productivity, lowered costs, and improved product quality. Continuous biomanufacturing also offers increased flexibility and robustness in process operation over traditional batch processes. However, the development and optimization of continuous manufacturing of biotherapeutics requires a detailed understanding of the bioprocess fundamentals that are often possible only through a thorough analysis of batch and fed-batch operations. Furthermore, one of the challenges associated with continuous mAbs production is the necessity to closely monitor drug product critical quality attributes (e.g., mAb glycosylation, aggregation) to implement real-time process control and ultimately meet FDA’s regulatory requirements. Here, we aim to establish a bench-scale upstream mAb production platform integrated with advanced process analytics to facilitate critical modeling driven analysis and derisking of continuous biomanufacturing processes. We show results from our ongoing efforts to establish this test-bed platform for a model mAb (Trastuzumab) production using batch and fed-batch cultivation of a recombinant mammalian cell line. We evaluate the impact of several upstream process parameters (e.g., media composition) on critical quality attributes like mAb glycosylation. Next, we highlight an integrated sampling system developed to facilitate on-line liquid chromatography/mass spectrometry-based analytics for real-time monitoring of mAb N-linked glycosylation profile to modulate the upstream bioreactor cell culture process. Finally, we discuss efforts for integration of the continuous upstream bioprocess platform with a validated upstream process model to achieve real time process monitoring, optimization, and control for mAb production.

Continuous monoclonal antibody (mAb) biomanufacturing and integrated process analytics for mAb N-linked glycans analysis

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.