Definition of the process control strategy is a key element of the Quality by Design framework for biopharmaceuticals and relies on both manufacturing parameter control capabilities as well as process understanding. In this presentation, we will share a case study on how a holistic understanding of the downstream process for a monoclonal antibody product was used to demonstrate robust control over CQAs. Key elements of downstream process design for multiple unit operations will be discussed along with a summary of the resulting process control performance for product aggregates, host-cell proteins (HCPs), and other quality attributes. The clearance capabilities for HCPs and aggregates were evaluated over chromatographic and filtration steps, including those using synthetic depth filters. These clearance capabilities were assessed via small-scale spiking studies, “skip-step” or “bypass” studies, and runs using worst-case feedstocks. We will share data from these experiments and discuss how the resulting information can be used in conjunction with manufacturing-scale data to build a thorough understanding of process robustness. Finally, we will conclude with examples of where results from this body of work were leveraged to manage the classification of controlled parameters in the final process control strategy.

Evaluation of downstream impurity clearance capability and implications for the process control strategy

ACS Spring 2022

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