Bispecific antibodies (bsAbs) have been engineered to have affinity for two different molecular targets, which can be used to target two molecules in proximity to encourage complex formation or an interaction between the two molecules. Some technologies require a Fab arm exchange (FAE) between two different parental monoclonal antibodies (mAb) to form a bispecific heterodimer. The FAE is initiated with a reduction event to dissociate monomeric parental mAbs into half-mAbs so they are free to associate as heterodimers. The reductant must then be removed to promote the reformation of disulfide bridges. At manufacturing scale, redox reactions can be logistically challenging and costly to execute; furthermore, large volumes of reductant containing hazardous waste need to be properly disposed of. In this work, alternative downstream process operations were developed and compared for their potential to require new manufacturing equipment and reduce the volume of costly and hazardous waste streams associated with the FAE reaction. These process alternatives were evaluated against the original process, evaluating process performance, product quality, facility fit, and ease of tech transfer.

Exploring options for the integration of bispecific Fab arm exchange reactions with standard downstream unit operations

2019 Spring National Meeting

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