The structural diversity and complex assembly pathways of bispecific antibodies (bsAbs) introduce significant challenges in downstream purification. Compared to monoclonal antibodies, bsAbs often present elevated levels of product-related variants such as mispaired species, half-antibodies, and aggregates. In addition, some bsAb formats exhibit reduced compatibility with conventional Protein A–based affinity chromatography or increased sensitivity to low-pH processing conditions. These challenges become particularly critical for clinical manufacturing where bsAbs must meet strict regulatory expectations.

In this GEN webinar, Joshua Orchard, a purification applications scientist with extensive experience in downstream process development of various modalities, will share strategies and experimental data to support the purification of bsAbs for clinical manufacturing.

Key takeaways from the webinar include:

• Common purification challenges unique to bispecific antibody formats, including mispairing, aggregation, and product instability
• Improved selectivity and process robustness with affinity capture approaches beyond traditional Protein A
• Strategies for controlling high aggregate levels earlier in the process to simplify downstream polishing
• Selection of the appropriate polishing chromatography modality (IEX, HIC, Mixed-mode) to address specific residual impurities to resolve closely related bsAb variants

Produced with support from: