Cracking Complexity: Leveraging Lessons Learned For Future Bispecific Development

By Dr. Karina Bora, Senior Principal Scientist for Global Analytical Development, Dr. Markus Fuereder, Associate Director for Global Process Development, and Eddy Berthier, Principal Scientist for Pharmaceutical Development for Biological Drug Product, Lonza

Bispecific antibodies (BsAbs) are accelerating toward the clinic while introducing greater complexity across characterization, manufacturing, formulation, and IND readiness. The article describes an adaptive, knowledge-driven development model that combines established platform methods with targeted customization. Experience from more than 70 bispecific programs enables teams to assess platform suitability before extensive experimentation, directing resources toward genuine molecule-specific risks. In analytical development, platform methods can often address size variants, charge heterogeneity, and purity, while specialized challenges such as chain pairing and mechanism-of-action-specific potency require tailored approaches. Similar principles extend to purification, where high-throughput screening, alternative chromatography modalities, impurity-removal strategies, and established process knowledge can accelerate development.

Formulation development also benefits from early, high-throughput assessment of stability, aggregation, and protein-protein interactions, helping teams identify developability risks and inform candidate selection. Across the CMC lifecycle, the approach emphasizes using platforms where appropriate, augmenting them with flexible toolboxes when needed, and generating data rapidly through parallel experimentation. By capturing lessons learned across programs and applying them to future development decisions, organizations can transform static platforms into adaptive systems that balance speed, flexibility, and scientific rigor while improving the predictability of complex biologics development through IND submission.