Developability assessment for monoclonal antibody drug candidates: a case study

Abstract

Various screening approaches are used by industry to evaluate development risks associated with discovery candidates. This process has become more complicated with biological therapeutics, a class dominated by monoclonal antibodies (mAb), and, increasingly, their derivative constructs. Effective early assessment for drug-like properties (DLP) can save time and costs by allowing a more complete consideration of issues that could impact the desired end result of a stable drug product. Here we report a case study of four IgG1 mAbs, with sequence variations in the variable domain region, screened as a set of possible drug candidates. Our comprehensive, tiered approach used a battery of analytical tools to assess molecular characteristics, conformational stability, colloidal stability, and short-term storage stability. While most DLP for the four candidates were developmentally acceptable and comparable, mAb-2 was associated with adverse colloidal properties. Further investigation of mAb-2 in an expanded pH range revealed a propensity for phase separation, indicating a need for the additional product development effort. Our results support that comprehensive DLP assessments in an expanded pH range are beneficial in identifying development options for promising molecules that show challenging stability trends. This adaptable approach may be especially useful in the development of increasingly complex antibody constructs.