To platform or not to platform: Strategic considerations for antibody formulation in early clinical development

Formulation development aims at finding the most stabilizing conditions for a particular therapeutic protein molecule. Typically, various combinations of buffer type, pH, and additional excipients are experimentally tested at different concentrations in a laborious process to identify a suitable formulation. It is therefore tempting to use a platform approach and apply previously successful formulations to similar proteins, particularly for monoclonal antibodies (mAbs), which typically only differ in their antigen-binding region. Such a platform approach comes with the risk that the protein is insufficiently stable in the platform formulation to be suitable for first-in-human studies. Formulatability assessment closes a gap between discovery and pre-clinical formulation development by taking the protein's physicochemical stability and formulation conditions into consideration. The evaluation of a protein candidate's biophysical properties during formulatability assessment provides data to facilitate the decision as to whether the molecule may be suitable for a platform formulation, or if an extended pre-formulation screening is required in order to identify conditions that promote conformational, colloidal, or chemical stability of the protein. We discuss how formulation scientists can put a risk-based mAb platform formulation approach into practice, including formulatability assessment, systematic pre-formulation and storage stability studies with platform analytical methods.