Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies

For the development of concentrated monoclonal antibody formulations for subcutaneous administration, the main challenge is the high viscosity of the solutions. To compensate for this, viscosity reducing agents are commonly used as excipients. Here, we applied two computational chemistry approaches to discover new viscosity-reducing agents: fingerprint similarity searching, and physicochemical property filtering. In total, 94 compounds were selected and experimentally evaluated on two model monoclonal antibodies, which led to the discovery of 44 new viscosity-reducing agents. Analysis of the results showed that using a simple filter that selects only compounds with three or more charge groups is a good ‘rule of thumb’ for selecting potential viscosity-reducing agents for two model monoclonal antibody formulations.