Intermolecular interactions in highly concentrated formulations of recombinant therapeutic proteins

Abstract

The subcutaneous administration of recombinant therapeutic proteins requires the use of highly concentrated protein formulations to provide the desired dosage in a single injection. These highly concentrated formulations can have very high viscosities, creating challenges in processing (e.g. by ultrafiltration), storage (e.g. enhanced aggregation), and delivery (e.g. injection through small bore needles). Recent work has begun to identify the key intermolecular interactions governing the behavior of these highly concentrated formulations, including the effects of different excipients that have been shown to reduce viscosity and enhance the stability of these formulations. These intermolecular interactions also have a significant effect on the filtrate flux and maximum achievable protein concentration that can be obtained during ultrafiltration used for final concentration and formulation of these therapeutic proteins.