Formulation and manufacturability of biologics.

An important challenge in the pharmaceutical development of a biologic is the optimization of safety and efficacy while ensuring the ability to manufacture the drug while maintaining quality and stability. The manufacturing process consists of several operational steps referred to as 'unit operations' where the biologic is subjected to different stresses and conditions that may compromise quality and stability. Moreover, recently the requirement for the development of subcutaneous formulations for high dose drugs, such as monoclonal antibodies, at high protein concentrations has created additional challenges for many of the unit operations. These challenges can be mitigated by modification of the manufacturing process and/or development of formulations to prevent degradation. In particular, formulations have been designed to minimize protein aggregation and decrease viscosity, which has led to successful manufacture of the biologic.