Protein Interfacial Instability of Mixing and Lyophilization During Drug Product Manufacturing Process Scale-Up and Tech Transfer

Abstract

Biotherapeutic product manufacturing is a complicated process that includes various unit operations, such as freeze and thaw, compounding, filtration, filling, lyophilization, inspection, packaging, storage, and transportation. During process steps in those unit operations, protein molecules may encounter stresses like shear stress and interfacial stress. These stresses could potentially negatively impact the drug product quality attributes, including formation of protein aggregates, formation of particles, or loss of protein due to adsorptions at the interface. Therefore, it is important to have a clear understanding of protein interfacial instability during drug product manufacturing. In this chapter, we will discuss in more details about various stresses that proteins encountered in the mixing and lyophilization unit operations, the relationship between the interfacial stress and protein stability, and explore strategies and best practices in order to evaluate and minimize the interfacial stress.