Evaluation of Interfacial Stress During Drug Product Development

Abstract

The impact of interfacial stresses on protein stability stems from many processes during development and manufacturing of biologic drug products, including, but not limited to, filtration, pooling, filling, packaging, storage, transportation, and administration. The magnitude of the interfacial stresses depends on many factors, such as flow rates of filling, rates of mixing during stirring, and duration of exposure to the air and/or oil in the primary container or device. Approaches that mimic real scenarios of interfacial stresses have been developed to evaluate the instability of proteins subjected to various interfacial stresses. This chapter will first introduce the stresses occurring at interfaces during drug product development and manufacturing unit operations, as well as review successes and limitations of the various models used to assess and predict risks of interfacial stress and develop robust and stable drug products. This chapter will then address transportation of materials to clinical sites and tools used to ensure the product is robust to transportation stress. Finally, we discuss protein instability induced by the stresses from changing excipient levels upon dilution of drug product at the stages of drug product preparation and administration by injection/infusion. Discussion of control strategies and current recommendations on the risk assessment of the interfacial stresses and mitigation strategies will be addressed.