文獻名：In-use interfacial stability of monoclonal antibody formulations diluted in saline iv bags

作者： Aadithya Kannan^ab, Ian C.Shieh^b, Petar Hristov^a, Gerald G.Fuller^a

^aStanford University, Stanford, CA, USA

^bGenentech, Inc., South San Francisco, CA, USA

摘要：The use of monoclonal antibodies (mAbs) for the treatment of a variety of diseases is rapidly growing each year. Many mAbs are administered intravenously using i.v. bags containing 0.9% NaCl (normal saline). We studied the aggregation propensity of these antibody solutions in saline and compared it with a low ionic strength formulation buffer. The mAb studied in this work is prone to aggregate, and is known to form a viscoelastic network at the air-solution interface. We observed that this interfacial elasticity increased when formulated in saline. In the bulk, the mAbs exhibited a tendency to self-associate that was higher in saline. We also studied the aggregation of the mAbs in the presence of polysorbate-20, typically added to formulations to mitigate interfacial aggregation. We observed that with surfactants, the presence of salt in the buffer led to a greater mAb adsorption at the interface and resulted in the formation of more particulate aggregates. Our results show that the addition of salt to the buffer led to differences in the interfacial aggregation in mAb formulations, showing that stress studies used to screen for mAb aggregation intended for i.v. administration should be performed in conditions representative of their intended route of administration.

關鍵詞：Monoclonal antibody(s); Adsorption; Surfactant(s); Formulation; Protein aggregation; Rheology; Protein formulation(s)