RT Journal Article SR Electronic T1 Impact of NaCl on Monoclonal Antibody Aggregation Induced by Agitation JF PDA Journal of Pharmaceutical Science and Technology JO PDA J Pharm Sci Technol FD Parenteral Drug Association (PDA) SP 465 OP 474 DO 10.5731/pdajpst.2023.012860 VO 78 IS 4 A1 Hong, Justin K.Y. A1 Liu, Wei A1 Zheng, Kai YR 2024 UL http://journal.pda.org/content/78/4/465.abstract AB Monoclonal antibodies (mAbs) are a successful class of therapeutics, but their development can be challenging due to the risk of degradation that could happen during manufacturing, storage, and clinical use. One of the common causes of degradation is agitation stress from transportation and clinical handling, which increases interfacial stresses to mAbs. For example, the preparation of the dose solution prior to administration often requires diluting therapeutic mAbs in intravenous (IV) infusion bags containing normal saline, which can substantially reduce the level of protective surfactant and increase the level of salt in mAb solutions. Then the interfacial stress in the subsequent transportation of IV bags can cause mAb aggregation or even particle formation. To better understand the complex interplay between dilution, interfacial stress, and salt, we studied the impact of sodium chloride (NaCl) on the aggregation of two mAbs under agitation stress. We found that the presence of NaCl accelerates the aggregation of both mAbs, but the aggregation mechanism, morphology, and reversibility are very different. Our results clearly highlight the impact of salt on mAb stability at the clinical in-use condition. We believe this study further increases our understanding of protein aggregation mediated by interfacial stresses and brings valuable insights to support development of mAb formulations for patients.