(106f) Investigating Surfactant Loss After Final Formulation

Surfactants are typically included in monoclonal antibody formulations in order to protect the protein against agitation-induced aggregation and surface adsorption which may occur during storage, shipment or administration. The addition of the surfactant normally occurs in the final step of the purification process, either prior to or after final filtration of the drug substance into the storage vessel. Frequently, protection of antibodies is greatest when the surfactant is added at a concentration above the critical micelle concentration (CMC) of the surfactant. In a recent campaign, a reduction in the surfactant level to below its CMC was observed upon product filtration. An investigation was launched to determine the cause of this loss. Potential contributing factors were identified and evaluated including the concentration of the surfactant, the membrane filter material, and the surface chemistry of the storage vessels. Additional factors were evaluated in order to better understand the mechanism of action, including examining surfactant loss in the presence and absence of protein, the impact of proteins with differing hydrophobicities, and an examination of different types of non-ionic surfactants. Potential causes for this surfactant loss were identified and a mitigation strategy was proposed.