Comparative Analysis of Anion Exchange Membrane Adsorbers for Endotoxin Removal During Ultrafiltration and Diafiltration Buffer Preparation

During the manufacturing of drug substances (DS), endotoxins are a commonly monitored contaminant and checked to ensure the safety and quality of the final product. In this study, we investigated endotoxin removal by commercial anion exchange membrane adsorbers during buffer preparation for an ultrafiltration and diafiltration (UFDF) unit operation as a risk mitigation strategy to meet DS endotoxin specifications. A bracketing design study was used to compare two quaternary amine (Q) modified membranes and one guanidinium functionalized hybrid adsorber for endotoxin removal from spiked buffers representing UFDF start and diafiltration buffer matrices. For the UFDF start buffer, Q-based membrane adsorbers were effective at the removal of endotoxin to the limit of detection in low ionic strength conditions, with one adsorber effective up to 24 mS/cm. Switching to a more complex UFDF diafiltration buffer, Q-based membrane adsorbers were impacted by additional buffer components. The guanidinium-based hybrid membrane adsorber demonstrated endotoxin reduction to the limit of detection from both buffer matrices, showing removal across a wide pH range (4.7-8.3) and conductivity as high as 43 mS/cm. These results demonstrate an operational window for buffers and selected membrane adsorbers to mitigate risk by limiting endotoxin contamination prior to UFDF operations in pharmaceutical applications.