Endotoxin recovery using limulus amebocyte lysate (LAL) assay.

A phenomenon initially reported by Chen and Vinther in 2013 [1], and now commonly referred to as low endotoxin recovery (LER), has prompted the Food and Drug Administration (FDA) to request specific data demonstrating the capability of the LAL BET method (i.e., USP <85>) to recover endotoxin from spiked samples over time.

Evidence against a bacterial endotoxin masking effect in biologic drug products by limulus amebocyte lysate detection.

Unlabelled: The inability to detect endotoxin using compendia methods is a potential safety concern for patients due to the lack of endotoxin removal capabilities at the fill-finish stage in typical aseptic biologic drug product manufacturing. We have successfully demonstrated endotoxin challenge study recovery methodology using mammalian cell-produced biologic drug products and drug substances in citrate, histidine, phosphate, and sodium acetate buffer formulations containing polysorbate, challenged with an endotoxin analyte, for up to 6 months of storage. Successful recovery was similarly demonstrated for a preserved, peptide-containing drug product formulation.