LER occurs when a known amount of endotoxin is added to a drug product but cannot be recovered or detected during testing over time. This is not a failure of the test itself, but rather a where the endotoxin molecules (LPS) are rearranged into structures that the Limulus Amebocyte Lysate (LAL) reagent cannot recognize. Common LER Triggers
If LER is found, develop a robust demasking protocol that can be consistently replicated in QC. pda technical report 82 pdf
FDA and EMA inspectors frequently cite TR 82 as the "gold standard" for evaluating whether a manufacturer has adequately addressed endotoxin masking. If your product contains polysorbates and a buffer, regulators expect to see an as part of your Biologics License Application (BLA). LER occurs when a known amount of endotoxin
Use "Natural Endotoxin" (NOE) vs. "Control Standard Endotoxin" (CSE) based on the report’s recommendations. FDA and EMA inspectors frequently cite TR 82