Expert view: Low Endotoxin Recovery (LER)

The Parenteral Drug Association (PDA) has recently published Technical Report No. 82 (TR82) on the topic of Low Endotoxin Recovery (LER), providing both consensus to the science and data behind the analytical issue, as well as to analytical and mitigation strategies. Dr Christian Faderl from bioMérieux explains the important implications of TR82 as well as presenting the ENDO-RS^® sample preparation technology for demasking endotoxin in affected biologics, as described in Case Study 7 of TR82.

What is low endotoxin recovery?

First reported by Chen and Vinther in 2013, the phenomenon known as LER has been broadly studied and identified in biologics and certain therapeutic proteins. LER is a temperature- and timedependent process and defined as loss of detectable endotoxin activity over time when using Factor C-based assays (LAL and rFC) when undiluted products are spiked with a known amount of endotoxin standards. Regulatory authorities also request hold‑time studies to determine the validity of the endotoxin release test methods during the review of BLAs for biotech products, as well as new methods to overcome the issue.