PDA TECHNICAL REPORT ON LOW ENDOTOXIN RECOVERY: IMPLICATIONS TO THE INDUSTRY

Presented by Dr Friedrich von Wintzingerode, Senior Manager, Global Analytical Science & Technology (gASAT) Microbiology, Global QC bei Roche
Since first reported by Chen and Vinther in 2013, the phenomenon known as low endotoxin recovery (LER) has been broadly observed in certain matrices commonly used for biologic formulations and certain therapeutic proteins. LER is defined as the inability to recover 50% activity over time when endotoxin is added to an undiluted product. LER is a temperature and time-dependent process, which usually does not occur immediately but after several hours to several days. Compendial LAL method qualification (Bacterial Endotoxin Test = BET per USP 85 EP 2.6.14 JP 4.01) does not include defined hold time conditions, which may explain why LER has not been detected by following compendial BET guidance. Because of the potential impact to patient safety and the complex nature of the LER issue, the Parenteral Drug Association (PDA) published a Technical Report (TR) on LER. This TR was authored by subject matter experts from academia, U.S. FDA, biopharmaceutical companies, and reagent suppliers/testing contractors. The PDA Technical Report on Low Endotoxin Recovery provides a science-based and data-driven strategy in dealing with the LER phenomenon. The author of this article, who acted as co-lead of the TR authoring team, provides first hand information that allows companies to develop product specific solutions to the LER problem.