Endotoxin Masking
LER has become a phenomenon in our industry and scientists largely agree that it is not a public health concern. There have been no reported endotoxin outbreaks due to a failure of the Limulus Amebocyte Lysate (LAL) endotoxin screening test. However, LER presents a problem in validating product hold times. Chelating agents combined with surfactants that are common in biological formulations are particularly problematic.
Scientific Articles on LER
- “Mechanism of Low Endotoxin Recovery Caused by a Solution Containing a Chelating Agent and a Detergent” (Masakazu Tsuchiya, PhD, 2019 May, Immunome Research Journal)
- “Endotoxins Standards and Their Role in Recovery Studies: The Path Forward” (Karen Zink McCullough, Radhakrishna Tirumalai, PhD, David Hussong, PhD, James Akers, PhD Dennis Guilfoyle, PhD, Robert Mello, PhD, Donald Singer, 2016 December, BioPharma Asia)
- “The Great LER Debate” (John Dubczak, 2016 January, Outsourced Pharma)
- “LER: Microbiology’s Hottest Urban Myth” (Dr. James Cooper, 2015 November/December, American Pharmaceutical Review)
- “Possible Mechanism of Low Endotoxin Recovery” (Masakazu Tsuchiya, PhD, 2014 November/December, American Pharmaceutical Review)
Along with the industry, we continue to research and study a variety of purified and native endotoxin preparations using all available in vitro and in vivo techniques. Our Endosafe® scientists have examined several formulations that appear to denature purified lipopolysaccharides (LPS), so they are no longer detectable by the LAL test or monocyte activation test (MAT), or in rabbits.
They have also defined native endotoxin preparations that approximate the natural endotoxin contaminants found in pharmaceutical manufacturing operations. These preparations have been shown to be resistant to LER. The in vitro and in vivo characterizations of the native endotoxin preparations continue to be investigated.
Endotoxin Test Methods Comparison
Today’s business environment demands agile, flexible, and resilient operations, which are directly dependent on the ability to test smarter and faster, but dated testing techniques strain productivity. Is your lab bottlenecking advancement with manual sample prep, subjective interpretation, siloed data, and rigid workflows?
Identify your Ideal Workflow
Discover the key differences between LER hold-time studies and QC sample storage hold-time studies in our informative case study. Learn about the regulatory requirements for Biologics License Application (BLA) submissions to the FDA and European Medicines Agency (EMA), and understand the impact of sample matrix on endotoxin testing using the LAL method.