Overview
LER has recenly become a significant issue and scientists largely agree that LER 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. LER does, however, present a problem in validating product hold times. Chelating agents combined with surfactants that are common in biological formulations are particularly problematic.
Next Steps
More research must be done to both understand and address LER. We are actively studying 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.
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SCIENTIFIC REFERENCES
Poster
- Aspects of Mechanism in Low Endotoxin Recovery (presented at the 11th Annual PDA Global Conference on Pharmaceutical Microbiology)
Articles- “Endotoxins Standards and Their Role in Recovery Studies: The Path Forward” (Karen Zink McCullough, Radhakrishna Tirumalai, Ph.D., David Hussong, Ph.D., James Akers, Ph.D. Dennis Guilfoyle, Ph.D., Robert Mello, Ph.D., 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)