Low endotoxin recovery (LER), also known as endotoxin masking, is a recently described but long-observed phenomenon. LER is the inability to recover known amounts of purified endotoxin from biological formulations. Check out our quick resources below to learn more. 




  • “Summary of LER Discussions” (Dr. James Cooper, Bacterial Endotoxin Summit) Request a PDF copy »
  • “Comparative In Vitro and In Vivo Low Endotoxin Recovery (LER) Assessment” (John Dubczak, 9th Annual PDA Global Conference on Pharmaceutical Microbiology) Request a PDF copy »
  • “Endotoxin Potency Change in the LAL Reactivity and Its Relationship With Pyrogenicity” (Masakazu Tsuchiya, PhD, 9th Annual PDA Global Conference on Pharmaceutical Microbiology) Request a PDF copy »


LER Impact

LER has become such a significant issue that recently an entire PMF Bacterial Endotoxin Summit (BES) was devoted to the topic. Scientists at the summit largely agreed 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.

You may also be interested in...

The 50th Anniversary of the LAL Reagent

The 50th Anniversary of the LAL Reagent

American Pharmaceutical Review conducted an interview with our technical team to discuss our horseshoe crab conservation, low endotoxin recovery and the future of LAL technology.

The Evolution of the Bacterial Endotoxins Test

The feature article in this issue of the Endosafe® Times reviews the development of endotoxin test methods and describes how the innovative LAL-dependent systems became standard compendial methods.

Endotoxins Standards and Their Role in Recovery Studies: The Path Forward

Information and feedback from the USP Microbiology Expert Committee studying endotoxin contamination suggest that broadening analyte options to include a well-defined native CSE calibrated against the RSE as long defined in the USP is not only a good scientific option, but is also an extremely pragmatic one.