A Controversial Topic Since 2013
Low Endotoxin Recovery (LER) is a controversial topic that has been circulating throughout the endotoxin detection community for the last years. This phenomenon is hypothetically described as a “masking effect” manifested in the biophysical formation of a complex that blocks the ability of Factor C, the main component in LAL detection, to bind endotoxin (J. Chen, Low Endotoxin Recovery in Common Biologics Products, presented at the 2013 Annual PDA Meeting, Orlando, FL, April 2013).
Two common drug excipients, polysorbate and citrate, have been identified as probable causes of the masking effect more commonly referred to as LER. These substances are estimated to be used in more than 70% of protein formulations (Maggio, 2012). There is also some evidence that phosphate-containing formulations may also be affected by LER. However, the LER effect has only been observed in combination formulations of the aforementioned excipients, and not in individual raw materials.
Key Points
- This "phenomenon" has been observed for more than 20 years, but never identified
- Underlying mechanism of action is still unknown
- Primarily affects formulations of polysorbate/citrate buffers
- Naturally occurring endotoxin (NOE) preparations and other 'de-masking' solutions are currently being evaluated
