Low Endotoxin Recovery

Abstract

 Endotoxin in the bloodstream presents a severe health risk already in small doses. Thus endotoxin tests are extremely important and mandatory for release of parenteral administered drugs. For detection of endotoxin, Limulus-based methods are the gold standard. Many Drug Products however cause interference with such detection methods. Very often this interference can be overcome by dilution, but not in the case of Low Endotoxin Recovery (LER). Excipients used for drug product formulations like citrate buffer in combination with polysorbates or even the active pharmaceutical ingredient itself are able to cause LER. This effect leads to failure in determination of correct endotoxin contaminations. A controversial discussion about the relevance of LER and the setup of these studies is ongoing. Here we present a review of the molecular mechanism behind LER and the factors that influence this effect. The importance of standardized protocols for LER studies to produce comparable results is summarized and an outlook for dedicated sample treatments that are able to overcome the LER effect is given.