Safety assessment of endotoxin related to drug products and medical devices: A review.

Endotoxin, also known as LPS, is the main component of the outer membrane of Gram-negative bacteria. It is released into the environment during cell division and cell death. Contamination of drug products and medical devices by endotoxin has been reported. Although endotoxin has been studied for its therapeutic uses treating diseases via the tolerance mechanism, more overwhelming evidence points to its toxicity. Extensive literature has reported its acute and chronic health effects and association with a variety of human diseases due to its action on innate and adaptive immune systems. Endotoxin is tightly regulated by health agencies through the regulatory limits for drug products and medical devices. Safety insurance of endotoxin is critical by drug product and medical device industries to ensure product quality and patient safety. The current paper aims to provide a state-of-art review of the endotoxin structure, the mechanisms responsible for endotoxin bioactivity and toxicity, the health effects associated with endotoxin, the challenges of endotoxin to drug product and medical device developers, and the safety assessment status of endotoxin in relation to drug products and medical devices. Based on the historical record and recent data analysis of drug products and medical devices in relation to endotoxin, it has been proved that endotoxin has minimal safety risk to patients for these industries.