Parenteral drugs or products are sterile preparations containing active pharmaceutical ingredients and excipients intended to be administered by injection, infusion, implantation or by any route aside from the alimentary canal. These drugs are typically packaged in either single-dose or multidose containers and their testing for pyrogens is critical to patient and animal safety. While a variety of microorganisms like bacteria, molds, yeasts and viruses can produce pyrogens, due to its high potency and ubiquitous nature, bacterial endotoxin is the only significant pyrogen of concern to the parenteral drug industry. Bacterial endotoxins are found in the outer membrane of gram-negative bacteria which are members of a class of phospholipids called lipopolysaccharides (LPS). LPS are not exogenous products of gram-negative bacteria. The release of LPS from bacteria like Escherichia coli, Proteus, Pseudomonas, Enterobacter and Klebsiella takes place after their death and lysis and is refractory to removal via sterilizing membrane filters.4 Therefore, it is possible to have a sterile solution that has sufficient endotoxin to be pyrogenic. The only practical way to avoid endotoxin contamination is to eliminate it at the outset by using endotoxin-free materials and aseptic techniques throughout the parenteral drug manufacturing process.
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