ABSTRACT
Why is a chapter on the bacterial endotoxin test (BET) included in a book on environmental monitoring? Because endotoxins, which are potent pyrogens, or fever causing agents, are by-products of viable and/or nonviable contamination of parenteral products by Gram-negative microorganisms. If we define a drug product’s ‘‘environment’’ as the combination of rawmaterials or active pharmaceutical ingredients (APIs) and their related processing environments, drug product manufacturing steps and their related environments, and laboratory testing and its related environment, we can demonstrate that major sources of Gram-negative contamination in the parenteral industry are environmental and include but may not be limited to the following:
& Acute and chronic problems with water systems and distribution loops & Raw materials and APIs, especially those obtained from natural sources & Nonvalidated cleaning and/or storage of manufacturing equipment & Nonvalidated hold times for nonsterile product formulations & Nonvalidated depyrogenation procedures & By-products of fermentations & Shedding of microorganisms by operators, and & The technique, equipment, and reagents used in the performance of the
test itself
The control of endotoxin in parenterals is not accomplished through endproduct testing, but is assured through careful system and process validation, value-added process control and thorough operator training. A validated test system and properly qualified analysts and an understanding of the benefits and limitations of the test method are essential to an accurate test result.
