Biomedical Applications of Limulus Amebocyte Lysate

This year celebrates the 30th anniversary of the licensing of Limulus amebocyte lysate (LAL) by the US Food and Drug Administration (FDA) as a test for the presence of endotoxin in biologicals, pharmaceutical drugs, and medical devices. LAL is currently recognized by several major pharmacopoeias and is used worldwide. That a suitable alternative for the detection of endotoxin has not supplanted LAL is indicative of its superior reliability. Since its discovery, LAL has proven its usefulness not only to detect harmful levels of endotoxin (as pyrogens) in pharmaceutical products, but has become an indispensable tool in controlling endotoxin in processes and equipment used to produce pharmaceuticals. Indeed, the exquisite sensitivity of LAL compared to other assays for endotoxin/pyrogen has proven extremely useful in monitoring high-purity water used as a prime ingredient or processing agent for all biologicals, drugs, and devices. LAL has also become the assay of choice for researchers studying both the clinical and the environmental effects of endotoxin. To highlight its usefulness, various specific applications of LAL including modifications of the assay to allow testing of complex substances will be described. Finally, although horseshoe crab mortality associated with LAL production is low, the LAL industry has taken steps to find a synthetic substitute and to produce reagents and methods that use much less LAL than traditional assays. That the horseshoe crab has uniquely contributed a test that profoundly affects the safety of pharmaceuticals should be celebrated and rewarded by continuing to protect this valuable resource.