LALTest

The LALtest, short for Limulus Amebocyte Lysate test, is an in vitro assay used to detect bacterial endotoxins in sterile pharmaceutical products, medical devices, and related preparations. Endotoxins, components of Gram-negative bacteria’s outer membranes, can cause fever and shock if present in injectable products. The test exploits the clotting properties of amebocytes from horseshoe crab blood, which react with endotoxins to form a detectable signal.

There are several methods within the LAL framework. The gel-clot method yields a visible gel when endotoxin is present; turbidimetric methods measure changes in turbidity; and chromogenic methods detect endotoxin presence through color development. All variants rely on the endotoxin-triggered activity of the Limulus amebocyte lysate, but they differ in sensitivity, speed, and instrumentation requirements.

Applications cover a wide range of sterile products, including parenteral drugs, injectable solutions, vaccines, ophthalmic preparations, and medical devices that contact the bloodstream or sterile sites. The test is standardized in major pharmacopeias, such as the United States Pharmacopeia (USP) and European Pharmacopeia (EP), and is used to ensure endotoxin levels stay below specified limits expressed in Endotoxin Units (EU).

Regulatory and ethical developments include the emergence of non-animal alternatives, such as recombinant Factor C (rFC) assays and Monocyte Activation Tests (MAT), which reduce reliance on crab-derived components. Some jurisdictions encourage or permit these alternatives as replacements or supplements to the LAL test.

Sustainability concerns center on the harvesting and bleeding of horseshoe crabs, which can impact wild populations. Industry and regulators have explored strategies to mitigate impact, including improved crab management and broader adoption of non-animal testing where feasible.