What is endotoxin and how is it tested and controlled?

Endotoxin (lipopolysaccharide, LPS) is a component of Gram-negative bacterial outer membranes that causes fever and potentially fatal reactions when injected. Testing methods include: Limulus Amebocyte Lysate (LAL) test using horseshoe crab blood extract (gel-clot, kinetic turbidimetric, kinetic chromogenic), and recombinant Factor C (rFC) assay (synthetic alternative). Specifications are product-specific based on route, dose, and patient population. Control strategies: using pyrogen-free water and materials, validated depyrogenation procedures (dry heat at 250C for 30 minutes), avoiding Gram-negative contamination, and process design to prevent accumulation. For biopharmaceuticals produced in E. coli, extensive downstream processing removes endotoxin. Documentation and trending ensure consistent control.