USP <85> - Bacterial Endotoxins Test

What it says

General Chapter <85> describes methodology for detecting and quantifying bacterial endotoxins using the Limulus Amebocyte Lysate test, applicable to parenteral drug products and medical devices, including gel-clot, turbidimetric and chromogenic method variations and their respective validation requirements.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• Endotoxin control is a distinct microbiological risk from sterility, a product can be sterile, free of viable microorganisms, while still containing endotoxin from dead bacterial cells, making this a separate and necessary control parameter for parenteral products.
• Method suitability testing, confirming the specific product does not interfere with the endotoxin test method through inhibition or enhancement, is a required precondition before routine testing results can be considered valid for that product.
• Endotoxin limits are calculated based on the product's maximum dose and route of administration, meaning the same raw test result can represent different levels of risk depending on how the product is actually used.

What inspectors look for

• Whether method suitability testing was performed and passed for the specific product before routine bacterial endotoxin testing began.
• Whether calculated endotoxin limits correctly reflect the product's actual maximum dose and route of administration.
• Whether water and raw material endotoxin control feeding into the manufacturing process is monitored as part of the broader contamination control strategy, not just tested at the finished product stage.

Related regulations