Navigating the regulatory landscape of the Bacterial Endotoxin Test (BET) involves a thorough review of guidelines from regulatory agencies such as the FDA, USP, and AAMI. While there is considerable overlap in the guidance from these agencies, there are also some points of obscurity that may be difficult to work through. A common reservation for those who perform compendial BET is whether the reagent they are using is FDA-licensed or not, and what that means in terms of FDA acceptance and USP chapter <85> compliance. An example of this will be looked at closely using FUJIFILM Wako’s kinetic chromogenic LAL reagent, Limulus Colour KY.

In 1987, the FDA published guidance for LAL testing titled Guideline on Validation of the Limulus Amebocyte Lysate Test as an End-Product Endotoxin Test for Human and Animal Parenteral Drugs, Biological Products, and Medical Devices. In 2011, the FDA determined that this document was obsolete and withdrew the guidance in lieu of USP and AAMI guidelines. There was dissonance in the requirements that the FDA stated in the document and those of the USP and AAMI. This included discrepancies regarding endotoxin limits, qualification and validation procedures, and medical device testing.