In May 2025, the U.S. Pharmacopeia (USP) will officially introduce Chapter <86> Bacterial Endotoxins Test Using Recombinant Reagents, which permits the use of non-animal-derived reagents for endotoxin testing. As a critical step for safety and quality control in pharmaceutical manufacturing, endotoxin testing traditionally uses Limulus Amebocyte Lysate (LAL), a natural reagent sourced from horseshoe crabs, to detect or quantify bacterial endotoxins present in a sample.
Chapter <86> aligns with USP's commitment to expanding animal-free methods by incorporating recombinant Factor C (rFC) and recombinant cascade reagent (rCR), which utilize endpoint fluorescence and chromogenic techniques, respectively, derived from gene sequences of factors found in the horseshoe crab. These recombinant reagents serve as alternatives to naturally sourced LAL, providing opportunity to reduce impact on the horseshoe crab population.
As an alternative to the traditional USP Chapter <85> Bacterial Endotoxins Test (BET), Chapter <86> requires users to verify the suitability of these recombinant reagent-based methods for their specific products, in line with USP <1225> and <1226> guidelines. Transitioning from <85> to <86> involves demonstrating product-specific method suitability, a practice consistent with the requirements of <85>, ensuring a seamless shift to more sustainable testing methods. It marks an important milestone in endotoxin testing by allowing users to choose between traditional Limulus Amebocyte Lysate (LAL) and recombinant reagents without the need for an additional validation step.
To learn more about USP Chapter <86>:
- Read our Application Note that demonstrates the compatibility of the Sievers Eclipse Bacterial Endotoxins Testing (BET) Platform with rCR across various pharmaceutical products
- Watch our 10-minute Q&A video with Mike Auerbach, Editor in Chief of American Pharmaceutical Review.