Evaluation of recombinant Factor C assay kits in comparison to compendial Limulus amebocyte lysate (LAL) assays for bacterial endotoxin testing

Authors:: Poster Author(s)

Abigail Workmeister, ORISE fellow, FDA/CDER (Student); Xin Bush; Jackie Cullinan; Rachel Carley; Opeyemi Ajayi; Patricia Hughes; Talia Faison; Scott Lute; Cyrus Agarabi; Sarah Johnson, FDA/CDER (Mentor)

Center:: Contributing Office

Center for Drug Evaluation and Research

Abstract

Poster Abstract

Current regulations for biological product manufacturing require testing for sterility, testing for pyrogenic substances, testing to ensure sterile and pyrogen free drug product batch, and in-process microbial tests for manufacturing process monitoring. Compendial methods of bacterial endotoxin testing utilize limulus amebocyte lysate (LAL) which is derived from horseshoe crabs. Along with sustainability concerns, LAL reagent has variability and interference from the Factor G cascade. Recombinant protein-based alternatives - recombinant Factor C (rFC) - have entered the market with promising specificity, reduced variability, and sustainability of the horseshoe crab populations. The use of an rFC endotoxin test was recently approved in two CDER BLAs and rFC tests are currently used to test more than 20 clinical products under IND development. Despite industry adoption, there is limited work in the public sphere showing unbiased side-by-side performance assessment of all commercially available methods to the compendial LAL methods. This study aims to identify potential failure modes of commercially available rFC assays and evaluate the comparability of the compendial LAL assays and rFC assay performance. This internal evaluation of rFC assay technology will provide data to support Agency best practices and guidance to ensure product and patient safety.