The article, written by Allen Burgenson, Lonza’s Global Subject Matter Expert for Testing Solutions, explores the history of LAL and the regulatory status of the recombinant Factor C assay to emphasize the acceptance of the assay by authorities.
In 1973, the FDA decided to regulate LAL because the product is derived from horseshoe crab blood. Later, in 1980, the pharmacopoeia adopted LAL as a compendial method. When Lonza (at that time Cambrex BioScience) developed the rFC product (PyroGene® rFC) in 2002, regulatory authorities (FDA, CBER and CDRH) concluded that rFC did not need to be regulated for use in testing pharmaceuticals. Another aspect for the quality of the assay is the quality of the reagents. The rFC reagents are made in the same FDA-licensed facility as our traditional LAL products. Lonza also filed a Master File with FDA/CBER in 2008 which contains the same information about reagents and manufacturing that would be submitted to FDA for a BLA or LAL. This Master File was cross-referenced by several pharmaceutical companies in preparing regulatory filings with FDA, resulting in the first product, Emgality® by Eli Lilly, being approved by FDA using the PyroGene® rFC. This clearly shows regulatory acceptance of the rFC assay, which was in fact already stated in the FDA 2012 Q&A Guidance. In our revision to the stimulus article we also presented data about detection of endotoxin from different species and did not find significant differences to LAL based methods. In addition, other labs confirmed that rFC assay was able to detect and quantifiy endotoxin from several different gram-negative species as well as the LAL assays. The data is published in scientific journals and references are given in the article.
In summary, we conclude that the rFC reagents perform as well as LAL reagents in detecting endotoxin of various species in different matrices in both our and our customer’s hands. There was no significant difference between rFC and kinetic chromogenic reagents. The FDA has determined that rFC reagents are acceptable for final product release, provided they are validated against the criteria found in USP <1225>.
Written by Ingo
Scientific Support Specialist
