Endotoxin Testing: A 20-Year Journey Toward Recombinant Innovation
In the competitive pharma industry, effective quality control programs are essential to ensure product safety and compliance. Traditional endotoxin testing methods have proven to be time-consuming, prone to errors, and to involve practices that may not align with your company's sustainability initiatives.
Thankfully, for over 20 years now, endotoxin testing has greatly evolved to more reliable and ethical methods like recombinant Factor C. From traditional LAL methods to today's recombinant technologies, the journey has been marked by scientific breakthroughs, regulatory evolution, and a shared commitment to patient safety.
A scientific breakthrough that changed everything
When Pr. Ding invented recombinant Factor C in 2003, the way pharmaceutical manufacturers conducted endotoxin testing was completely transformed, making it more simple, accurate and robust.
Whereas the LAL test involves a coagulation cascade of multiple enzymes, where each member switches on the next in the series, as a single enzyme-based assay the rFC alone is sufficient and invariable. This means that the quality control of the rFC-based endotoxin test kit itself is more straightforward compared to that of LAL-based test kits.
Thanks to the use of rFC, the endotoxin test is more efficient, standardized, integrated and cost-effective, ensuring the quality and safety of pharmaceuticals and medical devices for parenteral use. A growing body of evidence is also being established through studies regarding the valuable role of rFC in endotoxin testing, and this is also being increasingly recognized by regulators.
Regulatory bodies are now catching up: Ph. Eur. + USP introduce recombinant methods as compendial
Major regulatory evolutions have happened since Pr. Ding’s discovery, leading the way towards more ethical and efficient endotoxin testing.
2025 showed great progress in terms of regulatory changes for endotoxin testing.
- 🇪🇺 Through upcoming changes in European Pharmacopeia (Ph. Eur.) chapter 2.6.14 on Bacterial Endotoxin Testing standards, Europe is opening a new era in pharmaceutical quality control. With the introduction of Method G: Fluorimetric end-point method using recombinant Factor C (rFC) into Chapter 2.6.14, “Bacterial Endotoxins,” the Ph. Eur. is paving the way for definitive compendial adoption of a modern, sustainable substitute for the traditional Limulus amoebocyte lysate (LAL) assay.
- 🇺🇸 At the same time, the United States is also undergoing significant changes. One of the most notable updates is the introduction of USP <86>, which came into execution just recently in August 2025. Moreover, the recently updated Guideline for Bacterial Endotoxin Testing USP<1085>, effective from Feb 2026, now includes USP<86>.
What about masked endotoxins?
Low Endotoxin Recovery (LER) has long been researched and highlighted as a major quality concern.
Studies have revealed that LER can also be surfactant-specific and that masked endotoxins can activate immune responses. In response, the Parenteral Drug Association (PDA) formed an LER task force in 2015, which has since published a detailed report providing information, guidance, recommended procedures, and scientific findings.
Thankfully, recombinant methods such as bioMérieux’s ENDO-RS kit coupled with ENDOLISA, can help overcome LER: the application of the ENDO-RS sample-preparation method was assessed, and the results showed that endotoxins were reliably detected/unmasked under all the conditions tested.
The future of endotoxin testing is recombinant
The journey from the initial development of recombinant Factor C in 2003 to the comprehensive regulatory frameworks of 2025 highlights the collaborative efforts of scientists, regulatory bodies, and industry stakeholders. This progress not only reflects a commitment to innovation but also a dedication to ethical practices and environmental conservation.
Implementing and validating a robust method is not a road you have to walk alone! Partnering with bioMérieux for your Quality Control solutions means relying on a trusted and recognized expert to implement recombinant methods into your testing strategies.
