Advancing sustainable-endotoxin testing methods as an alternative to those derived from horseshoe crab blood

Recent news reports have called attention to efforts by environmentalists to protect horseshoe crabs by promoting synthetic methods to endotoxin testing for vaccines and injectable therapies rather than methods derived from the blood of horseshoe crabs.

While we appreciate the work of environmentalists in this regard, USP’s mission is first and foremost to protect patients and improve public health. This is our north star that guides all of our work. It is also the reason we were founded 200 years ago as an independent scientific organization.

Consistent with the approach we have been developing for the past several years, we are supportive of investigating the use of rFC in endotoxin testing. This is in line with our track record for switching to animal-free reeagents and tests. At this point in time, however, endotoxin tests using rFC do not benefit from the same level of real-world evidence as LAL, since LAL has been used for 30 years in FDA-approved products and rFC only for about 2 years now. Since the purpose of these tests is to make sure that the drugs being administered directly into the muscle tissue or the blood of patients don’t contain toxins that could harm them, we and other stakeholders believe it is reasonable to generate more evidence and for the FDA to have the ability to request additional validation if needed when approving products. A lot is at stake. One adverse incident might not only set back the adoption of rFC but could damage overall trust in vaccines or other injectables, already plagued by misinformation.

We are in an ‘interim’ period of time while the rFC-based methods are being adopted. Nothing prevents manufacturers from using rFC-based methods and we do not perceive unreasonable barriers. We will continue to support manufacturers and make sure they have access to guidelines and specifications for proper use. FDA will likely require drug manufacturers to validate that rFC results are comparable to LAL, but we anticipate this will be feasible for the parties involved. And it is ultimately in everyone’s best interest to make sure that products are beneficial to patients.