The Human Whole Blood Pyrogen Test : Lessons Learned in Twenty Years

Abstract

The whole blood pyrogen test was first described in this journal exactly twenty years ago. It employs the cytokine response of blood monocytes for the detection of microbiological contaminants with the potential to finally replace the still broadly used rabbit pyrogen test. The article reviews its development process, the current status of the test as well as the challenges and missed opportunities. The article highlights the enormous efforts of many people to get the test to where it is today. But it also shows the incredible missed opportunities for implementation and thus sparing about 400,000 rabbits still used for this purpose per year worldwide; in the EU, since the official acceptance of the test, the number of animals used for pyrogen testing did not fall but increased by about 10,000 to 170,000. The test is the first solution enabling adequate pyrogen testing of cell therapies, including blood transfusions, and medical devices, but has not been implemented for either application by authorities. As the test can quantitatively assess human-relevant airborne pyrogens, the contribution of pyrogens to chronic obstructive lung diseases and childhood asthma can for the first time be defined and home and workplace safety improved in the future.