02024nas a2200325   4500000000100000008004100001260003100042653001400073653002600087653003500113653002600148653001700174653003000191653003100221100002300252700001900275700002900294700002100323700001700344700002600361700001700387700002700404700002300431700002300454245013300477856007500610300001200685520097900697020002201676       2027                            d  c2027-01-01bAcademic Press10aEndotoxin10aEuropean pharmacopeia10aMonocyte activation test (MAT)10aNonanimal replacement10aPyrogenicity10aRabbit pyrogen test (RPT)10aUnited States pharmacopeia1 aJustine C. Watkins1 aThomas Hartung1 aIngrid Visseren-Hamakers1 aDilyana Filipova1 aHoward White1 aLuisa Ferreira Bastos1 aLove Hansell1 aMerel Ritskes-Hoitinga1 aCatharine E. Krebs1 aGail A. Van Norman00aChapter 18 - Phasing out animal tests: An analysis of the successful transition from rabbits to human-relevant methods in Europe  uhttps://www.sciencedirect.com/science/article/pii/B9780443265143000175  a289-3193 aEfforts to replace animal testing with human-relevant methods have advanced. Pyrogenicity quality control testing illustrates the progress of this transition well. The rabbit pyrogen test (RPT), once the gold standard, has limitations that prompted the development of in vitro alternatives like the monocyte activation test (MAT). While MAT is validated and accepted in the EU, the United States, Russia, and India, only the European Pharmacopoeia has fully phased out RPT, making MAT compendial. In contrast, RPT remains the gold standard in the United States, reflecting regulatory inertia and global inconsistencies. This chapter analyzes the historical, scientific, and regulatory evolution of pyrogen testing, comparing Europe and the United States. It finds the United States lags in phasing out RPT, and that even in Europe, the transition took nearly 40 years. Proactive regulation and simultaneous method phase-in/out are essential to accelerate future transitions.  a978-0-443-26514-3