Chapter 18 - Phasing out animal tests: An analysis of the successful transition from rabbits to human-relevant methods in Europe

Efforts 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.