The European Pharmacopoeia (Ph. Eur.) has historically included in vivo assays for testing pharmaceutical safety, specifically through the Histamine (2.6.10) and Depressor substances (2.6.11) chapters, which involve animal testing for histamine and depressor substances. However, these methods have been criticized for their non-specificity, variability, ethical concerns, and their origins from a time before the widespread adoption of good manufacturing practices and formal method validation. Consequently, the European Pharmacopoeia Commission, in its 177^th Session in November 2023, proposed the removal of all references to these animal tests from the Ph. Eur. This includes the elimination of general chapters 2.6.10 and 2.6.11, and the removal of related sentences in the Production section of monographs that refer to the control of substances lowering blood pressure without ensuring safety. Additionally, a new chapter, Histamine in active substances (2.5.47), is proposed to introduce physicochemical or immunochemical methods for histamine detection, supporting manufacturers in their control strategies. This move, prompted by adverse events linked to a GMP issue with gentamicin sulfate, represents a significant shift towards more ethical, reliable, and modern testing methods. Public consultation on the changes is scheduled for April 2024 in Pharmeuropa 36.2.