At its 180th session in November 2024, the European Pharmacopoeia Commission (EPC) decided to suppress the general chapters on Pyrogens (2.6.8), Histamine (2.6.10) and Depressor substances (2.6.11) from the European Pharmacopoeia (Ph. Eur.), all of which require the use of animals. It was also agreed to revise 14 monographs to delete either the reference to the histamine chapter or the requirement to eliminate or minimise substances that lower blood pressure.

Present in the Ph. Eur. since its first edition, these animal tests were added to ensure the safety of parenteral medicines, before the development of modern analytical techniques and GMP conditions. Their suppression is in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and other Scientific Purposes and is another step in the EPC’s ongoing efforts to replace, reduce and refine (3R principles) the use of animals for monograph requirements. Together with the suppression of Ph. Eur. general chapter 2.6.9. Abnormal toxicity in 2017, this landmark decision, which comes into force on 1 January 2026, signifies the end of general animal safety testing in the Ph. Eur.

The suppression of the general chapter Pyrogens (2.6.8), which describes a test in rabbits, follows the adoption of 57 revised texts from which the rabbit pyrogen test has been deleted, and a new general chapter Pyrogenicity (5.1.13), at the 179th EPC session in June 2024.

Both Histamine and Depressor substances describe tests that measure the effect of histamine and histamine-like substances, using guineapigs and cats, respectively. A strategy to delete those chapters and any direct and indirect references to them from the Ph. Eur. was endorsed at the 177th EPC session in November 2023. The rationale for this strategy is more fully discussed in the Histamine Strategy Paper published in Pharmeuropa Bio & Scientific Notes.

The three general chapters, 2.6.8, 2.6.10 and 2.6.11, will no longer feature in the Ph. Eur. as of the 12th Edition, in which the revised texts omitting the references to Histamine (2.6.10) and Depressor substances (2.6.11) will be published (implementation date of 1 January 2026).

See also:

• Outcome of the 180th session of the European Pharmacopoeia Commission, November 2024
• Alternatives to animal testing
• The European Pharmacopoeia Commission