International harmonization research on the bacterial endotoxin test in the Chinese Pharmacopoeia and ICH Q4B
CAI Tong
GAO Hua
HE Kai-yong
ZHU Ran
PEI Yu-sheng
Abstract：The bacterial endotoxin test(BET)is a key quality control method for controlling the pyrogen risk of injectable products and other sterile drugs.With the acceleration of the global integration in drug research and development,production and regulation,the harmonization of testing methods across various pharmacopoeias has become an inevitable trend.ICH Q4B guideline Annex 14 provides a harmonized assessment of the BET chapters in the United States Pharmacopeia(USP),European Pharmacopoeia(EP)and Japanese Pharmacopoeia(JP),and recommends their interchangeable use within the ICH region.The Pharmacopoeia of the People's Republic of China(ChP),as China's national drug standard,historically established its BET method based on the USP and has undergone continuous revisions to align with ICH harmonization efforts,gradually achieving international alignment.This article aims to conduct a detailed comparative analysis of the main differences between the BET in ChP 2020 edition and the ICH harmonized text,based on ICH Q4B Annex 14 and the relevant chapters of the USP,EP and JP,and to explain the background,principles,main content,and ICH Q4B harmonization considerations underlying the revision of the BET in the ChP 2025 edition.The study shows that the BET in the ChP 2025 edition further converges with the ICH harmonized text in terms of method description format,requirements for revalidation of limulus amebocyte lysate(LAL)reagents sensitivity,and certain calculation parameters.At the same time,considering China's national conditions and drug safety,it retains Chinese characteristics in aspects such as water for testing requirements,the average body weight standard for calculating endotoxin limits,gel-clot interference test,and retest requirements for the limit test.This revision reflects the ChP's principle of actively participating in international harmonization while enhancing scientific rigor and international competitiveness of standards,while also taking into account domestic regulatory practices and public health,thereby laying a more solid foundation for achieving mutual recognition in drug regulation.
Keywords：Chinese Pharmacopoeiabacterial endotoxin testICH Q4Binternational harmonizationlimulus amebocyte lysategel methodphotometric methodendotoxin limit value
Publication Date：2026-05-15
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：6( 897-902 )