The bacterial endotoxin test in the Chinese pharmacopoeia: A journey of international harmonization and national consideration

The Bacterial Endotoxin Test (BET) is a critical quality control measure for parenteral drugs and sterile medical devices worldwide. As the global pharmaceutical industry becomes increasingly integrated, the harmonization of pharmacopoeial methods is an inevitable trend. The Chinese Pharmacopoeia (ChP), China's official national standard, has undergone significant evolution in its BET chapter, transitioning from initially referencing the United States Pharmacopoeia (USP) to progressively aligning with the International Council for Harmonization (ICH) Harmonized Tripartite Guideline:Evaluation and Recommendation of Pharmacopoeial Texts for Use in The ICH Regions on Bacterial Endotoxin Test General Chapter Q4B (ICH Q4B). This article provides a comprehensive overview of the development of the BET in the ChP, with a special focus on the major revisions in the newly implemented 2025 edition. We detail how the ChP 2025 further converges with the ICH harmonized text in aspects such as method classification, procedural descriptions, and key validation parameters. Concurrently, we elucidate the scientific rationale for retaining specific "Chinese characteristics," such as stricter requirements for water for BET, a different standard for average body weight in limit calculations, and more stringent retest protocols for the gel-clot method, all of which are rooted in domestic regulatory practices and public health considerations. Furthermore, we discuss China's proactive approach to addressing emerging global challenges like Low Endotoxin Recovery (LER) and its pioneering research into resource-saving micro-methods. This review aims to offer international stakeholders a clear perspective on the scientific rigor, commitment to global standards, and unique risk-based considerations that define the modern BET in China.