Bacterial Endotoxin Testing: A Mandatory Requirement for Key Pharmaceutical Products
The primary objective of Bacterial Endotoxin Testing (BET) is to control the risk of pyrogens in pharmaceutical products and to prevent serious adverse reactions in humans, such as fever and shock. According to major pharmacopoeial standards, including the United States Pharmacopeia (USP) and the European Pharmacopoeia (Ph. Eur.), medicinal products that directly enter the bloodstream, come into contact with mucous membranes or damaged tissues, or are used in surgical or implantable procedures are subject to mandatory endotoxin testing. The specific categories are as follows:
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Pharmaceutical Categories
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Typical Variety
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Endotoxin Limits
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Units
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Core Basis / Application Notes
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Water for Injection |
Water for Injection, Sterile Water for Injection |
≤0.25 |
EU/mL |
· General Chapters of Chinese Pharmacopoeia as the baseline endotoxin limit for injection solvents and the internal control threshold for most injection preparations.Issued by the Pharmacopeial Convention |
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Large-Volume Intravenous Infusions (≥100 mL) |
Sodium Chloride Injection, Glucose Injection, Compound Electrolyte Infusion |
≤0.50 |
EU/mL |
· Specified in Pharmacopoeia: This limit shall not be exceeded for large-volume infusions (≥ 100 mL), to ensure the safety of high-dose administration.Issued by the Pharmacopeial Convention |
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Small-Volume Intravenous Injections (＜100 mL) |
Cephalosporin Antibiotics for Injection, Vitamin C Injection |
≤0.50 |
EU/mL |
· Calculated per the formula L=K/M (where K=5 EU/(kg·h)). The limit is established in combination with the maximum clinical dosage, with stricter requirements for some high-risk formulations. |
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Sterile Powders for Injection |
Piperacillin Sodium and Tazobactam Sodium for Injection, Lyophilized Human Serum Albumin |
≤0.25-0.50 |
EU/mg |
· Tested after reconstitution. The limit is converted based on the dosage of active pharmaceutical ingredients (APIs) / finished preparations. For biological products, the limit is typically controlled at 0.25 EU/mg. |
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Intramuscular/ Subcutaneous Injections |
Insulin Injection, Thymopeptide for Injection |
≤0.50-2.0 |
EU/mL |
· Adjusted according to administration frequency and dosage. Stricter limits apply to long-term administration / high-concentration formulations. |
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Intraocular Injections |
Anti-VEGF Intravitreal Injection, Intraocular Perfusion Solution |
≤0.20 |
EU/mL |
· Given the high sensitivity of intraocular mucous membranes, the limit refers to the standards for ophthalmic preparations in ChP. For some formulations, the limit is controlled at 0.1 EU/mL. |
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Blood Products |
Human Serum Albumin, Human Immunoglobulin for Intravenous Injection |
≤0.50 |
EU/mL |
· In accordance with the General Principles for Biological Products in Pharmacopoeia, the limit is calculated based on the maximum dosage per kilogram of body weight per hour to ensure infusion safety. |
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Vaccines |
Inactivated Influenza Vaccine, Recombinant Hepatitis B Vaccine |
≤0.10-0.25 |
EU/mL |
· Balancing immunogenicity and safety, the limit for vaccine adjuvant products is typically ≤ 0.1 EU/mL. |
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Dialysate |
Hemodialysis Solution, Peritoneal Dialysis Solution |
≤0.50 |
EU/mL |
· To avoid dialysis-related pyrogen reactions, the internal control limit for some products is ≤ 0.25 EU/mL. |
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Intrathecal/ Intraspinal Injections |
Spinal Anesthetics, Intrathecal Chemotherapeutic Agents |
≤0.20 |
EU/mL |
· Due to the high risk to the central nervous system (CNS), the K value is set at 0.2 EU/(kg·h), making the limit far stricter than that for intravenous administration. |