The terms "bacterial endotoxins" and "endotoxins" refer to a complex component of the outer cell membrane of Gram-negative bacteria (GNB). The endotoxin limit for a product is the endotoxin concentration that must not be exceeded in order to release the product for sale.
For parenteral products other than radiopharmaceuticals and therapeutics administered on a per square meter of body surface basis the endotoxin limit equation given in the USP is as follows:
Endotoxin limit = K/M
Where,
• K = 5 USP-EU/kg of body weight for any parenteral route of administration other than intrathecal, which is the threshold pyrogenic dose of endotoxin per kg of body weight. (Intrathecally administered products are those administered into the spinal canal so that it reaches the CSF).
• K = 0.2 EU/kg of body weight for intrathecally administered products.
• M = the maximum recommended bolus dose of drug per kg of body weight.
Note: when the product is to be injected at frequent intervals or infused continuously, M becomes the maximum total dose administered in a single hour period.
Example 1
Calculation of the endotoxin limit for a product to be administered via intramuscular or intravenous injection at a maximum bolus dose of 3 mL/person.
Maximum dose per kg (assuming a standard adult human body mass of 60 kg) = 3 mL/60 kg = 0.050 mL/kg
Endotoxin limit = K/M = 5 (EU/kg) / 0.050 (mL/kg) = 100 EU/mL
Example 2
Calculation of the endotoxin limit for a bolus dose of 3 mL/person delivered via intrathecal administration.
Maximum dose per kg = 0.050 mL/kg (as in Example 1)
Endotoxin limit = K/M = 0.2 (EU/kg) / 0.050 (mL/kg) = 4 EU/mL
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