Bacterial endotoxin sterile parenteral products

Although bacterial endotoxins are of microbiological origin, they are not lost with loss of viability. Of the sterilization processes commonly used in the manufacture of sterile parenteral dosage forms (see above), only dry heat is capable of destroying bacterial endotoxins in a reasonable time frame. There is therefore no practical way of removing bacterial endotoxins from finished drug products thus, they must be controlled at source. 

Bacterial endotoxins, or pyrogens, are substances that will cause a variety of symptoms such as a rise in body temperature when injected in large amounts into human or animal bodies. In pharmaceutical products and medical devices intended for parenteral injection, the absence of endotoxins has equal or greater importance than sterility. None of the other large-scale... 

Dry beat should be the method of choice for sterilization of heat-stable items that are damaged by moisture or are impervious to steam. It can in fact serve one or both of two functions it may serve as a method of sterilization or as a method of steriliziUion and depyrogenation (destruction of bacterial endotoxins). Absence of bacterial endotoxins is a biological quality of equal or greater importance to sterility for pharmaceutical products and medical devices intended for parenteral... 

The pharmacopoeias deal with ingredient water of two types. Purified Water and Water for Injection. The principal difference in biological quality between the two types of water is that Water for Injection is specified to be pyrogen-free (less than 0.25 Eu of bacterial endotoxin per mL). Only water of Water for Injection quality may be used to dissolve, dilute, or compound parenteral products, because endotoxins may pass through 0.22 pm sterilizing filters. Control of bacterial endotoxins is achieved in the first instance through control of microbiological contamination. 

Water for injections in bulk must comply with the requirements as formulated for Purified water. It must also be produced free of bacterial endotoxins and stored such that it remains free of them. It can be used for parenteral products and irrigations that are terminally sterilised. Water for injections, sterilised, must meet the requirements of sterility (sterility test) and the bacterial endotoxin content must not exceed 0.25 lU per mL. This is used for parenteral products and irrigations that are not terminally sterilised and for dissolving powders for injection immediately before use. 

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