Microbiological contaminants endotoxins

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. 

The moleciilia dimensions of bacterial endotoxins are too large to pass through reverse osmosis membranes, and therefore the process is permitted by the pharmacopoeias for production of Water for Injection. However, the outlet water from reverse osmosis units can easily become microbiologically contaminated by formations of films or slimes downstream of the membranes. At least two micraterfogical problems may be encountered with reverse osmosis. First, micit iological films may slough off into the water at unpredictable intervals or... 

In the manufacture and filling of terminally sterilised parenteral veterinary medicines, particular attention should be given to the need to minimise microbiological contamination of the product before sterilisation. Pyrogen contamination (endotoxin level) should be controlled to the same limits as for human medicines. 

Equipment cleaning and sanitization studies should address microbiological and endotoxin contamination for those processes intended or purported to reduce bioburden or endotoxins in the API, or other processes where such contamination may be of concern (e.g., nonsterile APIs used to manufacture parenteral products). 

Microbiological contamination of raw materials can lead to a finished product that does not meet the requirements for microbiological purity and in addition a high endotoxin level can be found leading to a pyrogenic response after intravenous injection. 

A recently published book provides an excellent survey of issues that relate to contamination with endotoxins (present in both viable and nonviable bacteria), their released cell wall constituents, and also viable bacteria in the pharmaceutical industry [1]. It is important to know both the content of the work environment (e.g., indoor air) and the pharmaceutical products themselves. The former provides information on possible sources of microbial contamination and the latter the purity of the final commercial product (or precursors in various stages in its preparation). In some cases it is vital to know the actual bacterial species involved in contamination culture-based methods are standard microbiological techniques which were the focus of Jimenez [1] and thus will not be discussed further. Any contamination (e.g., with endotoxins), regardless of the species of origin, is of utmost of importance (e.g., in determining the safety of a batch of antibiotics to be administered intravenously). This is determined optimally by non-culture-based methods. 

Freedom from pyrogenic contamination and endotoxins Freedom from particulate matter Physical, chemical, and microbiological stability... 

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