What is the purpose of removing endotoxin?

Endotoxin is a common contaminant of medical products that come from bacteria. The presence of endotoxin may come from the internal components of the production process or from random contamination of the product. Endotoxin can cause endotoxic - or septic - shock, tissue damage and even death. Removal of endotoxin before approval of the drug for release is therefore necessary to prevent the method of disease caused by the recipient of the drug. In bacteria generally divided into two groups, a gram of negative and gram positive, a gram of negative bacteria are very common. A gram negative marking comes from the occurrence of bacteria after the specific color process, called a gram of stains. Endotoxin is present in all gram negative bacteria, regardless of whether they cause disease.

Outer Part of gram negative bacteria contains lipopolysaccharides (LPS), which are used for structural stability. Endotoxin refers to this LPS part of the bacterium. For example, the E. coli cell contains about 2 million LPSmolecules. LPS is not only present in cells of living or dead bacteria, but also constantly relaxes into the environment. The release occurs during the growth and division of the bacteria and when the cell dies.

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LPS molecule has indirectly a harmful effect on the body. Endotoxin interacts with the immune system binding with cells in the blood called macrophages and monocytes. This binding causes an inflammatory response by releasing factors such as interleukin-6, interleukin-1 and factor of tumor necrosis. This inflammatory response leads to fever and sometimes to endotoxic shock and death.

These dangerous effects occur either in a single hdávka endotoxin or with repeated lower exposure levels. A dose of 1 nanogram LPS per millilitr product can cause an endotoxic reaction in mammals when the product is injected intravenously. People with diseases such as AIDS, leukemia or diabetes are particularly at risk of endotoxical shock.

geneticY modified gram negative bacteria are regularly used in the production of biologically active proteins and peptides. The presence of LPS molecules in production cells and ambient culture means that the product requires cleaning and removal of endotoxin. Lipopolysaccharide is a very stable molecule compared to proteins, withstands extreme pH and temperatures, so the removal of endotoxin requires complex removal techniques. Therefore, manufacturers use methods such as chromatography with ionication, ultrafiltration and chromatography based on membrane to remove or reduce endotoxin to an acceptable level.