Controlling Endotoxin contamination during peptide manufacturing

Endotoxin is a major constituent of the outer cell membrane of gram negative bacteria. Typically, endotoxins are released to surroundings when the bacterium dies and the cells are disrupted. Since bacteria can grow in nutrient-poor media such as water, saline, and buffers, endotoxins are found almost everywhere. Due to their ubiquitous nature, endotoxins are persistent biocontaminants that deposit and adhere to many materials. High concentrations are found where bacteria accumulate or are to be used for technical purposes, such as in bioprocessing.

In relation to this, Jyothi Thundimadathil has written an article for Controlled Environments.

Here is an extract:

“Though most peptides are made synthetically, Part 21 CFR 601.2 of U.S. Food and Drug Administration (FDA) regulations classifies peptides as specified biologics. Therapeutic quantities of most macromolecules do not pass easily through the skin or mucus membranes without penetration-enhancing techniques, such as detergents or electric impulses, increasing the likelihood of irritation or other side effects. For this reason, many protein and peptide drugs have to be delivered by injection or a nano-needle array.

As long as endotoxins get into contact with the skin or digestive system, they are tolerated quite well (certain lung diseases are known to be linked to endotoxin inhalation). For breathing, the limit for endotoxin in air is fixed at 20 ng/m3 or 200 EU/m3. For intravenous applications, the limit is 5 EU/kg body weight an hour according to European Pharmacopoeia, 1997. The term EU denotes the biological activity of endotoxins—one unit of EU corresponds to 100 pg of standard endotoxin.”

For further details see Controlled Environments.