Addressing Bacterial Endotoxin Contamination Incidences in WFI

The presence of endotoxin in sterile pharmaceutical products presents a significant risk to patients. The primary source of endotoxin is pharmaceutical grade water, due to the potential for Gram-negative bacteria to be present in the water system or outlets. The water source of greatest impact is Water-for-Injections (WFI), because this is used as an ingredient water.

To examine this issue, Tim Sandle has written a review paper examining three significant water system endotoxin contamination case studies.

In any form of pharmaceutical manufacture water is one of the most serious potential sources of microbiological contamination.  Water cannot be totally excluded from sterile products manufacturing facilities.  The primary focus on endotoxin control in pharmaceutical manufacture is on controlling it at its source – water.  If endotoxin is not controlled at its source it has the potential to create difficulties through manufacture to the finished product, potentially leaving no recourse but rejection.  Endotoxin is practically impossible to remove terminally from pharmaceutical dosage forms.

Well-maintained and operated water systems should not see endotoxin detected on a regular basis. Where endotoxin detection occurs, this is typically due to a special cause event, signifying that something untoward has occurred with the design or operation of the water system. To illustrate what can sometimes occur, as providing some learning points, this article presents three cases studies relating to WFI systems, relating to three different pharmaceutical companies.

Sandle, T. (2019) Addressing Bacterial Endotoxin Contamination Incidences in WFI Systems: A Review of Case Studies, Journal of GXP Compliance, 23 (3): 1-10 at: http://www.ivtnetwork.com/article/addressing-bacterial-endotoxin-contamination-incidences-wfi-systems-review-case-studies

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology