Endotoxins are components of the cell wall of gram-negative bacteria and pose a considerable risk to patients - especially with invasive or implantable medical devices.
The limit values for endotoxins are specified in various international standards and guidelines.
The endotoxin test is based on the specifications of the pharmacopoeia, whereby the limit values specified there apply primarily to medicinal products. These limits take into account the dosage and the form of administration, which play a critical role for medicinal products. However, these parameters are not directly applicable to medical devices. For this reason, the US Food and Drug Administration (FDA) has published a guideline on this topic*1. This guideline defines the following common limit values.
A lower endotoxin limit may apply for products that are in direct or indirect contact with the intraocular environment.
*1 U.S. Department of Health and Human Services, Food and Drug Administration (2012). Guidance for Industry: Pyrogen and Endotoxins Testing: Questions and Answers.
*2 EU = “endotoxin unit” (per product)
The most important standards that define the test methods for endotoxins are:
These standards specify how the endotoxins in products, such as medicines or medical devices, are tested to ensure that they do not contain harmful levels of endotoxins.
CleanControlling uses the chromogenic LAL test (Limulus amoebocyte lysate) in the colourimetric variant. This method is based on the reaction of endotoxins with an enzyme from the blood of the horseshoe crab (Limulus polyphemus). In the presence of endotoxins, this enzyme triggers an enzymatic reaction in which a chromogenic substrate is converted into a coloured compound.
Advantages of the chromogenic LAL test:
The endotoxin test is preferably performed on sterile test specimens for the following reasons:
Representativeness for clinical use: As medical devices are generally used in sterile conditions, the analysis should reflect the final condition of the product.
If gram-negative bacteria are still present on the products before sterilisation, the sterilisation process can lead to the release of endotoxins. For this reason, it is advisable to test the products after sterilisation to ensure that they correspond as closely as possible to the actual conditions of use and no longer contain any harmful concentrations of endotoxins. This contributes significantly to ensuring the safety and efficacy of medical devices.
The control of endotoxins is a central component of product safety for medical devices. Compliance with international standards and the use of validated test methods such as the chromogenic LAL test ensure a reliable assessment of the endotoxin risk.
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