Bacterial endotoxins

Testing for bacterial endotoxins is regulated considerably less precisely for medical devices than the corresponding investigations for drugs or raw materials that are described in the Pharmacopoeias.

However, endotoxins can find their way into medical devices during the manufacturing process. It is therefore in the interest of every manufacturer to guarantee patient safety by performing appropriate monitoring.

As there are few binding regulations from the legislature, it is even more important that methods are developed and validated in close collaboration between the customer and the service laboratory and that their routine analysis are established. 
Would you like to know which tests are suitable for your products?

We are a GMP-certified and ISO 17025 accredited contract laboratory in Switzerland with many years of experience in the testing of medical products. We would be pleased to provide support for any of your questions

What are endotoxins?

Endotoxins are chemical compounds from the external cell membrane of gram-negative bacteria. They are lipopolysaccharides which can be released when bacteria die off and decay. They are classified as pyrogenes. If endotoxins get into the body, this can lead to different effects, depending on the place of entry.

Why should medical devices be tested for bacterial endotoxins?

Endotoxins from gram-negative bacteria can cause toxic reactions in humans (e.g. inflammatory responses, feelings of nausea etc.) and in the worse cases can even lead to an anaphylactic shock.

Pyrogenes can be present even for sterile products which are not carrying any viable bacteria. Heat sterilisation or irradiation often does not lead to the destruction of the lipopolysaccharide (bacterial endotoxins). They are very heat resistant and are degraded only at temperatures over 180°C.

Evidence of endotoxins

Generally, endotoxins can be proven by testing on rabbits, the limulus test (Limulus Amebocyte Lysate; given the shorter name LAL test) or by the EndoLISA test. Nowadays, in particular the LAL test is being used more and more often, because animal investigations are not considered to be in keeping with the times and are mandatory in only a few cases.

The LAL test is based on the coagulation or clotting of the lysed amebocytes that occur in the blood of the Horseshoe Crab (Limulus polyphemus) in the presence of LPS (Lipopolysaccharide).

Customer-specific methods for medical devices

Medical devices differ very greatly in terms of materials, function and appearance. Generally, there are no existing methods here and product-specific methods corresponding to the customer’s requirements must be developed. 
Examples of medical devices that need to be tested:

• Syringes
• Infusion sets
• Stents
• Balloon catheters
• Plasters

During the method development stage, the decision has to be made as to how they will be extracted and whether a kinetic chromogenic or a kinetic turbidimetric test will be applied. Both of these tests allow quantitative determination of the endotoxin content.

Validation of lal tests

Generally, product-specific validation is also necessary for the measurement of endotoxins. If analysis conforming with GMP is desired, then it is absolutely necessary to perform testing of three batches.

Only by performing validation, can one be certain that matrix effects do not occur and that recovery is guaranteed.

Our services in detail:

• Consultation on the LAL test
• LAL test (kinetic chromogenic or kinetic turbidimetric test)
• Method development and validation
• Routine testing
• Additional services are according to directory of services or upon request.