Endotoxins testing in medical devices

Medical devices and medical technologies industries share a lot in common with the field of in vitro diagnostics when it comes to their relation to bacterial endotoxins. Similarly, to IVDs, MDs are also under scrutiny for bacterial endotoxins present as an unintended contaminant in the production lines. In more recent development, new technologies are also targeting lipopolysaccharides to provide personalized medical care. In any case, given the potency of endotoxins, a strict quality control of the devices should be enforced in their production or in their uses to avoid putting patients’ safety at risk and comply with regulatory and medical obligations.

It is important to know that lipopolysaccharides or bacterial endotoxins have a different profile of pathogenicity. In fact, there is a wide range of diversity in terms of structures and pyrogenicity that requires different levels of concern and priority to deal with.

The main factor to consider when dealing with a production line is first to determine whether there is real endotoxin contamination or not. A positive LAL test does not necessarily mean that your Medical Device is contaminated by endotoxins. Many tests are showing false positive results because of interference. If endotoxin presence is confirmed, then determining the strain of origin of the contaminants is the second step to decide how to deal with it. 

By combining methods of structural characterization of endotoxins and pyrogen detection, it is possible to confirm the inflammatory potential of the endotoxin. Depending on the bacterial strain identified, and the site of contamination, then different cleaning methods could be considered as potential solutions: removal by different extraction methods, detoxification by chemical modification…

Thus, to determine the endotoxins’ origin is not only a matter of quality control over the production line, but also a necessary step to define the appropriate actions to solve a potential issue.

The quality control of a final product is essential, but it is also necessary to define the appropriate actions to solve a potential contamination issue in the production line. Endotoxins detection assays are required for such procedures. The reliability of such assays has a tremendous importance since the results will directly impact the release of the product on the market, or the actions to clean the production line before preparing the next batch.

Using efficient assays for endotoxin detection is a priority. For such reasons, analytical methods and validity assays need to be enforced in routines in order to get a reliable quality control on the production line over time. In some cases, the official tests recognized by the regulatory authorities (LAL, MAT, RPT) may fail due to interferences of the matrix, complex biological media or false positive data due to the presence of acidic polysaccharides, LPS absorbance, etc… This is why LPS-BIOSCIENCES has developed complementary analytical methods which can detect LPS in complex matrices or products without interference.

Measuring endotoxin levels is necessary in the medical device or the production line, but it could also be important to measure the interactions between the device itself and the endotoxins molecules.

Some devices are made with material that can absorb endotoxins or on the contrary catalyze reaction between endotoxins and human cells. It is known that Medical devices made with Hyaluronic acid are absorbing LPS molecules and making it hard to detect them with LAL test.  The material used for surgery like acrylic may interfere with human cells and increase inflammation response due to endotoxins. 

Some “smart” devices nowadays aim at changing and improving medical practices. It would be the case of smart plasters, that have the ability to send a signal in case of infection by changing color, or smart catheter, that can detect the beginning of an infection and then release an anti-bacterial treatment to deal with it early on.

To develop such devices, it is important to have reliable controls. For example, to detect a specific or a generic endotoxin that would serve as the biomarker the device is working on. Given lipopolysaccharides’ (LPS) diversity, specificity, and pathogenicity, having a quality LPS standard is fundamental for a successful device in terms of selectivity, sensitivity, and efficacy.