Webinar: Pyrogens in medical devices

Pyrogens are substances which, upon entering the human body, can trigger feverish reactions and inflammatory processes. A distinction is made between material-mediated and endotoxin-mediated pyrogenicity. Exogenous pyrogens (e.g. endotoxins) usually originate from bacteria.

Bacterial endotoxins constitute a particularly important group of pyrogenic substances. These may remain on medical devices even after sterilization, as they are released when Gram-negative bacteria die. For this reason, sterilisation alone is not always sufficient to minimize pyrogenic risks completely. Controlling and reducing microbial contamination during the manufacturing process is of great importance.

In particular, for medical devices intended for intrathecal use or those that come into contact with the central circulatory system, the assessment of pyrogenicity is a key component of product safety.

With the publication of EN ISO 10993-1:2025, the notes on material-related pyrogenicity were removed from the tables on contact-dependent biological effects. The reason for this is that material-induced pyrogenic reactions occur only very rarely.

The standard refers here to ISO 10993-11:2017, in particular Annex G, which describes substances that may cause pyrogenic reactions.

At the same time, EN ISO 10993-1:2025 refers to a scientific publication that questions the concept of material-related pyrogenicity as defined in EN ISO 10993-11.

This raises important questions for manufacturers of new products, which will be discussed in the webinar.

On 1 January 2027, following a nine-month implementation period, Edition 13.1 of the Ph. Eur. will come into force. This edition contains the revised Chapter 2.6.14 ‘Bacterial Endotoxins’, including the new Method G: a fluorimetric end-point method using recombinant factor C (rFC). This is a synthetic solution designed to reduce the use of animal-based methods.