July 22, 2025
Announcing a new medical device publication:
Borton, L; Coleman, K. 2025. “Material-mediated pyrogens in medical devices: Myth or reality?” ALTEX – Altern. Anim. Ex. doi: 10.14573/altex.2504231.
In this publication, Gradient Principal Toxicologist Lindsey Borton and Medtronic Sr. Distinguished Toxicologist Kelly Coleman used an evidence-based toxicology approach to determine whether material-mediated pyrogens (MMPs) exist in a medical device context, and whether the rabbit pyrogen test (RPT) could detect the presence of MMPs in/on a medical device. The implications have potential to reduce animal-based testing requirements.
Annex G of ISO 10993-11 lists 24 substances that are allegedly MMPs in medical devices and recommends using RPT for their evaluation. The scientists aimed to evaluate whether the Annex G MMPs are actually pyrogenic. They also explored whether compounds released from medical devices (extractables) could exert a hyperthermic response through uncoupling of oxidative phosphorylation, and reported the results of a survey of RPT failures and their root causes.
In brief, the study found RPT to be inadequate for biological evaluation of medical devices and suggested that it could be replaced with more effective methods. The authors recommend replacing the term “material-mediated pyrogen” with the specific classifications of “biological pyrogen” and “chemical thermogen.” Chemical thermogens can be detected and addressed through: (1) hazard assessment and (2) chemical characterization and toxicological risk assessment. Biological pyrogens that operate through the cytokine pathway (e.g., fungi, yeast, viruses, parasites, bacteria, bacterial endotoxins) should be managed through manufacturing controls. If manufacturing controls are insufficient, the in vitro monocyte activation test (MAT) can address a broad spectrum of biological pyrogens.
It was concluded that RPT could be replaced with a human blood cell test that detects all types of biological pyrogens.
Publication: Borton, L; Coleman, K. 2025. “Material-mediated pyrogens in medical devices: Myth or reality?” ALTEX – Altern. Anim. Ex. doi: 10.14573/altex.2504231.