Material-mediated pyrogens in medical devices: Applicability of the in vitro Monocyte Activation Test_suppl

Abstract

response. Therefore, this definition excludes substances such as endogenous signaling molecules (i.e., cytokines and prostaglandins), fungi, yeast, viruses, bacteria, and parasites. While these substances are known to be pyrogenic and may potentially come into contact with a medical device under contaminated processing conditions, the application of Good Manufacturing Practices is typically very effective at mitigating this risk.The International Organization for Standardization (ISO) developed and published the globally-harmonized ISO 10993 standards for evaluating the biocompatibility of medical devices. Regulatory agencies require that medical devices be tested for material-mediated pyrogenicity in accordance with ISO 10993-11:2017 Biological evaluation of medical devices -Part 11: Tests for systemic toxicity. Although the ISO 10993-11 standard is widely accepted, it has significant gaps. ISO 10993-11 lists substances known to induce pyrogenicity but does not include citations that provide evidence of their in vivo febrile response. Furthermore, the listed substances are rarely found in medical device materials or processing aides.In order to address information gaps in ISO 10993-11, this article will review the literature that identifies known pyrogenic