Material-Mediated Pyrogens: Myth or Reality? A Risk-Based Approach to Addressing the Endpoint of “Material-Mediated Pyrogenicity” for Medical Devices
Hosted by: SOT Medical Device and Combination Product Specialty Section and SOT In Vitro and Alternative Methods Specialty Section
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The ISO 10993-1:2018 standard provides a roadmap for conducting a preclinical biological safety evaluation of medical devices. The biological endpoints evaluated for a specific device depend on the nature and duration of contact with the patient. The standard recommends that all devices, except surface-contact devices that encounter intact skin or mucosal membranes, be evaluated for their ability to produce material-mediated pyrogenicity (MMP).
MMP is broadly defined in the ISO 10993-11:2017 standard as a "type of pyrogenicity [that] originates from non-endotoxin related factors." Annex G of the ISO10993-11:2017 standard lists 24 substances that are allegedly material-mediated pyrogens (MMPs) in medical devices. This annex recommends the use of the rabbit pyrogen test (RPT) to detect the presence of MMPs on devices and does not provide an option to use in vitro or non-testing alternatives.
This presentation describes the results of a recent investigation to determine whether MMPs exist in a medical device context and whether the RPT could detect their presence if they were on a device. To accomplish these goals, the study evaluated whether the Annex G MMPs are actually pyrogenic, explored whether compounds released from medical devices could exert a hyperthermic response through uncoupling of oxidative phosphorylation (UOP), and reported the results of a recent survey of RPT failures and their root causes.
The conclusions of this effort were (1) MMPs do not exist in a medical device context, but a small number of compounds could theoretically exert a hypothermic effect as UOPs if they were present in high enough amounts on the device and (2) there are no documented examples over the past five years of RPT failures that can be attributed to the presence of MMPs on the device. Based on these findings, the results of the study can be viewed in a risk-based context and used to support recommendations on how this issue should be addressed in standards and guidance documents
Speakers
· Lindsey Borton, MPH, Gradient
· Kelly Coleman, PhD, DABT, ERT, ATS, RAC, Medtronic
· Ron Brown, PhD, DABT, Risk Science Consortium LLC
Registration is required for this free webinar