Pyrogen Testing of Medical Devices

In September 2018, the PETA Science Consortium International and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) co-organized a workshop to discuss in vitro approaches for medical device pyrogen testing.

Pyrogens are a diverse group of substances and materials that can produce fever when introduced to the body. Medical products for implantation or injection must be shown to be free of pyrogens before they can be marketed. The pyrogen tests commonly used to meet regulatory testing requirements—the rabbit pyrogen test (RPT) and the bacterial endotoxin test (BET)—are performed using rabbits or haemolymph derived from horseshoe crabs, but non-animal replacements are available.

The workshop focused on the use of the monocyte activation test (MAT) as a standalone release test for medical devices that can replace the use of the RPT and the BET when satisfying biocompatibility and sterility testing requirements. Scientists and regulatory authorities from government and industry reviewed the MAT and discussed ongoing challenges. Participants also described industry experiences with the MAT and identified hurdles to its implementation.

A central element of this workshop was exploring the U.S. Food and Drug Administration Center for Devices and Radiological Health (FDA CDRH) Medical Device Development Tools (MDDT) program. This program allows device sponsors to qualify in vitro methods for use within a defined context of use as a replacement for animal-based tests used by the agency to approve medical device products for marketing. Workshop participants explored the process of developing an MDDT proposal to qualify the MAT as a replacement for the RPT and/or BET with input from FDA CDRH attendees.

Workshop agenda

Workshop presentations

Introduction and Overview: Monocyte Activation Tests Thomas Hartung, Johns Hopkins Center for Alternatives to Animal Testing
The FDA MDDT Program and Considerations for MAT Testing of Medical Devices Molly Ghosh, FDA/CDRH Biocompatibility Standards Task Group
Material Mediated Pyrogenicity and ISO/TC 194 Standards Anita Sawyer, International Organization for Standardization
Technical Committee 194
Alternate Pyrogen Tests Radhakrishna Tirumalai, United States Pharmacopoeia
Material-Mediated Pyrogens in Medical Devices Kelly Coleman, Medtronic
Pyrogen Detection on Medical Devices Anja Fritsch, Confarma
Monocyte Activation Test: A Relevant Alternative Tool for Medical Device Development Djikolngar Maouyo, PyroDex Testing
Monocyte-Activation-Test as a Pyrogen Test for Medical Devices Walter Zwisler, Zwisler Laboratorium GmbH

Supplemental information 

Pyrogen testing guidance and standards

FDA CDRH MDDT Program

Additional publications

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