Workshop: Predictive Models for Acute Oral Systemic Toxicity
In coordination with the ICCVAM Acute Toxicity Workgroup, NICEATM organized a global project to develop in silico models of acute oral systemic toxicity that predict five specific endpoints identified by ICCVAM regulatory agencies. These endpoints included identification of:
The project was sponsored by the ICCVAM Acute Toxicity Workgroup.
NICEATM invited scientists to develop and submit in silico models that predicted any or all of these endpoints. This workshop, convened in April, provided an opportunity for project participants to present their submitted models. NICEATM scientists also presented an evaluation of the rat acute oral systemic toxicity test reproducibility as well as the development of a consensus model that integrates submitted models to generate consensus predictions for acute oral systemic toxicity. Workshop participants also discussed next steps needed to encourage appropriate use of predictive models in regulatory contexts.
Workshop on the Monocyte Activation Test for Pyrogen Testing of Medical Devices
Pyrogens are substances that can produce fever when present as contaminants in a drug or medical device. Most pyrogens are biological substances derived from bacteria, fungi, and viruses; material-mediated pyrogens (MMPs), while less common, might also be present. Drugs for injection and medical device products for implantation or other systemic exposure should meet pyrogen limit specifications before they are marketed. Animal-based pyrogen tests are often conducted to investigate the presence of pyrogens. Non-animal monocyte activation tests (MATs) are widely available but infrequently used for pyrogen testing.
To review the MAT and discuss ongoing challenges to its widespread implementation for medical device testing, NICEATM and the PETA International Science Consortium (PISC) co-organized a September workshop. Meeting participants explored how the FDA Medical Device Development Tools Program could be used to qualify the use of the MAT as a standalone pyrogen test for specific medical device contexts of use. Participants generally agreed that the MAT could be qualified as acceptable for batch-release testing for microbial-based pyrogens; however, additional studies were recommended to demonstrate its ability to detect known MMPs. This testing would determine whether the assay can be used for both biocompatibility and sterility or if other information on MMPs would be needed to address biocompatibility. Participants also discussed information gaps on MMPs, potential test controls, and other challenges and opportunities for implementing the use of the MAT as a comprehensive pyrogen test.
More information about the workshop is available on the PISC website.