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Wednesday, August 12, 2026

11:00 am ET / 15:00 UTC

FEATURING:
Lindsey Borton, MPH, DABT, Principal Toxicologist, Gradient

Kelly Coleman, PhD, DABT, Senior Distinguished Toxicologist, Medtronic

ABSTRACTS

Kelly Coleman, PhD, DABT
New Approach Methodologies (NAMs) are reshaping medical device biocompatibility, but progress has been uneven across endpoints and regions. This keynote will examine where NAMs have succeeded, where they remain scientifically or regulatorily constrained, and what is still needed to advance the reduction and eventual replacement of animal testing for medical devices.
Three high‑priority areas that illustrate both the promise and current limitations of NAMs in device biocompatibility will be highlighted: in vitro irritation, material‑mediated pyrogenicity, and in vitro sensitization. Validation studies, ISO 10993 standards, and key regulatory issues will be discussed.
The rabbit skin irritation test was mandated for decades to evaluate device biocompatibility. In 2009, a comprehensive effort began that led to the largest validation study in ISO’s history. This 12‑year program culminated in ISO 10993‑23:2021, which requires the use of reconstructed human epidermis (RhE) tissues instead of rabbits. Difficulties, setbacks, the 2025 amendment, and the trajectory of global regulatory acceptance of RhE data will be covered.
Since 2006, the rabbit pyrogen test has been required by ISO 10993‑11 to screen for material‑mediated pyrogens (MMPs). A recent comprehensive review convincingly demonstrated that MMPs do not exist in medical devices, prompting revisions to ISO 10993‑1 and ISO 10993‑11. Details of these revisions will be presented, along with information on the in vitro monocyte activation test as a potential replacement.

The guinea pig maximization test (GPMT) has been compulsory for over 50 years to evaluate the sensitization potential of medical devices. To replace the GPMT, ISO/TC 194 Working Group 8 has organized a global validation study of in vitro sensitization assays that is now underway. Specifics of this ongoing effort and its implications for future regulatory practice will be provided.

Lindsey Borton, MPH, DABT
For nearly two decades, Annex G of the ISO 10993-11:2017 standard asserted that so-called "material-mediated pyrogens" (MMPs) arise from medical devices and recommended the rabbit pyrogen test (RPT) as the sole detection method. This assumption shaped regulatory expectations, driving routine use of rabbits for a hazard whose scientific basis had never been rigorously established. Our work set out to answer a deceptively simple question: do MMPs actually exist on medical devices, and if not, what is the most scientifically sound strategy for assessing pyrogen risk?

This webinar describes the results of the investigation which consisted of a comprehensive literature review and data manning of extractable chemicals and historical RPT results to demonstrate that MMPs do not appear to represent a meaningful medical device hazard. The outcomes of this effort were twofold: (1) MMPs do not exist in a medical device context. A small number of compounds could theoretically exert a hyperthermic effect as UOPs if they were present in high enough quantities on the device, but they could be detected with analytical chemistry and risk assessment. 2) There are no documented examples of RPT failures attributable to the presence of MMPs on the device; rather, endotoxin and test system incompatibility were identified as the primary root causes of RPT failures. The MAT can detect both endotoxin and non-endotoxin and serves as an in vitro means to detect biological contamination. While the non-animal methods are superior, the ISO standards have not caught up.

ABOUT THE PRESENTERS

Lindsey K. Borton, MPH, DABT, is a Principal Toxicologist and Engineer at Gradient with over 10 years of industry experience in medical device biological safety and risk assessment. At Gradient, she develops strategies for the biological safety assessment of medical devices in support of European, US Food and Drug Administration (US FDA), and other worldwide medical device regulations. Ms. Borton also performs toxicological risk assessments of extractable and leachable compounds for human health risk assessment. She earned her MPH in Regulatory Toxicology and Risk Assessment from the University of Minnesota and her BS in Biomedical Engineering at Michigan Technological University; Ms. Borton is also a Diplomate of the American Board of Toxicology (DABT).

Kelly Coleman, PhD, DABT, is a Sr. Distinguished Toxicologist, Bakken Fellow, and Technical Fellow at Medtronic, where he provides preclinical product development support. He is a U.S. Expert on two working groups (WG) of ISO Technical Committee 194: WG 11, responsible for the medical device toxicology risk assessment standard (ISO 10993-17), and WG 8, which develops the medical device sensitization and irritation testing standards (ISO 10993-10 and ISO 10993-23). Since 2009, he has been involved in New Approach Methodologies (NAMs) validation projects.
Dr. Coleman earned his Ph.D. in Toxicology from the University of Minnesota and is a Diplomate of the American Board of Toxicology, a European Registered Toxicologist, a Fellow of the Academy of Toxicological Sciences, and is certified in U.S. regulatory affairs for drugs and medical devices. He is also a past president of the Society of Toxicology's In Vitro and Alternative Methods and Medical Device and Combination Product specialty sections. In 2024, Dr. Coleman was inducted into the College of Fellows of the American Institute for Medical and Biological Engineering.

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