Medical Device Chemical Toxicological Risk Assessments: Applying Toxicological Principles to Meet the Challenge

Medical device chemical toxicological risk assessment is challenging because the risk assessor often needs to consider the many types of device intended uses, many types of materials used in design and manufacturing, and many types of intentional and unintentional chemicals that are or could be present in the final finished device. Medical device intended uses include the type of tissue contact, the contact frequency and duration, and the susceptibility of the device user to chemical exposure. Material factors include the material type (e.g., alloy, polymeric, ceramic, or natural), material properties (e.g., alloy surface characteristics, polymer plasticity, or polymer manufacturing process), and material chemical composition (e.g., chemical formulation, potent toxicants (if present), and the rate and duration of release). How to apply these considerations is described in the U.S. Food and Drug Administration (FDA) 2023 guidance Use of International Standard ISO 10993-1, “Biological evaluation of medical devices: Part 1: Evaluation and testing within a risk management process,” International Standard Organization (ISO) 10993 series, and ISO 14971. This presentation will describe how chemical toxicological risk assessment fits into the overall medical device biological risk management process (i.e., risk analysis, risk evaluation, or risk control). Additionally, what medical device use and chemical toxicological information to consider from the U.S. FDA 2023 guidance and ISO documents when estimating chemical toxicological risk will be covered, such as: approaches for characterizing the applicable chemical specific harm(s), estimating an exposure dose, deriving a tolerable intake (TI), and other critical factors to consider that could be useful in the determination of whether exposure to a medical device chemical presents a tolerable risk or could present a possible toxicological risk..

Presented by Alan Hood, Toxicologist at the US FDA/CDRH/OPEQ

Dr. Alan Hood is a toxicologist in the Office Product Evaluation and Quality (OPEQ) in the Center for Devices and Radiological Health (CDRH) of the U.S. Food and Drug Administration (USFDA). Dr. Hood provides consultation on chemical toxicological risk assessments, supports exposure and in silico toxicological research projects, and serves as FDA/CDRH Primary Liaison to US AAMI BE Working Group (WG) 11, Co-Chair of US AAMI BE WG11, and Convenor of ISO Technical Committee 194 WG 11 of international experts who develop medical device chemical toxicological risk assessment approaches. Dr. Hood earned his doctorate in toxicological science in 1997 from the University of Kansas Medical Center under the mentorship of Curtis D. Klaassen and completed a postdoctoral fellowship at the University of Dundee, Scotland.  In 2000, Dr. Hood began his career in toxicological risk assessment and regulatory science of food additives, where he developed a tool for estimating daily exposure to these substances. Dr. Hood expanded his toxicological risk assessment and regulatory science expertise in consumer and cosmetic products, commercial cleaning product formulations, and then the biological evaluation of cardiovascular, endoscopic, and urological medical devices. In 2016, Dr. Hood became a member of USFDA/CDRH/OSEL/DBCMS where he participates in regulatory science-based advancements of medical device chemical toxicological risk assessment.

Followed by Sandi Schaible, Executive Director, Analytical Chemistry and Regulatory Toxicology at WuXi AppTec

With over 25 years’ experience, Ms. Schaible is responsible for oversight and direction of WuXi AppTec’s Analytical Chemistry department in St Paul, Minnesota. The analytical staff she manages is responsible for providing custom chemistry testing services including extractables/leachables, materials characterization and target analysis testing, method development, method validation as well as standardized testing including compendial testing. Ms. Schaible received her Bachelors of Science in Chemistry from Winona State University, and has experience working in the pharmaceutical, medical device, environmental and R&D industries, including over 15 years of analytical experience in GLP, GMP, FDA and ISO regulated laboratories. Ms. Schaible provides technical guidance and testing program design, and is an international and U.S. delegate for TC 194, the technical committee for ISO 10993.

Sponsored by WuXi AppTec

WuXi AppTec has a state-of-the-art analytical chemistry laboratory, along with experienced scientists, chemists, and toxicologists, located in St. Paul, Minnesota. Our extractables/leachables team partners with our customers to support product safety with regulatory consulting, pre-clinical testing, and post-commercialization product testing support.  Our regulatory and technical experience with active participation and/or leadership on global committees allows us to anticipate regulatory trends.  Our chemistry program driving principle is complete chemical characterization.  This is our standard of practice as our chemists work closely with our toxicologists to provide the most mass-accurate data and virtually no unknowns in our chemistry reports.  Our technical and regulatory experts advise on test design and strategies for test plans while working closely to account for the product, indication, and patient population.  Furthermore, we stand behind our work – from test plans through clearance – responding to questions or other regulatory requests as part of the submission process.