Date/TimeAugust 24, 2022
A dramatic shift in regulatory opinions has occurred within the last several years regarding the concepts of Extractables and Leachables (E&L) testing of medical devices, commonly known as Chemical Characterization. Much of that change was driven by the 2020 revision to ISO 10993-18 (Biological Evaluation of Medical Devices – Part 18: Chemical Characterization of Medical Device materials Within a Risk Management Process).
However, at the same time, these opinions are ever dynamic; changing months or weeks apart to mutually exclusive positions. Those non-public positions are so fluid as to occasionally be unknown until a submission has received deficiency notices, even to the point of contradicting pre-submission approvals. By that point excessive time and money have been wasted, and potentially lives impacted in the process of devices not getting to market due to the perceived need for repeat testing.
On the other hand, while Part 18 is a valuable overview of critical study design considerations, it does not (nor could not) encompass all the intricacies of a process that must bridge concepts in toxicology, analytical chemistry and polymer engineering. Considerable decisions are still left up to the industry to justify based on the device-specific indications for use, and those justifications can vary greatly based on relevant, ongoing scientific investigation. This, in turn, leaves open interpretative review by aforementioned regulatory agencies who are challenged with the varying input they receive, both specific to the device and industry-wide.
Join NAMSA for this webinar to learn more about the foundations behind Chemical Characterization and to examine best practices deriving from it. Attendees can expect the following questions to be addressed throughout the webinar:
- Where did the concept of the Threshold of Toxicological Concern (TTC) originate and how was it justified?
- How was the TTC translated through multiple standards to the Dose-Based Threshold (DBT) described in 10993-18:2020?
- Why is exhaustive extraction performed in the context of the TTC?
- What is the FDA opinion on TTC, exhaustive extraction and Chemical Characterization study design?
- What are the challenges and practical limits in exhaustive end-point determination?
- What are the best practices going forward, and what are the practical challenges of meeting these?
Nicholas Keyes, MSPrincipal Chemist/Study Director, Analytical Services
Nicholas (Nick) Keyes is an Analytical Chemist with a BA in Biochemistry from Coe College (Cedar Rapids, IA) and MS in Environmental Engineering from Pennsylvania State University (State College, PA). He has spent nearly 7 years in the CRO testing industry of extractables and leachables in pharmaceuticals and medical devices. Prior to NAMSA, Nick was a bench chemist performing extractables and leachables screening of pharmaceutical products, container-closure systems and manufacturing equipment. He also developed, validated and executed targeted methods for leachables present in long-term stability and simulated use testing of pharmaceutical products. He has continued this work in the field of medical devices at NAMSA, taking on a Study Director role for a multitude of complex products, including bioresorbable and combinatory devices. He has developed and qualified screening methods for extractables and leachables testing (referred to as chemical characterization in ISO 10993-18), including the supporting Relative Response Factor (RRF) databases and Uncertainty Factor (UF) calculations. More recently, Nick has taken on an active role providing support in the regulatory approval process, bringing recent experience of the practical capabilities of methods used in chemical characterization to guide response outcomes.