On February 17, 2022, the American Chemical Society released a publication on behalf of the U.S. Food and Drug Administration (FDA) describing the current state and opinion of the FDA regarding chemical characterization processes and ways in which to improve them. In particular, the FDA’s response is intended to examine specific topics to promote continuous discussion regarding the disparities between where the industry currently stands and how alignment and proper development may occur.
NAMSA invites you to access the full publication by clicking here: Chemical Characterization and Non-targeted Analysis of Medical Device Extracts: A Review of Current Approaches, Gaps, and Emerging Practices.
The developers of medical devices evaluate the biocompatibility of their device prior to the FDA’s review and subsequent introduction to the market. Chemical characterization, described in ISO 10993-18:2020, can generate information for toxicological risk assessment and is an alternative approach for addressing some biocompatibility end points (e.g., systemic toxicity, genotoxicity, carcinogenicity, reproductive/ developmental toxicity) that can reduce the time and cost of testing and the need for animal testing. Additionally, chemical characterization can be used to determine whether modifications to the materials and manufacturing processes alter the chemistry of a patient-contacting device to an extent that could impact device safety.
Extractables testing is one approach to chemical characterization that employs combinations of non-targeted analysis, non-targeted screening, and/or targeted analysis to establish the identities and quantities of the various chemical constituents that can be released from a device. Due to the difficulty in obtaining a priori information on all the constituents in finished devices, information generation strategies in the form of analytical chemistry testing are often used. Identified and quantified extractables are then assessed using toxicological risk assessment approaches to determine if reported quantities are sufficiently low to overcome the need for further chemical analysis, biological evaluation of select end points, or risk control. For extractables studies to be useful as a screening tool, comprehensive and reliable non-targeted methods are needed. Although non-targeted methods have been adopted by many laboratories, they are laboratory-specific and require expensive analytical instruments and advanced technical expertise to perform.
In this Perspective, we describe the elements of extractables studies and provide an overview of the current practices, identified gaps, and emerging practices that may be adopted on a wider scale in the future. This Perspective is outlined according to the steps of an extractables study: information gathering, extraction, extract sample processing, system selection, qualification, quantification, and identification.
During the design of chemical characterization studies, NAMSA strives to recommend the most scientifically-supported approaches. While our teams continue to follow FDA and other international regulatory body guidance for extractable and leachable study design, scientific support is not always aligned with regulatory expectations. NAMSA, heavily involved within these FDA conversations, continues to push for more transparency and consistency from regulators and have requested they provide relevant, contemporary justification for recommendations.
To that end, NAMSA will release its opinion on specific topics of concern discussed by the FDA in the future. We also urge the industry as a whole to do the same: to start open discussions on these topics to help achieve a more consistent and harmonized approach to chemical characterization.
In closing, NAMSA looks forward to the renewal of in-person events where these conversations might take place. We hope to see working groups, on hiatus for the last two years, meet with renewed vigor and express perspectives not yet considered. This will surely help ensure the promotion of the goal of chemical characterization: to reduce the need for time-intensive animal testing and increased patient safety.
How Can NAMSA Help?
NAMSA, drawing from its 50+ year history of offering reliable chemical characterization and analytical chemistry solutions to Clients, provides an extensive range of testing services to help secure product safety, quality and consistency during all stages of development. Our processes are the most trusted in industry and help to efficiently define device components and enable assessment of reproducibility in manufacturing and processing.
To learn more, we invite you to set up a complimentary consultation with one of our experts: https://namsa.com/namsa-expertise/subject-matter-experts/. Or, you may learn more about our testing services here: https://namsa.com/services/medical-device-testing/.
Nicholas Keyes is an Analytical Chemist with a BA in Biochemistry and MS in Environmental Engineering. He has spent over six years in the CRO industry executing, designing, and directing Extractables and Leachables studies for pharmaceutical and medical devices.