A D V A N C E D M A T E R I A L S & P R O C E S S E S | A P R I L 2 0 2 1 5 2 FDAGUIDANCE ONMEDICAL DEVICES CONTAININGNITINOL New FDA guidance for Nitinol used in medical devices includes clarification on the use of computational modeling, as well as corrosion and biocompatibility updates. Matthew Di Prima, David Saylor, Shiril Sivan, and Jason D. Weaver U.S. Food and Drug Administration, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Silver Spring, Maryland On October 15, 2020, the U.S. Food and Drug Administration (FDA) released the guidance “Technical Considerations for Non-Clinical Assessment of Medical Devices Containing Nitinol[1].” While the draft of the guidance was released in April of 2019, the roots of the guidance can be traced back to the 2012 Workshop “Cardiovascular Metallic Implants: Corrosion, Surface Characterization, and Nickel Leaching.” Since that workshop, Nitinol specific considerations were addressed in the 2015 guidance “Select Updates for Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems” and some gaps in regulatory science were addressed through numerous research papers from the Center for Devices and Radiological Health (CDRH). With the increased adoption of Nitinol in non-cardiovascular applications, it became necessary to provide the agency’s thinking on the technical considerations for Nitinol in a broad, non-product specific document. This culminated in the guidance “Technical Considerations for Non-Clinical Assessment of Medical Devices Containing Nitinol,” which contains pre-market submission recommendations covering general Nitinol information, mechanical testing, corrosion testing, biocompatibility, and labeling considerations. CHANGES FROM DRAFT GUIDANCE While the public comment period for the draft guidance was open from April to June 2019, per CFR 10.115(g) (5), FDA guidance dockets remain open indefinitely for public feedback (https://www.regulations.gov/document? D=FDA-2019-D-1261-0002). During the open comment period, FDA received 93 comments from 11 commenters who spanned industry, test labs, and private individuals. While a majority of the comments were editorial in nature, multiple commenters asked about inclusion of the R-phase, clarification of what was intended by “established surface finishes” for Nitinol, and clarification on using computational modeling to predict Nitinol fatigue behavior. While these issues were addressed in the final version of the guidance, no major changes in the document were needed to address the comments, which implied that there was general agreement with the content of the guidance. This was expected, as the content was either in line with or updated from the 2015 guidance; therefore, industry and test houses had several years to understand FDA’s perspective on Nitinol testing. GENERAL INFORMATION The performance and behavior of Nitinol depends on multiple factors spanning material chemistry to heat treatment parameters. To ensure the correct considerations are applied for performance testing, the guidance calls for the material composition, manufacturing processes, expected Nitinol behavior (shape memory vs. pseudoelastic), and transformation temperatures to be provided. While it is anticipated that most Nitinol will conform to a recognized standard (e.g., ASTM F2063), the guidance asks for the material composition and a description of specific properties in cases where it does not. For manufacturing, the guidance asks for a high-level flowchart of the Nitinol manufacturing process from raw material to final device sterilization (if relevant), with special attention given to thermal and surface processes. As transformation temperatures are critical to the behavior and mechanical performance of Nitinol, the guidance asks for key transformation temperatures to be provided based on whether the Nitinol is intended for a shape memory or pseudoelastic application. MECHANICAL TESTING AND COMPUTATIONAL MODELING While mechanical testing on devices made from conventional metals like stainless steel is relatively common and well described in other standards and FDA documents, the unique thermomechanical response of Nitinol necessitates additional considerations to ensure accurate and consistent results. Among these considerations is the test environment, which is typically liquid to represent a physiologically relevant environment and to dissipate any heating effects caused by phase transformation[2]. Given how drastically the stress-strain behavior can vary with temperature[3], in order to ensure clinical relevance as well as consistency in results, the environment should be maintained at a physiologic 8 FEATURE 4
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