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 4 0.5 µg/kg/day, it is important to stress that this value is not protective against local effects of nickel exposure nor does it protect against nickel hypersensitivity. As there is no known lower limit of nickel exposure for eliciting an adverse reaction, the guidance recommends a warning label be included to counsel patients on the materials contained in the device, as well as potential for allergy/hypersensitivity to these materials. This recommendation aligns with feedback on patient communication received from the Nov. 13-14, 2019 Immunology Devices Panel of the Medical Devices Advisory Committee meeting[9]. RESEARCH SUMMARY The regulatory science-based research at the FDA’s Office of Science and Engineering Laboratories (OSEL) at the CDRH has focused on addressing key gaps in our understanding of the performance of medical devices containing Nitinol, especially with regards to durability and corrosion (Fig. 3). One of the key unknowns was whether the manufacturing process for Nitinol could influence its corrosion susceptibility and in vivo performance. Corrosion susceptibility assessments were combined with surface characterization to validate the appropriateness of acceptance criteria for corrosion resistance and their clinical relevance[10]. The impact of pre-strain on fatigue life[3] and whether the presence of fatigue[11] or fretting damage could impact the corrosion susceptibility[12] was also assessed. Least burdensome test methods to predict Ni ion release fromNitinol basedmedical devices using a shorter timeframe[13] were also studied along with computational models to predict Ni ion diffusion into theperi-implant tissue todetermine local andsystemicnickel exposure[14]. Novel digital image correlation techniques were also developed for characterizing strain at the micro level to better validate Nitinol computational models which may improve future fatigue performance predictions[15]. The impact of applied potentials on fatigue life was studied and an electrochemical technique to monitor fatigue processes in real time was developed[16]. The effect of test specimen surface area on the measured pitting corrosion resistance was also explored[17]. Ongoing work at OSEL focuses on evaluating in vitro to in vivo correlation for Nitinol performance, the impact of reactive oxygen species on corrosion resistance, and how test environment conditions used for bench testing can impact device performance. CDRH is also collaborating with the standards community to evaluate the fatigue to fracture methodology for medical devices containing Nitinol. To summarize, the research efforts at OSEL strive to develop least burdensome pre-clinical engineering test methods to enable safe and reliable medical devices containing Nitinol to reach the U.S. market quickly. CLOSING THOUGHTS Nitinol’s unique shape memory and pseudoelastic behavior have allowed for a number of innovations in medical devices. However, these same properties and behaviors can make the assessment of devices containing Nitinol more involved than when other materials are used. Although the FDA’s guidance “Technical Considerations for Non-Clinical Assessment of Medical Devices Containing Nitinol” elucidates critical considerations for Nitinol characterization, additional technical considerations may apply depending on the specifics of the medical device and/or patient population. ~SMST For more information: Matthew Di Prima, materials scientist, U.S. Food and Drug Administration, 10903 New Hampshire Ave., WO62 Room 2124, Silver Spring, MD 20993, 301.796.2507, matthew.diprima@fda.hhs.gov. References 1. Available at https://www.fda.gov/regulatory-information/ search-fda-guidance-documents/technical-considerations- non-clinical-assessment-medical-devices-containing-nitinol. 2. Wagner, et al., Structural Fatigue of Pseudoelastic NiTi shape Memory Wires, Materials Science and Engineering A, Vol 378, p 105-109, 2004. 3. A.R. Pelton, J. Dicello, and S. Miyazaki, Optimization of Processing and Properties of Medical Grade Nitinol Wire, Minimally Invasive Therapy & Allied Technologies, Vol 9, No. 2, p 107-118, 2000. 4. S. Gupta, et al., High Compressive Pre-strains Reduce the Bending Fatigue Life of Nitinol Wire, Journal of the Mechanical Behavior of Biomedical Materials, Vol 44, p 96-108, 2015. 5. K. Senthilnathan, et al., Effect of Prestrain on the Fatigue Life of Superelastic Nitinol, J Materials Engineering and Performance, Vol 28, Nov. 2, 2019. FEATURE Fig. 3 — Nitinol fatigue fracture surface after 29 million loading cycles. Fatigue striations from crack growth can be seen on the left while the dimpled region on the right is indicative of the final tensile overload. 6
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