The focus of the DG is on the technical assessments that should be included in any regulatory submission for a device made of Nitinol. In broad terms, these recommendations go beyond merely designating that the material is Nitinol. General information to be provided includes material composition, manufacturing, pseudoelastic and shape memory behavior, and transition temperatures. It is noted that each of these is variable and can be adjusted by the device manufacturer to achieve specific performance.
Recommendations on mechanical testing include both experimental and computational considerations. Here, the emphasis is on selecting and conducting tests that properly capture the clinical application. For example, it is noted that orthopedic staples may be extended prior to implantation and, therefore, it is recommended there be a preconditioning step prior to mechanical testing. It is also recommended that fatigue testing take place in phosphate-buffered saline and not in air. For computations, it is recommended that care be taken in selecting constitutive equations and the effects of stress/strain history.
The recommendations for corrosion testing emphasize that Nitinol’s corrosion susceptibility is dependent on the manufacturing and surface finishing processes used to make the device as well as potentially its geometry. In this regard, the FDA recommends testing should be performed on devices in final finished form after subjecting the device to preconditioning that simulates device implantation. This observation reflects the renewed emphasis on all material properties being a function of device design and manufacturing rather than being a function of only the raw material. It is also noted that corrosion can release nickel ions as well, resulting in mechanical compromise. Nickel is of concern because of allergic reactions in some people.
Biocompatibility testing is to follow the FDA's ISO 10993 guidance3. In addition to the usual biocompatibility considerations, there is emphasis here also on the potential effects of nickel ion release. The potential for nickel allergy reactions also results in a call for the following warning statement: “Warning: This device contains nitinol, an alloy of nickel and titanium. Persons with allergic reactions to these metals may suffer an allergic reaction to this implant. Prior to implantation, patients should be counseled on the materials contained in the device, as well as potential for allergy/hypersensitivity to these materials.”
As always, a DG is subject to an open-ended comment and review period, after which a Final Guidance might be issued with or without changes from the draft. While guidance documents are not regulations or requirements, they create a strong impetus to follow them, or to be prepared to justify why you didn’t.
FDA’s increased emphasis on materials, as seen in this DG, may see additional guidances for other specific materials or applications. These will either increase or decrease the compliance burden depending on what practices were being followed and accepted prior to any such guidance being issued.