The Food and Drug Administration (FDA), the US regulating authority, has published guidance describing technical considerations for non-clinical assessment of medical devices containing nitinol. The present document constitutes a final version of the draft guidance issued previously in April 2019. The guidance contains non-binding recommendations to be considered by the medical device manufacturers and other parties involved.
Regulatory Background
The present FDA guidance is dedicated to the medical devices containing nitinol – an alloy of nickel and titanium. This material is widely used in innovative medical devices due to its characteristics – pseudoelasticity and shape memory behavior. It is actively used for cardiovascular devices (e.g. stents, guidewires). According to the document, nitinol becomes more and more actively used in all areas of the medical devices industry. At the same time, nitinol should be treated in another way due to its thermomechanical behavior and processing sensitivity. Thus, the Agency developed the present guidance to address the specific issues associated with the use of nitinol in medical devices. The document outlines certain recommendations to be considered by the medical device manufacturers depending on the intended use of the medical device and its technological characteristics. The scope of the guidance covers any and all medical devices containing at least one patient-contacting component comprised of nitinol.
As it is stated in the document, nitinol is being actively used in medical devices for more than thirty years, and its use faces a significant increase nowadays, especially in medical devices intended for minimally invasive procedures. This material became widely used due to its ability to return to the original shape after being mechanically deformed or after heat is applied. Hence, components of medical devices composed of nitinol could withstand reversible deformations. At the same time, nitinol-containing medical devices require special considerations with regard to safety and effectiveness.
Nitinol-related Requirements and Specifications
The issues related to the manufacturing of nitinol devices are described in the scientific literature. Moreover, the American Society for Testing and Materials (ASTM) has developed the standards to be considered by medical device manufacturers. The aspects covered by the aforementioned standards include the terminology used, specifications for chemical, physical, thermomechanical, and metallurgical properties, and also the test methods to be used to evaluate the transformation temperatures and mechanical properties of the material.
One of the most important aspects associated with the use of nitinol in medical devices is related to corrosion resistance. According to the information provided in the scientific literature, corrosion resistance depends mostly on surface processing. The Agency emphasizes that the in vivo corrosion could lead to additional safety risks (e.g. biocompatibility risks). These issues are already addressed in the present guidance.
In order to harmonize the terminology used in the context of medical devices containing nitinol, the FDA provides the definitions of the most important terms including, inter alia, the following ones:
- Final finished form – a term used for a device or device component that includes all manufacturing processes for the “to be marketed” device including packaging and sterilization, if applicable.
- Shape memory alloy – “a metal which, after an apparent plastic deformation in the martensitic phase, undergoes a thermoelastic change in crystal structure when heated through its transformation temperature range resulting in a recovery of the deformation”.
- Preconditioning (simulated use) – loading, tracking, and/or deployment of test devices, as they would occur in clinical use.
Technical Recommendations for Medical Devices Containing Nitinol
In order to assist medical device manufacturers and other parties involved in operations with medical devices in achieving and sustaining compliance with the applicable requirements, the FDA provides a detailed description of the information to be provided in the context of the premarket submission. According to the general rule, the type of information to be provided depends on the classification of a medical device subject to review under the risk-based classification. In particular, the Agency states that the type and scope of the information to be provided should be determined on the basis of:
- The design of the medical device in question,
- The intended use of the device, and
- Classification of the device.
In case when the device is composed of several types of nitinol simultaneously, the appropriate information should be provided for each type of nitinol separately. Certain recommendations on the information to be provided in the course of premarket submission are also contained in the device-specific guidance documents. The Agency also recommends communicating actively with the Center for Devices and Radiological Health (CDRH).
It is also important to mention that since nitinol is mostly used for manufacturing patient-contacting components of the medical devices, the aspects addressed in the FDA guidance on biocompatibility based on the ISO 10993-1 should be also taken into consideration.
Information to be Provided
According to the document, the composition of the alloy, together with the way the manufacturing processes have been performed would actually determine the further characteristics of nitinol, while the desirable characteristics of nitinol will depend on the design of a medical device and its intended use. The FDA states that in case of prolonged exposure and permanent contacting devices a wide scope of information should be provided, while in case of limited exposure devices the requirements on the information to be provided would be lower. In some cases, it would be sufficient to provide the information on the functional testing performed to satisfy the requirements on the information to be provided in the course of premarket submission. However, if there is device-specific guidance dedicated to the particular medical device in question, the recommendations stated therein should be considered by the manufacturer.
The present FDA guidance on the nitinol-containing medical devices provides the following list of the matters to be covered by the information to be provided by the medical devices manufacturer:
- Material composition. This section should also include the references to the applicable FDA-recognized voluntary consensus standards the manufacturer may use to demonstrate the conformity of the device. At the same time, if the nitinol used in the medical device subject to review does not conform with such a standard, detailed information about its composition and properties should be provided.
- Manufacturing methods and parameters, including heat treatments and surface processing. This information should be also included in the submission due to the significant impact caused by the manufacturing processes on the actual characteristics of the material, and consequently, on the safety of the medical device containing nitinol. In particular, the FDA recommends providing a detailed description of all surface processing steps, including the final post-processing cleaning steps, paying attention to the way they impact biocompatibility of the medical device.
- Pseudoelasticity/shape memory behavior (these aspects are important since the device could be «tuned» to either have pseudoelastic or shape memory behavior).
- Transformation temperature, including the information on phase transformation temperatures of the final finished form.
Summarizing the information provided here above, the FDA guidance on medical devices containing nitinol outlines the most important requirements and recommendations related to the devices composed of the aforementioned material. The document also describes in detail the information to be provided by the medical device manufacturer in the context of premarket submission.
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