Medical Nitinol Shape Memory Alloy Standard

1 Introduction

Shape Memory Alloys (SMA for short) is an alloy material that can completely eliminate its deformation at a lower temperature after heating and increasing, and restore its original shape before deformation. Nickel-titanium shape memory alloy (hereinafter referred to as nickel-titanium alloy) is one of the most widely used shape memory alloys in the medical field. In addition to the shape memory ability, it also has a super-elastic effect. Much larger deformation recovery ability than ordinary metals, that is, the large strain generated during the loading process will recover with unloading [1]. The shape memory function and superelastic effect of Nitinol can effectively meet clinical needs. At present, implants such as covered vascular stents, esophageal stents, bone fixators, and cardiac occluders made of medical nickel-titanium alloys have been widely used in clinics [2-8]. Because of their long-term or permanent implantation in patients, The quality of its products is directly related to the life safety of the people. Therefore, it is allowed to be listed as an implanted medical device at home and abroad after being approved by the regulatory authorities. The standards for medical nickel-titanium alloy materials and implants, as an important technical basis for scientific supervision, have played a major role in supervision. This article analyzes the current status of medical nickel-titanium alloy materials and implant standards at home and abroad, in order to clarify the direction of standardization research in this field.

2 Domestic status

At present, there are 11 domestic special standards for Nitinol shape memory alloy materials and implants, as shown in Table 1. The main standard issuing agencies include the General Administration of Quality Supervision, Inspection and Quarantine (GB standard), the former State Food and Drug Administration (YY standard), and the Institute of Nonferrous Metals (YS standard). Related standards have basically covered the terms, specification requirements and test methods of Nitinol materials and implants.

Medical Nitinol Shape Memory Alloy Standard

Table 1 Domestic standards for Nitinol shape memory alloy materials and implants

3 International status

At present, there are 25 international special standards for Nitinol shape memory alloy materials and implants. See Table 2. The main standards issuing organizations include the American Society for Testing and Materials (ASTM standard), the Japanese Industrial Standards Investigation Committee (Japanese Industrial Standards, also known as JIS standards), Korean Industrial Standards (KS Standards), Brazilian National Standards (ABNT NBR Standards), French National Standard (NF standard). The content of the relevant international standards mainly involves the terminology, specification requirements and test methods of Nitinol materials, especially the method standards reflecting its shape memory function and superelastic effect. However, the contents of the standards issued by different organizations have certain overlaps and overlaps.

Medical Nitinol Shape Memory Alloy Standard

Table 2 International standards for Nitinol shape memory alloy materials and implants

4 Standard analysis in the field of nickel-titanium alloy materials and implants

4.1 Suitability analysis of existing standards at home and abroad

4.1.1 Domestic and foreign standard system architecture

Nitinol implant is an implantable device, so the evaluation of its safety and effectiveness involves a series of general standards and special standards, mainly composed of the following parts:

1) "ISO 10993 Biological Evaluation of Medical Devices" [9] series of general standards for evaluating the biocompatibility of medical devices (have been transformed into "GB/T 16886 Biological Evaluation of Medical Devices" series of standards);

2) "ISO 14630 General Requirements for Passive Surgical Implants" [10] General Standards that regulate the general performance of surgical implants (have been transformed into "YY/T 0640 General Requirements for Passive Surgical Implants");

3) "ISO 14602 Passive Surgical Implants Bone Joint and Joint Replacement Implants Part 1: Special Requirements for Bone Joint Implants" [11] special standards (transformed into "GB /T 12417.1 Passive surgical implants bone joint and joint replacement implants Part 1: Special requirements for bone joint implants) and other special product standards and method standards related to bone joint implants;

4) "ISO 25539-2 Cardiovascular Implants and Intravascular Devices Part 2: Vascular Stents" which regulates the performance of vascular stents [12] Special standards (have been transformed into "YY/T 0663.2 Cardiovascular Implants and Intravascular Devices Section" Part 2: Blood Vessel Stents) and other special product standards and method standards related to cardiovascular implants;

5) Table 1 and Table 2 list the specific standards for Nitinol shape memory alloy materials and implants.

The above five standards together constitute a relatively complete standard system for nickel-titanium alloy materials and implants. The standards contained in this standard system include not only general standards such as the biological evaluation of medical devices and general requirements for implants, but also special standards for specific implants (such as bone cement, vascular stents), and special The special standards for the characteristics of nickel-titanium alloy materials have the advantages of large macroscopic coverage and clear structure. The physical, chemical and biological properties of nickel-titanium alloy materials and implants can be systematically evaluated based on these standards. However, the main disadvantage of this standard system is that it cannot yet fully cover all the items approved by the regulatory authorities, especially the test methods for certain key performances.

4.1.2 The gap between standard requirements and existing standards

As mentioned earlier, nickel-titanium alloy implants are currently subject to regulatory approval before they are allowed to be listed. Therefore, by comparing the approval requirements with the currently issued standards, we can sort out the following performance methods that are required in the approval but are currently not based on standards.

4.1.2.1 Evaluation method of pulsation fatigue performance of Nitinol shape memory alloy occluder

Although the existing occluder standard "YY/T 2053-2017 Cardiovascular Implant Heart Occluder" requires the evaluation of the fatigue performance of the occluder, it does not list the corresponding test methods. There is no similar content in other domestic and foreign standards. Therefore, it is recommended to establish a corresponding fatigue test platform and evaluation method by simulating the biomechanical environment of the cardiac occluder under pulsating conditions.

4.1.2.2 Medical nickel-titanium shape memory alloy material or implantable nickel ion release model

Nickel ion is a kind of heavy metal ion. Excessive intake of nickel can cause central circulation and respiratory disorders, causing edema, bleeding or degeneration of the myocardium, brain, lung, and kidney, and may also increase the incidence of leukemia and cancer. Therefore, testing the release rate and content of nickel ions in the medical nickel-titanium shape memory alloy in the body can directly reflect the safety of its clinical use. However, the in vivo test time is long, the cost is high, and the accuracy of the test results is low (the sample interferes with the experimental results more). Therefore, in the pre-clinical evaluation stage, it is necessary to establish a reasonable in vitro release model. It is recommended to select appropriate simulation instruments, test conditions, test media, and nickel ion test methods according to the implantation time and location of the nickel-titanium memory alloy material and its implant, and establish a nickel ion release model for the implant.

4.1.2.3 Evaluation method of shape recovery ability of Nitinol shape memory alloy implants

At present, there is no unified standard method to regulate different nickel-titanium shape memory alloy implants, and the methods developed by each manufacturer are quite different. Therefore, objectively, it is impossible to compare the pros and cons of the shape memory function of the products of different enterprises, and it is also impossible to guide the survival of the fittest in related products through the unification of technical specifications. It is recommended to select the appropriate in vitro test environment, test conditions, and appropriate shape recovery performance evaluation indicators (such as size, mechanical strength, structural integrity, release performance, etc.) and test methods according to the implant location of the implant to establish the shape recovery ability Evaluation method.

4.2 Comparative analysis of domestic and foreign standards for nickel-titanium alloy materials and implants

4.2.1 Comparison of domestic and foreign standards

By studying the content of the standards, it can be found that a considerable part of the domestic standards are converted from international standards (see section "4.1.1" for details). The existing domestic standards are generally at the same level as the international standards, and the technical content is basically the same. However, in certain fields, my country's standardization work has taken the lead in the world, and has formulated standards that have never existed in the world. For example, the medical device industry standard "YY/T 2053-2017 Cardiovascular Implants and Cardiac Occluders" released in 2017 (which is currently being transformed into an ISO standard) has effectively filled the gap in domestic and foreign standards. This shows that as the proportion of my country's medical device industry in the world is increasing, the standards formulated by my country will also occupy a ratio that is compatible with its output value.

4.2.2 Domestic standards that need to be improved

By comparing the technical content of domestic and foreign standards, it sorts out the relatively mature foreign standards and the performance methods that have not yet been standardized in China. These areas need to carry out standardization work as soon as possible to narrow the gap between domestic and foreign.

4.2.2.1 Evaluation method of galvanic corrosion performance of medical nickel-titanium alloy

At present, YY/T 0695-2008 "Cyclic Potential Polarization Standard Test Method for Corrosion Sensitivity of Small Implant Devices" is mainly used in China to test the corrosion potential of the local corrosion susceptibility of small implants made of nickel-titanium alloy. However, this method cannot reflect the electrochemical corrosion (galvanic corrosion) that occurs between different metal materials. It is recommended to refer to the constant potential method listed in ASTM G71 "Standard Guide for Conducting and Evaluating Galvanic Corrosion Tests in Electrolytes" to establish a galvanic corrosion performance evaluation method for medical nickel-titanium alloys.

4.2.2.2 Test method for phase transition temperature of medical nickel-titanium shape memory alloy

At present, domestically, "YY/T 0641-2008 Standard Method for Measuring Phase Transition Temperature of NiTi Alloy by Thermal Analysis Method" is mainly used to test the phase transition temperature of NiTi alloy materials. However, since this method requires the test sample to be annealed at 800°C before the test, for Nitinol, such a treatment may change the phase transition temperature of the material. It is recommended to refer to "ASTM F2082-2016 Determination of Phase Transition Temperature of Nitinol Shape Memory Alloys by Bending and Free Recovery Tests" to establish a medical Nitinol alloy phase transition temperature test method.

5 Conclusion

This article systematically summarizes the current status of domestic and foreign standards in the field of nickel-titanium shape memory alloy materials and implants. By comparing the relevant product approval requirements and existing standards, we can sort out the performance methods that are required in the approval but there is no standard to be based on. At the same time, through the study of the content of domestic and foreign standards, the domestic standards that need to be improved are analyzed. After comparative analysis, in the field of nickel-titanium alloy materials and implants, China should focus on the evaluation method of pulsation fatigue performance of nickel-titanium shape memory alloy occluders, medical nickel-titanium shape memory alloy in vitro nickel ion release model, and nickel-titanium shape The evaluation method of shape recovery ability of shape memory alloy shall be carried out as soon as possible to standardize research, actively reduce the gap between domestic and foreign standards, and further improve the safety and effectiveness standard evaluation system of nickel-titanium alloy materials and implants, and provide a basis for the quality control of enterprises. The technical review of the regulatory authority provides guidance to better protect the people's safety in using machinery.