Metals and metal alloys are commonly used in implanted medical devices and in inserts like amalgam dental fillings, and these materials are sometimes in contact with parts of the body for extended periods of time. Part of the FDA's evaluation to determine whether a medical device is safe and effective involves reviewing information about metals and other materials used in the device.
On This Page
- Concerns About Immune Responses to Metal in Medical Devices
- Metal-Containing Implants
- Dental Amalgam
- Determining Medical Device Material Safety
- More FDA Information on Metals in Medical Devices
The FDA has heard concerns raised by patients and other device users, and we have received adverse event reports that note biological responses to certain metals used in medical devices. Based on our evaluation, we believe the current evidence, although limited, suggests some individuals may be predisposed to develop a local or systemic immune or inflammatory reaction when exposed to certain metals contained in select implantable devices.
The symptoms some people have noted may be limited to the region where the device is implanted or may be more generalized. Reported systemic symptoms include fatigue, rash, joint and muscle pain, and weakness. Although uncommon and varied, these symptoms can sometimes mimic more well-established inflammatory conditions, such as systemic lupus erythematosus.
The science around immunes response to materials in medical devices is expanding and furthering this science to improve patient treatment options and outcomes is a priority for the FDA. Lab tests commonly used to diagnose allergy-based sensitivities may not be adequate to identify susceptible individuals. To better understand how a patient responds to materials used in medical device implants and harness that information to improve the safety of devices in patients, the FDA is working to engage the public—in particular, scientists, patients, and health care providers—and industry stakeholders to determine the current state of the science, critical gaps in the existing science, and what approaches the FDA should consider.
The most common metals and alloys used in implants include stainless steel, cobalt-chrome alloy, titanium, and nickel-titanium alloy (nitinol). Other metals, such as gold, platinum, silver, iridium, tantalum, and tungsten, are also common in many medical devices.
Building on prior work and steps outlined in the Medical Device Safety Action Plan announced in 2018, the FDA conducted a comprehensive review of metals used in medical devices, due to concerns raised by patients and reported adverse events potentially related to biological responses to certain types of materials in medical devices. This is part of a broader review of the use of select materials in implantable devices.
The FDA announced, in September 2019, a paper on biological responses to metal implants. This paper presents the FDA's review of currently available scientific information related to metals and their use in medical implants. The paper focuses on how metal materials are impacted by a physiological environment, expected and potential toxicologic and immune system responses to the metal associated with an implant, as well as subsequent clinical manifestations. Just as importantly, this paper identifies where gaps and opportunities for further research exist in the current scientific evidence related to immunological responses to metal-containing implants.
Dental amalgam is a dental restorative material used to fill teeth damaged by tooth decay. Dental amalgam is a metallic compound consisting of liquid elemental mercury and a powdered alloy composed of silver, tin, copper, and other metals. The FDA announced, in September 2019, a paper on Epidemiological Evidence on the Adverse Health Effects Reported in Relation to Mercury from Dental Amalgam. The paper evaluates current medical literature related to neurological, cardiovascular, developmental, and other outcomes in populations exposed to dental amalgam and assesses the totality of the available evidence that includes prior assessments of dental amalgam conducted by the Agency. The FDA is interested in stakeholders' perspectives on our recent review, and any other new information, to help inform our understanding of the current benefit-risk profile of dental amalgam.
As part of premarket submission requirements, medical device manufacturers must submit information, such as biocompatibility data, to the FDA to show that the materials they plan to use in their device can safely be implanted in the human body. The data may include test results from engineering, bench, design verification, human factors, and animal testing, and clinical studies.
Part of the FDA's evaluation of the safety and effectiveness of a device involves reviewing information about the materials used in the device.
Medical device companies assess the biocompatibility of a material by testing how the human body responds to the material they plan to use in their device. This biological evaluation of medical devices is performed to determine if there is a potential adverse biological response resulting from contact of the device's component materials with the body and whether the associated risks are acceptable. The FDA recognizes the international standard ISO 10993-1, "Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process," which provides information on evaluating the biological response to medical devices, such as considering the physical and chemical characteristics of device materials and the nature, degree, frequency, and duration of device exposure to the body. However, the current international standard approach to biocompatibility testing is not designed to identify individuals who are likely to experience an inflammatory reaction to a particular metal because this risk and its clinical manifestations had not been well recognized in the past.
In addition, engineering testing is routinely done to evaluate the potential for metal wear and corrosion of a specific device through different possible mechanisms.
The FDA regularly conducts thorough reviews of the latest scientific evidence. We continue to find that most patients experience no adverse health effects from these metals interacting either locally where the devices are implanted or systemically throughout the body. However, after carefully reviewing the current scientific literature, reports in our public adverse event database as well as findings from post-approval and postmarket surveillance studies, we believe there's a need to evaluate through a comprehensive process concerns that were brought to light with particular devices, such as metal-on-metal total hip replacement devices and the permanent birth control implant Essure, a coiled wire that's composed of multiple metals, including nitinol (a nickel and titanium alloy) and stainless steel.
These efforts are just a few aspects of our ongoing evaluation of the effects of materials in at-risk patients. Our goal in taking these steps is to ensure that the benefits of devices made of metal materials continue to outweigh their risks. For the vast majority of patients this is the case and will remain the case as we go through these steps. However, for certain small subsets of patients who exhibit sensitivities to select materials, we must determine what additional actions we should take to make sure they are protected and understand the unique risks they may encounter.
- November 13-14, 2019: Immunology Devices Panel of the Medical Devices Advisory Committee Meeting
- Statement on continued efforts to evaluate materials in medical devices to address potential safety questions (September 2019)
- FDA Statement on Efforts to Evaluate Materials in Medical Devices to Address Potential Safety Issues (March 2019)
- Medical Device Safety Action Plan
- Metal-on-Metal Hip Implants
- FDA Activities: Essure
- Dental Amalgam
- FDA Office of Women's Health (OWH)-Funded Research: Medical Device Safety