The U.S. FDA has announced plans to modernize the regulatory framework pertaining to the review of certain medical device materials. According to a statement from FDA Commissioner Scott Gottlieb, MD, and Jeff Shuren, MD, director of the center for devices and radiological health, the FDA will be more closely evaluating the potential for certain materials to cause immune/inflammatory reactions in a small number of patients to improve understanding of materials, help uncover ways to identify patients predisposed to these reactions, and improve the overall safety and performance of medical devices.
“This is part of our continuing effort to advance opportunities for enabling modern materials to improve the performance of medical devices while also advancing our assurance of safety for these products,” Gottlieb and Shuren say. “We look forward to providing updates about our progress and ongoing research. We believe our continuing efforts will ultimately provide patients and doctors with better access to more effective and safer medical devices.”
The FDA’s statement notes that the United States is an unprecedented era of innovation in medical devices with advances in materials science that have led to technological breakthroughs such as the 3D printing of medical devices, continuous glucose monitoring patches for diabetes, and miniaturized brain implants to treat epilepsy and Parkinson’s disease. The vast majority of patients implanted with medical devices have no adverse reactions. The device works and performs as expected to treat medical conditions or help patients better manage their health.
However, a growing body of evidence suggests that a small number of patients may have biological responses to certain types of materials in implantable or insertable devices. For example, they develop inflammatory reactions and tissue changes causing pain and other symptoms that may interfere with their quality of life.
Materials used in today’s medical devices vary as widely as the devices themselves—whether the material is metal, plastic, silicone, an animal-derived product or some combination of these. Because, in the case of implantable or insertable devices, these materials come into contact with tissue or other parts of the body for sometimes extended periods of time, the FDA does a careful evaluation during the premarket review 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 unacceptable.
These steps help to address any risks that may be posed by, for example, the potential presence of harmful chemicals or materials that might trigger allergic or other adverse reactions in some individuals. While such testing generally has been a reliable predictor of a material’s safety, the FDA also recognizes the importance of advancing the science to evaluate device materials and patient risk factors both before and after devices enter the market to assure the optimal reduction of risks to patients and maximize benefits.
Once a device is on the market, the FDA has a number of tools in place to monitor a device’s benefit-risk profile as it is used in a real-world setting. These actions include working with companies to recall and correct issues that arise postmarket, issuing safety communications or other updates for health care providers or patients about safe use of devices, requiring boxed warnings or contraindications be added to labeling, requiring postmarket studies, and up-classifying devices to allow us to regulate them more stringently, as we did with metal-on-metal total hip replacement devices.
They are also working to fully implement the National Evaluation System for Health Technology (NEST) that will link and synthesize data from different sources including clinical registries, electronic health records and medical billing claims; this will help improve the quality of real-world evidence that will empower the FDA to more quickly identify, communicate and act on new or increased medical device safety concerns.
“Our understanding of medical technologies evolves over time,” Gottlieb and Shuren note. “As we learn more about long-term effects of materials and as materials science advances and new innovations become a reality, it’s imperative our regulation of devices evolves along with these advances to ensure patients are protected.”
Based on evaluation and discussions with experts elsewhere in the government and academia, the FDA believes the current evidence, although limited, suggests some individuals may be predisposed to develop an immune/inflammatory reaction when exposed to select materials.
The symptoms some patients experience may be limited to the region where the device is implanted or may be more generalized. Symptoms include but are not limited to fatigue, rash, joint and muscle pain or weakness. Although uncommon and varied, these symptoms may share common underlying immune/inflammatory pathways and mimic more well-established inflammatory conditions.
In the small subsets of patients who have reported these symptoms, the symptoms may not develop for several years following implantation. As a result, they may not be detected even in larger and longer clinical studies. To date, these symptoms have not been reported with most materials used in medical devices, including most metals. Moreover, when reported, they have tended to be limited to small subsets of patients.
As an example, some patients, mostly with a history of pre-existing allergies, may develop allergic skin lesions with certain device use. This risk is usually identified by patch testing for potential device material-related allergens. However, not all device-related reactions are allergic in nature. Therefore, the utility of skin patch testing is limited.
Enhancing the collective understanding of materials science could lead to identifying materials that may cause an exaggerated response in sensitive individuals and advance the development of safer materials. Development of new tests to identify at-risk patients would help ensure they do not receive implantable devices that contain the material to which they are sensitive, therefore further enhancing patient safety and advance a precision medicine approach to the selection of device interventions.
“It’s clear more work needs to be done,” Gottlieb and Shuren say. “To this end, we’re undertaking a broad effort to engage the public, scientists and industry stakeholders to gather information and help us determine the current state of the science, critical gaps in the existing science that need to be addressed, what approaches should be considered to further our understanding of medical device materials and improve the safety of devices for patients.
The FDA’s statement includes developments to regulations that will apply to breast implants, metals and nitinol in devices, metal-on-metal total hip replacement devices, and animal materials in devices, as well as the next steps in the process.
For further information, read the complete statement from the FDA.
“We’re seizing the chance to make a generational change in the framework for 510(k) reviews–one that advances its best features while making sure it keeps pace with modern innovation,” states the Agency. “In the coming weeks, we’ll provide additional updates on the status of our Medical Device Safety Action Plan and describe further steps we’re taking to promote patient safety. We’re proud of the work CDRH staff is doing to make sure that the devices we regulate are safe. We’ll continue to take new actions to strengthen the device program for the years to come.”