Device Implants Need Better Labels, Advisers Tell FDA
Link: https://www.medpagetoday.com/publichealthpolicy/fdageneral/83375?fbclid=IwAR2vISQtdSVCxiii95R_lA_yz6SYV6YWecfek7_Q60hlvf3IgSxG1d7yvRs
by Mary Jo M. Dales, Contributing Writer
GAITHERSBURG, Md. -- Improved declarations of the types of metals contained in specific implant materials and devices emerged as one of an FDA advisory committee's major recommendations.
Meeting here Wednesday and Thursday, the agency's Immunology Devices Panel of the Medical Devices Advisory Committee met to discuss and recommend solutions for problems associated with metal-containing implants, including but not limited to dental amalgam.
The fact that all contents of devices aren't spelled out in their labels was mentioned as problematic in expert and public testimony during the panel's meeting. Without knowing the precise components in a given implant or device, one cannot troubleshoot the source of an adverse event, presenters said.
"The panel is happy to say that industry in general and the panel in general support declaration of the composition of all these metal devices," Raj Rao, MD, panel chair, said in his summary comments. Also, "the panel generally feels that we need improved preclinical testing of devices that are to be placed in the body."
The panel's charge was to examine risks associated with an ever-increasing number of implanted devices, especially in regard to joint and hip replacements and the use of mercury-containing dental amalgams. While reactions to implanted devices are proportionally rare, the sheer number of hip, knee, cardiac, and other surgically implanted devices has been steadily increasing. Additional information on metal-containing devices, implants, dental amalgam, and metal in the body at large is needed, panel members concluded.
The best way to proceed to get this information is unclear, Rao said. Registries and longitudinal cohorts of some type may be helpful. On the flip side, the statistical rarity of these incidents also creates another opportunity where we may be able to get more information by studying isolated incidents where there have been failure, or some type of response, rather than studying the population at large.
"So there's two approaches: either identifying the problem areas and attack[ing] them with more intensity, or studying the population at large," he said. Retrieval studies and tissue and blood testing in patients who have had failures or immune responses may be another area of focus and study.
While metal components of the devices have been spotlighted for attention, "we've got to move beyond just mechanical corrosion testing to electrochemical corrosion testing as well, and possibly look into the role of biological tissues in speeding up or contributing to corrosion in some way," said Rao, professor and chair of orthopedic surgery at George Washington University in Washington.
"The panel feels that successful outcomes of procedures where devices are implanted in the body are multifactorial in their etiology. And success depends not just on the patient but it depends on the device. It depends on the surgeon. It depends on the technique used. And it depends on a number of mechanical properties of the device, in addition to immunological or other such processes," he said.
Because so much remains unknown about the reasons for adverse reactions to implants, the panel found it difficult to give the FDA any more clarity regarding the utility of available diagnostic and prognostic tests for pre- and post-procedural patient assessment or management of such reactions.
The validity of immune response testing either before or after surgery needs further study, Rao said. "I think the panel generally feels that a local inflammatory/immune response clearly occurs. There's also some question that a systemic immune response may occur. But it does not appear that we have the scientific weight of evidence or a scientific process that would clearly help us better understand the mechanism."
The committee did recommend that handling of patients' samples for immune response testing be standardized so the results are comparable.
The panel said prospective data preoperatively, then longitudinally postoperatively, would eventually provide better information on outcomes for patients who have joint replacements and implants. Because of the length and magnitude of this process, a federal body like the National Institutes of Health would need to be involved. It's unclear whether patient registries alone would have the depth and longitudinal information on the survival of these patients to provide these answers, the panel concluded.
Environmental triggers may predispose some patients to having a heightened response to a metal implant. "I don't think we have data at this time as to say what those environmental triggers may be, or what the predisposition of an individual patient will be to develop a heightened response to a metal implant," Rao summarized.
The panel generally determined that multiple device-related factors affect an individual patient's response. The extent of wear debris generated by the alloy composition, changes in the implant's microstructure, and how contact with other substances varies may all play a role.
Packaging should list the specific elemental compositions of each device, the panel recommended. Aron Yustein, MD, of the FDA, said the agency has already started to do that in other product areas such as breast implants.
Dental amalgam
Information reviewed at the meeting on risks of dental amalgam, said Rao, "confirms what was previously known and tends to move the needle a little further." Mercury-containing amalgams are a risk to the environment, patients, and potentially to the dentists who insert them. But an evidence gap remains about the life cycle of mercury in the body and environment.
"I don't think there has been any clear understanding of a quantified increase in risk," Rao said. But, he added, "the general direction should be to move away from using mercury-containing amalgams and towards nonmercury-containing products to deal with dental restorations," Rao summarized.
The panel generally agreed that knowledge has improved in distinguishing the role of mercury from dental amalgam versus seafood consumption and the health effects of inorganic mercury versus methylmercury, as well as the process of conversion between methylated and non-methylated form of mercury. However, current testing for mercury doesn't clearly distinguish the different types, so there's not enough information to determine the toxicity of one type versus the other or the relative content of one type versus the other in humans or in the environment.
The general public has largely not been told that potential risks associated with dental amalgam aren't clear, especially for children and other vulnerable subgroups. "The other significant gap is that the risks of removal of these amalgams are not entirely known," Rao said.
In the panel discussion of this issue, Mark Dykewicz, MD, professor of allergy and immunology at St. Louis University in Missouri, expanded on the concerns about possible additive effects of mercury neurotoxicity and other heavy metals. People, often underprivileged, are living in environments where they're exposed to lead plus mercury, he said.
"I think it's unconscionable that Medicaid children in some states are forced to get amalgam and may not be offered alternatives in an informed consent with their parents," he said. "Do we wait to see that there are neurocognitive problems before we take some action?"
Dykewicz said the U.S. should follow the Canadian model and avoid amalgam fillers as much as possible.
"I'll speak for myself and say that the evidence is there" to indicate dental amalgam isn't fully safe, added Melissa McDiarmid, MD, professor of medicine at the University of Maryland in Baltimore.
"We're not talking about digging amalgams out of people's mouths, but we need to stop planting them in particularly vulnerable populations" including children, pregnant women, and breastfeeding women and people who are already exposed to other neurotoxicants because of where they live.
Stephen Badylak, DVM, PhD, MD, professor of surgery at the McGowan Institute for Regenerative Medicine, University of Pittsburgh, commented that if dentists could buy alternatives to amalgam at lower cost, "this wouldn't even be a discussion."
He cautioned that risk communication to the public "needs to be cross-agency with very clear instruction to professionals and patients" to start to bend away from amalgams without inciting a panic to take out amalgams.
"Maybe, just thinking aloud, the FDA announcements for fish and for mercury levels in fish could be revisited to make that a more comprehensive announcement of the overall potential effect from mercury, from fish, from dental amalgams, and from the environment at large. That could be something to look into," noted Michael Weisman, MD, professor and chair in rheumatology at Cedars-Sinai Medical Center, West Hollywood, California.
