FDA to launch scientific review of implant biocompatibility, following patient reactions to certain materials

The FDA has begun to re-evaluate the state of the science around the materials used in long-term medical implants, pointing to a growing body of evidence that suggests a subset of patients may be predisposed to painful responses to the devices.

While the vast majority of patients have no adverse reactions to implants constructed of metal, plastic or silicone, the agency said some may still develop inflammatory responses and tissue changes several years following the initial procedure, with symptoms that might not occur until long after a clinical study.

Those symptoms, both local and generalized, can include fatigue, rash and muscle and joint pain, mimicking more well-known immune system conditions.

Symptoms have not been reported with most materials, including most metals—however, some patients with a history of pre-existing allergies have developed skin lesions while using certain devices, the agency said, and cautioned that not all device-related reactions are allergic in nature.

“It’s clear more work needs to be done,” wrote FDA Commissioner Scott Gottlieb and CDRH Director Jeff Shuren in an agency statement. “Enhancing our 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.”

This could include working to develop new tests to identify at-risk patients, modernizing the FDA’s review of medical device materials, issuing safety notices, and working with companies to recall and correct issues after devices are on the market, Gottlieb and Shuren said.

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Certain classes of devices may also undergo deeper scientific evaluations. Last month, the FDA reported that it has seen a jump in the number of cases of a rare type of cancer linked to silicone breast implants, which the agency has been tracking for years.

Specifically, the FDA said more cases of anaplastic large cell lymphoma, a rare type of non-Hodgkin's lymphoma that develops in the scar tissue surrounding a breast implant, have been confirmed in patients with textured implants compared to smooth ones, however the agency said it does not yet have enough definitive evidence of an association. The FDA is hosting a two-day advisory committee panel meeting later this month on its ongoing assessment of breast implants and long-term health effects.

In addition, Gottlieb and Shuren said they believe there’s a need to evaluate particular metal devices, including now-infamous metal-on-metal hip replacements—which have been the focus of thousands of international lawsuits against manufacturer Johnson & Johnson and its subsidiaries—as well as Bayer’s discontinued permanent birth control device Essure, made of coiled wire consisting of multiple metals, including nitinol and stainless steel.

Bayer and the FDA recently extended a postmarket study of Essure from three up to five years, and the agency called for additional blood testing to detect signs of immune responses.  

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Meanwhile, the use of the nickel-titanium alloy nitinol has increased, particularly in the construction of stents, guidewires and other devices used in minimally invasive procedures, due to its flexible properties, according to the FDA. The agency said it plans to publish a new draft guidance on the use of nitinol in the next few months.

And while there are no longer any approved metal-on-metal hip replacements marketed, they still remain implanted in people’s bodies. New interim results from FDA surveillance studies show significantly higher blood levels of metal ions, including cobalt and chromium, which can leach out of the implants over time as the parts rub together.

While not unexpected, some patients had higher blood levels with no symptoms, compared to some with severe symptoms with lower ion levels, the agency said.

An additional advisory panel meeting this fall will explore hypersensitivity to nitinol and other metals in devices, and the FDA also plans to publish a white paper summarizing the current scientific knowledge in the biocompatibility field.