FDA has set a November public meeting of the Immunology Devices Panel Advisory Committee and released a 149-page paper to discuss biological responses to metal implants. The announcements are follow-ups to FDA comments made earlier this year indicating that the agency is taking a closer look at metals used in medical devices, citing growing evidence that a small number of patients may have adverse biological responses to certain types of materials.
FDA’s report acknowledges that metal and metal alloys have been commonly used for medical implants for more than 100 years. It emphasizes that its recent focus on metals has been driven by industry events like metal-on-metal total hips in which metal wear/debris was associated with local pseudotumors and aseptic loosening of devices with the subsequent need for revisions.
FDA’s report is a study of metals that are commonly used in implants. The report, titled “Biological Responses to Metal Implants,” explains the types of metals innately present in the human body, the nonclinical pre-market evaluation of metal implants, the process of corrosion and metal ion release within the body or in contact with other metals, subclinical and clinical responses to metal implants, screening and diagnostic tools and current identified challenges. Orthopedics receives dedicated attention under coverage of corrosion, tissue and organ localization of inflammatory responses to metal implants and specific device areas, the latter of which mentions hip and knee replacement data.
In introducing the chapter on challenges, FDA notes “Gaps exist in both our knowledge base and the available tools that are necessary to understand and assess biological responses to metal implants in clinical and regulatory contexts.”
FDA cites the following fundamental challenges:
- The mechanisms underlying the biological responses to metal implants are not fully understood. Because of this, it is difficult to distinguish between the device- and patient-related factors in addressing safety and effectiveness concerns. Overcoming this challenge is necessary to help manufacturers design appropriate pre-market studies and develop appropriate acceptance criteria. Regarding testing, there are only a few validated tests that assess adverse responses to metal implants and there is no clear evidence or agreement on how these tests should be used for clinical and regulatory decisions.
- Scientists, clinicians and regulators do not use common terms and definitions. The term “metal allergy” is often used when discussing several different immunological responses to a foreign substance, many of which may have minimal or no involvement of true allergic reactions.
- Detection of subtle but consequential biological responses that may indicate a potential safety concern during post-market device monitoring
These challenges suggest FDA’s focus on the topic moving forward. The agency alluded to some discussion around these challenges will take place at the November 13-14 meeting in Gaithersburg, Maryland. (It will also be webcasted.) One purpose of the Immunology Devices Panel Advisory Committee meeting is to discuss advances in the scientific community’s understanding of immunology and ways that related emerging and evolving data can address risks to patients. The panel will also evaluate potential gaps in current scientific knowledge to determine future studies to strengthen steps to mitigate risks.
The release of the report and panel meeting topics indicate that discussion about adverse biological responses around metals will continue for some time.
Heather Tunstall is an ORTHOWORLD Contributing Editor.