Requirement for Pre-Market Approval for New and Existing Device
In January 2013, the FDA published a proposed order to allow for notice and comment regarding the FDA's recommendation to change the requirements for all metal-on-metal (MoM) total hip implants from premarket notification, to premarket approval, the most stringent regulatory category of the FDA's oversight for medical devices. A final order was published in February 2016 and the requirement for filing premarket approval applications was effective in May 2016. Since that time, all manufacturers of MoM total hip implants are required to stop marketing their devices and submit premarket approval applicationss that must be approved before the devices can be marketed. Premarket approval is based on a determination by the FDA that the application contains sufficient valid scientific evidence to reasonably assure that the device is safe and effective for its intended use, and requires manufacturers to apply for the FDA's approval before making changes to the device, its labeling or manufacturing, and imposes certain other annual reporting requirements.
There are no FDA-approved metal-on-metal total hip replacement devices marketed for use in the U.S. There are two FDA-approved MoM hip resurfacing devices available.
Postmarket Surveillance ("522") Studies – Interim Results (as of Dec 2018)
In May 2011, the FDA issued 522 orders instructing all five U.S. manufacturers of MoM total hip replacement devices on the market at that time, to conduct a postmarket surveillance study of their device. These postmarket studies consist of a clinical study of patient ion levels and clinical outcomes, as well as a separate explant analysis study of failed devices. While not all these studies have been completed, the following is a summary of the available data collected across the studies so far:
Patient Clinical Study: Interim analysis of these studies demonstrate that whole blood and serum metal ion levels (both cobalt and chromium) are significantly higher in MoM total hip replacement patients than in control patients without metal implants. Data from these studies suggest that the 7.0 ppb (µg/L) decision threshold is not optimal for the detection of adverse reactions as patients may have values above this level and are asymptomatic, or below and have adverse events associated with their MoM total hip replacement device. Substantial variability of metal ion levels and tissue changes, as noted in patients with similar MoM hips and post-implantation time periods, suggests the role of patient factors can be influential in patient outcomes of patients with MoM hips.
Explant Analysis Study: Detailed explant analysis results for over 2,000 failed MoM total hip replacement devices has been provided to the Agency. All explants were analyzed to determine the causes and modes of failure. Correlations between the amount of metal wear released, patient metal ion levels in blood, and local tissue changes were evaluated, when available. Based on this analysis, it appears that several surgeon, patient and design related factors may be associated with higher wear release and elevated metal ion levels in patients whose devices were explanted. Although the retrieval-derived factors may not be fully representative of the general patient population, this analysis highlighted the following factors in particular which may be associated with higher metal ion levels and wear release in patients whose devices were explanted:
- edge-loading of the acetabular cups (where the cup is predominantly loaded at the rim)
- wear of the modular taper junction
- larger head diameter
- designs with smaller cup coverage angles.
On average, the failed MoM total hips were associated with higher metal ion levels than overall study patients, and the failed MoM components exhibited higher wear than predicted by the nonclinical wear testing provided at the time of prior FDA premarket clearances. As a result, the Agency has participated in the development of additional ‘high-demand' wear testing protocols to simulate more extreme loading conditions.
International Standards Development (ASTM & ISO)
The FDA continues to play a significant role in the development of international standards (e.g., ISO/TC 150 Implants for Surgery; and, ASTM/F04 Medical and Surgical Materials and Devices). To address the specific clinical issues of MoM total hips, there has been considerable recent standards activities focused on the clinical diagnoses evaluation of MoM total hips as well as the development of improved methods for measure wear and predicting wear using hip joint simulators.
The FDA has collaborated with multiple partners, both domestically and internationally. These efforts have involved several research topic areas in addition to documenting the occurrence of and signs and symptoms associated with specific adverse events. Recent research efforts have focused on:
- Working with MoM manufacturers in:
- Developing, and working with standards development organizations to develop standards to address issues arising from the use of MoM devices,
- Supporting the development of technologies to improve image quality around metal implants, which is needed since the metal in the devices can prevent doctors from monitoring potential changes in tissues around the implant,
- Performing explant analysis of failed MoM total hips, measuring volumetric wear from both the bearing surfaces and modular taper junctions in relation to corresponding adverse events,
- Developing 'adverse' wear testing methods that better simulate the wear conditions seen clinically.
These research efforts have resulted in numerous peer-reviewed journal publications and ASTM Selected Technical Paper as well as presentations at international conferences and ASTM standards meetings.
- The FDA continues to review published medical literature, Medical Device Reports (adverse event reports) , postmarket surveillance study reports, and data from several orthopaedic device registries from within and outside the U.S. to better understand possible adverse events associated with metal debris from MoM hip implants.
- In 2011, the FDA Launched the International Consortium of Orthopaedic Registries (ICOR), an international collaborative effort that aims to harmonize and utilize the data available from these registries and that can allow for collaboration pertinent to the research and clinical management needs of MoM hip patients.