WASHINGTON -- The FDA wants makers of metal-on-metal hip implants to prove their products are safe if they want to continue to market them.
The implants have long been a subject of concern due to adverse reactions. An FDA review of more than 100 studies of metal-on-metal hip implants found that the artificial hips may pose problems for women and for patients who received larger-sized hip implants.
On Thursday the agency issued a "to require the filing of a premarket approval application (PMA) or a notice of completion of a product development protocol (PDP)" for metal-on-metal hip implants. Until this point, manufacturers were allowed to market the implants without needing to get a PMA, which would require the submission of safety and effectiveness data.
Manufacturers who submit a PMA "must include valid scientific evidence to demonstrate reasonable assurance of the safety and effectiveness of the device for its intended use," according to the proposed order.
The proposed order also offers "the opportunity for interested persons to request that the Agency change the classification of any of the aforementioned devices based on new information."
In a posted Thursday on the FDA website, the agency noted that "metal-on-metal hip implants have unique risks in addition to the general risks of all hip implants" because "metal release will cause some tiny metal particles to wear off of the device around the implant, which may cause damage to bone and/or soft tissue surrounding the implant and joint."
"The soft tissue damage may lead to pain, implant loosening, device failure and the need for revision surgery," according to the communication. "Some of the metal ions released will enter the bloodstream and travel to other parts of the body, where they may cause symptoms or illnesses elsewhere in the body."
The FDA said it currently "does not have enough scientific data to specify the concentration of metal ions in a patient's body or blood necessary to produce adverse systemic effects. In addition, the reaction seems to be specific to individual patients, with different patients having different reactions to the metal wear particles."
A 2-day meeting of the FDA's Orthopaedic Surgery and Rehabilitation Devices Advisory Committee last June yielded few recommendations for how the agency should deal with the implants. Many panel members at that meeting said that they were uncomfortable with making recommendations on the basis of the current data, none of which came from prospective, randomized trials.
In May 2011, FDA ordered post-market surveillance studies from all companies that make these systems. But the studies have been slow to get underway and may not provide useful information to physicians and patients, physicians warned in a New England Journal of Medicine article.
These devices also have been the subject to two significant recalls in recent years, as noted by FDA reviewers: the 2008 recall of Zimmer's Durom Acetabular Component because of inadequate instructions for use, and the 2010 recall of the DePuy ASR Total Hip due to higher-than-expected revision rates. The DePuy device is currently the subject of multiple patient lawsuits.
More recently, Smith & Nephew pulled its R3 Acetabular System metal hip socket liner from the market due to higher-than-acceptable annual revision rates in patients who had this device.
In its safety communication, the FDA recommended that orthopedic surgeons "select a metal-on-metal hip implant for [their patients] only after determining that the benefit-risk profile of using a metal-on-metal hip implant outweighs that of using an alternative hip system (metal-on-polyethylene, ceramic-on-polyethylene, ceramic-on-ceramic or ceramic-on-metal). Factors to consider include the patient's age, sex, weight, diagnosis, and activity level."
The agency also urged orthopedic surgeons to "Inform patients about the benefits and risks of metal-on-metal hip implants, including the risk that the hip implant may need to be replaced. Also discuss the patient's expectations and review the potential complications of surgery with a metal-on-metal hip implant."
The safety communication also encouraged other healthcare providers to be aware of the signs of possible metal ion adverse reactions in patients who have recently had metal-on-metal hip replacements. Symptoms to look for include:
- General hypersensitivity reaction (skin rash)
- Cardiomyopathy
- Neurological changes including sensory changes (auditory or visual impairments)
- Psychological status change (including depression)
- Renal function impairment
- Thyroid dysfunction (including neck discomfort, fatigue, weight gain, or feeling cold)
"Patients with metal-on-metal hip implants who develop any symptoms or physical findings that indicate their device may not be functioning properly, should be considered for metal ion testing," the FDA noted.
The agency will be accepting comments on its proposed order for 3 months after it is published in the Federal Register. Once a final order is published, manufacturers will have 90 days to file a PMA or PDP.