Mentor's Memory Gel silicone gel-filled breast implants are reasonably safe for a device lifetime of 10-15 years, according to members of FDA's General & Plastic Surgery Devices Panel.

In a 7-2 vote, the panel recommended approval of the implants with nine conditions at an April 13 meeting in Gaithersburg, Md., despite voting against approval for competitor Inamed a day earlier (see ¹ Also see "Inamed To Carry On Quest For Silicone Implant Approval After Panel Rejection" - Medtech Insight, 18 April, 2005.).

Panelist Stephen Li, PhD, Medical Device Testing & Innovations, criticized Mentor's original contention that the lifetime of the device falls between 25 and 47 years, with a failure rate of 50% at 25 years. Li maintained that a 50% failure rate cannot adequately define "lifetime."

Fellow member Amy Newburger, MD, Dermatology Consultants of Westchester, concurred with Li's assertion: "Over the expected lifetime of this device, if it's 25 years, I wouldn't have the assurance that the device is safe."

Panelist Cheryl Ewing, MD, University of California, San Francisco, proposed a device lifetime of 10-15 years as more comparable to the lifespan of many other medical devices.

Li extended his criticism to the firm's fatigue testing, which stretched the potential lifetime up to 61 years. "I don't believe that, but even if they're off by a factor of four, that's 15 years," he acknowledged.

Although Li voted against Inamed's PMA, he endorsed Mentor's application due to the lower rupture rates and availability of limited long-term evidence.

After an initial movement to reject the PMA was defeated 7-2, Mentor received the panel nod. Some panelists disclosed that the depth and breadth of their extensive recommended conditions of approval helped assuage outstanding safety concerns.

The panel recommended requiring Mentor to continue data collection of its core and adjunct studies through 10 years, with another FDA panel review to discuss updated data at the five-year mark.

The core study also should be expanded to include patients whose implants have been removed and to feature connective tissue disorder signs and symptoms and quality-of-life measures, according to the panel.

The panel further advised FDA to require that continued data collection be followed by an independent data monitoring committee under the agency's guidance.

In addition, the panel asked the agency to stipulate that silicone implants be prescribed as "tracked devices." Tracked devices are continuously monitored by the manufacturer - per an FDA order - to facilitate a notification or recall.

The panel also recommended that the firm establish a registry to collect data on pregnancy outcomes, breastfeeding effects, connective tissue disorder signs and symptoms and MRI and mammography results.

Mentor has already proposed a registry design, which may be modified after the panel's discussions. Other post-approval plans that were proffered by the firm should be fulfilled, the panel stressed.

Further, panelists advised FDA that the labeling should urge patients to receive an MRI five years after implantation and every two years thereafter, along with the caveat that women with a suspected rupture have their implants removed. The labeling should stress that MRIs to gauge implant status should not supersede regular mammograms.

Other conditions include requiring hands-on physician education before plastic surgeons are allowed to implant the devices. Panelists also requested that patient education be kept "separate and distinct" from the informed consent process.

Analysts following the silicone implant regulatory efforts of both firms had predicted that Mentor's application would be turned down following the panel's negative recommendation about Inamed.

With partial three-year follow-up data from its core study, Mentor's PMA application contained one year less of data than Inamed's, with about 26% of Mentor's patients not yet receiving their three-year follow-up visit.

While panelists were largely critical of Inamed's data analysis, Mentor's studies fared better. Panelist and biostatistician Brent Blumenstein, PhD, TriArc Consulting, who ultimately voted against approval for both firms, nevertheless called Mentor's statistical reviews "a pleasure."

Mentor's core study enrolled 1,000 patients - with 550 receiving augmentation, 250 undergoing reconstruction and 200 seeking revision - at 60 sites. A total of 420 patients were included in the MRI cohort to detect silent rupture; those patients had received MRIs at the one and two-year marks.

Rupture rates at three years were 0.5% for augmentation, 0.8% for reconstruction and 4.8% for revision. No ruptures were reported in the non-MRI cohort.

Because the rupture rates at three years were significantly lower than those for Inamed's patients - which climbed as high as 20% for reconstruction patients at three years - panelists expressed that Mentor better demonstrated safety.

The firm further emphasized the safety of its silicone implants by submitting data from a 101-patient British study, which evaluated patients with MRI that had a mean implantation duration of 8.8 years.

The study found an overall rupture rate of 8.9% by patient and 5.4% by implant, pointing panelists to a trend of long-term safety for the implants.

Panelists also stressed that Mentor successfully demonstrated that silicone leakage in the body is innocuous. Plastic surgeon Michael Miller, MD, University of Texas MD Anderson Cancer Center, emphasized that silicone implants should be considered safe "absent evidence that a ruptured implant is harmful, especially systemically."

Marilyn Leitch, MD, University of Texas Southwestern Medical Center, enthused: "I voted for approval of the PMA because I believe that the data presented for this implant and the review of the literature presents it as a safe and effective device with patients that are well-informed."

Mentor's initial PMA was submitted a full year after Inamed's. Due to a January 2004 "not approvable" letter, however, Inamed's lead waned, resulting in the two firms sharing a panel appearance (² Also see "Mentor Files Silicone Implant PMA Amendment, Catches Up To Inamed" - Medtech Insight, 6 September, 2004., p. 29).

Mentor Silicone Implant Panel Sobered By Approval Caveats

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