Medical Device Daily Washington Editor
GAITHERSBURG, Maryland – For the second time in 16 months, the orthopedics and rehabilitative devices advisory committee met to hear the case for and against the Menaflex 510(k), an application that in some minds is the poster child for all that is presumed to be wrong with the 510(k) process.
The device's sponsor, ReGen Biologics (Franklin Lakes, New Jersey), also sees the process as flawed, although for entirely different reasons. The firm had some backing in this perspective thanks to the panel's industry representative, Robert Durgin of Biomet (Warsaw, Indiana), who on two occasions attempted to prod the agency's representatives to divulge exactly what FDA intends to do with the recommendations of the panel.
After the meeting, Jeff Shuren, director of the Center for Devices and Radiological Health at FDA, said that the agency can avail itself of several options, including that “we could decide it's a class III device,“ hence forcing the company to conduct another clinical trial. However, he asserted that such a decision would not mandate that the other surgical meshes likewise be routed through a PMA.
Shuren also said that FDA had no motive for convening the panel other than “to seek additional scientific input,“ adding that the agency would announce its decision “in the coming weeks.“ Among the other options the agency could presumably exercise would be to impose special controls on the Menaflex, but given the legal wrangling that would likely ensue a decision to rescind the application – not to mention the fact that two advisory committee meetings implicitly gave the device a thumbs-up –FDA might conclude that a rescission is not its best option.
The contentiousness was evident prior to the start of the hearing. In a March 18 statement, ReGen's CEO, Gary Bisbee, says that ReGen “believe[s] this panel meeting to 're-review' the Menaflex clearance is unprecedented,“ arguing that the agency “has no legal basis on which to conduct“ another review. The firm claims a potential effect of “enormous instability in the device industry“ as a consequence of the second hearing and the possibility that FDA could yank the device from the market.
Bisbee says that the report filed by FDA last September on the Menaflex clearance wrongly alleges that a review conducted by the director of the Office of Device Evaluation, a position then held by Donna-Bea Tillman, PhD, failed to include members from the review team. He asserts that the agency had 10 representatives in on the meeting, “including the review staff.“ He also says that the September report mischaracterizes the Menaflex review memo filed by then-center director Dan Schultz, MD, as lacking “an adequate basis for his clearance determination.“
Bisbee says that Schultz's memo “relied upon numerous sources of information, including the prior advisory committee's in-depth evaluation of the Menaflex that included the concerns raised by“ the review team. He adds that FDA's report on the Menaflex application “fails to note that the explanation and record relating to the Menaflex clearance were more complete than the supporting documentation of over 95% of“ 510(k)s.
Durgin wasted no time in making industry's position clear. “My understanding is that ReGen challenges the accuracy of the [September 2009 FDA] report“ on the process that went into the clearance of the Menaflex, he said, adding, “the issue of greatest concern . . . is the regulatory process.“ Durgin posed two questions to the agency: “What does the agency intend to do with any recommendations?“ and “What process will the agency use in making determinations?“
Panel chairman John Kelly, IV, MD, of the University of Pennsylvania (Philadelphia), would have none of it, informing Durgin, “we're here to discuss the science, not the regulations.“
The contentiousness was not limited to the sponsor and FDA, however. A staunch opponent of the 510(k) program, Diana Zuckerman, president of the National Research Center for Women and Families (Washington), spoke during the afternoon public hearing, and started out her delivery by giving the panel a briefing on its responsibilities. She also critiqued the approval on several fronts, opining, “I think there's a public health question as to whether the 510(k) process should be used for implanted devices.“ She said, “any implant is going to have some kind of adverse reaction“ at some point, “so why approve or clear a product unless there's absolute proof of safety and efficacy?“
Responding to Zuckerman's instructions to the panel, Michael Epstein, MD, of Digestive Disorders Associates (Annapolis, Maryland), responded perhaps not entirely sincerely, “I appreciate you telling us what our job is.“ He also asked Zuckerman how much of the relevant information she had pored over, but she acknowledged having reviewed only the material that had been made available to the public.
One of the more remarkable developments at the panel is that a panel member long known as a skeptic's skeptic, Sanjiv Naidu, PhD, of Pinnacle Health Systems (Mechanicsburg, Pennsylvania), indicated on a couple of occasions that the Menaflex data were close enough to on-target for his purposes. During a discussion of device integrity, he said he was “convinced that this will not fail as FDA has depicted,“ adding, “as time goes on, this becomes a load-sharing device“ for support of the knee joint. Naidu also indicated that he was not disturbed by the prospect that the Menaflex did not reinforce the joint in the first year or so. “It is reinforcing at a later stage,“ he said.
During discussions of how well the Menaflex clinical trial data measured against the performance of predicates, including one indicated for use in the rotator cuff, Kelly summarized that the panel believed that the Menaflex “compares favorably to the predicate,“ with Naidu chiming in, “I think it's better.“
The panel concluded (without taking a formal vote) that the device's safety data were reliable. While efficacy was not demonstrated sufficiently to qualify as level 1 scientific evidence, the panel was largely comfortable with what it saw, especially given that any prophylactic effect on arthritis would require as much as a decade to demonstrate.
To repair or not: CMS and knee surgeries
As is usually the case with life science stories, this one has several moving parts. A healthcare spending consideration related to the Menaflex is the potential for this device to shift into use in Medicare patients. One of the implicit rationales behind the device is to ward off the onset of arthritis, although ReGen has indicated it has no interest in the Medicare population. Still, the arthritis issue was raised at least twice during Tuesday's hearing, and is salient to the Centers for Medicare & Medicaid Services inasmuch as loss of knee cartilage is believed to lead to degenerative knee disease, leading in turn to expensive knee replacement procedures.
According to a story appearing Monday in the Seattle Times, a study conducted by the Mayo Clinic (Rochester, Minnesota) indicates that knee replacements in Medicare eligibles are taking place increasingly frequently and in younger patients. The article says that hospital-discharge data collected by the Centers for Disease Control and Prevention indicate that about 800,000 patients underwent knee replacements between 1990 and 1994, but the number is said to have spiked to 2.1 million between 2002 and 2006 as the average age of patients fell two years, from 70 to 68.
Michele D'Apuzzo, a Mayo resident who led the study, was quoted in the Seattle Times article as saying that providers are “going to be seeing younger patients undergoing this procedure, but we may also see more failures and more revisions, and physicians and medical facilities need to prepare for that.“ The same might be said for payers.
CMS initiated a coverage analysis for the Menaflex analysis last year (Medical Device Daily, Aug. 31, 2009) and proposed last month to issue a national non-coverage decision, which would forbid local carriers from paying for the device. Absent an approved synthetic cartilage for use in the knee, however, CMS may find itself with a need to re-examine the Menaflex device sometime in the not-too-distant future, especially if a continuing stream of Menaflex data hint at a level of efficacy sufficient to allay FDA's concerns.
Mark McCarty, 703-268-5690