Medical Device Daily Washington Editor
GAITHERSBURG, Maryland – The mere fact of an FDA advisory committee meeting is anything but conspicuous, but the fact that such a meeting addresses a 510(k) is somewhat unusual.
Nonetheless, the orthopedic and rehabilitation devices panel met last Friday to discuss a 510(k) application by ReGen Biologics (Franklin Lakes, New Jersey) for its Menaflex collagen scaffold for use in the knee following partial removal (meniscectomy) of the cartilage, or meniscus. The company had failed twice previously in its attempts to win clearance after deciding early in 2006 to opt out of a PMA route (Medical Device Daily, Jan. 5, 2006).
While the panel did not conduct a formal vote for approvability, FDA nonetheless came away with an unambiguous message that it should allow the ReGen surgical mesh onto the market for this indication, which most likely was abetted by the admission by one of FDA's senior officer that the product had superior safety data compared to predicates.
During the morning open public hearing, the panel heard from Pamela Adams, formerly an industry representative on the committee, who spoke on behalf of the Orthopedic Surgical Manufacturers Association (OSMA; Germantown, Tennessee). She reminded panelists, "this is not a PMA regulatory application" and that the question of the day was whether the device is "as safe and effective as the predicate."
A 510(k), Adams said, "is not required to show absolute safety and effectiveness," just that it behaves like the predicate. She also asserted: "There is no merit to the criticism that devices are approved for market by comparisons to antiquated devices" because the agency requires comparisons to "the state of the art."
John Dichiara, VP regulatory affairs at ReGen, said the agency has cleared similar meshes for more worrisome uses such as in anal fistulas. He said the standard for FDA clearance is that the device serves as a substitute for "not an anatomical location, but a function," which is "to support soft tissue alone."
Dichiara mentioned that the ReGen is based on type 1 bovine collagen and that the device conformed to FDA's regulations that meshes provide "a scaffold to be replaced by the patient's own tissues." He also pointed out that more than 400 such devices have been approved for 17 new uses in the past six years.
Taking exception to FDA's view that the implant "was not found to have any benefit for patients with an acute injury," Dichiara said this position lacked context because the published article, which appeared earlier this year in the Journal of Bone & Joint Surgery, described a study that was designed to compare use of the device with chronic injury to the meniscus, such as is often found in osteoarthritis. He argued that the ReGen "needs to be compared to intended use, not as a comparison to partial menisectomy." The study was apparently constructed as a PMA study.
Kenneth DeHaven, MD, of the University of Rochester Medical Center (Rochester, New York), reminded the panel that "the number of meniscus repairs has been increasing" and that the only current treatment is partial removal of the meniscus or replacement with autograft tissue.
DeHaven said "in one of the first patients in the study, the tissue remains intact 11 years out," and that the supporting study data indicated that "implant patients had significantly more tissue filling" than those who had meniscus removed without the scaffold. The feasibility study "established tissue durability and safety to 5.8 years."
William Montgomery, MD, of San Francisco Orthopedic Surgery (San Francisco), told the panel, "we have more safety data than for any surgical mesh on the market." He stated that the device has been implanted in more than 2,000 patients in Europe for a complaint rate of 0.31%, but has engendered "no significant issues."
Larry Kessler, director of the Office of Scientific and Engineering Labs at the Center for Devices and Radiological Health at FDA, said the original application was for chronic soft-tissue injuries only, but that "the difference here is that it includes both chronic and acute" injuries. He also said that the article in JBJS indicated that the device was "not found to have any benefit for patients with an acute injury."
One of the things FDA took exception to regarding the study results, according to Kessler, was that "the tests do not tell us whether we have type 1 or type 2 collagen." He also said that "since all the primary endpoints failed, we are at a loss" as to whether to clear the device. He said the lack of convincing evidence regarding the primary endpoint is "critical because of the weight bearing nature of the knee." The primary endpoints indicated in the PMA trial were two measures of pain and one for self assessed function.
Kessler was asked by a panel member whether a predicate was forced to come up with more data than was generated by the study for the Menaflex. He said, "no, we haven't asked for any, but we haven't seen an application for this indication." On the other hand, he admitted that the device-related events seen with the ReGen were lower than seen in trials of surgical meshes indicated for different uses.
After discussing device-associated risk, panel chairman Jay Mabrey, MD, of Baylor North Texas Orthopaedic Specialists (Dallas), concluded that the panel "generally believes there is some evidence of tissue growth," but there is question as to the nature of the tissue. "The device does not appear to carry any additional harm or risk." CDRH chief Dan Schultz, MD, accepted that as the panel's conclusion.
The panel also concluded, "The device has fostered in-growth comparable to the predicate," Mabrey said, and that "histologic reactions nave been minimal." However, some panelists expressed concerns about whether the new tissue would stand up to the load imposed on the knee.
As for the indication, one panelist remarked that use of the device could delay the onset of osteoarthrosis, which he described as "an epidemiological time bomb." John Kelly, MD, of the University of Pennsylvania (Philadelphia), remarked that "anything that increases the surface area of the knee is probably good," adding that a collagen device "could serve as a substrate" for growth factors to regenerate cartilaginous tissue.
Lt. Col. Scott Shawen, MD, of Walter Reed Medical Center (Washington), said he was "very encouraged by the lengths to which this device has been studied."
Mabrey summarized that the panel "generally believes that for this particular clinical problem, the patient has no other choice" other than removing the cartilage. He reiterated some concerns about "this as being promulgated as the latest and greatest thing." The solution, he said, may be "some type of training and evaluation to be offered" in a cadaver lab or via surgical visitation.
As for safety and efficacy, Mabrey stated, "the panel generally believes that the device is safe, but its effectiveness remains to be seen," although "no outright problems with the device" are noted. He said "the sense of the panel is that yes, it is as safe and effective." The panel also generally agreed that the device was appropriate for use in both chronic and acute injuries.