In recent years there has been growing concern about this process of clearing medical devices based simply on substantial equivalence with a predicate. New products should not necessarily be assumed to have equal or improved safety and efficacy. The Institute of Medicine weighed in this past summer with a report on the 510(k) clearance process, calling it flawed in its ability to provide determinations about each device's safety and effectiveness.
The future of transvaginal mesh products is now entangled in these concerns. Unlike devices for endometrial ablation and transcervical hysteroscopic sterilization, which are justifiably classified as class III devices, all transvaginal mesh devices to date have been cleared as class II devices.
Since 2001, the FDA has cleared via the 510(k) approval process more than 100 synthetic mesh devices or kits indicated for POP repair, and more than 75 mesh devices to treat SUI (including 7 second-generation mini-slings), using the 510(k) notification process. None of the clearances were based on clinical data.
While there have indeed been some randomized clinical trials (in its recent review, FDA officials reported having looked at 22 randomized controlled trials and 38 observational studies on the use of mesh to treat POP), many of these trials have been designed and conducted with industry sponsorship.
The FDA typically calls upon its advisory panels to provide independent expert advice when specific issues or problems arise and when regulatory decisions need to be made both before and after approval of medical devices.
After issuing its “safety communication” last July, the FDA convened the Obstetrics and Gynecology Devices Advisory Panel in September to make recommendations regarding the safety and effectiveness of surgical mesh for repair of POP and SUI. Ironically, transvaginal mesh devices had previously been regulated by the FDA's Plastic Surgery Devices Panel.
The 2-day public hearing included presentations regarding adverse events and effectiveness of transvaginal mesh for POP and then SUI by FDA staff reviewers, key medical organizations, related industry as a consortium, and public advocacy groups as well as personal testimony by patients having undergone these procedures.
After hearing the testimony and an exhaustive discussion, the majority of panel members supported reclassifying mesh devices for POP from class II to class III. On the other hand, while the majority did not recommend the reclassification of devices for SUI, the panel concurred that more clinical data was warranted to establish the safety and efficacy of second-generation mini-slings.
The FDA's final regulatory decisions will slowly evolve as the issues of safety and effectiveness are balanced with reducing the burden for industry and continuing to foster a hospitable climate for medical innovation.
Adverse Event Reports
The FDA's safety communication released in July, which updated the 2008 FDA Public Health Notification, was generated by continuing concerns raised by rising reports of adverse events as well as concern voiced by the American Urogynecologic Society.
The adverse event reports have been compiled via the FDA's Manufacturer and User Facility Device Experience (MAUDE) database, which collects both mandated reporting by manufacturers and voluntary reports by physicians, patients, and any interested party. It is presumed that complications are generally underreported.
From 2008 to 2010, the FDA received 2,874 adverse event reports associated with urogynecologic mesh – about three times the number of reports filed from 2005 to 2007. Of these, 1,503 were associated with products for POP, and 1,371 were associated with products for SUI.
It is unclear, of course, how much of this increase reflects an increase in actual adverse events and how much stems from the increased use of mesh, an increased awareness of adverse events, possible duplication of reporting, and other factors that are inherent limitations of the reporting process. Moreover, the complication rate is not known because the total number of adverse events and the total number of implanted delivery systems are not known.
Erosion, exposure, and extrusion continue to be the most frequent and concerning adverse events associated with mesh used for POP and SUI. With its more recent review, the FDA has new concerns about the delayed appearances of erosion and mesh exposure. While there are few treatment cohorts to evaluate after 36 months, there have been a number of reports of long-term adverse outcomes – some at time points up to 60 months post procedure.
Moreover, the FDA is concerned about the risk for later development of dyspareunia and new pelvic pain from mesh contraction, retraction, vaginal shrinkage, and subsequent reoperation – problems not identified or flagged when the agency completed its last comprehensive review before issuing the 2008 notification.