Editor's Note: This story has been updated to include comments from a press release Coloplast issued on April 17, 2019, after publication time.
After years of controversy surrounding the use of surgical mesh for transvaginal repair of pelvic organ prolapse (POP), FDA has ordered Boston Scientific and Coloplast to stop selling the mesh on the U.S. market immediately. The agency said the manufacturers have not demonstrated a reasonable assurance of safety and effectiveness for these devices, which is the premarket review standard that now applies to them since FDA decided they were high risk in 2016.
“In order for these mesh devices to stay on the market, we determined that we needed evidence that they worked better than surgery without the use of mesh to repair POP. That evidence was lacking in these premarket applications, and we couldn’t assure women that these devices were safe and effective long term,” said Jeffrey Shuren, MD, director of the FDA’s Center for Devices and Radiological Health. “Patient safety is our highest priority, and women must have access to safe medical devices that provide relief from symptoms and better management of their medical conditions."
But considering how long these devices were on the market, and how many women have complained of major health problems since having transvaginal procedures that use surgical mesh, some say the action is too little, too late.
"Everyone at Medical Device Problems applauds this decision, but we feel it was not made soon enough," Amanda Dykeman, co-founder of Medical Device Problems, said on behalf of the patient advocacy group. "These mesh devices were on the market for over 20 years, leaving tens of thousands of women to live with permanent disabilities and disfigurement."
The group also said the action taken by FDA on Tuesday is a step in the right direction but does not go far enough because it does not address other mesh devices that have been linked to similar life-altering injuries, such as hernia mesh.
"Today's announcement serves to highlight the structural defects in the 510(k) clearance process and serves as a warning for all other medical devices approved through this same pathway," Dykeman said. "While this is one great small step for one harmful medical device, thousands of devices that might not meet the basic litmus test of 'reasonable safety and effectiveness' remain on the market."
Surgical mesh used for transvaginal repair of POP was initially brought to the U.S. market through the 510(k) clearance pathway but in 2016 FDA reclassified the devices and told manufacturers they would have to submit and obtain approval through the more stringent premarket approval (PMA) review pathway in order to keep their devices on the market.
Boston Scientific filed two PMAs for its devices, the Uphold LITE Vaginal Support System and the Xenform Soft Tissue Repair System, and Coloplast filed a PMA for its device, Restorelle DirectFix Anterior.
"We are deeply disappointed by the FDA’s decision on our premarket approval applications (PMAs) for the Uphold LITE Vaginal Support System and the Xenform Soft Tissue Repair Matrix, and believe the inaccessibility of these products will severely limit treatment options for the 50% of women in the U.S. who will suffer from pelvic organ prolapse during their lives," Boston Scientific said in a statement provided to MD+DI. "Patient safety is always our highest priority and we will work closely with the agency to understand its direction and determine next steps."
Boston Scientific disclosed in an SEC filing that it expects FDA's decision to negatively impact the company's 2019 revenue by about $25 million. The company plans to assess any potential additional impact to the business and provide an update during its first-quarter earnings call on April 24.
A Coloplast spokesperson told MD+DI that the Restorelle DirectFix Anterior product represents 0.2% of global revenues.
"Coloplast is disappointed by the FDA decision to remove surgical transvaginal mesh as a treatment option for women suffering from pelvic organ prolapse," the company said in a press release issued Wednesday. "Coloplast has been committed to working with the FDA on the 522 clinical studies to document the long-term efficacy and safety of the products."
“While mesh sales to treat POP in women account for approximately 0.2% of our global revenue, we firmly believe that patients and their physicians should have a choice of therapies. We are disappointed with the FDA’s decision because it reduces the treatment options for women with POP. We remain committed to providing alternative therapies," Coloplast CEO Kristian Villumsen said in the press release.
Coloplast has alternative solutions for the same type of products including tissue products as well as alternative procedures for pelvic organ prolapse. The FDA’s decision is limited to mesh for the transvaginal repair of pelvic organ prolapse and does not extend to mesh used to treat stress urinary incontinence.
In February, FDA convened an advisory panel to solicit input from experts on how to evaluate the safety and effectiveness of surgical mesh for transvaginal repair of POP. The American Urogynecologic Society (AUGS) provided written testimony for that panel meeting in support of keeping the devices on the market. In its testimony, AUGS acknowledged the safety concerns around these devices and proposed ways to maximize the safety of their use while also improving the availability of well-trained providers to "more skilfully address the unintended outcomes associated with their use."
"AUGS feels that women are better served when there are more options for their treatment, and transvaginal mesh for prolapse is a very reasonable and possibly advantageous option for women to consider under certain conditions," the group said in its testimony. "... Different patients experience pelvic floor disorders differently, underlining the need for nonsurgical options, which may have decreased efficacy, but balanced against a lower risk of complication."
Ultimately, the panel recommended that to support a favorable benefit-risk profile, the effectiveness of surgical mesh for transvaginal repair of POP should be superior to native tissue repair at 36 months and the safety outcomes for surgical mesh for transvaginal repair of POP should be comparable to native tissue repair. FDA agreed with these recommendations, and because such data were not provided by the manufacturers in their PMAs, the agency decided not to approve them.
Boston Scientific and Coloplast now have 10 days to submit plans to withdraw these products from the U.S. market, FDA said. The companies are also still required to continue follow-up on patients already enrolled in their 522 studies.
Surgical mesh has come up a number of times in the past year through various media investigations.
Last year a 60 Minutes segment brought unwanted attention to transvaginal mesh devices with a particularly harsh focus on Boston Scientific (the company spoke out about the controversial story in an interview with MD+DI soon after the report aired). The report claimed that the company made transvaginal mesh devices using counterfeit materials smuggled from China.
Boston Scientific denied any wrongdoing and received support from surgeons as well as AUGS. These products, which tend to get lumped together as "pelvic mesh," are designed to treat women who suffer from pelvic organ prolapse or stress urinary incontinence. The implants are made with polypropylene resin, which has previously been linked to a wide array of patient complications. A month after the 60 Minutes report aired, a Massachusetts jury backed Boston Scientific in a product liability case involving two of the company's transvaginal mesh devices.
As Dave Pierce, president of Boston Scientific's urology and pelvic health division, told MD+DI in May, it would have been easier for the company to jump ship from the transvaginal mesh business, as many other manufacturers did, back when FDA put out a medical device directive regarding the use of mesh for POP and stress urinary incontinence. Instead, the company chose to stay in the space and work with FDA and medical societies like AUGS to address the concerns associated with the products.
"And we did so because we felt like females who have these issues need options and we're proud of the fact that we stayed in this business," Pierce said during that interview.
Keeping the mesh implants on the market required a significant investment on Boston Scientific's part, Pierce added, as the company has conducted studies mandated by FDA. The company has also worked with AUGS to ensure surgeons who use the products have extensive training, he said.
"You've seen other companies leave the space altogether. It would have been easier to do that," Pierce said. "But we, as an executive committee, made the decision to stay in this, to absorb the additional expense and complexity, because it's the right thing to do for women."
The Netflix documentary The Bleeding Edge also shed light on how surgical mesh has adversely impacted patients.
FDA is in the process of modernizing its 510(k) clearance pathway, which was adopted in 1976 and now accounts for the majority of medical devices the agency reviews. One of the biggest proposed changes has to do with the use of older predicate devices as a means of demonstrating the safety of new medical devices. Nearly 20% of current 510(k)s are cleared based on a predicate that's more than 10 years old. That's not to say the products are unsafe, the agency said, but it does mean that some devices may not be continually improving. FDA said it will pursue additional actions that will allow the agency to retire outdated predicates, especially in cases where safer or more effective technology has emerged.