Alex Nussbaum and David Voreacos
Bloomberg|October 20, 2011
Johnson & Johnson (JNJ), the world’s second-biggest health-care products maker, is battling lawsuits over a vaginal implant based on a similar device pulled from the market more than a decade ago for safety reasons.
The complaints are the latest to implicate the approval process for medical devices at the U.S. Food and Drug Administration, which has cleared faulty hip implants and malfunctioning defibrillators.
In the case of vaginal mesh implants, the FDA continued approving the hammock-like devices made by J&J and other companies based on their similarity to Boston Scientific Corp. (BSX)’s ProteGen even after it was pulled amid safety complaints. Today, the makers of the entire category of implants face more than 600 lawsuits from women who claim the devices caused serious injury.
“The FDA got caught with their pants down,” said Thomas Margolis, a pelvic surgeon in Burlingame, California, who treats patients for mesh complications. “The ProteGen should have told them, ‘Wait a minute, all of these mesh systems are bad.’”
The devices treat incontinence and a condition called pelvic organ prolapse, in which internal organs slump into the vagina. They were allowed on the market as result of the agency’s approval process, known as 510(k), which relies on the notion that if one device has been cleared by the FDA then similar devices need little if any testing in patients.
The FDA is under increasing pressure to change the system. Following a year of headlines about defective hip prosthetics, Congress has been pushing the agency for an overhaul of 510(k).
In July, the FDA issued a statement saying it is unclear whether prolapse implants provide any benefit over traditional surgery. The statement came three years after the agency first acknowledged a problem in a 2008 report that said mesh complications were serious, if rare. An advisory panel of physicians said last month that the FDA should demand more clinical testing of the devices.
“We learn from experience,” Jeffrey Shuren, the director of the FDA’s Center for Devices and Radiological Health said in an interview. “What you’re seeing now is the agency taking very targeted actions against specific devices where we have new information to suggest we should be taking a different approach.”
J&J says its vaginal mesh products are safe. Its Gynecare TVT, which was based on the Boston Scientific product, remains the “standard of care” for incontinence, said Matthew Johnson, a spokesman for the New Brunswick, New Jersey-based company. The device’s safety and efficacy have been demonstrated “by more than thirteen years of clinical data,” he said in an e-mail.
The chain of approvals that began with Boston Scientific’s device highlight a key flaw in the 510(k) process, said Amy Allina, a policy director at the National Women’s Health Network, a Washington-based advocacy group.
The system lets manufacturers win clearance for a product by citing its similarity to an already approved device, known in FDA jargon as a “predicate.” That second device can be cited as the basis for a third, the third to clear a fourth and so on.
“If a first iteration is recalled, they don’t necessarily look at the second, third or fourth things that are based on that,” Allina said in an interview. The system, she said, “is a mess.”
The story began in 1996, when Boston Scientific won clearance for ProteGen, the first vaginally implanted mesh designed specifically to treat incontinence. Two years later, J&J won approval for a similar device, called Gynecare TVT. Under the 510(k) system, J&J wasn’t required to conduct human testing because the company claimed its device was “substantially equivalent” to the Boston Scientific device.
A year later, Boston Scientific voluntarily pulled about 20,000 ProteGen meshes, saying it had received 123 reports of problems, including discomfort, painful sex, and erosion of vaginal tissue. Nonetheless, J&J and at least two other manufacturers, American Medical Systems and Covidien Plc (COV), soon came out with products that traced their design back to ProteGen.
The FDA has said it doesn’t know the number of women who have received the implants since 1998, though it estimates almost 300,000 were used in 2010.
All were approved through the 35-year-old 510(k) system, used by the FDA to review some 90 percent of device applications each year. The same process was used to clear the 93,000 artificial hips pulled by J&J last year due to high failure rates, as well as hundreds of external heart defibrillators recalled since 2005 by Minneapolis-based Medtronic Inc. (MDT)
Designed to vet low-risk devices such as surgical drapes, 510(k) also become a gateway for items like joint implants and vaginal mesh that can claim a tie to older products, said Diana Zuckerman, president of the National Research Center for Women & Families, a Washington advocacy group that has pushed for more device testing.
Patients who received the devices say the result has been years of pain. Lana Keeton, a 64-year-old steel broker from Austin, Texas, said she received her J&J implant in December 2001 to treat incontinence symptoms following a hysterectomy.
Once implanted, pieces of the synthetic fabric began flaking off, migrating through Keeton’s body and scraping against internal organs, she said in an interview. Keeton said she has undergone 17 medical procedures, including five surgeries, to remove mesh debris from her body.
“It’s like removing gum from your hair,” she said. “You can never get all of it out.”
Keeton’s lawsuit was dismissed by a federal judge in Miami in August 2007. U.S. District Judge Ursula Ungaro threw out the case before it reached a trial, ruling Keeton “has not produced sufficient evidence” to support her claim, according to court documents. Undeterred, she went on to found Truth in Medicine, a nonprofit group pushing for a recall of the devices.
J&J still faces more than 270 suits from women like Marian Goldberg, a retired social worker from New York. Goldberg, 66, received the TVT and another vaginal mesh, J&J’s Prolift, in 2007. Since then, she said, the devices’ failure has led to permanent pain, nerve damage and incontinence worse than the original condition the meshes were meant to treat.
The TVT was “approved without being tested on its own merits. That in itself is unconscionable,” Goldberg said in a telephone interview. “Then to have been allowed to stay on the market when it was modeled on a device that was already impaired is unbelievable.”
In a report released in January, the FDA acknowledged concern about the use of recalled predicates, saying the practice could “put patients at risk.” The agency said it would consider 25 changes to the 510(k) system this year, including stricter guidelines on what products can be cited to back new devices.
In July, the U.S. Institute of Medicine, a non-profit that advises the government on medical issues, warned of risks from clearing devices based on old products. About 29 percent of devices cleared through 510(k) are no longer on the market, and though the FDA often can’t say why they were pulled, they remain available to cite as proof of new products’ safety, the report said.
Boston Scientific cited five predicates for ProteGen, including hernia slings and fabric used in cardiac surgery, FDA records show. Two years later, J&J named ProteGen as a basis for the Gynecare TVT, noting in its application that “technologically, both the new device and predicate device are the same.”
By that time, complaints about Boston Scientific’s device were already filtering into the FDA. A year after J&J’s TVT won clearance, Boston Scientific voluntarily recalled about 20,000 of its meshes.
J&J’s Gynecare TVT later became a predicate for the IVS Tunneller I, made by Dublin-based Covidien, and the Sparc Sling, made by the American Medical Systems unit of Endo Pharmaceuticals Holdings Inc. (ENDP), based in Chadds Ford, Pennsylvania. Those, in turn, were cited to clear future versions, each said to be “substantially equivalent” to its predecessors, according to FDA records.
It’s unclear what steps, if any, the FDA took at the time of the Boston Scientific recall to scrutinize other meshes. The agency didn’t respond to requests for information about how it handled the ProteGen and similar products. In 2003, Boston Scientific settled 738 suits over its mesh for an undisclosed sum.
The safety debate has presented a conundrum for manufacturers, who have avoided clinical tests for the devices by calling them similar to one another yet now say the products have advanced far beyond the earlier versions.
“There are much more modern and improved devices out there,” said Ginger Glaser, a senior regulatory affairs director for American Medical Systems. “It’s not necessarily, ‘if this one was a problem, all the other ones are a problem,’” she said.
The FDA advisory panel disagreed. The 17-member group, comprised mostly of pelvic surgeons, recommended at last month’s hearing that some vaginal meshes be reclassified as high-risk devices requiring new studies to stay on the market.
While the devices may still prove a viable option for well- trained surgeons, there’s not enough evidence to say that all are “ready for prime time,” panelist Cheryl Iglesia, a surgeon and associate professor at Georgetown University Medical Center, said during the hearing.
The FDA appears to be inching toward a similar decision. At the September hearing, Colin Pollard, director of the FDA’s obstetrics and gynecology devices branch, said it may take as long as three years to issue new rules. Until then, current models can stay on the market, he said.
That’s too late for many women, said Allina, of the National Women’s Health Network.
“There are women who have these products inside of them and are living with the harm that was done to them,” she said. “It’s a terrifying thing to roll the dice with.”
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