Laurie McGinley, Washington Post: March 25, 2019.

Women who say they were harmed by breast implants demanded the Food and Drug Administration take new steps to protect consumers, including providing more information about potential risks and banning devices linked to the most serious complications, including cancer.

Telling searing stories about broken health, disrupted families and lost careers, the women pressed an FDA advisory panel to recommend more long-term research, bans or restrictions on certain products and a beefed-up informed consent process so that women have a clear understanding of the risks and benefits of the devices before they opt for surgery.

“I was not warned” about the risks of implants, Jamee Cook, an advocate and former ER paramedic, told the FDA’s expert committee. Cook, who lives near Dallas, said that after getting implants in 1998, she suffered for years from swollen lymph nodes, chronic fatigue, migraines and a low-grade fever. She said she eventually had the devices removed, after which many, but not all, of her symptoms eased.

The FDA said recently it is taking a closer look at implants, which have sparked anger and contention for decades. The agency asked its General and Plastic Surgery Devices Advisory Committee for recommendations on a raft of issues, and Cook’s testimony was part of a two-day hearing, which continues Tuesday, on the key issues.

Several plastic surgeons pleaded with the panel to proceed carefully, saying that implants generally are safe and an important option for women who want breast augmentation or reconstruction after breast cancer surgery. They said that women’s choices should not be curtailed. About 400,000 women a year get implants, 75 percent for cosmetic reasons and the rest for reconstruction after breast-cancer surgery.

Many of the dozens of patients who attended the meeting at FDA’s headquarters in Silver Spring, Md., wore ribbons to graphically state their concern about two types of illnesses they say are linked to implants. Black and white ribbons symbolized what’s now called “breast implant illness,” a constellation of autoimmune problems that includes joint and muscle pain and allergies and fatigue. Pink and green ribbons signified an uncommon lymphoma that health authorities around the world, including the FDA, link to some implants.

Anastasia Allmendinger, a 53-year-old resident of Newport News, Va., said that she got implants in 2010 and years later was diagnosed with the cancer, called anaplastic large cell lymphoma, or ALCL. She underwent surgery to remove the implants, chemotherapy and a stem-cell transplant, and is now doing well, but said that manufacturers should be held accountable for the illnesses and women should be better informed. Experts say that many patients can be successfully treated only with surgery.

Many of the advocates who spoke on Monday called for a ban on textured implants — the kind most strongly linked to the cancer. There is some evidence the problem could be caused by bacterial infections involving the implants, researchers said.

The FDA has identified 457 cases of the lymphoma and nine deaths in the United States. Six hundred cases and 17 deaths have been reported worldwide.

On the other main illness of concern — the one linked to autoimmune and connective-tissue disease — the FDA and the patient community have long been at odds.

Thousands of women have complained about autoimmune and connective tissue problems on social media but the FDA has repeatedly said that the “weight of evidence” does not show implants cause “systemic” illness.

That opinion was challenged last September, when researchers at MD Anderson Cancer Center found that silicone implants were linked to higher rates of autoimmune disorders such as scleroderma and rheumatoid arthritis than found in the general population. A leading author, Mark Clemens, said the study didn’t prove cause and effect but signaled a reason for concern.

The FDA immediately expressed skepticism, saying the study was flawed. But Binita Ashar, the agency’s director of surgical devices at the FDA’s Center for Devices and Radiological Health, also said the agency is stepping up its long-term surveillance of implants and using patient registries to track complications from the devices.

That view was repeated in the agency’s announcement about the meeting that began Monday. The FDA said that “there is not sufficient evidence to show an association between breast implants and rheumatologic or connective tissue disease diagnoses.” But it added, “there are numerous breast implant patients convening on social media to discuss a wide variety of symptoms that they are experiencing – symptoms which may or may not meet the diagnostic criteria to be categorized as a disease.”

Diana Zuckerman, president of the National Center for Health Research, said in an interview she doesn’t understand “why the FDA seems so close-minded” about the scientific evidence that at least some women have developed autoimmune diseases as a result of their breast implants. “We have always said we don’t know what the percentage is — just that for women who are sick, getting them out makes them better,” she said.

Zuckerman presented data on Monday from a study that her group conducted involving more than 400 women who had their implants removed because they were having health problems. In the vast majority of cases, she said, the women’s health improved. The study has not been published yet. […]

See the original story here.

Matthew Perrone, Associated Press: March 25, 2019.

Government medical advisers said Monday it’s too soon to ban a type of breast implant that has recently been linked to a rare form of cancer, saying more information is needed to understand the problem.

The Food and Drug Administration panel didn’t recommend any immediate restrictions on breast implants after a day reviewing the latest research on the risks of the devices, which have been subject to safety concerns for decades.

The FDA has been grappling with how to manage emerging science that shows the implants can trigger a rare form of lymphoma that grows in the scar tissue surrounding the breasts. The agency identified about 450 cases of the cancer worldwide, including 12 deaths. Almost all of the cases involve a type of textured implant that is designed to stop implants from slipping and to minimize scar tissue.

But the majority of the 19 panelists — including plastic surgeons and cancer experts — said it was too soon to remove the products from the market.

“Do we want to get into the situation where we pull one sweetener and the replacement is even worse?” said Karla Ballman, a biostatistician at New York’s Weill Cornell School of Medicine. “I think a knee jerk reaction of just pulling something without knowing what the replacement will be might get us into more trouble.”

Estimates of the frequency of the disease range from 1 in 3,000 women to 1 in 30,000. It grows slowly and can usually be successfully treated by removing the implants. The FDA said it has also received reports of the disease in smooth implants — which account for most of the U.S. market.

Another panelist said a ban on textured implants would be an “extraordinary overreaction.”

But that opinion wasn’t unanimous. The panel’s consumer representative stressed the risk to women who get implants for reconstructive purposes after breast cancer surgery and could face a second cancer.

“I think that’s so much of a risk that they need to be taken off the market,” said Roberta Brummert. Her comments set off cheers from dozens of women who attended the hearing.

In the U.S., roughly 400,000 women get breast implants each year; 100,000 women get them after cancer surgery.

On Tuesday, the same FDA panel will make recommendations on studying and defining the risks of long-term chronic conditions with breast implants. Thousands of women have blamed their implants for a host of other chronic ailments, including rheumatoid arthritis, chronic fatigue and muscle pain.

Patients and advocates have used the recent scrutiny to call for new warnings and restrictions on implants.

“Don’t ignore us. We are real,” said Holly Davis, of Charleston, South Carolina.

Davis, 60, said she experienced chronic pain, hair loss, rashes and memory loss after receiving silicone gel-filled implants following a double mastectomy in 2002. Davis said she learned her implants had ruptured when they were removed in 2017; her symptoms have since resolved.

She and other patients want the FDA to require manufacturers to give standardized risk disclosure information to all women considering implants.

“We need to know what we’re signing up for — it can’t be a surprise down the road,” Davis said.

In the U.S., most women choose silicone implants, which are considered more natural looking than saline implants. Both types have a silicone outer shell.

The panelists also heard from researchers who theorize, based in part on animal studies, that silicone that leaks from implants can trigger or exacerbate immune system disorders in certain patients.

In 1992, the FDA temporarily pulled silicone gel implants from the market because of fears they might cause breast cancer, lupus and other disorders. But when studies seemed to rule out most of the disease concern, regulators returned them to the market in 2006.

But critics of that research noted its shortcomings at Monday’s meeting.

“The studies at that time were not very good and did not have the statistical power to determine rare diseases,” said Diana Zuckerman, president of the nonprofit, National Center for Health Research, which published an analysis of more than 20 breast implant studies last year. The group concluded that virtually all were too small or too short or didn’t focus on patients who had their implants long enough to develop problems.

The FDA says on its website there is no “apparent association” between breast implants and chronic, debilitating diseases, such as connective tissue disease.

However, earlier this month, the FDA appeared to signal a shift in its thinking. The agency said it would begin studying whether certain materials used in breast implants, metal hips and other devices can trigger health problems in patients.

“We believe the current evidence, although limited, suggests some individuals may be predisposed to develop an immune-inflammatory reaction when exposed to select materials,” the agency said in a statement.

See the original article here.

Maria Rachal, MedTech Dive: March 21, 2019.

When FDA Commissioner Scott Gottlieb and device center chief Jeff Shuren teased next week’s advisory panel tackling breast implant safety, it was tucked into a broader communication on postmarket safety efforts.

But in the four months since, FDA and a domino line of regulators and scientists have flagged upticks in known cases of breast implant associated anaplastic large cell lymphoma. The form of non-Hodgkin lymphoma has been traced to at least nine U.S. deaths. And University of Southern California plastic surgeons published the first known case of similar disease in a recipient of buttocks implants.

Last week, FDA announced an initiative to scrutinize device materials’ biocompatibility, including in the case of silicone breast implants, pointing to potential harmful autoimmune reactions to the devices.

With days before the two-day meeting, the FDA chided Sientra and Johnson & Johnson-owned Mentor for not adequately meeting post-approval study standards, citing low recruitment and poor data and follow-up rates. The only other market competitors are Allergan, whose textured breast implants lost CE marking last December, and privately held Ideal Implant, the newest entrant to the U.S. market.

The FDA is expected to release background materials and specific panel questions prior to the March 25-26 meeting, but none were published as of late Thursday morning ahead of what appears to be at least the eighth advisory committee meeting on breast implants since 1991, according to an agency timeline.

The agenda Monday is set to focus on BIA-ALCL, and Tuesday slated for discussion of everything else: use of MRI screening for silent rupture of silicone gel filled breast implants, surgical mesh in procedures like breast reconstruction and mastopexy, registries for postmarket surveillance, and real-world data and patient perspectives in regulatory decision making.

Here are some facts to know before the meeting.

[…]

What the Watchdogs Say

The panel could follow in the footsteps of those who weighed in on Essure, who advocated for better informed consent for patients; FDA ultimately issued the product a “black box warning,” which is reserved for calling out serious or life-threatening risks on a package’s label.

Madris Tomes, a former program manager at FDA who now analyzes adverse event data through her company Device Events, said the black box warning was not effective for patients in the case of Essure, and probably wouldn’t make a significant difference for potential breast implant recipients either.

“The patient won’t see a black box warning because they don’t see the box for the [product] that’s going to be implanted in them,” she said.

National Center for Health Research President Diana Zuckerman agreed that a black box is possible, and while FDA rarely recalls devices and already oversaw a long moratorium in this device category, she said a partial market removal of textured implants in particular wouldn’t be unheard of.

This is a greatly shortened version of the article.  To read the entire article in MedTech Dive, see here.

Mia de Graff, The Daily Mail: March 20, 2019.

Days before a hearing on breast implant safety, US regulators have sent warning letters to two of the top implant manufacturers involved.

In the letters, the US Food and Drug Administration reprimanded Mentor and Sientra for historically failing to complete the safety studies required for medical devices to stay on the market.

If the firms do not have completed data within 15 days, the FDA warned, their blockbuster silicone implants could be pulled from the market.

The warning is a gesture to patients that the FDA intends to be firm with breast implant manufacturers, whose products have stayed on the market for years without adequate safety data, despite ranking in the highest-risk bracket for medical devices.

It comes amid global concerns over the safety of silicone breast implants, which have been officially linked to cancer of the immune system, and are alleged to cause autoimmune disorders.

Lauren Dunn, NBC News: March 19, 2019.

Less than a week before a major hearing on breast implant safety, the FDA issued two warning letters to implant manufacturers, citing their failure to do proper safety studies.

The letters sent to Mentor and Sientra warned that certain implants could be pulled off the market if the companies didn’t fulfill the agency’s requirements, which ask that manufacturers continue safety studies even after the devices are approved.

According to the letters, Mentor failed to enroll enough people in these studies. Sientra had poor follow-up rates.

“The FDA has the authority to say you either have to study it or take off the market and the company has the incentive to do one or the other,” Diana Zuckerman, president of the National Center for Health Research, told NBC News.

Zuckerman also called the letters “surprising but encouraging,” and questioned whether the FDA would take action if the companies failed to comply with the warning letters.

“You can’t assume that just because they sent the warning letter, it’s anything more than the FDA flexing their muscles,” Zuckerman said. “If the companies don’t get scared enough to comply, the big question is whether the FDA will follow through.”

In a statement to NBC News, Mentor, said it had made “multiple attempts” to discuss study requirements for its MemoryShape breast implants with the FDA.

Denise Grady and Roni Caryn Rabin, New York Times: March 19, 2019.

David Lim, Medtech: March 6, 2019.

Under Gottlieb’s tenure FDA rolled out a number of medical device initiatives, some mandated by the landmark 21st Century Cures Act, such as guidances on breakthrough devices, CLIA waiver improvements and least burdensome device review.

Other policies, such as the agency’s proposal to examine limiting manufacturer reliance on 510(k) predicate devices older than 10 years came in the midst of criticism the agency is too lax in its regulatory oversight.

But Gottlieb often left device decision making to Shuren, a sign he trusted the career staffer to run the show.

“At CDRH, really what he was doing was letting Jeff Shuren do his thing. It was Jeff driving it and Gottlieb giving him permission to do so,” Brad Thompson, a digital software attorney at Epstein Becker & Green, told MedTech Dive.  “I don’t mean to minimize that. There are some commissioners who would have said no, just saying yes to Shuren was significant.”

But Gottlieb was not hands off either. He regularly jointly announced medtech initiatives with Shuren including efforts to stand up a Pre-Cert Program for software as a medical device, which “at least created the impression that Dr. Gottlieb was very involved and proactive” in the device space, according to Jeffrey Shapiro, a device attorney at Hyman, Phelps & McNamara.

“I didn’t see an initiative from the device center that it hadn’t been working on to some extent in the last few years,” Shapiro said. “I don’t see a big change unless the new commissioner somehow has a different set of priorities or ideas about device regulation.”

President of the National Center for Health Research Diana Zuckerman agreed, telling MedTech Dive the true impact of Gottlieb’s exit on the device center will depend on if his replacement “will continue to let Jeff Shuren run the show or want to make changes.”

It’s unclear who will take Gottlieb’s place, but some in industry fear a less conventional, more typical Trump administration candidate. During the last FDA chief search, the rumored nomination of Peter Thiel associate Jim O’Neill, who advocated against mandating companies prove the effectiveness of new products, spooked some.

Bakul Patel, FDA associate center director for digital health, is another CDRH leader who shepherded the Pre-Cert Program from conception to its current proposal. His presence will maintain additional normalcy at CDRH, according to Thompson.

The agency is in the process of collecting feedback on the latest working model for the Pre-Cert Program, which has drawn fire from Democrats and some in industry for potentially overstepping FDA’s statutory authority.

Gottlieb and Shuren also worked together to stand up the National Evaluation System for health Technology (NEST), a real world evidence collection initiative tied to a postmarket surveillance push denoted in the Medical Device Safety Action Plan.

Transparency via social media may also take a hit with exit of Gottlieb, widely considered an effective communicator for FDA with his robust presence on Twitter. ​Twitter-less Shuren has kept a relatively low public profile compared to the commissioner.

“The most immediate change at FDA will no doubt be a radical slow-down in the news flow. Gottlieb is a genius at offering a constant stream of newsy updates, packaging almost any FDA guidance or workshop into a larger more gripping narrative,” Cowen Washington Research Group’s Rick Weissenstein said in a note. “In the absence of the constant, agency-directed messaging, those outside groups could start to reshape the narrative.”

Shuren, who has served as director of CDRH since 2010, has been the source of many of the center’s novel ideas over the past decade. For example, ​he recently co-authored a JAMA Viewpoint article advocating continuing to leverage RWE.

“We anticipate that decentralized network models, such as PCORnet and NEST, although still in their infancy, will emerge as appropriate models to harness the breadth of electronic data generated in health systems,” Shuren jointly wrote.

Abernethy, if appointed, will likely be supportive of the effort, according to Thompson.

Another potential downside for FDA will be a lack of a cheerleader to Congress. Senate HELP Committee Chairman Lamar Alexander, R-Tenn., praised Gottlieb’s time at the agency, noting he has worked closely with Congress and implemented Cures provisions aimed at bringing more medical devices to market faster. Rebecca Wood, who served as FDA chief counsel under Gottlieb, echoed the sentiment to MedTech Dive.

Gottlieb secured a nearly $50 million boost in appropriations for a spate of device and radiological health programs FDA recently received in the February package.

“He was one of the most politically astute commissioners. He knew how to get Congress on his side much more successfully than most FDA commissioners are able to do,” Zuckerman added. “It’s really actually unlikely that his successor will be as good at that.”

See the original story here.