FDA busted two manufacturers of silicone gel-filled breast implants this week for failure to comply with post-approval study requirements.
The agency sent warning letters to Irvine, CA-based Mentor Worldwide, a unit of Johnson & Johnson, and to Santa Barbara, CA-based Sientra for deficiencies in each company's post-approval study for silicone breast implant approvals.
Breast implants have been a source of contention between patient advocacy groups, industry, and FDA for decades. Implants were banned from the U.S. market from 1992 to 2006, and the devices have been the cause of an overwhelming number of lawsuits. When FDA lifted the 14-year moratorium on silicone breast implants in 2006, each manufacturer was required to conduct six post-approval studies to further characterize the safety and effectiveness of their breast implants and to answer additional scientific questions about the long-term safety of breast implants that the premarket clinical trials were not designed to answer.
“Post-approval requirements are critical to ensuring the safety and effectiveness of the medical products we regulate and we’ll continue to hold manufacturers accountable when they fail to fulfill these obligations,” said FDA Commissioner Scott Gottlieb. “We’re issuing these warning letters based on the manufacturers’ low recruitment, poor data, and low follow-up rates in their required post-approval studies. We expect these manufacturers to meet the pre-specified study requirements in order to ensure the collection of long-term data that can be used to inform long-term patient safety."
FDA said its warning letter to Mentor noted "several serious deficiencies" in the manufacturer's post-approval study for its MemoryShape breast implant, first approved in 2013. According to the agency, Mentor failed to enroll the required number of patients in the study, had poor follow-up rates with patients who were enrolled, and had significant data inconsistencies in the study. The data inconsistencies include poor patient accounting and missing race and ethnicity data, the agency noted.
After reviewing several interim study reports Mentor submitted on the post-approval study, FDA initially concluded that progress on the study was adequate. However, the agency said it did advise the company of concerns about patient enrollment, follow-up rates, and data inconsistencies and that Mentor failed to address these concerns.
Sientra received a warning letter for poor follow-up with patients, according to FDA. The company reported a follow-up rate of 61%, which the agency said is below the target follow-up rate. FDA said it notified Sientra via an interim study report that the study progress was inadequate because of low follow-up rates, but the company failed to address the issue.
Both manufacturers have 15 working days to respond to the warning letters with details about how the noted violations will be corrected. FDA said it may pursue applicable criminal and civil penalties if the companies do not comply.
This action follows a notice FDA issued last week about taking a harder look at materials used in medical devices and potential adverse biological response resulting from contact of certain materials with the body over extended periods of time. Silicone breast implants were one of the specific types of medical device materials mentioned in that statement.
Breast implants on the market today have a silicone outer shell, with either a textured or non-textured surface, and are filled with silicone gel or saline. Over the years there have been reports of risks associated with breast implants, such as capsular contracture, implant rupture, and breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). More confirmed cases of BIA-ALCL have been reported in patients with textured surface implants that in patients with smooth-surface implants, the agency said.
Breast Implants Linked to Rare Diseases
As MD+DI reported last year, there was a study published in the Annals of Surgery linking silicone breast implants with a handful of rare diseases. An FDA expert pointed to flaws in that particular study but acknowledged the need for better postmarket evidence generation.
The authors of the study analyzed nearly 100,000 breast implant procedures gleaned from FDA-mandated postmarket studies for implants made by Mentor and Dublin, Ireland-based Allergan. According to their analysis, silicone implants are associated with higher rates of Sjögren syndrome, scleroderma, rheumatoid arthritis, stillbirth, and melanoma.
Despite finding fault with the study, FDA did acknowledge such reports in its recent statement about medical device materials.
"We’ve also heard from patients who are concerned that their implants may be connected to other health conditions that could be associated with their immune system’s response to these devices, resulting in symptoms like chronic fatigue, cognitive issues, and muscle pain," FDA said.
The agency said it does not have definitive evidence linking breast implants with these conditions, but "we're looking to gain a fuller understanding of this issue to communicate risk, minimize harm, and help in the treatment of affected patients."
More to Come on Breast Implant Safety
FDA said this topic will be addressed at a public meeting of the General and Plastic Surgery March 25-26. The agency also mentioned two different breast implant registries it is involved with to learn more about how these devices perform and interact with the body's tissues at the cellular and organ levels. One is the Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma Etiology and Epidemiology (PROFILE), which collects real-world data on patients with confirmed diagnosis of BIA-ALCL. The other is the National Breast Implant Registry which is designed to provide a platform for evaluating real-world data on the safety and performance of breast implants.