The US Food and Drug Administration (FDA) sent warning letters this week to two breast implant manufacturers over their failures to comply with FDA’s post-approval study (PAS) requirements.
The warning letters were made public by FDA late Tuesday and sent to Sientra and Mentor Worldwide on Monday for being in violation of two of the seven requirements established as part of their devices’ conditional approvals. They underscore an emerging FDA enforcement trend around PAS requirements.
The requirements were set as conditions of the manufacturers’ 2013 premarket application (PMA) approvals. Failure to comply with the requirements, therefore, resulted in violation of the PMA orders.
The warning letter to Johnson & Johnson's (J&J) Mentor Worldwide noted
violations of two requirements that mandated the manufacturer evaluate the long-term performance of its MemoryShape breast implants under general use conditions in the postmarket environment, as well as enroll 2,518 women receiving these implants and an additional 300 women undergoing a different type of aesthetic surgery for comparison.
In response, spokesperson for J&J's Mentor unit told Focus:
"Mentor takes all of its regulatory commitments very seriously and is disappointed with the FDA’s decision to issue a warning letter despite our good faith efforts to address post-approval study requirements. We look forward to addressing this further with the FDA."
Sientra was found
to be in violation of two other requirements that ordered the manufacturer to evaluate the long-term clinical performance of its Sientra Silicone Gel implants under general use conditions in the US and to follow the enrolled study subjects on an annual basis for 10 years. Sientra did not did not immediately respond to a request for comment.
The warning letter to Mentor Worldwide pointed to several PAS deficiencies dating back to February 2017, whereas the letter to Sientra noted one deficiency in its PAS. Both manufacturers were cited for poor follow-up rates with patients in each PAS. Other deficiencies cited in Mentor Worldwide’s PAS include failure to enroll the required number of women in the study and study data inconsistencies.
Both breast implant manufacturers were directed to respond to the agency within 15 working days from 18 March with detailed information on how they intend to correct the violations.
The warning letters come amid an FDA investigation into breast implant associated-anaplastic large cell lymphoma (BIA-ALCL) cases in medical device reports, with the latest action being a letter FDA sent
to health care providers to raise awareness on 246 new BIA-ALCL cases since 2017. They follow on the heels of the EU’s move to recommend
use of smooth implants rather than textured based on its review BIA-ALCL cases.
“FDA has issued several warning letters in recent years to manufacturers who did not adequately fulfill certain postmarket study requirements, reflecting the agency’s commitment to take more aggressive actions against manufacturers who fail to comply,” the agency said
. Ocular Therapeutix, for example, drew
an FDA warning letter just last October over failure to comply with PAS requirements previously set as part of the conditional approval on the manufacturer’s ReSure Sealant. All three manufacturers marketing duodenoscopes in the US were warned
last March over 522 postmarket surveillance studies.
The enforcement actions form part of the agency’s work to advance its recently updated
Medical Device Safety Action Plan. They also coincide with the shift toward active surveillance through greater use of real-world data and real-world evidence from patient and product registries, as well as large datasets of health systems across the US. FDA recently coordinated with professional associations to develop two registries in the breast implant space—the Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma Etiology and Epidemiology and the National Breast Implant Registry.