WARNING LETTER
Sientra Inc
MARCS-CMS 573436 —
March 18, 2019
Product:
Medical Devices
Premarket Approval (PMA)
Recipient:
Recipient Name
JoAnn Kuhne, MSN, RAC
Recipient Title
VP, Regulatory Affairs and Quality Assurance
Sientra Inc
420 S. Fairview Ave., Suite 200
Santa Barbara
,
CA
93117
United States
Issuing Office:
Center for Devices and Radiological Health
10903 New Hampshire Avenue
Silver Spring
,
MD
20993-0002
United States
WARNING LETTER
VIA UNITED PARCEL SERVICE
March 18, 2019
JoAnn Kuhne, MSN, RAC
VP, Regulatory Affairs and Quality Assurance
Sientra, Inc.
420 S. Fairview Ave., Suite 200
Santa Barbara, California 93117
Dear Ms. Kuhne:
The Food and Drug Administration (FDA) approved your device, Sientra Silicone Gel Breast Implants, under Premarket Approval (PMA) Application, P070004, on March 9, 2012. In addition to the periodic reporting requirements, FDA ordered your firm to conduct a Post-Approval Study (PAS) in accordance with 21 C.F.R. § 814.82(a), to provide information on the long-term device performance of Sientra Silicone Gel Breast Implants under general conditions of use in the U.S. For your reference, the approval order is attached, which details the PAS requirements that were imposed as a condition of approval for your device.
Under 21 C.F.R. § 814.82(a)(2) and (9), FDA may impose post-approval study requirements as a condition of device approval when necessary to provide reasonable assurance, or the continued reasonable assurance, of the safety and effectiveness of the device under the conditions of use prescribed, recommended, or suggested in the labeling of the device. Specifically, FDA may require as a condition to approval the continuing evaluation by the applicant of the safety, effectiveness, and reliability of the device, including the number of patients to be evaluated, as well as other requirements FDA determines are necessary to provide continued reasonable assurance of the safety and effectiveness of the device.
As discussed in detail below, your firm has failed to comply with the post-approval study requirements imposed under 21 C.F.R. § 814.82(a) for your device. The Silicone Gel Breast Implant US Post-Approval Study (US-PAS) requirements, detailed in item 3 of the PMA approval order dated March 9, 2012, are shown below. Specifically, you have failed to comply with requirements 1 and 3 shown below.
1. Evaluate the long-term clinical performance of Sientra Silicone Gel Breast Implants under general conditions of use in the U.S.
2. Enroll 4,782 women receiving Sientra Silicone Gel Breast Implants and 300 women undergoing other aesthetic surgery as the comparison group within 90 days of PMA approval.
3. Follow the study subjects annually for 10 years.
4. Collect data on the following safety endpoints, via annual patient questionnaires: connective tissue diseases (CTDs), rheumatologic and neurologic signs and symptoms, cancer (lung and breast, including the potential of breast implant interference with mammography and delay of breast cancer detection), suicide/attempted suicide, local complications (including infection, rupture, and rupture rate following mammography), reoperation and implant removal, reproductive complications, lactation complications, and congenital deformities.
5. Collect effectiveness data from study participants' responses to questions addressing their perceived quality of life and satisfaction with their breast implants.
6. Collect data from physician evaluations at 1, 5, and 9 years
7. Conduct device explant analyses for all devices retrieved from women enrolled in the study.
FDA received your firm’s study protocol for the US-PAS (P070004/S003) on March 30, 2012. The protocol, submitted in accordance with requirements in your PMA approval order, was approved on May 29, 2012.
(b)(4)
in the FDA-approved protocol sets forth expected follow-up rates at years 2, 5, 8, and 10 of
(b)(4)
, respectively, which were established to ensure a minimum retention rate of
(b)(4)
by the end of the study. Your study is in initial follow-up stages. According to your most recent US-PAS Interim Progress Report (P070004/R032, received at FDA on March 8, 2019), the 3-year overall follow-up rate is
(b)(4)
% (
(b)(4)
), which is lower than any of the specified target follow-up rates at years 2, 5, 8, and 10. As stated in our letter dated May 16, 2018, your 10-year follow-up goal of
(b)(4)
% was agreed-upon to ensure that there is sufficient data to provide a meaningful evaluation of the subject device versus the control. You have already fallen below that retention rate at this early stage in the study.
We notified you in our May 16, 2018 letter that the study status on FDA’s website would indicate “Progress Inadequate” due to a poor follow-up rate (of
(b)(4)
%) at 2 years. Your 3-year follow-up rate of
(b)(4)
% shows that you have not met expected follow-up rates over the last three years and that you continue on a downward trajectory for retention.
Your firm failed to maintain the agreed-upon participant retention rate included in the approved protocol at this stage in the study period. This failure prevents adequate continuing evaluation of the safety, effectiveness, and reliability of the device at this stage (Year 3) and will prevent such an evaluation at the end of the study (Year 10). Moreover, this constitutes a failure to follow study subjects annually for 10 years. You are thereby in violation of the requirements established as a condition to your device’s approval under 21 C.F.R. § 814.82(a). Failure to promptly correct this failure may result in withdrawal of your PMA under 21 CFR 814.82(c).
FDA also advises that failure to conduct any post-approval studies in compliance with the institutional review board regulations in 21 C.F.R. Part 56 and the informed consent regulations in 21 C.F.R. Part 50 may be grounds for withdrawal of approval of the PMA.
You should take prompt action to correct the violation addressed in this letter.
Within 15 working days from the date of this letter, please provide a plan to address the issues described in this letter, or provide documentation showing that you have complied with your firm’s post-approval study requirements and notify this office in writing of the specific steps you have taken to correct the noted violation and to ensure that this violation or similar violations do not occur again. Please include supporting documentation of the corrective actions you have taken. If your planned corrections will occur over time, please include a detailed timetable for implementation of those corrections.
Your response to this letter should be identified as a “Post-Approval Study Protocol PMA Supplement”, sent to:
U.S. Food and Drug Administration
Center for Devices and Radiological Health
PMA Document Mail Center - WO66-G609
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
Finally, you should understand that there are many FDA requirements pertaining to the manufacture and marketing of devices. This letter pertains only to the issue of one post-approval study (PAS003) ordered as a condition of approval in your PMA approval order dated March 9, 2012 and does not necessarily address other obligations your firm has under the law.
If you have any questions about the content of this letter, please contact: Jennifer Stevenson at
(301) 796-5615
or via e-mail at Jennifer.Stevenson @fda.hhs.gov.
Sincerely yours,
/S/
Ann M. Ferriter
Director, Division of Analysis and Program Operations
Office of Compliance
Center for Devices and Radiological Health
Content current as of:
03/19/2019
Regulated Product(s)
Medical Devices
Topic(s)
Premarket Approval (PMA)