FDA provides pathway for sponsors seeking approval of breast implants
The Food and Drug Administration (FDA) yesterday revised its guidance document
for breast implant sponsors to more clearly define FDA's recommendations
for breast implant marketing applications and to reflect the availability of
new information about the framework for assessing the safety and effectiveness
of these products. The draft guidance document has been released for public
comment and is available at http://www.fda.gov/cdrh/ode/guidance/1239.html.
“The FDA, sponsors, and the clinical community have learned a great
deal about breast implants, especially silicone gel-filled breast implants,
over the last 10 years,” said Mark B. McClellan, M.D. Ph.D., Commissioner
of Food and Drugs. “Based on this knowledge, this revised guidance is
our view on the information needed to provide a reasonable assurance of safety,
and to allow women and physicians to make informed decisions about silicone
“FDA is committed to working with sponsors and the scientific community
to provide a clear, scientifically appropriate, and up-to-date pathway for demonstrating
safety and effectiveness, and we welcome comments on this draft guidance,”
Commissioner McClellan said.
This guidance document updates a previous version published in February 2003.
The previous version of the guidance document has been useful to sponsors and
FDA in preparing and reviewing pre-market approval (PMA) applications. By updating
its guidance document, FDA is more clearly identifying the type and amount of
scientific data that will allow FDA to evaluate whether these products are safe
The substantive new recommendations in the draft guidance document involve
mechanical testing, modes and causes of rupture, clinical study information,
postapproval requirements, and labeling. The new recommendations are as follows:
- The General Information section has been modified to recommend
that the mechanical testing be designed so that it can predict clinical outcomes,
such as how long breast implants will last before rupturing in the body.
- The Fatigue Rupture Testing of Total Device section has
been modified because the methods currently used do not appear to simulate
the observed rates of rupture. FDA is now recommending that a sponsor develop
a new test methodology that can accurately predict rates of rupture over time.
As stated in the guidance document, FDA believes that retrieval study data,
which accurately define the mode(s) and cause(s) of rupture, may be helpful
in the design of the new test methodology.
- The Bleed Testing section has been modified, updating
the previous section called Bleed Rates of Silicone Gel or Alternative Filler.
FDA now recommends that a sponsor develop a new gel bleed test that more closely
mimics conditions in the body to identify and quantify the chemicals that
bleed (leach) out of the shell over time. This information will help FDA in
evaluating the safety of these products, and will help provide adequate information
to women who might be considering breast implants.
MODES AND CAUSES OF RUPTURE
- A new section, Modes and Causes of Rupture, has been added
to the guidance document, updating the previous section called Retrieval Study.
The new section clarifies FDA's recommendation that a sponsor characterize
the modes and causes of rupture. These data will help predict how rupture
rates change over time and help allow an adequate assessment of the safety
of the product.
In the guidance document, FDA recommends that modes and causes of rupture
be addressed by the following:
• a retrieval study involving examination and testing of breast implants
that have been removed from patients
• an assessment of a sponsor's manufacturing processes for the
shell to determine whether any allowances for imperfections, such as bubbles
and contaminants, may be related to device rupture
• an assessment of the surgical techniques that increase the risk of
rupture to better guide doctors on the best way to implant these devices
• a comprehensive literature review of durability based on studies of
- The General Information section has been modified to clarify
that, although a sponsor may submit a PMA with a minimum of two years of clinical
data, this data may not be sufficient to demonstrate a reasonable assurance
of safety and effectiveness. FDA may recommend the submission of additional
premarket data to describe the rates of complications (e.g., rupture and re-operation),
to reasonably predict the safety profile of the device over its lifetime,
and to address safety concerns, such as the risk of gel migration for silicone
gel-filled breast implants. For example, if, after two years, a sponsor does
not have a sufficient number of patients, sufficient follow-up, or appropriate
analyses to reliably predict the rupture rate and the clinical consequences
of rupture over time, additional clinical follow-up may be recommended to
allow an adequate assessment of the safety and effectiveness of the device.
- A new subsection, titled Rupture of Silicone Gel-Filled Breast
Implants, has been added to the guidance document, updating the previous
subsection called Silent Rupture for Silicone Gel-Filled Breast Implants.
The revised section focuses on rupture as a whole, not just silent rupture,
and includes new recommendations for data collection. FDA now recommends that
a sponsor provide the following data as part of its Core Study:
• the rate and rate of change of rupture over the expected lifetime
of the device
• the frequency of ruptures observed (intracapsular, extracapsular,
and migrated gel). For all patients with ruptured implants undergoing explantation,
FDA recommends that a sponsor provide tissue sampling data of the surrounding
breast tissue and capsule to confirm whether or not gel implant constituents
• characterization of any local health consequences of ruptured implants.
The guidance document recommends that the duration of follow-up and the follow-up
rates of the subset of patients undergoing MRI screening for rupture (i.e.,
MRI cohort) should be adequate to define the silent rupture rate and, accordingly,
the overall rupture rate.
- The Connective Tissue Diseases (CTDs) subsection has been
modified to clarify our recommendations regarding data collection on CTDs
and CTD signs and symptoms. FDA recognizes that much has been learned over
the last decade on this issue, including data and analysis from the 1999 Institute
of Medicine (IOM) report on the safety of silicone breast implants, and that
the Core Study is not designed to examine a potential linkage between breast
implants and the development of CTDs. We do, however, recommend that a sponsor
collect information on diagnoses of CTD as part of the overall safety assessment
on its device.
- A new section, titled Supplemental Clinical Information,
has been added to the guidance document. Because of the limited size of a
Core Study, FDA recommends that a sponsor provide additional clinical information
on its device (e.g., retrospective or prospective data from adjunct and/or
European studies), as well as relevant information from the published literature,
to address the following issues related to implant rupture:
• the frequency of observed intracapsular gel, extracapsular gel, and
migrated gel, as well as the destination of the migrated gel
• a detailed description of the local health consequences experienced
by all patients with ruptured implants, including the severity of these consequences,
and their clinical course
• the incidence, prevalence, and timing of silent ruptures that progress
to symptomatic ruptures
• the incidence, prevalence, and timing of intracapsular ruptures that
progress to extracapsular ruptures.
- The section titled Supplemental Literature Information,
has been modified. FDA continues to recommend that a sponsor provide a supplemental
literature review on specific topics such as CTDs (including fibromyalgia),
mammography issues, neurological disease, ability to lactate, and offspring
issues (safety of milk for breastfeeding and second generation effects). However,
in this updated guidance document, FDA now specifies that it recommends a
current literature review beginning with the 1999 IOM report and explains
that the purpose of this information is to provide up-to-date information
for women who might be considering breast implants.
- The Postapproval Requirements section has been modified
to clarify that FDA may exercise its statutory authority to require sponsor
compliance with conditions of approval or other postapproval requirements,
• a Core postapproval study. For silicone gel-filled breast implants,
FDA believes that annual physician follow-up, rather than mail-in survey follow-up,
may be appropriate, primarily because some important complications, such as
silent rupture, cannot be assessed by the patient
• continued collection of bench data regarding modes and causes of rupture
• an education and certification program to train doctors with regard
to proper surgical technique, patient selection, patient monitoring, and
• management of complications in order to obtain access to the implant
• continuation or initiation of a registry.
- The Physician Labeling and Patient Labeling
sections have been modified to recommend that a sponsor include information
in the labeling for breast implants on the following:
• method(s) and frequency of screening for rupture
• clinical management of suspicious intracapsular and extracapsular
• gel bleed results
• other supplemental information based on a current literature review.
The recommendations in the guidance document will assist sponsors in providing
adequate information to allow FDA to assess whether the data demonstrate a reasonable
assurance of safety and effectiveness of breast implants. This information will
allow women and physicians to make informed decisions regarding the use of these