the Director of the new Office of Women's Health at FDA.

Mr. Shays. What we'll do is if we call on someone who is sitting
behind you we'll have them introduce themselves at that time. Dr.
Kessler, let me just say that in your business you have to have
thick skin, and I know you are a dedicated public servant. I know
there is going to be lots of disagreement on what you say, and
you're aware of that.



57

We're p^oing to try to stay on topic and deal with this extraor-
dinarily important issue. I am happy you were here for the testi-
mony of the three Members of Congpress, because I think it is a
good introduction to this issue and I appreciate your willingness to
listen to their testimony as well.

And so what I'm goin^ to suggest is that you give your statement
as you choose. I thmk it woula be good to summarize, but you've
heard the testimony before, you know the issue, and I think it's im-
portant for you to put everything on the record that you feel needs
to be put on the record.

We're going to go through and ask questions of the Members and
we'll do the 5-minute rule. If a Member needs to pursue a question,
we might give them a little more than 5 minutes and we will then
do a second pass with the Members that are here.

So, Dr. Kessler, welcome and thank you for being here.

STATEMENT OF DAVID KESSLER, DIRECTOR, FOOD AND DRUG
ADMINISTRATION, WASfflNGTON, DC; ACCOMPANIED BY
DONALD BRUCE BURLINGTON, DIRECTOR, THE CENTER FOR
DEVICES IN RADIOLOGICAL HEALTH; JOSEPH A. LEVITT,
DEPUTY DIRECTOR; AND RUTH MERKATZ, DIRECTOR, THE
OFFICE OF WOMEN'S HEALTH

Dr. Kessler. Thank you very much, Mr. Chairman. My prepared
testimony provides considerable detail about silicone gel-filled
breast implants and broader questions about medical grade silicone
used in medical devices. And Dr. Burlington will comment after I
am done on the broader questions.

Since that statement has been submitted for the record, I would
like to focus on its most important points. Although the scientific
and regulatory issues raised by silicone gel breast implants are in-
deed complex, the task of the FDA can oe simply stated. It is the
job of the FDA to ensure that breast implants are safe and effec-
tive.

The role of manufacturers is to provide evidence of safety and ef-
fectiveness. This is an affirmative duty. Simply put, manufacturers
must show that their products are safe. Because breast implants
were marketed for some 30 years because they were grandfathered
under the medical device law, there has been some confusion about
that point.

In April 1991, FDA called for the safety and effectiveness data
for these medical devices. That November, at a 3-day meeting, an
FDA advisory panel of outside experts agreed that the manufactur-
ers' data were insufficient to establish the safety and efficacy of
breast implants.

Nevertheless, the panel recommended continued availability of
the implants imder certain conditions while manufacturers col-
lected additional data under a strict time table set by the FDA,
After that meeting, FDA received a large volume of documents that
suggested that adequate quality control procedures were not in
place to prevent safety problems, that animal safety studies were
not consistently completed or even undertaken before the products
were promoted for use in women, and that indications of problems
including implant rupture, gel bleed and migration and contracture
had been evident years earlier.



58

This new information convinced us of two things. The advisory
panel needed to revisit the issue and women mi^t be at greater
risk than had been realized. On January 6, 1992, I requested a vol-
untary moratorium on the distribution and implantation of silicone
gel-filled breast implants.

The advisory panel met in February, reviewed the newly avail-
able data about implants and connective tissue diseases and the re-
lationship between implants and rupture and expressed greater
concern about implants than it had in November. The panel rec-
ommended that further use of implants be restricted to women par-
ticipating in clinical trials.

After 30 years of use, after this device had been implanted in an
estimated 1 million women, we still did not know how long it lasts
in the bodv? How often it ruptures? How frequently it had to be
replaced? And what are the consequences of that rupture?

To answer these questions and to preserve the option of access
for patients with breast cancer, on April 16, 1992, FDA lifted the
voluntary moratorium and announced that silicone gel breast im-
plants would be available with informed consent and under clinical
trials.

In the 3 years since 1992, important research has been under-
taken on some of the critical scientific questions concerning these
products. In these and other areas more research is still needed.

Let me take a moment to summarize the current state of knowl-
edge. Safety concerns fall into two categories, local complications
and systemic disease. Examples of local complications are implant
rupture, capsular contracture, infection and surgical complications.
Althougn my formal testimony cites several studies on the rupture
rate of silicone gel breast implants, the bottom line is that we still
do not know what that rate is or how it changes over time.

Several published studies suggest that the rupture rate may be
much higher than the 0.3 to 1.1 percent rate manufacturers origi-
nally estimated, and that the rate may increase as the implant
ages. In a 1992 published study, that analyzed the screening mam-
mograms of 350 women, there was a 5 percent rupture rate in
asymptomatic women who did not suspect a rupture nad occurred.
It was referred to as silent rupture.

In a 1995 study, investigators found frank ruptures in 51 percent
of patients and either frank rupture, severe silicone gel bleed or
botn in as high as 71 percent of^the patients. Published studies to
date suggest a rupture rate between 5 and 51 percent, an enor-
mous range, and unfortunately we do not know with any confidence
where within that range the real rupture rate lies.

While local complications are clearly related to the presence of
the breast implant, possible links between systemic disease and im-
plants are much more difficult to prove or disprove. We are talking
about a type of autoimmune disease called connective tissue dis-
ease including the very rare conditions such as scleroderma and
more common conditions such as rheumatoid arthritis. It is only
within the past year and a half that several epidemiological studies
of this possible connection have been published.

There are two important conclusions to be drawn from that. We
now have reasonable assurance that silicone gel implants do not
cause a large increase in traditional connective tissue disease.



59

These studies, however, cannot rule out either a small but signifi-
cant increased risk in traditional connective tissue disease or the
risk of atypical disease.

If 1 million women have silicone gel implants, even 1 percent
translates to 10,000 women. So for some women we still do not
have all the answers. In the end, Mr. Chairman, this is about get-
ting the important data FDA needs to protect and inform consum-
ers.

Dr. Burlington.

Dr. Burlington. Thank you, Mr. Chairman. If I may brieflv
touch on a couple of issues that Dr. Kessler has asked me to ad-
dress for him.

I'd like to make three points. First, silicone is not one product
but in fact a wide array of chemicals used in many different prod-
ucts. Second, that in the concern about the availability of silicone
materials, the agency and industry have worked closely together to
allow new silicone manufacturers to be used as material suppliers
by existing device manufacturers.

Third, the risk benefit assessment provided in the statutory
fi-amework is flexible. It's categorized according to the level of risk,
and it's appropriate given the broad array of products that we reg-
ulate as medical devices.

In addressing the question of biomaterials, if youll look to the
chart on my left, your right, you can see silicone products that are
in fact pol3aners. We have a drawing of a monomer that is one
building-block of these polymers. It has silicone and oxygen in the
center and carbon atoms going off the top and bottom.

These monomers are strung together in long chains and some-
times in circles in a wide array of ways. You can see in the second
line that they can be oils which are usually linear polymers with-
out a lot of substitutions and without a lot of cross-linking.

In the middle we have an illustration of gels where there is lim-
ited cross-linking, but usually not fillers. And these gels have a
semi-solid consistency. And at the bottom we have a drawing to il-
lustrate silicone elastomers which are highly cross-linked and con-
tain fillers and other substances in order to give them a rubberlike
consistency.

I assure you the chemistry of these products is almost as complex
as that which we know as organic chemistry. What we need to un-
derstand fi*om this is that there are a wide array of properties,
oft;en valuable properties in interactions with the human body that
are potentially attributable to these different chemicals.

They are not one — they are not all the same. The concerns have
been gfreatly less for the elastomers and for the oils. We have a
large number of approved products in these categories. In fact,
we've gone through and counted over 155 classes of products, either
approved or under investigation, including products that you have
illustrated on the exhibit table in front of us here and that we've
heard previously testified about.

The issue of materials availability, as this committee knows,
came to a head when Dow Corning in December 1992, annoimced
the discontinuation of implant-grade silicones to be effective in
March 1993, at least on the open market.



60

Subsequently, new companies have entered into the market place
and the agency and the industry have worked together to define
that minimal set of testing which would be appropriate to allow
substitution of materials from these new companies in the many
valuable applications. Where necessary, we have looked beyond
that minimal core set of testing and there is one particular product
previously at issue here, the hydrocephalus shunt, where because
of direct exposure to brain tissue, there is a particular concern
about the various chemicals used in manufacture of the elastomer
to make sure there is not a toxicity to brain tissue.

A second aspect of concern about that shunt is it contains a flap
valve, a valve to make sure that fluid drains out of the brain but
doesn't reflux back into the brain. That flap valve has got to open
at the right pressure. If it becomes sticky, as rubber is wont to do
over time, and doesn't open right, then the shunt won't function
right.

For that specific instance in a critical application we are working
with manufacturers to accelerate the testing and assure the contin-
ued availability of these critical products.

Beyond looking at substitute sources biomaterials, it's important
to understand that we don't look at the materials in the abstract.
We look at the materials in the context of a product in which they
are used, because the risk varies tremendously whether they are
used outside the body, on the surface of the body, for a temporary
implant or for a tube going through the body wall or for a perma-
nent implant. And that requires a different level of assessment of
what is the level of scientific data needed to assess safety and effi-
cacy.

The assessment is based on the standard of valid scientific data,
not conjecture. However, where there are risks because of areas
that are simply not known, where we did not have data to address
the risks, we must also take that into consideration in classifying
products into class 1, 2 or 3 and in terms of interpreting the stand-
ard for entering the market.

I believe this structure provides flexibility appropriate to the di-
versity of products that we regulate. Some are used for life or
death situations, like implantable cardiac defibrillators or hydro-
cephalus shunts. Others are as straight forward as tongue depres-
sors and clearly need a lesser level of data and scrutiny.

In summary, I would like to reiterate silicones are many mate-
rials, not one. The agency looks at these materials in the context
of the products in which they are used and the specific risks attrib-
utable and benefits attributable to those products. We have had a
lower level of concern about elastomers and oils than has been
raised about gel over the last few years, and the agency and indus-
try have continued to work together to assure availability of sili-
cones and silicone made products so that the health needs of the
American public can be met. Thank you, Mr. Chairman.

[The prepared joint statement of Dr. Kessler and Dr. Burlington
follows:]



61

Joint Prepared Statement of David A. Kessler, M.D., Commissioner, Food and
Drug Administration and D, Bruce Burlington, M.D., Director, Center for
Devices and Radiological Health, Public Health Service, Department of
Health and Human Services

Thank vou, Mr. Chairman. My neime is David Kessler, Commissioner of Food and
Drugs. With me this morning on the panel are Dr. Bruce Burlington, Director of
FD/Ts Center for Devices and Radiolocical Health (CDRH): Mr. Joseph A. Levitt,
Deputy Director for Regulations and Policy, CDRH; and Dr. Ruth B. Merkatz, Direc-
tor of our Office of Women's Health. I am pleased to be here this morning to discuss
the issues surrounding silicone gel-illled oreast implants and the implications for
other medical devicesuiat utilize medical grade silicone.

BACKGROUND ON SIUCONE BREAST IMPLANTS

Silicone breast implants came onto the market in the 1960s. They pre-date the
1976 amendments to the Federal Food, Drug, and Cosmetic Act (the Act), which re-

auires FDA to review and approve the safety and effectiveness of manj[ new medical
evices. Tliose amendments also require FDA to establish a systematic way to col-
lect and evaluate data relevant to devices on the market before 1976. Manufacturers
of these devices, when called to do so by FDA, are required by law to provide safety
and effectiveness data for devices, like breast implants, that had been marketed for
many years.

In January 1982, FDA published a proposed rule to classify silicone gel-fllled
breast implants into class III. The final rule was published on June 24, 1988. Under
the law, manufacturers have a minimum of 30 months following final classification
to submit the data on safety and effectiveness. On January 6, 1989, FDA aimounced
that silicone gel-filled breast implants were one of 31 class III devices with the high-
est priority for requiring the submission of safety and effectiveness data. FDA pub-
lished a proposed rule to require safety and effectiveness data on May 17, 1990.

FDA called for the safety and effectiveness data for silicone gel-filled breast im-
plants in a final rule on April 10, 1991. Premaiket Approval Applications (PMAs)
were due to FDA by July 9, 1991. Once submitted, the law gives FDA 180 days to
reach a final decision. Let me emphasize that the law reqruires manufacturers to
prove afHrmatively, with valid scientific data evaluated by FDA, that their devices
are safe and effective. Several manufacturers submitted data in the form of PMAs.
The applications from four of these manufacturers did include some clinical data.
The applications also contained, however, major scientific deficiencies. In the Agen-
cy's opinion, none of the applications provided sufficient data to assure safety and
effectiveness.

FDA brought to its General tmd Plastic Surgery Devices Panel the applications
from these four manufacturers. Despite their major deficiencies, FDA believed these
applications warranted public evaluation by the advisory panel. The purpose of the
panel was to advise FDA as to what we could tell the puolic about the safety and
effectiveness of these medical devices based on those data.

This advisory panel was composed of a broad range of experts, including rep-
resentatives from the fields of plastic surgery, oncology, epidemiology, internal medi-
cine, immunology, radiology, pathology, gynecology, toxicology, sociology,
biomaterials, and psydiology, as well as industry and consumer groups.

The panel spent three days, November 12, 13 and 14, 1991, hstening to informa-
tion regarding the PMAs, and hearing from physicians and pa.tients, advocacy
groups and others. Significant concerns were discussed regarding implant rupture*
bleea; and potential carcinogenicity of implant materials. Questions were raised
about the possibility that an inaplant might interfere with the detection of breast
cancer through mammography. On the otner hand, many individuals who testified
before the advisory panel presented information about the psychological benefits of
implants. The panel heard from those who strongly supported continued availability
of these implants, as well as from those who felt the devices were unsafe and urged
FDA to remove them from the market.

The panel's deliberations resulted in a series of conclusions and recommendations.
First and foremost, they concluded there were not sufficient data about the risks
and benefits of these devices. Basic questions were unanswered regarding the chem-
ical properties of the silicone gel, the physical properties of the implants, including
the uiefl, and the possible acK^erse effects of implants. The panel agreed with the
assessment of FDA scientists that the clinical data provided in the applications were
not adequate to allay safety concerns. Panel members expressed the view, however,
that the devices appeared to serve what could be viewed as a public health need.
They recommended, therefore, that silicone gel-filled breast implants continue to be
available under specified conditions, and that a patient registry be established while



62

manufacturers collect additional data. They also urged FDA to hold manufacturers
accountable to collect the additional data without delay.

After the meeting concluded, FDA became aware of information about the im-
plants that was not available for presentation to the panel.

First, FDA received a large volume of documents that suggested that adequate
quality control procedures were not in place to prevent ssSeiy problems, that animal
safety studies were not consistently completed or even undertaken before the prod-
ucts were promoted for use in women, and that indications of problems — including
implant rupture, gel bleed and migration, and contracture — ^haa been evident years
eariier. In addition, FDA was advised that some physicians and researchers were
suggesting an association between connective tissue disorders and breast implants.
The Agency contacted a large number of physicians who specialize in diseases of the
immune system. These individuals confirmed that there was a concern regarding a
possible link between silicone gel implants and the development of one of these ous-
eases.

We became convinced of two things. First, consumers might be at greater risk
than we had anticipated earlier. Second, the advisory panel needed to revisit its rec-
ommendations in light of this new information. On January 6, 1992, therefore, I re-
quested a voluntary moratorium on the distribution or implantation of silicone gel-
filled breast implants until FDA and the advisory panel had an opportunity to con-
sider the newly-available information. The manufacturers agreed to comply with the
voluntary moratorium.

Shortly afler the moratorium began, another issue of significant concern came to
light: the phenomenon of "silent rupture." These were situations where implant rup-
tures were undetected by the patient. In the case of rupture, the gel has the poten-
tial to spread through neighboring tissues. When rupture occurs, the standard prac-
tice is to have the device surgically removed and replaced.

We re-convened the advisory panel for a second meeting on February 18, 19 and
20 1992, to review this new information and reach a decision regarding the future
availability of silicone gel-filled implants. The committee was asked to look at the
incidence and hazards of rupture and bleed, the possible link to autoimmune dis-
ease, and the industry's record on testing, reporting and marketing of these im-
plants over the last thirty years. The members expressed heightened concern re-
garding the safety of the implants. The panel recommended:

• That further use of implants be restricted to women participating in scientific
protocols. Women who need breast reconstruction should be allowed unrestricted ac-
cess to the protocols. The number of augmentation patients, however, should be lim-
ited to that needed to answer specific safety Questions about the implants.

• That epidemiological studies be conducted to assess the risk of autoimmune dis-
ease, though concluding that no causal link had been established between auto-
immune disease and silicone gel-filled breast implants.

• Women with breast implants, even if asymptomatic, should be checked regularly
by their physicians. Women should not be routinely x-rayed to check their implants
ii they are not having problems. If a woman with implants is in the age eroup
where regular mammograms are recommended, she should be sure to have them.
Special mammography techniques are necessary in order to detect breast cancer in
women with implants.

• Manufacturers must provide adequate preclinical data on the implants, such as
the chemical and physical characterization of the implant materials and their resist-
ance to stress and rupture.

At this point, the Agency had three options on how to proceed under the statute.
It could: (1) approve the applications; (2) deny the applications; or, (3) if there was
a public health need, allow continued availability of the products while the manufac-
turers supplemented their applications with additional scientific data.

Approval was not justified given the absence of data to support a finding of safety
and efficacy. Complete denial of the PMAs would have resulted in removal of the
products from the market, making them unavailable even to women who required
reconstructive surgery. A compelling case had been made that a public health need
existed for women seeking reconstructive surgery. The Agency, therefore, decided on
a combination of the second and third options, based on the indications for use.

The PMAs for implants used in breast reconstruction were held open to allow con-
tinued availability while the needed data were collected. Consistent with the panel's
recommendations, we required that women seeking breast reconstruction with these
implants enroll in scientific protocols so that the needed scientific information would
be obtained. The deadline for completing the submission of data and the Agency's
subsequent review, as defined in the medical device law, has been extended indefi-
nitely Dased on public health need. The data required to complete the review must



63

be collected by the manufacturers and submitted to FDA. To date, those data have
only been partially collected.

tne PN^s for breast implants used in augmentation were oflicially denied by
FDA. These devices may be used for augmentation only with an Investigational De-
vice Exemption (IDE) in an FDA-approved research study.

In either case, for breast reconstruction or augmentation, silicone gel-filled breast
implants are available only through clinical studies conducted under a protocol. This
is the way to answer the questions of women, doctors, and FDA, and those of our
advisory panel of outside experts, regarding the safety and eflectiveness of these im-

Klants. With these actions on the PMAs on April 16 1992, the moratorium ended,
lanufacturers can fulfill their legal, affirmative obligation to demonstrate the safe-
ty and effectiveness of silicone gel-filled breast implants by conducting the required
clinical studies.

CURRENT INFORMATION REGARDING THE SAFETY OF SILICONE GEL

Today I would like to give you an update on the safety of silicone gel breast im-
plants based on the published literature and respond to some of your questions
about silicone in general. The good news is that in the three years since 1992, im-
portant research on these products has been undertaken, some by FDA staff, on
some of the critical scientific questions. In these and other areas, more research is
still needed. FDA has worked with the industry and academic community to encour-