tions. We've looked at the research to date. It allays concerns in
certain areas; it doesn't allay concerns in other areas. That data
has not been submitted by any sponsor to the agency to date. We're
even relying on published reports.
Mr. Shays. You know, with all due respect, we may end up with
no sponsors, and we may end up with no manufacturers, with that
kind of attitude. So it's almost a self-fulfilling prophecy. I think
your agency needs to help sort this out. I'd like to get this issue
in the second round. I appreciate the gentleman for vielding.
Mr. GUTKNECHT. I appreciate your comments, and I look forward
to hearing more.
Mr. Shays. Let me just say, to give everyone an update on where
we're at, we're going to get you out of here. Dr. Kessler, by 1:30.
And we're talking aoout a half-hour more. We are going to start
the next panel by 1:30, possibly sooner, but we will definitely start
it by 1:30.
We have two Members who haven't gone the first round, then
we're going to get into this issue, I think, in more depth in the sec-
ond round, with those Members who are here.
Dr. Kessler. Absolutely.
Mr. Shays. Mr. Fox.
Mr. Fox. Thank you, Mr. Chairman.
Doctor, since the 1992 moratorium, more than a dozen epidemio-
logical studies have been reported, in either complete or abstract
form, on the reported relationship between implants and connective
tissue disease, and no link has been found in any of them.
How could the FDA say, in its June 22 statement on the study,
that research is only beginning to emerge on this issue?
Dr. Kessler. Mr. Fox, Congressman, again, there are a number
of questions about breast implants: How long do they last? What
percent rupture? What are the consequences of those ruptures? The
epidemiological studies you refer to talk about the link between
breast implants and certain connective tissue diseases. That's why,
I believe, we made that statement.
Mr. Fox. But I'm saying, from your position, is there a causal
link between the silicone breast implant and any connective tissue
disease?
Dr. Kessler. The advisory committee, in 1992, stated there was
no evidence that supports a causal link between breast implants
and typical connective tissue disease. And I maintain that that
statement was the best science in 1992, and I think that statement
is also appropriate today. And I think there is much more evidence
today to back up that statement.
Mr. Fox. You say additional research is needed into ruptures and
autoimmune diseases. How long should it take to complete that re-
search to a degree that satisfies FDA
Dr. Kessler. If I know what the rupture rate is over a reason-
able period of time, using both retrospective and prospective stud-
92
ies, and that data is submitted, we will act very quickly on that
data.
Mr. Fox. Would it take months? Would it take years? Do you
know how long?
Dr. Kessler. For us to act on that data? Once that data is sub-
mitted to the agency, I think we can act within months.
Mr. Fox. What do you say to women with implants in the mean-
time?
Dr. Kessler. That's very important. And I think that is what I
said in our testimony today, that the evidence to date provides rea-
sonable assurance that there is not a large increase in risk in con-
nective tissue disease. I can't tell you that it rules out a small but
statistically significant increase. It doesn't rule out atypical forms
of disease.
And I don't know today how long these devices last and what
percent rupture, although I have some very significant concerns
based on the published reports. But those published reports on rup-
ture rate are not satisfactory. I think the patient selection and the
size of those studies are not very adequate.
Mr. Fox. I think the concern that the chairman and the commit-
tee have today with FDA saying, "We need to study it more and
study it more," is not acceptable, I think, to the American public.
I mean, in my opinion, if the FDA launched Apollo 13, it would still
be orbiting the moon because you want absolute certainty.
Dr. Kessler. Congressman, I think before you put an implant in
somebody, you should be willing and understand the consequences.
You should know what percent rupture, how long they last. There
is an affirmative duty on the manufacturer — ^beating up on the
FDA and holding FDA responsible for evervthing may be in vogue.
Mr. Fox. I think that Congress is seriously pursuing this because
we want to jointly make sure that we're protecting the public.
Dr. Kessler. I understand that, and I welcome that.
Mr. Fox. I think there still has to be an end point, Doctor, by
which the public can expect some definitive answers so we can
move forward.
Dr. Kessler. And what I said, Congressman, is that, when the
data is submitted to this agency that answers those questions, we
are committed to reviewing that data within months.
Mr. Fox. Well, don't you think the FDA needs to take a proactive
approach in making sure that the data, either independently re-
ceived or that which is already in good science, comes to some reso-
lution in the near term? Because I think that, while no one is try-
ing to bash FDA, I think the fact is, we need to work together to
make sure there's an end point to which the FDA comes to conclu-
sions, so that women who have to face this issue can do so with
as much available knowledge that you give them, as much as in-
dustry can give them.
Dr. Kessler. Congressman, you are correct. But my only point
is that we need certain partners in order to do that. We need in-
dustry and our sister agencies who are going to work together with
us to be able to get the answers to those questions.
Mr. Fox. Well, as a result of the silicone scare in 1992, which
was set off by FDA, don't you think there has been a spill-off effect
to development of new medical devices because of the fear by in-
93
dustry to offer them, because of the concerns that may be long-term
and time-consuming, whfle they may be life-saving or life-extend-
ing, they aren't offering them because of the concerns that have
happened as a result of what happened with the FDA scare on
breast implants?
Dr. Kessler. Let me ask, again, Mr. Marlowe to — ^you know,
there has been a lot of discussion about whether there is a crisis
in a lack of availability of silicone that has delayed or impeded the
development of new products and other products. I would like Mr.
Marlowe, who is an expert, to answer that.
Mr. Marlowe. Mr. Congressman, I think that it's fair to say that
there is a slowdown, if you will, in the development of brand new
medical device materials in this coimtry. There is perhaps a reluc-
tance to introduce some of these currently available materials in
areas where there is apparently a high risk associated with those
devices.
But I think that the materials remain available today. A manu-
facturer who wished to find a material to make a medical device
could find one today available in the marketplace.
Mr. Fox. Thank you, Mr. Marlowe, but my concern is, if we have
FDA not acting fast enough to get information with certainty to
women who need to have it, then we could have the ripple effect
that other medical devices that are needed by the public are not
going to be introduced in this country but rather in other countries
because we have been too slow to move ahead the approval process,
to get the scientific data, and to get the information back to a pub-
lic that is waiting for it. That's my concern with FDA.
Dr. Burlington. Mr. Congressman, we are seriously concerned
about that, as well, and the agency did, in fact, fall far behind on
its time schedule for review of devices. Over the last couple of
years, we have moved arduously to correct that.
We put in place a number of new policies. We have very substan-
tially shortened the time to review for the abbreviated applications.
We are working now with manufacturers to shorten time for the
comprehensive applications, PMA's, because we also believe that
having a vigorous industry, having new products is important to
the American public health.
Mr. Fox. We share that, obviously, with you to try to move
ahead, because the speed with which our constituents and your pa-
tients and our citizens can get it is very important, because we
want to have life-extending and life-saving devices available, and
we want to make sure we do it as quickly as we can.
Thank you, Mr. Chairman.
Mr. Shays. I thank the gentleman.
Mr. Chrysler, you have me floor.
Mr. Chrysler. Thank you.
Actually, I had the opportunity to communicate with Dr. Kessler
this year, in May, and he gave me a very good response by the end
of May. I had my questions answered, and I appreciate your
promptness in those replies. Maybe I would just have one quick
question.
You mentioned about the large study from the National Cancer
Institute, can you give me any further progress on that study?
94
Dr. Kessler. Sure. Let me ask Dr. Lori Brown to talk a little
about that study. She's our epidemiologist within this area.
Dr. Brown. I m Lori Brown. I'm from the Center of Devices and
Radiological Health also.
The study that you're talking about is one which is being con-
ducted at the National Cancer Institute by Dr. Louise Briton and
is subcontracted out to a company which is doing it. It will include
14,000 women who have breast implants and a control of 4,000, so
the total study population will be 18,000 women.
They are currently collecting the first phase of the data, which
is looking through doctors* records of women who have had breast
implants. "They have started now to contact women, and they are
getting information from these women. The third phase of the
study will be to examine the medical records of other doctors other
than the implanting surgeons who were involved. So you can see
this is a very large and complex study.
They are funded through 1996, and after 1996 they may seek
more mnding, but it's not clear whether they will or not. They have
completed some of the data collection, but data collection is ongo-
ing. The original intent of the study was to examine cancer — ^it's at
the National Cancer Institute — but they also will be studying con-
nective tissue disease and local complications.
That's the information that we have on that study. I am in con-
tact with Dr. Briton probably every couple months and so am keep-
ing up with the progress of their study.
Mr. Chrysler. Thank you very much. I yield back my time, Mr.
Chairman.
Mr. Shays. I thank the gentleman.
We're going to go through a second round of questioning, Dr.
Kessler. When I started out, I asked you if you were more con-
cerned with ruptures or autoimmune issues dealing with silicone
safety. And I didn't think you were very forthcoming, because, as
I listened to your response, you kept coming back to your concern,
and it was always on rupture, almost every time.
So I'm struck with the fact — I'd like to give you an opportunity —
are you concerned about silicone safety, or do you feel that there
have been enough studies done on this issue?
Dr. Kessler. I think that the studies on connective tissue dis-
ease, the Mayo Clinic study and the Harvard Nurses Study, as I
said before, I think those are good studies. I think that those allay
significant concerns on autoimmune disease. I don't see the same
good studies on rupture. I see some numbers that I see as high in
rupture; I don't see good studies.
Mr. Shays. I think that's helpful information. And I have to tell
you, as I read your testimony, it was clear that you were very con-
cerned about ruptures. After reading some of the testimony of wit-
nesses, I have a concern about that, as well. So describe for me the
study that would give the data on ruptures that would answer your
concerns.
Dr. Kessler. The first question you would have to answer is,
how long do you need to monitor that? When is there a suspicion
that these devices may fail, when they may fall apart, and over
what period of time? I think, if you look at the science to date,
there's reason to suspect that you're dealing, maybe, with a bath-
95
tub curve, where you see failure initially and then failure after a
period of time.
But that's only a hypothesis. So you need to be able to get rup-
ture rates over a period of time, and you may not be able to do that
and be able to wait, prospectively. There s a prospective study
under way by one company that has enrolled 12.000 patients. Now,
that's planned to go on for some period of time, but how do you ^et
the information at 7, 8 years where there may be a significant in-
crease? So you may have to go back and use a prospective study
as well as retrospective. It's tne totality of the evidence. There are
always going to be, Mr. Chairman, certain weaknesses.
Mr. Shays. No, I understand. I want to just kind of nail down
some of these key points. You've provided helpful information to me
to say that rupture is a bigger concern.
Dr. Kessler. It's a real concern.
Mr. Shays. In one sense, we have an advantage, because we
have people who for years had these devices, and we can go back
and look.
Dr. Kessler. Some of the science is a little difficult on that.
Mr. Shays. One of my concerns is, basically, we have 1980 tech-
nology, because I don't see a lot of manufacturers trying to incre-
mentally improve these devices.
My colleague gave this wonderful description, which I share, of
two trains coming and hitting each other, and you're basically de-
scribing in graphic detail what's happening, as if you're not a play-
er in this process, like maybe you can, you know, stop one trmn
and maybe we can get one train off the track.
I almost view it differently, that they are going parallel, and they
are never going to meet. And they've got to meet eventually, and
they are never going to get on the same track. That's why I believe
we can go on indefinitely.
You say manufacturers have an affirmative duty to provide and
submit data. So have you specifically outlined to manufacturers
what kind of data you want on ruptures, because that is your con-
cern?
Dr. Kessler. Again, I just want to be specific. The guidance that
we put out in 1992 covers a number of areas. Rupture is certainly
a very significant part of that. Let me let Dr. Burlington comment.
Dr. Burlington. Mr. Chairman, the guidance that Dr. Kessler
refers to provides a great deal of information on what we would
look to a manufacturer to tell us about the way the product is
made, about what its laboratory, what its animal testing, and tis-
sue culture testing might be.
Mr. Shays. I'm talking in regard to rupture right now.
Dr. Burlington. It is. however, somewhat vague regarding
what — ^it says what we're looking for; it doesn't get down to specif-
ics about how long, how many patients, that sort of thing.
Mr. Shays. Let me iust interrupt you, sir, if I could. Wouldn't it
be helpful, if you could nail down exactly what you need, to specifi-
cally spell it out to the manufacturers and get this process moving?
Dr. Burlington. Because of concern that manufacturers would
think that this was an insurmountable goal, either for this product
or for alternatives, I asked the staff to put together a workshop
which we held last fall, for alternatives, in part to address this.
96
with outside input from our external advisors. I believe that was
fruitful.
We now have one manufacturer who we're sitting down and talk-
ing with very specifically about what is appropriate, in terms of a
data package, to move forward with their product. I would welcome
the opportunitv to do that with one of the silicone gel manufactur-
ers. That would require a manufacturer coming forward and say-
ing, "We're serious about doing this. We're ready to do these trials."
Mr. Shays. Hold up a second. Hold on a second.
Dr. Burlington. Yes, sir.
Mr. Shays. I asked if you had any applications. You said you had
applications from two manufacturers. We know some manufactur-
ers have gotten out of the business. Are you saying that they are
not sincere in their applications? So, in a sense, is my question a
meaningless question? Do we have anyone who wants to get in this
business? Do we have serious applications?
Dr. Burlington. For silicone gel breast implants, we have two
applications which, as discussed earlier, are technically open, Mr.
Cnairman.
Mr. Shays. Do you view them as serious applications?
Dr. Burlington. I would welcome an opportunity for those com-
panies to come in and sit down and say thev are serious about this,
and move forward as rapidly as we can. I have not seen that hap-
pen.
Mr. Shays. Mr. Burlington, I don't mean to be disrespectful, but
they probably don't think you're serious either. Because, in my
judgment, this is a very serious issue Dr. Kessler — I feel like you
all are on the sidelines just waiting for somebody else to do some-
thing. And I would encourage you to be very proactive on this
issue.
We have nailed down, in my judgment, one issue: you are more
concerned by ruptures. So let's deal with rupture.
Dr. Burlington. Mr. Chairman, with due respect, I believe we
have made efforts to be proactive, specifically in putting out the
g^dances, specifically in putting out those offers to meet with com-
panies, and would welcome the opportunity to move forward on
that issue.
Mr. Shays. But you did state to me, Mr. Burlington, that you
weren't very specific as it related to rupture issues, that you were
very vague. I mean, I just heard you say it.
Dr. BURUNGTON. The guidance put out 6 months before I arrived
was, in fact, vague on the rupture. It addressed the generalities;
it did not address the specifics.
Mr. Shays. How long have you been there?
Dr. Burlington. Two and one-half years, sir.
Mr. Shays. So what prevents you, in 2V2 years, from being spe-
cific?
Dr. Burlington. We have moved forward, last fall, with an addi-
tional discussion. If a manufacturer is forthcoming, we will indeed
sit down.
Mr. Shays. I just want to say that that kind of attitude just con-
firms to me that we're going to get nowhere, that we will be in this
limbo. And I have some experience now, having had the second
hearing with FDA where we have this 180-day requirement on food
97
additives, and applications have been pending for 20 years. Obvi-
ously, that is not your fault, but the sense that the law doesn't
even have to be abided by.
Dr. Kessler. Congressman.
Mr. Shays. Yes, sir.
Dr. Kessler. I became Commissioner in December 1990.
Mr. Shays. Right.
Dr. Kessler. I wish the data was collected and submitted to the
agency to answer the questions at least, you know, a decade before.
Mr. Shays. OK They weren't.
Dr. Kessler. We need to get that data. We will work with com-
panies to get that data. Once that data comes in, we will review
that data. But let me make sure that I don't misspeak.
An application contains information on a lot of areas. It will con-
tain information on autoimmune disease. It will contain informa-
tion on tensile strength. It will contain information on chemistry.
I've not yet reviewed or audited like we do the published studies
that we've talked about; I've talked about them based on the lit-
erature.
We will look at the entire application. There will be weaknesses
in certain areas; there will be strengths in another. In the end, the
question is whether the data submitted to the agency allows the
agency to make a reasonable scientific judgment that the risks are
acceptable in light of the benefits.
I just don't want to say that the only data that needs to come
into the agency is rupture. We need to look at all the data.
Mr. Shays. Dr. Kessler, I don't disagree with the general thrust
of your comments, but all you do is confirm to me this issue will
never be resolved. It is a mind-set and an attitude on your part and
the departments's part that troubles me.
Let me just ask you, as it relates to the Food, Drug, and Cos-
metic Act, it says, The Secretary may not enter — ' mav not
enter — "into an agreement to extend the period in which to take ac-
tion with respect to an application submitted for a device subject
to a regulation promulgated under Subsection (b), unless he finds
that the continued availability of the device is necessary for the
public health."
So are you functioning under the "unless"?
Mr. Levitt. Yes.
Mr. Shays. OK Now, where is the agreement?
Mr. Levitt. At the time of that decision, we entered into written
agreements with each company which outlined all of the relevant
provisions. We set forth, concurrent at that time, a three-stage pro-
cedure, which was outlined in the Commissioner's statements at
that time.
Mr. Shays. We only have two companies; right?
Mr. Levitt. One company progressed to the second stage and
never pursued the third stage. The second company was never able
to satisfy existing regulations on good manufacturing practices:
meaning how you make the product, what its quality is, and what
is consistently between products. So that company never started
the prospective clinical trial stage.
In contrast, Mr. Chairman, if I might say — ^because you have a
clear concern about us being proactive.
98
Mr. Shays. I think you're proactive, but sometimes I think you're
proactive in the wrong way. And I don't mean that disrespectfully.
I think you can be very active and very determined, but I don't feel
this kind of determination to resolve this issue.
Mr. Levitt, If I may just say, in the area of saline breast im-
plants, we have been working with these very same companies. We
have set forth a research agenda and schedule, and those compa-
nies are pursuing that. One thing I derive from that is that we do
understand when the companies are seeking to perform the studies
and when the companies, for whatever of their own reasons, are
not.
Mr. Shays. I understand that companies — and I w£int to let other
Members ask questions — I understand that companies sometimes,
if they don't think they are going to like your answer, they aren't
eager to get the answer and may not encourage you to give them
the answer.
But it is your sworn testimony that there are agreements. Now,
have these agreements been modified, and are they in writing?
Dr. Kessler. I'd be happy to
Mr. Shays. I know. But are those — I thought your testimony was
that, basically, they couldn't abide by the agreement; they couldn't
meet what you wanted. We have only two people in this business,
probably we will soon have one, and maybe we will have none, and
you will still be waiting for some company to take an affirmative
action.
My point to you is this: You have both told me they have not met
the agreement.
Mr. Levitt. No, no, no. That's not what we said.
Dr. Kessler. I don't think I've said that. I'm not an expert in the
agreement at all.
Mr. Shays. You didn't answer the question, Dr. Kessler.
Dr. Kessler. I'm sorry.
Mr. Levitt. There are written agreements.
Mr. Shays. It is in writing.
Mr. Levitt. It is in writing. I honestly can't recall if it was modi-
fied along the way; it may have been.
Mr. Shays. We will have a second followup hearing, and we're
going to get into more depth here.
Mr. Levitt. Right. The agreement sets forth, as I recall it — it
will speak for itself.
Mr. Shays. Well, you know, since you don't really remember it,
we're not going to talk about it right now.
Mr. Levitt. All right.
Mr. Shays. The point, for the record, is, there is an agreement.
We will be able to get it, and we will be able to get you back here
and question you on it.
I will just say, for the record, before I turn to my colleague, that
I'm absolutely convinced that whether the trains are headed in the
same direction and they are going to crash, or whether they are on
separate tracks, never to meet, either scenario, it's a no-brainer; it's
never going to happen. We're never going to resolve this issue. It
is going to be in continued limbo, just like the 20-year pending food
additives applications.
99
And Dr. Kessler, I think you — I'm not asking you to do it — but
you need to delegate to someone to find a solution. It seems to me
you need to map out, in very specific terms, what you need, and
I don't think that agreement is going to be doing that.
Mr. McIntosh. Mr. Chairman, thank you. Let me also say, if you
feel you need to have more questions to get to the bottom of this,
I'm 100 percent behind your line of questioning there.
My question is — and I think that the chairman is onto something
here — that we're not seeing a rush of companies come forward to