regarding the classiiication of the devices; 2) biased selection of consultants to the
panel; 3) the unbalanced views of the speakers; and 4) a conflict of interest on the
part of the Chairperson. The Agency decided to set aside the recommendations of
the panel and re-examine the classification of muscle monitoring devices at a future
meeting of the panel.

Clinical Laboratory Devices Advisory Committee

• 5/1/95 — The panel voted (five to four) to require, as a condition of PMA approval,
that the sponsor for the ChemoResponse assay conduct additional reproducibility
tests at five to seven sites or reanalyze the data. The DCLD PMA Team asked the
sponsor to conduct inter-site reproducibility tests at three sites.

Device Good Manufacturing Practices Advisory Committee

• 5/29/91 — The panel recommended the Agency adopt verbatim ISO 9001 as the
standard for GMP compliance, adding elements FDA believed were important but
not addressed bv the standard. The Agency later determined it could not adopt ISO
9001 verbatim because a review of me language revealed potential enforcement

Sroblems. In addition, it is a copyrighted document. FDA deaded to revise its own
rMP regulation, incorporating provisions contained in ISO 9001.

NATIONAL CENTER FOR TOXICOLOCICAL RESEARCH

Science Advisory Board

• 11/16/93 — The full Board approved a draft report on the Nutritional Modulation
of Risk and Toxicity Program, which recommended that we separate and manage
the Program as two individual activities. After a review by NCTR management,
FDA decided to continue managing the two activities as a single program due to
the uncertainty of funding for one oT them, the Project on Caloric Restriction.

FDA ADVISORY COMMITTEES BY CENTER

Center for Bioloncs Evaluation and Research — 4
Center for Drug Evaluation and Research — 17
Center for Devices and Radiological Health — 19
National Center for Toxicolo^cal Research — 2
Center for Veterinary Medicme — 1
Center for Food Safety and Applied Nutrition — 1

Mr. Towns. That's clear. Mr. Chairman.

Mr. Shays. Yes. That's very clear. And, also, if you would state
what they are.

Dr. Kessler. Sure. I'd be happy to.

Mr. Towns. Let me just ask one more question, very quickly be-
fore I move on.

Dr. Kessler, in your testimony you suggest that the FDA will
only be able to make a final conclusion on the safety of silicone
breast implants when manufacturers submit additional data to
support their pre-market approval application. The problem I have
with that is many companies have no interest in financing further
studies because liability concerns have scared them out of the mar-
ketplace. Do you have any suggestions as to how you might encour-
age research? I think that that has to be a concern.



76

Dr. Kessler. Congressman, I think that is a very important
question that you asked. When there are important public health
questions and there isn't a company whose interested in doing the
research or producing a product, I think that there is a responsibil-
ity on the Federal Government, if it's an important public health
question, to get the answers.

For example, the NCI is doing a large study now on breast im-
plants, but the Federal Grovemment can always do more. I found
myself in a situation a year or two ago where no company was in-
terested in making certain drugs for tuberculosis, and we have an
increase in drug-resistant tuberculosis. There wasn't the incentive
to do that. We stepped in, we had to find somebody.

I don't manufacture drugs. I don't manufacture devices. I don't
test them myself. We do a little research, but we're really not pri-
marily a research organization, but we do work with our sister
agencies, the NIH, for example, and there certainly can be more
Federal research into important public health questions.

Mr. Towns. Well, you know, in closing out, what would you advo-
cate that we do. Let's switch the roles for a moment.

Dr. KESSLER. Just help me understand this. Specifically, get
more information and more data.

Mr. Towns. And encouraging research.

Dr. Kessler. Encouraging research into silicone. I think that
with the litigation environment, the research is not being pursued
in quite the way that many people would like, I think it s reason-
able to ask for more of a Federal presence in doing that research.

You need to understand, Congpressman, there has been a lot of
research, in the last couple of years. We know a lot more now than
we knew in 1991 and 1992, and a lot of the research that's been
done has been good. But there is certainly — there is no question
that more research certainly would be very helpful and very helpful
to us.

I would like very much to be able to answer the chairman's ques-
tion of when would I have the answers, but the problem is, I don't
do the major research myself, so I don't control that.

Mr. Towns. Thank you very much, Mr. Chairman.

Mr. Shays. With leave of the committee, I just want to just fol-
low up that point. That's where I have a problem with the FDA,
because I think it's incumbent on you to suggest exactly what you
need. I mean, we're really in this catch-22 situation as pointed out
by the gentleman here.

You have helped stimulate concern about what's happening.
There are court cases that are in process. You are not going to have
manufacturers seeking to get into this business. They're not going
to want to do the studies, but you're saying they have to do the
studies. So when I come back to my questions, I want to know spe-
cifically what you need in order to make a decision, and if there
are others around you who can get that answer in that time.

Mr. Mcintosh.

Mr. McIntosh. Thank you, Mr. Chairman. Let me start out by
saying that I don't think our concern here is whether manufactur-
ers can manufacture this product so much as whether women will
be able to have the product available to them when they need it.

/



77

And I did a quick count of the room and noticed that there were
about 86 women here presenL I may have miscounted one or two
so it could be off. If they are correct that 1 in 8 has an expectation
of getting breast cancer, that means that potentially 10 people here
to<my will suffer from breast cancer.

Now, if any one of them is reluctant to go and get a mammogram
or reluctant to get a surgery as Dr. Ganske and Mrs. Lloyd men-
tioned was possible, then I think we've done a terrible disservice
to them and every woman around the country. I think it's impor-
tant for us to note what this question, about it's the responsibility
of the manufacturers to do research, is really all about.

I mean, I think it's a dodge of the responsibility that all of us
have as government officials of reassuring people about the safety
of this particular procedure. And we heard from Dr. Ganske that
local complications are inherent in any surgical procedure. We
heard from Dr. Ganske that the studies, 17 studies, show that
there wasn't £iny connection between systemic diseases and breast
implants. And as far as I can tell, the record shows there aren't
any studies that ever indicate there is a serious connection between
those.

It looks to me like we're being asked to study this, literally, to
death in order to prove something that is perhaps statistically
unprovable. And I think the chairman's question is a good one, how
many more studies will we need all of which conclude that there
is not a connection before the agency is willing to make that state-
ment and go forward with the product approval?

Dr. Kessler. Congressman, you didn't ask Dr. Ganske, or no one
asked Dr. Ganske, how long these devices last, what percent fails
what are the consequences of that. You focused on autoimmune dis-
ease, and there has been good research on that, but the guidance
that we issued in 1992, on what we needed to know to be able to
answer the very important questions for women who have these de-
vices in them today, involves research on all those questions.

Mr. McIntosh. Let me interrupt you for a second, Dr. Kessler.
I think that is a red herring. I think that if you've got a chance
that somebody is going to avoid treatment for breast cancer, we
ought to let them know we don't know how long this will last. We
don't know whether there is a chance that a certain percentage of
them will disintegrate, but we do know that it is available today
and that there are women out there who have had this implant in
the past £ind they have lived perfectly healthy lives.

And we do know that all of the studies to date show that there
is no connection between some other disease.

Dr. Kessler. Congressman, we have worked very hard to encour-
age over the last year — ^you gave us responsibility for ensuring the
quality of mammography facilities and mammography awareness.
Every woman, certainly, who is in the appropriate age gproup and
younger women who have the risk factors should have a mammo-
gram. There are a lot of reasons why somebody doesn't want to go
for a mammogram; it's scary.

Mr. McIntosh. Why hasn't the agency articulated that factor in
this whole issue? Why haven't we lookea at the relative benefits of
going forward in approving this product?



78

Dr. Kessler. In 1991 and 1992, clearly the risks and the benefits
were weighed. The manufacturer has to submit data both on the
risks and the benefits. The availability of these devices, especially
for women with breast cancer, is very important. And that's why
we've continued to make these available through informed consent,
but I've also insisted that as we do that we also get the data so
we can answer the questions.

Mr. McIntosh. But, I guess, let me turn back to my original
question. How many more studies will we need that show that
there is no connection between the diseases in order to have a
product approval?

Dr. Kessler. The number of studies that it takes to answer a
basic question of how long do these devices last, what percent rup-
ture, what are the complications of that rupture. That's what it's
going to take.

Mr. McIntosh. And how many is that, in your estimation?

Dr. Kessler. A few good studies could be sufficient to do that.
But today I'm sitting before you and I can't tell you with any de-
gree of confidence what the rupture rate is or how long these de-
vices last.

Mr. McIntosh. Why do you need to know that before you can
allow a woman to make that choice that is potentially lifesaving?

Dr. Kessler. How does someone make a choice if you don't have
information. In informed consent, at least you give some informa-
tion.

Mr. McIntosh. Now, Dr. Ganske tells us that all devices eventu-
ally wear out and break and that it is standard procedure to re-
place them when that happens.

Dr. Kessler. That certainly wasn't the impression back in 1991,
where the rupture rate was generally viewed at about 1 percent.
Women deserve to have that information as part of an informed
choice and we need to get that information.

Mr. McIntosh. My problem is that until then, we're not going
to send them a clear signal that it's safe to go forward with this
and that some women will choose not to go forward with the proce-
dure and that on a cost benefit analysis, we're doing more harm
than good.

Dr. Kessler. Which procedure?

Mr. McIntosh. To have reconstructive surgery or to have a bi-
opsy?

Dr. Kessler. But again, I just want to emphasize as strongly as
I can the need for early detection. I agree with you. There are a
lot of reasons why people are scared to go in for a mammogram or
a biopsy, and I am very sympathetic to that. But that doesn't mean
that one should allow a device on the market if you have questions
for which — and for which there aren't answers. I am not aware of
a decrease in the number — ^perhaps you are — who didn't go for
mammograms during the 3 months when we said there was a vol-
untary moratorium.

Mr. McIntosh. But what we did hear earlier today is that
women delayed going forward with the process to correct the prob-
lem and that they continue to do so if there is a fear that the de-
vice will not be available, it will be unsafe.



79

Dr. Kessler. Dr. Merkatz perhaps can answer this question
much better than I can, Congressman. But my understanding is
women don't go in for mammograms for a lot of different reasons.

Dr. Merkatz. Well, I think one of the most important reasons is
that women need to be assured that the mammogram that they
will have will be a quality mammogram, and that is one of the rea-
sons why many women came to Congress to testify, for improved
quality in mamographies.

Mr. McIntosh. But is it your opinion that one of the reasons
that they may delay detection or treatment is the uncertainty
about reconstructive surgery?

Dr. Merkatz. We asked that question at our advisory panel
meetings in November and in February in 1992, and we're not able
to obtain any data to substantiate that claim.

Mr. McIntosh. Have you seen any data since then?

Dr. Merkatz. No.

Mr. McIntosh. And were you listening to the testimony earlier
today by Dr. Ganske?

Dr. Merkatz. Yes, I was.

Mr. McIntosh. Is that not persuasive?

Dr. Merkatz. I believe that there are many reasons. Women are
more afraid of breast cancer than almost any other disease — and
women need to be encouraged in order to have this procedure done,
and we are doing everything that we can at FDA. For example,
we've just opened up a new hotline to help women find certified fa-
cilities in their geographic areas.

Mr. McIntosh. Were you persuaded by Dr. Ganske?

Dr. Merkatz. It is hard to be persuaded based upon my own
clinical practice of over 30 years in terms of why women choose to
have a mammogram or not to have a mammogram. It's a very com-
plicated issue.

Mr. McIntosh. I think he was saying that some patients decline
or are reluctant to have surgery to treat them, after the disease
has been detected.

Dr. Merkatz. I think women will ask questions about whether
they need to have a mastectomy versus a lumpectomy, which is a
very important question for women to ask and that decision should
be given every consideration because even with reconstructive sur-
gery, I think most women, if possible, would prefer the
lumpectomy.

Again, the testimony was very compelling. I do not deny that,
but I do feel it's a very complicated issue.

Dr. Kessler. Congressman, can I just add one point, if I may.

Mr. McIntosh. Sure.

Dr. Kessler. Your concern and our concern is one of the reasons
why we allowed — again, with considerable controversy— continued
open availability of silicone implants for women for reconstructive
surgery with informed consent and data collection. That's why I
was persuaded to allow open availability.

Mr, McIntosh. I'll defer to later for other questions.

Mr. Shays. I thank the gentlemen, because we will have a second
round.

And at this time, Mr. Barrett, you have the floor.



80

Mr. Barrett. Thank you, Mr. Chairman. You talked about the
woman who could get it for reconstructive surgery. Under the cur-
rent FDA regulations, which women or when would women not be
able to have the open opportunity to do so?

Dr. Kessler. Let me let Dr. Merkatz talk about the eligibility
criteria under the protocol.

Dr. Merkatz. There are two types of breast implants currently
available for women with breast cancer. The silicone gel, which is
available through clinical trials. If a woman is in the clinical trial —
and this is open across the United States, the sites where clinical
trials are being conducted for silicone gel — so a woman with breast
cancer may have a silicone gel implant provided she is enrolled in
the trial; otherwise, she may have a saline-filled breast implant.

Mr. Barrett. What is the purpose for requiring her to be en-
rolled in the trial?

Dr. Merkatz. So that we can get the data that we have tried for
so long to obtain. And the trial also guarantees that she will have
an informed consent procedure used as part of having her recon-
struction done, that there would be a frank discussion about the
risks and benefits.

Mr. Barrett. Does that slow her down in getting the implant?

Dr. Merkatz. We do not think it slows her down. The kind of
discussion that is required in informed consent really is the kind
of discussion that should go forward when a woman is confronting
either type of implant surgery. It is not our impression that an in-
formed consent procedure would slow down the process.

Mr. Barrett. OK For the woman who wants a saline-filled
breast implant, she could get it if she's in a trial?

Dr. Merkatz. Exactly.

Mr. Barrett. OK. Let's go on. Go on to which women can't get
them. Who is being stopped right now?

Dr. Merkatz. Women who are — who would like to have aug-
mentation, cosmetic augmentation, surgery for other reasons, rea-
sons other than breast cancer are currently not being enrolled into
gel trials, but they may have saline implants.

Mr. Barrett. OK. Dr. Burlington, if your mother or your wife or
your sister said she wanted to have an implant, what would you
say to her?

Dr. Burlington. It would be my frank advice that we would
need to look at the reasons promoting that request. If it was a
question of reconstruction following mastectomy, I think that the
benefits attributable to that are different, that we've heard those
discussed earlier. I think there has been a strong feeling through-
out the community from our advisory panel and firom the agency.
Those benefits make sense to enroll in the trial through the reg-
istry, through informed consent. It's not a complex or lengthy pro-
cedure.

If on the other hand the issue is augmentation, the risk benefit
ratio is different, and in that case I would counsel that we wait and
find out when we have more evidence on specific products and
what their rupture rate is. After all, a woman contemplating ana-
tomic change through augmentation needs to knov^r how long is
that anatomic change going to last. When is she going to have to



81

be reoperated. What is the risk of scarring. Is she going to get the
anatomic change she's looking for.

Mr. Shays. Would the gentleman yield for a second?

Mr. Barrett. Yes.

Mr. Shays. He will definitely have his time. What I find interest-
ing is you talk about new products. We have a system right now
designed not to create new products. So if you're going to wait to
see what new products are going to come on the line, tell me, what
new products are you aware of that are going to come on the line?

Dr. Burlington. Mr. Chairman, we have a million women im-
planted, very large numbers with products quite similar to those
made bv the two companies that have applications still held open
but back with the companies.

Mr. Shays. That's not my question.

Dr. Burlington. These specific products don't have the sorts of
information I was just addressing.

Mr. Shays. That's not my question. You said that you would
counsel your wife or your daughter that you should see what new
products would come on line?

Dr. Burlington. What new information needs to be available, if
I may correct myself, Mr. Chairman.

Mr. Shays. OK. But are you aware of any new products that are
coming on line?

Dr. Burlington. Yes, Mr. Chairman, there is one company with
a current clinical investigation in this country.

Mr. Shays. And what company is that?

Dr. Burlington. We generally need to protect commercial con-
fidential information.

Mr. Shays. Have they taken out an application?

Dr. Burlington. Yes, for investigation Mr. Chairman.

Mr. Shays. So we have two companies that have taken out appli-
cations. Am I to infer that there is a third company that has taken
out an application?

Dr. Burlington. For a different type of product, Mr. Chairman.

Mr. Shays. OK I thank the gentleman for yielding.

Mr. Barrett. Dr. Kessler, what would you tell your mother if
she said she wanted to have an implant?

Dr. Kessler. I ag^ee with Dr. Burlington. I would just add that
I think you need to look at all the available procedures and the
risks and benefits of all tvpes of reconstruction.

Mr. Barrett. But you re talking to your mother. What are you
going to tell your mom? Your mom calls and says, what should I
do, David, you're a sharp guy, what do I do?

Dr. Kessler. Mr. Barrett, I'm a pediatrician.

Mr. Barrett. All right. Your daughter.

Dr. Kessler. I would certainly ask her to talk to her surgeon,
but I do think that there are a number of reconstructive options,
and you need to look at all those reconstructive options and look
at the risks and benefits. But it is not unreasonable to enroll in the
clinical trial and get information as long as you do it with your
eyes wide open.

Mr. Barrett. OK Let me ask, would you have one? I'm sorry,
I can't see your name there, I apologize.



82

Dr. Merkatz. You're talking to someone who doesn't even take
vitamins. I probably would msike a decision against any type of im-
plant, but that's my own personal feeling.

Mr. Barrett. OK. If I can now draw the distinction between the
breast augmentation and reconstructive surgery and I apologize if
I'm oflfendine anybody, but I may be showing my ignorance here.
I would think that many times when a woman wants to have it
after breast cancer, that she wants it — obviously, I think, in part
for cosmetic reasons. And it seems to me that we're drawing a dis-
tinction between cancer and if it's just pure vanity, it's just pure
vanity. But I don't know that that is necessarily a valid distinction.

Why is that a valid distinction?

Dr. Kessler. Congn^essman, it's one of the hardest questions that
we've gn'appled with. I think that the use in breast cancer is not
exactly the same as its use in cosmetics. I think that it's fair to
state that its use — reconstruction is an integral part, I mean, of
breast cancer therapy and as I said earlier, getting on with one's
life.

I think in the end it's very different.

Mr. Barrett. OK I don't disagree that for breast cancer it's very
important and it's part of therapy, which is the word vou used. My
question is, couldn't it be therapy in another situation?

Dr. Kessler. Sure. I mean, there are other conditions: colon
anomaly, certain congenital deformities, trauma, for which I be-
lieve we have also allowed access under the protocol. So it's not just
breast cancer.

Mr. Barrett. OK, you were talking about the procedure before
and the burden being on the company to come forth with the infor-
mation — and, I'm sorry, the gentleman to the left — ^maybe you
could tell me again the procedure as to how much more information
is going to be necessary, and the timeframe here. I think that you
were talking about the procedure that is used.

Mr. Levitt. As Dr. Kessler stated, we have tried to describe for
the companies, as we do with a wide range of products, the range
of testing that's needed, some of which has already been done, and
some of which hasn't. It's really out of our control now long it takes
the companies to perform those tests. It is at their option. We can-
not require them to do tests quicker than they have the resources
or will to do.

Mr. Barrett. OK. One final question for you. Dr. Kessler: Do
you agree with Mr. Traficant that Dow did not supply all the infor-
mation?

Dr. Kessler. When I agreed to come here. Congressman, I spoke
with the chairman and I had one request, and that is, if I could
stay on the public health and scientific issues and not get involved
in other issues. I apologize, but I would rather stay on the sci-
entific/public health questions.

Mr. Barrett. I understand. Maybe I can ask a followup question,
and maybe you don't want to answer this one either. If you do have
a situation where a company does not provide you with informa-
tion, in a generic sense, and you find out about that, what is the
response of your agency?

Dr. Kessler. There are regulations that do require data to be
submitted. If, in fact, there's a violation of those laws, then we



83

make referrals and work with our colleagues in the Department of
Justice. If, in fact, the documents — and let me just make sure coun-
sel will shake her head behind me — are "material" to our deter-
mination.

Mr. Barrett. OK Thank you very much.

I yield back the balance of my time.

Mr. Shays. Thank you.

We would now like to call on Mrs. Morella, and note for the
record, she is the only woman on this panel right now. You're going
to have a little more than an extra 5 minutes for your patience ana
your perspective.

Mrs. Morella. Thank you, Mr. Chairman. I may not need it, be-