UNITED STATES OF AMERICA

MEDICAL DEVICES ADVISORY COMMITTEE

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GENERAL AND PLASTIC SURGERY DEVICES PANEL

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MEETING

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FRIDAY, AUGUST 26, 2005

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The Panel met in Salons A, B, and C of the Hilton Washington, D.C.
North, 620 Perry Parkway, Gaithersburg, Maryland, at 8:00 a.m., Joseph
LoCicero, III, M.D., Panel Chairman, Presiding.

[PRESENT]{.underline}:

JOSEPH LOCICERO, III, M.D., ACTING PANEL CHAIRMAN

DAVID KRAUSE, Ph.D., EXECUTIVE SECRETARY

GRACE T. BARTOO, Ph.D., RAC, INDUSTRY REPRESENTATIVE

BRENT BLUMENSTEIN, Ph.D., VOTING MEMBER

LEELEE DOYLE, Ph.D., CONSUMER REPRESENTATVE

CHERYL A. EWING, M.D., VOTING MEMBER

[PRESENT (Continued)]{.underline}:

ANN MARILYN LEITCH, M.D., VOTING MEMBER

FRANK R. LEWIS JR., M.D., TEMPORARY VOTING MEMBER

MICHAEL J. MILLER, M.D., VOTING MEMBER

AMY NEWBURGER, M.D., VOTING MEMBER

[INDUSTRY and PUBLIC PRESENTERS]{.underline}:

MERRY LEE BAIN, Cook Biotech, Inc.

ERIC CAILLE, PMT Corp.

SERGIO J. GADALETA, Ph.D., Ethicon, Inc.

[FDA PRESENTERS]{.underline}:

NADA O. HANAFI, Office of Device Evaluation

MARJORIE G. SHULMAN, Office of Device Evaluation

SAM AREPALLI, Ph.D., Office of Device Evaluation

[I N D E X]{.underline}

[PAGE]{.underline}

Conflict of Interest Statement 6

Appointment to Temporary Voting Status 7

Introductions 9

[Tissue Expander]{.underline}

PMT Corporation Presentation:

Eric Caille 12

FDA Presentation 19

Panel Deliberation 33

FDA Questions 37

Classification Questionnaire and Supplemental

Data Sheet 47

[Wound Dressing with Drug]{.underline}

Industry Presentations:

Cook Biotech, Inc., Merry Lee Bain 60

Ethicon, Inc., Sergio J. Gadaleta, Ph.D. 66

FDA Presentation, Sam Arepalli, Ph.D. 74

Panel Deliberations 89

FDA Questions 89

Classification Questionnaire and Supplemental

Data Sheet 105

P-R-O-C-E-E-D-I-N-G-S

(8:09 a.m.)

DR. KRAUSE: Good morning, everyone. We\'re ready to begin the second day
of our meeting. My name is David Krause. I\'m the Executive Secretary of
the panel. I\'m also a reviewer in the Plastic and Reconstructive
Surgery Devices Branch, Division of General, Restorative, and
Neurological Devices.

I\'d like to remind everyone that you are requested to please sign in on
the attendance sheets which are available just outside the doors. At
that table you may also pick up an agenda, a panel meeting roster, and
also some information about today\'s meeting.

Also, there\'s information about how to find out about future meeting
dates through the Advisory Panel phone line and how to obtain meeting
minutes, and there\'s also information about our Website.

Before I turn the meeting over to Dr. LoCicero, I\'d like to read two
statements into the record. The first is conflict of interest, and the
second is the deputization to voting status.

The Food and Drug Administration is convening today\'s meeting of the
General and Plastic Surgery Devices Panel of the Medical Device Advisory
Committee under the authority of the Federal Advisory Committee Act of
1972.

The Advisory Panel meeting provides transparency into the agency\'s
deliberative processes. With the exception of the industry
representative, all members of the panel are special government
employees or regular federal employees from other agencies who are
subject to federal conflict of interest laws and regulations.

FDA has determined that members and consultants of this panel are in
compliance with federal conflict of interest laws, including but not
limited to 18 USC 208 and 21 USC 355(n)(4). Under 18 USC, Section 208,
applicable to all government agencies, and 21 USC 355(n)(4), applicable
to FDA, Congress has authorized FDA to grant waivers to special
government employees who have financial conflicts when it is determined
that the agency\'s need for a particular individual\'s services
outweighs his or her potential financial conflict of interest.

Members and consultants who are special government employees at today\'s
meeting have been screened for potential financial conflicts of interest
of their own, as well as those imputed to them, including those of their
employer, spouse or minor child related to the discussions of today\'s
meeting. These interests may include investments, consulting, expert
witness testimony, contracts, grants, CRADAs, teaching, speaking,
writing, patents and royalties, and primary employment.

The agenda on August 26 involves a discussion of the classification of
two pre-amendment medical devices, tissue expanders and wound dressing
with a drug.

In accordance with 18 USC, Section 208(b)(3), a waiver has been granted
for Dr. Newburger. A copy of the written conflict of interest waiver
statements may be obtained by submitting a written request to the
agency\'s Freedom of Information Office, Room 12A-30 of the Parklawn
Building.

In addition, Dr. Bartoo is participating as the industry representative
acting on behalf of all related industry and is employed by Decus
Biomedical.

Finally, in the interest of public transparency with respect to all
other participants, we ask that they publicly disclose prior to making
any remarks any current or previous financial involvement with any firm
whose products they may wish to comment upon.

This statement will be available for review at the registration table
during this meeting and will be included as a part of the official
meeting transcript.

Thank you.

Additionally, we have the appointment to temporary voting status.
Pursuant to the authority granted under the Medical Device Advisory
Committee Charter, dated October 27th, 1990, and as amended August 18th,
1999 and November 16th, 1999, I appoint Frank R. Lewis as voting member
of the General and Plastic Surgery Devices Panel for this meeting on
August 26th, 2005.

For the record, this individual is a special government employee and
consultant to the panel or other panels under the Medical Device
Advisory Committee. He has undergone the customary conflict of interest
review and has reviewed the material to be considered at this meeting.

Finally, I would like to note for the record that Dr. Joseph LoCicero,
has consented to serve as the Chairperson for the duration of this
meeting, and it\'s signed by Dr. Daniel Schultz, Director, Center for
Devices and Radiological Health.

At this time I\'d like to turn the meeting over to the Chairman, Dr.
LoCicero.

PANEL CHAIR LoCICERO: Good morning. My name is Dr. Joseph LoCicero, III,
and I am the Acting Chairperson for the General and Plastic Surgery
Devices Panel.

Today the panel will be making recommendations to the Food and Drug
Administration on the classification of tissue expanders and wound
dressings with a drug which are both presently unclassified
pre-amendment medical devices.

Before we begin the meeting, I would like to ask our distinguished panel
members who are generously giving their time to help the FDA in these
matters and the other FDA staff seated at the table to introduce
themselves. Please state your name, your affiliation, your position, and
your area of expertise.

I\'ll begin with myself. I\'m Dr. Joseph LoCicero, III, and I am a
thoracic surgeon. I\'m currently the Chair of Surgery at the University
of South Alabama in Mobile Alabama, and of course, I\'m a voting member.

Dr. Doyle.

DR. DOYLE: I\'m Leelee Doyle. I\'m a Ph.D. reproductive physiologist by
training. I\'m the Assistant Dean for Faculty Development and a
Professor Emeritus of Obstetrics and Gynecology at the University of
Arkansas for Medical Sciences, College of Medicine. I\'m the consumer
representative. I\'m a nonvoting member.

DR. BLUMENSTEIN: I\'m Brent Blumenstein, Biostatistician working out of
Seattle. I\'m a voting member.

DR. BARTOO: My name is Grace Bartoo. I\'m the General Manager of Douglas
Biomedical. I\'m a biomedical engineer. I\'m the industry
representative, and my expertise is medical device development in
clinical trials.

MR. MELKERSON: I\'m Mark Melkerson. I\'m the Acting Director of the
Division of General, Restorative, and Neurological Devices.

DR. LEITCH: I\'m Marilyn Leitch. I\'m a surgical oncologist and
Professor of Surgery at the University of Texas, Southwestern Medical
Center in Dallas.

DR. MILLER: I\'m Michael Miller. I\'m a Professor of Plastic Surgery at
the University of Texas, M.D. Anderson Cancer Center, and I\'m a voting
member.

DR. NEWBURGER: I\'m Dr. Amy Newburger. I\'m a clinical dermatologist in
private practice in Scarsdale, New York. I teach at St. Luke\'s
Roosevelt Hospital Medical Consortium. My expertise is in cosmetic
dermatologic procedures and contact allergy.

DR. LEWIS: Mike Lewis, Executive Director of the American Board of
Surgery, and my expertise is as trauma surgery and critical care.

DR. EWING: Cheryl Ewing. I\'m a surgical oncologist, faculty member in
the Department of Surgery at the University of California at San
Francisco.

DR. KRAUSE: I\'m David Krause.

PANEL CHAIR LoCICERO: Thank you.

At this time we\'ll begin the discussion of the classification of tissue
expanders. We\'ll start with a presentation by Mr. Eric Caille, the
General Manager of PMT Corporation. This will be followed by the FDA
presentation, after which there will be a general panel discussion of
this topic followed by a more focused panel discussion aimed at
answering the FDA\'s questions.

Following the panel discussion, we will complete the reclassification
work sheet and supplemental work sheet. The vote on these work sheets
will constitute the panel\'s recommendation to the FDA.

There will also be time for public comment before the vote.

I\'d like to remind the public observers at this meeting that while this
portion of the meeting is open for panel observation, public attendees
may not participate except at the specific request of the panel.

We will begin with Mr. Caille\'s presentation.

MR. CAILLE: Good morning. My name is Eric Caille. I\'m the General
Manager for PMT Corporation. With me is Darren Singer, engineer for PMT
Corporation.

PMT would like to present information in support of classification of
tissue expander to Class II.

The background. To give you some background on PMT, we\'re a Minnesota
based corporation. We have about 80 employees. We\'ve been manufacturing
tissue expanders for the last 20 years. We developed our first tissue
expanders in 1984 with Dr. Allen Van Beek, plastic surgeon.

And we currently make several thousand expanders per year, about four to
5,000, and it\'s a variety between extremity expanders and breast
expanders, probably about 60 percent extremities.

If we look at the tissue expander principal operation, essentially
tissue expanders are used to provide an even and controlled expansion of
dermal and epidermal tissues. A typical application in cosmetic
reconstruction would be second or third degree burn or correction of
skin discoloration or if we use breast expanders, to create a well
vascularized pocket to receive a prosthetic device, such as mammary
implants.

Typically tissue expanders are used for a maximum of 90 days. They are
temporary devices.

A tissue expander is essentially a silicone balloon. It\'s composed of
vulcanized silicone shell and silicone backing material. They\'re made
in various shape and sizes, depending on what the surgeon wants.

For inflation purposes there is a molded silicone part that can be
either attached to the expanders via a tube or also it can be built in,
the expander, directly.

Expanders are inflated with sterile saline solution. They are provided
sterile and are for single use. There\'s a number of companies that have
obtained FDA clearance through the 510(k) process. We know of Mentor,
Inamed, Silimed, Specialty Surgical. There\'s also a number of foreign
manufacturers. We know, for example, five French manufacturers. I don\'t
think they\'re selling in the U.S., but there\'s a number of them.

A few years ago we looked at clinical literature to identify some of the
risks associated with tissue expansion. What we found was hematoma
infection, exposure of course device, deflation, pain reported by
patient usually, and infection. None in the literature that we reviewed
reported any serious injuries or death to the patients using tissue
expanders.

Lastly, actually we reviewed new articles, and I think I have a copy for
you in the literature that you have. What we found is new articles. One
of them looked at 171 patients tracked over a seven-year period and
found that breast reconstruction using tissue expanders resulted in
shorter hospital stays. The literature also stated that tissue expansion
for pediatric cases, such as birth defects, had a high level of safety
and efficacy.

In general, the literature has suggested that the proven benefits of
tissue expanders have far outweighed the limited complication and
associated risk.

In terms of safety assurance, there\'s a number of standards that we use
in manufacturing tissue expanders. In particular, the first one, ASTM
F1221-03 is specific to tissue expansion, standard specification for
soft tissue expanders.

If you look at this one, this standard address biocompatibility and
physical characteristic. To tell you a little bit about it, I\'m sure
Darren knows more, but addresses the strength of the shell and inflation
port, the over extension, up to 200 percent, the fusion of critical and
noncritical joints. It also addresses the repeated puncturing of the
injection port.

There\'s a large number of MDR on the FDA database, and we decided to
look at our complaint instead of maybe share with the panel our
experience with some of the failures of the device. So we looked at five
years of complaints, from January 2000 to December 2004, and we do track
complaints, you know, for trending and quality purposes.

We in that five-year period manufactured probably about 20,000
expanders. We had, I think, a total of complaints less. I think it was
about 100. So that gave us about .5 percent of total production were
complaints, and the majority of complaints received were from deflation
issues. About 60 percent of complaints were deflation.

When we do investigation, we found that these complaints could be
traced. What we found were slashes, puncture, which could be indicative
of the surgical instrument slashing the expanders. There is almost no
mechanical failure of the device.

The remaining complaints we had were incorrect connection of port with
expanders. In some cases we had incorrect manufacturing, that is, the
tubing coming out of the wrong side or we made the wrong shape for the
doctor.

In summarizing our complaint we did not receive reports of serious
injury or death to any patient.

In conclusion, we would like to recommend a classification of tissue
expanders as Class II device for the following reason. Tissue expanders
have been in use for 20 years with the low complications rate.
Historically there\'s no evidence of serious injury or death. Tissue
expanders are relatively simple devices, provided sterile and for single
use. Tissue expanders manufactured in conformance with F12-2103 standard
provides assurance of safety and efficacy for this device, and then we
believe that the other issues can be adequately addressed in the
labeling of the device.

Thank you.

PANEL CHAIR LoCICERO: Thank you.

Are there any questions for Mr. Caille?

(No response.)

PANEL CHAIR LoCICERO: I have one question. How long have these devices
been implanted in a particular individual? What\'s the longest one of
these devices has been?

MR. CAILLE: A particular device, you mean?

PANEL CHAIR LoCICERO: Any of your devices, how long have they remained
in place?

MR. CAILLE: Our labeling indicates no more than 90 days. They are
reporting complication of some expanders being left in the body for up
to six months, but of course, that\'s against manufacturing. That\'s off
label uses.

PANEL CHAIR LoCICERO: Are there any other questions? Yes, Dr. Lewis.

DR. LEWIS: Have any of the ruptures occurred spontaneously or have they
all been associated with instrumentation or manipulation?

MR. SINGER: I would say of our complaint review the rupturing is more
from a surgical instrument. It is no rapid rupture. Most of the
complaints are leakage or depletion. The tissue expander feels soft to
the touch instead of a complete deflation at one time.

DR. LEWIS: Do you know if there have been any cases of tissue loss over
the expander other than in irradiated areas?

MR. CAILLE: We don\'t know.

DR. LEWIS: You can\'t answer that.

DR. LEWIS: Thank you.

MR. CAILLE: Thank you.

PANEL CHAIR LoCICERO: We will now start the panel deliberation portion
of the meeting. Let\'s begin with \-- sorry. We have the FDA
presentation. Sorry.

MS. HANAFI: Good morning. My name is Nada Hanafi. I\'m a reviewer in the
Plastic and Reconstructive Surgery Branch in the Division of General
Restorative and Neurological Devices.

Today I will be presenting the proposed classification of the tissue
expander device. I\'d like to take this opportunity to thank the panel
for being here again today.

This slide outlines the topics I intend to go through during this
presentation. The Medical Device Amendments Act of 1976 established
three classes of medical devices, and this was depending on the
regulatory controls required to insure reasonable safety and
effectiveness, and these were described in detail in my review memo as
well as during yesterday\'s presentations.

If a device is not a Class I or Class II or Class III, it is an
unclassified device. The tissue expander device is a pre-amendments
unclassified device.

Currently tissue expanders are regulated by the 510(k) pre-market
notification process, and in the time period of 1978 to 2004, FDA has
cleared 41 tissue expanders, 510(k)s. So FDA is seeking the panel\'s
input on whether or not to classify tissue expanders into Class II.

The special controls guidance document purpose has already been
presented to the panel during yesterday\'s discussions, and this slide
just repeats that.

So the following slides will provide an outline of the suggested draft
special controls guidance document for a tissue expander. Sections 1
through 3 are primarily boilerplate language. Section 4 would be to
scope, and this would identify the limitations in terms of device
description, indications for use and intended use.

Section 5 is the device description. Although FDA did not believe this
section would be controlled to mitigate any of the identified risks, FDA
believed that this section would provide much of the recommended
information to complete the review of a 510(k) submission for a tissue
expander.

And this was also described in detail in my review memo, but to outline
would require a detailed description of the device components, the
material composition, and the mechanism of filling the tissue expander.

Section 6 would identify the risks to health and FDA\'s proposed
controls to mitigate these risks. I will discuss this later on in the
presentation.

Section 7 to 10 of the draft guidance document would describe the
controls required to mitigate the risks to health. Section 7 would be
the preclinical testing, and this is dependent on the actual device
design.

Sections 8 and 9 are boilerplate language and are consistent throughout
medical device guidance documents.

Section 10 would be the labeling recommendations, which are specific for
a tissue expander device.

So what is a tissue expander? A tissue expander is an inflatable
silicone elastomer shell. It comes in various shapes, round or
rectangular, and sizes. It is inserted under the skin at the area to be
expanded and gradually filled with sterile saline, which causes the skin
to stretch and grow over time.

A tissue expander is not intended for use beyond six months.

FDA would like to make it clear that a tissue expander device is not a
breast implant. A breast implant is a Class III device, and it is
reviewed through the pre-market application PMA process. A breast
implant has shells made with different material properties. They come in
different shapes with height and projection and sizes, and a breast
implant has a different intended use.

So FDA is proposing the following identification for a tissue expander
device. A tissue expander is an inflatable silicone elastomer shell
filled with normal physiological saline injection grade intended for
temporary, less than six months implantation to develop surgical flaps
and additional tissue coverage in a variety of applications.

So in order to assess the potential risks associated with a tissue
expander device, FDA reviewed the adverse events reported through the
medical device reporting system, and this slide shows that the top
device problems were explanation, deflation and leaks. The top patient
problems were surgical procedure, infection, and pain.

The reasons for explanation and surgical procedure were not provided.
However, it can be assumed that these were due to complications, such as
skin trauma or device failure.

The risk to health for tissue expanders was assessed by a review of the
MDRs, the published literature, and the 510(k)s of clear tissue
expanders. This table identifies the risks to health and proposed
controls to address these risks.

You will notice that the table includes pain as a risk. So subsequent to
sending the panel packages, FDA added pain as a risk to health because
it was one of the top patient problems. We believe that pain can be
mitigated through the directions for use provided in the labeling.

You will also notice that no clinical data is proposed as a control to
mitigate any of the identified risks to health. This is because FDA
believed that based on the scope of the device the other controls
identified would be sufficient to address any of the risks to health.

However, should the scope of the device change in terms of the use, its
material or design, FDA would recommend clinical data be submitted in a
510(k) application.

So to conclude, this slide repeats the identification of a tissue
expander device, and FDA is proposing that the tissue expander be
classified to cost you (phonetic) special controls. The special controls
employed would be a detailed guidance document.

I\'d like to thank the panel for their attention and would you now
please discuss the classification topics outlined in the slide?

Thank you.

PANEL CHAIR LoCICERO: Thank you.

Ar there questions for the FDA? Dr. Bartoo.

DR. BARTOO: Just one question with regard to your comment about pain
being mitigated through labeling. How exactly is that going to be done?

MS. HANAFI: I would be through the directions for use. So it\'s actually
described in detail in my review memo, and we believe that pain would be
due to filling the tissue expander too quickly in a short period of
time. Also the surgeon would have to track that surrounding tissues,
healthy tissue so that you wouldn\'t cause skin necrosis or sloughing of
the skin and so forth.

PANEL CHAIR LoCICERO: Dr. Lewis.

DR. LEWIS: In your definition, you included the normal saline, but that
really isn\'t part of the device. That\'s only what people choose to
play with. They could probably fill it with other things. Is that
relevant to the description?

It would seem like that \--

MS. HANAFI: It is relevant because a tissue expander is intended to be
filled with saline. If they decide to fill it with any other filler,
that would be changing the scope of the device. So then we would
probably require clinical data.

Could you clarify what other fillers you\'re thinking of?

DR. LEWIS: Well, air for example could be used. I think any fluid medium
that would inflate it under pressure. Air might escape one in saline,
but there\'s no reason it wouldn\'t have the same characteristics
otherwise.

But the issue, I guess, is just that saline is not part of the device
and, therefore, it\'s not clear why it\'s included in the definition of
device

MR. MELKERSON: This is Mark Melkerson. We would consider the device to
be your instructions for use, and if it includes using saline to inflate
it, that would be considered part of the device.

Actually saline is regulated as a drug in other parts of the agency.

MS. HANAFI: Also, just as an addition, the 510(k)s cleared so far have
been filled with saline. So we are classifying the pre-amendments
device, which is filled with saline.

Any other questions?

DR. KRAUSE: Yeah, I just wanted to second what Nada just said, which is
that we are here to classify the pre-amendments device, and since we\'ve
cleared like Nada said, like 41 510(k)s, every one of those have been
filled with saline, and the instructions specifically state that.

So that\'s one of the reasons why we include that as a part of the
definition of the device. If that changes, because we\'ve had people ask
about other fillers, and to this point nobody has shown us that they\'re
as good or better than saline or as safe or as effective. So that\'s one
of the reasons that we keep that as part of the definition.

PANEL CHAIR LoCICERO: Dr. Miller.

DR. MILLER: The devices that are used in standard tissue, the nerves and
blood vessels, how does using it for those type applications fall into
your scheme?

MS. HANAFI: Okay. I think you\'re probably referring to tissue
approximaters. I\'m not sure about that. So I actually don\'t know the
answer, but I thought that Mark might.

MR. MELKERSON: Let me clarify. Are you talking things like stents for
opening vessels and other tissue expanders in that context?

Those would actually be classified as other devices. These are basically
in the dural, dermus layers, submucosa.

MS. HANAFI: Submuscular.

MR. MELKERSON: Right.

MS. HANAFI: Implantation. I\'m not sure if that answered your question.

DR. MILLER: Well, there are some people who have worked on standards to
lengthen blood vessels, whether it was too short to do a particular ‑-

MR. MELKERSON: That would actually be a cardiovascular product and
regulated as a different product.

DR. MILLER: Or nerves, then use thick skinned nerves.

MR. MELKERSON: Same thing. that would be in our neural product area, not
in the plastic and reconstructive surgery device area. When we classify
a device, it\'s for the intended use. That\'s why your identification
identifies an intended use and a description of the device.

So devices that fall outside that identification and indication for use
would then be looked at as a different product and then that product,
we\'ll look to see if it has already been classified.

MS. HANAFI: Just to add onto that, all the pre-amendments and the tissue
expanders cleared so far have been for this actual identification for
tissue expansion, but we haven\'t cleared any for nerve expansion.

Any other questions?

PANEL CHAIR LoCICERO: Dr. Leitch.

DR. LEITCH: On the risk to health and controls, you put adverse tissue
reaction. Specifically what does that refer to?

MS. HANAFI: That would be to a foreign body or a material reaction.

DR. LEITCH: Okay.

PANEL CHAIR LoCICERO: The section of your guidance document dealing with
testing, Section 7, preclinical testing, refers to one standard; 2025 I
believe it was. Though we\'ve heard this morning about a number of other
ASTM standards, 1221.03, 1221.92, et cetera. Does the FDA have opinion
concerning those other ASTM standards?

MS. HANAFI: I\'ll let Mark Melkerson.

MR. MELKERSON: In our guidance document we generally will identify all
applicable standards. I believe the standard that we refer to as a
specification, which actually refers to some of those other standards
that are listed in the industry presentation.

PANEL CHAIR LoCICERO: So the FDA would have an exhaustive list of ASTM
standards.

MR. MELKERSON: Well, ASTM or any other voluntary consensus standards
that are applicable to the product.

PANEL CHAIR LoCICERO: Any other questions?

Thank you \-- oh, sorry. Dr. Newburger.

DR. NEWBURGER: Sorry. Is it relevant to put into the guidance document
sample testing? I know that we\'ll look at that exhaustively with
questions, but considering what area these are going to be implanted in,
one might expect to see repeated trauma or torque to certain areas where
the breast implants might be.

My experience is that when you have something reported on an MDR, really
it only represents perhaps ten to 15 percent of the adverse events.
People just tend not to report that.

So I\'m wondering is there going to be in the guidance document any type
of approximation of what might be happening for the short term that the
device is applied?

MS. HANAFI: Well, we requested material property testing, and I outlined
that we have injection site testing, valve competency testing, and
self-sealing patch testing, and the actual preclinical testing that
would be recommended would be dependent on the actual device design.

I understand you\'re asking if we would request cyclic fatigue testing,
and we haven\'t, I don\'t believe, in any of the 510(k)s we\'ve cleared
so far requested that, but that\'s probably due to the same material
being used, but if the material should change, then we could request
that. So it\'s totally dependent on the actual design of the device.

But seeing as this is not a permanent implant and it\'s intended for
temporary use, we don\'t believe we\'d put it in our guidance document,
but if that is one of your recommendations, FDA would be willing to
consider that.

Any other questions?

PANEL CHAIR LoCICERO: Okay. Thank you.

MS. HANAFI: Thank you.

PANEL CHAIR LoCICERO: Now we will start the panel deliberation portion
of the meeting, and I would like to note for the record that the voting
members present constitute a quorum as required by 21 CFR, Part 14.

We have had both the FDA and industry presentation concerning tissue
expanders, and I\'d like to ask Dr. Leitch to begin discussion of the
temporary use of tissue expanders.

DR. LEITCH: Well, I think that is reasonable to consider this as a Class
II device. I guess the main issue for its use is the possibility of
device failure, which the only consequence, of course, is that you have
to have another one replaced, but that is an operative procedure, and
that has certainly been discussed with other implant devices, the rates
of reoperation relative to the implantation.

And these are at more risk for injury as the risk for deflation because
of inflation of the implant device, and so I think in the labeling of
that, and I think this is done generally, that that point be emphasized,
that that is a risk that exists for the patient in terms of deflation
and requiring a second operation.

PANEL CHAIR LoCICERO: Okay. Dr. Miller?

DR. MILLER: And I think classification as a Class II is a sensible thing
to do.

PANEL CHAIR LoCICERO: Okay. Any other comments?

DR. MILLER: Well, it has been a long experience, several decades with
these devices, and I think that their performance is pretty well
understood clinically. i think they have been an enormous benefit to
patients and solved many very difficult problems in terms of
reconstructive surgery that otherwise would have required more elaborate
methods or methods that are not successful or inconvenient or more
risky. So these have been a tremendous contribution to reconstructive
surgery.

I think that I\'m glad that they\'re becoming regulated under a good
framework, and to me a Class II designation is a reasonable one.

PANEL CHAIR LoCICERO: Dr. Newburger.

DR. NEWBURGER: I agree with a Class II classification for these devices.
My experience has been, from what\'s happened with my patients, has been
outstanding, and when they\'re used in the intended fashion, they have
virtually been problem free. I think it\'s very reasonable.

PANEL CHAIR LoCICERO: We\'re still in sort of a general comment area. So
maybe you might want to comment on tissue reaction for these short-term
devices. Is that an issue that we should be addressing?

DR. NEWBURGER: My clinical experience has not led me to know of any
adverse local reactions. My experience has been primarily with patients
where vast amounts of tissue have had to be resected for the purposes of
not only cosmesis, but minimizing the risk of molecular degeneration of
these lesions, and it has been uniformly outstanding.

I\'ve seen with patients who have undergone procedures over the course
of years no problem.

PANEL CHAIR LoCICERO: Dr. Lewis.

DR. LEWIS: I would agree with the Class II classification. I think
there\'s sufficient experience with these to have pretty fully evaluated
what the problems are.

The issue of including pain as one of the effects I would quibble a
little bit with since I think the pain is largely due to too rapid
expansion and is a medical practice issue rather than device issue per
se. But I guess you could argue that.

PANEL CHAIR LoCICERO: Dr. Ewing.

DR. EWING: I think the classification of Class II is very appropriate.
We have found in our practice when patients are undergoing breast
reconstruction to use a tissue expander as a temporary place holder
prior to the implant seems to decrease our complication rate as far as
wound breakdown and skin breakdown. So we have found them very effective
when we\'re reconstructing patients.

PANEL CHAIR LoCICERO: Dr. Doyle.

DR. DOYLE: It seems to me from what I hear and what I read that
classification II is very appropriate, but it sounds like there is a
great deal of benefit with a minimum of risk.

PANEL CHAIR LoCICERO: Dr. Blumenstein.

DR. BLUMENSTEIN: From all that has been said before, it seems like Class
II is appropriate.

PANEL CHAIR LoCICERO: Dr. Bartoo.

DR. BARTOO: I have nothing further to add.

PANEL CHAIR LoCICERO: Okay. We\'ve sort of combined two discussions
here, and I think everybody has had an opportunity to speak to the
general issues, but also to begin to address the FDA\'s first question
of a focused discussion.

And we\'re not going to work on the reclassification questionnaire
during this portion of our discussion. We\'ll do that after the
questions are answered.

So let\'s be sure that we\'re set. The proposed classification of the
tissue expander is Class II, and that descriptive information for the
intended use is appropriate.

Does anyone want to add to your discussion that this will be a Class II
device and that the description is appropriate?

(No response.)

PANEL CHAIR LoCICERO: Mr. Melkerson, on the point of Question 1, is the
FDA satisfied with the discussion?

MR. MELKERSON: Yes, we are.

PANEL CHAIR LoCICERO: Okay. Question 2, please discuss the risks to
health for tissue expander device.

Dr. Ewing.

DR. EWING: Well, I think the health risks have been identified. There\'s
always a risk of infection with foreign bodies or a risk of deflation of
the device, which has been point out is usually related to sharp
instruments.

But I don\'t think that the risks outweigh the weight of the benefits of
the device.

PANEL CHAIR LoCICERO: Dr. Lewis.

DR. LEWIS: I think the risks as described in two presentations are
accurate and appropriate, and I wouldn\'t expand on that.

PANEL CHAIR LoCICERO: Dr. Newburger, any additional?

DR. NEWBURGER: I understand from my colleagues in my community in
plastic surgery that they do appreciate a temporary reduction in some
tissue mass underneath the tissue expander, but that this is expected
and transitional, just a pressure reduction.

PANEL CHAIR LoCICERO: Okay. Dr. Miller.

DR. MILLER: I think any time you see a procedure with a 20 or a 30
percent complication rate, it always makes you a little uncomfortable,
and this is associated with that. However, I\'m glad that the
perspective is being taken that you need to separate out complications
due to the device, complications due to the operator, and complications
due to the nature of what you\'re trying to do, and some of these
procedures are just fraught with complications because of the nature of
what we\'re trying to accomplish with reconstruction that have a high
complication rate almost no matter what you do if you attempt it.

And operator issues which require good training and judgment for where
the device is placed and where decisions are made and this sort of
thing, but I think if the complications are directly traceable to the
device, they\'re probably extremely low, and so I think that should be
the main consideration for this panel, are ones which are causally
weighted to the device itself.

PANEL CHAIR LoCICERO: If I can ask the question, if taking some of these
patients who would have a potential high risk with the tissue expander,
what would be an alternative if the expander were not available?

DR. MILLER: You would have to generate \-- for a large area of soft
tissue need, the options are secondary healing, which may never occur in
some patients, to develop a full sized surgical flap that\'s adequate
for the defect, which creates a defect where you harvested from and is a
difficult tradeoff to make sometimes and may require very elaborate
surgical procedure to get the tissue where you need it. Those are
probably the two main alternatives to a tissue expander.

And the beauty of the tissue expander is that you can gradually increase
the net tissue available locally, and in the right patient it\'s an
excellent solution to a difficult problem.

PANEL CHAIR LoCICERO: Okay. Thank you.

Dr. Leitch.

DR. LEITCH: I would agree with many of the comments of Dr. Miller. I
think from the patient\'s perspective in trying to inform the patients
properly about these devices is to try to make clear in the working the
separation between the nature of their health problem that they start
with and how the device might impact that.

That was one of the reasons I had the question about the adverse tissue
reaction. I don\'t want that to be interpreted as might be interpreted
for silicone gel or something. You know, I want that to be clear that
that is the foreign body reaction that occurs around a foreign body so
that it\'s not construed to be something worse than that.

So I think a lot of the labeling for something like this, where patients
might interpret it to be a more serious risk, that that needs to be
descriptive to say it\'s related to what you\'re trying to do with the
procedure in terms of getting more tissue available in the area.

PANEL CHAIR LoCICERO: I\'m going to just ask Dr. Newburger if that\'s
your understanding as well.

DR. NEWBURGER: You\'re asking me is my understanding that the foreign
body reaction is simply the result of foreign material out there as
opposed to a reaction specifically to the silicone elastomer?

I don\'t have the information to assess that, but I\'m willing, since
it\'s a short-term device that\'s being used, to not kick up a fuss.

PANEL CHAIR LoCICERO: Dr. Miller.

DR. MILLER: I don\'t know where the dividing line is between clinical
practice and between need to regulate the device because there are some
specific circumstances where tissue expansion can have some undesirable
results. For example, in children all of the tissues are more malleable,
and when you try to expand an area in a child, you may deform the
underlying structure as well, and that\'s something that a person needs
to be aware of who\'s using one of these in a child.

I don\'t know if that is something which needs to be mentioned in a
guidance document, specifically a device, or just something that is
involved to train. I defer to FDA on that.

The other area is in the head and neck where you\'re standing against
structures like the trachea perhaps or large blood vessels because
whenever you place one of these devices you have to be mindful of what
you\'re pushing against on the deep side of the device, and this is a
matter of training in surgical experience and judgment. It may not be a
regulatory issue.

PANEL CHAIR LoCICERO: It might be something that could be addressed in
labeling.

DR. MILLER: Yes.

PANEL CHAIR LoCICERO: Okay. Dr. Bartoo.

DR. BARTOO: With regard to the risks that are related to the device
itself, I think these are things like infection and adverse tissue
reactions. There\'s standards that are very well known that seem to
control these types of risks very effectively. So, therefore, I think
with the risks that have been identified, you know, there are good
mitigations for these.

PANEL CHAIR LoCICERO: Dr. Blumenstein?

DR. BLUMENSTEIN: No further comments.

PANEL CHAIR LoCICERO: Dr. Doyle.

DR. DOYLE: Nothing to add.

PANEL CHAIR LoCICERO: On Question No. 2, is the FDA satisfied with the
discussion?

MR. MELKERSON: Yes. Thank you for the comments, and I do believe the
issues of use in younger patients is also a concern that we need to
think about.

PANEL CHAIR LoCICERO: Question No. 3, please identify any other risks to
health for these devices that have not been discussed.

I think we\'ve sort of gone through that. Does anybody have any
additional risks that they wish to mention?

(No response.)

PANEL CHAIR LoCICERO: Mr. Melkerson, do we need to address anything else
here?

MR. MELKERSON: Thank you very much.

PANEL CHAIR LoCICERO: Thank you.

We will now proceed to the open public hearing session regarding tissue
expanders. All persons addressing the panel are asked to speak clearly
into the microphone as the transcriptionist is dependent on this as a
means for providing accurate record of this meeting.

We have no one scheduled to speak. Is there anyone here who wishes to
address the panel concerning tissue expanders?

(No response.)

PANEL CHAIR LoCICERO: Let\'s take a short break at this point, a
ten-minute break, and we\'ll begin at five after nine.

(Whereupon, the foregoing matter went off the record at 8:59 a.m. and
went back on the record at 9:11 a.m.)

DR. KRAUSE: If everybody can please be seated, we can complete our
tissue expander portion of the meeting.

Thank you.

PANEL CHAIR LoCICERO: Okay. We will now fill in the questionnaire for
classification and supplemental data sheet.

Ms. Shulman of the Office of Device Evaluation will assist us as we go
along.

We will vote on the completed questionnaire and supplemental data sheet.
It will become the panel\'s recommendation to the FDA.

Ms. Shulman.

MS. SHULMAN: Thank you.

Good morning. Okay. We have the forms again, and again the top of the
form, panel member, generic type of device, and today\'s date.

Okay. Question No. 1, is the device life sustaining or life supporting?

PANEL CHAIR LoCICERO: I think the sense of the group is I can see the
answer to that one is no.

MS. SHULMAN: No. Question No. 2, is the device for use which is of
substantial importance in preventing impairment of human health?

PANEL CHAIR LoCICERO: My sense here is?

DR. LEITCH: Yes.

DR. MILLER: Yes.

PANEL CHAIR LoCICERO: Okay. Yes, it looks like yes is going to be the
answer for Question No. 2.

MS. SHULMAN: Thank you.

Number three, does the device present a potential unreasonable risk of
illness or injury?

DR. LEITCH: No.

PANEL CHAIR LoCICERO: I\'m hearing no from everyone. So the answer to
that one is no.

MS. SHULMAN: Thank you.

Number four, did you answer yes to any of the above three questions?
That answer is yes, and we can go on to number six.

Is there sufficient information to establish special controls in
addition to general controls to provide reasonable assurance of safety
and effectiveness?

PANEL CHAIR LoCICERO: From our discussion from earlier, the answer to
that seemed to be yes. Is there any objection to answering yes?

(No response.)

MS. SHULMAN: Thank you.

PANEL CHAIR LoCICERO: The answer to number six is yes.

MS. SHULMAN: Number seven, if there is sufficient information to
establish special controls to provide reasonable assurance of safety and
effectiveness, identify the special controls needed to provide such
reasonable assurance for Class II.

PANEL CHAIR LoCICERO: Okay. Dr. Leitch, is guideline sufficient? Do we
need any additional other than the guidelines document?

DR. LEITCH: I think guidance document will be sufficient.

PANEL CHAIR LoCICERO: Guidance document. Guidance document, everybody is
shaking their head in agreement. So guidance document.

MS. SHULMAN: Thank you.

PANEL CHAIR LoCICERO: Okay. Again, we can skip number eight and number
nine because that only has to do with performance standards, and number
ten because that\'s only for Class III devices.

Question 11, identify the needed restrictions. The first one is only
upon the written or oral authorization of a practitioner licensed by law
to administer the use of the device, and then the additional ones for
use only by persons with specific training or experience in its use, use
only in certain facilities, or any others.

PANEL CHAIR LoCICERO: I think everybody will agree to number one. Dr.
Miller, concerning the issue of specialized training, is that something
that should be stipulated?

DR. MILLER: I don\'t think you need special training beyond surgical
training and training in reconstructive surgery.

PANEL CHAIR LoCICERO: Dr. Newburger?

DR. NEWBURGER: Agree.

PANEL CHAIR LoCICERO: Agreed. Dr. Lewis agrees.

Dr. Ewing?

DR. EWING: Agree.

PANEL CHAIR LoCICERO: Agree. Dr. Doyle?

DR. DOYLE: Agree.

PANEL CHAIR LoCICERO: Agree. Dr. Blumenstein?

DR. BLUMENSTEIN: Agree.

PANEL CHAIR LoCICERO: Dr. Bartoo.

DR. BARTOO: Agree.

PANEL CHAIR LoCICERO: Dr. Leitch.

DR. LEITCH: Agree.

PANEL CHAIR LoCICERO: Okay. And then the use in certain facilities as we
have discussed during this panel meeting, that that is implied because
of the type of device this is, that it would be placed in certain
facilities but would not require a stipulation. Does everybody agree
with that statement?

Okay. So the panel feels that for Question 11 that prescription is the
appropriate.

MS. SHULMAN: Thank you.

Okay. Now I can move on to the supplemental data sheet. And, again,
Questions 1 or 2, the generic type of device and the Advisory Panel.

Okay. Question 3 is device and implant, and that\'s defined as being
implanted longer than 30 days.

PANEL CHAIR LoCICERO: By definition it is longer than 30 days. The
device is intended for use up to six months. Then this would be an
implant. So is that agreeable with the panel?

And the answer appears to be unanimous.

MS. SHULMAN: Thank you.

Number four, the indications for use in the device labeling, again, we
can say as presented earlier this morning or you can add anything you
wish to at this point.

PANEL CHAIR LoCICERO: Dr. Lewis, do you agree with the wording we talked
about, the salient issues? Are you comfortable with the \--

DR. LEWIS: I am.

PANEL CHAIR LoCICERO: Yes. Okay. Is everyone else agreeable with the
labeling as discussed?

And the answer is yes. So we are going to say as discussed.

MS. SHULMAN: Number five, the identification of any risks to health
presented by the device. Again, you may say as presented or add anything
you wish to.

PANEL CHAIR LoCICERO: We had a fairly exhaustive discussion concerning a
variety of risks both from the FDA and from the panel. Does anyone wish
to add any additional?

There are no additional comments. So we\'re going to say as discussed.

MS. SHULMAN: Thank you.

Number six, the recommended advisory classification and priority. The
classification is II and the priority, again, is high, medium or low,
and how fast would you like us to work on this proposed regulation?

PANEL CHAIR LoCICERO: Dr. Miller, you probably use this more than any of
us here. How fast would you like to see this done?

DR. MILLER: I think a medium or a low priority would be appropriate.
Probably low priority I think is most appropriate probably.

PANEL CHAIR LoCICERO: Since there are already 41 approved.

DR. MILLER: Yes.

PANEL CHAIR LoCICERO: Okay. Does anybody have any objection to low
priority?

(No response.)

PANEL CHAIR LoCICERO: Low priority.

MS. SHULMAN: Thank you.

Number seven, if the device is an implant or is life sustaining or life
supporting and has been classified in a category other than Class III,
explain fully the reasons for the lower classification with supporting
documentation and data.

And, for example, you may say that the general and special controls can
handle the risk or it\'s not an unreasonable risk.

PANEL CHAIR LoCICERO: I think we\'ve had a discussion concerning all of
the risks involved. Does anyone wish to add any additional comments to
what we discussed?

(No response.)

PANEL CHAIR LoCICERO: Seeing no additional comments we will say as
discussed.

MS. SHULMAN: Thank you.

Number eight, the summary of information, including clinical experience
or judgment upon which the classification recommendation is based,
again, you may say \"as presented in the panel meeting\" or you may add
anything you wish to at this point.

PANEL CHAIR LoCICERO: Does anyone wish to add additional comments to
what we discussed this morning?

(No response.)

PANEL CHAIR LoCICERO: So this will be as discussed.

MS. SHULMAN: Thank you.

Number nine, the identification of any needed restrictions on the use of
the device in addition to the prescription statement that we handled on
the general device questionnaire.

PANEL CHAIR LoCICERO: We had talked about the issue of special
precaution to children as an important issue for labeling. Other
additional things that we want to add to what\'s been discussed?

It\'s still during the discussion. I just wanted to emphasize that that
was a point brought up that was not in the materials presented. Any
additional risks?

I think we can say as discussed.

MS. SHULMAN: Thank you.

Okay. On the next sheet we may skip Question 10 because that only
applies to Class I devices.

So Question 11, if the device is recommended for Class II, recommend
whether FDA should exempt it from pre-market notification.

PANEL CHAIR LoCICERO: Dr. Newburger, what\'s your recommendation?

DR. NEWBURGER: It should not be exempt.

PANEL CHAIR LoCICERO: So nonexempt status.

DR. NEWBURGER: Nonexempt.

PANEL CHAIR LoCICERO: Does the panel agree with that?

Everybody is in agreement that it should be nonexempt.

MS. SHULMAN: Okay, and then Question 12, if there\'s any existing
standards that you know of that you wish to add other than the ones that
were discussed this morning in the panel meeting.

PANEL CHAIR LoCICERO: Okay. There are standards, and the discussion was
that Dr. Melkerson assured us that the FDA would list all appropriate
standards applied to this product. Is there any additional that anyone
is aware of?

(No response.)

PANEL CHAIR LoCICERO: So this will be as discussed and recommended.

MS. SHULMAN: Thank you.

Now, if you will please vote on the completed forms as a Class II
nonexempt device subject to the special controls guidance document.

PANEL CHAIR LoCICERO: Okay. During this panel meeting we have had
consensus for everything. I just want to read for the record that the
industry representative and Dr. Doyle are nonvoting, but we have invited
their comments all the way along.

So for the purpose of voting on this, let\'s see a show of hands
concerning approval of the classification as outlined in the work sheet
and the supplemental material.

(Show of hands.)

PANEL CHAIR LoCICERO: Approval, and the vote is unanimous.

MS. SHULMAN: Thank you very much.

DR. KRAUSE: Could everybody please pass their work sheets to me? We
appreciate it. Thank you very much.

PANEL CHAIR LoCICERO: After deliberations, we\'ve decided to move ahead
with the next section. So we will begin at this time to discuss
classification of wound dressing for a drug. We\'ll begin with a
presentation by Ms. Merry Lee Bain from Cook Biotech. Her presentation
will be followed by a presentation by Dr. Sergio Gadaleta of Ethicon.

These industry presentations will be followed by the FDA presentation.
Following the FDA presentation we will have a general panel discussion
of this topic, followed by a more focused panel discussion aimed to
answer the FDA\'s questions.

Following the panel discussion, we will complete the reclassification
work sheet and supplemental work sheet. The vote on these work sheets
will constitute the panel\'s recommendation to the FDA.

There will also be time for public comment before the vote.

I would like to remind the public observers at this meeting that while
this portion of the meeting is open to public observation, public
attendees may not participate, except at specific request from the
panel.

Let\'s begin with Ms. Bain.

MR. MELKERSON: Just for the record, Ms. Bain, do you have copies of your
presentation?

MS. BAIN: No, I don\'t.

MR. MELKERSON: If you can get a copy, you can give it to the
transcriptionist.

MS. BAIN: Okay.

MR. MELKERSON: Thank you.

MS. BAIN: Thank you.

I\'m Merry Lee Bain, Vice President of Regulatory Affairs at Cook
Biotech, Incorporated.

Cook Biotech manufactures the Oasis wound matrix, which is a natural
matrix that supports the management of all partial and full thickness
wounds.

On behalf of Cook Biotech, I want to thank the panel and the FDA for the
opportunity to speak today and for the consideration of the
classification for wound dressings with drug.

We at Cook Biotech believe that wound dressings with drug, biologic or
animal based components are properly classified as Class II devices. We
believe such wound dressings are a category of devices that can be
adequately regulated with special controls, including guidances that
utilize existing product standards and quality control procedures.

Regulation as Class II products will, therefore, provide a reasonable
assurance of safety and effectiveness. Although we haven\'t had the
benefit of hearing the FDA presentation, we have concerns about the
scope of this proposed classification. It\'s our belief from earlier
discussions with the agency that the new classification CDRH was
considering would include wound dressings that have drug, biologic, or
animal based components.

However, the proposed identification for the device and the agency
background material provided on the FDA Website several days ago did not
appear to contemplate wound dressings with biologic or animal based
components as part of the new classification.

The new classification does not appear to cover dressings with biologic
or animal based components that have also been cleared under product
code FRO or other unclassified wound dressings.

I understand from a conversation with agency personnel just moments ago
that classification for products with biological components may also
fall under this classification being proposed. So we just ask for
clarification of everything that will be encompassed by this proposed
classification.

We believe that the liquid bandage classification and the numerous
product codes currently used for collagen wound dressings, interactive
wound dressings and/or wound dressings that contain drug or biologic
components have been inconsistently applied, thus suggesting that an
additional classification for wound dressings could add clarity to the
regulatory process.

Only liquid bandages and certain surgical dressings classified in 1999
are actually classified, and those surgical dressings specifically do
not include dressings that have a drug, biologic or animal based
component.

Collagen wound dressings, interactive wound dressings, and wound
dressings that contain drug or biologic components are unclassified
devices. Therefore, we request that the agency clarify the kinds of
wound dressing this new classification would and would not include.

Based on the history of regulation of wound dressings, we believe it
wholly appropriate that the Class II classification proposed today
include wound dressings that have biologic components to enhance the
basic device function of wound management and clarify how products with
animal based components will be regulated in order to adequately
encompass wound care products currently marketed.

It\'s important to note that while many of today\'s wound dressings are
more complex than simple liquid bandages or collagen dressings, they are
not necessarily interactive wound dressings with preserved cells. They
may include antimicrobial components, growth factors, or other drug or
biologic components that enhance the primary purpose of protectively
managing a wound.

Simply stated, these wound dressings are much more complex than the
gauzes and dressings that were considered when the original device
categories were created. In other words, the original categories did not
contemplate the array of wound dressings marketed today.

The lack of adequate classifications for these complex devices stifles
innovation because it is difficult to obtain reimbursement, and
reimbursement is typically not commensurate with the complexity and
benefit of the products. Many companies are unwilling to invest in the
research and development for new wound dressings when the reimbursement
process remains so uncertain and fails to recognize the complexity of
these devices.

Thus, the proposed category being discussed today is important to
clarifying the regulatory and reimbursement status of today\'s more
complex wound dressings.

We urge the panel and FDA to proceed cautiously in developing new wound
dressing classifications because so many dressings are already on the
market and new classifications could affect currently cleared products
and products already in development based on the regulatory pathways
known.

We appreciate the opportunity for public participation at this early
stage in the classification process and believe it is critical that FDA
keep the public abreast of the agency\'s thinking so that there\'s ample
opportunity for all stakeholders to comment.

If new classifications are proposed and finalized, we would also
encourage the agency to review and revise again with public input any
guidance on wound dressings. As the agency has stated in the materials
distributed for panel review, many of these wound care products have a
long history of use. This long history of use must be taken into
consideration when defining requirements for 510(k) submissions for
similar products because many of the issues identified in the proposed
guidance sections have already been addressed through clinical
experience with the predicate products.

Therefore, in accordance with the least burdensome approach much of the
testing described in the proposed guidance should be required only for
truly novel components of wound dressings. As such it will be very
important to allow opportunity for public comment on draft guidance
being considered.

Thank you very much.

PANEL CHAIR LoCICERO: Thank you.

Are there questions from the panel for Ms. Bain?

(No response.)

PANEL CHAIR LoCICERO: thank you.

MS. BAIN: Okay.

PANEL CHAIR LoCICERO: Let us now continue with Dr. Gadaleta\'s
presentation.

DR. GADALETA: Good morning, and thank you for allowing me to present
Ethicon\'s recommendation on the classification of wound dressings with
drugs.

The world of wound dressings can be sort of split up into three general
areas: wound dressings without drugs that are generally indicated for
absorbing wound exudate, supporting a moist would healing environment,
et cetera. These drugs have been classified as Class I and do not
require a 510(k) for marketing.

On the opposite end of the spectrum, you\'ve got dressings with drugs
that are indicated to actively promote wound healing. There are known as
interactive wound dressings, and FDA has classified these as Class III
devices.

And then somewhere in the middle we\'ve got dressings with broad
spectrum antimicrobials that are generally intended to prevent
colonization of the wound dressing itself, and it\'s this group of
devices that I\'d like to address this morning.

The Food, Drug, and Cosmetic Act prescribes how we generally classify
devices. Class I devices generally require general controls to provide
reasonable assurance of effectiveness and safety.

Class II, general controls plus special controls.

And finally, Class III where general controls and special controls are
not adequate, and the device supports or sustains human life is of
substantial importance in presenting impairment of human health or
presents unreasonable risk of illness or injury.

Now, these wound dressings with broad spectrum antimicrobials that are
intended to prevent contamination of the dressing, I went through sort
of the classification checklist, if you will, to arrive at a conclusion.
These devices do not support or sustain human life. They are not of
substantial importance in preventing impairment of human health, and
they do not present unreasonable risk of illness or injury.

We believe that general controls are probably not adequate to provide
reasonable assurance of effectiveness and safety, but we do believe that
special controls are adequate.

In summary, wound dressings with drugs that are intended to prevent
colonization of the dressing have the same intended use as wound
dressings without drugs. In general, they\'re technologically identical
to wound dressings without drugs. They do not support or sustain human
life, are not of substantial importance in preventing impairment of
human health, and do not present unreasonable risk of illness or injury.

Therefore, our recommendation is that we classify these devices as Class
II and have special controls that would actually demonstrate that the
device plus the drug, in fact, prevents colonization of the wound
dressing, and there are appropriate data to demonstrate that device is
safe.

Thank you very much.

PANEL CHAIR LoCICERO: Thank you. Any questions?

DR. MILLER: I have one more question.

PANEL CHAIR LoCICERO: Yes.

DR. MILLER: I wonder if you consider the dressing with drugs to be
substantially equivalent to those without drugs, then what\'s the
purpose of adding the drug to the dressing?

DR. GADALETA: The addition of broad spectrum antimicrobials actually
prevents the dressing from being colonized by some type of microbe.
That\'s the intent of the drug.

DR. MILLER: Under what circumstances would you want to use a dressing
with an antimicrobial in it as opposed to a dressing without one?

DR. GADALETA: That would be a good question for a clinician. Sorry.

DR. KRAUSE: I was just wondering perhaps if Mark or Stephen or if you
want me to do it, if we should comment on Ms. Bain\'s discussion about
the fact that we\'re not including the dressings that have animal
derived components, and also we\'re just calling it a wound dressing
with a drug. Do you want me to?

Because I think there might be a little confusion. Should I just fill
that in?

PANEL CHAIR LoCICERO: Stephen, do you want to?

CDR. RHODES: Does anyone have any questions for Dr. Gadaleta before?

PANEL CHAIR LoCICERO: Any additional questions?

DR. BARTOO: Can you just summarize the types of complaints you\'ve
received at your company regarding these types of devices?

DR. GADALETA: Our group in regulatory affairs isn\'t responsible for the
complaints. I don\'t feel adequately prepared to address it, but I
don\'t think that there is much difference between the complaints we
receive between the wound dressings with drugs versus the wound
dressings without drugs.

PANEL CHAIR LoCICERO: Any additional questions?

(No response.)

DR. GADALETA: Thank you.

PANEL CHAIR LoCICERO: thank you.

CDR. RHODES: This is Stephen Rhodes.

I can address the question about the classification of wound dressings
made from animal source tissue. As I mentioned yesterday, a panel
recommendation is a necessary step for a classifying pre-amendments
devices. In fact, when we were planning for this panel meeting, we
discovered that, in fact, years ago this panel did make a recommendation
to us on the correct classification for animal dressings made from
animal source tissue.

And so we are actually working on the classification process for those.
The recommended classification by the panel was Class II, and our
process is that we will write a [Federal Register]{.underline} notice,
issue a draft guidance for comment, and there will be a period of
comment from the industry for that classification.

So today we are not asking you to classify products made from animal
source tissue. Just wound dressings made by drugs. Okay?

MR. MELKERSON: Stephen, do you also want to address the issue of
interactive in terms of what is being considered here?

CDR. RHODES: Yes, I think we\'ll get into that a little bit in our
presentation, but there are wound dressings that we consider interactive
that are Class III PMA products, where the actual dressing contains
materials that are designed to promote healing in the dressing generally
with cellular materials.

And we have approved them and classified them to the PMA process. So,
again, those are not what we\'re discussing today.

PANEL CHAIR LoCICERO: Just for clarification, we\'re excluding
biologicals or just animal source tissue and interactive agents?

CDR. RHODES: Right. Today we are not talking about animal source
tissues, and not talking about interactive agents. We do have some wound
dressings that contain a biological, thrombin specifically. They would
be eventually considered in this classification as a drug, wound
dressings with a drug.

Our animal source material we don\'t regulate as a biologic. So
collagen, for instance, would not be considered a biologic.

PANEL CHAIR LoCICERO: Okay. Is the panel clear on what we\'re
deliberating on?

Okay. Thank you.

Now we\'ll hear the prepared presentation by the FDA.

DR. AREPALLI: Good morning. We are here this morning to seek the panel
recommendation to classify wound dressings with drugs. My name is Sam
Arepalli, Plastic and Reconstructive Surgery Devices Branch, Division of
General, Restorative and Neurological Devices.

This morning I will be presenting device identification, classification
issues and health risk aspects of this device under consideration.

The next two slides give you the outline of my presentation. I\'ll be
providing a definition of the device under consideration, the reasons
why FDA believes that the device under consideration should be
classified into Class II, the regulatory history of the device, the FDA
Class II device clearance document about which several speakers spoke
earlier, and finally, FDA\'s classification proposal for the subject
device.

Here is the definition of wound dressing containing a drug. It is a
sterile or nonsterile product in which the primary mode of action is
provided by the device component. It is intended to cover a wound, to
absorb exudate, to provide or support a moist wound environment and to
control bleeding or fluid loss. It consists of nonabsorbable materials
and contains added drugs, such as antimicrobials, and it is presently
unclassified. So far we have been clearing these devices as unclassified
devices.

Also, please note the topical wound dressings that do not contain drugs
are classified as Class I exempt devices.

FDA believes it is appropriate if this device is classified into Class
II because of the following reasons. We have years of experience
regulating these devices, that is, since 1976. We understand the device
specifications and performance characteristics like bench testing,
animal testing, and clinical data that are needed to evaluate and
control the safe materials.

And finally, classification to Class II meets the FDA mandate to apply
the least burdensome approach to regulating medical devices.

Now I\'ll give you a brief regulatory history of this device. Wound
dressings with drugs are pre-amendment devices, that is, they were in
commercial distribution before 1976. These devices were not classified
at the time of Medical Device Amendment of 1976 to the Food, Drug, and
Cosmetic Act. These devices are being treated as unclassified devices
and are cleared through a process that is a pre-market notification
process.

A few examples of these are boric acid containing adhesive bandages,
antimicrobial adhesive bandages, and mercurochrome. These devices have
been in commercial distribution since 1920s and \'30s.

The FDA cleared over 50 dressings with drugs in the last seven to eight
years. Some of the recently cleared wound dressing products with drugs
are listed in these two slides. These dressing contain drugs like
silver, bismuth subgallate, methylene blue, crystal violet, and
chlorohexidine.

The dressings with silver that are indicated for minor cuts and scrapes
were cleared as OTC products.

We believe that this product should be classified and regulated as Class
II device using FDA Class II guidance document as a special control.

So what is a special control guidance document? A Class II special
control guidance document is intended to provide guidance by conveying
the agency\'s current thinking on a specific topic under consideration.
It provides the agency\'s recommendations on how to address the issues
presented in the guidance.

However, a firm needs only to show that the device needs the
recommendations of the guidance or in some way provides equivalent
assurance of safety and effectiveness.

The next three slides will give you a flair of how a Class II device
guidance document looks like. This topic has been covered in depth by my
colleagues earlier, and therefore, I\'m not going to deliver too much
time on this topic other than to show you the different sections of the
guidance document and tell you that the proposed Class II special
control guidance document for this device under consideration will be
very similar to this guidance document. These are the sections.

So if this product is to be regulated as a Class II device, what are
different adverse events that are seen with this product and what are
different health risks that this product might have and how we can
handle these risks by special controls are the issues we need to
discuss.

With such a database of adverse events, we are medical device reporting
that are MDR system, and the product for the FRO for these devices
cleared in the last seven to eight years, and found a total of 36
adverse events that are reported. So these are the adverse reports that
are present or displayed on this slide.

This slide shows the kind of adverse events for these products. They
range from blistering to inflammation and infection.

After doing the MDR reports, we believe that this product, the health
risks can be taken care of by the proposed controls present in the FDA
special controls, that is, Class II guidance document. For example,
compromised sterility will be handled by device labeling and animal
studies, injury by animal studies and device labeling and clinical data.
And pain also will be handled by clinical data.

Thus each one of the potential risks posed by this product can be
handled by a Class II device controls present in FDA\'s special controls
guidance document.

Therefore, FDA is proposing that this device under consideration be
classified into Class II, that is, with special controls. The special
controls employed in this case would be a detailed guidance document.

Okay. Again, the identification and proposed classification of this
device is given here again. Identification, a wound dressing containing
a drug is a sterile or nonsterile product in which the primary mode of
action is provided by the device component. It is intended to cover a
wound to absorb exudate, to provide support and moist wound environment
and to control bleeding or fluid loss. It consists of nonabsorbable
materials and contains active drugs such as antimicrobials.

Finally, classification will be Class II. The preferred classification
for this device is Class II with special controls, and these special
controls will be developed through good guidance practice.

Thank you very much.

PANEL CHAIR LoCICERO: Thank you.

Does the panel have questions for the FDA? Yes, Dr. Leitch.

DR. LEITCH: On the identification, the control of bleeding, is that
referring to a thrombin dressing?

CDR. RHODES: Yes.

DR. AREPALLI: So we can say yeah.

DR. LEITCH: I\'m sorry?

DR. AREPALLI: Yes, I think so, yes. Stephen?

CDR. RHODES: Actual indications, intended uses are what was on the
market prior to 1976. That\'s what we\'ve put up in our identification,
and so there were wound dressings that didn\'t contain thrombin that are
for control of bleeding, and the mechanism is as a covering, you know,
as a tamponade.

So that specifically is referring to the general class of the wound
dressing. We tried to sort of incorporate some of the different intended
uses in our identification that we\'ve seen.

DR. LEITCH: I guess I might think of that as kind of misleading in some
way. I mean, if it\'s more the mechanical part of bleeding control being
compression or tamponade, I think that\'s different than, you know, the
drug inherent in the device as being responsible for the control of
bleeding.

CDR. RHODES: Right, and the identification, I think the distinction is
that we try \-- the identification states that the primary mode of
action of this product is the device action, and while it does contain a
drug or drugs, the primary effect, in other words, the mechanism of
action for the intended use is the actual device.

DR. LEITCH: So the idea of the dressing without anything in it to be the
control of bleeding?

CDR. RHODES: Right. We have some dressings that do not contain drugs
that are indicated for controlling of bleeding. Those are Class I
devices.

PANEL CHAIR LoCICERO: At the risk of confusing the issue, I guess there
were some battle dressings designed to stop bleeding by tamponade, and
those have been available before regulation, and that any additional
agent to stop hemorrhage is an adjunct to the intended use.

CDR. RHODES: Right. I mean, some of these dressings are used for
military use. So, yeah, there would be actually controlling bleeding.

But to fit into this classification, the primary mode of action of this
product would be the actual device function.

PANEL CHAIR LoCICERO: Right. So if we were to take an old dressing that
was intended for stopping hemorrhage by tamponade and add an agent as an
adjunct to stopping bleeding, that that would fit in this class?

CDR. RHODES: Well, we have a process by which we evaluate what is the
primary mode, whether it\'s being provided by the device or by the drug
or biological, and if the actual primary mechanism is provided by a
drug, then it\'s regulated in the Center for Drugs, and if the primary
mechanism is by a biologic, it\'s regulated in the Center for Biologics.

PANEL CHAIR LoCICERO: Is the crystal ball getting clearer?

(Laughter.)

PANEL CHAIR LoCICERO: Dr. Miller.

DR. MILLER: I think the difficulty with this whole thing is that these
are not really distinct categories. Every dressing in some ways is an
interactive dressing, I mean, interacts with the wound. It\'s hard to
say, you know, even a saline dressing is not interactive because it is.
It\'s affecting the wound environment. So it\'s difficult to separate.

But my question to the FDA is say a company comes with a dressing
designed not to be interactive but contains a drug. How do you confirm
that it, indeed, doesn\'t interact with the wound in some way?

You know, it\'s untenable to say they put a specific revenue and then
hit its epithelialization as well as bacterial, and they bring it as a
non-interactive dressing, but in fact, it does interact with the wound
in a negative way. How do you sort that out in terms of this process?

CDR. RHODES: I\'ll take that. This is Stephen Rhodes again.

Well, the initial step is an evaluation, again, to make sure that the
primary mode of action of this product is the device function. Then we
look at biocompatibility information, animal information, in some cases
clinical information, to look at the extent of drug that is in the
product and can be released into the wound, and we involve our Center
for Drugs to evaluate those issues.

Ultimately, we then go through our decision making process about whether
this product is substantially equivalent to other wound dressings that
are currently marketed. So that the potential effect of a drug is
evaluated by both bench and animal and in some cases clinical data.

MR. MELKERSON: This is Mark Melkerson.

Maybe putting it in my engineering terms, we would entertain marketing
submissions under 510(k) if it were Class II. During the review process
if it becomes apparent that the agent being added, whether drug or
biologic, had a primary mode, it would actually go and consult with our
Office of Combination products to actually request that a designation of
lead center be identified.

If it\'s something that we\'ve seen before, as Stephen Rhodes has
identified, we would evaluate that particular agent in terms of
preclinical or clinical data showing that it was as safe and effective.

So if you put something on that performed worse than a predicate
product, it would be found not substantially equivalent, and again,
going into it, forcing that product into a PMA mode.

So the review process by classifying it would put it into there would be
an evaluation versus current wound dressings which are without drugs,
are Class I exempt. They don\'t even have to submit anything to the FDA
to determine whether or not it\'s safe and effective as a predicate
product.

DR. MILLER: So there\'s like a process where you confirm that the device
actually is not such a device before you can sort of default into this
category.

MR. MELKERSON: It performs no worse than the predicate product. In other
words, when we\'re going through the review process, as you said, it\'s
not a discrete set of products. There\'s kind of a continuum.

The issue with what the product does as long as the primary mode of
action is to keep the wound area covered and moist is the intent. The
adjunct of adding a component to the drug either to keep the
contamination down in the wound dressing itself; you\'re getting into
that area of who has lead or what\'s the lead center. That pretty much
comes up to have we seen the product before. If we have, then it\'s
under the 510(k) process. If it\'s a new entity, then that is generally
one that we would refer off to the Office of Combination Products and
identify what would be the primary mode of action for that product.

So that\'s usually where our decision point is. Have we seen it before?
And that\'s the 510(k) process on a \"me, too\" product versus \"I\'m a
new entity\" or \"I\'m not even an approved drug\" or biologic would
kick it out of our normal review process.

CDR. RHODES: I absolutely agree with you about the distinction or
questionable distinction between interactive and noninteractive. In
fact, that\'s more of a historical terminology, and in our slides in our
guidance, we wouldn\'t use that term at all because it\'s actually
confusing.

Our regulations don\'t use that terminology. So I\'d kind of like to get
away from that.

PANEL CHAIR LoCICERO: Any other questions or comments?

(No response.)

PANEL CHAIR LoCICERO: The Office of Combined Products, what is that?

MR. MELKERSON: Office of Combination Product is actually at the
Commissioner\'s level, and their purpose is actually to identify and
assist the different centers in identifying what center will lead a
review in a particular product, and that goes across device areas.

PANEL CHAIR LoCICERO: Further questions?

(No response.)

PANEL CHAIR LoCICERO: Thank you.

We will now start the panel deliberation portion of the meeting. This is
before questions. Are there any additional comments prior to addressing
the FDA\'s questions?

Are we all clear on the category of agent that we\'re talking about,
device that we\'re talking about?

(No response.)

PANEL CHAIR LoCICERO: Okay. I guess it\'s time then that we begin to
focus the discussion on the FDA questions. Those questions have been put
up by Dr. Arepalli.

We are not going to discuss at this time the reclassification
questionnaire. We will do that after the discussion of the questions is
complete, and please consider these questions as we respond.

Number one, please discuss the proposed classification for wound
dressing with drugs. Please also discuss what descriptive information
and intended use should be included in the classification
identification.

Let\'s begin with Dr. Lewis.

DR. LEWIS: It seems to me the recommendations we\'ve heard both from
industry and the FDA are all consistent, and they\'re also consistent
with a long period of use of these and the extensive experience which
everyone has.

So I believe that the appropriate category would be Category II and
recommend that.

PANEL CHAIR LoCICERO: Okay. Dr. Ewing.

DR. EWING: I agree with those comments.

PANEL CHAIR LoCICERO: Dr. Doyle.

DR. DOYLE: I have nothing to add.

PANEL CHAIR LoCICERO: Dr. Blumenstein.

DR. BLUMENSTEIN: Agree.

PANEL CHAIR LoCICERO: Dr. Bartoo.

DR. BARTOO: Agree.

PANEL CHAIR LoCICERO: Dr. Leitch.

DR. LEITCH: I agree Class II is reasonable, and I think that the
discussion that we\'ve had today about trying to be specific about what
you\'re talking about in these dressings is critical.

You know, for me reading the identification as it stood, I think it
could be construed, you know, that there is some other interactive stuff
going on, and somebody could put a dressing in under that.

But you know, if the agency kind of understands what they\'re doing
there, then I think it\'s acceptable.

PANEL CHAIR LoCICERO: Dr. Miller.

DR. MILLER: I think it should be Class II as well. I guess my only
concern is just that there be confirmation that this is, indeed, sort of
a passive dressing because obviously things are being created and
manufactured that have all kinds of materials in them and we market it
as superior to saline or a Davis solution or something, and now we are
concerned are these things that are put in these dressings that are not
intended to affect the wound but actually do affect the wound. I guess
as long as there\'s a process that is in place to insure that the ones
that are classified as dressings with drugs not intended to affect the
wound bed, then I would feel comfortable with classifying those as Class
II.

Dr. Newburger.

DR. NEWBURGER: I agree with Dr. Miller\' comments.

PANEL CHAIR LoCICERO: Okay. Just in terms of semantics, the
identification statement says that these devices are sterile or
nonsterile. I think that includes the universe of sterility, and those
can be eliminated from the statement.

So it would read, \"The wound dressing containing a drug is a device.\"
Is everybody okay with that? It just shortens it for us.

Mr. Melkerson, are these comments adequate to answer FDA\'s questions?

MR. MELKERSON: I believe, yes, and to the point on trying to clarify the
scope, that would be something that we would actually try to address
with the guidance document itself on what actually fits in and what
doesn\'t fit into this category, at least on the first cut, which may
also address the industry comments of being clear on what\'s included
and what\'s not included.

And the guidances are both for industry and the FDA.

PANEL CHAIR LoCICERO: Can we have the questions again?

Question No. 2, please discuss the possible risk to health that may be
associated with wound dressings with the drug.

Dr. Newburger.

DR. NEWBURGER: I have some real concerns about potential risks with
these wound dressings with drugs. The first red flag would be the
development with the resistance to antimicrobials. We\'re seeing a
tremendous increase in the community not only in MRSA but other super
bugs.

And I think that many of these topical antibiotics which are going to be
added to these drugs will further make it difficult to treat secondary
wound infections and open wounds by creating resistance.

So it will certainly change the colonization organisms that reside in
the individual who\'s using them.

Second of all, we see the use of merthiolate, an aerosol, over the
course of decades has led to tremendous sensitization in the population
in general. Somewhere around five percent of individuals of my vintage,
how are they contacted if they are allergic to an aerosol, initiated
from administration that this is a topical into open wounds such as
Greg\'s knees.

We are seeing a tremendous increase in these that is a contact allergy
to Neosporin and cross-reacting topical antibiotics, as well as
Bacitracin, and this is just from repeated use.

If we want to induce sensitization in someone, we will apply a
medication under inclusion for an extended period of time. We certainly
see that in humans as well as in sensitization models, and I\'m
concerned that we will start to see tremendous increase in sensitization
and whatever antibiotics and equivalents are used.

Besides that, we\'ve done a tremendous amount of patch testing or
contact allergy testing in our practice, and one of the issues is this
is a situation where you are putting a potential allergen on someone\'s
skin for simply 48 hours, and sometimes you can, just with that 48
hours, you can reduce sensitization.

So I see that there are substantial potential risks with the use of
these, and I think that those should be addressed clearly in the
guidance document with very big labeling, nothing on microfiche.

PANEL CHAIR LoCICERO: Okay. Understood.

Dr. Miller.

DR. MILLER: I think I guess in response to some of the things just
mentioned that most of the antimicrobial dressings don\'t pose so much
of a risk for creating resistant strains because the materials aren\'t
used to treat systemic infections. They\'re things like silver, bismuth,
things that are very toxic antiseptics really, I guess, and bacteria
don\'t get resistant to those necessarily like antibiotics.

I don\'t know. I think that, again, in terms of classifying things that
exist, there\'s no problem, but as new things come out I would be
concerned about this sort of issue if somebody comes out with a dressing
that has an antibiotic that is used systematically to control the
colonization in the dressing that needs to be considered, and I guess
that seems like a separate issue to what we\'re talking about here, but
I just want to be sure that it is.

PANEL CHAIR LoCICERO: Dr. Newburger.

DR. NEWBURGER: Excuse me. There are some bandages on the market that
incorporate neomycin in them already, and certainly does cross-react
with some of the medications that are used systemically.

DR. MILLER: Yes. Those that do cross-react or whatever, that\'s not a
trivial problem.

PANEL CHAIR LoCICERO: I think it recognizes that both issues are
important, potential resistance and Dr. Newburger\'s point concerning
skin sensitivities is significant and needs to be addressed by the FDA
in some form, guidance document labeling, whatever.

Dr. Leitch.

DR. LEITCH: I agree with the comments that have been made so far.

PANEL CHAIR LoCICERO: Dr. Bartoo.

DR. BARTOO: I\'m looking at the table of possible risks and controls
that was sent to us in our panel packet. Under skin trauma, the list of
controls are animal testing and/or clinical data, and I was wondering
whether biocompatibility testing would be appropriate for that, you
know, if it\'s a skin reaction to the dressing.

The other question I had is some of the things related to like sterility
compromised with infection. It sounded like we were going to have both
sterile and nonsterile. So I was just wondering in terms of the risk how
that plays in because if it\'s a nonsterile product, then the sterility
controls wouldn\'t apply.

And then just finally there was a category called injury, and you know,
my understanding is that all of these are potential injuries. So I
wasn\'t quite sure whether that should actually be a risk per se and
whether the person should control specifically for injury.

PANEL CHAIR LoCICERO: I think those are excellent points. The tissue
trauma or the injury was raised specifically about the adhesive portion
of the dressing. So that\'s something that would need to be addressed,
but I don\'t think that came up with Dr. Newburger, but adhesive
sensitivity can be an issue as well. Should that be addressed in the
guidance document?

DR. BARTOO: If it is a potential problem, I think it should be in terms
of biocompatibility.

PANEL CHAIR LoCICERO: So addressed as biocompatibility?

DR. BARTOO: Potentially. I mean, I\'m not the clinician. So if that\'s
the appropriate way to control that.

PANEL CHAIR LoCICERO: Dr. Newburger.

DR. NEWBURGER: Certainly, we do see contact sensitivity to various
adhesives not only those that contain some latex moiety, but that\'s
easier to recognize than sensitization within a wound to a topical
antibiotic. For example, someone may just assume that their wound is
getting a little worse because it is getting more inflamed or perhaps
blistering, whereas if you\'re going to have an allergic reaction to the
adhesive, you will see a very sharp geometric reiteration of that
pattern, and the consumer could easily identify that and say, \"Oh, I\'m
allergic. I had better stop that.\"

So that is a significant issue, but I think it\'s something that\'s not
actually quite as risky to the consumer because it is recognized and
stopped.

PANEL CHAIR LoCICERO: Additional comments?

DR. BARTOO: No. That satisfies my comments.

PANEL CHAIR LoCICERO: Okay. Dr. Blumenstein.

DR. BLUMENSTEIN: No additional comments.

PANEL CHAIR LoCICERO: Dr. Doyle.

DR. DOYLE: No additional.

PANEL CHAIR LoCICERO: Dr. Ewing.

DR. EWING: Just one question. The wound dressings, their primary
function is to promote wound healing with epithelialization. What is the
gold standard that these dressings have been compared to? For instance,
is it saline or Decon solution or do they have to prove that they
actually do promote wound healing as part of the acceptance for this
classification?

CDR. RHODES: This is Stephen Rhodes.

Each new product basically makes an argument that they\'re comparable to
an already marketed product in this category. So as has been discussed,
this is quite a broad category of products currently. So there\'s quite
an array or pool to try to build your argument on. So it really depends
on the particular product.

And what we do is we look at, again, bench testing and animal testing
and biocompatibility data and sometimes clinical data to see how
comparable it is.

DR. EWING: Okay.

PANEL CHAIR LoCICERO: Dr. Lewis, in terms of these dressings that might
be used to assist in stopping the bleeding, I think we\'ve all seen
where stretchy tape has been used, particularly by some nurses or other
professionals, where the skin is damaged.

Do you think that should be an issue addressed in the guidance document?

DR. LEWIS: Well, these dressings, as I understand it, don\'t have
adhesive attached to them. We\'re dealing here with gauze and whatever
it is impregnated with for the dressings, but I didn\'t see described
that they have self-adhesive or elastic adhesive on them.

The problems you mentioned certainly are true when you have elastic tape
and you apply it under tension. You certainly can easily damage the skin
where we get blistering and other problems, so it\'s a distinct hazard.

It\'s a generic type of hazard irrespective of the dressing which it\'s
holding in place. So I don\'t see that it\'s a property of the dressing
so much as it is of the tape and the manner in which it is applied.

PANEL CHAIR LoCICERO: Okay, but if a product were presented to the FDA
that contained or that had an adhesive portion to it, then that would
need to be addressed in this guidance document?

MR. MELKERSON: Yes, it would.

PANEL CHAIR LoCICERO: Okay. Are there any additional comments concerning
health risks?

(No response.)

PANEL CHAIR LoCICERO: Mr. Melkerson, does this answer Question 2?

MR. MELKERSON: I believe it does. Thank you.

PANEL CHAIR LoCICERO: Question No. 3, please discuss whether special
controls listed in the FDA guidance document are adequate.

We partially addressed this question, but I want to be sure that we
cover other areas of the guidance document, and we\'ll start with Dr.
Bartoo.

DR. BARTOO: No other comments.

PANEL CHAIR LoCICERO: Okay. No other comments.

Dr. Blumenstein?

DR. BLUMENSTEIN: No further comments.

PANEL CHAIR LoCICERO: Dr. Doyle.

DR. DOYLE: No additional.

PANEL CHAIR LoCICERO: Dr. Ewing.

DR. EWING: No further comments.

PANEL CHAIR LoCICERO: Dr. Lewis? None.

Dr. Newburger, none.

Dr. Miller, none.

Dr. Leitch?

DR. LEITCH: None.

PANEL CHAIR LoCICERO: No additional comments.

Mr. Melkerson, does this sufficiently answer Question 3?

MR. MELKERSON: I believe so, yes.

PANEL CHAIR LoCICERO: Okay. We\'re going to take a short break now and
resume at 10:30.

(Whereupon, the foregoing matter went off the record at 10:19 a.m. and
went back on the record at 10:37 a.m.)

DR. KRAUSE: Okay. I think we can get back to work. If everybody could
please take a seat, we could resume our meeting and hopefully finish up
soon.

Thank you, everybody. Now, back to Dr. LoCicero.

PANEL CHAIR LoCICERO: Thank you.

We will now proceed with the open public hearing session regarding wound
dressings with a drug.

All persons addressing the panel are asked to speak clearly into the
microphone as the transcriptionist is dependent on this as a means of
providing accurate record of this meeting.

We have no registered speakers concerning this issue. Do we have anyone
in the audience who wishes to address the panel at this time?

(No response.)

PANEL CHAIR LoCICERO: No one has volunteered to speak before the panel.
Since there are no requests to speak in the open public hearing, we will
now proceed with the classification questionnaire and vote.

Ms. Shulman of the Office of Device Evaluation will assist us as we go
along.

We will vote on the completed questionnaire and supplemental data sheet
that will become the panel\'s recommendation to the FDA.

I think we\'re pretty prepared on this mechanism by now. Ms. Shulman.

MS. SHULMAN: We\'re just waiting for all the members to get back.

Okay. Thank you again.

On the general device questionnaire, please fill out the panel name,
panel member, and the date and the generic type of device.

All right. Question No. 1, is the device life sustaining or life
supporting?

PANEL CHAIR LoCICERO: I think the panel I can see shaking heads. This is
not a life sustaining, supporting device. So no.

MS. SHULMAN: Thank you.

Number two, is the device for use which is of substantial importance in
preventing impairment of human health?

PANEL CHAIR LoCICERO: Well, let\'s see. Dr. Miller says yes. Let\'s kind
of go through everybody because I can see a disparity here. Dr. Miller
says yes.

Dr. Leitch?

DR. LEITCH: Yes.

PANEL CHAIR LoCICERO: Yes. Dr. Bartoo.

DR. BARTOO: Yes.

DR. BLUMENSTEIN: Yes.

PANEL CHAIR LoCICERO: Yes. Dr. Ewing.

DR. EWING: Yes.

PANEL CHAIR LoCICERO: Dr. Lewis. Now says yes.

Dr. Newburger, yes.

So if we come to consensus, that\'s yes.

MS. SHULMAN: Thank you.

Number three, does the device present a potential unreasonable risk of
illness or injury?

PANEL CHAIR LoCICERO: Okay. This is unreasonable risk of injury, and
everybody is shaking their head no. So the answer to this one is no.

MS. SHULMAN: Thank you.

Number four, did you answer yes to any of the above three question? The
answer is yes. So we go to number six.

Is there sufficient information to establish special controls in
addition to general controls to provide reasonable assurance of safety
and effectiveness?

PANEL CHAIR LoCICERO: And I\'m seeing heads shaking. I\'m aware that the
answer is yes to this one.

MS. SHULMAN: Number seven, if there is sufficient information to
establish special controls to provide reasonable assurance of safety and
effectiveness, identify below the special controls needed to provide
such reasonable assurance for Class II.

PANEL CHAIR LoCICERO: We\'ve been discussing the guidance document and
what we would put in the guidance document. Are there any suggestions
for additional controls?

DR. EWING: I have a question about the performance standards again. You
know, that the efficacy of the product has to be demonstrated that it
actually promotes wound healing and will not inhibit wound healing.

MR. MELKERSON: That\'s actually part of the review process. The
performance standard is actually something that you have to meet a
certain performance of that device, and right now the existing ones
would be like radiology standards, in other words, not having too much
exposure.

PANEL CHAIR LoCICERO: Is that sufficient? Do you feel it requires
performance standards?

DR. EWING: Yes.

PANEL CHAIR LoCICERO: You do want to have performance standards as a \--

DR. EWING: Huh-un. Just the guidance.

PANEL CHAIR LoCICERO: Okay, okay. So the guidance document will be
sufficient for this.

MS. SHULMAN: Thank you.

Again, we may skip Question 8 and 9 because we only have to deal with
performance standards, and Question 10 because that\'s only for a Class
III device.

Question No. 11, identify the need of restrictions. Again, the first one
is the prescription statement, and then the others are additional use
only by persons with specific training or experience in its use or use
only in certain facilities and any other you may wish to add.

PANEL CHAIR LoCICERO: Our standard has been that this be by
prescription. Do we feel this needs to be by prescription?

Yes. Dr. Newburger.

DR. NEWBURGER: Aren\'t by design some of these over-the-counter?

MR. MELKERSON: Yes, that is actually where I was going to clarify. Of
the products that have already been cleared for marketing, some are over
the counter.

PANEL CHAIR LoCICERO: So because that\'s the case, then not all will be
by prescription.

DR. KRAUSE: However, your recommendation can be whatever you think. So
you don\'t have to go along with what we\'ve done.

MR. MELKERSON: That is correct.

PANEL CHAIR LoCICERO: Okay.

DR. KRAUSE: We\'re not trying to force this one way or the other.

PANEL CHAIR LoCICERO: Dr. Miller.

DR. MILLER: I think it sort of depends on the situation. If you\'re
talking about in the nature of the found, if you\'re talking about a
Bandaid has something in its like neosporin, which is over the counter,
that may be not a problem.

If you\'re talking about a large or deep skin wound, the amount of
material you put in, it\'s a different situation. So how do you handle
that? Do you prorate treatment?

MR. MELKERSON: Dr. LoCicero.

PANEL CHAIR LoCICERO: Yes.

MR. MELKERSON: The over-the-counter indications for minor scrapes and
burns, it was not anything more than that.

DR. LEITCH: So the labeling can address that?

MR. MELKERSON: That is correct.

PANEL CHAIR LoCICERO: So if you say no here, there are sections in this
class or i f you say yes, then \--

MR. MELKERSON: For a product to be over-the-counter, you have to be able
to identify for the lay person appropriate directions for use. So if
you\'re talking minor cuts, scratches and burns, it was considered that
you could provide appropriate labeling. Therefore it could be over the
counter.

DR. KRAUSE: You know, an example of what Mr. Melkerson is talking about
is when we had these products that somebody wants to label for over the
counter, the over-the-counter labeling must be understandable by
somebody of an eighth grade reading level, okay, and normally the
indications for use that we write or allow the company, that we accept
from the applicant is something along the lines of the product is over
the counter for minor scrapes, minor burns, and then it says it may also
be used under the care of a health care professional, and then we would
list things like pressure ulcers and the kind of things that you would
expect would be overseen by a doctor or nurse practitioner or somebody
like that.

So even though some of these are over the counter, with very, you know,
simple indications, and then also the labeling must have instructions
for the patient at what point they should go see a doctor if they see
redness or irritation or those kinds of things that are listed as
symptoms that would cause them to go back to their doctor.

MS. SHULMAN: And this is Marjorie Shulman.

If it helps any, if one of the devices is prescription and a company
wishes to come in for an over-the-counter indication, that\'s a new
indication and new indications always require a new 510(k). So we would
have to review that before it went over the counter.

PANEL CHAIR LoCICERO: So just for clarification, if we don\'t choose
prescription, then it becomes a matter of indications and interpretation
by the FDA.

MS. SHULMAN: Correct.

PANEL CHAIR LoCICERO: Okay. So does that help in determining?

DR. MILLER: I\'m sorry. Given those, and if these dressing by definition
that go in this class are passive coverage in the material and the
agents for the material are going to interact with the wound, I\'m not
sure they have to even have a prescription.

PANEL CHAIR LoCICERO: Okay. So does anyone want a restriction?

(No response.)

PANEL CHAIR LoCICERO: There will be no restrictions on this. I get the
sense from the panel that there are no restrictions.

MS. SHULMAN: Thank you.

Now we can move on to the supplemental data sheet.

Question 1 and 2 are the generic type of device and the Advisory Panel.

And Question 3 is device and implant.

PANEL CHAIR LoCICERO: I would not want to be around if it were beyond
six months.

(Laughter.)

PANEL CHAIR LoCICERO: I think the answer to that one is no.

MS. SHULMAN: Is no.

DR. MILLER: Could I ask a question? I\'m sorry to prolong it, but this
goes back to some terminology that I think we should have talked about
earlier, but when you say \"dressing for the drug,\" when you say
\"drug\" to me that means something which has an effect of the body, you
know. So I wonder if we should call it \"dressings with drugs\" or it
should be called \"dressings with agents\" or \"dressings with
chemical.\" You know, drug to me implies it interacts.

So maybe that\'s the \--

PANEL CHAIR LoCICERO: Dressing with a compound?

DR. MILLER: I just throw that thought out.

MS. SHULMAN: I guess it\'s the terminology the FDA uses, you know, how
you think of these things. If the things that are in this are drugs,
then \--

MR. MELKERSON: A product is either a drug, a biologic, or a device or a
combination product, and these are actually combination products even
though the devices have the lead. So anything that combines any one of
those three is a combination product by definition, and our regulations
are split up drugs, devices, biologics, and the Office of Combination
Products determines which center has the lead and which center would be
supportive of that review process.

PANEL CHAIR LoCICERO: So either animal, vegetable or mineral.

All right. Are we okay with that now?

MS. SHULMAN: Okay. Question 4, the indications for use in the device
labeling, again, you can say as presented or you can change or add
anything.

PANEL CHAIR LoCICERO: Does anybody want to add something to our
discussions?

(No response.)

PANEL CHAIR LoCICERO: So as discussed.

MS. SHULMAN: Number five, the identification of any risk to health is
presented by the device, in addition to the ones that are presented at
the panel meeting.

PANEL CHAIR LoCICERO: I think we were pretty clear in the panel meeting
what additional risks need to be included in the guidance document. Are
there any that anyone has thought of since then?

(No response.)

PANEL CHAIR LoCICERO: No additional. So as discussed.

MS. SHULMAN: Thank you.

Number six, the recommended Advisory Panel classification and priority
of the classification is II, and again, for priority, high, medium or
low.

PANEL CHAIR LoCICERO: Okay. Priority, Dr. Newburger.

DR. NEWBURGER: I place this as medium priority because I\'d like to see
some structure to the guidance document.

PANEL CHAIR LoCICERO: Okay. Dr. Lewis.

DR. LEWIS: I vote low.

PANEL CHAIR LoCICERO: Okay. Dr. Ewing?

DR. EWING: Low.

PANEL CHAIR LoCICERO: Dr. Doyle.

DR. DOYLE: Low.

PANEL CHAIR LoCICERO: Dr. Blumenstein?

DR. BLUMENSTEIN: Low.

PANEL CHAIR LoCICERO: Dr. Bartoo?

DR. BARTOO: Low.

PANEL CHAIR LoCICERO: Dr. Leitch.

DR. LEITCH: Low.

PANEL CHAIR LoCICERO: Dr. Miller.

DR. MILLER: Low.

PANEL CHAIR LoCICERO: Dr. Newburger, you\'re outruled. So this is going
to be low.

MS. SHULMAN: Low. Thank you. We\'ll do our best.

Number seven we may skip because it is not an implant or life sustaining
or life supporting.

Number eight, the summary of information including clinical experience
or judgment upon which the classification recommendation is based.
Again, you may say as presented today in the panel meeting or add any
additional comments.

PANEL CHAIR LoCICERO: Dr. Miller, any additional comments?

DR. MILLER: No comment.

PANEL CHAIR LoCICERO: Okay. Dr. Leitch, no.

DR. LEITCH: No.

PANEL CHAIR LoCICERO: Dr. Newburger.

DR. NEWBURGER: No.

PANEL CHAIR LoCICERO: Dr. Lewis.

Dr. Ewing.

DR. EWING: No.

PANEL CHAIR LoCICERO: Dr. Doyle.

DR. DOYLE: No.

PANEL CHAIR LoCICERO: Dr. Blumenstein.

DR. BLUMENSTEIN: No.

PANEL CHAIR LoCICERO: Dr. Bartoo.

DR. BARTOO: No.

PANEL CHAIR LoCICERO: Okay. So as discussed.

MS. SHULMAN: As discussed.

Question nine, identification of any needed restrictions on the use of
the device.

PANEL CHAIR LoCICERO: Are there any additional restrictions that are in
place?

(No response.)

PANEL CHAIR LoCICERO: No one has volunteered to speak. So as discussed.

MS. SHULMAN: Question No. 10 we may skip because it\'s for Class I
devices.

Question No. 11, if the device is recommended for Class II, recommend
whether FDA should exempt it from pre-market notification.

PANEL CHAIR LoCICERO: I get the sense from our discussions that this
should be nonexempt. Is there any objection to nonexempt status?

(No response.)

PANEL CHAIR LoCICERO: Okay. By consensus, nonexempt.

MS. SHULMAN: Thank you.

And Question 12, any additional existing standards?

PANEL CHAIR LoCICERO: Is anyone aware of standards?

(No response.)

PANEL CHAIR LoCICERO: So the guidance document will be the guide.

MS. SHULMAN: Thank you very much, and if we can vote on the forms as
completed as a Class II device requiring 510(k), subject to the special
control guidance document.

PANEL CHAIR LoCICERO: Okay. We\'re about to vote on dressings with drug.
We\'ve completed the work sheet and supplemental data sheet, and we\'re
voting for approval of the classification as included in the
documentation.

Let\'s have a show of hands for approval.

(Show of hands.)

PANEL CHAIR LoCICERO: Okay. Opposed?

(No response.)

PANEL CHAIR LoCICERO: Abstained?

(No response.)

PANEL CHAIR LoCICERO: For. Okay. It\'s a unanimous vote for.

MS. SHULMAN: Thank you very much for your time.

PANEL CHAIR LoCICERO: We need the documents brought to the center.

DR. KRAUSE: Yeah, please pass the documents to me, and thank you.

PANEL CHAIR LoCICERO: Mr. Melkerson, do you have any final comments on
today\'s proceedings?

MR. MELKERSON: Just that I\'d like to thank the panel and wish all
classification panels, especially in the last two days, would have gone
as smoothly. Past history, you\'ve actually impressed me quite a bit in
finishing early both days.

And also I\'d like to extend again the FDA\'s thanks to Dr. Doyle and
Dr. Miller for their service to the panel.

PANEL CHAIR LoCICERO: Very good. I\'d like to add my thanks to
everybody\'s participation on the panel. It\'s been a great experience,
and I think everyone has been very interactive, we would say.

So with that, the session is adjourned.

Thank you.

(Whereupon, at 10:57 a.m., the meeting was concluded.)