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:

 

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):

 

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:

 

MERRY LEE BAIN, Cook Biotech, Inc.

ERIC CAILLE, PMT Corp.

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

 

FDA  PRESENTERS:

 

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

                                              PAGE

 

Conflict of Interest Statement ................. 6

Appointment to Temporary Voting Status ......... 7

Introductions .................................. 9

 

Tissue Expander

      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

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 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.)