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

8:59 a.m.

MS. SCUDIERO: Good morning, everyone. We are ready to begin this meeting of the Orthopedic and Rehabilitation Devices Panel. I'm Jan Scudiero, I'm the Acting Exec Secretary for this Panel, I'm a reviewer in the Division of General and Restorative and Neurological Devices.

Mr. Hany Demian is the Executive Secretary for this Panel, and he is on detail right now to another part of the agency.

First some housekeeping matters. If you haven't signed the attendance sheets at the doors, please do so. The agenda information for this meeting is at these tables.

Advisory Committee website information on upcoming meetings, summary minutes, and transcripts, are also on these tables. I want to announce, now, the tentatively scheduled meetings for the Orthopedic and Rehabilitation Devices Panel for the year 2004.

You may wish to jot these down. They are March 22nd, and 23rd; June 3rd and 4th; August 12th and 13th; and December 2nd and 3rd. Remember, these are tentatively scheduled, in case we need the times.

Before I turn the meeting over to Dr. Yaszemski I'm required to read two statements into the record, the Temporary Voting Member Statement, and the Conflict of Interest Statement.

First the Temporary Voting Member status. Pursuant to the authority granted under the Medical Devices Advisory Committee Charter, dated October 27th, 1990, and amended April 20th, 1995, I appoint the following as voting members of the Orthopedic and Rehabilitation Devices Panel, for the duration of this meeting on December 11th, 2003; Dr. Edward Cheng, and Dr. Fernando Diaz.

For the record, these people are special government employees, and are consultants to this panel, or another panel, under the Medical Devices Advisory Committee. They have undergone the customary Conflict of Interest Review, and have reviewed the materials to be considered at this meeting.

This was signed by Dr. David W. Feigal, Director, Center for Devices and Radiological Health, on December 2nd, 2003.

And now the Conflict of Interest Statement. The following announcement addresses conflict of interest issues associated with this meeting, and is made part of the record to preclude even the appearance of an impropriety.

To determine if any conflict existed the Agency review of the submitted agenda for this meeting, and all financial interests reported by the Committee participants.

The Conflict of Interest statutes prohibit special government employees from participating in matters that could affect their, or their employer's, financial interests.

The Agency has determined, however, that the participation of certain members and consultants, the need for whose services outweighs the potential conflict of interest involved, is in the best interest of the government.

Therefore a waiver was granted for Dr. Kinley Larntz, for his financial interests in firms at issue that could potentially be affected by the Panel's recommendations.

The waiver allows him to participate fully in today's deliberations. Copies of this waiver may be obtained from the Agency's Freedom of Information office, room 12-A-15 of the Parklawn building.

We would like to note, for the record, that the Agency took into consideration other matters regarding Doctors Edward Cheng, Maureen Finnegan, and Steven Li. These panelists reported current or past interests involving firms at issue, but in matters that are not related to today's agenda.

The Agency has determined, therefore, that these panelists may participate fully in the deliberations. In the event that the discussions involve any other products or firms not already on the agenda, for which an FDA participant has a financial interest, the participant should excuse himself, or herself, from such involvement. An exclusion will be noted for the record.

With respect to all other participants we ask, in the interest of fairness, that all persons making statements, or presentations, disclose any current or previous financial involvement with any firm whose products they may wish to comment upon.

And now I turn the meeting over to Dr. Yaszemski.

CHAIR YASZEMSKI: Thank you, Ms. Scudiero. Good morning, everybody. My name is Dr. Michael Yaszemski, I'm an orthopedic surgeon. I work at the Mayo Clinic in Rochester, Minnesota, with a special interest in orthopedics or spine surgery. I'm also a chemical engineer with a special interest in tissue engineering.

I'd like to note, for the record, that the voting members present constitute a quorum, as required by 21CFR14. At this meeting the Panel will be making a recommendation to the Food and Drug Administration on an FDA initiated reclassification proposal to reclassify the intervertebral body fusion device, also called a cage, intended for spinal fusion procedures in a skeletally mature adult, with a generative disk disease at one or two levels, from C2 through C7, and L2 through S1, using autogenous bone graft.

This proposed device identification does not include, for consideration, combination products, such as the intervertebral fusion device using morphogenetic proteins, and scaffolds.

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 the matter being discussed today, and other FDA staff seated at this table, to introduce themselves.

When your turn comes please state your name, your area of expertise, your position, your institution, and your status on the panel, whether as a voting member, a deputized voting member, a consumer representative, or industry representative.

I'd like to start to my left. Dr. Naidu?

DR. NAIDU: My name is Sanjiv Naidu, I'm an orthopedic surgeon, and also material scientist. I'm an associate professor at Penn State College of Medicine, I'm a voting panel member.

CHAIR YASZEMSKI: Thank you. Dr. Larntz

DR. LARNTZ: I'm Kinley Larntz, I'm a statistician, Professor Emeritus, University of Minnesota. I also work as an independent consultant, and I'm a voting panel member.

CHAIR YASZEMSKI: Thank you. Ms. Wells?

MS. WELLS: My name is Cris Wells, I'm the Director of Clinical Operations at the Translational Genomics Research Institute in Phoenix, Arizona. I am the consumer rep on this panel.

CHAIR YASZEMSKI: Thank you. Ms. Maher?

MS. MAHER: Sally Maher, I'm the Senior Director of Regulatory Affairs and Clinical Research for Smith Nephew Endoscopy, and I'm the industry rep on this panel.

CHAIR YASZEMSKI: Thank you. Dr. Witten?

DR. WITTEN: Celia Witten, the division director of the Reviewing Division at FDA for these products.

CHAIR YASZEMSKI: Thank you. Dr. Cheng?

DR. CHENG: My name is Edward Cheng, I'm a professor at the University of Minnesota, the area of practice is orthopedic oncology and joint reconstruction.

CHAIR YASZEMSKI: Thank you. Dr. Finnegan?

DR. FINNEGAN: Maureen Finnegan, I'm an associate professor at UT Southwestern in Dallas. My areas of expertise are fracture in sports, and I'm a voting panel member.

CHAIR YASZEMSKI: Thank you. Dr. Li?

DR. LI: My name is Steven Li, I'm the President of Medical Device Testing Innovation in Sarasota, Florida. And my areas of interest are biomaterials, bioengineering, and testing.

CHAIR YASZEMSKI: Thank you. Dr. Diaz?

DR. DIAZ: My name is Fernando Diaz, I'm a neurosurgeon with a special interest in spine reconstruction. I'm professor of neurosurgery at Wayne State University, and I am the senior VP for medical affairs at the Detroit Medical Center.

CHAIR YASZEMSKI: Thank you, Dr. Diaz. Next, Ms. Barbara Zimmerman, Chief, Orthopedic Devices Branch, will update the Panel on several matters related to the Panel, since the last meeting of the Panel on August 2001. Ms. Zimmerman?

MS. ZIMMERMAN: Thank you. I'm going to go through a list of the -- we haven't had an update in quite some time, so I'm going to go through the list of previous Advisory meetings, and what has come of those devices that were discussed at the previous meetings.

On November 20th, 2002 Panel meeting, the Independence iBOT 3000 Mobility System was reviewed at that time, and the FDA approved that device on August 13th, 2003.

On August 9th, 2001, the Ascension Metacarpal Flangial Finger Joint was reviewed at that time, and approved on November 19th, 2001.

On January 10th, 2002, the Infused Bone Graft with LT-Cage for lumbar tapered fusion was reviewed and approved on July 2nd, 2002.

At a panel meeting that occurred some time between 1997 and 2000, I actually couldn't find the exact date of this panel meeting, a PDP was discussed for the Encore Keramos Ceramic on Ceramic Hip System. This PDP was approved on November 26th, 2003.

At a July 20th, 2000 panel meeting the Osteonics ABC System and the Trident System, which is a ceramic on ceramic hip system, was approved on February 3rd, 2003.

We have had several recent reclassification actions. The reclassification petition for Mobile Bearing Knees has been submitted by OSMA on June 13th, 2003, and is under review by the Agency at this time.

There was a reclass, the metal on polymer porous coated uncemented femoral knee joint prostheses, and unicompartmental metal on polymer uncemented femoral tibular knee joint prostheses were reclassified into class 2, on March 24th, 2003, and this was published in the Federal Register.

The Reclassification Petition for metal on metal total hip hiparthroplasty devices, which was reviewed at the August 8th, 2001 panel meeting was denied on September 6th, 2002. However, the FDA continues to work with OSMA, and hopes that a subsequent petition will be submitted at a later date.

The metal on polymer constrained hip joints were reclassified into Class 2 on April 2nd, 2002. And then resorbable calcium salt bone void filler was classified into Class 2 on June 2nd, 2003.

There is a 510(k) clearance that I would like to bring to your attention. This is for the DePuy Delta Shoulder. It was cleared on November 18th, 2003. It is designed such that the ball of the articulation is incorporated into the glenoid prostheses, and the cup of the articulation is incorporated into the humoral prosthesis, i.e., a reversed shoulder. It is indicated for patients with rotator cuff deficient shoulder joints.

That is all I have, thank you.

CHAIR YASZEMSKI: Thank you, Ms. Zimmerman.

Today we will begin with the FDA presentation, then we will hear two industry presentations, and then proceed to the open public hearing.

We will next have the Panel deliberation portion of the meeting, beginning with an introduction of today's topic, that will be led by Dr. Diaz. After having a general discussion the Panel will address the FDA questions, then the Office of Device Evaluation, Classification, Reclassification coordinator will guide the Panel in the completion of two forms.

One, the reclassification questionnaire, and two, the supplemental work sheet. The Panel's vote on these two documents will constitute our recommendations to the FDA.

We ask, at this time, that all persons addressing the Panel speak clearly into the microphone, as the transcriptionist is dependent on these means to provide an accurate record of the meeting.

And I will ask your indulgence if during your talk you haven't done that, and I will gently remind you to do so. So please bear with me if I do that.

We are also requesting that persons making statements during the open public hearing clearly state his or her name, affiliation, and the nature of any financial interest he or she may have in this, or another medical device company, if any, and disclose if anyone, besides yourself, paid for your transportation and accommodations to this meeting.

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

We will now have the FDA presentation on the proposed reclassification. The FDA presenter is Ms. Jodi Anderson, a reviewer in the Orthopedics Device Branch.

Ms. Anderson?

MS. ANDERSON: Good morning. Thank you all for being here this morning. I'm going to present an FDA-initiated proposal for the reclassification of intervertebral body fusion devices.

And from this point forth, for the case of simplicity, I'm just going to refer to these devices as cages.

Let me begin with an anecdote. Last night my husband and I were eating Chinese food. At the end of the meal we received fortune cookies and, I think, as an accepted means of choosing the fortune cookie, I chose the fortune that was pointed my way.

Opening the cookie it says, you will make a change for the better. I digress and point out that my lucky numbers are 1, 12, 23, 38, 40 and 25.

Anyway, let me move on. This morning I'm going to discuss four major topics. I'm going to present a background of medical device classification. The Panel has just heard this, but for everybody in the audience perhaps this will be helpful.

I'm going to give a regulatory history of cages. I'm going to give an FDA initiated cage reclassification proposal, and then I'm going to go through, briefly, the questions for the Panel.

And at this time, actually, the Panel is not going to be commenting on these questions, I'm just providing them so that you have a heads up as to what you will be discussing shortly.

Medical device classification, where did it come from? The 1976 amendments of the Food, Drug and Cosmetic Act, provide regulations for the classification and regulation of medical devices intended for human use.

The Act established three categories, or classes, of medical devices depending upon the regulatory controls needed to provide a reasonable assurance of their safety and effectiveness.

There are Class I devices, which require general controls; Class II devices, which require special controls; Class III devices, which require pre-market approval.

I'm going to describe what each of these controls are in the next couple of slides. What are general controls? General controls provide a means of ensuring the reasonable safety and effectiveness of Class I devices.

General controls include things like prohibition against adulterated or misprinted devices, pre-market notification/submissions, or 510(k)s, the quality system regulations, which includes design controls, good manufacturing processes, or GMPs, and registration of manufacturing facilities.

What are special controls? Well, in the instance that general controls are insufficient, special controls are added to provide the reasonable assurance of safety and effectiveness of Class II devices.

Special controls include things like Guidance Documents, Performance Standards, Post-Market Surveillance, Clinical Data, and Labeling. And special controls are going to be the focus of much of our later discussion, or much of my later discussion.

Class III devices are life sustaining, or life supporting or, particularly, in the instance of orthopedic devices, present an unreasonable risk for causing illness or injury.

Insufficient information exists to determine the adequacy of general and special controls. So Class III devices are regulated by using valid scientific evidence presented within a pre-market approval application, or PMA, to establish the safety and effectiveness of the device.

I could go on to a long discourse regarding what consists a valid scientific evidence, and what does not, but I think that that would confuse this discussion. And if you have that question feel free to bring it up with me later.

So, reclassification, the FDA can change the class of a medical device to a different regulatory class. In fact, FDA is required to clarify and reclassify devices into the lowest class that can reasonably assure the safety and effectiveness of the device.

I wish I could just say S&E, but that would be confusing. When can a device be reclassified? A Class III device can be reclassified when FDA can identify the risks associated with the device, and the manner in which these risks can be controlled by general and special controls.

And while we are doing this we hope to maintain a least burdensome approach. So let me get into cages. Having reviewed regulatory background, I will move on to describe the devices for which propose the reclassification.

So we consider cages to be implanted single or multiple component spinal devices made from a variety of materials, for example, titanium alloys or polymers, that fill the intervertebral disk space, for example, hollow threaded cylinders, mesh cylinders, fenestrated rectangular blocks, trapezoidal cubes, or wedge shaped solids, and they are available in a variety of sizes.

The following describe the approved indications for use of cages. They are approved for the following indications, skeletally mature patients with degenerative disc disease, also known as DDD.

DDD is defined as discogenic back pain, with degeneration of the disc, confirmed by patient history, and radiographic studies. The patients can also have up to grade 1 spondylolisthesis, or retrolisthesis, at the involved level.

Let me make an important note. Each of the currently marketed cages has its own indications for use. The above simply lists all the indications which are currently legally marketed.

The following are the intended uses which have been approved for cages. Spinal intervertebral body fusion procedures, at one or two levels, between C2 and C7, or L2 and S1. They are used with or without supplemental fixation.

They are used with autogenous bone graft, and they are implanted by a laprascopic and open posterior approach, or an open anterior approach. Again, let me point out that each of the currently marketed cages has its own set of intended uses. Again, the above list simply lists all the intended uses which are legally marketed.

So how are cages classified? Cages were first marketed in the U.S. after 1976 amendments to the Food, Drug, and Cosmetic Act. They are Class III post-amendment devices, which require an approved PMA prior to marketing.

Since 1996 CDRH has approved seven intervertebral body fusion devices. Six have been PMA devices using autograft, and one has been a PMA device, which is a combination product, because it incorporates BMP with the cage.

This is the fun part, roll call, if you will. The following lists the cages that have received approval by the PMA process. If your name is called, or if your company is called, as I read this list, please feel free to stand up and wave. Just kidding, you can just stay seated.

This includes the BAK, the BAK Proximity, the BAK Vista, which are manufactured by Sulzer Spine-Tech; Ray TFC, and RAY TFC Unite, by Howmedica Osteonics; the Lumbar I/F Cage, by DePuy Acromed Interfix, Interfix RP, LT-Cage, PEEK LT-Cage, manufactured by Medtronic Sofamor Danek; the BAK/C, by Sulzer Medica, or Sulzer Spine-Tech, excuse me; the Affinity, manufactured by Medtronic Sofamor Danek; and the Infuse, which is a combination product, again, used with BMP, manufactured by Medtronic Sofamor Danek.

In addition to the devices I just listed, being described in marketing applications, they have also been well described in publicly available literature.

Because reclassification petitions rely only upon publicly available information only that information will be referenced in this presentation.

So what have we learned from the literature? We have learned about the device descriptions, the device specifications. We have learned about an efficacy profile, and we've learned about a safety profile, or the risks associated with cages.

A two year study of the Ray TFC demonstrated a 96 percent fusion rate at the two year point, 65 percent good or excellent results, 21 percent fair, and 14 percent poor.

At the four year time point the BAK demonstrated a 95.1 percent fusion rate. At the two year time the LT-Cage had a 93 percent successful fusion rate, and 72 percent overall patient satisfaction.

The following point is presented clearly after looking at some of these studies. In cases where studies are conducted in a rigorous and well controlled fashion, results are repeatable.

That isn't always the case. Others have not always been able to duplicate these high success rates. In fact there have been many instances of high complication rates, and high revision rates.

In the Zdeblick article "Interbody Cage Devices", he states: Failures are the result of technical difficulties and poor patient selection. This isn't, actually, unexpected. In fact, most medical devices require appropriate patient selection, and detailed surgical approaches to assure optimal outcomes.

So what have we learned about the risks? Based on the information gathered from MDR reports, and the literature, we have learned about the following risks associated with cages.

Device related risks include loosening, end cap separation, extrusion, migration, malpositioning, device fracture, deformation, and wear.

Patient related risks include vascular injury, neurological injury, urological injury, infection, non-union, vertebral fracture, subsidence, and end-plate collapse.

With this information at hand FDA proposes cage reclassification. We propose the cages be reclassified from Class III to Class II. We believe that the risks associated with the device can be controlled by general and special controls.

We also believe that down classification meets the FDA mandate to apply the least burdensome approach to device regulation. Let me state the crux of my argument. And if your coffee hasn't kicked in, now is the time to pay attention.

What I've described does not imply that FDA knows all that there is to know about cages. What we have learned to this point leads us to believe that the risks associated with the device can be controlled by general and special controls, and no longer need to be controlled by a PMA.

Let me just let that sink in for a moment. So what special controls would we use? Guidance documents are one of the special controls that can be used to address risks.

We believe that, in fact, we can develop a guidance document to address the risks imposed by cages. And let me point out that this guidance document has not yet been developed, and I'll refer to it in the future as a TBD guidance document, not to be determined, but to be developed.

The guidance is intended to convey the Agency's current thinking on cages. It will provide the Agency's recommendations on how to address the issues presented in the guidance.

And let me stress this, a firm need only show that its device meets the recommendations of the guidance, or in some other way provides equivalent assurances of safety and effectiveness.

What would this guidance document include? And, again, let me stress that this is the to be developed guidance document. It would include introduction and background material, content and format of the submissions that would be required.

It would describe the scope of the guidance, a device description of the device, the cage, labeling, and training. It would also provide a comprehensive description of the pre-clinical testing required in a 510(k) submission that would occur if the device were reclassified.

This information would include biocompatability information, sterility information, and mechanical testing. This mechanical testing, again, would be comprehensive and would include compression bending, both static and dynamic, torsional testing, again, static and dynamic; shear testing, both static and dynamic, and subsidence testing.

The guidance document would also reference standards, material standards such as the titanium alloy standard, or the PEEK standard. It would include biocompatability standards, ISO 10993, for instance; and testing standards, like the most recent F2077-03, which describes test methods for cages.

We are quite confident in our ability to create this guidance document. And, in fact, this guidance document will be similar in format and content to guidance documents for spinal devices that are already available to the public. That would include the spinal IDE guidance, and a spinal 510(k) guidance.

And if you don't have a copy of these in your hot little hands, you can just go over to the web, note the address, and find them.

So in an effort to describe our thinking I will provide you with the patient related risks associated with cages, and the manner in which we believe special controls can be used to control these risks.

And, again, the TBD is to be developed guidance document. So we believe that patient related risks, and I won't read through the list again, can be mitigated by information included in this guidance document, that would include information describing surgeon training, product labeling, and material biocompatability.

Also I will give you our feel about the correlation of device related risks, and the manner in which we believe special controls can be used to control these risks.

Again, TBD, to be developed guidance document would include things like surgeon training to mitigate the risks, product labeling, material biocompatability, and particularly the mechanical testing, compression bending, torsion, subsidence. Actually expulsion isn't supposed to be there.

I apologize for the next two slides. In fact my mentor, who taught me how to make slides, would be having a coronary if he saw all of this information on one slide, but I really had no choice.

I'm going to present to you FDA's proposal for cage reclassification. The device description. The intervertebral body fusion device is an implanted single, or multiple component spinal device, made from a variety of materials, including titanium alloys, for example, Ti-6AL-4V, and polymers; for example PEEK, or Polyetheretherketone.

Such a spinal implant assembly would consist of a construct intended to fill the intervertebral disc space, for example, hollow threaded cylinders, mesh cylinders, fenestrated rectangular blocks, trapezoidal cubes, or wedge shaped solids.

The implant is available in a range of sizes, and may be angled to fit the patient's anatomical and physiological requirements. The implant may have a variety of features, some of which include spiked teeth on the inferior and superior surfaces of the implant, and through holes intended to allow bony ingrowth, and end caps.

The intended uses and indications. The interbody fusion device is intended for spinal fusion procedures, in skeletally mature patients, with degenerative disc disease, DDD, at one or two levels, from C2 to C7, and L2 to S1.

DDD is defined as discogenic neck and back, or neck or back pain, with degeneration of the disc confirmed by patient history, and radiographic studies.

These DDD patients may also have up to Grade spondy, or retrolisthesis at the involved levels. The implant is intended to be used with autogenous bone graft, and implanted by a laprascopic and open posterior approach, or an open anterior approach.

So let me summarize. FDA does not know all that there is to know about cages. We have learned a great deal about the risks associated with cages, however, and we believe that the risks associated with the device can be controlled by general and special controls, and no longer need to be controlled by a PMA.

I'm going to briefly go through the questions that are going to be posed to the Panel, in a bit, just so you have a heads up. Question one is going to be please discuss the descriptive information and intended use presented in the reclassification identification.

Question two is going to be, please discuss any specific pre-clinical testing criteria you believe are needed to characterize the intervertebral body fusion device.

Question three, please discuss the risks to health for the intervertebral body fusion device. Question four, much like question three, please discuss any other risks. And by that I mean risks that I haven't identified, or that we haven't identified, to health, for these devices that have not been presented.

And question five is, do you believe special controls can be developed to adequately control the risks associated with this device?

Thank you very much.

CHAIR YASZEMSKI: Thanks very much, Ms. Anderson. Does anyone on the Panel have questions for Ms. Anderson? Dr. Finnegan.

DR. FINNEGAN: I know that everyone is uncomfortable with performance standards, but could you outline for us what the difficulties are in asking for some performance standards?

MS. ANDERSON: I guess the difficulty with asking for performance standards is it sets forth a criteria that everybody need meet. At this point I think we are open to justifications for why certain performance data are going to be physiologically acceptable.

So we would rather see a justification for a specific case, rather than outlining if you meet this, this, and this, then you are okay.

DR. FINNEGAN: Can you bear with me for a second? If you look at total joints with the polymers for the acetabular cups, if they had had performance standards there might not be as many people walking around with a whole bunch of ugly looking bones.

So I guess that is the reason for my question, we don't know the ten year out, particularly if you have a mixed component, well even if you just have metal, but if you have mixed component with aging changes in the spine.

So I guess that is my concern, how do you capture that data sooner rather than later?

MS. ANDERSON: I'm not certain I completely understand your question. Are you asking for information that describes how these devices are going to perform ten years out or --

DR. FINNEGAN: What I'm suggesting is that you don't have the information. I guess that is my translation of performance standards, is if you put in -- let me back up for a second.

We know if we put in metal and polyethylene, and there is significant demand on those materials, that mix of materials, that you will get polyethylene wear on the body response to polyethylene wear in a very specific manner, which we did not know when we started total hips.

MS. ANDERSON: Let me go ahead and change your question around a little bit, because what you are asking about is efficacy regarding cages.

And actually what I've just presented is actually not a discussion of all the efficacy of cages. In fact what I'm doing, and what I am presenting, is more of a risk management proposal.

So my proposal isn't focusing on all of, again, what I've presented is that we don't know everything that there is to know about cages, especially if you go out at the ten year point.

What I'm saying is that what we know about cages today leads us to believe that we are certain, we know of the risks that cages bring forth, and that these risks can be mitigated using special controls, instead of using a PMA.

If we were to approve a PMA for a cage we would still have the same questions that you are proposing, we wouldn't know what would happen at the ten year time point.

Celia, I see you heading towards the microphone. Is there something you wanted to add?

DR. WITTEN: Yes, just that -- I just want to say that this is part of our questions for you all, to the Panel, have we identified the risks, and can they be mitigated with the controls that we are proposing.

DR. FINNEGAN: And I guess my question is, could a guidance document include those kinds of things? I don't understand, I guess, what performance standards are separately from guidance documents.

DR. WITTEN: Well, a performance standard is a specific term which to us means that there is some number, you know, some target that something absolutely has to meet in order to get on the market.

I think we've only promulgated one in the whole history of FDA. You have to do it either by regulation or by law.

DR. FINNEGAN: So our concerns could be put into a guidance document?

DR. WITTEN: Yes. And if you know, for example, that -- I mean, what we usually do with testing is you do testing compared to a predicate. So for the kind of test that Jodi just listed we would look at the test results and the sponsor would compare how their device performed compared to a predicate.

And, you know, we would see whether those differences gave us concern about the new device. But if there are some things that you know that represent a target that sponsors should meet, you know, in general unless they can provide a justification for something else, or if there is something that we know about what the test results should be, that would certainly be good information for us.

But that is, you know, what we do is when we have something in the Class II is we look at the testing, and we compare it with devices on the market to see whether the new device will perform equivalently to the old device, on the things that we know how to measure, which are the kind of things that Jodi just mentioned on the list.

DR. WITTEN: So performance standards aren't a long term assessment?

DR. WITTEN: No, what we look at is the guidance would provide you a framework for making a comparative assessment of the new device that was proposed for market, compared to the device that was already on the market.

CHAIR YASZEMSKI: Thank you, Dr. Witten, and Dr. Finnegan. Dr. Naidu?

DR. NAIDU: Mine is a more simple question, but it does concern the guidance document. Is the FDA proposing to develop a guidance document for metallic cages and plastic cages separately? Or are you going to split this at all, or are you just going to generally classify them all under one?

MS. ANDERSON: I think our current thinking is the development of one guidance document and, as Dr. Witten mentioned, if you believe that it would be necessary to create the guidance for two separate, we would be open to hearing it.

I think our current belief is that the testing is going to be more or less the same regardless of the material composition, to a certain point.

So that both PEEK cages and titanium cages would be tested similarly. For instance, with a PEEK cage you might focus more on shear testing, the generation of wear debris, where that might not be of concern for a titanium cage.

But I think both of those issues could be addressed in one guidance document.

DR. NAIDU: Thank you, Ms. Anderson.

CHAIR YASZEMSKI: Thank you, Ms. Anderson. Any other questions for Ms. Anderson? Dr. Larntz??

MS. ANDERSON: I didn't present any statistics.

DR. LARNTZ: But I found some things to talk about, Jodi.

MS. ANDERSON: Why does that not surprise me?

DR. LARNTZ: I just want to make sure we are clear, or I'm clear. A guidance document can have guidance with respect to performance.

MS. ANDERSON: It can.

DR. LARNTZ: And that is a very important aspect. But it is also a guidance document, it is not a requirement for every detail.

MS. ANDERSON: In fact I believe I mentioned that. I think I tried to state very clearly that these are recommendations, and that industry can either provide the information required, or provide a justification for that information's omission.

DR. LARNTZ: Right. That is all I wanted to make sure, you know, performance standards as some of us are thinking about them I think are in other guidance documents, for instance, throughout the Agency, but they are not called performance standards, they are guidance.

MS. ANDERSON: Correct. What I'm talking about is, indeed, a guidance document. And a guidance document is a suggestion, it is not a mandate.

CHAIR YASZEMSKI: Thank you, Dr. Larntz. Other questions for Ms. Anderson?

MS. ANDERSON: I will be available for further questions later if you change your mind.

CHAIR YASZEMSKI: Thank you, Ms. Anderson. We are now going to have two industry presentations. First we will hear from representatives of the Orthopedic Surgical Manufacturers Association, OSMA. Mr. Robert Zoletti, and Dr. Scott Tromanhauser.

Mr. Zoletti? Are you going to be okay, sir? Can you go ahead as is?

MR. ZOLETTI: It looks like it is going to work.

Good morning, I'm Robert Zoletti, director of clinical and regulatory affairs, Cortek, Inc., a developer of spinal implants and instrumentation. I'm speaking today as a representative of OSMA, the Orthopedic Surgical and Manufacturers Association.

I didn't get any fortune cookies yesterday but I did, by joining OSMA, get the fortune of doing this presentation. I got that -- that was given to me because I asked about cage reclassification.

The Orthopedic Surgical Manufacturers Association is a trade organization whose membership consists of 29 manufacturers of orthopedic surgical appliances, implants, instruments, equipment, and orthobiologics.

Since its inception in 1954 OSMA has actively participated in standards development, patient education, product labeling, guidelines, international activities, and support of multiple reclassification petitions.

The cooperation and interaction with FDA and health care professionals on issues that lessen the regulatory burden and improve application of device law, and continue to be the major objectives of OSMA.

All the companies that hold PMAs for intervertebral body fusion devices are OSMA members. OSMA supports reclassification of intervertebral body fusion devices, generically known as cages, as stated in the proposed CFR listing.

OSMA member support for this reclassification petition has been cautious. There is some concern, among current PMA holders, that the scope of the reclassification be narrowed during the classification process in a manner that may not permit clearance of newer design cages under a 510(k).

Therefore three OSMA members that hold PMAs for interbody fusion cages are currently withholding access to their unpublished clinical data pending the outcome of the Panel meeting.

No OSMA member company has opposed reclassification. The current classification language proposed by FDA is generally supportive, and clearly allows for design beyond cylindrical titanium cages.

We see this reclassification as part of a continued effort to appropriately classify spinal implants. We encourage the Panel to support the language FDA has used, in the FDA proposal, for reclassification of the intervertebral body fusion device. I have said that enough times and it doesn't want to come out.

This position goes hand in hand with the least burdensome provisions of the Food and Drug Administration Modernization Act of 1997. There has been a long history of cages, and a long history of spinal to body fusion procedures.

Burns of Great Britain reported the first lumbar interbody fusion in 1933, using autogenous bone. Posterial lumbar interbody fusion was first performed in the early 1940s.

During the 1970s and early 1980s Bagby managed cervical spinal instability in horses by means of interfusion using the Bagby basked, a hollow, extensively perforated stainless steel cylinder. Using the Bagby basket as a foundation, the Bagby and Kuslich implant, known as the BAK, was developed.

The first human implants were conducted under an IDE in 1992, and the first PMA was approved in 1996. The Bagby and Kuslich method of lumbar interbody fusion was published in "Spine" in 1998, reporting the results of 947 patients treated from 1992 to 1995, with chronic discogenic low back pain, by interbody fusion using the BAK cage.

RAY reported two year follow-up data, 208 patients, using the RAY titanium fusion cage, in the March 1997 issue of "Spine".

Two year results were reported by Brantigan et al, using a PEEK carbon fiber-reinforced cage, in the June 2000 issue of "Spine".

In all three studies fusion rates were high, between 90 and 100 percent, and clinical outcomes were favorable, at 85 to 97 percent of patients reporting improvement in pain, or function, compared to pre-operative levels.

These studies resulted in the first PMAs for cages, which were approved in 1996, seven years ago. Hundreds of thousands of cages have been implanted in the lumbar and cervical spine throughout the world. In the U.S. alone the number of procedures using metal cages is a total of 145,000 since the year 2000.

As mentioned previously fusion success with cages has been reported to be in the range of 90 to 100 percent. Although fusion procedures have not proven to be a cure for all patients, there is evidence supporting the benefits of this procedure.

The 2001 Volvo Award clinical study, "Lumbar Fusion versus Non-Surgical Treatment for Chronic Low Back Pain" by Fritzell et al., a randomized control multi-center study concluded that lumbar fusion in a well informed and selected group of patients with severe and therapy resistant chronic low back pain, can diminish pain, improve function more effectively than commonly used non-surgical treatment.

This, which is also a very hard slide to read, is a list of, a sample list of some of the journal articles published from cage studies.

Although interbody fusion devices are currently regulated as Class III products, and have required extensive clinical studies in PMA approval, other spinal implants do not have these requirements.

FDA currently regulates a number of implants using the spine as Class II, or unclassified. All are reviewed via the 510(k) process. This slide is a list of the FDA product codes and classifications for spinal implants.

These products include pedicle screws, rods, plates, hooks, connectors, and vertebral body replacement devices. Again, all approved by 510(k). Recently pedicle screw 510(k), KO31855 Spinal Concepts Insight Pedicle Screw System, was cleared for a number of codes, including NKB, which is Class III pedicle screw system for degenerative disc disease.

This clearance was obtained using clinical test data, including data collected in accordance with ASTM 1717, and ASTM 1798. The product code shown, in the previous slide, Class II vertebral body replacement devices, are the most notable for comparison to spinal cages.

They are often similar in design, and materials, to interbody fusion cages. They replace the vertebral body and disc, instead of replacing just the disc. Fusion between the vertebrae are often possible.

Vertebral body replacement products are cleared for thoracic and lumbar spine solely on mechanical test data, without the need for clinical study.

This is an example of vertebral body replacement devices, on the left, and cages on the right. You can see the similarities.

The guidance document for spinal system 510(k)s, list the testing necessary to support substantial equivalence of vertebral body replacement devices as static compression, or compression bending, dynamic compression, or compression bending, static torsion, dynamic torsion, and expulsion.

Additional testing may also be necessary depending on the design of the vertebral body replacement system. Similar test requirements can be applied to cages.

Title 21CFR Part 860 provides for the procedures for medical device reclassification. Section 860.130 states: The Commission may change the reclassification from Class III to Class II if the Commission determines that special controls, in addition to general controls, will provide reasonable assurance of the safety and effectiveness of the device, and there is sufficient information to establish special controls to provide assurance of safety and effectiveness.

An analysis of interbody fusion device adverse events has been conducted using MDR data. The type of adverse event, and the special controls that could address the adverse event are shown in the slide.

The analysis indicates that the combination of biocompatability testing, materials standards, mechanical testing, and labeling, in combination with QSR general controls, can address the adverse events found.

These occurrence rates are extremely low compared to the number of implants used. Other non-device specific events are also addressed with controls, as shown in this slide.

Standards that could be used to assure the safety and effectiveness of cages are essentially those used for other Class II orthopedic spinal implants. These standards encompass, among other things, the variety of test methods and labeling requirements.

After more than ten years of use the risks associated with interbody fusion devices are well known, and can be controlled by special controls such as standards shown on the previous slides, and general controls.

OSMA would like to voice some additional considerations for the Panel. First, OSMA would like the FDA and the Panel to consider that posterior or internal fixation systems are often used with cages.

We propose that the reclassification language allow optional use of supplemental internal fixation systems with cages. Second, OSMA encourages the Panel, and the FDA, to consider expanding the language to include use of allograft bone, or other approved bone substitutes.

Under the current approvals, PMA holders are required to complete post PMA studies. The burden of these post PMA studies should be ended now. Next, IDEs currently underway should be allowed to close, and sponsors should be allowed to file final reports if the device complies with the reclassification requirements.

Also, the current classification statement indicates use from C2 to C7 and L2 to S1. OSMA suggests the language not restrict spinal levels. The Panel should be aware that the FDA has required labeling for some cage products, such as, should only be used by surgeons who are experienced in spinal fusion procedures, and have undergone adequate training for this device.

Another variation is to require the phrase "appropriate training". In addition, FDA required some, if not all companies, as a condition of PMA approval, to conduct courses as part of the approval order.

We strongly encourage this Panel to advise the FDA staff that the companies are not in a position to determine when training is adequate, or appropriate, and that companies, per se, should not be required to conduct training courses.

The situation is particularly the case with cages where OSMA believes that the use of cages has matured, and that surgeons now receive training with those products by other surgeons, as part of their education.

Doctors should train doctors, the companies should not be required to conduct training courses. A new requirement for clinical data should be for truly new designs that cannot be otherwise be found substantial equivalent.

In the infrequent situation that clinical data may be required, to demonstrate substantial equivalence, the scope of the study should be no burdensome.

PMA data, including available SS&E data, cannot be used at this time, by other companies, or by the FDA to support submissions, or this reclassification, without release by the PMA holder.

OSMA member companies have been reluctant to open their PMA data, for public release, to support this reclassification. Once released this data can be used to support the approval of similar products by other companies.

There is concern that the reclassification may be denied, or the language may be revised, during the clarification process to only reclassify threaded titanium cages, an approval that several of these companies hold under the current PMAs.

The release of data to FDA will be reevaluated after this Panel meeting, and compose language for reclassification orders are viewed. Support for release of data is dependent on the proposed reclassification language.

IDE study data published in respected peer review journals, as referenced earlier, while not providing complete information, does provide valid scientific evidence that interbody fusion devices are safe and effective.

OSMA supports the reclassification of interbody fusion devices under the proposed language, and requests the Panel, and the FDA, review the additional considerations presented above.

The reclassification is seen as providing the same level of control required for other spinal implants currently in use. A reasonable assurance of safety and effectiveness can be established through special and general controls.

Thank you for your time.

CHAIR YASZEMSKI: Thanks very much, Mr. Zoletti. Do any of the Panel members have questions for Mr. Zoletti? Dr. Li.

DR. LI: Yes, thank you for your presentation. On one of your early slides you gave a little table that showed us the number of metal cage procedures that were done since 2000?

MR. ZOLETTI: Correct.

DR. LI: Do you have a sense that those numbers include revisions? In other words, are all these primary implants, or are some of these implants revisions?

MR. ZOLETTI: I don't know that. The data is from Millennium Research, and I didn't see it broken out that way.

DR. LI: Do you have any idea what the revision, the number of implants sold for revision, is?

MR. ZOLETTI: I don't.

DR. LI: And the other question I have for you is on the MDRs, in total joints we estimate that, typically, less than one percent of implant failures are actually reported to the MDR.

Do you have any sense for what that number is for your product?

MR. ZOLETTI: I don't have a sense. I know these products are still under PMA and that companies have procedures in place for submitting MDRs, as they are reported to them.

DR. LI: Just as kind of a back of the envelope exercise I took your table, that you presented with the number of implants since 2000, and I got something close to 200,000, you had a couple of greater than.

So I just took 200,000 just to round it off. And if I took the best clinical series we've got there, their reparation rate was, for device removal, was like 1.1 percent, in which case the number of MDRs reported was actually 12 times lower than were actually reported in these clinical series.

And in the worse series that we got for clinical evaluations, 14 percent of 148 implants were reimplanted. And if it was 14 percent of your 200,000, that would be 28,000 devices that have been removed, yet there is only 183 reported in your MDR.

So at that ratio the percent reported by the MDR is very close to what is reported for total joints, which is less than a percent.

MR. ZOLETTI: Okay.

CHAIR YASZEMSKI: Dr. Finnegan?

DR. FINNEGAN: You would like these sort of to be considered equivalent, I'm assuming, to the vertebral body replacements. And I'm wondering what materials the vertebral body replacements are made of. You don't really mention that.

Are they all metal, and are they all titanium?

MR. ZOLETTI: I'm not familiar with all of the products. I believe they are metal and perhaps PEEK, but I'm not sure.

CHAIR YASZEMSKI: Thank you, Dr. Finnegan. Dr. Li?

DR. LI: A follow-up question. Your table that you represented was metal cage procedures. Do you have any numbers for the non-metal cage procedures?

MR. ZOLETTI: They weren't available to me.

DR. LI: Any idea what that number is, is it a tenth, a half, a quarter?

MR. ZOLETTI: I would be completely speculating. You have to ask the companies that are doing those cages.

DR. LI: Okay.

CHAIR YASZEMSKI: Thanks, Dr. Li. Other questions? Dr. Larntz.

DR. LARNTZ: Yes. You asked some additional considerations, allow the use of allograft, and other approved bone substitutes.

I looked at your document, which you provided, which we just got today as far as I know. It is dated December 4th, but it seems to have been printed on December 9th.

And I'd like to know if there is any analysis, statistical analysis, to back up that additional consideration?

MR. ZOLETTI: First of all, on the dating of the document, the document was provided to the FDA on the 4th, and I printed it again today for you, as it had not been provided.

As far as the statistical analysis for the additional considerations, did you mention a specific one?

DR. LARNTZ: Additional consideration, it says, allow use with allograft bone, and other approved bone substitutes.

MR. ZOLETTI: So you are asking have there been specific studies done to that?

DR. LARNTZ: Well, if we are going to do that I think we need some evidence to support that, if we are going to consider it. You are asking us to consider it, that is what I see here.

MR. ZOLETTI: Okay. I don't have any references that I can specifically go to, but Dr. Tromanhauser can talk about the use of that material in his procedures.

DR. LARNTZ: Right. I mean, I read the papers you provided, and I didn't see any particular analysis showing equivalence, or non thereof. You also asked for expansion beyond the levels that are used.

Again, do you have statistical analysis that shows that the use of these devices in other levels is basically equivalent to the ones that are proposed here?

MR. ZOLETTI: No, I don't.

CHAIR YASZEMSKI: Thank you. Other questions for Mr. Zoletti?

(No response.)

CHAIR YASZEMSKI: Seeing none, we will move on. Thank you, Mr. Zoletti.

MR. ZOLETTI: Thank you.

CHAIR YASZEMSKI: We will ask Dr. Tomanhauser to come and give his presentation.

DR. TROMANHAUSER: I brought with me a tool that I commonly use in my office. (Inaudible)

CHAIR YASZEMSKI: We have to ask you, sir, to speak into the microphone.

DR. TROMANHAUSER: -- put your hands on that, in a regular basis. This is a key ring full of cages, just so you can take a look at that.

Dr. Yaszemski, Panel Members, thank you for allowing me to present this morning. My name is Scott Tromanhauser, I'm an orthopaedic spine surgeon at the New England Baptist Hospital in Boston, Massachusetts.

I'm a member of the Boston Spine Group, which is a six surgeon, two physiatrist group who specialize in the treatment of adult degenerative disorders, and adult spinal disorders in general.

Just so you know who I am, I did my undergraduate work at the University of Buffalo Medical School at Albany Medical College. My residency at the Albany Medical Center Hospital, my spine surgery fellowship at the New England Baptist Hospital, where I have been in practice since 1992.

I also performed a NASS Clinical Traveling Fellowship in 1996. I'm a clinical instructor in orthopaedic surgery through Tufts University School of Medicine. My hospital is an associated orthopaedic surgery residency teaching hospital for the New England Medical Center, which is a Tufts affiliate, and the University of Massachusetts Medical School.

We have six residents in orthopaedic surgery at our hospital, which is predominantly an orthopaedic surgery hospital; 85 percent of the cases that we do are orthopaedic surgery. And we have three spine surgery fellows in our department. I'm also the chairman of the Institutional Review Board at my hospital.

I can speak about cages because I have a ten year experience with cages. I was a principal investigator at our institution for the BAK cage, during its IDE days. I was a co-investigator for the RAY TFC cage, TIBFD cage from Medtronic, the Novus-LT/BMP cage, and the -- presently the Cortek Polylok cage. I also was a co-investigator for the RAY Threaded Cervical Cage.

I wanted to state that I support the FDA proposal for the reclassification of interbody fusion devices for the following reasons. Why should I do that? We may have skipped over a slide that I had, earlier.

My disclosure is that OSMA paid my way here, and no other fee involved. I am a stockholder in Cortek, as a co-founder.

The reason I support this reclassification is that I can speak with ten years of experience of primary and revision surgery involving fusion cages. I am very familiar with the risks of this surgery, with the ways it can fail.

A large portion of my practice is revision surgery. The Baptist is the unfortunate recipient of most of the revision cases in New England. And I have to say that many of the spinal implants that we use, on a regular basis, are already classified as Class II, and carry essentially the same risks in their use, such as pedicle screws and rods, spinal plates, whether placed ante or posterially, and vertebral body replacement devices. Which, by the way, probably carry greater risks than the use of interbody fusion devices.

The level of surgical skill required to use cages is similar to other Class II spinal implants, and is commonly taught, at least in our training program at the Baptist and, as well, in my residency training to the residents, and certainly to the fellows.

I'd like to make one point that I'm not sure is always clear to everyone. And that is the success of interbody fusion cages can be defined in two ways, and this is the way I explain it to my patients. There is technical success, and there is clinical success. Technical success means, did it fuse, was there any device related adverse events. So that is really cage performance. And I want my cages to predictably create fusion.

Clinical success, on the other hand, has nothing to do with the cage, unless the cage fails itself. It has more to do with patient selection. We all know that we have sort of hit a ceiling with improvement and function, and pain, with most fusion procedures. And it is because of our limitations in patient selection.

And in my experience probably 50 to 70 percent of the cases that I do I use some sort of interbody fusion device, each one chosen specifically for the problem at hand, whether there is deformity, osteoporosis, revision surgery, and what the goals are of the surgery in general.

My point of view on reclassification, and some of it reflects OSMA's position, as I thought about this problem, and I had their input, I would ask that you don't limit the use of supplemental fixation with cages. That is a decision we like to make, and I realize that your mandate is not to tell us what to do, but it would be nice, from the surgeon's point of view, to have the FDA support for what we do, on a regular basis.

We would like to allow the use of allograft bone, and other bone graft substitute. And, Dr. Larntz, if I can address the question you asked Mr. Zoletti, although we don't have any data to present to you today about allograft bone, the archetype interbody fusion devices was allograft bone.

Femoral rings, for example, have a very long history of use in the spine, and continue to be used, and have actually had a resurgence in the last number of years. There is a long history of the use of allograft bone in the spine.

Whether you use allograft bone alone, whether it be inside a cage, there may not be a lot of difference on how that performs. I can't give you data, or point to specific studies, but if you would require that, we can certainly provide it.

I would also ask that the use not be limited to specific spinal levels. One of my partners, Dr. Frank Rand, does an awful lot of deformity surgery that often involves the mid-thoracic and upper lumbar spine, where cages become the best way to correct deformity, and he might be working at T11, T12, L1, L2.

So to limit their use, again, doesn't give us, as surgeons, any support from the FDA on the use of these devices. I would also not like to have any specific cage limited in surgical approach, unless it is clear that it can't be used in any particular way, except from an anterior approach, or except from a posterior approach.

Certainly there are some cages that are too large to be implanted from the back so they are, by necessity, implanted from the front. But most cages that are used in the back can also be put in through the front.

And, again, I would agree with Mr. Zoletti that surgeons should be training surgeons. I'm always, I think, disappointed by the experience I get from companies with training sessions. And I agree that they are not in the best position to decide who is trained to do a procedure and who isn't.

And there are certainly a lot of opportunities for surgeons who may be out of training for some time, to get hands-on experience through the American Academy of Orthopaedic Surgeons, through the North American Spine Society, through the Neurosurgical Societies. There are plenty of opportunities. So to require a company to do training doesn't seem quite appropriate to us.

Thank you. And if there are any questions, perhaps some of those questions that were asked earlier, I might be able to help you with. I don't recall them, but --

CHAIR YASZEMSKI: Thanks very much, Dr. Tromanhauser. Questions for Dr. Tromanhauser? Dr. Li.

DR. LI: Yes, thank you for your presentation. Can I ask you, in your practice, in your institution, what percentage of your procedures are for revision of these fusion devices?

DR. TROMANHAUSER: These particular fusion devices probably a small number. I think most of the revision cases are done because someone hasn't used an interbody fusion devices. And I will explain that further.

Fusion rates, in general, are not as good when a posterior procedure is done alone. And some times if an anterior procedure is done alone, it is not good enough for that particular situation, either.

Most of the revision procedures that I do are posterior infusions that have gone wrong, in which case we are trying to increase our chances of fusion by adding an anterior construct, a cage for example, in the intrabody space with bone, to increase our fusion rate.

We are also going to, of course, revise the posterior construct, whatever it may have been. There are, certainly, revisions of failed cages. Typically it is a cage system that was used alone in the front, perhaps at multiple levels.

And I agree with Tom Zdeblick, most of those failures are surgeon failures, if you will, or technical difficulties; placed poorly, undersized, inappropriately sized. And, again, that is a training issue.

I think your controls address that, and I hope I have answered your question.

DR. LI: Did those device failures include both metal and polymeric devices?

DR. TROMANHAUSER: Few polymer devices because there are fewer out there, in general. But, yes, it involves both.

DR. LI: And my last question for the moment, is -- we have an interesting case where we have a device that depends on fusion for success, yet there is no test for fusion prior to placing it into a patient.

So are you comfortable, as a surgeon, if the next company walks into your door with a device that says, I don't know what it would be, but let's say it just looks very different than a cage you are used to using.

Are you satisfied that the currently existing tests, do you feel comfortable that you would get fusion, or that it would survive the --

DR. TROMANHAUSER: You mean the standards for testing, of do you mean --

DR. LI: Yes. With the currently existing guidelines and regulations, there is no test for fusion, and there is no test for fracture. There is fatigue, but there is no test for fracture.

So someone comes in to you with a device that looks very different, made with a material that you have no experience with, would you be comfortable saying, because it has gone through these tests, that currently exist, that you would be comfortable in using it in patients?

DR. TROMANHAUSER: I guess the answer would be yes. As a matter of fact, when a sales representative comes to my door with a new device, the first thing I ask them is, show me the biomechanical data, I want to see how this thing holds up, how does it fail.

DR. LI: Well, that is my point, actually. There is no data that is required of them to prevent fusion data, because I don't know how you would get it. And there is no requirement to show you any fracture data.

DR. TROMANHAUSER: But there is --

DR. LI: So the data they would give you would be very complete with a couple of glaring exceptions.

DR. TROMANHAUSER: Well, there is repetitive --

DR. LI: There is fatigue, but not fracture.

DR. TROMANHAUSER: -- fatigue testing.

DR. LI: Right, there is fatigue, but not fracture.

DR. TROMANHAUSER: Well, I guess if it meets the fatigue testing standard, which most of these devices do, I would expect it to perform adequately for fusion.

We are looking for something that will hold up for six to twelve months. And in my experience the cages that we use now, that has never been an issue. I haven't seen a cage fracture, ever. I have certainly seen them fail in other ways, but not because the cage itself has failed mechanically, I guess, would be the best way to put that.

DR. LI: I guess my question was inspired, actually, by your key ring, where several of the polymeric constructs actually have fractures and voids in them.

So I would wonder that if you put those in a particular place, on a heavy person, who picks up a 20 kilogram weight, you are putting 4,000 newtons of load on this device that might be precracked or have voids in it.

DR. TROMANHAUSER: There are broken devices on my key ring?

DR. LI: Yes, there are.

(Laughter.)

DR. LI: There are.

DR. TROMANHAUSER: Well, I don't know which one it is, but --

DR. LI: I will show you later, if you would like.

DR. TROMANHAUSER: I know there is one in there that is a model, and it is not the real --

(Laughter.)

DR. TROMANHAUSER: That has not been my experience, that is all I can say. And I have been at this for a while. I haven't seen any broken cages.

CHAIR YASZEMSKI: Thanks, Dr. Li. Dr. Naidu?

DR. NAIDU: In fact your key ring inspired a few of these questions that are coming up.

DR. TROMANHAUSER: What did I bring that for?

(Laughter.)

DR. NAIDU: In your practice, in the last ten years, have you used the plastic cages at all?

DR. TROMANHAUSER: Yes.

DR. NAIDU: What percentage would you say that --

DR. TROMANHAUSER: I use, what I think you are referring to, is the DePuy Carbon Fiber PEEK cage. And there is also the Cortek Polylok, which is under IDE now.

We use the AcroMed interbody fusion device for posterior approach to fusion. I do it less often because I tend to be an anterior surgeon. I think it is, in my hands, a better operation.

Certainly there are more people doing PLIFs, than doing ALIFs, posterior lumbar interbody fusions, than doing anterior lumbar interbody fusions. My experience with that device is no different than it is with metal cages. I have not had one fail on me, except by non-union, for example.

DR. NAIDU: But you've been using mostly carbon fiber reinforced cages?

DR. TROMANHAUSER: Mostly metal cages.

DR. NAIDU: Mostly metal cages. And you occasionally use the carbon reinforced PEEK. Now, on your key chain I saw four plastic cages, one appears to be made purely of neat PEEK, and two others do not seem to be reinforced as well.

I see on reinforced, out of four. Do you know how many of these pure polymeric neat matrix materials are floating around just as cages, or are they all carbon fiber reinforced?

Because the literature that we got, today, for this review, was mostly carbon fiber reinforced cages. Do you know how many of these are floating around, just plain old plastic, without any reinforcement?

DR. TROMANHAUSER: The only polymer cages, I guess as I think about that, that I'm aware of are the Acromat interbody fusion devices. And they also have a vertebral body replacement, which I think they may be calling the intervertebral body replacement.

I forget what they call it, stackable cage is what it is called, and it is carbon fiber PEEK device. Other than those two, I'm not aware of any other, other than the large grey one you have in your hand, that is the Cortek Polylok device that is not carbon fiber filled, and that is under IDE right now.

DR. NAIDU: So this is purely PEEK?

DR. TROMANHAUSER: Pure PEEK.

CHAIR YASZEMSKI: Thanks, Dr. Naidu. Any other questions for Dr. Tromanhauser? Dr. Finnegan. Dr. Cheng?

DR. CHENG: Thanks for your talk. I was wondering, I think there is an important distinction to make during these talks today, to the FDA as well as to the manufacturers, that there is a difference between stability providing structural stability and fusion.

And that is not always emphasized in the documents, or provided by the FDA and the manufacturers. It is a point that was brought out in Dr. Zdeblick's article, and I think it is important to realize.

So I'm wondering, my question to you is, how do you asses, immediately post-operatively, you provide stability. But how do you asses whether or not you have provided fusion in the long term? Is it just a failure, or the lack of loosening over time? Or at what point do you consider your patient to have a successful biological fusion?

DR. TROMANHAUSER: Well, that is an excellent question. It is an issue that has come up before the FDA before. And how do you assess fusion? Most of the IDEs, the data, have included these bending films which, I would have to be honest to say, we think are inadequate, but it is what the standard is.

I can tell you, in my practice, the way I asses biofusion in every single case, is with CT scan with reformatting images. We have outstanding software, and an outstanding spine radiology team, so we demand the best of them.

We have twelve orthopaedic spine surgeons at my institution. And unless they do a good job, they are in trouble. So I assess them with CT. There are ways of doing fusions to help you make that assessment.

For example, with a threaded cage, placed anteriorly, for example, you can go a little bit shorter, leave enough room in the front of the cage to place a good -- a bit of bone graft, so that you get what is called a sentinel fusion.

If you see that solid sentinel fusion then you feel very good about it being fused. You don't have to have it, in order for it to be fused. And, in fact, evaluating fusion status inside a cage is very difficult, even with the best of CT scan software.

So we assume, if someone is doing well, there are no loosencies around the cage, that would indicate loosening, that it is fused. Even if we don't see sentinel fusion, and we can't tell it any other way.

But I think there are ways to make that determination, including the way you do the surgery, and the way you image it.

DR. CHENG: Would it be fair to say that given the methods you have just described, I think most orthopaedic surgeons have a good sense, in a long bone fracture, of when there is enough bony ridging, or healing, biologically, that it will withstand the physiologic loads of every day life.

But in the spine that, perhaps, our ability to do that is not quite as good, even with the sophisticated CT scanning you are mentioning, because a few spicules of cancellous bone, seen through the holes in a cage, or elsewhere, as you are suggesting, outside the cage, may not give you the same level of confidence as the long bone fracture. Is that true?

DR. TROMANHAUSER: Well, I can say that your ability to image a long bone fracture is certainly a lot easier.

DR. CHENG: Okay. I do have one second question and that is, you've mentioned some rationale for reclassification. And I'm just wondering, part of that was based on previous Class II implants, such as the pedicle screws.

And everyone in this room is familiar with the history of the Class Action lawsuit that took place in the last years. And I'm wondering, during the process of reclassification, what can we do, in terms of your thoughts, in providing a process whereby we avoid something down the road, such as what took place with the pedicle screws scenario?

In other words, is there -- no one wants to see that debacle replayed, again, in five years for cages as it has for the pedicle screws and other devices that other of our colleagues, and other specialists have dealt with.

So how can we prevent that from happening during our discussions today?

DR. TROMANHAUSER: Well, that problem started just as I was in training. My recollection of it, correct me if I'm wrong, there were two issues. There were screws that broke, and there were failures of fusion.

My impression at the time was that there was a lot of confusion about the danger of pedicle screws, because some people had a bad result. And there are always people who will not do well with surgery of this nature, whether they are fused or not fused.

Certainly if screws break they are not fused. That is not, necessarily, a failure of -- it is a failure of the screw, clearly, but it is more an indication that they didn't fuse. Then there is the whole patient selection problem that I don't think you can address.

There will always be people who don't do well, who will always raise these questions of product deficiency when, in fact, it is not the product that failed, they were not selected properly.

And that is our biggest challenge, it is the next step that we need to take in this field, it is trying to find a way to select patients more appropriately. Those people we can help we should try to help. Those people that we clearly can't help, we have to stop operating on.

And we haven't gotten to a point where we can always predict who is who. The best way for you to address, I think, that problem is to make sure the devices don't break, and then make sure that they provide the stability that they should, that the testing is adequate.

And beyond that I'm not sure there is much more you can do, because patient selection is in the physician's hands.

CHAIR YASZEMSKI: Thanks, Dr. Tromanhauser. Dr. Finnegan, you had a question?

DR. FINNEGAN: Yes, I wanted to address training. I, obviously, agree with you that surgeons should train surgeons. But, the fact of the matter is, you've been doing this a very long time, but the spinal surgeon in mid-America hasn't been doing this for a long time.

Can you give us some idea on how long do you think the average spinal surgeon, who has not just come out of a fellowship, has been exposed to this? And what I'm thinking of is the transition time.

I mean, there is a group of people that need to get some really training to do this, they are good spinal surgeons but haven't been exposed. So how long do you think your fellows, or our department's fellows, or the Mayo fellows have been exposed to this?

DR. TROMANHAUSER: I guess I'm not quite understanding. How long will it take for them to learn the procedure?

DR. FINNEGAN: No. There are spinal surgeons who are about ready to retire who don't want to know about this. There are the fellows that you trained yesterday who know everything there is to know about it.

And then there are people in the middle who are not in academic centers, who are doing good spine surgery, providing very good service, to mid-America, who have not been exposed to this. And that is the training I'm interested in, and how big do you think that group is?

Do you think it is 50 percent of the spinal surgeons in the country?

DR. TROMANHAUSER: I would tend not to think so. I think that the -- most of the people who are, this is pretty sophisticated spine surgery. I don't think you have general orthopaedic surgeons in North Dakota doing spinal fusions of this nature, unless they've had some training.

I don't think it is the case that Dr. Smith in North Dakota saw this in a journal and said, gee I saw that patient last week, calls the rep, has him come in. I don't think that is happening.

The exposure for an anterior approach is pretty specialized. We use a vascular surgeon in every single case. Not every spine surgeon does. So that is a pretty good obstacle for them to do that.

So what you are left with are people who are actively involved in the professional societies, the North American Spine Society, the Neurosurgical Societies, the Academy, who have the opportunity to see that sort of training every time they go to a meeting, unless they don't go at all.

And if someone is, I guess, that --

DR. FINNEGAN: But they are not doing hands-on, because hands-on is fairly expensive.

DR. TROMANHAUSER: But the Academy does hands-on workshops, and so does NASS.

DR. FINNEGAN: And volume enough to cover the people who don't -- because, with all due respect, actually one of our residents is in South Dakota, is a spine surgeon, has been out for about 12 years, does extremely work, I'm sure does anteriors. But he is the type of person that I'm thinking about that, you know, wouldn't have been exposed to, and trained and will be interested in doing it.

DR. TROMANHAUSER: But will also, probably, take the time to go to those meetings, I would guess. I would hope so.

CHAIR YASZEMSKI: Thank you. Dr. Naidu, you had another question?

DR. NAIDU: Yes, a clinical question. You are the founder of Cortek, correct?

DR. TROMANHAUSER: Co-founder.

DR. NAIDU: Co-founder. Now, the implant that I saw was a neat PEEK cage. It is a basic question, actually. Have you seen two neat PEEK parts wear together, have you seen the particulate debris generated?

DR. TROMANHAUSER: No.

DR. NAIDU: Okay.

CHAIR YASZEMSKI: Dr. Larntz?

DR. LARNTZ: I'm intrigued, always intrigued with sort of saying it doesn't work because we selected the patient poorly. That is easy to say after the fact.

What I need to know is I need to know how hard people are working, and how many data bases they are creating, and what they are really trying to do to get a real decision analysis algorithm for patient selection.

I, it seems to me that there probably are some predictive factors, or maybe we will find out that there is an element of chance, in this world, which some of us do believe in. Maybe we believe the whole world is run by chance, actually, but that is a different story, and we will go there later.

But can you believe there really will be a patient selection algorithm that will be effective? I heard what you said, it is up to the individual surgeon to make that decision.

I trust all surgeons, of course.

DR. TROMANHAUSER: Why do I doubt that?

DR. LARNTZ: But it would seem to me your experience, if your experience is on 100 or 1,000 patients, there are how many, 200,000 of these implanted. Surely we have data bases that are large enough to do at least some level of decision analysis to take care of this patient selection problem.

It is very nice, you know, when Dr. Zdeblick says at the end, patient selection is the problem. It is very easy to say that at the end. And that is easy to say that is why they failed, because we didn't select them right, after the fact.

But I need to know, before you do the surgery, which patients to select. So is there an effort done, is there an effort being made, sorry for this little spiel, for a decision analysis? A formal decision analysis.

DR. TROMANHAUSER: Well, it is interesting you should ask me that question, Dr. Larntz, because I spent the last five or six years working on exactly that kind of problem.

I just had a chapter published in a book called "Advances in Spinal Fusion", I presented papers at the American Medical Informatics Association, and at NASS, on predictive modeling for spinal fusion, using a neural network-based predictive model.

And what I tell my patients, this is the most difficult problem. I say, listen, I think you are a good candidate. All the things that I have available for me to choose you, and to evaluate you, tell me you fall into the bucket that says you are a reasonable candidate. But I'm going to tell you, you could be one hundred percent better, and think I'm God, you could be no better at all, and want to sue me, but you may be solidly fused, either way.

And there is something about these patients that we don't understand. Pain is a very complicated entity. And until we understand pain better we don't even understand the mechanism of the production of pain from a degenerative disc.

It isn't instability per se, because as soon as I cut out the disc I know the pain in general is going to be gone. My job, then, is to fill the gap I made by taking out the disc. That is why we are here today.

And until we can subdivide those patients into, by some indicator, whether it is some kind of test, or some other psychological -- I mean, people have come up with psychological testing, MMPIs, there is a lot of different ways.

And, yes, there are some people whose profiles we know will fail every time. The 54 year old worker's compensation patient who is 50 pounds overweight, smokes, narcotive addicted, has no family support, may have a personality disorder, who knows, that guy is not going to do so well.

You come to me with back pain I assume you are an upstanding citizen. If you don't smoke cigarettes, and you are healthy otherwise, I hope my government has chosen you appropriately.

(Laughter.)

DR. LARNTZ: I'm just a statistician, not a role model for anything else.

DR. TROMANHAUSER: So we do make those judgements. My role, as a physician, is to try to help everybody I can, but not turn away anybody who could benefit. So what we accept is a certain failure rate to try to achieve that goal.

DR. LARNTZ: And I understand that. But what I think is very, very important, we don't often see these algorithms distributed, and shown to people, and told. And sometimes these papers don't always get published in the most obvious places, and so on.

And I think we do, you know, just a feature of light, we need to do more of this formal decision analysis, and make it available. And recognize, sure, your chance -- and fusion is a different issue, I think, than patient success, and that is --

DR. TROMANHAUSER: That is exactly right, that is the point I tried to make.

DR. LARNTZ: I agree with previous panels we have on that said we can always get a device that will fuse but do we know it is going to help the patient is a different issue, and I think you made the same point.

But in fact I think that we don't do enough of using the real data we have to make these decisions. And I think it is going to be a multi-varied complex algorithm. And I appreciate you using fairly sophisticated data in analytical, or maybe we should call them data mining technologies which are very useful in this area.

So I advocate continuing to do that. Thank you for your answer.

DR. TROMANHAUSER: We may want to take that conversation off line as a statistician. It is very interesting work.

CHAIR YASZEMSKI: Thank you so much. Other questions for Dr. Tromanhauser?

(No response.)

CHAIR YASZEMSKI: Thanks very much for your presentation and discussion, Dr. Tromanhauser.

DR. TROMANHAUSER: Thank you.

CHAIR YASZEMSKI: We are now going to hear representatives by Biorthex, Inc. We have Dr. Benrabah and Mr. Leroux, in whatever order you would like to go. May I ask, sir, do each of you have a presentation, or will one of you present?

DR. LEROUX: My name is Michel Leroux, I'm going to do the presentation, if I can find it somewhere.

CHAIR YASZEMSKI: Thank you.

DR. LEROUX: Again, my name is Michel Leroux, I'm vice president of research and development of Biorthex company. I have a PHD, I only have a PHD in biomechanics, but I have some experience with interbody fusion cages, and spinal surgeries.

I think we cannot add much to the excellent previous presentations. And you can say that we agree with most of the arguments. On the other hand, we have a little short point we would like to stress today.

Just to start, I will try to give you an overview of this presentation, just try to present the company, our experience with IFDs, and our position relative to the proposed statement.

We are a very small company, we are a small spinal device developer and manufacturer. Let's say that we are more a research and development company. So we don't have a lot of sales. We are a quite young company, the company was founded in 1996.

We have an office in Sioux Falls, South Dakota, and the French Canadian accent, is coming from our head office based in Montreal. As I said, we have a short experience with IFDs, so we have performed 500 surgeries, not 500,000, but 500 surgeries around the world, except in the U.S.

We already have two IDEs approved, and clinical trials are going to start very soon. The results we have, actually, are not that long, since this device has been introduced on the market less than two years ago, so we have 1.5 to 2 years' results.

And up to now we have very, very good results with the cage that I will present a bit later, is different than what is actually in the U.S. market. So we have one reoperation, and it was not device related.

I think we had a high fusion rate, close to 97 percent. I would say that most cages implanted in Europe are done stand-alone, without posterior fixation. So I believe that even if flexion/extension is not a standard foolproof, I believe that when there is no anterior fixation, you have a good fusion rate.

We have very good clinical outcome. Pain and function improvement. We had, also, good satisfaction from the surgeons. And since we are not doing any posterior fixation, usually the patient is going back home sooner, and back to normal activity, also, sooner.

I didn't present any statistics, or anything. But if you want to have a review of this data, they are referenced in the document available at the entrance.

Now, you know better Biorthex. We would like to express, today, our support to the intervertebral body fusion reclassification proposal. U.S. patients and surgeons will benefit of a faster access to new products on the market.

I think it is very important that, also, that if more U.S. surgeons are using new devices, new and/or improved device, I think it will also reflect on other surgeons and patients around the world. So I think it is very important here to get American access and to get expertise from North American surgeons to be able to reassure foreign surgeons and patients.

We agree with the proposed CFR listing, maybe with the exception of the first sentence in section 1, identification, where it states that the device made from a variety of materials, including titanium alloys, and polymers.

We strongly believe that to refer to generic materials does not support complete safety and efficacy of the device made out of such material. That is why we have special controls in everything.

On the other hand we believe that it may have, the statement should, the identification of materials may induce some bias in the evaluation of new devices. As example, we can have new titanium device that may not fit all the controls, and everything. So you have some kind of a bias that, okay, submit a titanium we are going to approve this device.

On the other hand we may have some device made of other material that may be suitable for fusion cage, and it may have a more difficult access to a 510(k) if it is made of another material than titanium or PEEK.

Actually we are quite aware of at least one other material that presents the requirements for such device, it is nitinol. I think that this material fits all the recognized material standards, we have the ASTM F-2062, and this standard identify underlie the specification for wrought nickel titanium shape memory alloy for a medical device and surgical implants.

I think we have experience, also, in biocompatability, since we have a lot of other device on the market made out of nitinol. We are talking of cardiac stents, or vascular stents for different use, sutures, occluders, filters, bone anchors.

If we look at Medline research on nitinol, you will see that there is close to 800 publications with close to 800 in 2003, just related to nitinol in medical application.

We believe that it is a sure material for medical applications. Let's say that nitinol is also available in a porous form to permit tissue and growth and attachment. Biocompatability of the porous nitinol has been assured through ISO 10993, Biological Evaluation of Medical Device, and through adherence to existing material standards for nickel titanium alloy.

Porous nickel-titanium, nickel titanium has been used in some countries for more than 15 years as an interbody fusion device, in different surgical procedures.

As I said previously we recently introduced in Europe two of those device, one lumbar, two lumbar sorry, and a cervical interbody fusion devices made of porous nitinol in more than 500 patients which is not that bad.

Two hundred patients were treated for lumbar disease, while 300 of those patients were treated for cervical disease. The result, collected through introductory trials, proved the device to be at least as safe and effective than competitors on the market.

For sure we are a small company, we don't have a lot of market, so we are able to follow, very closely, the surgeons using our device. So we are very close to these patients.

So being able to do this kind of follow-up is a good thing, because we really realize that when this device is used mostly stand-alone procedure without posterior fixation, and mostly without any bone graft, we have very good, very good success with most of the users, right now, across the world.

We also, with this device, porous nitinol device, we also meet all the mechanical testing standards, compression, tension, torsion, expulsion, fatigue, subsidence, animal testing, and everything.

It reflect by the decision of the FDA to accept two of these IDEs for IFDs. Labeling is also an important part, and we realize that we may have some concern relating to the nickel content of nitinol.

On the other hand we know that stainless steel also has a large percentage of nickel in there. So we believe that special labeling, and keep the patient aware and follow-up of this condition, will help to bring this device to the market, and prove that it is safe and effective.

So from our point of view there is some other material than titanium alloys and polymer, that can be suitable to manufacture interbody fusion devices. We strongly believe that the general reference to generic materials does not support the complete safety and efficacy of the device, and that identification of only two materials imbues some bias in the 510(k) evaluation of these new devices.

We are, then, proposing or suggesting the following changes. The actual proposition we have in the document, and we think that, probably, the most resolvable way is to just put the interbody fusion devices made of a variety of materials that fulfill the requirements of general and special controls.

I think that you already discussed previously, are we going to have, let's say, the guidance for titanium alloy, guidance for PEEK. I believe that the best solution is to have a single guidance to cover all aspects, all materials, and not only titanium alloy, and PEEK.

And, for sure, if everybody feels comfortable with new, other materials, we can try to improve the list of these materials in the text, just to get the similar access, or same chance to everybody to be accept through a 510(k). Thank you.

CHAIR YASZEMSKI: Thanks very much, Dr. Leroux. Also my apologies, you were not listed as Dr. Leroux for your --

DR. LEROUX: That is okay.

CHAIR YASZEMSKI: -- incorrect introduction of you before. Do we have questions from the Panel for Dr. Leroux?

(No response.)

CHAIR YASZEMSKI: Seeing none, thank you for your time.

We are going to move on now, if we can, and shift gears just a little bit, to the open public hearing portion. And prior to doing this, we will state that we received no requests for anyone to speak at the open public hearing, but that opportunity exists for anyone who would like to.

So I will ask now, is there anyone present who would like to address the Panel at this time? If you would like to do so, please identify yourself and come forward.

(No response.)

CHAIR YASZEMSKI: Seeing nobody we will do the following. The next portion of the meeting is going to be the Panel deliberations. But I'm going to recommend that we take a short break now, a ten minute break, and give everybody an opportunity to stretch, and use the rest room if they need to.

It is now 20 minutes to 11. If possible I would like to ask everyone to come back and be seated at 10 to 11, and at that time we are going to ask Dr. Diaz to move forward with his presentation. So we are adjourned for ten minutes.

(Whereupon, the above-entitled matter went off the record at 10:42 a.m. and went back on the record at 10:52 a.m.)

CHAIR YASZEMSKI: Welcome back, everybody. I would like to call the meeting back to order and remind the public, again, that while this meeting is open for public observation, public attendees may not participate, except at the specific request of the Panel.

We will now begin the Panel discussion. A deputized voting member of this panel will open this part of the meeting with remarks. Dr. Fernando Diaz will give his remarks on the proposed reclassification.

After that the Panel will have a general discussion, after which the Panel will focus their deliberations on the FDA questions. Then Ms. Shulman will guide the completion of the reclassification questionnaire, and supplemental data sheet forms.

Finally the Panel will conclude their deliberations by voting on the completed forms, and setting out their recommendation to the FDA.

The Panel can ask the sponsor, or FDA, questions at any time. Prior to Dr. Diaz' presentation, I would like to ask for comments from Dr. Witten. Dr. Witten?

DR. WITTEN: Yes, thanks. I just want to clarify what we think we are doing or, at least, what FDA thinks it is doing with this reclassification, in light of some of the comments made by the three industry presenters, which we certainly appreciated hearing.

And these comments relate to what was said about the use of supplemental internal fixation, the use with allograft bone and other approved bone substitutes; the spinal levels, and the use of other materials for cages.

So let me just say that, and perhaps it should have been part of the device description. But our proposal is to reclassify all of the device, the existing PMA devices, other than the one that uses BMP.

And so one of those devices is with additional internal fixation, so the intent was to also reclassify that device. And that may mean that the language needs to also say with and without supplemental internal fixation.

Since that is our intention, that is the intention of the proposal. And so perhaps that language needs to be added.

As far as some of the other things, the use with allograft bone, and the spinal levels, and the other materials, I will just make the following generic comments, which is that we can only reclassify what we've actually seen. That is what we have actually approved.

So the reclassification would be for, you know, the existing products. And then what would happen, if a sponsor came in with something different, a different material, or a different level, or to be used with a different something other than allograft, is we would evaluate that through the substantial equivalence process, and see whether or not the product with data, or without, with whatever the sponsor provided, was able to demonstrate substantial equivalence to the products that we had already cleared.

And so based on that substantial, the review process, we might decide that we need some types of additional information, or not, and could include, you know, anything could include bench testing, animal testing, potentially clinical data.

So that would be part of the review process. So, in other words, in our minds this would leave it open to have these different types of devices, but we would need a demonstration of substantial equivalence in order to make that determination.

So when you are talking, I think that clarifies at least what we think we are doing with the proposal. In your discussions, if you have any specific comments about what kinds of information, or what kinds of testing, that you think we might want to think about, or whether you think that there is, you know, some specific concerns that you would like to highlight about this approach, either one, please we welcome those comments as well.

CHAIR YASZEMSKI: All right. Thanks very much, Dr. Witten. Dr. Diaz?

DR. DIAZ: Yes. I've been asked to give a presentation from the Panel perspective on what these devices mean and what, based on the literature available to us, and my personal experience, these devices can be viewed from the perspective of changing classification.

I would like to view it from the perspective of safety and efficacy, as opposed to what you heard earlier, start with indications and with patient selection.

I realize that that is not what we are here to see but that is, very often, the critical aspect of what we do. Spine surgeons are required to make very specific decisions in the choice of instrumentation they use, based on the indication for the right patient, for the right tool, to provide the appropriate outcome.

Patient selection is, without a doubt, the most critical part in this process. We may have the best tool in the market, if that tool is used for the wrong person, the tool will fail.

If the patient has comorbidities that will not allow for the patient's use of that particular device to be successful, the device will fail through no fault of the device itself, through no fault of the surgeon, him or herself, but through the fault of the comorbidity selection of that patient.

A patient who is a smoker, a patient who has additional diabetes, hypertension, or cancer; a person who has a work compensation history of pain and disability will likely not be successful, or as successful as the right person for the right indication, with the right tool.

In regard to the cages themselves as you heard this morning, the cages come in a variety of flavors, colors, shapes and sizes. The best description are those which are metal, those which are non-metal, mostly PEEK supported by carbon fiber, or some other coating material.

The shape can be square, or box in nature. They can be cylindrical with or without threads. The approach can be anterior or posterior, depending on the patient habitus, depending on the patient's risk status, depending on the selection by the surgeon.

The approach in the application of the device makes a difference on failure of the device. Again, not predicated on the device itself, but on the application used by the surgeon in choosing one approach versus the other.

Success we measure by two criteria, one is clinical criteria, the other one is mechanical criteria. The one that we want to look at the most is the clinical success rate, is the patient's pain and neurological problem resolved.

If that is the case, very often, the device in and of itself, and what it does, will not make a whole hell of a lot of difference to any of us. We will be satisfied with the outcome because the patient is doing better.

The reverse is more common, where we have a patient that has an outstanding mechanical success, with a fusion that is as solid as a rock, but the patient continues to complain of pain, or neurological dysfunction.

What we are being asked to do is, really, to reclassify a set of devices that are very comparable to a set of devices that are already classified at a different level. Vertebral body replacement devices are almost identical in shape, size, form, and application to what the intervertebral body devices do.

There is very little difference in those two set of applications in the type of instrumentation we use; the approach in which they are used, the application for which they are used, and the success rate that they will provide.

What I would like to leave you with, as a conclusion, is that the device, in and of itself, may not answer all the things that we want to answer today. The success rate, be it clinical or mechanical, may or may not be predicated entirely on the device itself, but on the patient selection, in that there is a group of devices that we have already approved, as a level II set of devices that are nearly identical to those we are using for intervertebral disc replacement. Thank you.

CHAIR YASZEMSKI: Thanks very much, Dr. Diaz. We are going to proceed now to a general discussion. What we will do, in this general discussion, is ask the Panel members to speak to any of the presentations that have been given, call back any of the presenters to the podium, to ask them specific questions or, in general, to comment on the issues before us.

Once we feel that we've had an adequate discussion of a general nature we are going to move to a specific discussion of each of the five questions that the FDA is asking us to consider today.

When we move to that portion of the discussion, if I can, I'll ask Ms. Anderson to project the questions, one at a time, and we will go around to each panel member, and ask each panel member, to make a comment on each question.

Let's open the general discussion now. Panel members? Dr. Finnegan.

DR. FINNEGAN: I have a question now for Dr. Witten, although this may not be the person I should ask.

One of the things, besides supplemental fixation, people have talked about is surgical approach. Are you considering, also, in the guidance documents opening that up, or may I ask how you plan to approach that?

Or perhaps a more generic question, do most Class II have limited surgical approaches per their guidance documents?

DR. WITTEN: Well, I think our thinking was to, you know, to reclassify the devices generically and then have the specific instructions, the sponsor can have specific instructions, and we would look at those and see whether or not that device, with those instructions for use, was substantially equivalent to what was on the market.

I mean, there is products, some of the products approved right now are approved with -- there are different approaches represented by the products group right now, currently.

DR. FINNEGAN: Then I guess my next question would be can all of these products be used with all of the approaches?

DR. WITTEN: Maybe I didn't answer clearly, then. So can I try again? So in a product, you know, when we clear a product it has to have the product and instructions for use for that product.

So it doesn't necessarily mean that any product would get generic instructions for use, of use anyway you can. The sponsor would need to propose instructions, the product and the instructions, and we would look at that.

DR. FINNEGAN: I hate to be a real pain in the derriere, but I'm going to be one. You, what is the word I want, you put as a Class II IM femoral rods. And am I assuming that you put them to go from the hip towards the knee, and so then when some of us decided to put them from the knee towards the hip, we were violating the guidance document?

DR. DIAZ: Maybe I can answer that. There are some of these products that can be used either from the anterior or the posterior approach. Not all of them, uniformly, can be used that way.

But there is a distinct group of them that can. The quality, the safety, and the efficacy, does not really change much in those products, depending on the approach. There are some that have very unique specific applications for the anterior approach.

The prime example is the LT-Cage that is a conical cage, that can only be placed through the front. And so with that caveat the approach does not really matter a lot for the majority of them.

DR. FINNEGAN: And that was my concern. My concern is when you do a PMA you want to put in the safest way possible so that you can get the best results. But when it goes into the real world if, in fact, it can be as a surgeon feels comfortable and, perhaps, the situation dictates, then I would be concerned that it not be limited by the PMA instructions.

DR. DIAZ: Yes. The safety there is really predicated in the surgeon's experience, the patient's habitus, the accessibility to the approach, and the location of the problem.

CHAIR YASZEMSKI: Thank you, Dr. Finnegan, and Dr. Diaz. Other questions, comments? Dr. Naidu.

DR. NAIDU: You know, it seems as if we are discussing two different issues here. One is clinical results, which Dr. Diaz explicitly stated, and it is based mostly on patient selection, rather than the device itself.

And if the patient does well it doesn't matter what the device is, and we have a great outcome. But I'm not so sure it is that simple. I mean, materially, you have two different materials here. You have metallic and you have polymeric.

The polymeric materials, even though you've defined the matrix as PEEK, you can vary that in many ways. And, for example, one of the products in the key chain that was presented was a pure knee PEEK. It can be reinforced, and those are -- I mean, I think material importance is also a key issue here.

You can't dismiss that because if those plastic devices fracture, in vivo, and neat PEEK is, essentially, a soft material. If it wears, PEEK on PEEK wear produces terrible debris.

I'm not so sure that we have enough special controls. My concern is that I'm not so sure that we have enough special controls to classify polymeric materials, and metallic materials under one single guidance, that is my concern.

I'm not so sure that the tests that are mentioned so far here really fulfill all the criteria for one guidance document. It may be that we need to split these devices into a metallic, pure metallic component, and polymeric components, and write two separate guidance documents.

I mean, I think there are two issues here. Because the polymeric materials are not equal to metallic, no matter what you say. I mean, it may be that patient's outcome is important but, nevertheless, in extreme cases where the polymeric materials fail, the results can be devastating.

You know, polymeric wear debris is, especially PEEK wear debris is terrible. I mean, I'm going to ask Dr. Li to comment on that further. Do you have any --

CHAIR YASZEMSKI: Dr. Li?

DR. LI: I happen to have a comment on that. Actually I have a page of comments on that. I completely agree with you. I also agree that the polymeric and metallic devices should be considered separately.

We have a couple of issues here. The few clinical results that we've gotten here seem to indicate that the devices is safe and efficacious. And the reports are very few of an actual device failure.

However, I will say that the MDR is a particularly bad place to use that data set to convince yourself that, in fact, fracture doesn't occur, and what level it occurs, or doesn't occur. It is something on the order of a tenth of a percent in this case.

So I go out for two things. Either that they, in fact, don't break which would be good, but then it would just be plain fortunate, because there is no test, for instance, for fracture. And the loads that I've seen are way under what they should be, for instance, for a 200 pound person picking up a ten pound weight.

The loads being applied to these devices are about one quarter the loads that you would see. So I'm unconvinced that the materials testing, for the polymer side, especially, is sufficient.

Specifically they call out PEEK, and they give us a PEEK guidance document. But that PEEK guidance document is, specifically, for neat PEEK. There is no guidance document for reinforced anything, in this device, including PEEK.

So, and even if there was, don't underestimate the ability of the bioengineer to screw up a good product by changing something small, like the length of the fiber, the type of the fiber, orientation, molecular weight of the polymer, the list goes on forever, for the ways that I could screw this up.

So it could be that they are not breaking, but it could be just a fortunate happenstance that these particular groups don't break. But, for instance, if you make it a Class II it would be, if you change it from PEEK to PEK, or you use -- there is resorbable ones, there is a whole host of polymers that could find their way into it.

I don't believe that the existing tests would guarantee that they, in fact, will not fail. And, actually, that kind of separates also into the cervical placements, and the lumbar placements.

The cervical loads are, in fact, very low under any condition. But because the -- because body weight actually plays a big part in the lumbar loads, the lumbar loads are substantially higher, maybe ten times higher.

So I think that it is a little bit dangerous, on the polymeric side, if you have something surviving in a cervical application, that you would guarantee that it would survive in a lumbar application.

It might, but if it does, at the moment, we are just lucky. And the other thing that I'm uncomfortable with, a little bit, is that although these are fusion devices, there is no test for fusion.

So if someone comes in with a different material, a different structure, a different geometry, it seems so far that everything that has been tried has fused. But, again, don't underestimate the ability for us to come up with something that, in fact, won't fuse. Because, in fact, we have no way to pretest that.

And the only way we are going to find out now is when the surgeon puts them in and all of a sudden finds a very low fusion rate.

And I have a question for Dr. Larntz, now that I get off my soap box. In looking at the data that we presented, are you convinced, in fact, that all these devices are equivalent to each other?

CHAIR YASZEMSKI: Dr. Larntz, go ahead.

DR. LARNTZ: Wow, that is -- am I convinced that they are equivalent to each other? Well, of course, they are not equivalent to each other. But that is not, you know, statistically equivalent, I think -- I have done no analysis to answer your question.

And I can't imagine that they are actually exactly equivalent. But I don't think that is a requirement that we have here, okay? I think there is going to be a range of performance.

I looked at these shapes and I'm not, you know, I don't know anything about this, but they sure seem different in the shape. They sure seem different in all kinds of characteristics which all of you engineers can do all the testing.

I do have a comment, I'm going to make a comment later about testing. But I think that all these devices have, I mean, is it seven that have been passed? I can't remember now, it is six or seven, anyway, that have been passed.

And there is six that are like the ones that we are asked to reclassify. If you look at the data that they have, they are all effective devices, with respect to what they are aiming at. They are all -- if you read the papers, I mean, they are pretty -- I realize that I made a big deal of patient selection, because there is always going to be patient variability.

But these devices that we are asked to be reclassified, statistically, I haven't seen a great deal of difference across them. How is that? Nothing obvious.

But, you know, if someone comes in with a very low fusion rate, but the device may, in fact, work clinically for all I know, right? I mean, we have been in this panel before where people say, well it is supposed to do just what it is supposed to do. If it is supposed to be a fusion device we are going to count it, and that is good.

But we don't know if that is going to translate to clinical success. I would rather have a device that I don't care if it fuses, I'd rather have a device that has clinical success. And I think that is very hard to predict, besides patient selection.

So sorry to go around your question but I think -- I don't think that we have any strong evidence that this group of devices that we see here are very, very different, with respect to performance. And I do agree that patient selection, patient mix is a big part of performance.

CHAIR YASZEMSKI: Thanks, Dr. Larntz. Mr. Melkerson, do you have a comment?

MR. MELKERSON: I'm Mark Melkerson, Deputy Director for the Reviewing Division and some clarification and some examples.

In terms of polymeric materials, we would consider each change to the polymer a new material. And to address those types of things it could be something as simple as animal testing, to clinical data.

And the example I would bring forth would be what was done for bone fixation appliances made out of resorbable polymers of various types, found equivalent to metallic implants.

Initially that was required, they had to have clinical data to demonstrate that they were equivalent in clinical success to a metallic plate for the same indications for use.

Later that information was backed down after we had gained experiences with families of polymers, backed down to just requiring animal data. So under the 510(k) process we are allowed to ask for clinical data for those things that are, indeed, different.

And they as we gain experience with families, or particular polymers, back down those requirements to animal studies, or just bench top testing.

CHAIR YASZEMSKI: Thanks very much, Mr. Melkerson. Dr. Cheng?

DR. CHENG: Just a question for Steve. I thought I heard you say that there are no tests for failure of these devices, did I hear you say that?

DR. LI: There is no test for fracture. They have a fatigue test, but fatigue and fracture are really not the same thing. The fatigue test is actually very dependent upon the geometry and method of loading, and the amount of load that you apply.

It is not really a basic material property. So different things, for instance, can have a very high fatigue strength, but a very low fracture rate. So the issue here is that they are two different properties.

And I would worry, especially in the early stages where fusion hasn't occurred, and the device is basically left to stand on its own, to support whatever load it is going to see, that -- again, I'm not really talking about the current devices, I'm really worried about could be coming on down the line.

That you could have a device that would survive a fatigue test at the time they proposed but would, in fact, fail a fracture test.

CHAIR YASZEMSKI: Dr. Li, may I ask you for a clarification? The tests that you speak of were not in the material that was presented to us, but these tests could be done, is that correct? They could be specified, a fracture test could be asked for?

DR. LI: Yes, they could be. But they are currently absent in any of the documents that we have gotten so far.

DR. CHENG: Maybe I'm misunderstanding something. But I'm reviewing the guidance documents, in the back of our packet, and it seems to me that static testing is, in addition to fatigue testing, static testing to structural failure is required.

DR. LI: Again, that is not a fracture test. In other words, is the difference for me applying a test to bend this pen, as opposed to breaking.

All the static tests are, basically, low speed, very slow test design to get a material failure point. It would be the difference between breaking a stick and then pulling a stick so much that it breaks that way.

So, in other words, fracture is a specific failure mode that is not addressed in any of the tests that we've got. This is not bad mouthing any of the existing tests. It just doesn't address the issue of fracture should they change the material geometry, or the percent of filler, or whatever.

DR. LARNTZ: Could I ask a question --

DR. CHENG: One second, if I could continue? The reason is because the FDA hasn't requested that, or the reason is because the test doesn't exist?

DR. LI: No, the test exists. Let me give you an example. For instance, the highly cross linked polyethylene that is used in acetabular components now passes all the fatigue tests, but yet has a fracture strength of one/one hundredth of that, of the none highly cross linked poly.

In other words, so it is unlikely that you are going to break a highly cross linked cup by repetitive loading but it is possible, it is one hundred times more likely, that if there is a pre-notch in the wrong place, loaded at a certain time, that the cup will actually break.

So fatigue and fracture are not the same thing. And the tests exist for fracture, they are just currently not called out in this particular device. And, again, I'm more worried about the polymeric structures than I am the metal structures.

DR. CHENG: I see, okay. I have a separate issue I will take up later.

CHAIR YASZEMSKI: Dr. Larntz?

DR. LARNTZ: I just want to clarify. I think I might be a little lost. We have no guidance document for this set, right? We have an example of a guidance document in the back for other devices, but am I right that you are going to develop a guidance document if this goes to Class II, is that --

DR. WITTEN: That is right, the guidance documents which were provided are to give you an idea of the kind of information that is in a guidance document. And also -- well, there is two, there is one on clinical studies, and there is one on 510(k)s for the other devices.

So I think it gives a fair idea of the kinds of things that --

DR. LARNTZ: Right. But if we want to ask for a particular test, if we want to suggest those, and put those -- then that is --

DR. WITTEN: Well, that actually is part of our questions, which is, if you've identified the risks, can you identify special controls.

DR. LARNTZ: Okay, I just wanted to make sure.

DR. LI: I will say that it is not in their PMA either. The fracture testing is also not in the existing PMA requests and documents. We can add them on, but that is the basis for which I was making my comments.

DR. LARNTZ: But these devices that have been approved, and this panel has approved, and I sat here once or twice and approved something, and I actually stood over there once or twice, and we've approved something too.

I think these devices are working. I mean, we are not questioning the devices now, I don't think. We are questioning whether or not they can be down classified, if the Agency has enough information to go to Class II, and if we can specify and help the Agency in laying out how they should ask for tests.

If a fracture test seems to be important I'd hate to think, and I'm not sure if our industry rep might comment on this, that we are going to ask all these already approved devices to go back and do fracture testing? I don't think we are going to do that.

DR. LI: No, well --

DR. LARNTZ: Nor do I think of a new one -- well, okay.

MS. MAHER: Can I add something?

CHAIR YASZEMSKI: Ms. Maher, go ahead.

MS. MAHER: I'm Sally Maher, the industry rep. I think Dr. Li, you are implying that these things won't go through a thorough review if they are 510(k) for a new material. And that, in fact, isn't true.

There will be a guidance document developed, it will be a very thorough review. And if there is a new material the FDA and the sponsor would work together to develop a test that appears to be the most appropriate for it.

And I think we have discussed a lot -- I've heard a lot of discussion about the PEEK versus the metal. You've never requested the fracture test for the cages that are currently on the market. We haven't seen it as an issue yet, for the cages that are currently on the market.

And maybe if Mr. Christianson, who works for a company that makes one of the PEEK products, would want to talk a little bit about the testing t they do do on their products, it may alleviate some of the concerns.

DR. LI: Again, can I clarify a little bit? I'm not disparaging, in any way, the products that we have in front of us at the moment. And I'm even willing to believe, optimistically, that fractures are rare.

But let me point out two things. One, we don't really know what the failure rate is because the only thing we are going by is the MDR reports, and a couple of clinical studies done by the investigators who are proponents of the device.

So I would say, first of all, we don't exactly know what the fracture rate is. And certainly, unfortunately you showed the key chain, that some of those devices on the key chain are fractured.

And if you would put those into a 200 pound guy, picking up a 10 pound weight I would be surprised, in fact, if that device didn't crack all the way through.

So the fact that we don't have any, I think, is good. But I'm worried that that is just because we have been lucky. And so as we go on down the line, and we down classify, I just want to be sure that these controls are in place so that when you change structure, and change materials, or change whatever, that those tests exist.

In fact I would recommend, in fact, if you take the optimistic view that, in fact, fracture doesn't occur currently, that you measure the fracture toughness of the current devices, and all future devices have to be that fracture toughness or more.

So I would go back and recommend that you, in fact, do the fracture toughness testing on the existing devices but use that, essentially, as a guideline for at least the minimum fracture toughness of all future devices.

MS. MAHER: I would actually suggest we not use the key chain as an example, since it has been knocking around in a car, and a briefcase, for God knows how long, it is not a sterile --

DR. LI: Well, let me just say that those devices are not unusual for polymeric composite devices.

CHAIR YASZEMSKI: Thank you. I think if I can summarize this discussion, when we have issues like these we will be able to communicate them to FDA as concerns, and they can be incorporated in the FDA's assessment of what special controls are needed.

So this is good, and we do have a method in place to include them. I would like to ask one more thing, if I might, and I will get to Dr. Cheng.

I want to give an opportunity for our patient representative to speak if she would like to. Ms. Wells, is there anything you would like to add?

MS. WELLS: Not at this point. The thing that is a bit confusing to me is the fact that these devices have been around in another format. In other words, as a spinal replacement in Class II.

So I know the concern is here, as far as the polymers are concerned. But I think with the guidance documents we are going to be okay with looking at the different polymers versus the metal.

CHAIR YASZEMSKI: Thank you very much. Dr. Cheng?

DR. CHENG: I have a concern that I don't know if it is addressed in the questions to us, so I just wanted to bring it up.

If I were a patient about to undergo placement of one of these devices for arthrosis of my spine I think the long term complication that I would be worried about most would be adjacent segment disease.

And I know a number of factors that determine your risk for that depend on anatomic location, and how many segments are fused. But the question I might ask the spine surgeons on this panel, and perhaps in the audience, is there -- does the type of device implanted, or perhaps I should say the rigidity of the device implanted, play a role in determining the risk for subsequent adjacent segment disease in the long term?

DR. DIAZ: Maybe I can answer that. The problem that arises with the implantation of an intervertebral device, and the acquisition of a fusion, is that you basically immobilize a segment. So you take that segment out of the biomechanical

activity of the spine.

When you do that you increase the load above and below, like Dr. Li was saying, by a series of newtons. And so the mechanical work becomes greater for that segment, and there is no difference between the structure of the device being metal, or being plastic or PEEK.

The ultimate result will be fusion in both. And if that is what happens the common denominator will be increased load at the level above and below. So the device itself plays very little to no role in the ultimate development of additional disease.

DR. CHENG: I guess I was wondering if the modulus of elasticity is different enough that the stress, or the number of newtons, apply to the adjacent segment may change, as is the case for implants in other areas of the body.

DR. DIAZ: The reality of the difference in the modulus of elasticity is that the probability for fusion is increased with the PEEK type device, because it is more of a load -- it is not load bearing like the metal cage is, it is more load sharing.

So the probability for fusion is heightened with a plastic, or a PEEK device, versus a metal device. Ultimately, though, if at the end of the nine months, as was mentioned earlier, if the spine is fused, the end result is no different.

CHAIR YASZEMSKI: Thanks, Dr. Diaz. Dr. Finnegan?

DR. FINNEGAN: I'd like to address the concern about metal versus polymer. In the literature that we were given the polymer studies all had posterior instrumentation with the polymers.

Do we know of any polymers that are used without posterior instrumentation? Because that is a totally different dynamic.

DR. DIAZ: The experience in the literature has been that when you use a posterior approach, almost uniformly, irrespective of the kind of material you use, be it metal or be it polymer, the likelihood of success is considerably less than if you use the device with the additional of internal instrumentations, spinal fixation.

The reason for that is because you destroy the facets on both sides, and you create an unstable spine. So the addition of devices is just to prevent mobility.

DR. FINNEGAN: Yes, because you go through three columns. But my concern, more, is has anyone done an anterior approach with the polymers, without posterior fixation?

DR. DIAZ: In fact some of the newer devices are used that way. And there is a couple of papers here that are showing encouraging results using just the pure anterior approach. I believe one of these is, I can't remember exactly which one it is.

Maybe I am thinking of the metal one that just promotes the use of purely the anterior approach, the BAK. But the tendency, in general, is that if you disturb little the other two columns, the probability for success, if you use the ideal structure, is going to be greater.

DR. FINNEGAN: But my concern, and I agree with what has been said before, is that the load on the polymer is significantly different if you go anterior and it is taking all of the load, as compared to if you do a combined anterior posterior.

DR. DIAZ: But when you put the device alone here, the elasticity of the material itself, from my experience, has been such that fracture has not been a problem, fusion has occurred in the vast majority of cases.

And I think that is what the literature bears. I understand the concerns for the fracture and the load stress on the material. But I don't think that has been a problem. I would like to hear what others have experienced.

CHAIR YASZEMSKI: May I make a suggestion? I've noticed that the discussion items have been, now, sort of going into areas that have been asked in specific questions by the FDA, but we are going back and forth among a few of them.

And it may be time, if no one has any objections, to move to the FDA questions, and we will continue with the same discussions, but in the format of one question at a time.

DR. LARNTZ: Can I make my one final comment?

CHAIR YASZEMSKI: Dr. Larntz, go ahead, while Ms. Anderson is getting her slides up.

DR. LARNTZ: I said I would like to make one comment. And I noticed that you rely on ASTM testing, and standards. And let me remind us that they are not all perfect, and that often the FDA should require more testing than is indicated in these documents.

For instance, in the F-136 document to pass a material you have to test two samples. Two. You've got that? If they both pass, material passes. If one fails, though, in typical -- I didn't say that, I was going to say in typical engineering fashion, I didn't say that.

But if one fails, actually it doesn't say if one or more fails then, in fact, what you can do is test two more. If they pass it passes. Now, I just did a simple calculation because I didn't have too much to do.

And I said, what if this material has a failure rate of 50 percent, what if it does? Just, for instance, to pick a number out of the air, which I don't consider very good, you know, 50 percent failure rate.

This testing procedure advocated by ASTM would only pass 32.5 percent of the materials. Do you hear me? Even at a 50 percent failure rate the testing procedure, we would catch actually 67 percent. Is that good? It is not good enough as far as I'm concerned.

So let's be very careful in just saying we are going to use an ASTM procedure, make sure -- and I know that you have good statisticians who can help you with sample sizes, and so on, so that you have actually good evidence.

And I know that you would do that. But I just want to make sure we just don't say we are going to use an ASTM standard, especially ASTM standards that advocate such rotten statistics.

CHAIR YASZEMSKI: Go ahead, Dr. Li.

DR. LI: I'm not quite sure where else to put this comment. Not to beat a dead horse but the one difference, another difference between the polymeric and metal constructs is that I think the polymeric materials, especially the composite ones, are going to be much more notch-sensitive than a metal.

If you put a nick into a relatively thick piece of titanium not much, probably, is going to happen. But if you put a nick into a composite, typically you reduce both the fatigue and fracture life by orders of magnitude.

And, in fact, in one of the publications we've got here, two of the devices out of 74 were broken interoperatively out insertion. Fortunately they noticed.

So that is another thing that is different about the polymeric, and the metal device. The metal device is, essentially, more surgeon proof, if you will, especially if you are going to have additional affixation appliances around that device.

CHAIR YASZEMSKI: Thanks, Dr. Li. Well, we are going to do the specific questions. I would like to ask every panel member, individually, to make a comment on the question. And if you have nothing to add to that question, please just say so, and we will move on to the next person.

We are going to go clockwise and start with a different person each time. And so for the first question I'm going to start with Dr. Naidu, and the next question Dr. Larntz, and the third question Ms. Wells, and then we'll move along around and everybody will get a chance to speak.

The first question is to please discuss the descriptive information and intended use presented in the reclassification identification.

MS. ANDERSON: For your ease I'm just putting up the device description. And if you want to break this question into two, look at the device description first, and then I can switch slides.

CHAIR YASZEMSKI: That will be fine, a little easier to do. And let's give Dr. Naidu a moment to look at the device description and then ask him for comments, and then move on to Dr. Larntz.

DR. NAIDU: I have several issues that I would like to bring up to the attention of the Panel. I think we are talking about two different devices here.

That has been my opinion after looking at all the clinical data, as well, because all the papers that we have been presented to date, numerous results on metallic cages are available.

However, there is paucity of data with regards to polymeric devices. Therefore classifying these into Class II, as a unit, both polymeric and titanium, into Class II category, I have a difficulty not only as a surgeon, but also as a scientist, because these polymeric devices are -- they behave differently.

And all the points that Dr. Li has made are very valid. In addition to not having fracture data, which is a big issue here, the wear of PEEK material, there is no wear data.

I mean, you know, you may have a solid fusion, your clinical results are great. But if the device is broken, and if it does wear in-site, it could resorb the bone again. So it could regress.

Therefore I don't think that we are talking about equal devices here. I think that it may be best to divide these into two separate devices, polymeric devices, and metallic devices, and put one in Class II.

And, I don't know, as far as the other two, as far as the polymeric devices maintain them as Class III, even though the spinal body devices have been approved to date. I mean, I wasn't there on that panel, but I have to speak my mind today.

So I think we are talking about two different things. That is my general comment, that is my general tendency. And I think that in light of the paucity of clinical data presented, I mean, all the industrial presentations today have pointed to metallic cages, more than anything else.

When one asks about polymeric cages, I can't get any intelligent answer. So, therefore, I'm a little frustrated in pulling these two components, and downgrading them both into Class II.

So it is my opinion that it should be divided into two. Thank you.

CHAIR YASZEMSKI: Thanks very much. And I think to make it a little easier to go around, we will go around to everybody on the first part of question one, and we will change the slide to the second part of the question and go around again. Dr. Larntz?

DR. LARNTZ: What is the first part of the question?

CHAIR YASZEMSKI: The one that is up on the screen now.

DR. LARNTZ: The description?

CHAIR YASZEMSKI: Yes, sir.

DR. LARNTZ: I agree with the description. CHAIR YASZEMSKI: Good, thank you. Ms. Wells?

MS. WELLS: I agree with Dr. Naidu.

CHAIR YASZEMSKI: Thanks very much. Ms. Maher?

MS. MAHER: I actually disagree with Dr. Naidu, and I disagree for several reasons. There is a long history of having the same classification for different materials that are being used.

And a good example is vertebral body replacement devices, which are used for almost the identical indication as this, or very similar anyway. They are Class II and it is my understanding, while I'm not in that industry, that they are both polymeric and metal vertebral replacement devices on the market, with not a huge issue with them with fracture or anything else.

And I think, I don't know the right person to call on, in the audience right now, to talk to that, that has polymeric BPRs, or polymeric cages, but I think that would be a good time for somebody to come up and talk to us a little bit about what else is out on the market in Class II.

CHAIR YASZEMSKI: And perhaps we can be thinking about that and go around the table, and then we will call on somebody in the audience at the conclusion of the comments from the Panel.

Dr. Witten, if you have something to comment I would like to ask you, but I am going to come specifically to you at the end, if you could. Dr. Cheng?

DR. CHENG: I just note in the identification of the device, it is, in addressing the manufacturer's concerns, it is inclusive, the statement says including titanium alloys and polymeric, it is not an exclusive statement, and does not state that the cages have to be made of these.

So it is a rather inclusive statement. In fact, from comments today, I wonder if it shouldn't be revised to be more specific. And the second issue is, if one splits the category as Dr. Naidu and, I believe, Dr. Li are suggesting, that essentially means that you are looking at two down classifications into Class II. You would have to address all these questions separately. Is that correct, Dr. Witten?

DR. WITTEN: Yes.

DR. CHENG: Yes, okay.

CHAIR YASZEMSKI: Thank you. Dr. Finnegan?

DR. FINNEGAN: Well, given as how you have us way ahead of schedule, I don't have a problem with dividing into two, and I actually agree with Dr. Naidu. I think that needs to be done.

CHAIR YASZEMSKI: Great, thank you. Dr. Li?

DR. LI: I agree with Dr. Naidu, and also Dr. Cheng, that the description is basically completely open ended in a variety of materials, and basically opens us up to absolutely everything.

And we've only really had two materials that have actually any data, on the titanium alloy and specifically PEEK, that is carbon reinforced. We have no data for any other material, or material combinations.

I think the device description is way too broad.

CHAIR YASZEMSKI: Thank you, Dr. Li. Dr. Diaz?

DR. DIAZ: Well, I hate to be the dissenting person on this table, but I disagree with Dr. Naidu. The ultimate accomplishment of the device will be to achieve fusion. The success of the operation is predicated in the device providing sufficient support to last for long enough for the bone to be formed into a solid union.

The success of the device is not predicated on the device being forever supportive of the body weight. And there is additional bony material that is placed there by the surgeon to achieve that structural stability, ultimately, frequently supplemented by internal fixation and by external forms of support.

So I really do not believe that the fact that one is metal, and the other one is not metal really, ultimately, will give us what we want out of the device. So I think that division is, in theory, good but, in practice, unnecessary.

CHAIR YASZEMSKI: Thank you, Dr. Diaz. Ms. Anderson, can we put up slide two?

MS. ANDERSON: Yes.

DR. LI: While she does that can I ask Dr. Diaz a question?

CHAIR YASZEMSKI: Go ahead, Dr. Li.

DR. LI: In the devices that are polymeric, where you say the bone shares the load with the device if fusion is successful, is there any biomechanical data that tells you how much load is taken by the device, and how much load is taking by the bone that grows in?

DR. DIAZ: If you use just the device alone, in the biomechanical testing that has been done for the polymeric device, the modulus of elasticity is equivalent to cortical bone. And so it is comparable to normal human bone.

The metal is ten times more rigid and, in fact, it is less successful at achieving fusion because it does not allow for sharing of weight, but it prevents the sharing. So if anything you want the device to allow for load sharing, rather than preventing it.

DR. LI: My question is, do you have a sense for how much load is shared, is it ten percent, fifty percent, ninety percent?

DR. DIAZ: I don't think I can answer that.

CHAIR YASZEMSKI: Thank you. We are going to continue on around now with Dr. Naidu, the second part of question one is up on the board for us to read. And I will ask everybody, again, to go around the table and comment on it, if they would like to do so.

DR. NAIDU: I agree with the intended use.

CHAIR YASZEMSKI: Dr. Naidu, thank you. Dr. Larntz?

DR. LARNTZ: I agree.

CHAIR YASZEMSKI: Thank you. Ms. Wells?

MS. WELLS: I agree.

CHAIR YASZEMSKI: Thank you. Ms. Maher?

MS. MAHER: I agree.

CHAIR YASZEMSKI: Thank you. Dr. Cheng?

DR. CHENG: I agree.

CHAIR YASZEMSKI: Thank you. Dr. Finnegan?

DR. FINNEGAN: I have problems with point four. I think that allograft probably should be considered, and I really think that the surgical approach should be left up to the surgeon.

CHAIR YASZEMSKI: Thank you, Dr. Finnegan. Dr. Li?

DR. LI: My only comment, I generally agree, my only comment would be if you are going to do testing on these devices that the loads in the lumbar area are significantly higher than the cervical. So if you are going to do some mechanical testing, to cover all bases, you probably want the mechanical testing loads to be done either appropriate to the device, which means if you test it for cervical use it may, in fact, not survive the lumbar use.

But if you pass the lumbar use it probably would survive the cervical use.

CHAIR YASZEMSKI: Great. Thank you, Dr. Li. Dr. Diaz?

DR. DIAZ: My only concern here is that I think that limiting the location, or the site of application of the device is somewhat restrictive because, basically, what we are doing in practice in surgery is we want to have the availability, and the opportunity to replace as many of these things as need to be replaced.

And restricting the use of these devices to very defined areas I think is artificial. It is not the way medicine is practiced.

CHAIR YASZEMSKI: Thank you, Dr. Diaz. Dr. Cheng?

DR. CHENG: It seems to me, though, that from Dr. Witten's directions that we can only down classify what has already been approved. It doesn't mean you can't do that, it just means when you do it it is an off-label indication for the product. Is that correct?

DR. WITTEN: Well, I would say, additionally, that is right. What you said is correct, and what I said additionally is that this would leave it open to someone to, you know, come in with an application that had a different level, or a different bone use, for example.

But they would need to show that they were substantially equivalent.

DR. CHENG: Right. So although Dr. Diaz' concerns are germane, it doesn't -- I don't think it limits the surgeon.

DR. DIAZ: No, I understand that. I just wanted to make sure that the point was brought up on the table.

CHAIR YASZEMSKI: All right, thanks, Dr. Cheng and Dr. Diaz. Now, because I ask the question of Dr. Witten, the proposal was made before by Ms. Maher that, perhaps, an industry representative would like to speak, and she specifically mentioned Mr. Christianson of OSMA.

Are you here in the audience, Mr. Christianson? And if so, would you like to speak? We welcome you to do so if you would like. And, again, the usual, identify yourself, etcetera, etcetera.

MR. CHRISTIANSON: Thank you, Dr. Yaszemski. I'm Bill Christianson, I'm the vice president of Clinical and Regulatory Affairs with DePuy Spine. And I'm also president of OSMA, the Orthopaedic Surgical Manufacturers Association.

However, to answer the questions that some of the Panel members have raised, I will be answering on behalf of DePuy Spine. My company is the one who is currently the PMA holder for one of the polymeric interbody fusion cages.

And I would like to answer some of the questions that I heard, and perhaps where there might be some open questions, yet. First of all, with regard to testing.

There is an ASTM test standard for interbody fusion cages, it does address static and fatigue testing. And that same standard is applied to polymeric and to metallic cages. So any cage that would be cleared by the FDA would have to pass this FDA test standard.

And there are mechanical engineers at the FDA who sit on these same ASTM committees, so FDA's concerns are reflected in the testing that is done. The testing is very rigorous, fatigue is applied in compression shear so it is worse case scenario for the interbody fusion cages, and the polymeric designs are designed to withstand that.

Even though I agree they have different performance characteristics than metallic cages do, nevertheless they do withstand normal lumbar spinal loads in this ASTM test methodology. And the loading standards are different for the cervical and the lumbar devices.

So FDA recognizes that the loading scenarios are different. Second, I heard multiple questions about particles, and particles being bad, for example. My company performed animal testing before we went into humans with these polymeric cages, sacrificed the animals at 6 months, 12 months, 24 months, had an independent pathologist look at the slides, looking specifically for particulate debris.

While a few particles of debris were found, there was no indication that there was any adverse histological response associated with that. In addition there are several peer review publications, in the literature, on retrieved cages, primarily failed cages.

And the pathologist there does comment on the presence of particulate. And, again, has never noted the, what I presume your concern is, is osteolysis associated with the presence of cages. So there are polymeric and metallic cages out there, particles have been noted in all those instances.

And the type of osteolysis that one sees in hip and knee implants has not been noted to date in the spine. Are there any other particular polymeric related questions that perhaps I could answer, since I'm familiar with the work that my company has done?

CHAIR YASZEMSKI: Thanks, Mr. Christianson. Any panel members have questions for Mr. Christianson? Dr. Finnegan.

DR. FINNEGAN: I have two. Do they look at lymph nodes when they looked at particulate matter?

MR. CHRISTIANSON: Yes, in the animal study that we did, before we went into humans, we did total organ sacrifice. So we looked at all the filter organs, we looked at spleen, liver, and lymph nodes.

And in none of those cases did we find any material outside the immediate region of the interbody fusion devices in the sacrificed animal.

DR. FINNEGAN: And my second one is in your clinical studies do you have posterior fixation with your devices or not?

MR. CHRISTIANSON: For the product that we currently have approved we do have posterior fixation. However, we have two devices in IDE right now that are stand-alone anterior devices. One of the lumbar spine, and one of the cervical spine.

CHAIR YASZEMSKI: Thank you. Dr. Naidu?

DR. NAIDU: When you say particles from retrieved specimens, were these components intact, or were they fractured?

MR. CHRISTIANSON: In the case of the polymeric components they were intact. And I can't recall, in my review of the literature, ever seeing a report of a fractured metallic device.

DR. NAIDU: So they were not fractured polymeric components that were wearing?

MR. CHRISTIANSON: That is correct.

DR. NAIDU: -- particulate debris from an intact component that was retrieved, and you are talking about peripheral particulate debris?

MR. CHRISTIANSON: Yes. There is one report, in the literature, of a fractured particular cage that came from Sweden. These products have been available in Europe since about 1991. And there was a report of one case from Sweden where there was an infection at the treated level, a failure to fuse, and the cage fractured in situ in the post-operative period.

That histologic sample was reviewed by the same pathologist whose report on the retrieval studies, and while there was copious production of particulate debris associated with the fractured cages, he saw only histological signs consistent with the infection, and none that would suggest to him that an osteolytic process, related to the particulate present in that level occurred.

DR. NAIDU: I don't know how you can determine that from a pathological viewpoint because infection in particulate debris you will have white cell infiltration, you will have giant cell -- I don't know how you can make that as a pathological diagnosis, I don't see how you can differentiate the two.

That is the first issue. My second question is, you were talking about static and fatigue testing. We are talking about a different issue, fracture toughness. Is there anything with fracture toughness done on these polymeric components?

MR. CHRISTIANSON: I'm not an engineer, I do know that the static fatigue test is an array that is very similar, that is performed on metallic devices. But I don't know specifically what this fracture toughness standard is.

So, perhaps, that is something that could potentially be developed through the ASTM process.

CHAIR YASZEMSKI: Thank you. Other questions? Dr. Li?

DR. LI: On your instances where you have seen polymeric wear, but no osteolysis, what was the follow-up time on those?

MR. CHRISTIANSON: The animals that we sacrificed were sacrificed at six, twelve, and twenty four months. So twenty four months was the length of follow-up there.

On the retrieved specimens the length of time that I recall, from reading the literature, is anywhere from three to six months at the short end, to somewhere in excess of 36 months.

DR. LI: Because typically, like in a polyethylene case, where there is probably more wear, it takes three to five years for osteolysis to occur. So not too surprising that at short times no osteolysis was visible.

MR. CHRISTIANSON: The IDE subjects from my company were first implanted in '91, and there is a report, in the literature, from the developing surgeon on the ten year follow-up on his particular series of cases.

And, again, he is not reporting any osteolytic activity that he has seen. That is a single surgeon series, however, that is not the whole study.

DR. LI: And your animal test, just for detail, was there a control, for instance polyethylene, where you know you are going to get osteolysis in that same time period?

MR. CHRISTIANSON: There was not. These were consecutive series of animals where the control was allograft bone in this particular series, not polyethylene.

DR. LI: Thank you.

CHAIR YASZEMSKI: Thanks, Mr. Christianson, for your commentary. Dr. Witten, I'm going to ask if I may ask you a question before we ask if we've answered you.

As you have seen, there is a wide spectrum of opinion among the Panel members on question 1 that the FDA has posed to us. The main disagreement appears to be with respect to whether metallic and polymeric devices can be treated the same, or whether they should be separated.

And I'd like to ask your counsel, from the FDA perspective, as to whether should the Panel agree that certain testing, certain controls are necessary, that those controls could they, from the FDA's perspective, be appropriately applied so that devices of all materials are covered, and some don't get treated differently under a blanket decision.

Or might they need to be separated? Because as I understood your charge to us in the beginning, our charge is to asses whether devices can be adequately covered by special controls.

If our concerns about fracture toughness, about wear debris, are concerns that need to be applied to special controls, would the FDA be satisfied if those controls were applied to materials of all compositions?

In other words, would you need to separate? In other words, the controls, we could say the controls need to be made. Perhaps they might not need to be applied to materials that are metallic. But we could suggest to you that the special controls be applied to all material, and then you would have your discretion as to when to invoke them.

And I want a little bit of guidance as to whether this discussion about separation is appropriate from the FDA's perspective, or if we can satisfy your needs by lumping all materials together?

DR. WITTEN: Well, I'm a little confused by the question. But let me try to answer --

CHAIR YASZEMSKI: And if I see that you are answering differently, I'll try to rephrase it a little bit.

DR. WITTEN: What I think you are saying is that if the Panel thinks that the risks, you know, there may be additional risks depending on the materials but thinks these can all be reclassified, and can suggest controls for those risks if, you know, those risks apply to the particular devices can you do that under one classification?

CHAIR YASZEMSKI: That is the question, yes.

DR. WITTEN: Yes, you can do that. Now, if the Panel thinks that that may not be the case and they need to be handled separately then, obviously, you need to separate them.

CHAIR YASZEMSKI: Great, thank you. Having heard that from you, have we adequately discussed question one to the FDA's satisfaction?

DR. WITTEN: Well, I would say yes except for one thing which is we have a considerable respect for your expertise, too, in this area. And if you have any additional comments on this question, or any of the others, we would appreciate hearing those as well.

CHAIR YASZEMSKI: Thank you. My opinion is that there are great differences among materials. However, by articulating those differences we can recommend something to FDA such that special controls can be applied to all classes of materials and that it would be appropriate to keep them together. That would be my opinion.

We would like now to proceed to question number 2. Ms. Anderson? We are going to start this time once it is up, and everybody has had a chance to read it, with Dr. Larntz and continue to go on a clockwise fashion.

Question two, discuss any specific preclinical testing criteria you believe are needed to characterize interbody fusion devices. Dr. Larntz?

DR. LARNTZ: Well, first of all I take the point of view that since this device is very similar to a vertebral body replacement device, that the testing that is done for that device should be the starting point for our testing that is done for this.

So in looking at the 510(k) guidance I would say that you are certainly going to need to do the testing that is labeled there, the fatigue testing, the static testing.

I, of course, have to say, I of course say if you are doing SN curve, and you are only doing it at maximum load, I think that is difficult to get a curve out of that, if you do it at one point. It says to do six samples.

You know what I'm going to say. I'm going to say you are going to have to do more samples than are in here to get a real valid reading on that. But I realize that this is the standard that has been set before. I just don't agree with the standard and the amount of testing that is required.

And I think I've said this before, I will say it again, probably before we are through. But the fatigue testing, the static testing, and the additional testing that is specified for vertebral body replacement, which includes static compression, compression bending, dynamic compression, compression bending, static torsion, dynamic torsion, expulsion, and the exceptions that are listed there.

And I actually, since these devices, my understanding and if I understood Dr. Diaz correctly, these devices are basically the same, or very close to the same devices. So it seems to me that the testing should be the same, or very close to the ones that we already have here.

And I don't have additional ones to add.

CHAIR YASZEMSKI: Great, thank you very much, Dr. Larntz. Ms. Wells?

DR. WITTEN: I have no comment.

CHAIR YASZEMSKI: Thank you. Ms. Maher?

MS. MAHER: I would actually like to agree with Dr. Larntz for one of the first times.

CHAIR YASZEMSKI: Thank you. Dr. Cheng?

DR. CHENG: No, I think the mechanical testing is the issue in the preclinical test.

CHAIR YASZEMSKI: Thank you. Dr. Finnegan?

DR. FINNEGAN: I will agree with whatever Dr. Li --

(Laughter.)

CHAIR YASZEMSKI: Dr. Li, you are up.

DR. LI: With that pressure filled statement -- I think the thing, the specific thing I would like to add is the fracture toughness testing. And I would also -- I don't believe that what I think I read has the worse case scenario for loading in these tests is actually the worse case scenario.

I think the loading and the positioning, I can think of several probably clinically relevant conditions that would present much higher demands to the device than what the test currently asks for. So my two specific would be that -- and, again, this is really not disparaging, in any way, the -- I want to say this many times.

I'm not disparaging, in any way, the current devices that are on the market. I'm just going to assume they work as everybody says. I'm really worried about the next device coming down the pike.

And I think to make sure that we continue to have this excellent result, you are going to need fracture testing, and increase the demands on the actual dynamic testing.

CHAIR YASZEMSKI: May I ask, Dr. Li, what would your opinion be regarding testing for different portions of the spine? Would you suggest, for example, a test that would be adequate and appropriate to serve in the lumbar spine, and have all devices meet that, or would you suggest separate fracture toughness criteria for lumbar and cervical applications?

DR. LI: Well, I guess I can answer that two ways. I would prefer to have separate requirements because I hate to over demand a device. But then if Dr. Diaz wants the option of taking a device that was meant for the cervical area, and using it in the lumbar, then I would just presume that everything should pass the lumbar.

I'm not saying that you would do that, Dr. Diaz, but someone might be tempted to, in fact, use the device in a place that it wasn't intended for.

CHAIR YASZEMSKI: And for these applications, may I ask you one more question, do you feel that the fracture toughness and fatigue testing would be okay, or would you also do the load to failure testing that is currently done, and have the complete series?

DR. LI: I would not take away any resistance test, and I would add the other two tests.

CHAIR YASZEMSKI: Okay, thank you. Dr. Diaz?

DR. DIAZ: I agree with what Dr. Larntz said. I think that basically capsulizes my thinking.

CHAIR YASZEMSKI: Thank you. Dr. Witten have we adequately addressed FDA? Our opinion seems to be more uniform on this, that the existing testing is appropriate, and that the addition of fracture toughness testing would be a recommendation that we would make to FDA.

Have we adequately answered your concerns on question number 2?

DR. WITTEN: Yes. I was just wondering, Dr. Naidu, since we started with Dr. Larntz?

CHAIR YASZEMSKI: I'm sorry, Dr. Naidu, I apologize for not coming back around to you. Dr. Naidu, comments?

DR. NAIDU: Well, I agree with Dr. Li as far as adding the fracture toughness. But the only other issue that I am concerned about is when this device does fracture, the device, the components rubbing on each other becomes a big issue.

Neat PEEK is very soft, and so I think particularly debris also needs to be studied. And neat PEEK is not -- the particulate debris is not benign. And even though the published literature may not state so, it is not benign. It is in my thesis, I can show it to you later.

CHAIR YASZEMSKI: Thank you, Dr. Naidu. Dr. Witten, I will now add, let me ask Dr. Cheng, if Dr. Cheng has a comment. Go ahead, please.

DR. CHENG: I was just thinking about all the discussion we had about the differences in materials, but there hasn't been much discussion about the difference in geometry. And that, of course, makes a big difference in what we've just been talking about.

And so I think that these tests will cover all these issues and perhaps the separation of materials is not as important as we were saying because, obviously, regardless the material is going to have to pass the test.

CHAIR YASZEMSKI: Thanks, Dr. Cheng. Other comments?

(No response.)

CHAIR YASZEMSKI: Dr. Witten, I will append to my prior description of Dr. Naidu's comments that, perhaps, one should consider that if a device fractures, that wear debris tests might be an appropriate part of the test armamentarium.

With that, have we adequately answered FDA's concerns on question number two?

DR. WITTEN: Yes, thank you.

CHAIR YASZEMSKI: Thanks very much. Ms. Anderson, may we ask for question number 3? And we are going to start with Ms. Wells once that is up. And I will try to include Dr. Larntz when I come around.

MS. ANDERSON: I'm going to switch the slides so it presents the risks that we've already identified, so you can just add to them.

CHAIR YASZEMSKI: Okay. Please discuss the risks to health for the intervertebral body fusion device.

MS. ANDERSON: You can go start discussing, and I will switch slides as quickly as I can.

MS. WELLS: At this point, representing the consumer, the issues that were brought up, as far as patient selection was concerned, and as far as clinical satisfaction on the patient end, again, that has a lot to do with the physician and the surgeon, and which device is implanted.

As far as the classification I really don't see -- I don't have any additional comments.

CHAIR YASZEMSKI: Thank you very much. Ms. Maher?

MS. MAHER: I don't have any additional comments at this time.

CHAIR YASZEMSKI: Thank you. Dr. Cheng?

DR. CHENG: I think my only concern is that we have looked at the risks from the papers that have been described, but all of them, the length of follow-up for the length of time that the device has been implanted in their trials, either for the FDA required trials, or other ones.

And so I think there might be some long term ones that we are not looking at. And, as I said earlier, my main concern would be adjacent segment disease. And I have to think, in spite of what Dr. Diaz is trying to reassure me with, he also stated that some devices are more rigid than others.

And, therefore, I have to think that the risk of, if that is clinically significant, then the risk of adjacent segment disease is going to be higher, perhaps with more rigid devices, than with devices that aren't as rigid.

CHAIR YASZEMSKI: Thanks, Dr. Cheng. Dr. Finnegan?

DR. FINNEGAN: I'm going to pick up on something that Ms. Wells said. I think that the surgeon is really important in this, both for patient selection, which has been discussed, and also the technique.

And I understand that training is "a resource drain on the company", but in Texas we call that cow paddies, because they get major benefits from contact with surgeons, contact with patients, everything else.

So some form of company contribution to training until this is a regular part, spinal surgery training I think would be appropriate.

CHAIR YASZEMSKI: Would you think it appropriate that any such training be required, or should it be at the discretion of the surgeon and/or the company?

In other words, if the company wants to make it available, great. And if the surgeon wants to take it, great. Or would you want anything more than that?

DR. FINNEGAN: I agree that NASS and the Academy, and a few other groups have facilities to do this. This is really expensive, especially if you go to cadaveric work. And, therefore, my recommendation would be that the companies assist in educating the spinal population.

And I would, actually, suggest for this particular thing, because it is different, and it technically can be catastrophic, that it be recommended.

CHAIR YASZEMSKI: Thank you. Dr. Li?

DR. LI: I have nothing to add to that list of risks.

CHAIR YASZEMSKI: Thanks very much. Dr. Diaz?

DR. DIAZ: I agree wholeheartedly with Dr. Finnegan. I would be, perhaps, a little bit more emphatic that it is the responsibility, in a way, of the companies to bring all the people who want to complete this type of surgical procedure to really be, if not supported, at least somehow assisted in acquiring the education.

It is ultimately to their benefit to see that it gets done properly.

CHAIR YASZEMSKI: Thank you. Dr. Diaz, may I ask you an additional question? Could I ask you to comment on Dr. Cheng's potential concern about adjacent segment disease?

DR. DIAZ: Yes. I still go back to the same statement I made earlier. The end result is going to be fusion, and the fusion is going to be achieved by either device.

The effect on adjacent segment disease is not immediate, it is a process that evolves over the course of months or years. And so if that is the way it is going to happen, it usually will happen after the fusion is complete irrespective of whether the cage is metal or PEEK.

DR. TROMANHAUSER: Thank you. Dr. Naidu?

DR. NAIDU: All my concerns have been expressed previously, I have nothing else to add.

CHAIR YASZEMSKI: Thank you. Dr. Larntz?

DR. LARNTZ: No additional comments.

CHAIR YASZEMSKI: Thanks very much. Dr. Witten, there again seems to be a convergence of opinion on question number 3, that the surgeon is a very important link here, and that it would be good if some attention were paid to training him or her, and providing education in the use of these devices.

A concern was brought up about the potential for adjacent segment disease. And the idea was put forth that that is going to occur after a fusion, most likely, and be little effected by the properties of the device that is used to achieve that fusion.

Have we had adequate discussion on this issue, from FDA's perspective?

DR. WITTEN: Yes, thanks.

CHAIR YASZEMSKI: Thanks very much. We are going to go to question number 4 now.

MS. ANDERSON: Actually question number 4 is so closely related to question number 3 I believe you've already answered it.

CHAIR YASZEMSKI: Then I will go right to Dr. Witten. Dr. Witten, question 4, discuss any other risks to health.

DR. WITTEN: I was thinking that you had answered that.

CHAIR YASZEMSKI: Have we had an adequate discussion to satisfy FDA, or should we go around the table one more time?

DR. WITTEN: I think it would be -- you might just ask if anybody has anything to add, because some people were discussing these risks, and some people were discussing those risks.

CHAIR YASZEMSKI: So asked. Does anybody want to talk about anything else related to health?

(No response.)

CHAIR YASZEMSKI: Seeing none, Dr. Witten, have we adequately discussed this? Ms. Anderson, can we go to question five?

MS. ANDERSON: You like watching me go up and down.

CHAIR YASZEMSKI: The question, as she is putting it up is, do you believe special controls can be developed to adequately control the risks associated with this device? Ms. Maher?

MS. MAHER: I believe that the special controls in the form of a guidance document similar to the guidance document for vertebral replacement devices would be sufficient to control the risks.

CHAIR YASZEMSKI: Thank you, Ms. Maher. Dr. Cheng?

DR. CHENG: I do think special controls can be enacted but I think the -- maybe it is more a process issue, not germane to just -- not limited to just this device. And that is the MDR, for so many of the devices that we implant, as surgeons, and we see the complications related to some of them years later.

I personally have done many operations where I am not -- I don't actually know if I had to fill out an MDR on a certain device. So there needs to be an improvement in the MDR process because the current process, as it exists, is useless.

And it does not achieve the objective that is stated.

CHAIR YASZEMSKI: Thanks, Dr. Cheng. Dr. Finnegan?

DR. FINNEGAN: I'm going to be a royal pain, again. Dr. Witten, I have a question. How come GE knows I have their dishwasher, but nobody in this room, sitting in the audience, knows that I have a plate?

I mean, technology now is such that device tracking should be a no-brainer. So I think that we need to look at device tracking, specially with these devices.

DR. WITTEN: And when you say tracking do you mean that the sponsor should be able to track the devices?

DR. FINNEGAN: Somebody needs to know, I mean, my question is basically GE knows I have their dishwasher. But you don't know I have a plate in my arm. And my question is, why?

CHAIR YASZEMSKI: Dr. Witten, if you want to think about that while we go around the room, fine. If you want to answer it now, go ahead.

DR. WITTEN: Well, I'll just say that if there is some -- I can't really answer it generally. But if there is something specific that you think that is needed here, you know, we would certainly be interested in knowing what that was, and why, for this particular group of devices.

DR. FINNEGAN: Well, I guess we could start with this particular group of devices. Because if, as the concern is, there is wear particles, and we see in ten years that we have huge osteolysis and some cord problems, then a lot of people are going to be unhappy.

So I think the risks here are potentially significant. And I think the reason for having a device data base, and device tracking, is because right now surgeons don't, you know, don't always know. Somebody has to go back through the chart and see if the patient has the device.

So that, basically, it is recall long-term complications. And there are phenomenal examples. There are the pores that came off the first Hungerford micropores. There is the polyethylene in acetabular components.

I mean, there is just -- we have been through this so many times, and the information technology now is such that we really probably need to take this seriously.

CHAIR YASZEMSKI: Thanks, Dr. Finnegan. Dr. Li?

DR. LI: Yes, I agree with Dr. Finnegan. We are asked -- this reclassification is a little different than the previous ones I have been on, I have been on the bone cement, and the metal on metal one, where there actually was a much longer time period of clinical follow-up, you know, some times 20 or 30 years in the case of bone cement.

But here we are asked, actually, to reclassify a device that I think the longest follow-up I saw on one of our papers was four years, but that was only 11 out of 947 patients.

So the vast majority of the data is two years and less. Now, it just raises a question about what the long term -- so I don't really know what special control you could add, other than if you could follow these patients up somehow.

The other issue that, again, I also don't know what to do about, is that these are fusion devices with no laboratory test for fusion. So these devices are, apparently, working great the way they are.

Again, my worry is in the future. I don't know what special control that would be, because there is no laboratory model for fusion, not that I can think of, or that I'm aware of.

So the two worries are that we don't know what the long term results are, but I don't know what the special control would be. And we don't have any way to measure fusion. But, again, I don't know what the special control would be.

And perhaps a way around this issue of do you test everything the same, is to have two guidance documents. In other words, you could have -- because I would hate to test a material like a metal for problems that are only going to happen on a polymer. I don't think that is actually reasonable.

So maybe the solution around this is to have two guidance documents, one for a metallic component, and one for a non-metallic, for instance.

CHAIR YASZEMSKI: And then we have the ability to suggest to FDA that they do that.

DR. LI: Right.

CHAIR YASZEMSKI: Thanks, Dr. Li. Dr. Diaz?

DR. DIAZ: In general I agree with the comment of having the same standards that are used for the interbody vertebral replacements as the basic process of assessment.

In regard to Dr. Finnegan's comment about tracking of these devices, by the company, being an attorney as well, and knowing HIPAA, currently HIPAA prohibits any company having any clinical information pertinent to the patient.

And perhaps we need to go back to HIPAA and change that. But until that is changed I don't think we can ask the companies to provide us with tracking of devices that they are not legally allowed to get.

And the third comment is the issue of these being fusion devices. They are not fusion devices, they are spacers. The fusion devices is the autograft, or the allograft that is placed to exert the fusion and become osteo-conductive for the body to eventually complete the fusion.

The device is purely a structural gadget that allows the space to remain the same until the body forms bone osteoblasts and completes the process of fusion. The device doesn't do the fusion.

DR. LI: Can I ask a question of Dr. Diaz?

CHAIR YASZEMSKI: Go ahead, Dr. Li.

DR. LI: Do you believe, then, that the design of the material has nothing to do with fusion, then?

DR. DIAZ: No, that is not what I said. In the prior comments I have indicated that the metal device is a load bearing. So it is less likely to allow a fusion than the load sharing that the PEEK allows.

It is more successful with the load sharing device, than with the load bearing. But the fusion itself is really not the result of the device, it is the result of the available osteoconductive tissue that you put in between the device and the two bony surfaces, and ultimately the ability of the bone, or the human body to complete the fusion.

DR. LI: Not to quibble over nomenclature a little bit. So what you are telling me is that the modulus of the material plays a role in the fusion?

DR. DIAZ: It facilitates it greatly, yes.

DR. LI: Correct. So that tells me that there is a material property, or design aspect of the device that influences the amount of fusion.

For instance, you would probably be against me giving you a cage with a higher modulus than titanium? As an example.

DR. DIAZ: Well, in general terms you are correct. In the detail of how this happens is, perhaps, minuscule in reality, and probably beyond the scope of what we are discussing.

CHAIR YASZEMSKI: Thank you, Dr. Diaz. Dr. Naidu?

DR. NAIDU: All of my thought have been discussed adequately.

CHAIR YASZEMSKI: Thank you, Dr. Naidu. Dr. Larntz?

DR. LARNTZ: This issue is difficult for me because I look at the examples we have, and I look -- the examples we have are actually, we have all successful examples. And I'd like to know if these tests can pick out a cage that will fail.

And I don't know that because I don't have examples of failed cages, and their mechanical, and pre-clinical, and all testing. So it is a case where we are trying to pick out, it is like all the people with prostate cancer are males, so male must be the reason, you know?

So -- and it is to a certain extent. There is other problems there, to. So I don't, I have real trouble thinking of what is going to be predictive of failure. And I know, I think I'm in a position where I'm going to say I don't have anything to add, except I'm actually disturbed, if I might say, that the vertebral body replacement was Class II, when this was Class III.

If I heard the comment correctly, it is a more risky replacement than this one, if I heard the comment correctly this morning. Well, that is a different issue, I guess.

So I guess I don't have anything to add. I worry about not suggesting clinical data of some sort, as a -- it is always a possibility, I think. And it is a possibility even with 510(k) to suggest clinical data.

And with respect to fusion, the way we measure fusion is we put these devices in people, and then we do some flexion extension, I'm sorry, CTs, or whatever we do, okay? But that takes -- well, some people say it takes six months if you do it in the cervical, and a year in the lumbar.

But the FDA seems to say two years, right? Isn't that what we've always had, I think? And so if they are really fusion devices, then the only way to test for fusion, that I know of, is clinically.

And so I'm torn between saying, gee, these things seem to be pretty safe, everything seems to be pretty good. But, again, I don't know what the failed devices are like. And then saying, it seems to me that there is a potential for devices not working, that we probably missed, by the kind of testing that we have.

So I guess I will stop with those general comments that don't add anything.

CHAIR YASZEMSKI: Thank you, Dr. Larntz. Ms. Wells?

MS. WELLS: I have no additional comments.

CHAIR YASZEMSKI: We are going to go, we are going to end where we started, with Ms. Maher.

MS. MAHER: I have a few additional comments to make. First, regarding vertebral body replacement devices, versus cages. The cages first came on the market after 1976, so they would automatically have gone into Class III, while the other product was a Class II.

I believe that the interbody replacement device gives us further evidence as to why this device could, very successfully, be placed into Class III, and the risks ameliorated by the special controls, such as already exists for the vertebral body replacement.

Regarding device tracking, as a patient, most patients don't want to be tracked. And, for instance, GE knows where your dishwasher is. They do not know where it is if you move. They know where it is, they don't know where you have gone. These devices traVel with these patients.

Device tracking is a very, very difficult thing to do, to maintain where these patients are and, I think, should only be done in cases where there is a sever risk to patient health, to be able to find these patients quickly, such as a heart valve.

I would have a hard time supporting any other reason for device tracking. Thank you.

CHAIR YASZEMSKI: Thanks, Ms. Maher. Dr. Witten, again we have general consensus on this issue, that perhaps special controls can be put into place and the suggestion was made that a potential way to do that may be separate guidance documents for different types of device within the general Class II classification.

There was some concern given about long term follow-up, some concerns about tracking, on both sides. Have we, adequately, discussed this, from your perspective at FDA?

DR. WITTEN: Yes, thanks.

CHAIR YASZEMSKI: Thanks so much. What I would like to suggest that we do now is break for lunch. It is almost 20 minutes after 12. Perhaps we can take about 45, 50 minutes or so, and try to get back about 1 o'clock.

We will start, when we come back, filling out the questionnaire and supplemental data sheet, and then we will proceed to a vote.

Mr. Melkerson, do you have a comment?

(No response.)

CHAIR YASZEMSKI: Okay, let's break for lunch now, for 45 minutes.

(Whereupon, at 12:19 p.m., the above-entitled matter was recessed for lunch.)

A-F-T-E-R-N-O-O-N S-E-S-S-I-O-N

1:09 p.m.

CHAIR YASZEMSKI: I'd like to call the meeting back to order. Now that we've addressed the FDA's questions, we will complete the classification questionnaire, and the supplemental data sheet.

Ms. Marjorie Shulman, of the Office of Device Evaluation, will assist us, as we go along. Thank you.

After Panel discussion of each question, I will note our answer for each blank on the data sheet, and Ms. Shulman will record it on the overhead for us. And I think Ms. Anderson will actually do that.

We will vote on the completed questionnaire, and supplemental data sheet, and it will become the Panel's recommendation to the FDA. I'm going to ask about questions regarding this procedure in a moment.

I want to ask Ms. Maher, however, for one more comment before we move to this. Ms. Maher?

MS. MAHER: Thank you. I actually have three comments because I had time, over lunch, to do a little bit of thinking. First of all I was thinking of the other fusion devices that are out on the market.

And, Dr. Cheng, the issues you brought up on the level above, and degenerative disc disease, etcetera. And those other devices are all Class II, and all raise the same issue, or potential of issues that are there.

So I'm not sure it is an additional risk that these devices have, that the other cages, or rods on the market don't already have. Second, VPRs are made out of PEEK as well. As a matter of fact, VPR is made out of the same material as their cage, and they are not suffering any of the issues that we have brought up, and they are Class II and did all the testing that was disclosed, earlier, for that product. So, again, I think that alleviates some of the issues we've discussed on additional testing. Third, and this is probably the most important point, is the FDA on a very regular basis, deals with 510(k)s that are the next step, the next step of a design, the next -- where it is going.

And they are very skilled at having us give them all the information that exists in the guidance document, looking at it and saying, Sally, this is a different indication, you need to give me more information.

The new more information may be animal testing, it may be bench testing, and it may be clinical testing. Or the answer may be, Sally, this is so new you need to go do a PMA.

It is just something that they are skilled at, and it has to be done on a case by case basis, as they are moving forward, not something that I think we, as a panel, can sit here and hypothesize what is going to happen two, three years, down the road from there.

So I just sort of wanted to summarize that all together and express my concern that we have been going off on these tangents when, in fact, these devices really do, from the risk and benefit of them, belong in a Class II, with the FDA there to give the oversight when the 510(k)s come in to determine if that is appropriate for that specific device, and that specific indication and material that they are there for. Thank you.

CHAIR YASZEMSKI: Thank you, Ms. Maher. Ms. Shulman?

MS. SHULMAN: Good afternoon. First I just want to read a couple of statements. The general device questionnaire is designed to aid in the determination of a proper class for all medical devices, and a medical device shall be placed in the lowest class which will provide adequate controls to reasonably assure the safety and effectiveness of the device.

And the first three questions, questions 1, 2, and 3, pertain to the degree of risk of the device, and can be answered broadly. So with that, we can start.

We will start, everyone will have to fill out their own form. If you can please put your name on the top, and today's date, and all. And we will collect everyone's form at the end. And there will be one main form for the vote.

CHAIR YASZEMSKI: Thank you. So let's move, are we ready to move to question 1? Is the device life -- how about I turn it to you and let you be the reader, if that would be okay with you?

MS. SHULMAN: That is fine. Number one, is the device life sustaining, or life supporting?

CHAIR YASZEMSKI: Dr. Cheng, how about we start with you this time?

DR. CHENG: No.

DR. FINNEGAN: No.

DR. LI: No.

DR. DIAZ: No.

DR. LARNTZ: No.

CHAIR YASZEMSKI: Dr. Naidu?

DR. NAIDU: No.

CHAIR YASZEMSKI: We have no as the answer for question one. Question 2?

MS. SHULMAN: Question 2, is the device for use which is of substantial importance in preventing impairment of human health?

CHAIR YASZEMSKI: Dr. Finnegan?

DR. FINNEGAN: Yes.

CHAIR YASZEMSKI: Dr. Li?

DR. LI: Yes.

DR. DIAZ: Yes.

CHAIR YASZEMSKI: Dr. Naidu?

DR. NAIDU: Yes.

DR. LARNTZ: Yes.

CHAIR YASZEMSKI: Dr. Cheng?

DR. CHENG: I said no, I read this as preventing impairment. Is this preventing or treating impairment? Maybe that is why I read it --

CHAIR YASZEMSKI: Shall we have discussion, or a point of order? If there is general agreement I might make a motion that we accept the yes, and ask the person who voted no, in this case Dr. Cheng, if you would be okay with a yes vote from the Panel on this?

DR. CHENG: It is perfectly fine. I just was explaining why I voted no.

CHAIR YASZEMSKI: Thanks so much. We, as a panel, will fill in yes to question number 2. Number 3?

MS. SHULMAN: Number 3, does the device present a potential unreasonable risk of illness or injury?

CHAIR YASZEMSKI: Dr. Li?

DR. LI: Is this the device of the ones that we have been asked to review? Then the answer is no.

DR. DIAZ: No.

CHAIR YASZEMSKI: I'm sorry, I was not paying attention. Go ahead, Dr. Li, I didn't get your answer.

DR. LI: I said no, if we are talking about the devices we got data for.

CHAIR YASZEMSKI: Thank you. Dr. Diaz?

DR. DIAZ: No.

CHAIR YASZEMSKI: Dr. Naidu?

DR. NAIDU: No.

CHAIR YASZEMSKI: Dr. Larntz?

DR. LARNTZ: No.

CHAIR YASZEMSKI: Dr. Cheng?

DR. CHENG: No.

CHAIR YASZEMSKI: Dr. Finnegan?

DR. FINNEGAN: Maybe.

CHAIR YASZEMSKI: And for the point of filling out the --

DR. FINNEGAN: I will accept no.

CHAIR YASZEMSKI: -- would you be okay with no? Okay. We are going to fill out no to number 3.

DR. FINNEGAN: Okay.

CHAIR YASZEMSKI: Ms. Shulman?

MS. SHULMAN: Number 4, did you answer yes to any of the above questions, that answer is yes, so then we would go to number 6, we would skip number 5.

Number 6, is there sufficient information to establish special controls, in addition to the general controls, to provide reasonable assurance of safety and effectiveness?

CHAIR YASZEMSKI: Dr. Diaz?

DR. DIAZ: Yes.

CHAIR YASZEMSKI: Dr. Naidu?

DR. NAIDU: Yes for metallic, no for polymeric.

CHAIR YASZEMSKI: Dr. Larntz?

DR. LARNTZ: Yes.

CHAIR YASZEMSKI: Dr. Cheng, whenever you are ready?

DR. CHENG: Sorry, no.

CHAIR YASZEMSKI: Dr. Finnegan?

DR. FINNEGAN: I actually agree with Dr. Naidu, yes and no.

DR. LI: Same answer.

CHAIR YASZEMSKI: Yes and no. Okay, well, this is a --

DR. DIAZ: Maybe we need a point of clarification here.

CHAIR YASZEMSKI: Okay.

DR. DIAZ: Does this question mean to ask general controls in and of themselves, alone, or sufficient?

CHAIR YASZEMSKI: No, what this says is that do we feel that we can implement special controls so that these devices will be safe and effective? If we feel that special controls, in addition to the general controls, which would exist if it were a Class I, if we feel that special controls cannot be put in place, that would make it safe and effective, then it remains in Class III and we are done.

If we feel that special controls, be they for the devices all considered together, or the devices if we look at metal and polymeric separately. If we feel that we can control the safety and effectiveness by suggesting to the FDA special controls on these devices, then the answer to this has to be that we say yes, and we move on to discussing those special controls.

DR. CHENG: I'm sorry, I read the wrong question. The answer to number 6, in my opinion, is yes.

CHAIR YASZEMSKI: Well, we have some yeses and some combination yes and nos. I'm going to suggest, unless there is someone who strongly disagrees, that we answer this yes, so that we can discuss those special controls, and then we will vote on those.

Any disagreement with me putting yes down for this?

(No response.)

CHAIR YASZEMSKI: We are going to put yes to number 6. Ms. Shulman?

MS. SHULMAN: Number 7, if there is sufficient information to establish special controls to provide reasonable assurance of safety and effectiveness, identify the special controls needed to provide the reasonable assurance for Class II devices.

CHAIR YASZEMSKI: Dr. Naidu, I'm going to start with you, and you may, these special controls may be special controls that you apply to the class of devices, be they metal or polymeric, or they may be special controls that are different for the polymeric devices, or the metal devices, as you see fit.

So I will ask you what you think they are.

DR. NAIDU: You mean pick one or more, is that what you are asking me?

CHAIR YASZEMSKI: Yes, sir.

DR. NAIDU: Guidance document, performance standards, I'm not sure how practical device tracking is, but it would be nice to have that as well, and testing guidelines. All of them.

CHAIR YASZEMSKI: Okay, thank you. Dr. Larntz?

DR. LARNTZ: I think special controls can be implemented using a guidance document.

CHAIR YASZEMSKI: Thank you. Dr. Cheng?

DR. CHENG: I said yes to guidance document, and I think device tracking is very important. There is no way we can predict what will happen in the future, and if some unknown complication develops that is the only way we can either identify it, find it, and then notify the appropriate individuals.

And then testing guidelines, according to the fatigue fracture, testing that we -- I'm sorry, not fatigue, fracture testing we were just talking about earlier this morning.

CHAIR YASZEMSKI: Thank you. Dr. Finnegan?

DR. FINNEGAN: I would agree with Dr. Naidu's vote.

CHAIR YASZEMSKI: And so that is for all four?

DR. FINNEGAN: Yes.

CHAIR YASZEMSKI: Dr. Li?

DR. LI: I would be for guidance document, testing guidelines. If I could figure out a way to do device tracking I would suggest that. The only other thing I will raise, I don't really know how to work this in, also a study of retrieved devices.

I mean, one of our questions is really what is the failure mode, if any, specially in the polymeric devices. But we have very little, if any, analysis of retrieved devices.

So, for instance, a study of 100 retrieved devices may show no signs of fracture and fatigue, even in large heavy occupations, in which case that would go a long way to alleviate our concerns.

DR. TROMANHAUSER: Thank you.

DR. LI: My answer is retrieval analysis.

CHAIR YASZEMSKI: Dr. Diaz?

DR. DIAZ: I would go along with the guidance document, the performance standards, the testing guidelines. And I think the idea that Dr. Li just brought up is actually a very good one. It would be very simple to retrieve those devices and subject them to testing again. So I would add that, also.

CHAIR YASZEMSKI: Thank you. And for point of clarification, could we fit study, retrieval analysis study in one of the testing, or shall we put that in other?

MS. SHULMAN: Other.

CHAIR YASZEMSKI: Okay, so we have a vote for other, or a suggestion for other. I think that to fill these out we clearly are going to have to make recommendations to FDA as to what we would consider in a guidance document, in a performance standard, for device tracking, etcetera.

But I think we can get to the detail after we have completed the sheet. So I think we are going to have to come back to this, unless you suggest we flesh out the details of these, at the present time?

MS. SHULMAN: Not necessarily all the details, but we do have to flesh out the performance standard versus guidance document. Remember, the performance standard is the rule making, and the guidance document is --

CHAIR YASZEMSKI: That is a good point. For those three of the voting members who voted for performance standard, would you feel that your concerns could be met if the items you would put in a performance standard were put into a guidance document? Comments?

DR. NAIDU: Yes, that should be reasonable.

DR. FINNEGAN: I'm not sure, because we go from sort of regulated to, you know, if the weather is right, and you feel like it. And that is a little concerning.

MS. MAHER: May I make a comment on that, please?

CHAIR YASZEMSKI: Yes.

MS. MAHER: Sally Maher. I actually think the guidance document is the most suitable way to go. One of the problems, if you were to try and go performance standard are that it will take a long time for it to be implemented, goes through notice and comment rulemaking.

It becomes almost like an act of God that you must do, which wouldn't allow any growth in this technology, or industry, at all. When you say, well, guidance documents whether you want to do it or not, that is really not a true statement.

The fact of the matter is, from an industry point of view, we either follow the guidance document to make sure that we can answer the questions, and even then, quite honestly, the FDA will come back and ask us for significant more information, because our issue is a little outside the guidance document.

Or we write a very detailed rationale explaining why the guidance document is not applicable to our device because of a different change in the technology to take it to the next step, and then would provide testing or equivalent information that will support it.

When you go to performance standards what is going to happen is we are going to tell them what we think it needs to say. They are going to, eventually, enact it somewhat like an act of God that will become a rule that happens. And it will never change, and you will never see any advances in this technology, at all.

I would also like to make a comment on this device tracking concept. I'm not sure why we want to hold the Class II devices which, as we've discussed, are very similar to vertebral body replacement devices that are already out there in Class II, to a significantly higher standard than they currently are as Class III, or than the DBRs are at this time.

So I understand some of the concerns that I'm hearing, but I'm not sure that you all understand the implications of what you are asking for. And I honestly believe that a guidance document that sets out the type of testing that we would like to see, the labeling that needs to be there, etcetera, is really the best way to go.

Retrieval of cages when they are explanted, that is great if you can get them back. You don't always get them back, they come back some times, they don't come back other times.

Many times if there is something that has gone on the hospital will maintain them, because there is litigation that might or might not be involved. I'm not sure that will show a lot of information.

But I know, at least on the joint side, there are people that do analysis of retrieved joints on a regular basis. But it is not a requirement for the industry to get them back. And I don't see how you could require the industry to get a cage back, after it has been explanted.

I just don't see how it can happen. The industry doesn't know when you've explanted a cage, necessarily. So I'm having a hard time seeing how that could happen.

CHAIR YASZEMSKI: May I ask, Dr. Witten, for clarification on this, with respect to Dr. Finnegan's concern, that if it is in a guidance document the industry people can do or not do it at their discretion.

Is that true, or is it a guidance document that still allows the FDA to insist on certain things being done prior to giving a clearance? Can we have clarification on that, so that we can flesh out these two?

DR. WITTEN: Well, what a guidance document does is it will -- it will describe what the risks are and identify a number of ways in which the sponsor of the product can do testing to address those risks.

I mean, there is other things, too, like device description, and so we certainly would look at all -- if the sponsor gives us an application, we certainly would look at all the elements.

And I think the way we look at it is it gives a path to a sponsor for being able to get to market that, you know, this is sort of a recipe to do your testing that we can look at and we will have a good understanding for comparison.

It does leave open, to a sponsor, to provide some alternative demonstration of safety, or effectiveness, safety and effectiveness of their product.

So I don't think it is -- I would say it gives some flexibility in the sense that the sponsor doesn't have to follow exactly that method in order to demonstrate the safety and effectiveness of their product.

But on the other hand I wouldn't say it allows them to just do anything, or give us anything they want. Now, a performance standard, of which there is only one, as far as I know, in the history of FDA, just to give you some idea of performance standards.

If you know there is something about the product that you know that to be a safe and effective product, that it must, under the following test conditions, for example, have exactly the following results. And that would be the case for performance standard.

So I think that clarifies the --

CHAIR YASZEMSKI: That does, thanks.

DR. WITTEN: And then for tracking, I just will say it is correct that these products aren't currently being tracked to the patient as Class III devices, and that the other spinal implants are also not currently tracked devices.

So if it is something you are recommending, I think it would be helpful for us to have an understanding of what, in this case, we are looking for. Or if it is a general statement that we think is a general matter of policy, FDA should track all implants.

In other words, is there something specific here that we need.

CHAIR YASZEMSKI: Thank you, Dr. Witten. Dr. Cheng?

DR. CHENG: Well, the answer to that question to clarify about the device tracking, which I mentioned and others did, I think it should be tracked to the patient. I don't think there is anything specific to this device, as opposed to other devices.

But I think the investment, given our current technology right now, has come down in terms of requiring one to track to the patient. And the reason to do it, Sally, is because if we had known about problems related to certain devices we could have prevented the continued implantation of those devices and saved untold costs, financial, physical, emotionally, of patients in terms of fractured T-28 stems, catastrophic failure of polyethylene cups, those are just two examples.

History is replete with examples of situations where our sensitivity of any monitoring to detect a problem in an implant or device, is not sensitive enough to pick it up early enough so that patients are not continually harmed by the device.

If a surgeon didn't notice the problem related to the sulzer cup problem, who knows how long it would have taken before it would have been noticed? It was not picked up by MDRs, or anything else.

Most of this comes about because physicians eventually report it in their meetings. But if there was a device tracking, and registry maintained by manufacturers, or by the guidance, I'm not saying industry has to necessarily do it.

Then I think we would have noticed at a much earlier stage in the process, problems, and prevented those problems from continuing to replicate themselves.

MS. MAHER: So then I would guess it is your opinion that all implants should be tracked?

DR. CHENG: That is correct.

MS. MAHER: So it is not specifically relevant to cages, it is just all implants?

DR. CHENG: Right.

CHAIR YASZEMSKI: I would say through this discussion a great part of the value of what happens here is the discussion that FDA hears. They hear both sides of it, and then they will act based upon the pros and cons that are put before them.

For purposes here I'm going to make a suggestion which we, of course, will vote on, and all the voting members will get a vote. But I'm going to make a suggestion that I'm hearing that we should check device tracking, on number 7, we should check testing guidelines.

I will suggest that we check the guidance document, and not performance standards, based upon the discussion and clarification that Dr. Witten has given us, and that we include those things we wanted to put in performance standards, in guidance document. And then we move on to number 8. I also note that the study of the retrieved devices, if we include it, will have to go under other. And I think that I would like to ask Dr. Li how -- we want to be careful that we do everything that must be done to make it safe and effective.

But also look at the other side which may be that it may be practically difficult to get retrieved devices back to the company. I would like to hear your thoughts as to whether perhaps we could put study of retrieved devices as a recommendation under testing guidelines, or should put it as a separate requirement that we would ask FDA to implement under other.

Dr. Li, your thoughts, pluses and minuses on that?

DR. LI: Let me answer the practicality question first, because I think it is a good one. Our lab, when I was in special surgery, and continue now, has been doing retrieved implants for 15 years.

In special surgery we collected over 10,000 devices, over that period of time. And my experience is retrieval analysis is as successful as you work at it.

So if you actually establish a program for retrieved devices, in fact surgeons we found are more than glad to send us all their retrieve devices. As far as what companies can do, there is one company in the breast implant business, that actually gives you a rebate on a revision.

So, in other words, if you -- if someone comes in with a damaged breast implant, and they need a revision, if you send in the one that was broken, if will, they will actually give the hospital, or the surgeon, a rebate on the device.

Now, I'm not suggesting that this be done here. But I am suggesting that the retrieval analysis is as successful as you want it to be. So I think from a practical standpoint the details could be worked out, either with the company, or with an independent lab, or independent hospitals, I think that can be done.

And, again, I don't think you need tens or thousands to get a good picture on performance. Now, as far as where you put it, under testing guidelines, or as other, I'm not sure I understand the real difference.

CHAIR YASZEMSKI: I'm not sure it matters, either. And I was going to suggest, just for ease of putting things together, that we include it as one of the testing guidelines.

DR. LI: I have no problem with that, if there is no difference.

CHAIR YASZEMSKI: Okay. I will include among testing guidelines we are going to suggest, as part of the vote, to include analysis of retrieved specimens. Ms. Shulman, may we move on to number 8?

MS. SHULMAN: Did you want to vote on number 7, that that is what everyone agreed upon?

CHAIR YASZEMSKI: Okay. I will ask it this way. Are there any concerns raised by anybody that we do something other than check guidance document, device tracking, and testing guidelines, to include study of retrieved devices under number 7? Dr. Larntz.

DR. LARNTZ: I just want to clarify, on the analysis of retrieved devices, this has to come after approval? I mean, this is a post-market, post-approval requirement for these devices?

CHAIR YASZEMSKI: Dr. Witten, I'm not sure I know how to answer that. Can I get your interpretation of that question?

DR. WITTEN: Well, I think your recommendation could be whatever you recommend. But if you leave it open then probably one of the things we would explore would be if it fits under our discretionary post-market surveillance program, which is mostly for studies.

I don't know that we have ever done this. But -- or you could make a recommendation that people study these, and do this prior to market. I'm not sure exactly how they would do that, though.

CHAIR YASZEMSKI: And, again, I will remind all of us that what we vote on is not binding on FDA, and they need to hear both sides of any arguments for the things that we vote on.

And at the end, when we have a completed document, and we vote on that document, regardless of what the vote is, whether it is unanimous one way or the other, or whether it is split, we will go around the table and ask everybody to explain why they voted the way they did, and that message does get to FDA as they make their decisions with the companies. Dr. Li?

DR. LI: I'd like to explain, this is what I had in my mind for the purpose of the retrieval analysis, is that I think that one of the shortcomings, if you will, in this product is that there is no long term data.

In other words, the longest term data of any kind of significance is about two years. And we have a smattering of data out maybe to four years. So we don't really know what the long term performance is in any kind of organized study.

So the retrieval analysis, in my own conscience, is a way that I could essentially make myself feel better that, in fact, things are not going in the worse possible way, and they would validate the excellent performance that we seem to be getting for the current devices, and it also establishes a baseline for future devices.

So that is my reason for doing the retrieval analysis. I had not intended it to be a pre-approval condition.

MS. MAHER: Had you intended it to be for the life of the product, forever more the companies must get these back and do an analysis? Because I think that is what --

DR. LI: No, I think --

MS. MAHER: -- very overburdensome. The other thing I would question is, you say we don't have much history. But, again, these are very, very similar to vertebral body replacement devices, and there is a fairly long history of those being out there.

So I would say that there is actually more of a history than we are actually alleging. But that being said I think we need to make it clear to the FDA, if you are talking about this retrieval, that it is a limited number for a limited time, not forever and always, once you have this device in the market you must try to get every device back, because that would be impossible.

DR. LI: Well, I'm not sure about the impossible part but it wasn't -- it was not my intent to add a burden for the company to follow all these devices forever. And I think our history in studying retrieved analysis actually says that you don't have to do that to determine the failure mechanisms and modes of these devices.

In other words, as time goes on you are going to get devices that come back after a couple of weeks because of infection, and you are going to get some that come in after, maybe, twenty years after an autopsy retrieval.

So you are going to get in a retrieval collection a span of devices, just as a natural course of collecting retrieved devices. And I think it will, in our past history, it has shaken out very reasonably quickly what the failure modes are after that.

And I think independent labs may be actually, like ours, are in a position to continually gather these and study these forever, where I would not burden the company to do so.

CHAIR YASZEMSKI: Dr. Diaz, please go ahead.

DR. DIAZ: I think if we include device tracking it has to be also in a very limited time span. If we assume that the device is intended for the facilitation of the completion of a fusion, and that fusion has taken place in the lapse of six to nine months, there is no need to continue tracking these devices for eternity when, in reality, their useful life has, in fact, expired.

So if the device fails, as Dr. Li indicated then, for sure, you need to know what thing is doing, and if you get it out, get it out and check it. But if the patient has had a successful fusion, I think it is onerous on anyone, be it the companies, the government, the physician, or anybody, to keep track of these things forever.

CHAIR YASZEMSKI: Dr. Cheng?

DR. CHENG: Just two points to address your inmediate concern, Dr. Diaz. I'm a tumor surgeon, and the oncologic potential for materials is not realized within just a couple of years. So there are some long term effects that device tracking would be helpful to know about.

The second point is I think we have to be a little bit careful in our comparison to vertebral body devices. While there are some parallels, as has been pointed out, by several individuals in the Panel and in the audience, the experience I think is a rather -- the number of procedures of vertebral body replacements is very small fraction, compared to those undergoing disc surgery.

So the ability of that to state that it is useful to compare it vertebral disc replacement is rather limited.

CHAIR YASZEMSKI: Thanks, Dr. Cheng. Dr. Finnegan?

DR. FINNEGAN: I would like to follow-up on that because the vertebral body replacements, as I understand it, are Class II because they are pre-eminent materials. And I would be willing to bet that if they actually had to go through the present day process they would not be a Class II, they might actually even be an HDE.

So I think that to compare the two is actually mistaken.

CHAIR YASZEMSKI: Thanks, Dr. Finnegan. Dr. Diaz?

DR. DIAZ: My concern with the issue of the potential oncogenic capacity of the materials I think has already been addressed in other devices that have been studied with comparable material structures.

I think we would be trying to reinvent the wheel to check to see whether titanium alloy, or carbon fiber, or PEEK, have a potential oncogenic ability if that has already been evaluated, assessed, and checked for other devices.

So I still go back to my idea of limiting the evaluation only to the time on which the device accomplishes a fusion or doesn't.

CHAIR YASZEMSKI: Other discussion?

(No response.)

CHAIR YASZEMSKI: For purposes of this I will read this again, and recognize everybody is going to get a chance to vote. We are not voting that this is going to go to FDA, we are going to agree how to fill this sheet out.

And we are all going to look at the sheet at the end, and we are going to vote yes or no on the sheet. And if anyone, for example, likes most things on the sheet, but disagrees with one or two, they can vote no, and transmit the message to the FDA that I voted no because of number 6, or number 7, etcetera.

And, again, one of the important things, in addition to the outcome of the vote, are the reasons for voting, and that the FDA gets the messages for and against each one of these components.

Having said that I'm going to propose that we fill out number 7 with a check and guidance document, with a check and device tracking, and include Dr. Diaz' limited time span, that we can vary and in a generic sense say, until fusion occurs.

And check testing guidelines, and include in that retrieval analysis. Does anybody dissent to filling out the sheet like this for number 7, upon which we will subsequently vote?

(No response.)

CHAIR YASZEMSKI: Ms. Shulman, number 8.

MS. SHULMAN: Number 8 and number 9 we get to skip because that only has to do with performance standards. Number 10 we can skip because that is only for a Class III device.

So on the second page, number 11, identify the needed restrictions. The first one is the basic restriction legend. And then the others are on top of that, use only by persons with specific training, or experienced in its use, only in certain facilities, or other.

CHAIR YASZEMSKI: Let's start this thing with Dr. Diaz, if we can. And would you suggest we check any, and if so, which ones?

DR. DIAZ: I think for sure the box on the use only by persons with specific training or experience is a necessity. I can see, for the various reasons that were presented earlier, that we could allow people without training to make use of them.

I am torn, a little bit, with the box that follows, the use only in certain facilities. We could follow the suggestion made earlier, that these things are being used only in centers where people with specialized training reside, and where the experience exists.

But some of these individuals may move away to other facilities where if they, themselves are performing it, in essence the capacity to do it is already existent there, since they have just relocated.

So my suggestion would be to only check the one box.

CHAIR YASZEMSKI: Okay, thank you, Dr. Naidu?

DR. NAIDU: I agree. I'm not sure the first -- I mean, I would assume that persons with specific training or experience would also be lawfully licensed practitioners, so I don't know what the first one is, the first box is meant to do.

But I do agree that use by persons with specific training experience in its use should be sufficient.

CHAIR YASZEMSKI: Thank you. Dr. Larntz?

DR. LARNTZ: Use only by persons with specific training and experience in its use.

CHAIR YASZEMSKI: Since we are filling out the sheet now, I ask for a point of order, if I might. I would like to hear whether Ms. Wells and Ms. Maher have anything to suggest to this sheet. May we do that, since we are not voting right now?

And if that is okay I will ask Ms. Wells for suggestions.

MS. WELLS: I don't have any additional.

CHAIR YASZEMSKI: Thank you. Ms. Maher?

MS. MAHER: I actually would have voted to have it on written or oral authorization from practitioner licensed by law, because I think that in your medical school training now people are adequately trained on these already, on how to use them.

And, therefore, we would be taking care of them, we could have discussion earlier about surgeons training surgeons. And I think going to that next step down adds a little bit of extra bells and whistles that I'm not sure necessarily needs to be there.

CHAIR YASZEMSKI: Thank you. Dr. Cheng?

DR. CHENG: I will check the first two boxes. Dr. Finnegan?

DR. FINNEGAN: The first two boxes.

CHAIR YASZEMSKI: Dr. Li?

DR. LI: I will defer to my surgical colleagues.

CHAIR YASZEMSKI: I think that I will now ask, since we've had some suggestions for checking the first box, some for checking the second, and some for checking both, I will ask if it would be acceptable to everyone if we check both? I don't see anything to be lost by checking both.

And, again, FDA will get our message during the discussion. So if there are no persons who would be against that, we will check the first two boxes for number 11, and move on to the supplemental data sheet.

MS. SHULMAN: The supplemental data sheet is designed to provide a device description, intended use, risk to the device, the recommended class, and the scientific support for the class, and proposed level of controls.

So with that the first is generic type of device, the advisory panel, device and implant, so we can go through those. Number four indications for use. You are welcome to say as was presented in the overheads, on the slides, unless you had any changes to that.

CHAIR YASZEMSKI: Okay. Well, let's do this. Rather than go around to everybody, let's start with the recommendation for as presented in the overhead, and open it up to anyone who wants to add or subtract from that.

Do we have that overhead from before, is that something that is easily retrievable, so that everyone can look at it? It is in the package, okay. And we've had a fairly thorough discussion. I think if anyone would like to suggest either deleting or adding to what we've seen and discussed today, as indications for use, please so identify.

Otherwise I'm going to propose that we take Ms. Shulman's suggestion and list, for number four, as described in the presentation.

(No response.)

CHAIR YASZEMSKI: Hearing none, let's move to number 5.

MS. SHULMAN: Number 5, the identification of any risks to health presented by the device. We can also go with what was presented in the overheads today, or you can have any additions that you may want.

CHAIR YASZEMSKI: When we discussed the questions to FDA, what we discussed about health risks, were those that were presented in the device, and then we had, for a recap, a discussion of potential long-term risk at adjacent segment disease, that seemed to be resolved by noting that once the fusion was solid, that this probably was more dependent upon the change of local mechanical properties of the functional spinal unit after fusion, than by any of the properties of the material, per se.

And the second thing that we asked was to emphasize the importance of the surgeon and her or his education and training. If there are additions to that, please let's entertain them now, otherwise we will also fill number five out with as presented.

(No response.)

CHAIR YASZEMSKI: I will do that for number 5.

MS. SHULMAN: Number 6, the recommended advisory panel classification and priority. The classification from the first page is Class II, and the priority that you would vote on would be high, medium, and low. And that would be how fast do you want us to go back and work on this reclassification, is it a top priority, medium?

Of course there are no time frames associated with high, medium, or low.

CHAIR YASZEMSKI: We, of course, are going to vote. But having gone through the first sheet and with an aim at a potential motion for Class II, I'm going to suggest that at the moment we put Class II in here, and then we will entertain discussion about it and, of course, vote on it.

But the priority, may I hear, if we fill in Class II for the certification that we will vote on, let me hear about the priority. Dr. Diaz?

DR. DIAZ: Since we know that the guidance can move at a glacial pace, in many things, and there is no time commitment to high, medium, or low, why don't we just put high and let the process evolve as it will?

CHAIR YASZEMSKI: And we will -- if there are no objections, we will put high. Number 7, Ms. Shulman?

MS. SHULMAN: If the devices and implant are life sustaining, and life supporting, and has been classified in a category other than Class III, explain fully the reasons for the lower classification, with the supporting documentation and data.

And just as a suggestion here you can say that the general and special controls can handle the risks, or unreasonable risks, or you can put as was discussed today in the Panel meeting.

CHAIR YASZEMSKI: And perhaps I might suggest that the discussion that led to our filling out the device questionnaire in number 7 will suffice, and be part of as discussed in the Panel meeting.

We have just gone through filling out about the guidance document, device tracking, and testing guidelines. So unless there are, again, objections I will suggest that for number 7, general special controls with the additional recommendations as presented and discussed at the Panel will be our answer to number 7.

MS. SHULMAN: Number 8, summary of information including clinical experience or judgement upon which classification recommendation is based. And once again you can say the information presented today.

CHAIR YASZEMSKI: I will so move that we do that, and ask if there are objections?

(No response.)

CHAIR YASZEMSKI: Seeing none, let's move on.

MS. SHULMAN: Number 9, the identification of any needed restrictions on the use of the device. We can refer to question 11 of the general questionnaire we already had the specific training and all. And you can add any others here.

CHAIR YASZEMSKI: Again, I will suggest that we refer to question 11, and ask if there are objections to not adding anything else?

(No response.)

CHAIR YASZEMSKI: Seeing none, let's move on.

MS. SHULMAN: Number 10 we will skip, because that is a Class I question. Number 11, if the device is recommended for Class II, recommend whether FDA should exempt it from pre-market notification.

CHAIR YASZEMSKI: Can you clarify for us so we understand what we are saying, by exempt and non-exempt?

MS. SHULMAN: That if there is not exempt, if there is an exempt then no one would have to submit a 510(k) for these devices.

CHAIR YASZEMSKI: And if it is not exempt, they would have to meet a 510(k) pathway?

MS. SHULMAN: Yes.

CHAIR YASZEMSKI: DO I hear a recommendation for non-exempt. Are there any objections to that?

(No response.)

CHAIR YASZEMSKI: Seeing none we will fill number 11 out as non-exempt. Number 12?

MS. SHULMAN: Any existing standards applicable to the device, device subassemblies, or device materials. The standard reference could be standards directed by professional groups, standards groups, or manufacturer.

CHAIR YASZEMSKI: Dr. Finnegan?

DR. FINNEGAN: Is this where we could bring in our concern about the difference between metal and non metal?

CHAIR YASZEMSKI: Ms. Shulman, would that be appropriate?

MS. SHULMAN: Yes.

CHAIR YASZEMSKI: How should we state this? Dr. Naidu, suggestions as to how we might communicate our concerns regarding the nature of the material composition in number 12?

DR. NAIDU: I think we have discussed this in detail. I mean, I think the most important thing is that polymeric materials are inherently different from metallic components, especially in this manufacturing methods.

There can be great variations in this, and therefore specific testing that we recommend, such as fracture toughness, and after the component fractures, the wear particles that were generated from fracture components, and I think those need to be delineated.

CHAIR YASZEMSKI: I might -- if I may make a suggestion? Since there is a transcript of everything that we said, this entire discussion will be on the transcript. And if we can refer to that transcript in our concerns, regarding the wear, the particulate debris, the fracture, etcetera, as have all been discussed, would it be appropriate to refer to the Panel transcript, the discussion that we've had regarding material properties as we answer number 12, here?

MS. SHULMAN: That is fine.

CHAIR YASZEMSKI: Would that satisfy you?

DR. NAIDU: And in addition lack of clinical data. That is the only other thing that I would like to add, adequate clinical data for the polymeric material, that is the only other issue that I'm concerned with.

CHAIR YASZEMSKI: Objections?

(No response.)

CHAIR YASZEMSKI: I'm not certain how to pull this. I'm looking at number 12 and it speaks existing standards applicable. And I'm not certain how we would communicate lack of clinical data to FDA under number 12, although that communication will be clear from the discussion we had.

DR. WITTEN: And number 10 is really asking what existing standards are applicable to the device.

CHAIR YASZEMSKI: Number 10? Number 12.

DR. WITTEN: We are on 12. Did I say 10? I meant 12. Number 12 is asking for existing standards that are applicable to the device. So it is asking, you know, when we talked about these special controls, are there some specific standards that should be part of the special controls. That is what that is asking.

CHAIR YASZEMSKI: I will ask if any of the Panel feels that there are standards. I guess my thought would be that we haven't discussed specific standards, we have discussed specific concerns, which will of course be transmitted to FDA.

Dr. Li, may I ask your commentary on that? I think the concerns are going to be well transmitted to FDA. And I guess this question is asking whether, perhaps like ISO or ASTM standards that we are aware of. And I don't believe that we discussed any of those.

DR. WITTEN: Well, we referenced some of them in our presentation.

MS. MAHER: There were a lot of them reference --

CHAIR YASZEMSKI: Can we, would it be appropriate, then, to reference the standards that were in the presentations that were made today, and the discussion that followed regarding them?

MS. SHULMAN: Yes. And if you want to amend the general device classification questionnaire number 7 about the clinical data question, and what you just brought up, that will be in the record for that, for the special controls.

CHAIR YASZEMSKI: Okay, that would be good. And that will be under the guidance document, of number 7?

MS. SHULMAN: Correct.

CHAIR YASZEMSKI: Does that satisfy you, Dr. Naidu, to put the concern regarding clinical data under the guidance document, number 7, on the general device questionnaire?

DR. NAIDU: Yes, thank you.

CHAIR YASZEMSKI: And for number 12, on the supplemental sheet we will refer to the standards that occurred in the presentations today, and the discussion regarding those standards that followed. Dr. Li?

DR. LI: Again, I'm not sure we are going to be redundant. So are you asking for -- I guess my issue is there are some tests that I would like to see done that weren't presented on your list, because --

MS. SHULMAN: This is where you would list them.

CHAIR YASZEMSKI: I think the way I'm reading this, and I will ask Ms. Shulman and Dr. Witten if I'm reading this incorrectly. For number 12 we would put existing standards.

And I would think that if the test you are referring to, our tests that have an ASTM or ISO standard, yes, they go here. If they are not, then they would go under testing guidelines, in number 7, under general device classification sheet.

DR. LI: I understand.

CHAIR YASZEMSKI: Which are they?

DR. LI: Well, I was thinking of things that have ASTM or ISO guidelines existing.

CHAIR YASZEMSKI: Okay. I'm not going to ask you to remember the numbers now, but if in general you can say what the tests are, we can attach the numbers to them later. What tests did you have in mind?

DR. LI: There is an ASTM and ISO standard for fracture toughness testing, mainly typically use a J or a K test, but typically for medical devices the sample requirements for K tests are too large, so J tests are typically used, when they are used for factory toughness testing.

There are also, none of -- your standard on PEEK is for neat PEEK, and the absence of fibers. But there are ASTM and ISO standards for composite materials and devices, and their subsequent testing.

So I would look, there are a bunch of those, I would have to go back and look specifically to see which would be appropriate for this particular application. But there are existing tests that define composite makeups and how you subsequently test them for fracture and fatigue, which are not covered by the list that you provided us so far.

CHAIR YASZEMSKI: Dr. Witten, would it be acceptable to FDA if we noted not the specifics tests, but that these are tests on fracture toughness and composite device, mechanical properties that we will supply the actual ASTM ISO numbers at a later time.

For purposes of this sheet, would this suffice?

DR. WITTEN: Yes.

CHAIR YASZEMSKI: Thank you. Next, Ms. Shulman?

MS. SHULMAN: So the last thing left would be to just vote on the sheets.

CHAIR YASZEMSKI: So if I -- we will have to vote, first, that we agree on the sheets. I think we have done it on a point by point basis. But I will review the answers and then ask everybody to vote yes or no, that they feel the sheet is filled out appropriately.

Then I'm going to ask Dr. Diaz for a motion. So first let's look at the sheets. The general device classification questionnaire, is it life sustaining or life supporting? No.

Is it for a use which is of substantial importance in preventing impairment of human health? Yes. Does it present a potential, unreasonable risk of illness or injury? No.

Number 4, yes. Number 6, is there sufficient information to establish special controls, in addition to general controls, to provide reasonable assurance of safety and effectiveness? Yes.

Number 7, if there is sufficient information to establish special controls to provide reasonable assurance of safety and effectiveness, identify them below.

We have checked guidance document, which will include the request for clinical data. We have checked device tracking, and stated that we feel it is for a limited time span, until fusion occurs.

We checked testing guidelines, which will include fracture toughness testing, and retrieval analysis in addition to tests that have been done for the devices that have already been approved throughout the PMA pathway.

We moved -- actually, I have to step back. The reason I'm hesitating is that I don't see that we answered number 9. Did we, and did I miss it? For device recommended for certification into Class II, should the recommended regulatory performance standards -- excuse me, it is for performance standards only, excuse me. So we skip 8, 9, and 10, pardon me.

Eleven, identify the needed restrictions. We checked the first two, only upon the written or oral authority of a practitioner licensed by law to administer and use the device.

And the second one, use only by persons with specific training or experience in its use. Moving to the supplemental data sheet, the indications for use in device's labeling. We are going to say as described in the presentations today.

Number five, identification of any risks to health presented by device, as described in the presentations today. Number 6, recommended classification and priority, Class II priority high.

Number 7, we stated that general and specific controls with recommendations as discussed at the Panel today. Number 8, a summary of information including clinical experience, as discussed at the Panel meeting today.

Number 9, identify an identification of any needed restrictions on the use of the device, as discussed in number 11, on the general device classification questionnaire.

Number 10 is not applicable. Number 11, if device is recommended, recommend whether it should be exempt from pre-market notification. We checked not exempt. Number 12, are there existing standards applicable to the device?

We are going to ask for fracture toughness standards, and composite device material property standards, that we will supply the specific numbers for, from ASTM and ISO, at a later time.

I'm going to go around and ask for a vote as to whether these sheets are filled out to your satisfaction. May I ask for a point of clarification? We are voting now just to say that everybody agrees that the sheets are appropriate?

Maybe I should say it this way. Since we've been through this, are there any objections to the sheets, as I've written them? Dr. Finnegan.

DR. FINNEGAN: Just a point of order. On number 5, for the supplemental data sheet, did you not want to say as discussed? Because the discussion was a little bit more than as described.

CHAIR YASZEMSKI: Yes, as discussed at the Panel meeting. Thank you, Dr. Finnegan. Other comments? Dr. Li?

DR. LI: Just to -- I'm not sure I need to add this, but as far as in section 12 of the supplemental data sheet, I was wondering if the FDA could reexamine what worse case scenario is in the testing.

Because a lot of the testing that is described in the guidelines we provided, that they would be tested in the worse case scenario. But then looking at the actual test I don't believe there are actually what I would consider the worse case.

So it would be -- it really is an amendment to the guideline, other than to reevaluate what they are going to accept as the worse case.

CHAIR YASZEMSKI: May I suggest that since 12 is asking for existing standards, that we put our recommendations regarding reassessment of the worse case into number 7 from the general device certification questionnaire under testing guidelines?

DR. LI: That would be fine.

CHAIR YASZEMSKI: And then we can make language that suggests that they do just that, based on the discussion we are having now.

DR. LI: That would be fine.

CHAIR YASZEMSKI: Dr. Cheng?

DR. CHENG: Well, my only quibble is this device tracking thing. You know, this is not onerous on the people we are asking. Basically you hook the patient, getting the patient's Social Security number who is getting a device, to the tag number for the device, and that is it.

And whether they keep it for two years until fusion occurs, or 20 years, is not going to make a big difference. But you need to have the information. If you don't have the information, then you don't have it. So I don't think there needs to be a time limit.

DR. DIAZ: Well, my concern with that concept is that it does not really limit itself to the acquisition of the Social Security number and name, rank, and serial number, but it requires some form of monitoring.

And that form of monitoring can be as simple as an annual letter from the patient saying, hello, how are you, Merry Christmas, or something like that. Or to a very intrusive evaluation of the patient, including radiographic testing, biomechanical studies of spine, etcetera, etcetera, etcetera.

I mean there is no definition, there is no limit on that.

MS. MAHER: And, actually device tracking really just means that the manufacturer is required to track where the patient lives at all times. And I can actually tell you, from experience, I run a patient registry, and we've got three years, almost four years worth of data into it.

And it is a fairly simple registry, I send them a form every year. And they respond, and when they respond I send them a check for 25 dollars. You would think that these people would want to stay informed, because it is a two page form that they get to fill out, they get a 25 dollar check.

Quite honestly each year the number goes down of people who are even interested in allowing me to voluntarily track where they are, and follow that with them. Now, in this case when you mandate device tracking, you are mandating that we, the manufacturer, keep track of where these patients are, for the rest of their lives.

Because that is really what the device tacking regulation does. And I honestly don't see where that brings anything, any benefit, necessarily, to the companies, or to the industry, or to you all.

That provision was originally put in place when the Shiley heart valves fractured. And part of it was because it was so hard to find out who had Shiley heart valves to begin with, to tell them they should come back in and get it replaced.

So that is where it is looking, how you can quickly get a hold of these people, to tell them there is a problem, to tell them to come back in and get it replaced. These patients will have had their backs fused, but hopefully the spine will have fused, the cage will be fused in there, or are you going to be taking this out? What is the benefit for being able to know that Sally Maher had a spinal cage put in her back 20 years ago, and it is still walking around fine?

I mean, you wouldn't be sending me forms to find out if I'm walking around fine, you just would know where I live to be able to find me.

CHAIR YASZEMSKI: Thank you. May I ask, Dr. Witten, you counseled us before --

DR. CHENG: Could I respond to that?

CHAIR YASZEMSKI: Go ahead, Dr. Cheng.

DR. CHENG: I run patient clinical studies as well, there is no question it is difficult to get people to respond to you, and that is not what I'm advocating here.

If you tag this to the patient's Social Security, then the federal government knows where you are.

MS. MAHER: We are not allowed to use Social Security numbers.

DR. CHENG: Well, that is a different issue for the FDA to deal with, okay?

MS. MAHER: We can't use the Social Security number.

DR. CHENG: That is a fact. Then you don't have to do it, let the FDA do it. What I'm saying, the principle of tracking devices is important. Despite the hissing in the audience, no one knows the incidence of oncologic tumor development after prosthetic device.

It is low, I'm not denying that, okay, and I don't think it is a major issue. But I'm just saying if my mother is going to undergo a cervical cage, and five people have become myopathic because of an osteolysis from a cervical cage, three years after fusion, I want to know about it.

And no one is going to know about it, unless you keep track. There is no way you are going to know anything, unless you keep track of the information.

MS. MAHER: Then I think we need to go to Congress and have them change the law.

DR. CHENG: That is not a problem. I mean, that is a problem, but that is a different issue, and the FDA will have to address that. But the recommendation for this panel is, at least that I'm trying to propose, is that it is important for us to keep track of information.

MS. MAHER: So, again, you are proposing that the FDA track all implants, not just final cages?

DR. CHENG: Sally that is what I said, yes.

CHAIR YASZEMSKI: May I ask, Dr. Witten, you mentioned to us before that performance standards have been used incredibly infrequently. What is the frequency with which device tracking is used?

DR. WITTEN: There are a few tracked devices. I can't tell you what they are -- how many? There are two to five. The only one in our division are dura mater allografts, which are treated as medical devices.

So it is not very frequent.

CHAIR YASZEMSKI: It is very infrequent.

DR. WITTEN: And let me just say that, I think just for clarification to us, FDA, to FDA, which is I think that the term tracking in our regulations, in our minds, is what Ms. Maher mentioned, which is being able to locate the patient.

It doesn't include any kind of data collection, it is just being able to locate the patient if there is something that happened with the product that makes you want to go back and discuss it further with the recipients.

CHAIR YASZEMSKI: Recognizing that, and recognizing, also, Dr. Cheng's plea, which is that we should know where these things are, and that you folks will consider both the pluses and minuses when we make our recommendation to you, I'm going to propose that unless there are objections we leave it as it is, we will leave it checked, and you can act upon it as you see fit.

So if there are no objections I'm going to state that we are in agreement that the sheets are filled out to the satisfaction of all of us, to be presented now to vote upon in a motion.

And I'm going to ask if Dr. Diaz would make a motion?

DR. DIAZ: Yes, Mr. Chairman. I would like to move that that the Panel for Orthopedic and Rehabilitation Devices accept the reclassification of the Intervertebral Body Fusion Devices from Class III to Class II, following the described guidelines that we discussed in the General Device Classification Questionnaire, and complemented by the Supplemental Data sheet.

CHAIR YASZEMSKI: Thank you. Do I have a second?

DR. FINNEGAN: Second.

DR. LARNTZ: Second.

CHAIR YASZEMSKI: Dr. Finnegan has seconded it, we have a third. We have had quite a bit of discussion. If anyone has additional things that they would like to add at this point, I will open it up and ask for further comments.

But if there are none I'm going to state that we are ready for a vote. And what we will then do is I will ask for a restatement of the motion, either by Dr. Diaz or by me, and I will start going around the room.

Now, this time I'm going to start, when we do vote, I will start with Dr. Naidu, we will record the vote. So not seeing any further discussion, may I ask you, Dr. Diaz, just say it one more time, and as soon as you are done saying it we are going to ask for a yes or no, or an abstention from everyone, starting with Dr. Naidu, and moving clockwise.

DR. DIAZ: I don't know if I can say it verbatim the same, but I will try. I would like to move that the Panel for Orthopedic and Rehabilitation Devices approve the reclassification of the Intervertebral Body Fusion Devices, known as cages, from Class III to Class II, based on the description that we have outlined pm the General Device Classification Questionnaire, and complemented by the Supplemental Data sheet.

CHAIR YASZEMSKI: Thank you. Dr. Naidu?

DR. NAIDU: Yes.

CHAIR YASZEMSKI: Dr. Larntz?

DR. LARNTZ: Yes.

CHAIR YASZEMSKI: Dr. Cheng?

DR. CHENG: Yes.

CHAIR YASZEMSKI: Dr. Finnegan?

DR. FINNEGAN: Yes.

CHAIR YASZEMSKI: Dr. Li?

DR. LI: Yes.

CHAIR YASZEMSKI: Dr. Diaz?

DR. DIAZ: Yes.

CHAIR YASZEMSKI: The motion has carried unanimously. It is the recommendation to the Panel, to the FDA, that the intervertebral body fusion devices be reclassified into Class II, with the guidance document, and the other recommendations as presented in the supplemental data sheet and the general device classification questionnaire.

I'm going to ask now each panel voting member an opportunity, give an opportunity, regarding the reason for his or her vote. Then I'm going to ask, after that is done, the consumer representative, and the industry representative, if they would like to make any comments.

Dr. Naidu, comments?

DR. NAIDU: You know, I think I have stated my opinions pretty clearly, previously. And I don't have anything else to add.

CHAIR YASZEMSKI: Thank you. Dr. Larntz?

DR. LARNTZ: Yes, I certainly support this reclassification. I do want to say one last plea, when implementing the standards testing that care be taken in doing the evaluation. I think Dr. Li was saying maximum load.

I think it can be done at various loads, and in fact the testing should be done in a statistically valid fashion, as proposed in some of the standards.

CHAIR YASZEMSKI: Thank you. Dr. Cheng?

DR. CHENG: I have no further comments.

CHAIR YASZEMSKI: Dr. Finnegan?

DR. FINNEGAN: The only comments I would make were in the supplemental document for number 4, I do think that the surgical instructions need to go to the surgeons and are no longer necessary for the FDA.

And I would really like to see allografts considered, although I understand that it may not be part of what is presently available.

CHAIR YASZEMSKI: Thank you, Dr. Finnegan. Dr. Li?

DR. LI: My only discomforts that I have remaining are we are approving down classification on a specific device for which we have actually very little long term data. However, on the other side of that coin, there is nothing in the short term data that would lead me to believe that bad things are about to come.

Which actually then puts my worry in devices yet to come. Because there is, we have been fortunate, for some reason, blessed with a very good success rate of these devices, but I don't think there is complete understanding for why they are performing the way they are exists.

CHAIR YASZEMSKI: Thank you, Dr. Li. Dr. Diaz?

DR. DIAZ: My only additional comment is just a restatement of what I said earlier, that I think that the applicability of these devices needs to be broader, and not limited to very specific segments of the spinal column, and that the use of the devices be approved, or allowed, at multiple levels throughout the spine, with the appropriate devices is designed for each space.

CHAIR YASZEMSKI: Thank you, Dr. Diaz. Dr. Witten?

DR. WITTEN: No, I think you were going to ask for comments.

CHAIR YASZEMSKI: Ms. Wells?

DR. WITTEN: No comment.

DR. TROMANHAUSER: Thanks very much. Ms. Maher?

MS. MAHER: I actually think that this is a good decision, these devices clearly have no more risks than the other spinal fusion devices that are currently on the market. Thank you.

CHAIR YASZEMSKI: Thanks to everybody, I appreciate the time and energy the Panel members have spent, and the FDA, I appreciate your service. Thanks to the FDA for preparation, and to the Petitioners, and to everyone who came today.

This meeting of the Orthopedic and Rehabilitation Devices Panel is now adjourned.

(Whereupon, at 2:12 p.m., the above entitled matter was concluded.)