U.S. FOOD AND DRUG ADMINISTRATION THIRD ANNUAL CENTER FOR DEVICES AND RADIOLOGICAL HEALTH/ CENTER FOR BIOLOGICS EVALUATION AND RESEARCH MEDICAL DEVICE USER FEE AND MODERNIZATION ACT (MDUFMA) STAKEHOLDER MEETING Gaithersburg, Maryland Thursday, November 17, 2005 2 1 PARTICIPANTS: 2 3 MARK BARNETT 4 DANIEL SCHULTZ 5 JESSE GOODMAN 6 LINDA KAHAN 7 JOANNE LESS 8 DIANE MALONEY 9 ROBERT YETTER 10 MARTHA LOUVIER 11 DONNA-BEA TILLMAN 12 DON ST. PIERRE 13 TIM ULATOWSKI 14 MICHAEL MARCARELLI 15 STEVE NIEDELMAN 16 GINETTE MICHAUD 17 PATRICIA LOVE 18 STEVE SYKES 19 20 21 22 BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 3 1 PRESENTERS: 2 3 MARK LEAHEY 4 JANET TRUNZO 5 BOB BRITAIN 6 MARLENE VALENTI 7 CLAUDIA MILLER 8 MARLENE KEELING 9 PATRICIA SHRADER 10 DIANE WURZBURGER 11 LINDSEY WADE 12 NAOMI HALPERN 13 ANTHONY BLANK 14 JACK LASERSOHN 15 DIANA ZUCKERMAN 16 MAC McKEEN 17 DENNIS HAHN 18 ROBERT DURGIN 19 ALAN TOTAH 20 21 * * * * * 22 BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 4 1 P R O C E E D I N G S 2 (9:08 a.m.) 3 MR. BARNETT: Okay. Welcome to 4 this third annual public meeting on the 5 Medical Device User Fee and Modernization 6 Act, which everybody knows as MDUFMA. I'm 7 Mark Barnett, Assistant Director for 8 Education and communication -- who else is 9 that talking there? 10 MS. KAHAN: I'm sorry. Hold on one 11 second, Mark. 12 MR. BARNETT: So much for the 13 stereo portion of our broadcast. Now we're 14 back to mono. Anyway, as I was saying, I'm 15 Mark Barnett; I'm the Assistant Director for 16 Education and Communication in FDA's Center 17 for Devices and Radiological Health. And I'm 18 going to be your moderator today. 19 A quick piece of housekeeping. 20 When you registered out there today, you 21 should have received a package which contains 22 the meeting agenda and a list of the BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 5 1 attendees that are going to be here, a list 2 of the guidances that we've issued under 3 MDUFMA so far, some important web addresses, 4 information on how to get transcripts, and 5 most importantly, information on where to get 6 lunch. And so if you didn't get that 7 package, you can get one during the break. 8 Well, as we all know, MDUFMA 9 authorizes the FDA to collect fees from 10 manufacturers to help offset the cost of 11 reviewing applications for new medical 12 devices. And it also has some important 13 provisions about things like third-party 14 inspections and special requirements for 15 manufacturers who reprocess devices that are 16 labeled for single use. 17 Now, as everybody in this room also 18 knows, MDUFMA is going to expire on 19 October 1, 2007. And so today's meeting is 20 particularly important because it's going to 21 serve as a vehicle for us in the FDA to get 22 your input and recommendations on what any BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 6 1 reauthorized MDUFMA legislation ought to look 2 like. 3 Specifically, we want to know what 4 you think has worked well with MDUFMA so far, 5 and whether there are things about MDUFMA 6 that ought to be changed in the future. And 7 so this meeting is basically a listening 8 session for the FDA. There are familiar 9 faces out here, so I know that many of you 10 know that this is not the first MDUFMA 11 listening session that we've had. 12 We've held similar public meetings 13 in 2003 and 2004, and in fact, we based many 14 of the actions that we took in implementing 15 MDUFMA on what you told us during those 16 meetings. So today, we're going to continue 17 that commitment to listen. As before, this 18 meeting is going to be transcribed so that we 19 can review what was said here today, and 20 we'll use what we learned from this session 21 as we prepare for the possibility of new 22 legislation. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 7 1 Let me say a few words about the 2 format for the meeting. It's going to 3 consist of six separate sessions, each one 4 covering a different aspect of MDUFMA. Now, 5 during the entire day, there's going to be a 6 standing FDA -- actually a sitting -- but 7 we'll call it a standing FDA panel, sitting 8 up here, and I'll introduce them in a few 9 minutes. 10 And then also during each of the 11 six sessions, one or more FDA subject matter 12 experts are going to come up and sit with the 13 other panel and listen to presentations from 14 stakeholders who have registered to speak in 15 advance. Each of these registered speakers 16 are going to have up to 10 minutes for their 17 presentations, and I'll give a little signal 18 when there are two minutes left, and then 19 again at the one minute mark. 20 Now, I might mention, if you are 21 one of those registered speakers, you were 22 told in advance about the 10-minute limit, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 8 1 but if you didn't receive the information, 2 and you know now that your presentation is 3 significantly longer than 10 minutes, this 4 will be a good time to kind of mentally edit 5 it down so that you can fit the time limit. 6 After each one of the speakers, 7 there's going to be a few minutes in which 8 the FDA panelists are going to be able to ask 9 the presenters for clarification or for 10 additional information. We want the FDA 11 folks to understand what you're saying. It's 12 important. And so if they have any questions 13 for you, that's the time they are going to 14 ask you. 15 Now, at the close of each of the 16 six sessions, we're going to open the floor 17 to those people who may have registered to 18 speak this morning when they arrived, and 19 after that, we will open the floor to 20 comments from anybody in the audience who 21 wants to speak. But one important ground 22 rule about speaking from the audience, and BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 9 1 that is that the comments ought to address 2 only the subject matter of the panel that we 3 just had. 4 In other words, we just had a panel 5 on the third-party inspection program, your 6 questions or comments ought to address that 7 topic and not something else. We've also set 8 a time limit for the comments from the floor 9 so we can stay on time and allow everybody to 10 speak. So on the comments from the floor 11 we're going to go no more than five minutes. 12 And again, I'll give a reminder when there is 13 one minute left and then call a halt when 14 it's over. 15 Okay, so much for introduction. At 16 this point, we do have some words of welcome 17 from Dr. Dan Schultz, who is Director of the 18 Center for Devices and Radiological Health, 19 who could not be with us today, but he is on 20 video; right? And we're going to show the 21 video now. Is that how it works? Okay. 22 Dr. Dan. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 10 1 MS. RICE: I need to get in here. 2 MR. BARNETT: You got to get in 3 here? Okay. 4 MS. RICE: And I need the laptop. 5 MR. SCHULTZ: Good morning. My 6 name is Dan Schultz, director for the Center 7 for Devices and Radiological Health. I want 8 to take this opportunity to thank all of you 9 for coming to the annual MDUFMA stakeholders 10 meeting, and to assure you that while I can't 11 be with you in person, I am certainly with 12 you in spirit and committed to the mission 13 that you are embarked on. 14 Our mission, getting safe and 15 effective devices to market in a timely 16 fashion, is certainly essential to the 17 purpose of this meeting. Over the last year, 18 we've hired a number of highly qualified 19 engineering, medical, and statistical staff 20 to enhance the expertise of the Center in 21 evaluating new devices. 22 We've also been able to increase BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 11 1 professional development as well as 2 increasing the use of outside experts to 3 assist in our mission. We held a record 4 number, more than 500 pre-meetings with 5 industry, which as you know, is a vital part 6 of getting good submissions and an efficient 7 review process. 8 We've performed very well against 9 MDUFMA goals, both 510(k) and PMA in the 10 areas of cycle goals and decision goals. 11 We've also worked hard on the other 12 commitments in the Secretary's goal letter, 13 such as developing GMP and BIMO inspectional 14 timeframes, issuing many device-specific and 15 special control guidance documents and 16 updating our IT infrastructure, especially in 17 those areas designed to increase the 18 efficiency of the review process. 19 During the last year, we've also 20 started to work on developing a more focused 21 and proactive post-market program that will 22 enhance the pre-market review process and BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 12 1 improve the efficiency of that process by 2 allowing our staff to consider and use 3 information when evaluating device 4 modifications and new devices. 5 This will also allow us to move 6 more quickly to identify post-market issues, 7 to act on those issues and resolve them, and 8 quickly notify the health care and patient 9 communities to improve the safety and 10 effective use of those products. 11 We recognize that MDUFMA user fee 12 revenue is tagged to improvement of the 13 pre-market review program. But we need to 14 make sure that we don't lose sight of the 15 importance of the post-market program to 16 fulfill our mandate to ensure the safety and 17 effectiveness of medical devices throughout 18 the product life cycle, and to maintain the 19 confidence of the U.S. public in the products 20 that we regulate. 21 Information we learn from 22 post-market on how a device works in the real BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 13 1 world, when and how it may fail, is critical 2 to our pre-market review process. We've also 3 been focusing on several important critical 4 path initiatives, including development of 5 simulation-based engineering and medical 6 imaging technology that will help in the 7 assessment of new stent designs; developing 8 clinically relevant animal models to improve 9 the prediction of device toxicity on injured 10 tissue in critically ill patients; working 11 with our trade associations and academic 12 communities in the development of new 13 statistical models for predicting the 14 effectiveness of cardiac stents; and to be 15 able to measure and improve long-term safety 16 of these devices. 17 I want to stress the importance of 18 your participation at this critical point in 19 the MDUFMA process. Next spring, we'll be 20 starting re-negotiation for MDUFMA 2. We 21 need to hear from all of our stakeholders. 22 Unlike previous years where FDA provided BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 14 1 updates on our implementation progress, this 2 year is dedicated as a listening session for 3 the Agency. 4 As Mark mentioned, there will be 5 several main topics for which we would like 6 your feedback. This is your opportunity to 7 tell us what you liked and what you didn't 8 like about MDUFMA. We need you to be as 9 specific as possible with your 10 recommendations for MDUFMA 2. 11 Together, we have the opportunity 12 to use the knowledge and experience of the 13 last three years to make a good program even 14 better. I have no doubt that with all of our 15 resolve and commitment, we will accomplish 16 that goal. 17 Thanks very much, and have a great 18 meeting. 19 MR. BARNETT: Okay, thank you, Dan. 20 Our next speaker is live. 21 (Laughter) 22 MR. GOODMAN: I think. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 15 1 MR. BARNETT: We think he is. Dr. 2 Jesse Goodman, who is Director of FDA Center 3 for Biologics Evaluation and Research. 4 Jesse. 5 MR. GOODMAN: Sure. Good morning 6 everybody. We really do appreciate your 7 presence here, and I'm really just going to 8 briefly echo, I think, Dan's comments. You 9 know, I think it's remarkable, the progress 10 we've made in the last couple of years. I 11 think I speak for both the centers, but I 12 have the most knowledge specifically about 13 ours. 14 And I think it's also particularly 15 remarkable that MDUFMA has enabled us to do 16 that in a time when resources have otherwise 17 been quiet constrained for the agency. From 18 my point of view, first of all, I want to 19 thank the people who have worked with us on 20 that. And that includes the industry 21 associations and specific companies who I 22 think have been very helpful in identifying BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 16 1 issues where we can work together better, and 2 have also been responsive when we've raised 3 our issues. So I thank you for that, and we 4 sure look forward to that continuing. 5 The other comment I was going to 6 make is that I think some of the improvements 7 in the performance measures, review time and 8 number of cycles, are terrific, and they help 9 achieve the goal that Dan mentioned, which is 10 getting safe, effective products to benefit 11 people more quickly, and I think that has 12 really happened. 13 But I think something that is a 14 little harder to measure has also happened, 15 which is quality and consistency have been 16 maintained, and in many cases improved. So I 17 think those are very important, we're very 18 proud of it and the MDUFMA resources have 19 been really critical. 20 The other thing we've done, and 21 this has been cultural within the FDA, but I 22 think the resources have also helped with BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 17 1 this, is we've been able to turn our 2 attention to our internal processes and our 3 collaborations. And I think CDRH and CBER 4 are working together very well in a 5 bidirectional way, and we're relevant, we're 6 getting, I think, high quality guidances out 7 that are meaningful across the industry. So 8 I think those things are good too. 9 Dan mentioned the post-market, we 10 too are more and more trying to integrate 11 that with the pre-market process in the 12 approval, and again, we do look forward to 13 discussing that as part of continuing MDUFMA. 14 And finally, I would like to say, in our 15 area, the tremendous promise of devices, I 16 mean, everybody -- it is very graphic when 17 you have a new defibrillator or a prosthetic 18 device, et cetera, et cetera. 19 But we have many devices that are 20 absolutely essential for the well-being of 21 the American people and for dealing with some 22 of our public health threats. You know, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 18 1 whether it's new infectious agents that 2 threaten the blood supply, BSE, or 3 confronting issues like mass vaccination, and 4 the promise of devices for meeting those 5 needs. 6 Another area that is relevant to 7 the critical path that Dan mentioned is in 8 combination products and tissue-engineered 9 products, and I think that's a perfect 10 paradigm where we and CDRH are working 11 together to make things easier for innovation 12 and bring future products to people. So you 13 know, we just do look forward to your input, 14 and I think even more than that, to 15 continuing to work together. 16 I think it's a very productive 17 interaction between FDA and the industry. I 18 think consumers benefit and are another 19 important group to provide input, and we just 20 thank you all, the industry and consumers, 21 for your support and trust in this. 22 Thank you. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 19 1 MR. BARNETT: Thank you, Jesse. 2 Let me now introduce the permanent panel 3 that's going to be up there all day, and as I 4 introduce them, I'll ask them to raise their 5 hand, because people in the back can't see 6 their name cards. 7 Linda Kahan is Deputy Director of 8 the Center for Devices and Radiological 9 Health. Joanne Less is Associate Director in 10 that Center for Clinical Research and 11 Government Affairs. Diane Maloney is 12 Associate Director for Policy in the Center 13 for Biologics Evaluation and Research, and 14 Bob Yetter is Associate Director for Review 15 Management in the Center for Biologics 16 Evaluation and Research. 17 And I'll ask Linda to just say a 18 few words of introduction if you would. 19 MS. KAHAN: Thank you. Can you 20 hear me? First of all, let me tell you that 21 Dan has been to Taiwan, and he actually cut 22 his trip short. He may be able to make a BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 20 1 guest appearance today later in the meeting. 2 He was getting back last night. And he 3 really did want to be here, and he may still 4 be able to do that. 5 I wanted to also echo what Dan and 6 Jesse have said, and thank you for coming to 7 the meeting today. As Dan suggested, this is 8 a little bit different than the meetings 9 we've done in the past. But I don't want 10 anyone to think for a minute that we are not 11 willing and able to provide information. And 12 one of the reasons that you've gotten the 13 handouts that you have is that we have put 14 all the information that we've been 15 constantly making available on our websites. 16 And most of you are veterans of 17 using that tool, but in case you haven't had 18 an opportunity to do that, please make sure 19 that you do take advantage of all the 20 information that's out there, including the 21 guidances that have been put out as part of 22 the implementation of MDUFMA, and the reports BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 21 1 that are available right through the website. 2 I wanted to also echo something 3 that Dr. Goodman said about what it means to 4 get resources in this fiscal environment. I 5 think that all of us are painfully aware of 6 the natural disasters and the international 7 unrest that have plagued the world and our 8 country over the last years. And it is 9 really a very bleak situation for most of the 10 government in terms of fiscal funding and 11 resources. 12 And as you know, before MDUFMA, the 13 medical device program was one of those 14 programs that was continually losing 15 resources. Even when we had supposedly 16 steady funding, we were in fact losing 17 resources because of inflation. So the fact 18 that we are now visible, and that we're one 19 of the programs that gets funded and gets 20 thought about when limited resources are 21 being distributed really is a tribute to the 22 work that our stakeholders have done to make BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 22 1 this possible. 2 And we're very appreciative of that 3 and we hope that that's going to continue, 4 because it's made a huge difference in the 5 way we can work, and in our ability to work 6 with the industry to get safe and effective 7 products to market quickly. 8 I wanted to just also point out 9 that this is just the beginning of the 10 process. We are very anxious to hear from 11 people today about what's happened over the 12 last couple of years that they think has 13 worked well, and as Dan said, things that 14 need to be done differently and better in the 15 next iteration of MDUFMA. 16 We here at the FDA kind of have a 17 two-pronged job over the next two years. One 18 is to continue to work on the commitments for 19 the goals and the other things that we have 20 promised to do through the Secretary's letter 21 until '07; and at the same time, we need to 22 gear up for what we can plan to do hopefully BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 23 1 when MDUFMA is reauthorized in '07. 2 So we're kind of working on both of 3 those tracks. And the purpose of this 4 meeting is to really get input from you about 5 how to work that second piece of it based on 6 the three years of experience that we've had. 7 I also want to remind people in case you 8 didn't realize that there will be another 9 public meeting in the fall, at which we will 10 be able to talk about these things again, and 11 have another year of experience to put under 12 our belts. 13 And I also wanted to let people 14 know that under the statute, once we work 15 with our stakeholders to actually come to 16 some tentative agreement about what ought to 17 be in the next version of MDUFMA, that will 18 be made publicly available through a Federal 19 Register notice, and people will have chance 20 to comment on that. 21 And as Jesse pointed out, the 22 importance of having consumers and BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 24 1 practitioners and health care professionals 2 give us some input is a big help to industry 3 and to the FDA, because everybody is 4 interested in that same goal, which is to get 5 good products out there as quickly as 6 possible. So with that, Mark -- 7 MR. BARNETT: Okay. Thank you, 8 Linda. I think we're ready now for 9 Session 1, which is on the "User Fee 10 Structure," and I'm going to ask Martha 11 Louvier to come up and sit with us. She is 12 from the Office of Management in FDA. 13 She is taking the place of Frank 14 Claunts, who was going to be here but could 15 not make it. 16 MS. LOUVIER: Good morning. 17 MR. BARNETT: Now that she is 18 seated, we have the full panel. Let me call 19 in our first speaker, who is Mark Leahey, of 20 the Medical Device Manufacturers Association. 21 MR. LEAHEY: Thank you, Mark. 22 First, I want to begin by thanking BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 25 1 Dr. Schultz, Dr. Goodman, the staff at CDRH 2 and CBER, and Cindy Harris for putting this 3 meeting together. I think it is a great 4 opportunity for all of the stakeholders to 5 get together and talk about what is working 6 and what improvements need to be made. 7 And I'm pleased, this is my third 8 year at the meeting, and I'll have to say 9 that I think some of the issues that we had 10 address in the past have been remedied as 11 part of the MDUFMA trigger fix in August. So 12 hopefully it will be an opportunity again to 13 identify those things that need some tweaking 14 and improving the future. But I think three 15 years into the program, we are in a better 16 shape than when we started, and I think 17 that's a tribute to everybody in this room. 18 So again, by way of background, let 19 me just start off by saying that I'm the 20 Executive Director with the Medical Device 21 Manufactures Association. We're a trade 22 association based in Washington, representing BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 26 1 hundreds of medical technology companies, 2 many of which are small- to medium-sized 3 companies, and I think that's indicative of 4 the industry itself. 5 Prior to the trigger fix in August, 6 the user fee system was volatile and 7 unpredictable for the industry. I think this 8 is evident by the fee increases that we 9 saw -- just in the first two years of the 10 program, we saw fee increases jump between 55 11 and 60 percent for both 510(k)s and for PMAs. 12 You'll see here, the PMA fee, which 13 started off at $154,000, jumped to $239,000 14 and change in just two years, and the 510(k) 15 fee jumped from $2187 to more than $3500 in 16 just two years. And this is something that I 17 think the entire industry voiced concerned 18 about, these types of dramatic fee increases 19 that I think, to everyone's credit, there was 20 a recognition that these fees were not 21 sustainable. 22 Another issue that I think we had BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 27 1 prior to MDUFSA is the fact that the 2 structure allowed FDA to collect more per 3 submission if they saw a decline in 4 fee-generating submissions. Certainly, we 5 understand the need for FDA to have a stable 6 source of revenue, but the industry also 7 needs that stability. 8 And the structure prior to the 9 trigger fix did not provide that. And again, 10 these increases were unsustainable for 11 99 percent of the industry. And if we want 12 to continue to develop innovative, safe, and 13 effective products for America's patients, 14 it's vital that the entire industry has the 15 ability to innovate. 16 Another note: Prior to MDUFSA, and 17 hopefully we'll see a reverse here, there was 18 a dramatic drop in the number of 19 fee-generating submissions after the user fee 20 was created. So hopefully -- there could be 21 many reasons for that, but I think the 22 numbers indicate that there was a dramatic BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 28 1 drop, and hopefully that the lower fees or 2 the stabilized fees will provide an 3 opportunity for those submissions to 4 increase. 5 So where are we now after MDUFSA? 6 Fees are much more predictable for the 7 industry. And I think this is the biggest 8 success under the program moving forward, 9 that for the first time, the elements -- the 10 compensating and work load adjustments 11 that -- a large portion due to the dramatic 12 fee increases we saw in the first couple of 13 years -- are no longer in place. 14 The fee increases are capped at 15 8-1/2 percent annually. I think that the, 16 industry was hoping for something along the 17 lines of inflation, but recognizing that we 18 still wanted to provide FDA resources to fund 19 them without needing dramatic cuts, it was 20 settled on an 8-1/2 percent annual increase, 21 which I think in the long term, it's still, 22 I'll have to see if that's the acceptable BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 29 1 rate of increase, because that may be 2 difficult to sustain long-term, but we can 3 take a look at that. 4 I'm also very pleased that it 5 eliminated the workload and compensating 6 adjustments as I just spoke of, and this is 7 something I'm sure many of you will be happy 8 to hear. During the first MDUFMA 9 stakeholders meeting, I talked ad nauseum 10 about the need to eliminate these. During 11 the second, I did as well. 12 Now I can congratulate everyone 13 here for making those decisions. I think it 14 was something that was shared by many. And 15 we're just pleased that we now have, again, I 16 think, the right equation for developing the 17 fees moving forward. 18 And the final important point that 19 was made as part of our provision, as part of 20 MDUFSA, is the fact that it provided greater 21 fee relief for companies under $100 million 22 in annual revenues. You know, this is BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 30 1 something prior to the development of MDUFMA, 2 back in 2002, MDMA was trying to push for a 3 number higher than $30 million. We were 4 unsuccessful, but we're pleased that now we 5 have this $100 million threshold. 6 We know for certain that there are 7 companies out there in that $30- to 8 $100 million range that were withholding 9 regional PMA submissions, PMA supplements, 10 because it wasn't in their regulatory budget 11 to file, and now they're moving forward. So 12 I think to FDA's credit, the revisions that 13 were made under MDUFMA hopefully give them 14 the resources they need to move forward, but 15 also allows the industry to move forward and 16 innovate. And I think that's the ultimate 17 goal of this program. 18 So user fees, what's ahead? I 19 think we need to evaluate the value of user 20 fees. Now what do I mean by that? Well, I 21 think two things are important to this 22 component, the first being what the actual BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 31 1 fee amount is. And that's something that we 2 need to address. The other is something I'll 3 address on a later panel, which is, what does 4 that fee provide in return as it relates to 5 ensuring the patients have safe and effective 6 products more quickly? And that relates to 7 performance goals. 8 So I don't think in trying to 9 determine what a reasonable fee is, I don't 10 think you can just look at a dollar amount, 11 alone in and of itself. You have to look at 12 the dollar amount in conjunction with the 13 performance that's being achieved. Again, 14 this goes along with fees being reasonable 15 and rational, look at fees and performance 16 together. 17 We also need to ensure that fees do 18 not increase at unsustainable rates. I think 19 that again, we took a huge step in the right 20 direction in dealing with eliminating the 21 workload and compensating adjustors and 22 having that 8-1/2 percent cap in place. And BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 32 1 I think the industry will get together and 2 determine what is a sustainable fee increase 3 moving forward. 4 There also needs to be an 5 understanding that the fees are meant to be 6 additive to appropriations and not 7 substituted. And this is something that I 8 think shouldn't be looked over. Again, when 9 everyone got around the table and the 10 industry agreed to pay I think almost close 11 to -- generate almost close to $80 million in 12 the first three years of the user fee 13 program -- this was meant to be additive to 14 hire new employees to help enhance the 15 process. But unfortunately, we saw the 16 congressional appropriations that were 17 promised under MDUFMA and committed to under 18 MDUFMA were not delivered in the first couple 19 of years of the program. 20 And I think there is a concern that 21 a lot of the user fee dollars again that were 22 meant to be additive were actually used to BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 33 1 supplement the congressional appropriations. 2 And again moving forward, we really need to 3 make sure, and I know a lot of this falls 4 outside the ability of FDA to guarantee that 5 the monies are there, but do what we can to 6 ensure that the user fees aren't just used to 7 plug in a drop in congressional 8 appropriations. 9 I think the final thing we need to 10 do is determine FDA's actual resource needs 11 related to the pre-market review program. 12 And again, to FDA's credit, they worked with 13 Dr. Geiger to try to get at some of this 14 information, and Dr. Geiger recently put out 15 his report. I think there is some good 16 information to be gathered there, but I think 17 there are some shortfalls related to really 18 flushing out what the resource needs are on 19 the PMA side, between PMA -- original PMAs, 20 PMA's supplements. 21 But again to FDA's credit, I think, 22 that they have put some internal data BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 34 1 collection mechanisms in place that will 2 hopefully provide better data to be collected 3 on, again, what the resources are for 4 original PMA, what they are for the 188 5 supplements, and hopefully now that they are 6 in that process of gathering that 7 information, we will really get a better 8 understanding of what the resource needs are. 9 And then once we can determine that, I think 10 it has to be understood that the user fees 11 are not meant to cover that entire cost of 12 that, that the user fees again should be 13 supplemented with the Congressional 14 appropriations and should play a part in 15 assisting FDA but not the overwhelming 16 majority. 17 MR. BARNETT: Two more minutes. 18 MR. LEAHEY: Well, here we are. 19 User fee, what's ahead? Looking forward, 20 we're looking forward we're looking forward 21 to working with FDA, the folks within the 22 other industries and the Hill to ensure that BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 35 1 patients have timely access to safe and 2 effective medical technologies, and that 3 smaller companies continue to have the 4 ability to innovate. And I think again, the 5 stakeholder meeting today is certainly a sign 6 that there is an element of a partnership 7 involved here that Dr. Schultz spoke of last 8 year. 9 I think we look forward to working 10 with everybody. Again, MDMA is committed to 11 making this program work, so long as we can 12 ensure that smaller companies aren't harmed 13 and that patients ultimately are the winners 14 with safe and effective medical products and 15 they get access to that in a timely fashion. 16 So with that, I will conclude, thanks. 17 MR. BARNETT: Thank you, Mark. And 18 let me ask the panel, before you step away. 19 Is there anyone that needs clarification on 20 that or has any questions for Mark? If not, 21 thanks very much, and let me ask our next 22 speaker to come up, Janet Trunzo of AdvaMed. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 36 1 MS. TRUNZO: Good morning, my name 2 is Janet Trunzo. I'm the executive vice 3 president for technology and regulatory 4 affairs at AdvaMed, the Advanced Medical 5 Technology Association. We represent over 6 90 percent of the medical devices sold in the 7 U.S., and we're the world's largest medical 8 device trade association. 9 First of all, AdvaMed would also 10 like to thank FDA for providing stakeholders 11 the opportunity to comment on the various 12 aspects of MDUFMA. AdvaMed also would like 13 to recognize Dr. Schultz and Dr. Goodman and 14 all of the CBER and CDRH staff for all the 15 hard work and effort they have made in 16 implementing the provisions of MDUFMA. 17 My comments today are going to be 18 limited to two areas: The elements of a 19 reasonable user fee program; and also, I'm 20 going to make a few comments about FDA's cost 21 analysis study. First, I would like to talk 22 about the elements, make a few statements BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 37 1 about the fundamental elements of a user fee 2 program. 3 First and foremost, medical device 4 user fees are additive to the FDA's device 5 budget, and never are or have been intended 6 to supplant FDA's base device budget. In 7 fact, Section 101 of MDUFMA states the 8 following: "Congress finds that the public 9 health will be served by making additional 10 funds available for the purpose of augmenting 11 the resources of FDA." 12 In fact, under MDUFMA, the 13 additional resources provided were a 14 combination of industry user fees and 15 congressional appropriations. The user fee 16 program in fact was designed intentionally, 17 such that the industry contribution was 18 intended to not exceed 15 percent of FDA's 19 entire device base budget. And indeed this 20 is the case and remains so. 21 So what does the medical device 22 industry expect from user fees? Well, it's BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 38 1 quite simple. We expect reasonable fees. We 2 expect that the fees will not increase 3 drastically from one year to the next. We 4 also expect adequate appropriations from 5 Congress. Last, but definitely not least, we 6 expect improved performance for the industry 7 contributions. Representatives from AdvaMed 8 member companies will be commenting later on 9 performance during the later panels. 10 Turning now to FDA's cost analysis 11 study: In September of this year, FDA issued 12 its cost analysis study on determining the 13 unit cost for the process of medical device 14 review. And I don't know if any of you got a 15 chance to look at it. It's quite a lengthy 16 report. 17 But after reviewing the report, and 18 also after hearing some presentations from 19 Dr. Geiger, who is the author of the report, 20 I would like to offer the following comments: 21 First, there are some limitations in the 22 data, and those limitations were noted BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 39 1 actually by the author himself. Data in this 2 report reflect the '03 and '04 activity. 3 And although FDA recently trained 4 its staff on making improvements to the time 5 reporting system, data collected in '03 and 6 '04 were not precisely collected, such that 7 the time spent on original PMAs and the 8 various types of PMA supplements were clearly 9 delineated. 10 Second comment: In reviewing the 11 calculations for determining the unit costs, 12 it appears that FDA used information from the 13 FY '03 and FY '04 financial reports that it 14 makes to Congress under the requirements of 15 MDUFMA. And it shows -- if you look at those 16 reports themselves, those financial reports, 17 it talks about the budget and how much of the 18 FDA budget was used for device review 19 activities. 20 So that information from that 21 report is combined with the cost analysis 22 study. Please note also that device review BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 40 1 activities encompass a lot of activities. 2 They are not just the time that the FDA 3 reviewers spend on the actual review of the 4 application; they also include the support 5 activities, center-wide expenses, including 6 rent utilities, field investigations, and 7 general agency and administrative costs. 8 In the cost analysis report, FDA 9 allocated both indirect and direct costs to 10 the various types of applications, and then 11 divided the number of applications completed 12 during the time reported in the report, 13 that's '03 and '04, and came up with the unit 14 cost. When using the data from this report 15 in the future, we must bear in mind that the 16 reported unit cost represents a fully loaded 17 cost, and in their totality represent a 18 significant portion of the FDA's total base 19 budget for devices. 20 I also would remind the agency as 21 it contemplates using this information in the 22 future, and drawing upon what I said earlier BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 41 1 in this presentation, that the device user 2 fees are intended to augment the FDA's device 3 base budget. 4 In closing, we very much look 5 forward to working with FDA for the 6 re-authorization of MDUFMA. 7 We look forward to designing a 8 device user fee program that incorporates all 9 the basic elements of a workable user fee 10 program that I noted earlier, and at the same 11 time, provides FDA with the additional 12 resources it needs so that patients have 13 timely access to safe and effective medical 14 technology. Thank you. 15 MR. BARNETT: Thank you, Janet. 16 Let me turn to the panel now and ask if any 17 one has any questions of Janet. 18 MS. KAHAN: I wanted to ask, is 19 there another presentation for this panel? 20 I'm going to wait; can we ask questions at 21 the end, if we have some? 22 MR. BARNETT: Okay. All right BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 42 1 Janet, stay tuned then. And our next speaker 2 is Bob Britain, of the National Electrical 3 Manufacturers Association, or NEMA. 4 MR. BRITAIN: NEMA, we represent 5 manufacturers of medical imaging equipment 6 and radiation therapy equipment. So we have 7 a very special part of the medical device 8 manufacturing community. And again, I echo 9 the thanks of Mark and Janet, the panel, FDA, 10 putting this all together. I wanted to 11 specially thank Ms. Less for moving this 12 program into November, out of December. 13 Remember, I have never been able to get to 14 this because of the RSNA in Chicago. Thank 15 you. 16 Something else special about this 17 industry: We've worked very hard with FDA 18 when we were first negotiating MDUFMA to have 19 an exemption from user fees for manufacturers 20 that use third parties for 510(k)s. So many 21 of our manufacturers actually use third 22 parties and do not pay the user fee. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 43 1 So the other thing special about 2 this part of the industry is that we're 3 mainly 510(k); very few products go to market 4 in medical imaging through the PMA process. 5 So we have not been, so to speak, hit as hard 6 as many of the other medical device 7 manufacturers that put their products through 8 the PMA process. 9 So therefore, I essentially support 10 everything that Mark and Janet have said. 11 The increases in 510(k)s have been 12 substantial, if you look at the percentage 13 increase, but if you look at the total, going 14 from 2000-something to 3000-something hasn't 15 been too hard on the industry. 16 I support the predictability. 17 Things -- increases have to be predictable. 18 You know, industry works from budgets, too. 19 And we can't be taken by surprise. We do not 20 support trying to backfill on shortfalls from 21 the year ahead to the previous year. And I 22 think that's not supportable, it's not right. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 44 1 You've got to do the best job you 2 can in predicting the number of PMAs and 3 510(k)s coming in. You are going to hit the 4 mark sometimes and you are not going to hit 5 the mark at other times. But when you're not 6 hitting the mark, it usually means that you 7 don't have the numbers coming in, you don't 8 have the numbers of supplements and PMAs and 9 510(k)s that are coming in -- so you're doing 10 less. You're not expending the resources 11 that you thought you might have to spend. 12 Gee, forgot to put my -- all that is to say 13 that in the last three years, the 20 to 30 14 percent increases have been quite excessive. 15 We are thankful that AdvaMed and 16 MDMA were able to negotiate a cap, which was 17 8.5 percent last year, and we support that. 18 Long-term, however, I'm not sure that is the 19 right number. 8.5 percent a year seems like 20 a lot to me going forward. So we need to 21 establish some reasonable formulas going 22 ahead. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 45 1 The other thing I'd like to say is 2 that throughout this day, from the three 3 trade associations, you're probably going to 4 hear a lot of concerns, issues, but probably 5 not going to hear a lot of solutions. We're 6 going to be working this spring, we're going 7 to be sitting down with FDA, trying to work 8 out solutions to MDUFMA 2 in 2007. 9 So I think we have to be careful 10 what we can say today in how to fix things. 11 So what you're going to hear today is 12 concerns more than solutions. Thank you. 13 MR. BARNETT: Bob, thank you. 14 Again, let me ask the panelists if they have 15 any questions. Linda, you had a question 16 that you wanted to ask. Do you want to do it 17 now? 18 MS. KAHAN: Let me start. One 19 question that I had, and I guess maybe Mark 20 could be the best person to try to answer 21 this, but I think that one of the things that 22 we've struggled with and that we'd sort of BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 46 1 like some ideas about -- and I realize that 2 you're not offering solutions, but what are 3 the tools that we, meaning all the 4 stakeholders: Industry, consumers, Congress, 5 FDA, can use to figure out when a fee 6 situation creates a disincentive for small 7 businesses, for industry? 8 I think one of the concerns that 9 you have put on the table, as has AdvaMed, 10 NEMA, and everybody else, is that we want to 11 make sure that nothing in this program 12 undermines innovation or limits the ability 13 of small companies to get on the market. I 14 guess I was wondering if you have any ideas 15 about how we get to that. 16 MR. LEAHEY: The first answer is to 17 ensure that the fees are reasonable, and I -- 18 MS. KAHAN: Well, that's my 19 question. My question is how do we -- 20 MR. LEAHEY: I think probably the 21 fee increases that we saw the first two years 22 were unreasonable, and that's one of the BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 47 1 reasons why we saw a dramatic drop in the 2 number of submissions. So I think that 3 there's some evidence that the current system 4 was not working as intended, that it was 5 having a stifling effect on innovation. 6 I think the other issue may, you 7 know -- oftentimes, you hear, well, these 8 folks are in business, and it's the cost of 9 doing business. I think the response that 10 many of them feel is, again, if the 11 government would like to regulate an 12 industry, it certainly has that right to do 13 so. But the government needs to fund those 14 regulations. And this was never something 15 that was initially a burden for these 16 companies for the decades and decades of 17 innovation, and this is something relatively 18 new on the horizon. 19 And one of the things that the 20 industry was told -- I guess this was part of 21 the pitch from folks -- was that this is a 22 sound business decision. This will result in BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 48 1 faster reviews, enhanced performances et 2 cetera. And quite frankly to date, that 3 hasn't played out. That I think the jury's 4 still out as to whether or not user fees are 5 a sound business investment, and I think 6 that's what we really need to do and look at 7 over at the course of the next two years to 8 determine -- these folks are innovators, and 9 they do run businesses. 10 And again, it goes back to one of 11 my slides, I think, about last year, the 12 benefit of the bargain. We need to look at 13 what are we getting for the user fees. And 14 so I think it's hard to determine -- to say X 15 number of dollars is unreasonable. I think 16 it's very easy to say that X number of 17 dollars with no enhanced performance is 18 problematic, because there, the company would 19 not would view it as, again it is diverting 20 resources from the R&D and other areas. 21 MS. KAHAN: Thanks. 22 MR. BARNETT: Anyone else on the BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 49 1 panel want to question? Anyone in the 2 audience want to respond to what they just 3 heard? 4 MR. LASERSOHN: I have something. 5 MR. BARNETT: Come on up to the 6 mic. Please identify yourself, first. 7 MR. LASERSOHN: I am Jack Lasersohn 8 from the National Venture Capital 9 Association. I want to strongly support what 10 Mark just said. The question of 11 reasonableness for these fees cannot be 12 looked at in the abstract. Our company spent 13 millions of dollars a month in the start-up 14 phases to get products through the FDA. 15 So even fees of $100,000 or 16 $200,000 or $300,000 for a key PMA in the 17 context of that is not problematic. What's 18 problematic is not having performance results 19 that justify the payment of the fees. So I 20 think that is the balance at least the 21 venture funded medical industry would really 22 like to strike: Rather than a particular BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 50 1 concern on the absolute level or the absolute 2 level of increases, we would be happy to pay 3 for increases if they are commensurate with 4 performance increases. 5 MR. BARNETT: Thank you. Is there 6 any one else in the audience who wants to 7 respond to anything they've heard. Mark? 8 MR. LEAHEY: Again while the 9 venture community is very important, I think 10 we need to also be careful that there are a 11 lot of companies out there without venture 12 funding. So to increase the fees across the 13 board without that sensitivity is something 14 that we need to look at the entire landscape 15 of the space. And recognizing again, when we 16 move forward here, it's important to look at 17 all elements of the fees, the performance, 18 and look at all the different folks who are 19 participating, small venture backed, large 20 medical technology companies and those 21 companies that aren't venture backed. 22 MR. BARNETT: Thank you. Before we BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 51 1 close out this panel, anyone else? 2 Bob Britain, step up. 3 MR. BRITAIN: This has nothing to 4 do with what's been said, but I think it 5 should be said. And that is this -- the user 6 fee process, whether it's here in the United 7 States or in Japan or China or Canada, is a 8 cost-shifting process. Somebody's got to pay 9 for it; somebody pays for the user fees. The 10 cost of medical devices increases because of 11 them. 12 Medicare pays for your user fees; 13 the whole health system is paying for the 14 user fees. I didn't want to leave here 15 without saying this because the whole world 16 is looking at you and saying, "user fees are 17 okay," and the whole medical device industry 18 is faced with a worldwide user fee system 19 which is dearly going to cost patients, 20 Medicare systems, third-party payers, a lot 21 of money. So just keep this in mind when you 22 want to consider your increases year after BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 52 1 year. 2 MR. BARNETT: Thank you, Bob. 3 Janet Trunzo -- 4 MS. TRUNZO: AdvaMed represents 5 small, medium, large manufacturers, and I 6 just would like to reiterate a point that I 7 made in my presentation, that companies -- 8 and it kind of builds on what the 9 representative from the National Venture 10 Capital Association said, is that paying a 11 user fee, there is an expectation that if a 12 company pays a user fee, that there will be 13 improved performance. 14 And that philosophy and that 15 expectation is an expectation not only of 16 small companies, medium sized companies and 17 large companies, all companies expect some 18 return in the performance and predictability 19 in the performance as a result of a user fee. 20 Thank you. 21 MR. BARNETT: Thank you, Janet. 22 Anyone else before we call it a close for BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 53 1 this panel? Then I'll say going, going, gone 2 for this particular panel. I guess we've all 3 talked ourselves out here, right? 4 Then it's time for a break, 15 5 minutes. It's now 10:00, so why don't we be 6 back here, at 10:15. 7 Thank you. 8 (Recess) 9 MR. BARNETT: We're ready to start, 10 so please have a seat. Thank you. 11 We're ready to begin now with our 12 session 2, which is on premarket review 13 performance goals, and up with us to join the 14 permanent panel are two FDA subject matter 15 experts, Donna-Bea Tillman, who is Director 16 of the Office of Device Evaluation in CDRH, 17 and Don St. Pierre, who is with the Office of 18 In Vitro Diagnostic Device Evaluation and 19 Safety with CDRH. 20 And our first presenter is Mark 21 Leahey, again, with the Medical Device 22 Manufacturers Association. Mark? BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 54 1 MR. LEAHEY: Thank you, Mark. And 2 unlike years past when I had the pleasure of 3 speaking five times during one of these 4 meetings, I'm pleased to note that I'm only 5 speaking three times, and we're halfway home 6 after this, or more than that. 7 Again, we spoke a little bit about 8 performance in the first panel. Again, the 9 importance of not looking at fees isolated, 10 but looking at fees in relationship to 11 performance. And I think that this is 12 something, probably one of the more critical 13 elements of MDUFMA 2 if we're to get there 14 that needs to be addressed, because again, it 15 goes to the heart of the value of the user 16 fee. 17 So performance issues. The goal of 18 MDUFMA was to ensure patients' timely access 19 to safe and effective medical technologies. 20 Now, back in 2001, there were a lot of 21 attempts to try to enhance FDA through 22 various reforms short of a user fee, but then BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 55 1 ultimately the user fee component entered the 2 equation. And one of the things that we 3 heard consistently from FDA and from others 4 was that if you a pay user fee, it will 5 enhance review times by approximately 6 25 percent. And again, I think when you talk 7 to a lot of CEOs, if they're told that things 8 will improve by 25 percent, then a reasonable 9 fee is something that they consider to pay. 10 The problem was that the goals were 11 developed with limited data, and this is no 12 fault of anybody's other than just time. You 13 know, when you're trying to get a sense as to 14 where FDA -- what their performance criteria 15 were, what the data was, back in 2001, when 16 there weren't necessarily the proper ways to 17 collect that data, I think it caused a 18 problem, and people just put their best guess 19 out there as far as what they thought would 20 represent 25 percent enhanced performance. 21 However, three years into the 22 process, we certainly have more data that is BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 56 1 available. And I think it's evident when you 2 look at the data that the goals 3 themselves -- and this is not -- again, I 4 want to clear that I make the distinction 5 between FDA's actual performance and the 6 goals -- because to FDA's credit, they've 7 exceeded the goals in many many cases, and 8 exceeded them substantially in some cases. 9 But when we're talking about the 10 MDUFMA goals in comparison to the actual 11 performance from FDA in the years leading up 12 to MDUFMA, it's not clear that they represent 13 enhanced performance. 14 And I think when you look on a 15 percentage basis of the total number of 16 submissions, 510(k)s represent about 17 90 percent, and PMA supplements represent 18 about 8 or 9 percent, and PMAs represent 19 about 1 percent. It's clear that in most 20 cases, those FDA/MDUFMA decision goals didn't 21 necessarily reflect enhanced performance. 22 But as I said again, they're exceeding these BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 57 1 performance goals. So there is some good 2 news here. 3 But I think as we move forward to 4 MDUFMA 2 and re-evaluate the goals, I think 5 they should be that; goals; something that 6 you strive for, not something that you're 7 already achieving. And remembering that the 8 ultimate goal is an efficient and effective 9 review. 10 We need to keep the focus on the 11 final review times. The cycle goals are 12 certainly important, but something that I 13 know we've spoken to -- the entire industry I 14 think has shared some concern about the 15 efforts to maintain or meet -- cycle goals 16 may have a -- may have an adverse impact on 17 meeting the decision goals. And I think we 18 need to find a balance that still ensures 19 that we are monitoring FDA's early 20 performance in the review process as far as 21 meeting certain time goals of getting 22 requests for additional information and BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 58 1 certain letters out. But we can't lose sight 2 of the ultimate end goal here of performance 3 in ensuring that a patient has access to that 4 technology. 5 Here are just a couple of slides 6 that I put together to illustrate. Again, 7 this is not looking at FDA'S actual 8 performance, this is solely looking 9 at -- it's looking at FDA's actual 10 performance prior to MDUFMA, and then 11 comparing that to what the MDUFMA goals lay 12 out. And here, you're dealing with the 13 percentage of 510(k) decisions, FDA decisions 14 within 90 days. And again, looking at the 15 numbers here, in 2000, 2001, 2002, FDA was 16 reviewing between 77 and 80 percent of their 17 510(k)s within 90 FDA days. The goals laid 18 down in MDUFMA allow FDA to review, I think, 19 75 percent in '05, 75 percent of the 20 submissions in '06 in 90 days, and then it 21 goes up to 80 in '07. 22 And again, to their credit, I think BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 59 1 86 percent or so was the number for '03-'04. 2 So they are exceeding these goals, but as we 3 look forward to MDUFMA 2, I think we need to 4 ensure that the goals highlighted in 5 the -- there's a second goals letter in 6 MDUFMA 2, an actual enhanced performance. 7 And I think 25 percent, you know, that was 8 the number that was thrown out in MDUFMA 1. 9 That's a good place to start. 10 And then, you know, whether it's 11 90 -- I don't know what the actual goals 12 themselves need to be, but it's something we 13 need to look at. Again, looking at 180-day 14 PMA supplements which represent I think 15 another decent segment of the submissions 16 that FDA reviews, prior to MDUFMA between 17 2000 and 2002, there were anywhere between 18 90-94 percent of 180-day supplements -- were 19 receiving an FDA decision within 180 days. 20 However, the goals under MDUFMA 21 allowed that number to drop to 80 percent in 22 '05, 85 percent in '06, and 90 percent in BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 60 1 '07. 2 And again, I think FDA is meeting 3 and exceeding the goals in many cases, but I 4 think there's an inherent problem when the 5 goal that was established under MDUFMA that 6 was talked about at 25 percent enhanced 7 performance in many cases actually 8 represented a decline in performance with the 9 status quo. And I think this is something we 10 need to address moving forward; are these 11 realistic but also aggressive performance 12 goals, in conjunction with a reasonable fee. 13 And that's going to be the way I think this 14 program succeeds moving forward. 15 Original PMAs. Again, prior to 16 MDUFMA, looking at the baseline between 17 2000-2002, 86 percent of the submissions had 18 an FDA's decision within 320 days, and 19 90 percent had an FDA decision in 347 days. 20 So that's kind of the baseline in which we 21 were operating prior MDUFMA. And I think 22 it's important to note that over the course BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 61 1 of first three years of this program, the 2 industry has contributed close to $80 million 3 in user fees. Congress has appropriated 4 approximately $30 million, with hopefully 5 more to come. 6 So it's not an insignificant amount 7 of resources that are being invested into the 8 FDA here. And then when you look at that 9 investment coupled with the goals that are 10 laid down in MDUFMA in FY '06, the goals 11 state that 80 percent of the decisions need 12 to have an FDA decision in 320 days. Again, 13 this allows for a drop from 86 percent. And 14 then in '07, 90 percent need to have an FDA 15 decision in 320 days, representing 16 approximately a 4 percent improvement. 17 So these are things that we need to 18 take a look at, and certainly, again, we 19 appreciate FDA's efforts to exceed the goals. 20 By no means do I think that they 21 are only trying to work to achieve the goals 22 and move on. I think the evidence indicates BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 62 1 otherwise, that they have taken steps to 2 improve that. But again, I think even the 3 steps to improve probably don't come anywhere 4 close to the 25 percent enhanced performance 5 that the industry was I guess promised or 6 committed prior to MDUFMA. That's something 7 we need to work on moving forward. 8 MR. BARNETT: Two minutes, Mark. 9 MR. LEAHEY: Perfect. I think we 10 need to re-evaluate both the cycle and the 11 review goals. Again, as I said earlier, we 12 do not want the cycle goals to impede the 13 process. I think they are important to 14 measure kind of the process, and ensuring 15 that there is communications early on in the 16 process. But we don't want the fixation on 17 the cycle goals to detrimentally impact the 18 overall review process. 19 And I think the goals should 20 reflect more than the status quo. So that 21 would I think clearly indicate that the 22 current goals need to be enhanced. And we BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 63 1 need to work with FDA, Congress and the 2 stakeholders to determine real and reasonable 3 goals. And this is something I look forward 4 to over the course of the discussions this 5 springtime. I think we all have to remain 6 focused that the ultimate goal here is to 7 enhance patient care. And I think if we keep 8 that as a primary focus, hopefully everything 9 else will fall into place. So thank you. 10 MR. BARNETT: Thank you, Mark. 11 Anyone on the panel wants to ask Mark a 12 question? Okay. If that's the case, let's 13 go on to our next speaker, Marlene Valenti, 14 with AdvaMed. 15 MS. VALENTI: Good morning. I'm 16 Marlene Valenti, and I'm the vice president 17 of Regulatory Affairs for Cordis Corporation. 18 And as Mark indicated, I'm also an AdvaMed 19 representative. I actually am the 20 chairperson for that PMA task force. And as 21 I told some of you during the break, I'm also 22 a very happy hurricane survivor from Wilma. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 64 1 As we all know, MDUFMA mandated 2 user fees, and we've heard over and over this 3 morning in regards to one of the key 4 objectives, and that was to reduce cycle 5 times from the time of submission to getting 6 that product onto the market. And that it 7 obviously includes both cycle goals as well 8 as performance goals, decision goals. 9 And we would like to commend FDA in 10 regards to the fact that have met most of 11 their 2005 performance goals, and based on 12 the numbers, actually most of the 2006 goals 13 also. 14 With that, and as Mark indicated 15 before, we are very happy that those goals 16 were met, but we have to go back to looking 17 at the key objective in regards to this 18 provision. And several FDA officials have 19 recently publicly stated in regards to 20 whether or not it really has met that 21 ultimate intent of that regulation, they've 22 indicated that in some cases, yes, and in BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 65 1 some cases with unintended consequences. And 2 I think when they speak to that point, what 3 they're talking about is that in some cases, 4 FDA is managing by the cycle times and the 5 decision times rather than pulling back and 6 looking at the big picture in terms of the 7 overall time from submission to market 8 release of that product. 9 If you talk to industry, I think 10 they would definitely agree with that 11 position. And in fact, I think industry 12 would say that the objective is very 13 infrequently met. In terms of industry, 14 here's some perspective in regards to first, 15 the PMA supplement non-approvable letters. 16 And if you look at the numbers that came out 17 in fiscal year 2003, it was about a 18 15 percent where we were receiving 19 non-approvable letters; that went up to over 20 40 percent in 2004. And that is very 21 significant in the aspect of obviously 22 getting the product to the market as quickly BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 66 1 as possible, and also allowing us to have 2 predictable review times. 3 We don't have the numbers for 2005 4 yet. I know AdvaMed has asked for those 5 numbers, but in terms of looking at the 6 preliminary numbers that were published, and 7 also just conversations with our members, we 8 do suspect that it's not any better, and it 9 may actually be higher than the 2004 number. 10 In addition, we've had some 11 conversation with the 510(k) working group 12 that was just headed up by Catherine Beath. 13 And they are indicating that they're seeing 14 an increase in NSC letters that are not 15 substantially equivalent. 16 So again, it seems from our 17 perspective that the FDA is managing to the 18 cycle and the decision goals rather than 19 pulling back and looking at the overall time 20 from submission to market. Now, in regards 21 to the path forward, I'd love to stand here 22 and say that we have all the answers and be BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 67 1 able to provide those to you today. We can't 2 do that, but what we can say is that in 3 discussion with our members, we strongly feel 4 that more guidance documents are needed, and 5 that that will facilitate the review cycle, 6 and that these guidance documents need to be 7 kept up-to-date and really reflect the 8 current thinking of FDA, so that when a 9 manufacturer goes through that guidance 10 documents, uses that for an application, that 11 they are putting in that application what FDA 12 is looking for and therefore not receiving a 13 non-approvable letter. 14 And one of the key ones that I know 15 we have been working with FDA for many years 16 on is the PMA change guidance document. And 17 I'm very happy to hear that FDA is treating 18 that as a priority to get that out. But we 19 really feel that is an important document for 20 us, because it really will provide 21 transparency on what type of submission is 22 required. In addition, AdvaMed is extremely BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 68 1 willing to work in a collaborative manner to 2 help develop innovate ways to improve the 3 process, and also in regards to the guidance 4 documents. We would love to be working with 5 FDA upfront. 6 I think one case that we can point 7 to in terms of what did work was working with 8 Dr. Gross' group, with OSB, in regards to the 9 conditions of approval. And we met with him 10 several times before he actually published 11 the guidance document. And I think having 12 that opportunity to provide to him what 13 worked and what didn't work allowed him to 14 put out a guidance document in a very, very 15 quick manner in terms of getting it out 16 there. 17 And it's something that pretty much 18 reflects most of the opinions that we had put 19 forward in terms of the key elements with the 20 conditions of approval. So if we were to 21 cite an example in terms of what would work, 22 I would encourage you to look at that BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 69 1 process. Thank you. 2 MR. BARNETT: Thank you, Marlene. 3 Again, anyone in the panel who want to ask a 4 question or some clarification? If that's 5 the case, let's go to our next speaker, 6 Marlene Keeling, who's with the Chemically 7 Associated Neurological Disorders. 8 MS. KEELING: Good morning. I'm 9 Marlene Keeling. I am president and a 10 founding director of Chemically Associated 11 Neurological Disorders, or CANDO. I want to 12 thank the FDA for the opportunity to speak 13 before this stakeholder meeting. 14 I'm here representing consumers of 15 medical devices. In particular, I will 16 address the approvable letter with conditions 17 recently sent by the FDA to the manufacturers 18 of breast implants. My concern is not with 19 the time it took the FDA to respond to the 20 manufacturer's PMA application, but the 21 science behind the decision to approve this 22 Class III device. My concern is with the BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 70 1 proprietary or secret conditions as set forth 2 by the FDA for ultimate approval. 3 The Washington Post quotes a cover 4 letter recently sent by Mentor to plastic 5 surgeons stating: "In anticipation of a final 6 gel breast approval, the FDA is requiring 7 that study doctors send a letter to their 8 study patients to remind them of the 9 importance of their commitment to continue 10 their one-, three-, and five-year follow-up 11 visits." 12 Does this mean that the FDA is only 13 going to require the manufacturers to follow 14 the breast-implanted patients for five years? 15 In networking with thousands of 16 breast-implanted patients, we know that often 17 it takes seven years or more after 18 implantation for symptoms of systemic disease 19 to appear. 20 The most common local complication 21 of implants is encapsulation. It is 22 well-recognized that this is an inflammatory BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 71 1 response in the body's attempt to wall off 2 this foreign material. Recently, there has 3 been much written about inflammation and its 4 role in systemic disease. Common sense tells 5 me that after a number of years, and when 6 these implants start to degrade, it 7 overwhelms the immune system and 8 detoxification ability of the human body. I 9 would like to briefly review the record of 10 the FDA and breast implant manufacturers. 11 Seventeen years ago, the FDA 12 classified all breast implants into the 13 Class III category because of reports of 14 adverse events in the medical literature. 15 Fourteen years ago, PMA submitted by the 16 manufacturers did not contain sufficient data 17 to warrant a review by the FDA. 18 Thirteen years ago, FDA decided to 19 allow silicone gel-filled implants on the 20 market only under controlled clinical 21 studies. Nine years ago, FDA sent a letter 22 to manufacturers detailing information needed BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 72 1 for core studies. This year, FDA sent 2 manufacturers an approvable letter with 3 conditions after reviewing only one, two and 4 three years of data. 5 My understanding is that the 6 current third generation implants being 7 considered for approval had been manufactured 8 since 1988. The question then becomes why 9 did the manufacturers not have 13 years of 10 data, or even 9 years of data? I believe I 11 know why, after networking with thousands of 12 breast-implanted patients. 13 The incidence of complications 14 becomes too high of this non-life-saving 15 device, and the women are not being followed 16 in many cases as required by the FDA, 17 especially after they develop local 18 complications or systemic disease. 19 In 1997, when I filed my first 20 Citizen's Petition regarding breast implants, 21 the manufacturers were being allowed to quote 22 a 1 percent rupture or failure rate, and many BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 73 1 women were being told that their implants 2 would last a lifetime. This was the 3 information that women were using to make a 4 decision as to how much risk they were 5 willing to take. After independent MRI 6 research by the FDA, it was determined that 7 the rupture rate was 77 percent, with 8 silicone seen outside of the scar capsule 9 21 percent of the time. 10 Manufacturers then changed the 11 wording in the product insert to simply say, 12 "Implants may not last a lifetime." As 13 stated by the Washington Post: "Some of the 14 major reservations voiced by the FDA 15 scientists and 2005 advisory panel experts 16 involve the relatively limited amount of 17 long-term information about the implant's 18 effect on women's bodies." 19 Paul Wooley, director of research 20 for orthopedic surgery at Wayne State 21 University, recently stated: "It's been 22 suspected for at least a decade that heavy BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 74 1 metals used in manufacturing of implants 2 might cause problems for women who receive 3 these implants." Independent research by the 4 FDA published after the IOM review in 1999 5 found an increased incidence of fibromyalgia 6 in breast-implanted women. Independent 7 research by the NIH, also published after the 8 IOM review, found an increased incidence of 9 some cancers in breast-implanted women, 10 including brain and lung cancers as well as 11 others. 12 I find it curious that when the 13 manufacturers pay for studies, they do not 14 find an increased incidence of systemic 15 disease for the most part. Former Mentor 16 employees reported to the New York Times that 17 data was falsified regarding breast implants. 18 One employee, who was a former product 19 evaluation manager from '96 to '98, said 20 Mentor never met basic quality standards for 21 implant manufacturing while he was there. 22 One employee who supervised BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 75 1 Mentor's complaint department said she 2 received about 6000 complaints of ruptured 3 implants in each of her three years at the 4 company. 5 However, in a recent filing with 6 the FDA, Mentor stated that it received a 7 total of 8060 rupture complaints from 1985 to 8 2003, or approximately 400 a year. How can 9 the FDA rely on any data submitted by Mentor 10 under these circumstances? Inamed stated at 11 the 2005 FDA advisory panel hearings that 12 their gel implants did not leak platinum. 13 Mentor stated that their implants did leak 14 platinum, but that it was in a zero valence. 15 CANDO submitted data to the FDA after that 16 advisory meeting on a woman with 1997 Mentor 17 third generation gel implants, and her 18 4-year-old son born after implantation. 19 Both were found to have significant 20 amounts of ionized platinum in their urine, 21 with a valence up to +4. Ionized platinum is 22 on the suspected list as being a BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 76 1 neurotoxicant, immunotoxicant, respiratory 2 toxicant and a sense organ toxicant. Dow 3 notified the EPA in 1996 of substantial risk 4 to their platinum catalyst used in the 5 manufacturing of breast implants. 6 Any detectable level of ionized 7 platinum is a health hazard. The more, the 8 worse it is. Several families with children 9 born after implantation testified at and sent 10 documentation to the FDA of significant 11 platinum urine levels up to 382 parts per 12 billion per liter of urine. 13 In an ongoing research project, 14 CANDO has now tested the urine of 20 children 15 born to breast-implanted mothers. Why is 16 this research being ignored by the FDA? 17 History will reflect that it was under your 18 administration that these devices that 19 rupture at an alarming rate and spill 20 chemicals and heavy metals into a woman's 21 body were approved. 22 MR. BARNETT: Two minutes, please. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 77 1 MS. KEELING: Sure. Due to the 2 combined lobby effort of the chemical 3 companies, the manufacturers and the plastic 4 surgeons -- these are the beneficiaries who 5 have the money to do clinical trials -- it 6 would be negligent should the FDA allow these 7 manufacturers to follow these women for only 8 five years. It would be negligent for the 9 FDA not to require the manufacturers to 10 follow-up on any children born to 11 breast-implanted women enrolled in a clinical 12 study, or not to require platinum urine 13 testing. 14 Because the chemicals and heavy 15 metals used in the manufacturing of medical 16 devices are considered proprietary 17 information or secret, consumers must rely on 18 the FDA to protect them and advise them of 19 potential risk. If approval is given, will 20 consumers be advised that their implants may 21 leak heavy metals, and these heavy metals, if 22 ionized, may cross the placental barrier and BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 78 1 brain barrier? 2 I would consider it grossly 3 negligent of the FDA not to require the 4 manufacturers to inform consumers of this 5 important information when making an informed 6 decision on how much risk they are willing to 7 take when implanted with these devices for 8 many years and during their childbearing 9 years. 10 Thank you. 11 MR. BARNETT: Thank you, 12 Ms. Keeling. Does anyone on the panel need 13 clarification or question? If that's the 14 case, we go to our last speaker, Bob Britain 15 of NEMA. 16 MR. BRITAIN: I'd like to welcome 17 Dan Schultz to the meeting. You made it from 18 Taiwan? You want to say, "What's in a 19 number?" Thirty years ago, the Medical 20 Device amendments came out, and there was 21 established 90 days and 180 days -- does 22 anyone in the room know how those figures BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 79 1 were established? Anyone? Other than a 2 political decision? 3 How many resources and hours we 4 have spent trying to defend those numbers is 5 amazing. I think 90 days is pretty good for 6 510(k)s; I think 180 days is probably short 7 for PMAs. It's hard to get a PMA through the 8 process with advisory committee meetings and 9 scheduling and that. But I want to leave you 10 with a good note, at least from the medical 11 imaging industry, since we're mainly 12 510(k)-oriented. 13 The 510(k) process is working very 14 well for us. Most of our 510(k)s are getting 15 through in 90 days. Also, the third-party 16 review process is taking under a total of 90 17 days, so we're feeling pretty good about 18 this. We probably had some ups and downs 19 trying to get digital mammography devices 20 through the PMA process, but that was a very 21 high profile -- at times very touchy issue, 22 and we had to be very careful about the data BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 80 1 and how it was derived. And FDA needed to 2 take some time to make those critical 3 decisions for those PMAs. 4 So on the whole, basically, it's 5 fun to be the last person on the panel, 6 because I can say that we certainly agree 7 with everything the first two speakers said. 8 And I'll leave it at that. 9 MR. BARNETT: Okay, thank you, Bob. 10 Anyone want a clarification on that? If 11 that's the case, is there anyone here who 12 would like to come up to the mic say a few 13 words? Sure, come on. Please identify 14 yourself. 15 MR. LASERSOHN: Jack Lasersohn from 16 the National Venture Capital Association. I 17 would like to endorse in part, and disagree 18 to some extent, with the first two industry 19 representatives. On the one hand, while we 20 absolutely believe it is appropriate to focus 21 on quantitative goals; for example, cycle 22 times and review times, it is very important BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 81 1 to remember, too, that you should not merely 2 focus on goals simply because they are 3 measurable. And I think one of the issues 4 that we have a real concern about is the 5 exclusive focus on quantitative goals simply 6 because they are measurable. 7 The biggest concern for the 8 venture-backed medical industry, that segment 9 of the industry, is really not how fast a 10 review is completed at the end of a cycle, 11 but rather how long the entire approval cycle 12 takes. And by that I mean not merely the FDA 13 review at the end, but the entire PMA 14 process. 15 Shaving 10 or 20 days off of the 16 end of a five-year PMA process that has cost 17 on average $40 million or $50 million is a 18 commendable goal. It's certainly not 19 something I would object to, but I have to 20 say that in the context of the companies that 21 we represent who are really almost always 22 looking to produce very innovative, unusual, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 82 1 almost revolutionary devices, that goal 2 really only affects perhaps 1 or 2 percent of 3 the total cycle time, which can typically be 4 in a PMA, which is unfortunately what most of 5 our companies end up doing are very fat 6 510(k)s, it can be four to five years. So I 7 think that we are going to be asking in this 8 MDUFMA 2 review to begin to try to focus on 9 qualitative goals of improvement that can 10 improve the entire cycle. 11 The other thing that I would say, 12 and in this regard I strongly endorse the 13 views of AdvaMed -- the data that was put up. 14 It is very important to be careful to not 15 have a result that produces wrong decisions 16 more quickly. And that to a great extent is 17 what we hear from the representatives of our 18 industry. That is, we can get decisions on 19 PMAs and in various cycles at 90 days or at 20 75 days, but they are the wrong decisions, 21 and we then have to go back and spend endless 22 cycles trying to fix these decisions. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 83 1 So making bad decisions or punting 2 that as asking for more information, more 3 quickly does not -- while it does technically 4 reach the goals of the cycle times -- has not 5 improved the overall cycle of getting these 6 devices to the market more quickly. 7 Thank you. 8 MR. BARNETT: Thank you. 9 MS. KAHAN: Can I ask a clarifying 10 question? Can you describe what you're 11 talking about in terms of these qualitative 12 goals? Are they things that you think FDA 13 needs to be doing, the industry -- 14 MR. LASERSOHN: Well, it's always 15 both, right; it's always collaborative. For 16 example, we find really when we look at where 17 the biggest delays and the biggest problems 18 are in the entire approval cycle, we find 19 it's very often at the front-end of the 20 cycle, not at the back-end of the cycle; for 21 example, in an endless negotiation over 22 endpoints in clinical trials and clinical BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 84 1 trial design. Now, we do recognize that that 2 is because we are almost always showing up at 3 the FDA with something that they have never 4 seen before. That's the nature of the 5 venture capital industry, to be revolutionary 6 rather than evolutionary. But there has to 7 be a better way to manage this other than a 8 one- or two-year education process. 9 We recognize the need for an 10 education process, defining the goals of an 11 acute AMI trial, for example -- for an 12 interventional device for acute AMI if the 13 FDA has never seen it before and the 14 physician community doesn't really understand 15 it yet, can clearly take time. 16 On the other hand, it shouldn't 17 take one or two years. We need to figure out 18 a faster way to accelerate the collaboration. 19 And that's what we are going to be -- as one 20 example -- and that's one of the things we 21 will be focusing on. 22 MS. KAHAN: Thank you. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 85 1 MR. BARNETT: Thank you. Anyone 2 else in the panel? Anyone else in the 3 audience want to come up and say a few words? 4 Yes, please. 5 MR. McKEEN: My name is Mac McKeen. 6 I'm with St. Jude Medical. And I'd like to 7 echo and reiterate Ms. Valenti's call for the 8 release of the PMA change guidance document. 9 Such a guidance is key for manufacturers to 10 consider when both sustaining the performance 11 of currently marketed devices as well as 12 iterating and developing new versions of 13 these marketed devices. 14 I say that in a real context in 15 that there was a draft guidance out there 16 that AdvaMed had actually worked with FDA in 17 developing, and it served as a very good 18 guide. Granted it was draft and not 19 official. I think it was pretty widespread 20 throughout the industry -- providing a 21 framework of what were the boundaries, when 22 to submit, when to do an annual report, and BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 86 1 how to document such product iterations. 2 In addition, such a guidance would 3 also serve FDA's post-market program by 4 helping to clarify annual reporting criteria. 5 It's not one of life's big mysteries, but 6 making that more transparent and clear as to 7 what goes in an annual report versus document 8 file, or a supplement for a PMA product I 9 think will be helpful for both parties and 10 clearly to the product lifecycle for FDA. 11 So I'd mention that the original 12 version was essentially complete, at least in 13 my use and practice of that device -- clearly 14 now, over time, it may have evolved, and it 15 can have some new items included. But 16 clearly, the 510(k) product has had a 17 guidance in place for years and it's been a 18 very effective tool, so I think we need to 19 build on that. 20 MR. BARNETT: Thank you. Anyone 21 else? All right. If that's the case, let's 22 go on -- yes? BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 87 1 MR. ST. PIERRE: Since we're ahead 2 of time -- I'm just going to ask one 3 question. The earlier presentations, the two 4 presentations from Mark and Marlene, talked 5 about the fact that FDA is meeting the 6 performance goals, but maybe the performance 7 goals aren't enough. And managing the 8 premarket program or the programs within a 9 center require managing and lot of different 10 principles. So if you're looking just at the 11 goals of review times, that's not nearly the 12 entire picture. 13 So can you put a weight on how 14 important some of the other aspects are, so 15 if you look at like guidance document 16 develop -- like in our office, we 17 probably -- from the last two years to the 18 previous two years, we've tripled the 19 guidance document output. 20 How much weight should that take 21 from the cycle goals or the decision goals? 22 We've given, as Dan mentioned in his opening BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 88 1 remarks, you know, 500 meetings. So we've 2 increased the number of meetings, and I 3 realize they're getting harder to schedule, 4 but they've actually gone up. So that's an 5 important aspect of the program that factors 6 in, too. 7 And I know the Agency's been giving 8 lots of presentations, more educational 9 presentations and things of that nature. And 10 at least in the IVD industry, I'm sure that 11 the rest of the medical device industry isn't 12 any different. There's a lot more innovation 13 that seems to be going on, and it's moving 14 very quickly. 15 And a lot of those newer 16 technologies seem to be going out quicker. 17 We're doing lots more de novo applications 18 and getting newer technologies out what I 19 think are pretty quickly. So how much can we 20 wait all those different things to see, am I 21 managing correctly, to just to give -- you 22 know, to split the resources all that way, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 89 1 because I could take them all off the other 2 things and just put them on just reviewing 3 the submissions that come in, so that's a 4 short-term gain, but probably a long-term 5 loss. So can you help the Agency try to 6 wait -- 7 MR. LEAHY: I don't know if I can 8 put specific percentages or weights 9 associated with each of those different 10 initiatives. I think they certainly are all 11 important, and I think the next panel is 12 actually qualitative performance. I mean, 13 this one was focused on the premarket 14 performance goals. 15 I think certainly, the meetings 16 before submission takes place are important. 17 To get it right, the guidance documents are 18 very, very helpful. And I think those are 19 things that'll be brought up in the next 20 session as far as qualitative issues. 21 One of the things I will say is, I 22 don't think it has to be an either/or BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 90 1 approach. I think when you have an 2 $80 million infusion from the industry, when 3 you have Congressional appropriations, 4 maintaining the status quo or simply 5 enhancing it a little bit is something that 6 should be achieved and is being achieved, but 7 I don't think those other things have to be 8 taken off the table. 9 So I don't view it as an either/or 10 approach. I think you're moving in the right 11 direction on all fronts, and I would hate to 12 have it be viewed as an either/or. I think 13 they are complementary, and I think that's 14 indicative of the way you structured this 15 program, where in this session it's the 16 premarket performance goals, the next 17 session, it's a qualitative goal. 18 So I think you're moving in the 19 right direction. I think we just need to 20 enhance all areas moving forward, because 21 again, this is a substantial investment on 22 behalf of the industry. And for that BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 91 1 investment, we really need to see returns. 2 You know, we are seeing returns, but we need 3 that to continue to improve. 4 MR. BARNETT: Anyone else want to 5 respond to Don's question? Yes. 6 MS. VALENTI: I would echo a lot of 7 what Mark said in regards to the fact that 8 you really can't say it's an either/or, it's 9 a combination. And like the gentleman said 10 in terms of the whole cycle, we do need to 11 look at the whole cycle in making sure that 12 we're managing appropriately in regards to 13 that. 14 And we don't want to just look at 15 the end. You know, we want to look at the 16 entire cycle, and I know we have some 17 comments in regards to the qualitative goals 18 that were set also. But I think in terms of 19 when we do talk about the review times, it's 20 important to look at how it's being managed 21 in terms of the cycle times versus the 22 decision times or the overall time. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 92 1 And I think we've had numerous 2 conversations, not only myself, but others, 3 in terms of with branch chiefs, and they've 4 indicated that even if they're not sure 5 whether or not they can make a decision 6 within 180 days, they issue a non-approvable 7 letter because they're managing to that cycle 8 time. So even if they're on the fence or not 9 even the -- they're pretty sure you can do 10 it, but they're not 100 percent sure, they're 11 indicating that they're issuing 12 non-approvable letters. 13 So I think there is a lot of 14 flexibility even with what we have today in 15 the funds that you have today, to be managing 16 it a little bit differently, to be able to 17 manage the entire life cycle. 18 MR. BARNETT: Thank you. Anyone 19 else? We have two here. Bob. 20 MR. BRITAIN: Well, I hope this 21 will be helpful. I think that a guideline is 22 a heck of an investment. It's worth doing, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 93 1 and it's worth doing well. At what cost, I 2 don't know, but if you don't have an 3 established guideline, the reviewers are 4 going to have their own. They're going to 5 have the things that they tick off. So 6 invest your resources in 510(k) guidance and 7 PMA guidance, and how you deal with that in 8 pitting that against the actual reviews, I'm 9 not sure, but guidance is a worthwhile 10 investment. 11 MR. BARNETT: Thank you. Go ahead. 12 (Phone Interruption) 13 MR. LASERSOHN: Sorry. 14 (Laughter) 15 MR. LASERSOHN: That's inevitable. 16 Two points: I absolutely agree that the 17 quantitative goals are very important. On 18 the other hand, I would point out again, 19 citing AdvaMed's presentation, that it is 20 possible to meet quantitative goals very 21 often by changing the rules or by asking 22 questions along the way. So for example, if BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 94 1 in fact a non-approvable letter rate goes up 2 while the cycle time goes down, that is not a 3 good outcome. So I would suggest, for 4 example, that if in fact we are going to have 5 quantitative goals, that situations like that 6 have to be considered, and one obvious 7 solution is that the cycle time goals will be 8 penalized to the extent that there are 9 increases in non-approvable letters. 10 So I would say that's point number 11 one. With respect to guidance documents and 12 other things, I do have a different position 13 than the rest of the industry, because again, 14 we are representing the segment of the 15 industry that is almost always doing 16 something new, by definition. And the 17 guidance documents almost never help us, they 18 almost always hurt us, because there's an 19 attempt to squeeze a particular completely 20 novel technology that nobody has ever seen 21 before into an existing guidance document. 22 And what we find is the first two BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 95 1 meetings that we have with the FDA over a 2 period of three or four months is 3 demonstrating that in fact this doesn't fit 4 into a particular guidance; you cannot apply 5 a particular guidance because it's completely 6 different. 7 So I think guidance can be very 8 helpful for those things for which it is 9 appropriate, you know, the 14th drug-eluting 10 stent -- it's a pathway that's 11 well-understood. There should clearly be a 12 guidance on how to get a drug-eluting stent 13 approved. But the first drug-eluting stent 14 is much more problematic. 15 MR. BARNETT: Thank you. Anyone 16 else? Yes, two more. 17 MR. McKEEN: Mac McKeen again, with 18 St. Jude. I just would like to recommend 19 that FDA work within an existing guidance. I 20 mean, there's been call for new guidance this 21 year in terms of the review process, and this 22 FDA clock. In fact, that's one of the BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 96 1 guidances, is how we calculate the FDA clock; 2 the stops and starts. And I think in the 3 end, that's what could put pressure or roll 4 up into that metric of when this thing gets 5 approved. 6 What I would suggest is that the 7 Agency give reviewers of PMA and PMA 8 supplements more discretion, and perhaps even 9 incentive, to engage in interactive reviews 10 rather than deficiency letters, because 11 deficiency letters stop the clock, and then, 12 tagger it, and then the industry has to get 13 back to restart the clock. 14 And certainly there is occasion 15 where that's necessary if there's a gap or a 16 hole in the content of the submission. But 17 in many cases -- or in some cases, I should 18 say -- pretty straightforward questions may 19 be contained elsewhere in the submissions or 20 easily answered through an interactive e-mail 21 or a phone conversation. 22 In business, that's how we get BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 97 1 things done. We don't stop the car and get 2 out to fix it. We keep having meetings and 3 working together collaboratively to keep this 4 whole process moving forward. So again, not 5 new or novel by any means, but I think it's a 6 part of the FDA review process that can be 7 easily expanded within the current guidance. 8 MR. BARNETT: Thank you. There was 9 another one there. Yes, please. 10 MR. ST. PIERRE: Well, I hope 11 that's actually happening now. And actually, 12 I agree with those other speakers, too, 13 decision goals are much important than cycle 14 goals. So let's focus on that. 15 MR. BARNETT: Since you haven't 16 spoken before, identify yourself. 17 MR. HAHN: Dennis Hahn, Ethicon 18 Endo Surgery. I'd love to give you a number 19 in terms of the number of guidance documents, 20 but again, it's a qualitative goal; it's 21 difficult to give. The concern that I have 22 is that all of our MDUFMA goals are based on BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 98 1 the back-end of the process. User fees are 2 based on -- once all of the data has been 3 collected, it's based on the review cycle, 4 and all the performance goals are based upon 5 that. 6 One of the things that we're 7 missing, and Linda, to your point earlier, as 8 we look forward to MDUFMA 2, we really need 9 to focus both quantitative and qualitative 10 goals on the front end of the process, and 11 that is things like the IDE review process, 12 and even more importantly -- and I have only 13 an NF 2, but really pre-IDE meetings, both 14 the quality and the ability to schedule. 15 What I have been seeing in my NF 2 16 is that pre-IDE meetings are being pushed to 17 the very limit because of the focus on cycle 18 time in terms of PMA review and so trying to 19 schedule a pre-IDE meeting is very difficult, 20 it takes the full 60 days at best, to try to 21 get all of the players together; both from 22 the Agency and from industry. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 99 1 So my focus for at least MDUFMA 2 2 is to look at some of the leading indicators, 3 which is really the early phase in the IDE 4 phase. 5 MR. BARNETT: Thank you. Anyone 6 else. Well, Don, you started a good 7 conversation there. Thank you. 8 MR. ST. PIERRE: I'm not on the 9 next panel. 10 (Laughter) 11 MR. BARNETT: Well, several people 12 have talked about qualitative performance 13 goals, and now we've got a session on that, 14 so thank you, guys. 15 And let me call up the next two FDA 16 subject matter experts, both from the Office 17 of Compliance, Tim Ulatowski and Mike 18 Marcarelli. 19 Our first speaker is Pat Shrader, 20 with AdvaMed. 21 MS. SHRADER: Good morning. My 22 name is Pat Shrader. I'm vice president of BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 100 1 corporate regulatory for Becton Dickenson, 2 and I am speaking today on behalf of AdvaMed. 3 My topic is qualitative goals, and I 4 certainly appreciate the nice lead-in from 5 both Don St. Pierre and other members of the 6 audience who have already spoken about this, 7 and have emphasized the importance of some of 8 these qualitative goals in making sure that 9 the intent of MDUFMA is really met. 10 First, I would like to add my 11 compliments to the compliments of some of the 12 earlier speakers to FDA for being able to 13 meet many of the explicit performance goals 14 for MDUFMA. I think FDA has made a lot of 15 progress in this area. It's been a lot of 16 hard work on both sides, but it's been some 17 very important work. 18 We talked last year about 19 qualitative goals, and particularly 20 scheduling of meetings, modular PMA reviews, 21 bundling and pre-approval GMP audits, and 22 we've seen improvements in some areas, and in BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 101 1 other areas, we see additional opportunity 2 for improvement. 3 And let me point out that one of 4 the downsides of speaking about qualitative 5 goals is that these things aren't measured, 6 and we don't have good metrics around them, 7 so much of what I will be sharing with you is 8 anecdotal information. 9 But those of you who deal with 10 things like customer complaints or 11 constituent complaints on a day-to-day basis 12 realize that you can get a pretty good feel 13 for how things are really working based on 14 the amount of background noise around 15 something. 16 I did want to point out, if you 17 look at CDRH's 2006 priorities, you will see 18 that the performance record in fiscal year 19 '05 has been good, and also that there has 20 been focus on more than just the performance. 21 It's been on a change in the culture, and I 22 think this is particularly important to tie BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 102 1 in to the qualitative goals; that the 2 coordination of all the activities that lead 3 to the quickest possible time to market for 4 products, and the accountability on both 5 sides, both industry and FDA, is something 6 that we need to pay attention to. And I 7 think we also appreciate the fact that FDA 8 has identified continued improvement as one 9 of their goals. 10 So "Scheduling of Meetings," you 11 have already heard a few words about that in 12 the goals letter that was done at the time of 13 MDUFMA in 2002. FDA and the industry stated 14 that both agreed that the use of informal and 15 formal meetings is critical not just to 16 ensure high application quality, but also to 17 ensure speedy reviews. 18 Yet AdvaMed members are currently 19 indicating that scheduling of meetings is 20 becoming more and more a concern, and I think 21 it goes without saying that improvements in 22 scheduling are going to be important to BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 103 1 assure that the overall intent and the 2 specific performance goals are met. 3 So I would encourage us on both 4 sides to try to develop some meaningful 5 metrics around scheduling of meetings, how 6 long does it actually take to get meetings 7 scheduled, and how does that play into the 8 full review cycle? 9 PMA Modular Reviews. The Industry 10 has always been very supportive of modular 11 review. It has a lot of benefits in that as 12 you finish up a particular area, 13 pre-clinical studies, for example, you can go 14 ahead and put the submission in, get 15 questions on the table, get those questions 16 answered, and optimistically not have to go 17 back and re-review that. 18 It also provides an opportunity for 19 FDA to get some of the work done ahead of 20 time and really to be able to focus on the 21 clinical data as the last piece of 22 information that goes into the review cycle. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 104 1 FDA's perspective on modular PMAs has been 2 mixed, some people seem to favor them, other 3 people are concerned about the additional 4 resources that are required, but certainly 5 from an industry perspective, we would 6 encourage you to continue this program. And 7 more importantly, we think there should be 8 specific performance goals for modular PMAs, 9 and would be interested in seeing this as an 10 element for MDUFMA reauthorization. 11 And in terms of setting metrics for 12 that module should be closed and in a timely 13 fashion, and in order to do so, questions 14 would have to come back from FDA to the 15 company in a very timely fashion, and we are 16 suggesting that 75 days for questions, and 90 17 days to review a completed module, should be 18 appropriate. 19 I don't believe that we talked 20 about bundling last year, but bundling was a 21 real concern that the industry brought up 22 back again in 2002. On both the device and BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 105 1 the diagnostic side, there were concerns that 2 FDA would try to find a way to split a 3 product or a product line into too many 4 separate applications in order to collect the 5 fee. And in reality, that's not what has 6 happened. 7 On the medical device side, 8 bundling, I think, has been very effective. 9 On the in-vitro diagnostic side, it may 10 require some reconsideration. FDA did put 11 out a guidance on bundling. A specific 12 example provided by one AdvaMed member is 13 that that guidance specifies that for 14 anti-microbial susceptibility tests, one 15 submission is required per drug, and can 16 cover both gram positive and gram negative 17 organisms. 18 In fact, that has not always been 19 the case, the actual decision is made on a 20 case-by-case basis, and the result of this is 21 that the fees for some in-vitro diagnostic 22 products are disproportionately large. Just BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 106 1 to provide one example for one particular 2 product platform, 56 submissions were 3 required that actually covered only 22 4 products. So in that case, the effective 5 510(k) fee was $8000 per product. 6 And ending on a positive note, last 7 year, we mentioned the need for coordination 8 in the timing of pre-approval inspections, 9 because various AdvaMed members were noting 10 that these were holding up the final PMA 11 approval. And we also noted that this was 12 not only responsibility on the part of FDA, 13 but also that it was important for sponsors 14 of PMAs to be sure that this was incorporated 15 in their project planning, and that in fact 16 they would be prepared for their pre-approval 17 inspections at the appropriate time. 18 The good news this year is that the 19 noise level around this issue seems to have 20 gone down substantially, indicating that in 21 more and more instances, FDA is able to 22 appropriately schedule the pre-approval BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 107 1 inspections so that they don't in fact hold 2 up the final decision. 3 So in summary, what I'd like to say 4 is that we have certainly seen some 5 significant areas of improvement in 6 qualitative goals. There are still some 7 opportunities that remain in a variety of 8 areas. I think both FDA and the industry 9 agree that these are important, and these are 10 areas in which we should try to establish 11 some baseline metrics, and wherever possible, 12 some goals for a MDUFMA reauthorization. 13 Thank you. 14 MR. BARNETT: Thank you, Pat. Is 15 there anyone on the panel who wants 16 clarification. Yes, Joanne? 17 MS. LESS: Pat, sorry, I don't have 18 much of a voice. One of the previous 19 speakers mentioned the difficulty in 20 scheduling pre-IDE meetings. 21 MS. SHRADER: Yes. 22 MS. LESS: And in your slide, you BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 108 1 just referred to meetings in general, so are 2 you seeing it across all the three program 3 areas, or still predominately in IDE area? 4 MS. SHRADER: I think it crosses 5 this all three program areas. My own 6 experience has been with informal meetings, 7 and scheduling is becoming difficult. 8 MS. LESS: Okay, thank you. 9 MR. BARNETT: Tim? 10 MR. ULATOWSKI: Yes, Pat, perhaps 11 you want to respond, or it may generate other 12 responses after you, because I think you are 13 the only scheduled speaker, but anyway, a 14 couple of things: What are your views in 15 regard to pre-IDE meetings and IDE meetings, 16 participation of compliance folk to discuss 17 GMPs and BIMO aspects during the course of 18 the early days of investigations? 19 MS. SHRADER: Well, I think 20 certainly getting input on any expectations 21 around inspections, whether they be BIMO or 22 GMP inspections, is important. So I think BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 109 1 that having participants from FDA who can 2 address those areas and give some insight 3 into what they maybe looking for and what 4 their concerns might be would be appropriate. 5 MR. ULATOWSKI: You mentioned the 6 "not ready for inspection" aspect. 7 MS. SHRADER: Yes. 8 MR. ULATOWSKI: What has the 9 industry done, to your knowledge, to make 10 improvements in regard to this aspect? 11 MS. SHRADER: Well, I think that 12 the trade associations have certainly carried 13 the message home to all of their members that 14 this is a collaborative effort, and for 15 industry to make this process work as well as 16 it should, that it's very important that we 17 be very mindful of timing and scheduling, be 18 mindful of the workload that FDA has and make 19 sure that we are in there prepared and 20 talking to the appropriate people at the 21 appropriate time. So I think the 22 associations have done a good job of letting BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 110 1 their members know. 2 MR. ULATOWSKI: Let me just ask a 3 third question: People are keeping track of 4 my questions here. What are your views 5 regarding what I will call early intervention 6 inspections; for example, on BIMO, as a means 7 to reduce total process time for PMAs? 8 MS. SHRADER: I'm not clear what 9 you mean by "early intervention." 10 MR. ULATOWSKI: Meaning inspections 11 during the early course of investigations to 12 perhaps reduce the back-end load on the BIMO 13 inspections, when things are coming to a head 14 at the end. 15 MS. SHRADER: Well, I would have to 16 give that a little additional thought. One 17 concern that I would express is that I don't 18 think that the BIMO inspections can be 19 terribly early in the process, because 20 experience with clinical investigation 21 suggests that you select your investigators, 22 get all your agreements in place, you go in BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 111 1 and train the investigators. 2 But depending on the device, there 3 may be a learning curve, and as a result, 4 companies do try to monitor their studies 5 carefully, and in fact, may intervene early 6 themselves to try to either make changes in 7 techniques, changes in devices, or changes in 8 training for investigators. So I think 9 earlier rather than later is a positive, but 10 I would caution against trying to get 11 involved too early in the course of a 12 clinical investigation. 13 MR. ULATOWSKI: Thank you. 14 MR. BARNETT: Anyone else on the 15 panel who wants to add anything? How about 16 in the audience? Yes, we have a lot of them, 17 okay. 18 MS. VALENTI: To the last point, I 19 would reiterate what Pat indicated in regards 20 to the clinicals: That we do have to 21 intervene early on in the process sometimes 22 in order to correct those. So I think it is BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 112 1 more appropriate for the sponsor to do that 2 rather than using the resources of FDA to do 3 that. 4 So moving it not necessarily at the 5 end, but closer to the end would probably be 6 more appropriate. But your question in 7 regards to having the Office of Compliance at 8 the meetings early upfront during the IDE 9 process I think is very critical, especially 10 for combination products. And where we are 11 looking at which of the GMPs and QSR should 12 apply for that product, I think in that case, 13 it would be very critical. 14 MR. BARNETT: Thank you. Before we 15 go to the next one, let me ask our 16 transcriber, if someone has spoken before, is 17 it still necessary to identify themselves? 18 Where are you, transcriber? 19 COURT REPORTER: No, unless I can't 20 remember their names. 21 MR. BARNETT: So it's only when 22 they haven't spoken before. Thank you. All BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 113 1 right, who is next? 2 MR. DURGIN: Bob Durgin with 3 Biomet. I just want to speak about one of 4 the things that I think we have seen work 5 well from our experience, and that is the 6 Office of Compliance's review of 7 manufacturing modules of PMAs. I want to 8 compliment the Office of Compliance for their 9 internal metrics. 10 I know there are no performance 11 goals in this area, but we have seen very 12 good performance on those internal metrics. 13 There has been good accessibility of the 14 staff, informal discussions during the review 15 process. And we have also seen very timely 16 scheduling of a pre-PMA inspection. 17 I guess the one area where I think 18 there is still some room for improvement is 19 similar to what we see in the other 20 performance goals, that there be focus on the 21 total decision time as opposed to meeting 22 just the individual cycles for reviews. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 114 1 I think we have seen in one of our 2 PMAs a number of letters where the 3 internal -- I think it's 30-day goal -- has 4 been met, but ultimately there were more 5 cycles than I think was necessary in the 6 process. But overall, I think it really has 7 been an area that's worked well and there has 8 been significant improvement. 9 MR. BARNETT: Thank you. Anyone 10 else? We had several hands earlier. Please? 11 MR. LASERSOHN: First of all, I 12 apologize for stepping up here each time. I 13 didn't realize that we could present at the 14 end of each session, so I going to do it this 15 way. First, a caution, as I said before: 16 Trying to apply quantitative metrics to 17 qualitative performance goals is very 18 problematic, and the natural tendency is 19 always to measure something -- it would not 20 matter what it is -- whether that is really, 21 what matters or not. 22 And for those of you who do BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 115 1 clinical trials, you know that that's always 2 a problem, measuring things, or you tend to 3 measure what you want to measure or what's 4 easy to measure, and sometimes the stuff 5 that's much more difficult to measure is the 6 stuff that really matters. 7 So I will get to that point in a 8 second. But speaking of quantitative goals 9 with respect to qualitative, as the last 10 speaker indicated, the total cycle time for 11 regulatory approval is what matters to our 12 members. 13 And clearly one of the things that 14 we can do is begin to measure that, so that 15 instead of thinking about merely the cycle at 16 the end of a four- or five-year approval 17 process, we really need to start to keep 18 track of the total time for an approval of a 19 product, starting from the very first 20 communication, for example, by a sponsor with 21 the FDA with respect to a particular 22 approval. We have to begin to measure that. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 116 1 And I think that we would find that beginning 2 to focus on that, just to at least measure 3 it, would be very, very productive. 4 With respect to the qualitative 5 types of improvements that we can make for 6 qualitative outcomes, I think we have to look 7 at broader regulatory changes rather than 8 trying to quantify performance measurements. 9 So for example, we will be proposing in this 10 next cycle that the entire risk-based 11 assessment process be given much much greater 12 priority, and that a risk-based approval 13 process really be defined as a separate 14 process. 15 A sponsor should be able to put 16 things to request that approval cycles be in 17 a different category, even if they are PMA or 18 510(k) or de novo 510(k), that we can create 19 a new category, a new pathway on a risk-based 20 basis. 21 Similarly, we believe that it's 22 necessary to begin to think about a separate BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 117 1 process for novel devices. That is, if one 2 of our companies walks in with something that 3 we know you have never seen before, it really 4 makes no sense to attempt to fit it in into 5 an existing PMA or 510(k) process, and there 6 should be a mechanism for requesting -- not 7 an expedited process; that's not at all what 8 we are talking about, but a process that 9 recognizes the novelty of a particular 10 device, and as a result, is going to bring 11 different resources of the FDA to bear and 12 make additional resources of the FDA 13 available to avoid the problem of negotiating 14 endpoints for a year or two in an IDE trial 15 because the reviewer has simply never seen 16 such a thing before and is going through a 17 long learning curve. 18 So we are going to be emphasizing 19 qualitative changes in process, or new 20 qualitative processes in order to address 21 these qualitative performance requirements. 22 MR. BARNETT: Thank you. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 118 1 MR. ULATOWSKI: I have one 2 question. 3 MR. BARNETT: Yes, please. 4 MS. KAHAN: Could you clarify what 5 you mean about that first category of risk 6 based -- I'm sorry, risk-based products -- 7 and we usually think of it as risk benefit. 8 Are you talking about qualitative -- 9 MR. LASERSOHN: Well, of course, 10 risk benefit is a safety question, and there 11 is an explicit de novo 510(k) process which 12 is a risk-based process, but it technically 13 applies only to products that don't fall into 14 other categories. 15 What we are going to request, for 16 example, is that on products that we believe 17 are demonstrably safe, that we can put them 18 into a different review category and treat 19 them in a different way so that there is an 20 explicit understanding, not so much at the 21 top of CDRH, which frankly we think works 22 very, very well, but at the staff level of BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 119 1 CDRH, that they must consider risk 2 adjustments to, for example, the endpoints of 3 clinical trials. 4 This is, I would say, of all of the 5 things that we encounter, the risk-benefit 6 discussion around the question of what kinds 7 of assurance of efficacy do we need, what 8 kinds of evidence do we need, has been one of 9 the most difficult problems we've faced with 10 the FDA in the past five years. 11 That is, there should be an 12 adjustment -- since the statute requires for 13 a reasonable assurance of efficacy -- there 14 should be an adjustment of the efficacy 15 evidence requirements based on the relative 16 safety or lack of safety or risk of the 17 device. 18 And while the top of the CDRH 19 clearly understands that, that is really not 20 understood at the staff levels, so we think a 21 process that would elevate, for example, that 22 aspect of a particular approval would help BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 120 1 the staff to apply the correct metrics. So 2 that's the kind of suggestion that we would 3 be making. 4 MR. BARNETT: Someone else up here 5 had a question? It's answered, okay. Anyone 6 else in the audience want to speak? Yes, 7 sir, come on up. 8 MR. TOTAH: Good morning, Alan 9 Totah with Cyberonics. Just one point I 10 think I would like to make to the panel, have 11 you consider: when companies develop not only 12 new, unique technology, but if they are 13 developing new indications that the Center 14 has never had to deal with before, we would 15 ask that where the reviewing branch or 16 division does not have that expertise, and I 17 know we have to separate your jobs a little 18 from our jobs, but in reality most of us in 19 the regulatory profession, we are all doing, 20 roughly, the same thing. 21 If the company has an expertise, 22 which they obviously do since they have gone BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 121 1 through a trial to develop the data, we would 2 ask that they should consider meeting with 3 the company if the company is willing, so 4 that we can provide some in-depth knowledge 5 about the new indication, the expertise to 6 help the process of determining safety and 7 effectiveness a quicker process. 8 We often know that within each 9 division, they may not have all the 10 expertise, and they will go to another 11 division to get that expertise, but in some 12 cases that doesn't even exist. And for some 13 unique products or indications, the expertise 14 may reside fundamentally within that company. 15 And I know, speaking for my 16 company, and I'm sure many other companies 17 here, we're very willing to meet with FDA 18 early in the review process to help provide 19 education, answer questions, to help the 20 review process move more quickly. So that's 21 my only comment. Thank you. 22 MR. BARNETT: Thank you, anyone BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 122 1 would want to respond to that? Okay, anyone 2 else in the audience? Going, going and gone 3 for lunch. 4 It's time to eat now; you have 5 gotten in your handouts some local places 6 where you can eat. There is also a dining 7 room in the hotel. 8 I have 11:30 a.m., why don't we 9 plan on being back here at 12:30 p.m. 10 Thanks. 11 (Whereupon, at approximately 12 11:30 a.m. a luncheon recess was 13 taken.) 14 15 16 17 18 19 20 21 22 BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 123 1 A F T E R N O O N S E S S I O N 2 (12:41 p.m.) 3 MR. BARNETT: We're ready now to 4 begin the fourth of our six sessions, this 5 one on the third-party inspection program. 6 Our FDA representative joining our standing 7 panel is Steve Niedelman, with the Office of 8 Regulatory Affairs of FDA. And our first 9 speaker under this topic is a return -- oh, 10 you can. Look who's here! Yeah, please, 11 sure. 12 SPEAKER: Thank you. 13 MR. SCHULTZ: Good afternoon. I 14 got to listen to part of the discussion this 15 morning, and I just want to tell you that I'm 16 incredibly impressed with all the great ideas 17 that were expressed here this morning. 18 I found myself agreeing with the 19 majority -- I can't say everything -- but the 20 majority of what I heard in terms of all the 21 various areas that we need to work together 22 to try to find some improvements, whether it BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 124 1 be looking at innovative products that we 2 don't fully understand, whether it be looking 3 at the review process and making sure that 4 we're focusing on what it is that really 5 needs to be done, and whether it be looking 6 at resource issues that clearly, clearly are 7 part and parcel of making sure that we're 8 able to accomplish all of these lofty goals. 9 So I just wanted to say hi, I got 10 to do it on a little tape, but I just wanted 11 to say hi in person and to thank each and 12 every person that came to this meeting, and 13 to tell you that we are certainly looking 14 forward to working with you to try to realize 15 a lot of what you are discussing here today. 16 Thank you very much. 17 MR. BARNETT: Thank you, Dan. And 18 now for our first scheduled speaker for this 19 session, we have a return of Bob Britain from 20 NEMA. 21 MR. BRITAIN: I'm sure you can hear 22 me; I just can't hear myself over this air BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 125 1 conditioning unit up here. I think most of 2 you know the original intent for seeking 3 legislation to allow for third-party 4 inspections was to be a win-win situation for 5 both FDA and industry. 6 Now FDA would receive inspection 7 reports of participating manufacturers every 8 two years, whereas at least several years 9 ago, FDA inspection frequency was as high as 10 every six years, so this would have been a 11 big boost to FDA. 12 Manufacturers, on the other hand, 13 would submit to more frequent inspections, 14 with the thought that the FDA inspections 15 could be meshed with EU notified body audits, 16 making the whole process more efficient. We 17 will not know for sure whether this goal is 18 achievable until the process is up and 19 running, which it isn't yet. Since a large 20 number of medical device manufacturers have 21 global businesses, it makes sense to push the 22 third-party inspection concept globally or BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 126 1 even regionally. 2 And to do this successfully, 3 however, you need to have a successful track 4 record, and this is where FDA comes in, as 5 many countries with developing programs look 6 to FDA as the gold standard. And this is why 7 it is so important that the third party or 8 accredited persons program works 9 successfully. If it doesn't, we will have 10 much difficulty selling this abroad. 11 A few concerns. There are many 12 issues that need to be addressed and solved 13 before this program will be successful. The 14 process for accrediting accredited persons 15 and their organizations has been slow and 16 arduous and expensive for both FDA and the 17 accredited person organizations. It is 18 simply not simple to qualify auditors or 19 these organizations. 20 Scheduling prequalification audits 21 is difficult. FDA's availability rarely 22 coincides with the manufacturers' audit BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 127 1 schedule. So far, only five of fifteen 2 organizations in MDUFMA are accredited to 3 perform inspections. And since it has been 4 several years since MDUFMA was enacted, I 5 don't know how many of the auditors have to 6 be actually retrained. I'm not sure about 7 that. 8 Besides the problems in getting the 9 accredited persons and their organizations in 10 place, the current program is cumbersome and 11 far from user-friendly. Entering the program 12 and staying in the program for manufacturers 13 has yet to be tested. On paper, it has its 14 drawbacks. Having to change accredited 15 persons after so many inspections may be a 16 burden for some manufacturers. These reasons 17 alone may limit the participation by 18 manufacturers in the program. 19 Even if some manufacturers make it 20 through the hoops and hurdles, participation 21 will be small in the beginning. You have to 22 expect that. It took several years to be BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 128 1 considered the third -- we saw this with the 2 510(k) third-party review program, because it 3 took several years to be considered a 4 worthwhile program for FDA. 5 The bright side is that many of us 6 in the industry are optimistic about the 7 accredited persons program; we want to make 8 it work. But it will be a matter of trust 9 and willingness on FDA's part to work with 10 the industry to make the program, number one, 11 least burdensome and efficient, and to be 12 done at reasonable cost. And so we have 13 hopes. We need to make it work; we need to 14 take it global. That's the only thing that's 15 going to save this industry from hundreds of 16 inspections. Thank you. 17 MR. BARNETT: Thank you, Bob. 18 Anyone on the panel want to respond to that? 19 MR. NIEDELMAN: The only thing I 20 would like to just suggest, and Bob knows 21 some of this: We do have five accredited 22 persons that are currently available, and BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 129 1 those who are Class II and III manufacturers 2 should shortly be receiving a letter that I 3 just signed a few days ago indicating that 4 these five are available, but there is new 5 guidance out there since the middle of 6 September on how to use the AP Program. And 7 we certainly encourage firms to offer their 8 facilities as audit sites so we can get more 9 of these APs through the system as rapidly as 10 possible. It is not easy, as Bob said, to 11 schedule a lot of these audits. 12 MR. BARNETT: Thank you, Steve. 13 Anyone in the audience want to respond? 14 Let's go to our next speaker, Diane 15 Wurzburger, from AdvaMed. 16 MS. WURZBURGER: Good afternoon. 17 Diane Wurzburger, Director of Government 18 Affairs from Siemens Medical Solutions, 19 representing AdvaMed this afternoon. Thank 20 you for having the opportunity to speak. 21 First, I would like to say that 22 AdvaMed concurs with Bob Britain's points BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 130 1 just now, what NEMA said. I think the 2 experience has been pretty consistent in our 3 industry with this program. 4 But I would like to add emphasis to 5 a few of the points that are important to our 6 members. While the program has been received 7 initially by industry with great expectation, 8 of course, to improve the efficiencies with 9 respect to our inspection programs, we're 10 still facing several practical challenges, as 11 Bob noted. 12 First of course is with those 13 manufacturers who have volunteered thus far, 14 they are faced with the difficulty of 15 scheduling the prequalification inspections. 16 And additionally, the entry requirements of 17 the programs themselves are very cumbersome 18 and complex. Both of these issues have 19 frustrated industry, who have -- again, the 20 primary interest of participating in this 21 program to make more efficient their 22 inspectional program. So we hope that FDA BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 131 1 will consider those concerns and review those 2 for us. 3 We would like to recognize, 4 however, the effort FDA has taken with 5 respect to implementation of the program. As 6 Bob noted, similar to the third-party review 7 program, every new system implementation 8 takes time and has some bumps on the road, 9 and we hope that we can work together to 10 resolve those issues and move forward with 11 the program. 12 Thank you. 13 MR. BARNETT: Thank you, Diane. 14 Anyone want to respond to that? Anyone in 15 the audience want to respond or have a 16 comment? If not, we'll go to our next 17 speaker, Lindsey Wade, from the National 18 Research Center for Women and Families. 19 MS. WADE: Hi. My name is Lindsey 20 Wade, and I'm a policy associate at the 21 National Research Center for Women and 22 Families. We're a non-profit, non-partisan BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 132 1 advocacy center that works to improve the 2 health and well-being of women and children 3 in the United States. I'm here today mostly 4 to remind the FDA that the concerns shared by 5 public health advocates, consumer advocates, 6 and patient advocates about third-party 7 review in 2002 still exist. 8 At the National Research Center for 9 Women and Families, it's our position that 10 third-party inspections weaken safety 11 precautions. To put it more bluntly, the 12 accredited persons program creates an 13 inherent conflict of interest that is 14 unacceptable. The third-party inspectors 15 have little incentive to find problems, 16 because there is no firewall between the 17 inspector and the company that hires them. 18 Manufacturers can attempt to 19 influence the accredited persons with high 20 payments and promises of increased future 21 business. The accredited persons can curry 22 favor by consulting rather than strictly BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 133 1 auditing manufacturers and overlooking 2 problems they identify. The client-employer 3 relationship is very different from the 4 inspector-inspectee relationship that should 5 exist in this situation. 6 Accredited persons even promote 7 their ability to improve their client's 8 business, virtually eliminating the 9 possibility that they are unbiased auditors. 10 For example, one AP claims that "Our founders 11 sought out and recruited more of the best 12 auditors in our business because they know 13 that it is auditors that make the difference 14 to you. You will find that our auditors are 15 fair and consistent; they are 16 service-oriented and look for ways to add 17 value to your company." 18 "Our auditors won't tell you how to 19 run your business, they will help you 20 understand the requirements and the various 21 ways you can fulfill them. We will partner 22 with you in order to improve your systems and BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 134 1 therefore your bottom line." 2 And from our perspective, the APs 3 aren't supposed to be partners, they are 4 supposed to be inspectors and auditors. 5 Further evidence of the conflict of 6 interest that exists between the 7 manufacturers and the accredited persons is 8 the fact that manufacturers provide 9 accredited persons with testimonials and 10 offer to serve as references to increase 11 their AP's future business. And I just would 12 like to briefly read excerpts from some 13 testimonials. 14 This one is from an American device 15 company to an American accredited persons 16 company. It starts off with: "I feel like we 17 are in a partnership, and I see tangible 18 value to our relationship. We have had 19 assessors at both companies on an annual 20 basis for many years who worked for our 21 former registrar. We had no idea what we 22 were missing." BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 135 1 "All your assessors are very 2 thorough and professional and take their 3 responsibility seriously. I felt like they 4 were there not only to assess our companies 5 but to help us become better. They obviously 6 cannot consult, but they can and did offer 7 comments in how others had addressed similar 8 issues. In short, we can't be happier. 9 Please pass along my sincere thanks and 10 congratulations to your entire organization, 11 and feel free to share my comments with 12 others as you feel appropriate." 13 Similarly, another letter commends 14 the AP for an excellent job, and says: 15 "Please do not hesitate to use me as a 16 reference." 17 It's entirely out of character for 18 an inspectee to offer such services to an 19 unbiased inspector. And there is no question 20 that this sort of communication reduces that 21 accredited person's ability to be unbiased. 22 Just to clarify this with an analogy, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 136 1 consider local county public health 2 departments and the inspections of 3 restaurants. 4 Local city and county departments 5 of health are responsible for ensuring that 6 restaurants comply with local ordinances in 7 order to ensure that the restaurants comply 8 with requirements for sanitary food prep 9 areas and other issues. Without these 10 inspectors making inspections on a regular 11 basis to all the restaurants that we go to, 12 we would have no assurance that we're eating 13 food that is safe to eat. 14 If those restaurants were able to 15 hire a private inspector to guide them and 16 partner with them, the public might not ever 17 know about problems that exist in the past or 18 currently with health hazards at that 19 restaurant. With the system with public 20 health employees reviewing restaurants to 21 make sure that there is safe food 22 preparation, there is a public record of that BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 137 1 restaurant's behavior, whether it is good or 2 bad. 3 We understand that the Center for 4 Devices and Radiological Health is 5 underfunded and understaffed. However, we 6 would prefer fewer reliable inspections to 7 yearly biased reports from third-party 8 investigators. 9 Thank you for the opportunity to 10 speak today. 11 MR. BARNETT: Thank you, Ms. Wade. 12 Any comments or reactions from the panel? 13 And if that's the case, that's the last of 14 our three. 15 So let me open the floor to 16 comments or reactions to any of the things 17 that you heard during this panel. Anyone 18 want to say anything about this, about 19 third-party inspections? Comments that we 20 haven't heard before? Okay, if that's the 21 case, we're ready then for the next session. 22 Steve, thank you. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 138 1 MR. NIEDELMAN: Thank you. 2 MR. BARNETT: We'll call up Ginette 3 Michaud from the Office of Device Evaluation 4 at CDRH, and we're going to be talking now 5 about reprocessing of single-use devices. 6 And our first speaker is Naomi Halpern from 7 the Association of Medical Device 8 Reprocessors. Naomi? 9 MS. HALPERN: I'm sorry. Hi, I'm 10 sorry to keep you waiting. I'm Naomi 11 Halpern. I'm an attorney specializing in 12 providing advice to companies and individuals 13 with respect to the regulation of medical 14 devices and pharmaceuticals by the United 15 States Food and Drug Administration. My 16 firm, Olsson Frank and Weeda, is regulatory 17 counsel to the Association of Medical Device 18 Reprocessors, or AMDR. 19 AMDR is the trade association 20 representing the legal, legislative and 21 regulatory interests of third-party 22 reprocessors of medical devices labeled for BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 139 1 single use. AMDR's members represent 2 approximately 95 percent of the commercial 3 reprocessing industry. 4 It's worth reiterating what we've 5 said in the past, which is that prior to the 6 enactment of MDUFMA; reprocessors were 7 already subject to the same regulatory 8 requirements as original equipment 9 manufacturers. The safety record of 10 reprocessing has always been and continues to 11 be excellent. Today, more than 30 million 12 devices have been reprocessed and used in 13 this country without any evidence of 14 increased risk to patients. 15 The fact that certain devices 16 labeled by their original manufacturers as 17 being for single use that can safely be 18 reprocessed is widely recognized by the 19 clinical community, which has repeatedly 20 expressed overwhelming support for and 21 confidence in the safety of the reprocessed 22 devices. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 140 1 Reprocessors use state-of-the-art 2 validated procedures to clean, sterilize, and 3 restore their devices, and every device is 4 tested or inspected before being returned to 5 service. 6 America's finest medical facilities 7 use reprocessed devices, including 13 of the 8 14 hospitals ranked by U.S. News and World 9 Report in 2004 as America's top hospitals. 10 These institutions include Massachusetts 11 General, Brigham and Women's Hospital, The 12 Mayo Clinic, The Cleveland Clinic, and Johns 13 Hopkins University. It defies belief to 14 argue, as some have and continue to do, that 15 these fine institutions would put their 16 patients at risk in order to save money. 17 To the contrary, these facilities 18 use reprocessed devices because they have 19 studied the issue thoroughly and they have 20 determined that reprocessing is safe. 21 In light of the strict regulation 22 that was in place at the time that MDUFMA was BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 141 1 enacted, and in light of the safety record of 2 reprocessing, it is difficult to find any 3 public health rationale for MDUFMA's 4 reprocessing provisions. 5 Rather, it seems entirely clear 6 that economics were the driving force behind 7 these provisions, which were the product of 8 OEM's continuing frustration with the 9 economic threat posed by reprocessing. 10 Nevertheless, MDUFMA does contain some 11 important messages about reprocessing. 12 First, Congress clearly stated that 13 there are cost savings associated with using 14 reprocessed devices. Therefore, Congress 15 said, we want to ensure continued access to 16 safe and effective reprocessed devices. 17 Second, Congress intended that 18 MDUFMA be implemented in the least burdensome 19 manner consistent with FDAMA. AMDR has seen 20 its role over the past year as being in part 21 to keep reminding regulators of these 22 objectives as the Agency goes about BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 142 1 implementing the statute. 2 So where are we now? FDA continues 3 to implement MDUFMA, and reprocessors are 4 complying with the requirements. 5 First, I would like to talk about 6 the MDUFMA-imposed requirement that 7 reprocessors make supplemental validation 8 submissions for some of their previously 9 cleared devices. Despite feeling that the 10 requirement may not have been implemented in 11 the least burdensome manner, as required by 12 FDAMA, our members have complied with this 13 new requirement, and FDA has completed its 14 review of most of these submissions. 15 Much more than the typical 510(k) 16 submission, the process of submitting 17 validation data has been an exercise in 18 working with the Agency to determine what a 19 submission was going to have to contain and 20 what it was going to have to look like. The 21 process of clarifying and responding to 22 questions about submissions occurred in the BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 143 1 context of a very tight deadline for 2 concluding the process. An enormous amount 3 of work was required to gather the 4 FDA-required information. 5 At the end of the day, many of the 6 submissions were cleared by the Agency. For 7 the submissions that were not cleared, AMDR's 8 members ceased shipping the devices that were 9 covered by those submissions. But AMDR's 10 members estimate that more than 95 percent of 11 their products lines were made legally 12 marketable. 13 We are aware that OEMs have 14 continued to assert that the issuance of "Not 15 Substantially Equivalent," NSE letters, to 16 the reprocessors just confirms their 17 oft-stated allegation that it is not possible 18 to establish that the reprocessing of some of 19 these devices is safe and results in 20 effective devices. 21 I want to remind you that all of 22 these devices were previously cleared by the BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 144 1 Agency. Safety was not the issue. And in 2 fact, the Agency has publicly clarified that 3 the fact that a particular submission was not 4 cleared before the deadline does not mean 5 that the devices were unsafe in FDA's 6 opinion. 7 The issuance of an NSE letter means 8 only that to date, the data and information 9 submitted were not sufficient to support a 10 finding of substantial equivalence, and 11 therefore, to be cleared by FDA. Indeed in 12 some cases, the NSE letters reflected nothing 13 more than the lack of sufficient time to 14 develop and submit the information due to the 15 Agency's imposition of a non-statutory 16 deadline. 17 In other cases, NSE letters were 18 issued because the reprocessor did not make a 19 submission or withdrew an initial submission 20 after making a business decision that the 21 economics of the market did not justify the 22 expenditure of the substantial resources that BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 145 1 would be required by the SVS process. 2 In short, as a factual matter, an 3 NSE letter does not establish that the device 4 covered by the letter is not safe or 5 effective, and there is clearly no 6 justification for the assertion that an NSE 7 letter is evidence that the submitter is not 8 capable of producing a safe or effective 9 device. 10 Over the last year, AMDR's members 11 have continued to work cooperatively with the 12 Agency, and many of the submissions that were 13 initially designated NSE have now been 14 cleared. In the past year, of course, 15 certain OEMs have continued their efforts to 16 persuade Congress to revisit the marking 17 provision of Section 301 of MDUFMA, and 18 specifically to apply that provision only to 19 reprocessors. 20 It's worth remembering that when 21 Congress was in the process of drafting 22 MDUFMA, FDA took the position that marking of BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 146 1 devices would have value, and in fact, it 2 would be helpful from a regulatory point of 3 view if all devices were marked. At the 4 time, OEM industry representatives were 5 willing to commit to doing that. 6 MR. BARNETT: Two more minutes. 7 MS. HALPERN: Congress, when 8 enacting the provision, specifically 9 emphasized that the section applies to all 10 devices, not just single-use devices. OEMs 11 afterwards recognized that complying with the 12 provisions would be burdensome, and for that 13 reason, OEMs returned to Congress to ask them 14 to amend Section 301 to apply only to 15 reprocessors. Congress yielded to this 16 pressure, and the Act was so amended. 17 AMDR's members will comply with and 18 flourish under the additional regulatory 19 burdens. In the last year, we have seen 20 further efforts from the OEMs to use the 21 regulatory process to further their economic 22 agenda. Specifically, there have been BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 147 1 several petitions from trade associations 2 asking FDA to add more devices to the lists 3 of reprocessed devices that require the 4 submission of validation data. 5 In general, we believe that these 6 requests have failed to include any credible 7 public health rationale. In the last few 8 months, FDA has, in response to these 9 petitions, added heart positioning devices 10 and endoscopic and microscopic devices to the 11 list of devices that require 510(k)s with 12 validation data. AMDR's members do not 13 oppose the requirement for 510(k)s for heart 14 positioning devices. 15 But AMDR believes that in fact, all 16 heart positioning devices should be subject 17 to 510(k) requirements. The exemption for 18 heart positioners appears to be based on the 19 fact that they are covered by the same 20 classification regulation as forceps, 21 retractors and other relatively simple 22 devices. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 148 1 However, the heart positioners and 2 stabilizers of today are much more 3 complicated devices that allow a surgeon 4 actually to lift and turn the heart. The 5 failure of such a device during surgery, 6 whether it is reprocessed or not, could 7 easily cause serious injury to a patient, and 8 the AMDR urges FDA to consider up-classifying 9 all of these devices and requiring 510(k)s 10 for all of them. 11 Apart from heart positioners, AMDR 12 strongly urges FDA to preserve the 510(k) 13 exemption for all currently exempt 14 reprocessed single-use devices, and to 15 decline to require SVSes for additional 16 devices. Finally, this year, we have seen an 17 upswing in activity on the state level to 18 enact legislation to burden reprocessing. 19 Typically, the OEMs involved in 20 pushing these efforts suggest to legislators 21 that despite the stellar safety history of 22 reprocessing, these bills are necessary BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 149 1 because safety of reprocessing cannot be 2 established. Although they have not to our 3 knowledge provided legislators with actual 4 examples of patient harm, they have 5 distributed photographs that purport to 6 establish that reprocessed devices may not in 7 fact be clean. In fact, they may show you 8 these photographs today. 9 However, to date, these OEMs have 10 to our knowledge been unable or unwilling to 11 authenticate these photographs, and the 12 bottom line is that there is no credible 13 evidence that devices reprocessed in 14 compliance with FDA requirements present any 15 risk to patients beyond the risk that is 16 associated with reprocessed devices. Let me 17 skip through most of this and just finish up. 18 I do want to say that one aspect of 19 the state level activity is informed consent 20 provisions. The purpose of informed consent 21 is to advice patients when a procedure 22 involves increased risk. However, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 150 1 reprocessed devices are as safe and effective 2 as the original equipment, and are in fact 3 arguably more stringently regulated. 4 Therefore, there is no legal, medical, or 5 ethical basis for imposing informed consent. 6 That said, AMDR does not oppose 7 state-level informed consent legislation that 8 honestly seeks to increase patient awareness 9 of medical device safety. Such a bill would 10 apply equally to OEMs, many of whom have 11 recently experienced serious safety problems 12 associated with their own devices. 13 Just a few weeks ago, FDA announced 14 that it had seized devices manufactured by 15 one major OEM because FDA inspections had 16 revealed that the firm is continually out of 17 compliance with GMPs. A few months ago, 18 another OEM acknowledged that it knew, that 19 it had not told doctors or patients for three 20 years about a flaw in its device. 21 Let me just say that reprocessing 22 saves hospitals substantial amounts of money. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 151 1 It's good for patients, it's good for 2 hospitals, it's good for the environment. 3 The good news for hospitals is that despite 4 the additional regulatory burdens that have 5 been increasingly placed on the industry, 6 reprocessing is continuing to flourish and 7 also to drive prices down of original 8 equipment itself. 9 In short, reprocessing plays a 10 vital role in our health care system because 11 it is one of the few ways that hospitals can 12 achieve substantial cost savings while 13 maintaining the absolute highest standard of 14 patient care. The implementation of MDUFMA 15 has presented some new hurdles this year, 16 hurdles that the industry does not believe 17 are warranted, but they are hurdles that the 18 industry is meeting and will continue meeting 19 in the coming year. Thank you. 20 MR. BARNETT: Thank you, Naomi. 21 Anyone on the panel want to respond or ask a 22 question? Anyone in the audience? Okay, if BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 152 1 that's the case, let's go into our next 2 speaker from AdvaMed, Tony Blank. 3 MR. BLANK: Good afternoon. I have 4 two promises: One, I'll make sure I finish 5 on time; second, I have no gross pictures. 6 Just one response to the comments before with 7 regards to the provision of validation data, 8 is where data that under the quality system 9 regulation one would expect any medical 10 device manufacturer to have in their files 11 and at their fingertips and ready to be 12 bundled into submission. 13 So when I put together the outline 14 for this, I thought a little bit about the 15 attempts my little brother has given to me to 16 teach me the game of golf. He has told me 17 that I have made significant progress, 18 although I still have some lingering 19 challenges, and one of the things I need to 20 work on is my follow-through. 21 So progress that has been made. 22 There was a Congressional mandate in MDUFMA, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 153 1 lots of changes came as a result of that; for 2 example, there were revisions to the MedWatch 3 form to capture the reprocess status of a 4 device if there was an event associated with 5 it. FDA has issued numerous guidance 6 documents to provide direction to industry on 7 reprocessing. 8 They have done a marvelous job, I 9 would say, and should be congratulated for 10 the vast rapid review of the supplemental 11 validation data submissions. There have been 12 some exemption terminations which we as 13 AdvaMed believe are warranted and valid for 14 very valid reasons. 15 And with the recent MDUFSA 16 legislation, there was a narrowing of the 17 Section 301 provisions to reprocess 18 single-use devices. 19 So sort of significant progress has 20 continued in terms of the continued review 21 and termination of exemptions when warranted; 22 for example, stone dislodgers, orthodontic BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 154 1 brackets. There have been continued reviews 2 and calls for supplemental validation data, 3 again, I believe when warranted, specifically 4 endoscopic accessories and heart stabilizers. 5 There are some lingering 6 challenges, however. There is, as you can 7 imagine, continued pressure on FDA from a 8 variety of stakeholders: The OEMs, the 9 hospitals, the reprocessors. There is a 10 tremendous amount of education that must 11 continue, I think, that needs to be balanced 12 and fair. For example, if a single-use 13 device fails after it has been reprocessed, 14 there can be no underlying problem with the 15 original device. 16 So if the product was designed, 17 manufactured, labeled as a single-use device, 18 and it made it through the single-use and it 19 was subsequently reprocessed and that device 20 failed, there was nothing wrong with the 21 single-use device. Any failure, by 22 definition, is associated with the BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 155 1 reprocessing. Period. 2 If a reprocessed single-use device 3 fails or there is an event, the report must 4 always go to the reprocessor. Another 5 significant challenge that lingers is proper 6 AMDR reporting. As I said, there has been a 7 change to the MedWatch form. However, we 8 have to admit and recognize, I believe, that 9 there is an inherent disincentive for the 10 user facilities to acknowledge, when 11 reporting events, that the event was 12 associated with the device that had in fact 13 been reprocessed. 14 And frankly -- which gave birth to 15 the Section 301 provisions at the 16 beginning -- there is an inherent lack of 17 awareness by physicians and by health care 18 practitioners generally and by patients as to 19 whether or not the device that is used on 20 them has in fact been reprocessed. 21 So working on the follow-through, 22 we think it's important, and in fact it is BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 156 1 critical, that we continue to follow-through 2 as Congress has intended. There is a quote 3 from the House report; here is a quote from 4 the Senate report, from the recent 5 legislation, and I won't read it to you. 6 However, at the very beginning, the 7 Senate is very explicit: "Reprocessed 8 single-use devices are not generally marked 9 to identify the reprocessors. Adverse events 10 associated with the reprocessed device may 11 therefore be misattributed to the original 12 manufacturer, not to the reprocessor." The 13 reason these provisions to Section 301 have 14 been introduced is to lead to the marking of 15 reprocessed single-use devices. 16 The Senate has stated that the 17 reason for this provision is to ensure that 18 the practitioners and the hospital 19 administrators know that the device that they 20 are using has in fact been reprocessed, and 21 it cannot work as intended unless health care 22 providers, original manufacturers, device BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 157 1 reprocessors and FDA can readily and 2 accurately identify when an SUD has been 3 reprocessed. This is also taken straight out 4 of the Senate report language. 5 The Senate recognized that there 6 has been, associated with the failure to 7 accurately identify reprocessed devices, 8 inadequate reporting, which fundamentally 9 challenges the underlying cornerstone of 10 FDA's post-market surveillance system. 11 Congress believes, believed, and 12 continues to believe there is no reason for 13 FDA to delay implementation of this 14 provision, and the committee expects 15 reprocessors to implement its requirements as 16 soon as possible. 17 So in sum, great progress, not sure 18 my brother would say that about my golf game. 19 However, challenges do remain, but patient 20 safety, regardless of any pressure from 21 anybody else, must always be tantamount and 22 first. And that's it. Thanks. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 158 1 MR. BARNETT: Thank you, Tony. 2 Does the panel have any response or questions 3 for Tony? Anyone in the room want to say 4 anything? If that's the case, let's go to 5 our final speaker, Mark Leahey, from MDMA. 6 MR. LEAHEY: Thanks Mark, and I 7 promise this is the last time I will be 8 getting up today. I want to, I think, go a 9 little beyond what Tony mentioned. I think 10 he highlighted a lot of the important steps 11 that had been taken to ensure patient safety 12 in this area. But I want to specifically 13 focus on FDA's recently published draft 14 guidance for industry and staff, entitled 15 "Compliance with Section 301 of the Medical 16 Device User Fee and Modernization Act of 17 2002," as amended prominent and conspicuous 18 marks manufacturers' single use devices. 19 Now, before I go further, I think 20 that this is a critical moment here, probably 21 the first in the three years that I have been 22 participating in these stakeholder meetings, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 159 1 that I 100 percent agree and am aligned with 2 FDA's position on this. 3 MDMA agrees with FDA's 4 interpretation of Section 502(u) of the Food 5 and Drug Cosmetic Act as amended by MDUFMA, 6 which requires manufacturers of reprocessed 7 SUDs to mark the reprocessed device 8 prominently and conspicuously, with the name 9 of the reprocessor, a generally recognized 10 abbreviation of such name, or unique and 11 generally recognized symbol identifying the 12 reprocessor. 13 Section (v)(2) of the FDA guidance 14 document outlines the effective date for 15 implementing the reprocessor labeling 16 requirements of Section 502(u). According to 17 the guidance document, if the original 18 equipment manufacturer first marks the device 19 with its name or symbol before 20 August 1, 2006, the reprocessor must mark the 21 reprocessed device by August 1, 2006. 22 If the OEM first marks the device BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 160 1 after August 1, 2006, the reprocessor must 2 immediately mark the device. MDMA agrees 3 that the approach described in the FDA 4 guidance document clearly reflects the 5 language of the statute, and ensures the 6 legislation's goal of protecting patient 7 health is fulfilled as expeditiously as 8 possible. 9 Congress has repeatedly recognized 10 that unmarked reprocessed SUDs may pose 11 significant patient safety risk. When the 12 reprocessor of an SUD is not identified, the 13 FDA is prevented from adequately identifying 14 and controlling the risk posed by 15 reprocessing. FDA's NDR regulations are the 16 cornerstone of FDA's post-marketing 17 surveillance system for medical devices, as 18 Tony mentioned. These regulations require 19 manufacturers to report patient injuries and 20 product malfunctions to FDA. 21 This information enables both the 22 manufacturer and FDA to identify the safety BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 161 1 and/or effectiveness problems, and to take 2 any needed corrective action. Sometimes 3 these protective actions include recalls or 4 other notifications to the field to prevent 5 unnecessary patient injuries. This system 6 cannot work unless the health care providers, 7 the OEM and the FDA can readily identify when 8 and whom a SUD has been reprocessed. 9 Unless reprocessor devices are 10 clearly marked as such and the reprocessors 11 clearly identified, the OEM will likely be 12 erroneously identified as a source of a 13 reprocessed device. This may significantly 14 hinder or preclude FDA's ability to identify 15 and address safety and efficacy failures 16 associated with reprocessed SUDs. In light 17 of these serious public health concerns, 18 Congress required reprocessors to mark their 19 reprocessed SUDs by August 1, 2006, within 20 one year after the implementation of the Act. 21 Further, Congress indicated that 22 the reprocessors should mark their devices as BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 162 1 soon as possible. Congress suggested that it 2 should not take reprocessors a year to mark 3 their reprocessed devices, and discouraged 4 reprocessors from taking the entire year to 5 comply. 6 Specifically, in the MDUFSA report, 7 the committee stated, "Although Section 8 502(u) will first become effective twelve 9 months after the legislation is enacted, the 10 committee believes that it is clear how this 11 section applies to the vast majority of 12 reprocessed devices. And the committee 13 expects reprocessors to implement these 14 requirements as soon as possible for the 15 devices they reprocess, in the best interests 16 of post-market surveillance and the public 17 health." 18 In other words, reprocessors were 19 on notice as of August 1, 2005, that devices 20 currently on the market and for products 21 under development that the marking of devices 22 is a component of their required product BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 163 1 manufacturing, labeling development and 2 intake procedures to identify when a 3 previously used device is marked. 4 Reprocessors were given a full 12 months to 5 do so. The vast majority of devices that are 6 reprocessed require 510(k) pre-market 7 notification clearance prior to marketing. 8 This requires reprocessors to 9 develop and implement reprocessing 10 procedures, develop and print product labels, 11 labeling and packaging, and to ensure that 12 their manufacturing practices are in full 13 compliance with FDA's QSR before the 14 reprocessed device is ever marketed. 15 Marking the device with a 16 reprocessor's name or symbol, in addition to 17 other product labels and labeling that must 18 be developed, is a relatively minor aspect of 19 this process, and certainly does not require 20 an additional year to implement after 21 receiving clearance for marketing. 22 There is no justifiable reason for BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 164 1 permitting a reprocessor a year of anonymity 2 to hide from regulatory requirements 3 specifically designed to protect patient 4 safety. Under these circumstances, if the 5 concept of allowing reprocessors an 6 additional year to mark their reprocessed 7 devices has been a part of the discussions 8 between industry, patient advocacy 9 organizations, FDA and Congress in the 10 developing of MDUFMA amendments, industry and 11 the patient advocacy organizations would have 12 strongly objected and urged Congress not to 13 adopt this approach. 14 Therefore, I want to again 15 encourage and commend the FDA for the initial 16 draft guidance. And in closing, I want to 17 say again it's an area where MDMA certainly 18 supports FDA's position on this, and I think 19 it's certainly in the best interests of 20 patient safety. 21 Thank you. 22 MR. BARNETT: Thank you, Mark. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 165 1 Anyone on the panel want to respond or ask 2 questions? If that's the case, before we 3 close this panel, is there anyone in the 4 audience that wants to say anything, or react 5 about this particular issue of reprocessing 6 single-use devices? 7 Okay, that being the case, we're 8 ready for a break. It's listed on the 9 schedule as 15 minutes. I have 1:25, so why 10 don't we say about 20 minutes to 2:00. 11 (Recess) 12 MR. BARNETT: We're ready to go 13 into our sixth session, on other provisions, 14 and we have our standing FDA panel here: 15 Linda, Joanne, Diane and Bob. And we have 16 added to that Pat Love, who's here with the 17 Office of Combination Products in FDA, and 18 she's here in place of Mark Kramer, who 19 couldn't come, and Steve Sykes, who's with 20 the Office of Surveillance and Biometrics in 21 CDRH. 22 And our first speaker, a constant BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 166 1 lead-off speaker, Bob Britain from NEMA. 2 MR. BRITAIN: Pat, I'm not going to 3 say anything bad. 4 MS. LOVE: You're allowed. 5 MR. BRITAIN: Just a very brief few 6 words about combination products. I think 7 you all know what combination products are. 8 This isn't a new issue; it's been at FDA for 9 many, many years: Drugs and devices. 10 Medical imaging devices and contrast agents 11 are used together. Contrast agents improve 12 or enhance the image of x-ray, of magnetic 13 resonance, of ultrasound. And it's been a 14 problem in the past, because obviously, 15 combination products means two different 16 agencies that you're working with. 17 And the problem is the focus. You 18 need a focus at FDA, so when we had the 19 opportunity to work with FDA and the Capitol 20 Hill staff, everyone was pretty excited about 21 the possibility of putting an Office of 22 Combination Products together. And we worked BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 167 1 very hard to push this through because it's 2 pretty hard to get legislation that sets up 3 offices. It's not easy. 4 So we had very high expectations 5 when MDUFMA was passed and signed into law. 6 It gave the Secretary the authority to set up 7 this Office of Combination Products. And we 8 obviously had high hopes that it would 9 improve the approval process of contrast 10 agents with their use with MRI, et cetera, 11 ultrasound. And after many meetings with the 12 Office of Combination Products -- and I must 13 say the Office of Combination Products has 14 met with us on many occasions -- it's working 15 with us to try and see this through. 16 But we were finally advised that we 17 were a concomitant product instead of a 18 combination product, which kind of took the 19 wind out of our sails, because we probably 20 wouldn't accrue the same benefits and 21 efficiencies that we would have been if we 22 were a combination product. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 168 1 The interesting thing is, when we 2 were working on the legislation, everybody 3 thought this was a combination product, the 4 medical imaging and contrast agent. 5 Everybody. The Hill staff, industry. 6 So my only reason for being here 7 and spending a couple of minutes with you is 8 not to offer any solutions, because we intend 9 to keep working with the Office of 10 Combination Products. They seem to be happy 11 to continue to work with us even though we're 12 not a combination product. And so my only 13 reason to be here and tell you about this is 14 that it's a solution that MDUFMA did not 15 bring to us that we worked very hard to get. 16 And Pat, we will continue to work through 17 this. We don't know what the final solution 18 will be, but I think we'll get there. 19 MR. BARNETT: Thank you, Bob. 20 Anyone want to respond to that? 21 MS. LOVE: I just like to ask a 22 question, please, Bob. Certainly the BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 169 1 definition of combination products, those 2 that are separately provided under 3.2(e)(3), 3 talks a bit about mutually conforming 4 labeling and how things are specifically 5 identified. And as you alluded to, imaging 6 agents are not necessarily labeled in that 7 way. It's possible, but most of them aren't 8 at this point. 9 Do you have some general thoughts 10 or recommendations? I know you said you 11 didn't have a definite recommendation under 12 MDUFMA, but do you think that issues such as 13 this that might relate to classes of products 14 that are often used together, either 15 off-label or maybe there are co-development 16 questions -- do you feel that this is 17 something that should in some way be 18 addressed in MDUFMA, or are these things that 19 should be addressed as in the course of 20 providing the guidance, some of the issues 21 about the quality aspect of things that were 22 mentioned earlier? BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 170 1 Is this a guidance approach issue? 2 Is this something that you see in 3 clarification of mutually conforming labeling 4 issues? Where might this fall as a class 5 concept? Sorry to put you on the spot. 6 MR. BRITAIN: I don't know. I 7 should have said the reason this is so 8 important -- to find a solution. I don't 9 know where it is in guidance or pushing 10 contrast agent manufacturers harder and 11 faster to get these things approved -- but 12 the problem is the using community, the 13 radiologists, et cetera, that use MRI and CT 14 and ultrasound use contrast agents that are 15 not labeled to be used with MRI or CT, and so 16 the manufacturers of the equipment cannot 17 label or train the users because this is 18 off-label use. 19 And so this is why it's so 20 important to find a resolution, because the 21 real world is -- they are being used together 22 unapproved. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 171 1 Pat, I'm sorry, I just don't have a 2 solution for you. 3 MR. BARNETT: Anyone else on the 4 panel want to respond or comment? Someone in 5 the audience? If that's the case, let's call 6 our next speaker, who's Jack Lasersohn from 7 the National Venture Capital Association. 8 MR. LASERSOHN: Thank you very much 9 for inviting us to attend. I'm Jack 10 Lasersohn, and I'm a general partner at the 11 Vertical Group, which is a major medical 12 device venture capital firm. I'm past 13 chairman of the medical industry group at the 14 National Venture Capital Association, which 15 is the national trade association of the 16 venture capital community. Now, in this 17 talk, since this is the first time that we 18 have really presented in front of the FDA 19 stakeholder meeting, we really wanted to just 20 introduce who we are to a large extent to the 21 FDA, and put some context around why we have 22 a somewhat different view of some of these BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 172 1 issues than perhaps the rest of the industry. 2 That's what this talk will focus on. 3 By way of background, the National 4 Venture Capital Association is 500-member 5 venture capital firms. We have approximately 6 $100 billion under management at any given 7 time. 8 We're investing about $20 billion a 9 year in high technology start-ups, primarily 10 in the United States. Most of you probably 11 think of us as people who do the internet and 12 semi-conductors and computers. And that is 13 true, that is still about 60 to 70 percent of 14 the venture capital money flows. But in 15 addition, we have financed, for example, the 16 entire biotechnology industry, and 17 historically probably about 50 percent of all 18 medical device firms today. We're founded 19 with venture capital money. 20 About 100 million Americans have 21 benefited from the investment the venture 22 community has made in medicine over the last BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 173 1 25 years. Twenty-five million, we believe, 2 conservatively, have had their lives extended 3 or quality of life improved every year 4 through the use at this moment of technology 5 originally developed by companies funded with 6 venture capital. These are some of the areas 7 that we have made very significant 8 investments in. Heart disease has been a 9 leading area. 10 We did create, we founded the first 11 angioplasty companies in the 1980s, founded 12 the minimally invasive heart bypass, all of 13 the electroablation companies, first 14 implantable cardiac defibrillators, automatic 15 external defibrillators, and then 16 biotechnology, many, many drugs, including 17 ReoPro, Integrilin, tPA. In imaging, we 18 founded the first superconducting MRI 19 systems, the first ultrasound systems, the 20 first Doppler ultrasound systems, as well as 21 many other drugs for cancer. 22 So our activities are very broad BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 174 1 within the health care space. As I said, 2 medical devices in biotechnology make up 3 about 25 to 30 percent of all venture capital 4 activities right now, medical devices about 5 10 percent. And that's out of an annual 6 money flow of about $20 billion a year. So 7 about $2 billion to $3 billion a year right 8 now from the venture industries going into 9 medical device technology. 10 These are the first financing, so 11 these are classic start-up financings in the 12 life sciences area, including biotechnology. 13 They are pretty steady, at about 200 per 14 year. These are first financing, so start-up 15 companies in that segment. These are the 16 number of first financings in medical 17 devices -- '05 second quarter is an 18 aberration. It's historically been about 100 19 companies a year, so very, very active. 20 These are again start-up companies, first 21 financings for start-up companies in medical 22 devices. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 175 1 The investment that we're making 2 has continued to grow, it did peak in 2000 3 and 2001. But even in 2002 and today, it's 4 much, much higher than it was historically, 5 and we project that it will continue to 6 increase. The number of companies is very 7 steady. Again, this is total financing for 8 companies, not just start-up companies. 9 Second round financings, financings as they 10 get more mature, but 4- to 700 per year is 11 very typical of the number of companies in 12 the medical and life sciences area that's 13 been financed exclusively essentially by the 14 venture capital community. 15 And within that, the medical device 16 sector continues to be very strong, about $2 17 billion a year in all medical device 18 companies for venture capital, anywhere from 19 $400 to $500 million per quarter. One of the 20 points I would like to make that's very 21 important is that the funding requirements 22 for medical devices has just increased BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 176 1 dramatically, partly because of the 2 complexity of the technology, but also 3 because of the regulatory hurdles. 4 We started the first angioplasty 5 company in 1980. It cost $3 million to get 6 it to profitability, and then it was sold to 7 Eli Lilly. A very, very similar technology, 8 in fact simpler technology balloon, 9 kyphoplasty, we started in 1994, took 10 $75 million to get to the same point. That 11 number continues to grow dramatically. 12 One of the key points I think we 13 need to make is that we're investing in 14 revolutionary medical technology by 15 definition. 16 We will not fund VC technology as 17 much as it might be very important to evolve 18 technology along the line. Big companies do 19 that incredibly well, much better than we 20 can. So we're investing almost exclusively 21 in revolutionary technology, so the first 22 angioplasty company, the first MRI, the first BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 177 1 pulse oximetry, first ablation, ICDs, 2 neurostimulation, triple As. These were all 3 started by the venture capital community. 4 As a result of the novelty, we face 5 peculiar problems, different problems. 6 Often, the staff of the FDA has never seen 7 the type of device that we're talking about. 8 So we have an enormous learning curve hurdle 9 to get over with the FDA. There's always a 10 lack of precedence and pathways, and in some 11 cases, there are precedents that actually 12 hurt us. 13 I mentioned before that sometimes 14 having guidances can be difficult because we 15 have to get ourselves out of a particular 16 guidance pathway because what we're doing 17 really doesn't fit. 18 And we always face a tremendous 19 problem in clinical trial design and 20 interpretation because of the novelty factor. 21 So this brings a -- we really do have a 22 different emphasis -- not better, just BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 178 1 different -- than the rest of the industry. 2 And our focus is going to be on solving these 3 problems. To give you some idea of just the 4 kinds of things that we're doing right now, I 5 took a survey of the venture community. 6 And this is a snapshot in time 7 today of sort of what the venture community 8 is working on, you will see that many of 9 these things -- not all of them, but many are 10 things the FDA has never seen before. 11 So the very first spinal nucleus 12 replacements are going to be produced by the 13 venture community. They are going to be 14 showing up at the FDA. They are showing up 15 at the FDA right now and will be very 16 challenging. All of these are different in 17 kind than the types of products that you are 18 used to seeing. We agree with everything 19 that has been said before about the need for 20 transparency and consistency and 21 predictability. 22 We are very much in favor of fees. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 179 1 We have no problem paying fees if they are 2 based on performance. Our companies do have 3 money. Even though they are start-ups, they 4 are well-funded. They will pay for fees if 5 that will shorten the regulatory or improve 6 the regulatory outcomes. We do believe that 7 the whole concept of least burdensome is very 8 important, and our intention is in fact to, 9 as part of the MDUFMA process, to revisit 10 this. 11 MR. BARNETT: Two more minutes, 12 please. 13 MR. LASERSOHN: Thank you. At the 14 statutory level. We've tested this concept, 15 we think it really can work, and we're going 16 to be asking to think more about how to bring 17 the least burdensome process forward. 18 Obviously, we agree with meeting management. 19 All of the things that have been said before 20 about quantitative results are certainly 21 supported by us. I have also said that we 22 are in favor of new processes, particularly BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 180 1 for novel products. 2 I don't mean expedited processes, I 3 just mean processes that are able to draw in 4 different resources that have a different 5 pathway, not in terms of safety and 6 effectiveness, but in terms of the types of 7 pathways through the FDA. 8 We do think that HDEs are an area 9 that we should return to focus on. A draft 10 guidance has essentially shut down the HDE 11 process at the moment, requiring that sub 12 populate -- that you can essentially not have 13 off-label use is a matter of physical 14 reality. 15 We think that that is not a good 16 decision by the FDA. We would like to 17 revisit that. We think that creates an 18 opportunity for another pathway for truly 19 novel devices that really may not be able to 20 be approved through existing regulatory 21 pathways. 22 We support the critical path BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 181 1 initiatives. We want to collaborate with the 2 FDA in trying to define that. And our 3 intention going forward is to be as actively 4 engaged with FDA as possible and defining 5 some of these new ideas. Thank you. 6 MR. BARNETT: Thank you. Anyone on 7 the panel want clarification, have a 8 question? Yes. 9 MS. LESS: I just want to ask you, 10 what did you mean by continuous medical 11 application? Is that what you were talking 12 about earlier, risk-based approach? 13 MR. LASERSOHN: I don't know if I 14 used the word "continuous." If I did -- 15 MS. LESS: It was on the slide. 16 MR. LASERSOHN: Continuous was 17 probably a typo. The risk-based approach, if 18 that's what you're asking about, is again to 19 try to have a process that 20 defines -- particularly for the staff, not so 21 much for the higher level -- at CDRH, which I 22 think understands this concept well. That BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 182 1 defines for the staff ab initio at the 2 beginning of the process; that is, in pre-IDE 3 discussions, that decisions about the pathway 4 should be made consciously with a particular 5 level of risk in mind. 6 That is, if a device comes in that 7 really has proven to be, through feasibility 8 studies, for example, very likely to be very 9 low-risk, the level of evidence of 10 effectiveness should be adjusted accordingly. 11 And we have found -- and this is just one 12 narrow point, but we have found that this is 13 a -- that process, that discussion has taken 14 very often months or years to cycle with 15 acceptable results at the end, but has taken 16 a long time to get to the proper result. 17 MR. BARNETT: Any other questions 18 from panel? If not, thank you. And let's go 19 to our next speaker, Diana Zuckerman, of the 20 National Research Center for Women and 21 Families. 22 MS. ZUCKERMANN: While we're BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 183 1 waiting for the slides, I can say thank you 2 very much for the opportunity to be here. 3 I'm Dr. Diana Zuckermann. I'm president of 4 the National Research Center for Women and 5 Families. And here is my slide. Our center 6 is a non-profit research center, and we use 7 research information to work for programs and 8 policies that improve the health and safety 9 of women, children and families. 10 Just for a little background, my 11 background is as an epidemiologist, and I've 12 worked on Capitol Hill doing oversight on FDA 13 issues, so these are issues of particular 14 interest to me. And although there are not 15 too many consumer-oriented non-profits here 16 today, there are a lot of consumer-oriented 17 non-profit organizations that we work with on 18 these issues. And although they were not 19 able to be here today, we have been working 20 in coalition with them, and they do care a 21 lot about this particular legislation, even 22 though they weren't able to be here today. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 184 1 These are the healthy people that 2 we do research on. These are the people in 3 clinical trials in the PMAs. And so these 4 are the people that are very often studied 5 for hip replacements, or sometimes heart 6 valves and so on. 7 These are what I like to think of 8 as my baby boomer friends. And those of us 9 who are baby boomers know that there are lot 10 of spare parts that a lot of us are using. 11 And we're pretty healthy. And we use them 12 and we're very happy to have these medical 13 devices. 14 However, these medical devices 15 don't always last that long, and so one of 16 the concerns that we have about MDUFMA is to 17 make sure that resources are allocated in a 18 way that helps make sure that products are 19 safe for long-term use and that we know what 20 the long-term risks are. Because one of 21 these days, those of us who look like this 22 now, 10 or 20 years later or a little bit BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 185 1 more, are going to be the frail elderly. And 2 if those devices, if those hip replacements 3 or breast implants or whatever they are start 4 to fail, those people might be in a situation 5 where they're not healthy enough to have them 6 surgically removed and replaced at that time. 7 So that's one of the reasons why we 8 think that the long-term safety of many 9 medical devices are really very crucial. 10 Even if they last a long time and are very 11 good in the short run, we need to be aware of 12 what's going to happen in the long run, and 13 people need to know so that they can plan 14 accordingly. 15 So for example, if somebody knows 16 that a hip replacement is likely to fail 17 after some number of years, they might want 18 to have that hip replaced while they're still 19 healthy enough to have the surgery instead of 20 waiting to a point where they're too frail 21 and not able to do that. 22 In the guidance for industry, the BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 186 1 FDA had issued this guidance, as you know, in 2 September, regarding race and ethnicity data, 3 and the focus I'd like to talk about today is 4 the differences between who uses devices and 5 who it's studied on. The guidance for 6 industry specified that race should be 7 categorized the same way that it is for other 8 HHS agencies. 9 The FDA does not have regulations 10 or guidance that require adequate 11 participation levels, however, of either 12 racial and ethnic groups or age groups, or 13 sometimes even women and men. 14 So we have a situation where 15 people -- according to the guidance, there is 16 some suggestion of how people be categorized. 17 But there can be zero people in some of those 18 categories. And I have seen that -- in 19 looking at data for PMAs, I have seen 20 situations where there were zero 21 African-Americans, or perhaps one or two, 22 zero Asian-Americans, or perhaps one or two. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 187 1 Now, the differences in drugs and 2 devices is that for NDAs, the sponsors must 3 present a summary of safety and effectiveness 4 data by demographic subgroup. 5 And the IND holders must submit 6 annual reports with information about the 7 age, gender and race of subjects enrolled in 8 clinical studies. But there are no similar 9 requirements for medical devices. And we 10 think that's something that it's time to 11 really start looking at and using the 12 resources from MDUFMA as well as 13 appropriations to make sure that that's done. 14 Let's look at the NIH policy. The 15 NIH policy requires the inclusion of women 16 and minorities in all research involving 17 human subjects. 18 And the exception to the policy is 19 in situations where it would not work to 20 protect the health of the human subjects 21 because it would be unsafe, or if such 22 research is not needed. And we think this is BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 188 1 an excellent model for CDRH. 2 I'm going to talk a little bit 3 about cosmetic surgery. I think it's a 4 really good example, because we're talking 5 about devices and I'm talking about cosmetic 6 surgery involving devices such as -- wrinkle 7 fillers and breast implants are two good 8 examples where the product is not 9 life-saving. 10 So we're not dealing with something 11 that has to be rushed to market because 12 people's lives are at stake. And so for that 13 reason, we have to be particularly concerned 14 about the safety, short-term and long-term, 15 and the safety for all Americans, not just 16 white people who are already young and 17 healthy. In 2000, people of color accounted 18 for 14 percent of all cosmetic surgery 19 procedures in the country according to the 20 plastic surgeons. And in 2005, people of 21 color accounted for 20 percent of all 22 cosmetic surgery procedures, so it's on the BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 189 1 increase. 2 Unfortunately, many of these 3 wrinkle fillers and other cosmetic devices 4 are being approved without any useful 5 information about people of color. As I 6 said, the products are not life-saving, and 7 it is also important to note that these 8 products are often used off-label. So even 9 if they are safe for some groups or for some 10 procedures, they may be used for other groups 11 and other procedures. 12 We know that racial and ethnic 13 groups do respond differently to medical 14 treatments and devices, and of course FDA has 15 recently approved a prescription drug 16 specifically for African-Americans. 17 But let's look at how implants and 18 implanted medical devices might have a 19 different response. We know that 20 African-Americans are more likely to have 21 keloid scarring. We know that in response to 22 laser treatments, there is hypo-pigmentation BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 190 1 risk. And we also know that 2 African-Americans are more susceptible to 3 autoimmune disease. 4 Keloid scarring can occur after an 5 incision, and it's is more likely for 6 African-Americans and Asian-Americans. And 7 here is two examples of keloid scarring: The 8 woman has a scar on her ear from having her 9 ear pierced, and it's a huge, like ball on 10 the bottom of her ear. It looks like an 11 earring, but it's actually her scar. 12 And the scar on that ankle is also 13 from a cut. 14 Here are some granulomas in the 15 mouth region -- it's not so clear, but you 16 can see this was a cosmetic injection, an 17 approved medical device, and there was a 18 reaction with these rather large granulomous 19 lumps over the lip. 20 This one was in the forehead where 21 there was necrosis and the skin died and left 22 that not very attractive appearance. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 191 1 And as I mentioned, autoimmune 2 disease is of particular concern because 3 African-Americans are more at risk for 4 autoimmune disease, and implanted medical 5 devices, some may increase the risk of 6 autoimmune disease. 7 So for breast implants, there were 8 only a few, less than a dozen, 9 African-Americans and Asian-Americans in the 10 recent PMA for breast implants, even though 11 reconstruction with breast implants is 12 popular among African-American women and 13 augmentation with breast implants is very 14 popular among Asian-American women. 15 This is a sample photo for the 16 implant makers of what breasts are supposed 17 to look like after augmentation. And this is 18 what's called capsular contracture, where the 19 scar tissue hardens around the implant and 20 causes a distortion in the shape and can be 21 extremely hard and painful. Since we know 22 that there are racial differences in keloid BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 192 1 scarring, we do have to worry about scar 2 tissue development with implants. 3 MR. BARNETT: Two more minutes 4 please. 5 MS. ZUCKERMAN: This is a necrosis 6 after an implant. I just wanted to give an 7 example of Sculptra, a product that was 8 recently approved as a medical device for 9 HIV-AIDS patients but is now being widely 10 advertised for the horror and tragedy of 11 SmileLines for young women. So we need to 12 make sure that these products are safe for 13 everyone. And we need to make sure that the 14 post-market surveillance is also enough to 15 ensure the long-term safety for everyone. 16 And we know from experience and from the 17 report that FDA did that pre-market 18 agreements that require post-market 19 surveillance are not necessarily being 20 followed. 21 So we want to make sure it's safe 22 for everyone, again: Asian-Americans, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 193 1 Hispanics, everybody. Elderly people. I 2 want to remind you that the National Academy 3 of Science's report found some problems with 4 medical devices surveillance for children. 5 And we want to make sure that these products 6 are safe for our kids. 7 The NAS recommended among other 8 things post-market studies be a condition of 9 approval, and that those post-market studies 10 follow children for a long enough time to 11 make sure that the product accounts for 12 children's growth and development, and to 13 make sure that there are annual reports on 14 that to make sure that when medical devices 15 are used for children, whether on-label or 16 off-label, that they're safe. 17 I want to end with a quote from 18 Dr. Jane Henney, former FDA commissioner: 19 "It's only through the participation of the 20 many populations that will ultimately receive 21 a new product that we can ensure that the 22 medical products we approve are appropriate, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 194 1 safe and effective for all Americans and not 2 just a narrow cut of our country's 3 population." 4 Thanks very much. 5 MR. BARNETT: Thank you. Anyone on 6 the panel want to ask for clarification? If 7 not, I'd like to call a speaker who 8 registered today. She is Claudia Miller from 9 the University of Texas. Is she here? Okay, 10 come on up. 11 MS. MILLER: I'm a researcher, so I 12 guess I have a letter, handouts. I apologize 13 for that. 14 MR. BARNETT: Okay. 15 MS. MILLER: And I'll give you a 16 copy of my testimony as well. 17 Thank you for this opportunity to 18 talk about my views regarding improvements 19 that are needed to actually increase 20 safeguards for medical devices. I'm a 21 professor of environmental and occupational 22 medicine and a board-certified internist, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 195 1 allergist and immunologist at the University 2 of Texas Health Science Center in San 3 Antonio. 4 For more than a decade, my research 5 has been focusing on people who report 6 developing chronic multisystem illnesses, 7 headaches, memory and concentration 8 difficulties, depression, fatigue, chronic GI 9 problems, fibromyalgia following an 10 identifiable exposure; for example, implants 11 in the body or to pesticides and solvents 12 used during remodeling, or chemicals used 13 during the first Gulf War. 14 I've served as a consultant to the 15 Department of Veterans' Affairs on the Gulf 16 War veterans' illnesses, the EPA on sick 17 buildings, including its own headquarters 18 building here in Washington, the National 19 Institute of Dental and Craniofacial Research 20 on temporomandibular joint implants, the 21 National Institute of Environmental Health 22 Sciences, the National Toxicology Program of BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 196 1 the governments of Canada, Germany, Sweden 2 and others. 3 What unites these seemingly diverse 4 groups, patients with implants, Gulf War 5 veterans and sick building occupants, is the 6 fact that following a well-defined exposure 7 event, a subset of individuals appears to 8 lose their prior innate tolerance, their 9 natural tolerance, for a wide variety of 10 structurally unrelated chemicals. I compare 11 to the way that diabetics lose their 12 tolerance for sugar; they lose their innate 13 tolerance for exposures. 14 Thereafter, everyday exposures, 15 including commonly eaten foods, medications, 16 alcoholic beverages, caffeine and chemical 17 inhalants such as fragrances, diesel exhaust 18 and tobacco smoke -- exposures that had never 19 bothered these people before and don't bother 20 most of us, but now they're triggering myriad 21 often disabling symptoms in these 22 individuals. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 197 1 In environmental medicine, this 2 two-step disease process has come to be known 3 as Toxicant-Induced Loss Of Tolerance, or 4 TILT. It does not appear to matter whether 5 the exposure that initiated this process was 6 exogenous, like a chemical exposure to 7 pesticides, solvents; or endogenous such as 8 an implant. The body's response is 9 remarkable similar. 10 We've studied and reported on 87 11 people with surgical implants and I've given 12 you those papers. Three quarters of these 13 individuals had received breast implants. 14 Among the latter, 69 percent reported rupture 15 of an implant and 78 percent had one or more 16 implants removed. But these also include 17 other types of implanted devices, including 18 TMJ implants. Of those women who had 19 undergone explantation for breast implants, 20 almost half reported their health status as 21 greatly improved or somewhat improved. 22 Although we have not said all kinds BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 198 1 of implants, it appears that certain kinds 2 are more likely to cause this loss of 3 tolerance. Silicon gel breast implants, for 4 one, appear to cause these problems because 5 they tend to leak and rupture. TMJ implants 6 made of Teflon tend to cause similar problems 7 because the friction of the jaw joint, high 8 pressures cause the Teflon to flake off 9 basically inside the body. 10 And the fact that these are 11 long-term permanent implants often used by 12 relatively young patients means that 13 long-term research is especially important 14 before approval and post-market surveillance. 15 It's essential that MDUFMA ensure 16 adequate resources for long-term premarket 17 clinical trials and well-conducted 18 post-market surveillance. Using a validated 19 screening questionnaire which I've provided 20 to you, the quick environmental exposure and 21 sensitivity inventory, which is of very high 22 sensitivity and specificity and it's a BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 199 1 validating instrument to measure this problem 2 of chemical intolerance. 3 We found that the symptom severity 4 scores of implant recipients rival those of 5 environmentally exposed groups we were 6 studying, including Gulf War vets -- ill Gulf 7 War vets, I should add. 8 Compared to controls, implant 9 recipients also reported many more and more 10 severe adverse responses to everyday 11 environmental chemical exposures. Further, 12 implant recipients reported far more severe 13 reactions to a wide variety of foods, 14 medications, alcoholic beverages, caffeine 15 and other common exposures than did controls. 16 This is a new paradigm; we're not talking 17 about usually classified autoimmune diseases, 18 as have been studied in certain studies. 19 These are a much broader classification of 20 diseases, and this appears to be a new 21 paradigm for environmentally induced disease 22 that differs from classical toxicology and BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 200 1 allergy in important ways. 2 Toxicant-Induced Loss of Tolerance, 3 or TILT, for short, explains why infected 4 individuals may remain sick years after their 5 initial exposure. This is as a result of 6 subsequent triggering by everyday exposures 7 that they now have lost tolerance to. 8 Why do symptoms wax and wane in 9 such a bewildering fashion? Because 10 triggering exposures change over time in the 11 effects of these exposures, the symptoms 12 resulting from their exposures as they go 13 through the day overlap in time. Ironically, 14 affected individuals and their physicians may 15 be completely unaware of their intolerances 16 resulting from TILT because of a phenomenon 17 called masking. If people are reacting 18 adversely to multiple chemicals, foods, 19 drugs, and so on, and they are exposed to 20 these substances one after another during the 21 day, the symptoms resulting from these 22 exposures overlap in time. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 201 1 Again, that's called masking. As a 2 consequence, there is so much background 3 noise that patients can't identify, nor can 4 their physicians, any specific triggers for 5 their symptoms. They just feel bad most of 6 the time, with chronic fatigue or flu-like 7 symptoms that won't go away. 8 Recent Canadian studies done at the 9 University of Toronto indicate that genetic 10 polymorphisms may underlie who is more 11 vulnerable to developing Toxicant-Induced 12 Loss Of Tolerance. At the same time, no one 13 is able to predict, and this is very 14 important, which individuals will be 15 affected. 16 In September, I chaired a meeting 17 on TILT sponsored by two NIH institutes: 18 NIEHS and National Institute of Alcohol Abuse 19 and Alcoholism. There is a report on that 20 meeting from a journal I've given you. 21 Invited scientists explored 22 clinical observations, animal models, BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 202 1 neuroimaging and genetic approaches for 2 understanding this emerging new disease 3 paradigm. The implications for you are 4 clear. To safeguard health, you must 5 determine which types of implants are more 6 likely to cause loss of tolerance, and the 7 time frame for problems. 8 If certain materials are more 9 likely to cause serious health risks, they 10 should not be approved unless benefits 11 outweigh the risks. The FDA must assure that 12 there are adequate warnings on the label so 13 that patients can avoid the health risks and 14 respond quickly to remove the implants that 15 are starting to cause symptoms. 16 Unfortunately, that may be too late in some 17 cases. And since removal of cosmetic 18 implanted devices such as breast implants are 19 not covered by health insurance, it is 20 especially crucial that they be held to a 21 high safety standard. 22 Unfortunately, women who become ill BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 203 1 from their implants may not be able to afford 2 surgical removal. Our research indicates 3 that a substantial proportion of implanted 4 women with TILT become so debilitated that 5 they are no longer able to earn a living, and 6 therefore unable to afford surgical removal 7 for many years unless they become eligible 8 for Medicare or Medicaid. 9 Some become so ill over time that 10 they are not able to tolerate hospitals or 11 surgery, even if they could otherwise afford 12 to have their implants removed. 13 Today's meeting is focused 14 principally on the device industry's 15 perspective, but as a clinician, I'm here to 16 encourage you to ensure long-term safety 17 standards and to take into account this more 18 susceptible subset of the population that may 19 have exposures to various devices. 20 We cannot predict ahead of time who 21 is going to have adverse effects until we 22 have more science. Thank you. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 204 1 MR. BARNETT: Thank you. Anyone on 2 the panel want clarification on that? Okay, 3 now since this is the close of the last of 4 our six sessions, let me open the floor now 5 to questions from anyone about any of the 6 things you heard today; that is, any of the 7 six sessions. The only ground rule for this 8 one is that your comment apply to MDUFMA. So 9 let me do that. Anybody? You all talked 10 out? Okay, if that's the case, then let me 11 ask Linda if she wants to make a few closing 12 comments before we say goodbye. 13 MS. KAHAN: I just want to 14 reiterate Dan's appreciation for everybody 15 coming. I think that we did hear a lot of 16 good ideas, many of which focused on issues 17 that we ourselves of course have been 18 thinking about and that many of you have 19 brought to our attention before, and that 20 we're working on thinking about the right way 21 to go ahead, at the same time we're working 22 on meeting the current MDUFMA goals. BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382 205 1 We look forward to working with all 2 of you over the next year so that we can 3 again get a program in place that's even 4 better than what we've got, so that we can 5 get safe and effective products to the 6 American public as quickly as possible. 7 Thank you very much for helping us. 8 MR. BARNETT: Thank you all. 9 (Whereupon, at approximately 2:24 10 p.m., the PROCEEDINGS were 11 adjourned.) 12 * * * * * 13 14 15 16 17 18 19 20 21 22 BETA COURT REPORTING www.betareporting.com 202-464-2400 800-522-2382