1 1 2 3 4 5 6 7 FDAMA STAKEHOLDERS MEETING 8 APRIL 28, 1999 9 Boston, Massachusetts 10 11 Talking with Stakeholders About FDA Modernization 12 13 14 15 16 Boston University Medical School Keefer Auditorium 17 715 Albany Street Boston, Massachusetts 18 10:00 a.m. - 4:15 p.m. 19 20 21 22 LEE A. MARZILLI REGISTERED PROFESSIONAL REPORTER 23 18 Boulder Road Lexington, MA 02420 24 (781)862-4829 2 1 I N D E X 2 PAGE 3 OPENING REMARKS BY JOHN MARZILLI: 3 4 REMARKS BY DR. ARAM CHOBANIAN: 8 5 REMARKS BY MICHAEL DONOVAN: 15 6 PRESENTATION BY MARK ELENGOLD: 16 7 PRESENTATION BY JANICE BOURQUE: 48 8 PRESENTATION BY LISA RAINES: 64 9 QUESTIONS AND ANSWERS: 80 10 PRESENTATION BY LISA LOPEZ: 97 11 PRESENTATION BY CAROLYN JONES: 108 12 QUESTIONS AND ANSWERS: 127 13 14 15 16 17 18 19 20 21 22 23 24 FDAMA STAKEHOLDERS MEETING, 4/28/99 3 1 P R O C E E D I N G S 2 MS. FAIRFIELD: Good morning. Why don't we 3 get started. We're running a little bit behind, 4 and we'll get started and try and keep this on 5 track. My name is Paula Fairfield. I'm with the 6 Food and Drug Administration, and I'm just going 7 to give you some housekeeping information. Rest 8 rooms are just outside the door to the 9 auditorium. They will be on your right. 10 We're going to have a break after our third 11 speaker this morning from Genzyme Corporation, 12 and the break will be in the Wilkins Boardroom, 13 which is just down the hall on your left. It's 14 across the hall from the clock on the wall. 15 Lunch is going to be in the vicinity of 16 11:45, and that's going to be on the 14th floor 17 here in the medical center, and there will be 18 signs and people directing you to elevators and 19 around up to the 14th floor. 20 I would like to introduce at this time our 21 District Director at FDA, John Marzilli, from the 22 New England District Office. John? 23 MR. MARZILLI: Thank you very much, Paula, 24 and thank you, everyone, for getting here this FDAMA STAKEHOLDERS MEETING, 4/28/99 4 1 morning. I know if any of you came in on the 2 Mass. Pike -- and I came in on the Weston toll 3 link -- then I can assure you that people are 4 crawling along to get here. Normally I travel to 5 our office up in Stoneham, Massachusetts, and 6 don't experience the delight of Mass. Pike 7 morning traffic coming into downtown Boston, so 8 it was a novel experience for me, and I'm sure 9 I'll do as the director of security here did and 10 get here at 6:00 o'clock and have some coffee so 11 I won't have to be pulling my hair out as I'm 12 driving along the Pike. 13 But I want to thank folks for coming here, 14 and I can assure you, as the day progresses, bit 15 by bit you'll see these seats fill up because we 16 have over a hundred people registered for this 17 meeting, and it shows the tremendous interest in 18 the New England area of people from the biotech 19 industries in getting a chance to meet with us at 20 the Food and Drug Administration. 21 This is truly a historic meeting for the 22 Food and Drug Administration. We are having this 23 meeting today as an outreach with our 24 stakeholders across the country. The meeting FDAMA STAKEHOLDERS MEETING, 4/28/99 5 1 kicks off here in Boston this morning at 9:30 2 with the first of eight meetings that will be 3 held across the country. Our meeting will start 4 with the morning session with folks from the 5 District Office and folks from the Center for 6 Biologics. The day will progress where we'll 7 have speakers from industry addressing us as 8 well, folks that we're near and dear with that 9 we've had working relationships for a long time 10 here in the New England District, and are always 11 first and foremost to come forward and meet with 12 the agency, and we look forward to that 13 opportunity. 14 It's an important aspect of the FDA 15 Modernization Act for us to get together and hear 16 from our stakeholders, hear from the people that 17 we work with on a daily basis, and have a chance 18 to interact and maybe, to paraphrase Ed Cox, to 19 get a chance to say, "So how are we doing?" and 20 see where there's room for improvement and room 21 where we can work together. 22 It's an important opportunity for us as an 23 agency, something that we don't get to do very 24 often and something that this Commissioner has FDAMA STAKEHOLDERS MEETING, 4/28/99 6 1 highlighted as her first priority in taking over 2 the reins of the agency that she came on board. 3 So the FDA Modernization Act is Commissioner 4 Henney's, and I can assure you my, first priority 5 as District Director here in the New England 6 District, and it's important for us to take this 7 opportunity to meet with all of you. 8 As I said, there are seven other meetings 9 being conducted across the country. In Atlanta 10 we'll be having a stakeholders meeting with the 11 Office of Regulatory Affairs. They will also be 12 meeting in Chicago with the food industry. They 13 will be meeting in Kansas City with the 14 veterinary drug industry; in the San Diego area, 15 medical devices. In San Francisco we'll be 16 meeting with the biologics industry as well; and 17 in Philadelphia, we'll be meeting with the Center 18 for Drug Evaluation. 19 And, Paula, have I covered all the 20 meetings? And if I haven't -- oh, in D.C. we'll 21 be meeting with the world. Thank you. 22 And I'm sure all of you have clicked onto 23 our Web site and seen where these meetings will 24 be held. And for those of you that have fellow FDAMA STAKEHOLDERS MEETING, 4/28/99 7 1 workers that maybe couldn't make it to this 2 meeting, at the break you may want to call them 3 and tell them they can click onto their computers 4 on www.fda.gov, and click onto our FDAMA Web site 5 and see the Commissioner's broadcast 6 simultaneously on our Web site as well. So we'll 7 have a satellite broadcast that will be received 8 at eight locations across the country with FDA 9 participants. There will be other locations that 10 will be receiving the satellite downlink as well, 11 and people can also view it on their Web sites in 12 their offices. 13 This is a first for me as District Director, 14 and it's an exciting opportunity to take part in 15 this activity as it goes across the country and 16 get to meet with folks from the New England area 17 from the industry that we regulate here, and I'm 18 really looking forward to spending the day 19 together with all of you. 20 And I would like to thank Boston University 21 Medical Campus for hosting this meeting with us 22 today. It was encouraging to work with them, and 23 they have been the greatest of assistance to us 24 in putting this together. And I'd like to FDAMA STAKEHOLDERS MEETING, 4/28/99 8 1 welcome Dr. Aram Chobanian, the Provost of the 2 Boston University Medical Campus and the Dean of 3 the School of Medicine. I'd like to ask him to 4 come up here and welcome us to the site today. 5 DR. CHOBANIAN: Thank you very much, John. 6 It's a pleasure to have you all here today. I go 7 back with the FDA for a long time, for twenty-two 8 years served as a consultant to the FDA, chaired 9 the Cardiorenal Advisory Committee, and was on 10 the Orphan Drug Committee for quite a while, so I 11 feel particularly close to the group that we are 12 sponsoring today. 13 Boston University Medical School and Boston 14 University Medical Center is made up of different 15 constituents here. At the medical campus we have 16 four institutions, three schools and a merged 17 hospital. The three schools are the School of 18 Medicine, the School of Dentistry, and the School 19 of Public Health. In addition, as those of you 20 who are living in the Boston area know, we have a 21 hospital that is a merged entity that brought 22 together Boston City Hospital with our University 23 Hospital; and that merger has gone very well, and 24 we really have now a very unified medical FDAMA STAKEHOLDERS MEETING, 4/28/99 9 1 campus. 2 There is a lot of research activity here on 3 the campus. The total sponsored program 4 activity, if you include the school and the 5 hospital, exceeds $150 million this year; and 6 it's a broad range of research projects, some of 7 which are working with your companies, actually. 8 We range from the very fundamental work, 9 molecular genetics, all the way to translational 10 medicine, to studying devices in the animal care 11 facility, and to evaluating clinical 12 instrumentation as well. 13 There are thirteen nationally designated 14 Centers of Excellence, most of which are funded 15 by the NIH, some by other agencies, and those 16 included a wide range of activities. We have a 17 specialized center of research in hypertension, 18 in coronary heart disease, in Parkinson's disease 19 and Alzheimer's disease, in asthma, in chronic 20 pulmonary disease, in mass spectroscopy, where we 21 competed successfully for the National Mass Spec 22 Center, which collaborates now with people both 23 in academia around the country as well as with 24 industry. FDAMA STAKEHOLDERS MEETING, 4/28/99 10 1 We have a Navel Blood Research Laboratory 2 that's been very successful, and I know some of 3 the individuals here have worked with Bob Valleri 4 in that kind of setting. We have a Center of 5 Excellence in Women's Health and so forth. 6 The exciting part of what we're doing right 7 now that I think relates to some of your 8 activities is the BioSquare enterprise, which 9 some of you probably parked really in the middle 10 of that nine-acre complex, and we have a master 11 plan that's been approved that includes six 12 buildings. The first two buildings you see, the 13 second of the two, the Evans Medical Research 14 Building, will be completed in December or 15 January; and about forty percent of that building 16 is for commercial purposes, for biomedical 17 research for biotech companies. And we have a 18 third and fourth research building that has been 19 approved by the Master Planning Group. A garage 20 is going to be started in the summer, and a hotel 21 is currently being planned, and there are some 22 preliminary discussions with companies regarding 23 that. 24 In addition, our hospital here has a very FDAMA STAKEHOLDERS MEETING, 4/28/99 11 1 active plan. Many of the old buildings, Boston 2 City Hospital, will be demolished this year, and 3 a new ambulatory care facility that fits into the 4 style of the other older buildings that are here 5 will be constructed, probably beginning this 6 fall. So I think we're seeing a major change 7 here in the whole area, and it's going also with 8 the changes in the residential part of this area, 9 which is including now a large number of brown- 10 stone conversions to condominiums. And I can't 11 believe the prices that these condominiums are 12 now going for. You could have increased the 13 value fifty-fold. When I first came here, they 14 were selling for between $5,000 and $10,000, and 15 now they are about a half a million dollars. 16 So thank you all for coming. We really 17 appreciate the opportunity to host this and hope 18 you have a good day. 19 MR. MARZILLI: Dr. Chobanian, I'd like to 20 pronounce your name correctly, having my name so 21 often incorrectly pronounced. Dr. Chobanian, I 22 want to thank you and I want to thank your staff 23 for the wonderful job they have done for all the 24 logistics for this meeting. It's just been FDAMA STAKEHOLDERS MEETING, 4/28/99 12 1 really great. We really want to thank you and 2 extend our thanks on behalf of the Food and Drug 3 Administration for all the assistance you've 4 given us. Thank you very much. 5 And now I'd like to introduce Paula 6 Fairfield, our Public Affairs Specialist, and 7 Paula will tell us a bit about the logistics for 8 this morning. 9 MS. FAIRFIELD: Thank you, John. We're 10 going to have presentations from the Deputy 11 Director for the Center for Biologics Evaluation 12 and Research, Mark Elengold. Seated to Mark's 13 left is Steve Masielo, who is the Director of the 14 Office of Compliance at CEBER. 15 I'd like to ask the first three speakers if 16 they'd come up to the stage, please. We're going 17 to have presentations by Janice Bourque, 18 Executive Director of the Mass. Biotech Council, 19 James Weston, Vice President, Government Affairs 20 and Strategic Policy at Biopure, and Lisa Raines, 21 Senior Vice President from Genzyme Corporation. 22 After their presentations, we'll have a 23 short break. Then we'll continue with three more 24 presentations. Alison Taunton-Rigby, President FDAMA STAKEHOLDERS MEETING, 4/28/99 13 1 and CEO of the Aquila Biopharmaceuticals, Lisa 2 Lopez, Corporate Vice President and General 3 Counsel of Haemonetics Corporation, and Carolyn 4 Jones representing HIMA. 5 When the presentations are finished, we'll 6 have a period of questions and answers, and then 7 we'll have our lunch break, which will be up on 8 the 14th floor. At 1:00 o'clock the satellite 9 downlink presentation will begin. 10 If you look in your packets, you'll notice 11 on the left-hand side behind the agenda is a 12 form, FDAMA Stakeholders Meeting. If you'd fill 13 that out with the questions that you'd like faxed 14 to headquarters, we'll have people that will take 15 them from you and fax them directly. 16 Before the day is over, I'd like you to 17 complete the evaluation for the FDA video 18 teleconference and leave that with one of our 19 people out at the registration desk. 20 On that note, I'll turn the meeting over to 21 Mark Elengold. 22 MR. MARZILLI: Mark, I just had to make a 23 couple of announcements. 24 MS. FAIRFIELD: What did I forget? FDAMA STAKEHOLDERS MEETING, 4/28/99 14 1 MR. MARZILLI: No, no, I forgot. You know, 2 to err is human, since I made the mistake, 3 right? 4 First of all, is Michael Donovan still in 5 the house? I think he just walked out. I meant 6 to introduce him earlier but I didn't get a 7 chance earlier, so later I'd like to ask Michael 8 to come down because he was a great help to us in 9 putting all this together. 10 And, lastly, at the rear door there I'd like 11 the two ladies to step forward so I can introduce 12 them. In case you have any questions during the 13 day and you ask me, I will flag one of them down 14 to get the answer. And I want to introduce on 15 our left is Karen Archdeacon. Karen is a 16 Compliance Officer with the District Office. And 17 on our right is Ellen Madigan. Ellen is a 18 commissioned officer, and she is a biotech expert 19 in our Investigations Branch. So I can assure 20 you any questions you have for me, I'll be waving 21 to one of them to come down so I'll be sure to 22 get you all the right answer. 23 MS. FAIRFIELD: John and I make a good 24 team. What I forget, he picks up. FDAMA STAKEHOLDERS MEETING, 4/28/99 15 1 MR. MARZILLI: Thanks a lot. And now Mark. 2 And if Michael reappears, I will ask him to come 3 down and introduce himself because he was a great 4 help to us. 5 And here's the introduction. Let's have a 6 drum roll, ladies and gentlemen, for Michael 7 Donovan. Mike, come on down. 8 (Applause.) 9 MR. MARZILLI: I'd like Mike to introduce 10 himself and tell us a little bit about the 11 operation here because he was a great help to us 12 in putting the meeting together. 13 MR. DONOVAN: Welcome. My remarks are going 14 to be very brief. I'm not going to go over what 15 Aram has already described in terms of what's 16 happening around here. We're delighted to have 17 this group here today. I work on the BioSquare 18 project with Kathy Doyle who's up there on the 19 right with Thompson, Doyle, Hennessey & Everest. 20 And we're seeing, I think, unprecedented growth 21 going on in this area. This is a part of Boston 22 that is probably the next frontier, I think, for 23 development in commercial activity. And today 24 throughout the day I'll be around and Kathy will FDAMA STAKEHOLDERS MEETING, 4/28/99 16 1 be around. You'll probably see some information 2 regarding BioSquare. If any of you who are from 3 companies or, frankly, for that matter, from the 4 FDA, if you'd like to find out more about what 5 we're doing here, just feel free to talk to me or 6 talk to Kathy, and we'd be glad to answer your 7 questions and give you a tour or presentation 8 later on. Thank you. Welcome again. 9 MR. MARZILLI: And now, since I so rudely 10 interrupted, Mark Elengold. Mark? 11 MR. ELENGOLD: Thank you, John. It's a real 12 pleasure to be here. I always enjoy getting out 13 of Washington. I transferred there twenty-seven 14 years ago for a two-year assignment, and I have 15 been trying to get back out to the field ever 16 since, so the closest I get are meetings like 17 this. 18 I really want to thank everybody involved in 19 putting this together: Dr. Chobanian for making 20 this facility available, the folks at Mass. Medic 21 and the Mass. Biotech Council for their support, 22 particularly to Paula and John, folks back in 23 headquarters who did a lot of the work on it, 24 Lorrie Harrison, some of the other staff in our FDAMA STAKEHOLDERS MEETING, 4/28/99 17 1 Office Communications Training Manufacturers 2 Assistance. 3 And the first thing I'd like to do is just 4 introduce some of the other headquarters people 5 that are here so you know who they are and you 6 don't say anything to them that you might be 7 embarrassed about. John's already introduced 8 Steve Masielo, who is the Director of our Office 9 of Compliance and Biologics Quality. That is a 10 relatively new office that was formed by joining 11 our staff from the licensing products 12 surveillance people with our compliance folks to 13 make a more unified approach to product quality 14 and show how important that is to the compliance 15 effort. 16 Gail Sherman right here in front, who's with 17 the Division of Manufacturers Assistance and 18 Training, a division that in my former job I 19 created to give more emphasis to the fact that we 20 have to assist manufacturers even if we don't 21 have it in our statutory books that license do. 22 Gail's staff is the one that works in doing 23 outreach programs, and John and I have been 24 discussing various things we can do to work more FDAMA STAKEHOLDERS MEETING, 4/28/99 18 1 closely with New England folks. And so if you 2 have any ideas or needs, the person to talk to is 3 Gail and to John and Paula. We'll be back, and 4 we will continue our working relationship after 5 this meeting. 6 Also we have Bob Miller from our budget 7 office. Bob is the one who's responsible for 8 making sure I have the money to pay for plane 9 fares to come up here. And Bob, if you have 10 anything you want to talk about the FDA budget, 11 he's the guy to talk to. I was at a conference 12 call the other day and they referred to him as 13 "Bob show-me-the-money Miller." I've known Bob 14 a long time, and I'd never heard that one 15 before. 16 So that out of the way, let me explain why 17 we're -- how many people were at any of the 18 406(B) meetings last year? Very few, so I'll go 19 over this. 20 Part of the Food and Drug Modernization Act, 21 a process that in the creation and birthing of 22 was probably rougher than raising my twins for 23 twenty-one years, one of the steps was that we 24 would meet with our stakeholders, the people who FDAMA STAKEHOLDERS MEETING, 4/28/99 19 1 are affected by what we do, and consult with them 2 on what the priorities are. Last year we set up 3 very quickly a series of meetings to do that, and 4 if anyone doubts that they had a profound effect 5 on the way FDA does business, they'd be wrong. 6 We heard the message loud and clear from the 7 device folks that we regulate in CBER, and today 8 we'll be talking about our Device Action Plan, 9 which is a direct outgrowth of what we heard last 10 year at the two 406(B) meetings that we had, and 11 another industry exchange meeting that was held 12 with the Pacific region folks that is directly 13 attributable to that. 14 The way we did this last year was, we had it 15 on different days for different centers, and most 16 of them were in Washington. We in CBER had a 17 second meeting in addition to the Washington one 18 in Oakland, California. We believe that the 19 meetings are so important for us to learn that, 20 once again, we're the only center that's having 21 two. I'm chairing this one here, and Dr. Zinner, 22 our Center Director, is chairing one in 23 San Francisco later today. The difference is 24 that this year we're doing them simultaneously FDAMA STAKEHOLDERS MEETING, 4/28/99 20 1 featuring a video teleconference with Dr. Henney, 2 our new Commissioner. We say "new," but she's 3 had a stint as the Deputy Commissioner for 4 Operations where she was in charge of the 5 day-to-day operations of FDA, including the 6 operations of the Center, so Dr. Henney is not a 7 newcomer to FDA. 8 Part of that whole process is to have 9 questions answered from around the country, so 10 again I remind you what Paula said about this 11 ivory-colored form. And, please, if you have any 12 questions you'd like addressed, put them in, give 13 them to the folks in the back, and they'll get 14 them faxed to the teleconference. 15 Any questions that are not addressed during 16 the course of the teleconference, we will have 17 answered. We'll aggregate them. They will be 18 answered, and they will be posted on the Web site 19 within a few weeks. So even if we don't get to 20 your question during the telecast, we will try to 21 address all the questions and concerns. 22 The way we did this last year, and I think 23 we'll do it this year, is I'll do a hopefully 24 brief overview of what CBER is and the directions FDAMA STAKEHOLDERS MEETING, 4/28/99 21 1 we're moving in. Then we'll go to the panelists, 2 and what I'd like to do is have them do their 3 presentations. I think this group is doing it as 4 one, if I'm correct. So after they conclude 5 their presentation, my FDA colleagues and I will 6 ask any questions we have on their presentation. 7 Then we will open it up to the floor if anybody 8 on the floor wants to have any comments or put 9 questions to the group. After the first panel, 10 we'll take a break, and we'll repeat that with 11 the second panel, with the exception that we'll 12 probably go to questions and comments after each 13 speaker. Then we'll have lunch upstairs. Then 14 we'll come back for the teleconference. After 15 the teleconference, if we have not finished any 16 general questions, people who have not 17 registered, speakers who want to talk, we'll do 18 at the end. Otherwise we'll just wrap up and 19 adjourn. 20 Again I'll ask you to complete the 21 evaluation forms because the statute says we'll 22 do this at least once a year, and anything you 23 can give us feedback on to help us will be 24 appreciated. FDAMA STAKEHOLDERS MEETING, 4/28/99 22 1 Okay, let's see, I think I've got all of my 2 administrative notes done, and I guess we can 3 start with the slides. Again I want to thank BU 4 and the audiovisual folks. This is an amazing 5 facility. 6 This is our mission statement, and those of 7 you who were at this meeting last year, one of 8 the comments we received was that in our mission 9 statement, we didn't properly address the medical 10 devices we regulate. So we're in the process 11 right now of going through the internal 12 administrative measure of revising our mission 13 statement. And over on the right side of that 14 slide you see we're adding "and devices." That 15 shows we have learned, we have listened, and our 16 commitment. 17 These are the spectrum of products we 18 regulate. We used to do this as a rainbow, but 19 we kept adding products to it and the rainbow 20 wasn't big enough, so we went to the circle, 21 which kind of illustrates that our products are 22 related and do tend to flow from one to the 23 other. Again you'll notice down at the lower 24 left corner, we've inserted between Tissues and FDAMA STAKEHOLDERS MEETING, 4/28/99 23 1 Whole Blood "Medical Devices," again recognition 2 of what we've heard. 3 These are the tools we use to both enter the 4 Olympics and do our job. They are interlocking 5 systems we have of review, research, 6 surveillance, policy, and compliance. We have an 7 attitude that compliance is the last resort. We 8 would rather work through negotiation; but if we 9 reach a point where that's not possible, we have 10 the full tools of both the Food, Drug and 11 Cosmetic Act and the Public Health Service Act to 12 take regulatory action. 13 These are our vision statements. They are 14 in your handouts, so I'm not going to spend too 15 much time. It just reflects the history of the 16 biologics regulatory scheme that was started 17 actually before the Food and Drug Act, and the 18 Center for Biologics was originally the Division 19 of Biologic Standards of the National Institutes 20 of Health. It was transferred to FDA in 1972, 21 and then added the tools of the FD & C Act. And 22 if you see the last statement is the most 23 important, that our regulatory mission is our 24 guiding principle. FDAMA STAKEHOLDERS MEETING, 4/28/99 24 1 What are our strategic goals? Well, the 2 first goal, a high-quality regulatory process 3 which is managed and integrated from discovery 4 through postmarketing. We want it to be seamless 5 from the day that product is identified in a lab, 6 put in clinical trials, hopefully licensed or 7 approved, depending on the type of product, and 8 then postmarketing surveillance. 9 A high quality research program which 10 contributes directly to the regulatory mission. 11 Over the years that has been misunderstood. Our 12 research is directly aimed at our core regulatory 13 mission. To give you an idea of this, very 14 recently a magazine alleged that an illegal 15 vaccine was manufactured with an illegal 16 adjuvant, squalene. I was able to go to our lab 17 director, and within a week they were able to 18 develop a new method, previously unexisting, to 19 quickly screen for this illegal ingredient down 20 to parts per billion. And we had to be able to 21 have the research tools available. I can't even 22 pronounce many of them, but we have multi-toff 23 MNR. This was using electro-spray ionizing MNR. 24 And they tried four or five methods they came up FDAMA STAKEHOLDERS MEETING, 4/28/99 25 1 with in a week. They totally validated it, and 2 we're now able to run the regulatory samples. 3 Without that research base, we would still be 4 trying to disprove this allegation. So that's 5 the need for our research program. 6 A high quality diverse work force, 7 interactive information systems, and leveraging 8 resources. That's where we go out and partner 9 because Bob won't give us enough money to do 10 exactly what we need to do. Okay, Bob. 11 Okay, what are our priorities? Well, 12 Dr. Henney will be talking about her priorities 13 during the teleconference, and our priorities are 14 pretty much the same. Number one, implement FDA 15 reform. Just last week we published in the 16 Federal Register a required notice under FDAMA 17 adopting specific CDRH guidances, and that was a 18 milestone we were required to do and we met. 19 We have to meet or exceed the PDUFA FY99 20 performance standards. Just in case anybody 21 doesn't know the acronym, Prescription Drug User 22 Fee Act. 23 Take whatever actions are necessary to 24 assure the safety of and public confidence in the FDAMA STAKEHOLDERS MEETING, 4/28/99 26 1 nation's blood supply. Right now, approximately 2 what percentage, Steve? 50 some percent of the 3 blood supply is under consent decree? 60 some, 4 okay. That shows that a few years ago, we 5 realized the industry was not about to 6 voluntarily comply, so we now have court-imposed 7 sanctions and review of what they are doing. 8 Again, that was a last resort after voluntary 9 measures failed. 10 Facilitate the development and approval of 11 significant vaccine, blood and therapeutic 12 products. Just again going back to the history 13 of our center, the person who was the first 14 Director after it came in, Hank Myer, and his 15 then Deputy, Paul Parkman, were the actual 16 developers of the German measles, the rubella 17 vaccine. So we have a proud history of working 18 to actually develop the therapeutics and work 19 with the industry and the National Institutes of 20 Health where we are located to assure that the 21 development process is as quick and seamless. 22 And pursue excellence in research that is 23 directly targeted to the evaluation of 24 regulation, and I've already covered that, I FDAMA STAKEHOLDERS MEETING, 4/28/99 27 1 hope. 2 Improve our automated system support. You 3 can't do anything today without computers. I 4 don't think any of us would like to go back to 5 the era before e-mail, automated data systems, 6 and tracking of our things. Well, some of us 7 might want to, but when I get home tonight and I 8 have 140 for being out of the office for 24 9 hours, I don't know. 10 And continue to support efforts for a high 11 quality, diverse work force. 12 This gives you an idea of what we're up 13 against. If you look over here, the Prescription 14 Drug User Fee Act has really been a two-edge 15 sword for us. It provided additive resources to 16 the FDA to speed the approval of covered 17 products. One of the requirements of PDUFA, 18 however, is that we maintain a base level of 19 appropriated resources, that if we don't continue 20 to spend, we don't receive the user fees. And 21 over the past few years, as our budget overall 22 has been flat-lined -- and a flat-line budget 23 involves a basic decrease because of increased 24 salaries and costs -- the share of what we've had FDAMA STAKEHOLDERS MEETING, 4/28/99 28 1 available for the other products we regulate is 2 this little blue dot down there. So when people 3 ask why we're not doing as much as we could in 4 the medical device area, it's because to keep 5 this area here, we have to spend our appropriated 6 funds and take it from somewhere. You can also 7 see that this IAG CRADA has been constant or 8 increasing, and that's because we've turned to 9 leveraging and working with outside 10 organizations, getting grants from research 11 institutions, interagency agreements with NIH and 12 NIST to try and fund some of our product 13 characterization and regulatory development by 14 partnering with either early phase industry or 15 the NIH or NIST. 16 Interestingly enough, you can see that our 17 workload has been in the IND, or investigational 18 new drug area. In our case, it's really 19 investigational biologics. And you can see that 20 the level, aside from a dip for a few years -- 21 and if you plot the stocks of biotech companies, 22 those of you in the industry know that that 23 pretty much tracks declines in the biotech 24 stocks -- has been increasing again. And, FDAMA STAKEHOLDERS MEETING, 4/28/99 29 1 importantly, the percentage of biotech is really 2 up there. 3 These are numbers which are interesting. It 4 shows that while many of the products are coming 5 in as INDs, very few are leading to actual 6 applications. That's the next phase of product 7 development, and we're gearing up to handle as 8 they move from research into licensure. 9 User fee performance, you can see we're up 10 there at a hundred percent. We've met all our 11 goals, and we are going to continue to meet 12 them. 13 That's a really horrible slide. I can't 14 read it from here. This just shows our review 15 performance in numbers and percentages, and again 16 you have those in your packets. 17 And one of Dr. Henney's key priorities is 18 improving FDA in general, and our goal is to 19 improve CBER's science base. Again, we have a 20 proud history of research. Our predecessors have 21 worked with Dr. Salk and Sabin on the original 22 vaccines. Again, the people who are our 23 management back when I first joined the center 24 developed the rubella vaccine. And over the past FDAMA STAKEHOLDERS MEETING, 4/28/99 30 1 few years our science base has eroded, and we are 2 now in the process of rebuilding it because it is 3 necessary to make good and fast regulatory 4 judgments. 5 And these are the goals we've set for 6 ourselves in science: To realize the mission of 7 bringing products of new technology to the market 8 rapidly while ensuring their safety and 9 efficacy. Nobody benefits from rapid approval of 10 an ineffective or unsafe product, not even the 11 sponsor, because the long-term costs of having a 12 bad product out there are not even available to 13 them. 14 And to realize the mission of reducing risks 15 associated with products. I'm getting ready for 16 a hearing tomorrow in the House, and one of the 17 things we have to stress is: There is no medical 18 decision that is ever made that is not a 19 risk/benefit judgment. And it's very important 20 that both the products are approved when that 21 judgment in general is on the benefit side, and 22 the prescribers, or users, have the information 23 they need to make the correct evaluation. 24 And these are the strategies: Research, FDAMA STAKEHOLDERS MEETING, 4/28/99 31 1 standards development. Again, standards 2 development is very heavily interactive with the 3 industry. Surveillance, outreach, meetings like 4 this, and premarket review. 5 Training scientifically, these seminars, and 6 enhancing our databases. The meetings and 7 seminars is a key point because traditionally in 8 the federal government, when you start running 9 short on cash, the first thing you do is you 10 reduce travel because travel is extremely 11 expensive and you can't demonstrate a return on 12 investment. That is one of the things that's 13 eroded our science base. If our scientists can't 14 get out to meetings, present their results and 15 consult with colleagues, they are not at state of 16 the art. And so one of our goals is to increase 17 our folks' participation in major scientific 18 meetings. 19 Professional development, many of our 20 physicians have for a long time worked in 21 clinics, mainly free clinics or volunteer 22 clinics, a few hours a week to keep their medical 23 skills and patient treatment ideas up to the 24 standard. We're enhancing that by getting some FDAMA STAKEHOLDERS MEETING, 4/28/99 32 1 of our research types, our microbiologists, our 2 chemists, working in research laboratories in 3 universities part-time, four hours every two 4 weeks, to get some experience on what the real 5 world is in today's day and age. 6 Product testing, we are in the process of 7 developing a new standards group within the 8 center. 9 And infrastructure, for many years our lab 10 equipment was getting very old. It wasn't up at 11 state of the art. One of the few benefits of Y2K 12 means that some of that equipment has to be 13 replaced just so it will work next year. 14 And I think I've covered those in previous 15 slides. The key one I'll just repeat: 16 Anticipate public health needs and support 17 informed decisions. And that way, when we have 18 our traditional Friday night crisis and my pager 19 goes off at 9:00 o'clock and my wife starts 20 yelling about the FDA, I can pick up the phone 21 and get the people I need who can give the 22 information that is needed to make the right 23 public health choice. 24 And I think I've covered those. We'll just FDAMA STAKEHOLDERS MEETING, 4/28/99 33 1 shoot through those. You can read them. 2 Major initiatives of action plans: Two 3 years ago we were faced with the crisis of 4 confidence in the blood supply, and we developed 5 the Blood Action Plan. And by putting resources 6 and project management to it, we have been able 7 to move a lot of things forward very fast. 8 It has been so successful that we have 9 adopted the action plan approach for several 10 things: FDAMA/PDUFA II. We have accountability. 11 We have meetings. In fact, unfortunately I left 12 yesterday to come here and missed our quarterly 13 Status of Application meetings, where each of our 14 review officers gets up and gives the status of 15 all the applications they are working on; and the 16 senior management can listen, provide input, and 17 make assignments of additional resources or 18 whatever is needed. 19 Strategic Plan, we developed that four years 20 ago to give us a basic ten-year strategy. It has 21 been very successful in anticipating both our 22 budget problems and what we need to do to focus. 23 Team Biologics, I'm sure there will be some 24 questions about that. That was a way to bring FDAMA STAKEHOLDERS MEETING, 4/28/99 34 1 our inspection compliance activities into line 2 with the rest of the FDA. Twenty-five years 3 after biologics was absorbed in FDA, we still did 4 business in a major different way. Our 5 inspection program was conducted out of 6 headquarters, and some believed our GMP attitudes 7 and compliance activities were out of line. 8 We believe that because of the cutting edge 9 of our technology, our scientists really needed 10 to be involved in the inspectional approach. So 11 ORA and CBER got together, and we developed Team 12 Biologics. I'll go over it in a couple of 13 minutes. 14 Tissue Regulatory Framework, that's an 15 action plan that's developing strategies to 16 regulate tissues. Congress has for years been 17 talking about enacting statutes. They have not 18 yet done so, and we anticipate should it be done, 19 it will be another unfunded mandate, so we have 20 been working on how to come to grips with the 21 tissue issues without any additional funding or 22 resources. 23 The Blood Action Plan I mentioned was the 24 granddaddy of the Xenotransplant Action Plan. FDAMA STAKEHOLDERS MEETING, 4/28/99 35 1 That came to light with Jeff Getty and his baboon 2 blood marrow implant a few years ago. We decided 3 we needed to get together and be proactive. 4 There are companies developing human-gene-based 5 pig organs. Our own research lab discovered 6 porcine endogenous retrovirus, or PER, that's 7 genetic codes from viruses that were embedded in 8 porcine tissue. And we had some INDs for liver 9 assist devices, and when this was discovered, our 10 lab was able to do the research, find out they 11 were nonreproducing, nonreplicating, 12 noninfectious, and therefore didn't pose a risk. 13 The hold was very minimal, but we were able to 14 investigate it, reach an informed decision, 15 change the informed consent, and move on. Again, 16 the need for a research program. 17 The Device Action Plan, we'll go into detail 18 on that, and the ICH, so that the industry has a 19 single group of requirements to comply with 20 around the world. 21 Device Action Plan, in part spurred by the 22 device law changes included in FDAMA. And last 23 year we heard -- I heard it in Oakland, in D.C., 24 and then again in Irvine. We had a meeting back FDAMA STAKEHOLDERS MEETING, 4/28/99 36 1 in December to discuss this in Bethesda. And 2 what industry has said we don't provide is 3 consistency, harmonization with CDRH, a 4 transparent process they can understand, 5 facilitated reviews, guidance, and 6 communication. 7 So we have set up four teams as part of the 8 Action Plan: CBER/CDRH Coordination, Review 9 Performance, Compliance and Team Biologics, which 10 I'm the chair of, and the Outreach/Inreach, which 11 Mary Myers, who is the director of our Office of 12 Communications Training Manufacturers Assistance, 13 is in charge of. And that is designed to both 14 get our message and hear the messages of our 15 stakeholders in the device area, as well as deal 16 with our own employees who may not understand 17 what's going on. That's why we added the inreach 18 to the always traditional outreach. 19 Coordination has a bunch of action items. 20 The Intercenter Agreements are now many, many 21 years old. Aside from my gray hair, my memories 22 of the original Intercenter Agreements and 23 implementing the '76 drug amendments reminds me 24 just how old I am. We realize that technologies FDAMA STAKEHOLDERS MEETING, 4/28/99 37 1 and products have come down the pipeline that 2 weren't even thought of or imagined at the time 3 of those agreements, so we are working with CDRH 4 and, as a matter of fact, CDER, but we're 5 starting with the CBER/CDRH agreement. 6 A Re-engineering Work Group that was so 7 successfully set up by Bruce Burlington, we're 8 working with them to get their lessons learned so 9 that we don't reinvent the wheel. 10 We've published the FR Notice of 11 Concurrence. I think it was last Friday. 12 FDAMA training at CDRH, our people are 13 attending the training that CDRH reviewers get, 14 and in fact, on some products the CDRH reviewers 15 are attending our training. 16 Device Web page, if you look at our Web 17 site, you now have the devices separately, so you 18 don't have to go hunting through the material, 19 again a direct outgrowth of last year's 406(B) 20 meetings. And we are preparing guidances on 21 many, many issues relating to medical devices. 22 The CBER/CDRH Coordination Outcomes, 23 Commitment: The commitment to review devices in 24 a timely manner using the same standards as FDAMA STAKEHOLDERS MEETING, 4/28/99 38 1 CDRH. Coordination with them, cooperation, 2 communication, and again consistency. I believe 3 those of you who were at the meeting last year 4 can testify that that is exactly what we heard. 5 Review Performance, our review performance 6 in the device area is, quite frankly, very poor. 7 We realize that, and it's a result of funding. 8 The same people who do that have been involved in 9 providing the scientific support of those 10 injunctions on 60 percent of the nation's blood 11 supply. Compliance issues have to come first, 12 and as you saw in that one slide, we keep 13 reducing the amount available to other products. 14 We have a proposed reorganization in our Office 15 of Blood, and that will hopefully give more 16 attention and control. 17 Set Review Objectives, Implement Managed 18 Review Process. We developed a managed review 19 process to implement FDAMA and PDUFA. We are 20 extending that to include the blood process. 21 That is where we mapped out our business rules. 22 They covered three walls. We're now looking to 23 where we can re-engineer that. We have something 24 called the 2-B process that we're working on, and FDAMA STAKEHOLDERS MEETING, 4/28/99 39 1 that is almost finalized. When it is, it will be 2 up on our Web site. 3 And Develop Targeted Guidance for specific 4 products in specific areas. 5 Review Performance, again closely managed 6 process, define expectations and priorities, meet 7 time frames and deadlines, and maintain the 8 review quality. Again, no one benefits from a 9 poor product getting approved. 10 Compliance and Team Biologics, as I said, I 11 chair that group. 12 Review the device inspection policies, make 13 sure they are conforming with the CDRH policies, 14 except where the nature of the risk from the 15 product justifies an exception. We will not be 16 lowering standards, but we will identify the ones 17 where we can and evaluate that, and where they 18 are different, we're going to clearly explain 19 them, both to our own people and to the industry, 20 as well as why. 21 Training and guidance, we will be training 22 our own people, and we will be doing what we've 23 done traditionally in CBER, and after developing 24 the training program, hold a similar program FDAMA STAKEHOLDERS MEETING, 4/28/99 40 1 available to industry so they can hear the same 2 words the investigators hear. 3 Develop sterility and stability, I guess the 4 word got left off there, guidance for the 5 inspectional program, and GMP guidance for CBER 6 IVDs. That is an issue that came up frequently 7 last year, and we have a group that's composed of 8 CDRH, CBER and ORA, our field people, that will 9 be coming up with an explanation of what the 10 standards are, and if they are different, why. 11 ORA coordination, a transparent inspectional 12 process, just one that when our investigator 13 walks in, whether it's a district investigator or 14 Team Biologics team, you'll know what they are 15 going to be doing. 16 And a consistent compliance approach. Over 17 the years, we have heard that different districts 18 do things differently. In fact, I've heard that 19 for close to thirty years now. The way we're 20 handling that in the biologics area is part of 21 Team Biologics. We have two compliance officers, 22 one on the East Coast, one on the West Coast, to 23 coordinate our actions. So we have reduced the 24 number of people to oversee it, and so we get a FDAMA STAKEHOLDERS MEETING, 4/28/99 41 1 consistent approach. 2 Outreach/inreach, developing strategies I 3 talked about to explain what we'll be doing 4 there, or actually what we are doing doing here. 5 The 21st Century Biologic Products, when I 6 left the Center for Drugs and came over to 7 Biologics about eleven years ago, I had a long 8 conversation with my mother, who's my 9 reality-based check, and she said, "What's the 10 difference?" And I tried to explain to her that 11 blood and vaccines and other biotech things like 12 gene therapy, cellular therapy, monoclonal 13 antibodies, and she had no idea what I was 14 talking about. She has now learned by watching 15 the evening news that every time she hears about 16 one of these new products, she'll ask me, "Is 17 that thing I saw yours?" I say, "Yes, that's 18 ours." 19 It's clear that the future of biomedical 20 science is in the biologics area. So what are we 21 going to have to deal with? New biomedical 22 technologies, the safety of those, ethical 23 issues. I remember a happy time in my youth at 24 FDA when we used to say ethics weren't really our FDAMA STAKEHOLDERS MEETING, 4/28/99 42 1 issue; that was the IRB's and the institutions 2 themselves and the companies. That's not true 3 anymore. We really do have to get involved, 4 particularly things affecting the germ line, 5 where the ethical issue is part of the 6 benefit-to-risk equation. And the harmonization 7 of regulatory standards, both within FDA, but 8 more importantly, around the world. 9 Changing health care environment. I 10 remember telling people, and telling people on 11 the Hill particularly: "FDA doesn't get involved 12 in economics. We deal with safety and 13 effectiveness." In today's managed care 14 environment, that is part of the risk/benefit 15 equation. A technology that is incremently 16 better but costs a thousand times more, is it 17 worth it? And when you get into these 18 discussions, for those of us who started out as 19 FDA investigators, or as they were called when I 20 was, inspectors, life was easy. You dealt with 21 rat pellets in flour. You dealt with unsafe, 22 adulterated, or sub- or superpotent drugs. Now 23 we're involved with incremental change: Is a 24 product that's a thousand times more expensive, FDAMA STAKEHOLDERS MEETING, 4/28/99 43 1 that gives a person a one in one thousand chance 2 at a better outcome, worth it? Well, if you're 3 that one person, you think it is. And it's a 4 really strange discussion that gets involved with 5 how you make those decisions on whether the 6 approval is worth the increased risk or increased 7 cost. Again, we try and stay out of it. 8 Bioterrorism, two years ago I knew nothing 9 about bioterrorism. Now I have a Top Secret 10 clearance and I know more than I ever want to. 11 That is an important part of today's life. The 12 Department of Health and Human Services has been 13 given a large amount of money to purchase a 14 civilian stockpile of drugs, biologics, and 15 devices for use in terrorism. We are involved in 16 that and are advising the department, 17 facilitating development in dealing with that, 18 another thing that has been taking up enormous 19 amount of resources, and I'll say this again for 20 Bob's benefit, was not funded in this current 21 year's budget. Hopefully next year we will get 22 some, but it is a very important thing for the 23 civilian stockpile as well as advising DOD on 24 their actions. FDAMA STAKEHOLDERS MEETING, 4/28/99 44 1 Y2K Issues. You can't pick up the paper 2 today without finding out that January 1, the 3 whole world is going to collapse. I was reading 4 my local paper, and somebody in my neighborhood I 5 know for twenty years has turned into a raging 6 survivalist. She has more generators, dried 7 foods. You know, it reminds me, those of us old 8 enough, back in the '60s and the '50s with the 9 fallout shelters. Now, this is something I've 10 known for twenty years and I think is fairly 11 rational. And the hype given to this has reduced 12 the confidence of the public. So we're very 13 involved with working with our industry, working 14 with the department. We have a Y2K working 15 group. Those of you in industry will soon be 16 getting a letter from us to submit what you have 17 done with your Y2K preparedness. We have been 18 working on a shortage plan, which in addition to 19 our normal shortage operations, makes sure that 20 the products that we regulate will be there. 21 Again, another big job that is unfunded, and this 22 one's our bottom line. 23 In closing, I don't want this to be the last 24 time we communicate. In my last job, I was FDAMA STAKEHOLDERS MEETING, 4/28/99 45 1 pretty proud of the information systems that we 2 set up. I always used to keep this slide for 3 last because most of the people at meetings were 4 Internet-challenged. But now just about everyone 5 has access, and we have a fairly large Web site. 6 That's the address. And if you have a question 7 in general, you can e-mail it to that e-mail box, 8 and someone from our Office Communications 9 Training Manufacturers Assistance will either 10 answer it or get it to the person who can answer 11 it. 12 Questions for Stakeholders, this is the 13 purpose of this meeting. This was in the Federal 14 Register Notice, and this is what we've asked the 15 speakers to address. And aside from being in the 16 slides, they are on those question sheets as 17 well: 18 "What actions do you propose the Agency 19 take to expand our capability to incorporate 20 state-of-the-art science into its risk/benefit 21 decision making? 22 "What actions do you propose to facilitate 23 the exchange and integration of scientific 24 information to better enable FDA to meet its FDAMA STAKEHOLDERS MEETING, 4/28/99 46 1 public health responsibilities throughout the 2 product's life cycle? 3 "What actions do you propose for educating 4 the public about the concept of balancing risks 5 against the benefits in public health decision 6 making? 7 "What actions do you propose to enable FDA 8 and its product centers to focus resources on 9 areas of greatest risk to the public health?" 10 And, "What actions do you propose for 11 enhancing communications processes that allow for 12 ongoing feedback and/or evaluation of our 13 modernization efforts?" 14 And that's it for the slide talk. I'd be 15 happy to answer any questions or you can save 16 them for after the speakers. Anyone? That being 17 said, I thank everybody for their patience in 18 listening to me. 19 (Applause.) 20 And I want to thank the folks back at the 21 office that put that one together. If any of you 22 are interested in sharing these with 23 colleagues -- I know some companies, I hear from 24 people who have left the FDA, require you guys to FDAMA STAKEHOLDERS MEETING, 4/28/99 47 1 make out trip reports and things. These slides 2 have been posted on our Web site since 3 yesterday. So if you want them in color that you 4 can attach to e-mails and stuff like that, you 5 can just download it. They are in Powerpoint, 6 and you can get the entire set if you want to do 7 briefings within your own company. 8 The other thing is, as of yesterday, the 9 Device Action Plan, which was signed by 10 Dr. Henney last Friday, is posted there as well. 11 It was only approved last Friday, and we didn't 12 have enough time and we weren't real sure whether 13 we would be able to get it out here. And if you 14 are in that sector and you want to see the exact 15 plan that follows the tracks of what I had up 16 there but with the specific goals and the due 17 dates, that's there. 18 Okay, our first panel, Janice Bourque, 19 Executive Director Mass. Biotech Council; another 20 friend from last year, Jim Weston from Biopure; 21 and Lisa Raines from Genzyme, a very well-known 22 company here in the Northeast. And there's Steve 23 and John. And just go ahead. Do you want to 24 come up here? FDAMA STAKEHOLDERS MEETING, 4/28/99 48 1 MS. BOURQUE: We're going to use the 2 overhead. 3 Okay, well, thank you for allowing us to 4 speak again today. As was mentioned, we were in 5 Washington, D.C. last year, so welcome to 6 Boston. We've also had a recent visit with 7 Dr. Henney. She came and visited the Mass. 8 Biotech Council and the Device Council as well, 9 so we were pleased to have the opportunity to 10 talk with her about some of our concerns and what 11 some of her concerns are as well. And we have 12 worked closely with the local FDA office, and 13 I'll point out how well we have worked together 14 on a pilot program that was very successful and 15 has continued and ongoing. 16 Today we have, as I mentioned, three 17 speakers, myself, Jim Weston, and Lisa Raines. 18 And I'm going to talk a little bit about meeting 19 performance time lines, FDA reviewer training, 20 and advisory panels. Jim Weston is going to talk 21 about risk/benefit and consumer education, and 22 Lisa is going to speak about fast-track generic 23 biologics and pediatric exclusivity extensions 24 with regards to orphan biologics. FDAMA STAKEHOLDERS MEETING, 4/28/99 49 1 Just so you'll know a little bit about us at 2 the Mass. Biotech Council, we represent about 250 3 companies here in Massachusetts. They are mainly 4 small to medium size, and they range anywhere 5 from early stage companies of anywhere from two 6 to three people to full-scale commercial 7 manufacturing companies with several thousands. 8 The MBC has been in operation for about 9 fifteen years, and our primary mission is to 10 ensure that all biotech companies, whether they 11 choose to remain small or become fully integrated 12 companies, reach their full potential. 13 Last year the MBC had put together an FDA 14 White Paper in response to FDAMA and actually 15 tried to come up with recommendations on how to 16 actually carry out the implementation and write 17 the regulation and have input into the guidance 18 documents. It's one thing for Congress to 19 write. It's another challenge, I think, for the 20 FDA and for industry to work together to ensure 21 that the regulations reflect that legislation and 22 move forward. So we're very supportive of this 23 mission to ensure that there's prompt approval of 24 new drugs and therapies. And our primary goal FDAMA STAKEHOLDERS MEETING, 4/28/99 50 1 for the FDA, we know, and for the industry is to 2 ensure that these patients have access to these 3 therapies and that we're able to get them to them 4 as quickly as possible. 5 One thing I'll mention today, we do have 6 some copies of these slides. We will be 7 submitting an actual document to the FDA. I 8 think we have to about May 14, I think. And it 9 will be similar to our White Paper. It will be a 10 second White Paper with the actual text that will 11 go into further detail from these slides, and 12 that will be available. It will be up on our Web 13 site as well as directly supplied to the FDA and 14 to anyone who would like a copy of that. 15 For the first section on meeting the 16 performance goals, I'd like to speak briefly 17 about our last meeting. We had come up with 18 recommendations in our White Paper regarding 19 meeting performance goals, and since then a 20 guidance document has been released. And in this 21 guidance document we noted that we had made some 22 recommendations on dispute resolution, and we had 23 asked that the sponsor be able to provide 24 corrections to the FDA fifteen days from receipt FDAMA STAKEHOLDERS MEETING, 4/28/99 51 1 of minutes from the FDA, and that in return the 2 FDA provides response back to the sponsor fifteen 3 days from receipt of the correction from the 4 sponsor. We think it's very important that we 5 have firm time lines within the guidance 6 documents, and we believe those were not put in 7 there. And that way the expectations are very 8 clear from both sides just who has been operating 9 within the response time that's necessary. I 10 think to leave it open, again, leads us to a 11 position where we are now where it's up for 12 discussion, debate, and not necessarily being 13 able to have a sense that we are moving the time 14 line. 15 Secondly, with regards to meeting the 16 performance goals, with regards to fast-track 17 meetings and sponsor-requested fast-track 18 meetings, we wanted those meetings to be 19 scheduled within fourteen days of the request by 20 the sponsor. And then we also requested that the 21 meeting actually occur within thirty days of 22 receipt of the sponsor's request, and that again 23 was not noted or given firm time lines in the 24 guidance document, and we're hoping that there's FDAMA STAKEHOLDERS MEETING, 4/28/99 52 1 still an opportunity to put those expectations in 2 that guidance document. 3 With regards to FDA reviewer training, when 4 Dr. Henney was here, she indicated there were 5 three areas of great concern with her. One was 6 actually carrying out FDAMA implementation. The 7 second was on building the science base at the 8 FDA, and the third was addressing real safety 9 issues, and those were three of her primary 10 focuses that she addressed to us. 11 So with regards to building on the science 12 base, which I know some of the questions have 13 been asked, the MBC, as I mentioned earlier, has 14 a model program experience in the success area of 15 manufacturing. With John's local office, we've 16 been able to develop a preinspection pilot 17 program, and that we actually won in conjunction 18 with the local FDA office Al Gore's Hammer Award 19 for a model program on helping to reinvent 20 government and streamline it. So we have that 21 expertise. So what we'd like to recommend is 22 that we could develop a model program for FDA 23 training. 24 Now, we know the reviewers already receive a FDAMA STAKEHOLDERS MEETING, 4/28/99 53 1 great degree of training, but we think that 2 together with industry, we might be able to help 3 develop that science base further. And so what 4 we thought we could do is maybe create a 5 seminar-type format in which cutting edge 6 technology would be presented. And that could be 7 presented by academia, by industry, leaders in 8 this field of research that's going on who could 9 present this type of cutting edge technology to 10 allow the reviewers to come, ask questions, 11 present the work they are doing. 12 It really creates a certain synergy. It's 13 not for any one company or researcher to hope to 14 gain an "in" with the FDA. This is really to 15 talk about the science so the reviewers are right 16 there. It's a challenge for us as an industry to 17 stay up to date on all of the technology that's 18 being developed, so we can only envision it's a 19 real challenge for the reviewer as well. 20 I have a possible suggestion or solution. 21 We could do it in a neutral location. We'd love 22 to do it here in Massachusetts. There is a 23 facility, the Mass. Biologics facility, which now 24 comes under the purview of the University of FDAMA STAKEHOLDERS MEETING, 4/28/99 54 1 Massachusetts. There may be another facility as 2 well that I'm not aware of. But the reason why I 3 suggested this facility is because they already 4 have conducted FDA training there, and it is a 5 CDC alternative site, so we know they probably 6 have the necessary equipment and the presentation 7 rooms in order to do this. 8 And, similarly, seminars could be developed 9 so that it's reciprocal between the FDA and 10 industry. So if there are ways the industry has 11 shortcomings in terms of its ability to interact 12 or report or have discussions with the FDA, there 13 are things that we continually do, ways that are 14 ineffective, we certainly would welcome the FDA 15 to also give seminars to us in how we can do that 16 better. So we really see this as an interactive 17 opportunity to develop a model program. And 18 there may be some things similar. We certainly 19 don't want to say this is just something 20 associated with Biologics, but maybe this could 21 be expanded to include products. I mean, 22 whatever opportunities we see there. 23 The last point I'll make has to do with the 24 advisory panels. In our earlier White Paper, we FDAMA STAKEHOLDERS MEETING, 4/28/99 55 1 did ask for harmonization between the two 2 divisions. Currently CBER has what we believe is 3 a great operating policy, where they actually 4 submit to the sponsor their draft panel 5 documents; and that allows a sponsor then to 6 review and give comments back to the FDA before 7 it goes back to the advisory panel. That's very 8 important because let's say there was some point 9 that was made incorrectly or confusion over a 10 particular point. The sponsor has a chance to 11 correct it before it's actually spent a great 12 deal of time at the advisory panel going over 13 something that simply could have been clarified 14 ahead of time, so that when you're at the 15 advisory panel meeting, you're really focusing on 16 what is really crucial and important. 17 Right now CDER does not do that, rarely does 18 that, and we would just really like to see CBER's 19 policy harmonized and carried over into CDER. We 20 think there's a real opportunity to use the 21 advisory panel in the capacity that they were 22 originally intended. 23 And with that in mind, also I want to talk 24 briefly a little bit about the role at the FDAMA STAKEHOLDERS MEETING, 4/28/99 56 1 Advisory Panel. What we see the role of the 2 Advisory Panel -- and I was looking at some of 3 the documentation as to the description of the 4 role of the Advisory Panel. It was really for a 5 third-party evaluation mechanism for advice, 6 particularly regarding scientific controversies 7 or some cutting-edge technology that's really 8 challenging. It is important that the FDA note 9 the impact these Advisory Panel meetings has on 10 the industry. They are open public meetings. 11 They are often filled with a variety of 12 individuals, including investors, and they 13 greatly impact our ability to raise research 14 dollars. And even if you get an approval from 15 the Advisory Panel, we see fluctuations in stock, 16 that even with a positive result, we'll see 20 or 17 30 percent fluctuation on the stock. So it's 18 important to note that these panels, what they 19 say and do has great impact. 20 But we're very concerned about how the 21 panels are now being used. We think that perhaps 22 they are used too frequently and they are used 23 just to endorse what the FDA already used, not as 24 third-party evaluators. And so what we'd like to FDAMA STAKEHOLDERS MEETING, 4/28/99 57 1 recommend is that if the company has proven 2 safety and efficacy to the extent that the FDA 3 feels is necessary, to maybe not go into an 4 Advisory Panel review process, but go through 5 just a rapid-approval process, and really use the 6 Advisory Panel for controversial issues. 7 Additionally we also, because these are open 8 public forums, we're asking that the FDA consider 9 that these be closed forums, so that the 10 discussion really does not affect the outside 11 investors, the stock market or what not; that 12 really instead of having individuals in the room 13 who really don't necessarily need to be there, if 14 it's going to be a scientific discussion, to 15 really consider having closed Advisory Panel 16 meetings. Certainly the FDA could have anyone 17 there that they feel is important to be there, 18 but limit who exactly ought to be in that room. 19 Essentially also we'd like to maybe have 20 some conformity or best practices evaluated by 21 the advisory panels. I think companies have 22 various experiences on what worked well, how some 23 advisory panels really operated, they felt, to 24 both the benefit for the FDA and for the company, FDAMA STAKEHOLDERS MEETING, 4/28/99 58 1 as well as a third party and others that probably 2 did not operate as well, and that there might be 3 opportunities to develop conformity or best 4 practices to address the Advisory Panel. 5 I'm going to have Jim Weston now come up and 6 talk about consumer education and risk/benefit, 7 and then we'll have Lisa. Then we'll take 8 questions. 9 MR. WESTON: Thanks, Janice. As Mark 10 Elengold mentioned, most products in the American 11 marketplace really, especially medical ones, have 12 two facets. On one side, we know that they 13 really benefit users and often improve lives. We 14 also know that they are, however, rarely without 15 at least some risk, and that risk can result in 16 known or unknown side effects. Consumers must 17 often weigh the benefits and risks before using 18 these products, oftentimes with incomplete 19 information. 20 In order to address this issue, the FDA 21 asked us for responses to the question: What 22 actions do you propose for educating the public 23 about the concept of balancing risks against 24 benefits in the public health decision making? FDAMA STAKEHOLDERS MEETING, 4/28/99 59 1 We know that FDA's mission is to promote the 2 public health by promptly and efficiently 3 reviewing clinical research and taking 4 appropriate action on the marketing of regulated 5 products in a timely manner. Under FDA's Plan 6 for Statutory Compliance of last November, which 7 addressed the requirements set in Section 406 of 8 the FDAMA Act, several objectives were stated. 9 They included: Maximizing the availability 10 and clarity of information for consumers and 11 patients regarding new products, implementing 12 inspections and postmarket monitoring, and 13 ensuring FDA's access to scientific and technical 14 expertise. 15 Let's talk a little bit about some of 16 these. The ability to improve public education 17 and understanding about the concepts of balancing 18 risks against benefits in the public health 19 decision-making process could be enhanced with 20 several new and expanded concepts developed and 21 implemented by FDA, sponsors, patient groups, and 22 other governmental agencies. First, the concepts 23 of risk/benefit analyses should be expanded in 24 discussions and agreements between the FDA and FDAMA STAKEHOLDERS MEETING, 4/28/99 60 1 sponsors throughout the entire development 2 process. FDAMA provided a guideline for the 3 management of meetings between sponsors and the 4 FDA and the MBC, the Mass. Biotech Council, in 5 its July 18 White Paper provided points to 6 consider relative to the meeting section of that 7 document. In accordance with some of those 8 proposals which we made and agreed upon, there 9 should be during each critical meeting decisions 10 and agreements made relative to risks as well as 11 benefits. FDA should discuss the criteria 12 development agreements that will form the basis 13 of an acceptable risk as part of the overall 14 approval and development process. 15 Furthermore, if a product is to be discussed 16 at an Advisory Committee meeting as part of its 17 approval process, a summary of both the FDA and 18 sponsor agreements and opinions regarding the 19 risks/benefits of the drug which have occurred in 20 developing the development process should be 21 presented as well for a balanced review. 22 Secondly, the agency's criteria for 23 presenting well-balanced information to the 24 consumer needs to incorporate all aspects of the FDAMA STAKEHOLDERS MEETING, 4/28/99 61 1 health care system. Risk/benefit information is 2 provided in the package inserts which accompany 3 distribution of most prescription products. It's 4 also associated with ads for prescription 5 products, and a patient package insert is often 6 provided when a prescription product is 7 dispensed. But because of the complex nature of 8 this information and often the general lack of 9 public knowledge regarding the development 10 process, this information is often not read, is 11 either overlooked or can be misinterpreted if at 12 all read. 13 While other forms of communications are 14 becoming available -- for example, on Web sites -- 15 the same information is often provided in just a 16 different manner. In order to address this 17 concern, we would propose that FDA explore pilot 18 programs with effective education regarding 19 risks/benefits of prescription products, with the 20 primary public contact persons giving out 21 prescription medicines; that is, the prescribing 22 physicians or dispensing pharmacists. These are 23 the individuals with the background and training 24 to understand the risks/benefits and who can FDAMA STAKEHOLDERS MEETING, 4/28/99 62 1 directly assure that patients best understand the 2 risks and benefits of the products. This type of 3 program would be extremely beneficial, 4 particularly for fast-track products where there 5 are often high risks involved. 6 The FDA does have a Pharmacist Education 7 Outreach Program, and we encourage its 8 expansion. In today's managed health care 9 system, it's likely that insufficient time is 10 allotted or allowed for this purpose. Thus a 11 cooperative agreement must be reached between all 12 parties in health care systems, the sponsors, the 13 FDA, the physicians, the pharmacists, and often 14 health care peers, to be able to provide this 15 information in time to give benefit to patients. 16 Collaboration with all stakeholders -- i.e., 17 the media, the consumers, the patient groups, and 18 other federal agencies -- is encouraged. 19 Third, the timely dissemination of current 20 and cutting-edge "scientifically sound" 21 information regarding potentially new uses and 22 findings of drugs and biologics should be 23 expanded. This includes the dissemination of 24 information on unapproved new uses and timely FDAMA STAKEHOLDERS MEETING, 4/28/99 63 1 information regarding postmarketing surveillance 2 of new and existing products. 3 FDA and sponsors need to work cooperatively 4 to develop the full potential of the Internet as 5 a two-way communication tool as part of this 6 process. Information regarding new approved and 7 "scientifically sound" information on unapproved 8 uses should be readily available to consumers and 9 health care professionals in an effective 10 manner. In a similar manner, safety profiles and 11 updated safety information regarding products 12 should also be available freely on the Internet. 13 Information from FDA's Adverse Events Reporting 14 System should also be promptly posted. 15 And, lastly, the FDA in order to communicate 16 effectively with consumers and patients, needs to 17 enhance and expand the agency's collaborations 18 with industry, other governmental agencies, 19 academia, and patient groups. In this manner, 20 information exchange, scientific expertise, and 21 important interchanges regarding key information, 22 including risk/benefit analyses, can occur. We 23 strongly encourage FDA to expand its interactions 24 with the NIH, the National Institutes of Health, FDAMA STAKEHOLDERS MEETING, 4/28/99 64 1 regarding the science-based expertise and patient 2 education process. 3 And Lisa Raines? 4 MS. RAINES: I didn't make advance 5 arrangements for somebody to do my overheads, so 6 Janice is being very kind to help me out here. 7 In the remaining time, I'm going to address 8 three issues, each of which is fairly complex, 9 and so each of which is going to be addressed in 10 a fairly shorthand manner. And if there is a 11 minute or two remaining, I may take the 12 opportunity to offer some personal comments on 13 some of the issues that Dr. Elengold raised that 14 we've had some discussions on in the industry. 15 The first issue I'd like to talk about is 16 the new Fast Track Program which we're very 17 excited about, and in fact had the opportunity to 18 discuss with Dr. Henney when she visited Genzyme 19 for close to an hour just a few weeks ago. And 20 let me begin by saying that the concept of fast 21 track, which was developed in collaboration 22 between FDA, the Congress, and the industry, was 23 to look at best practices that FDA had already 24 adopted through the Accelerated Approval Program, FDAMA STAKEHOLDERS MEETING, 4/28/99 65 1 or through what we sometimes call "skunk works," 2 where individual reviewers had taken 3 extraordinary initiative to move products through 4 the pipeline in a rapid and effective way, and to 5 see if we could come up with some way of 6 institutionalizing and broadening the scope of 7 what we viewed as best practices that FDA had 8 already implemented. 9 I think to a significant extent we all 10 recognize that fast track initially builds on the 11 existing accelerated approval regulations. FDA 12 put out the guidance document required by the 13 statute a few months ago, and by and large, I 14 think it's been very well received by the 15 industry. It recognizes that fast-track products 16 may either be accelerated approval products based 17 on an approval on either a surrogate end point or 18 a short-term clinical end point, or it may be a 19 regular approval, and you've got the advantage of 20 rule and review in either case. But I'm going to 21 focus on the accelerated approval side because I 22 think that the regular approval side is the area 23 with which there's broadest experience and 24 broadest knowledge, both on the part of the FDAMA STAKEHOLDERS MEETING, 4/28/99 66 1 industry and the agency, and at the accelerated 2 approval side where there's still a lot of 3 clarity that we think could be injected in the 4 system. 5 As most of you probably know, in 1992, 6 largely in response to the AIDS crisis, FDA 7 adopted an accelerated approval regulation that 8 recognized that the risk/benefit analysis with 9 respect to a serious or life-threatening disease, 10 for which there was an unmet medical need, 11 required a greater degree of flexibility than 12 another headache remedy. And so FDA developed a 13 regulation under which they indicated that an 14 accelerated approval could be provided in the 15 absence of proof of effect on morbidity, 16 irreversible morbidity or mortality, if an effect 17 could be shown on a surrogate end point or a 18 short-term clinical end point that was reasonably 19 likely to predict clinical benefit. 20 This provision raises a couple of 21 questions. Scientists sort of take as a given 22 that a P value of less than .05 proves the 23 validity of an end point in affecting morbidity 24 or mortality; but when you talk about something FDAMA STAKEHOLDERS MEETING, 4/28/99 67 1 being reasonably likely, that's clearly less than 2 proving validity. And so the question is: How 3 much data do you need to prove that a particular 4 chosen end point is reasonably likely to predict 5 a clinical outcome? And we're not sure that 6 there is consistency or clarity on this point. 7 If you look at the examples in the past, 8 AIDS, I think, being a brilliant example, the one 9 with which there's most experience and the most 10 products and where the surrogate end point -- 11 namely, CD4 cell counts -- has now been validated 12 through showing increased life spans for people 13 who take the products approved under this regime, 14 there was evidence showing that a reduction in 15 the immune system eventually led to people 16 getting sicker and eventually dying. And so it 17 was hypothesized that if you could increase that 18 cell count and improve the immune system, that 19 you could make people live longer. But that 20 wasn't proven until long after people had 21 actually gotten these drugs after they were 22 approved, and really over the last year, where 23 major scientific conferences have come to a 24 consensus that the selected end points were FDAMA STAKEHOLDERS MEETING, 4/28/99 68 1 validated. But there was a good scientific basis 2 for expecting that the correlation was so close 3 between morbidity and a decline in the immune 4 system, that an improvement in the immune system 5 would in fact improve life span, and that's now 6 proven to be the case. 7 But as we looked at other non-AIDS products 8 and we look at noncancer products -- and AIDS and 9 cancer are the two principal areas where 10 accelerated approval has been used -- we found 11 great more debate as to how much data you need to 12 show that a particular chosen end point is 13 reasonably likely to predict clinical benefit. 14 Now, remember, in the case of all of these 15 accelerated approval products, there is a phase 16 for postapproval study requirement, which 17 essentially requires that the end point chosen be 18 validated and that ultimate clinical benefit be 19 proven. So the concept is that ultimately, yes, 20 we do need to prove clinical outcome as approved 21 by the product, but we can approve the product 22 short of that and collect the full validating 23 data on a postapproval basis. But how much short 24 of that provides adequate confidence for FDA to FDAMA STAKEHOLDERS MEETING, 4/28/99 69 1 believe there's substantial evidence of safety 2 and efficacy? 3 These are some questions that we would like 4 to ask and we don't have an answer for. We 5 believe that the industry and the agencies should 6 be collaborating on a discussion of these 7 questions, a discussion that I think has taken 8 place on a very ad hoc basis product by product, 9 but where there aren't general principles. 10 What the AIDS drug manufacturers were able 11 to do, for example, was show an increase in CD4 12 cell counts but not an improvement in mortality. 13 There are now some reviewers in CBER who believe 14 that you must not only show an improvement in the 15 chosen surrogate, but show the improvement all 16 the way up to a normal stage, which was not 17 required in the AIDS cases. 18 Remember also that these are for serious or 19 life-threatening diseases where the drug has the 20 potential to meet an unmet medical need. So 21 we're not talking about having this greater 22 flexibility except in those cases where there's a 23 compelling case that it's needed. 24 The second question, which is a really FDAMA STAKEHOLDERS MEETING, 4/28/99 70 1 difficult one to grapple with, addresses: What 2 do you do in the case of very, very rare 3 diseases? My company, Genzyme, sells a product 4 for one of the rarest diseases for which there is 5 an FDA-approved product, serozyme. There are 6 about a thousand U.S. patients. Serozyme is the 7 most common of about 40 genetic disorders of the 8 same type. There is very little data out there 9 regarding the history and pathology of these 10 other disorders. How is it possible then to 11 develop reasonably reliable surrogate or 12 short-term clinical end points when there's very 13 little historical control data available, and 14 where the patient population is so small that 15 it's almost impossible to get statistically valid 16 results even with a surrogate end point that 17 everybody agrees is appropriate? You could do a 18 clinical trial that requires every patient in the 19 United States to enroll in the trial for some of 20 these very rare diseases. How do you get there 21 from here in a way that makes it possible for 22 these products to be developed? 23 I want to just remark that FDA's fast track 24 guidance document does discuss in a footnote the FDAMA STAKEHOLDERS MEETING, 4/28/99 71 1 use of short-term clinical end points to serve as 2 the basis of an accelerated approval. There are 3 reviewers in CBER who have said short-term 4 clinical end points can serve as the basis of an 5 accelerated approval. 6 So is this an education issue, or are we 7 misunderstanding the type of short-term end 8 points? There were some examples given that 9 might serve as the basis of approval. And to 10 what extent can we look at the previous and, I 11 think, excellent FDA document that deals with the 12 design of clinical trials to look for cross- 13 confirmation of a surrogate end point and a 14 short-term clinical end point that overall 15 increases your confidence level but doesn't quite 16 get you to the level of statistical significance, 17 where there is a very small patient population in 18 particular? And these are really the two points 19 that I just mentioned, and they are in your 20 handout. 21 I'm going to move now to the issue of 22 generic biologics, and let me begin by saying 23 that we were very pleased with Dr. Henney's 24 response to the Senate indicating that she had no FDAMA STAKEHOLDERS MEETING, 4/28/99 72 1 plans to create a generic biologic approval 2 system. And we were further encouraged when she 3 was up here a few weeks ago and meeting with the 4 MBC where she elaborated on that response and 5 indicated that she believed that Congressional 6 intent would need to be demonstrated before FDA 7 would do that. And I think that's a wise 8 approach to take. 9 I think aside from the fact that the 1994 10 amendments to the Food, Drug and Cosmetic Act 11 don't address biologics and there's no legal 12 basis for biologics to go through a generic 13 approval process, there are some sound scientific 14 reasons to look at these large complex 15 macromolecules in a different way than the 16 simpler molecules that tend to be the basis of 17 most drug approvals. 18 However, we do have a concern with the fact 19 that some products that most of us non-FDA staff 20 think of as biologics, recombinant proteins, 21 lipoproteins, are sometimes regulated as drugs. 22 Some of these are products that predated the 23 Intercenter Agreement in which CBER and CDER 24 divvied up jurisdiction over these type of FDAMA STAKEHOLDERS MEETING, 4/28/99 73 1 products. Some of them have been assigned to one 2 center or the other since then, and we're aware 3 of disputes within the agency over which center 4 would get to regulate a particular recombinant 5 protein. 6 Those kinds of discussions, in our opinion, 7 for scientific public health reasons as well as 8 consistency and fairness reasons, should not 9 create a result in which one product might go 10 generic at some future point and the other 11 wouldn't, merely based on the convenience of the 12 agency. 13 The Intercenter Agreement, which was 14 developed when there was a dispute over a 15 particular product between the two agencies, is 16 based on a very elegant concept, and this is a 17 quote directly from the Intercenter Agreement. 18 I'm sure the CBER people are very familiar with 19 it, and on its face it seems that this concept is 20 very simple: You basically put the product in 21 whichever center it's appropriate to put it in 22 based on its physical characteristics, source 23 materials, or pharmacologic properties. 24 What we've seen, however, is that when you FDAMA STAKEHOLDERS MEETING, 4/28/99 74 1 actually try to apply these principles in 2 combination with the historic jurisdictional 3 interests of both centers, that you get some 4 inconsistent results. And these are just a few 5 examples that are real-life examples or that are 6 specifically stated in the Intercenter 7 Agreement. 8 For certain kinds of products, how you 9 manufacture a product determines whether it is 10 regulated as a drug or as a biologic. 11 Polynucleotide products, for example, if they are 12 made using recombinant DNA, are regulated as 13 biologics. The exact same molecule, if it was 14 extracted from tissue or chemically synthesized, 15 would be regulated as a drug. And yet it may be 16 for the exact same disease. It may have the same 17 molecular weight. It may have the same 18 composition. And the mere manufacturing method 19 determines, is it a drug or is it a biologic? 20 On the other hand, there are other products 21 for which the Intercenter Agreement says 22 manufacturing method is irrelevant. If your 23 product is a hormone, it gets regulated as a 24 drug, and it doesn't matter if it's a recombinant FDAMA STAKEHOLDERS MEETING, 4/28/99 75 1 product or a chemically synthesized product. 2 Similarly, vaccines and allergenic products are 3 regulated as biologics with regard to how they 4 are made. 5 So does manufacturing matter? The answer 6 is: It depends on the kind of product. And I 7 didn't see any clear scientific rationale for 8 differentiating between these two classes of 9 products and the general rule, except that 10 historically CDER has always done hormones and 11 antibiotics, and historically CBER has had 12 authority over blood, and statutory authority at 13 that. And so we had to carve out exceptions to 14 our general principles to conform with historical 15 jurisdiction, expertise, and other 16 considerations. 17 Again, the source materials matter. If you 18 take a product from blood, it's regulated by 19 CDER. If you take it from tissue, which contains 20 a lot of blood and which presumably has pretty 21 much the same product, it's regulated as a drug. 22 Furthermore, if a first-generation product 23 is derived from tissue and regulated as a drug, 24 then the second-generation recombinant product FDAMA STAKEHOLDERS MEETING, 4/28/99 76 1 will also get regulated as a drug, even though if 2 that second-generation product was developed 3 first, it would be regulated as a biologic. 4 So as these examples show, and there are 5 many others that will be in the more extensive 6 paper that we've prepared for you and that's just 7 going through all our MBC review process, these 8 general principles don't always have general 9 applicability. It's not always possible to 10 predict whether a product will be regulated as a 11 drug or as a biologic. Even where it can be 12 predicted, there can be unfairness. 13 I remember two companies, neither of which 14 was mine, developing products for ALS. Both were 15 common proteins. One was regulated as a drug; 16 one was as a biologic. It turned out both 17 products failed in the clinic. But to put 18 competitors in different centers with different 19 review groups, with different standards, and with 20 different implications for whether there was 21 going to be a generic version of their product 22 that would be substitutable at the drugstore in 23 the future, creates a competitive issue that 24 competitors are, I think, legitimately concerned FDAMA STAKEHOLDERS MEETING, 4/28/99 77 1 about. 2 Here are a couple of further exceptions to 3 the rule. Erythropoietin is a hormone produced 4 in the kidney. It's regulated as a biologic. It 5 did predate the Intercenter Agreement, but Amgen 6 has told me that they went to see Harry Meyer, 7 and Harry said, "Do you want it regulated as a 8 drug or do you want it regulated as a biologic?" 9 And Amgen says, "Well, we like the people in 10 biologics. They know the science. We'd like it 11 regulated as a biologic." And Harry turned to 12 Elaine Esper and said, "Okay, keep those 13 biologic." 14 That is not the way policies should be made, 15 and it has implications that even Amgen didn't 16 anticipate at the time. Similarly, the fact that 17 Genzyme decided to develop a non-recombinant GCR 18 product means that our recombinant product was 19 regulated as a drug. Had we gone directly to 20 recombinant, it would have been regulated as a 21 biologic. That has profound implications for 22 whether companies choose to develop first- 23 generation products and whether the patients have 24 access to those products earlier. FDAMA STAKEHOLDERS MEETING, 4/28/99 78 1 And, finally, the Intercenter Agreement 2 recognizes, and we agree, that if there's one 3 division in the agency that knows a lot about a 4 particular disease, it probably makes sense for 5 that division to do the review. But each center 6 has the authority to issue a license of either 7 kind, an NDA or BLA. I'm not aware of either 8 center having ever issued the type of license 9 that is typically provided by the other center, 10 and that may be something that's worth exploring 11 further. I'm going to go into that. That will 12 be a one-minute thing. 13 Given the fact that there's some randomness 14 on whether a biotech product is regulated as a 15 drug or a biologic, we believe that there should 16 be consistency with respect to whether such 17 products are subject to any kind of abbreviated 18 or truncated approval system. I won't go into 19 further detail on this, but you will see the 20 detail in our paper. There are good public 21 health reasons to say that minor differences in a 22 molecule should be demonstrated to be clinically 23 irrelevant before assumed to be clinically 24 irrelevant for that purpose. FDAMA STAKEHOLDERS MEETING, 4/28/99 79 1 If you move on to pediatrics, the pediatric 2 provision of FDAMA provides for a six-month 3 extension of market exclusivity if you do an 4 FDA-requested study and get the results before 5 your exclusivity expires. This extension only 6 applies to drugs. 7 Now, the only kind of exclusivity that 8 biologics get is orphan drug exclusivity, and we 9 have proposed and we would encourage FDA to 10 support legislation that amends FDAMA so that 11 orphan products, regardless of whether they are 12 drugs or biologics, are equally eligible under 13 the same circumstances for six-month exclusivity 14 extensions. 15 Thank you. 16 (Applause.) 17 MR. ELENGOLD: Just for the record, in case 18 you didn't notice, we're skipping the break. 19 Let's do questions. 20 MS. FAIRFIELD: Oh, you want to do 21 questions? Okay. After questions and answers, 22 we're really running late, so what we'll do is 23 break for lunch. And then the last two speakers, 24 Ms. Lopez and Ms. Jones, we'll have present after FDAMA STAKEHOLDERS MEETING, 4/28/99 80 1 the satellite downlink. 2 MR. ELENGOLD: I really am sorry I had to 3 cut you, Lisa, but just for the record, CBER has 4 many -- not many -- yes, many approved new drug 5 applications. A product that has been in the 6 news quite recently, avicerokylese (sic), is 7 regulated as a new drug application, not a 8 license. A lot of the plasma expanders are 9 regulated as NDAs. So we use all of the 10 available tools under the FDAC Act. We have 11 drugs, we have biologics, we have PMAs, and a 12 510(K)s. So CBER has used every bit of the 13 flexibility given us by the Act to affect the 14 right products. 15 MS. RAINES: Has CDER? I guess I should 16 have been more specific. 17 MR. ELENGOLD: Let me put it this way. I 18 worked there twelve years, and I don't remember 19 anything other than new drug applications, the 20 abbreviated new drug applications, Form 5s and 21 Form 6s, which don't exist anymore. 22 MS. RAINES: I should have been more 23 specific. 24 MR. ELENGOLD: Okay, I just have a couple of FDAMA STAKEHOLDERS MEETING, 4/28/99 81 1 questions. John, do you have any questions? 2 MR. MARZILLI: I'm all set. 3 MR. ELENGOLD: Okay, I just have a couple of 4 questions for Janice. One of the things you had 5 on your list was to use closed advisory 6 committees. How do you think that impacts on the 7 requirements we're under under the Federal 8 Advisory Committee Act? 9 MS. BOURQUE: In terms of making it an open 10 public forum? 11 MR. ELENGOLD: Yes. 12 MS. BOURQUE: I know that when I reviewed 13 the description of how that was going to be 14 conducted, I think we'll have to think about how 15 we can do this. It's really challenging, I 16 think, for our industry, where it's open to large 17 groups of individuals that we think don't lend 18 any kind of benefit to the meeting itself, but I 19 know it's challenging. You want to have an open 20 forum with people; there's nothing hidden. And 21 at the same time, there are some real challenges 22 as to why are the people there that are there? 23 MR. ELENGOLD: Yes, I've worked for FDA long 24 enough to remember the point in the early '80s FDAMA STAKEHOLDERS MEETING, 4/28/99 82 1 where the advisory committees changed from being 2 virtually empty rooms to lots of guys with at 3 that time briefcase-size cell phones. You know, 4 I remember that change. And I know somebody 5 mutters something, and we've actually had to 6 clear rooms because there were so many cell 7 phones ringing. 8 But it is a challenge. It is a requirement 9 that we're under under the law, and what I did 10 last year, and I'll request it again, where 11 people make suggestions like that, where it 12 appears to go against the legal advice we have 13 been given by our counsel, is say that we'd be 14 happy, if you want to have your counsel prepare, 15 you know, a justification and reason for that, 16 that we can present to our lawyers and committee 17 management people. That, we can do. But absent 18 that, I'm afraid, you know, that's one where 19 we're stuck with living with the law. We're not 20 only the law enforcers. We're the recipients of 21 law enforcement. 22 MS. BOURQUE: Right, and I think we'd be 23 willing to pursue that. 24 MR. ELENGOLD: I personally have been sued FDAMA STAKEHOLDERS MEETING, 4/28/99 83 1 by Sid Wolf for closing an advisory committee, 2 so. . . 3 MS. RAINES: Yes, if I can just add to that, 4 I think you're correct about the Advisory 5 Committee Act requiring open meetings. However, 6 proprietary information can be discussed in 7 executive session and is discussed by panels in 8 executive session. And the law provides that our 9 applications are confidential information, 10 including the data therein. And I think that 11 there is a way. Maybe you don't even call it an 12 Advisory Panel. Maybe you call it a meeting of 13 consultants. But there are mechanisms like 14 the executive session -- 15 MR. ELENGOLD: Meeting of consultants is 16 defined as a Advisory Committee by FACA. See, 17 that's the problem, but I don't want to get into 18 a lot of it, but I'm just saying, you know, we'd 19 be willing to consider it. And in fact, last 20 year after one of the things that FARMA brought 21 up at the 406(B) meeting, they did provide us 22 with a legal justification, and we have changed 23 some policies. So I'm just going to point that 24 out. FDAMA STAKEHOLDERS MEETING, 4/28/99 84 1 On the training issue, we have been working 2 with large groups over the years. One of the 3 problems we had is when we cosponsor with a 4 group, generally we're required to make that open 5 to anyone. And I'm just wondering if you have a 6 problem if we cosponsor something with you, that 7 we would have, you know, everybody flying in from 8 the West Coast as well. 9 MS. BOURQUE: No. I mean, no, no. 10 MR. ELENGOLD: Well, I'll invite you or 11 anybody else that's interested to get in contact 12 with Gail and work that out. 13 And, finally, we'd be willing, under some 14 changes made in the department policy, we can now 15 go into partnership agreements for those kinds of 16 things, even with specific regulating company. 17 And we have exercised that, and we encourage you 18 to do that. 19 Jim, the risk/benefit communications, I have 20 two questions for you on that. 21 MR. WESTON: Sure. 22 MR. ELENGOLD: The first one is, we agree 23 that that's a very important thing that FDA 24 should be doing. The problem is, when we're FDAMA STAKEHOLDERS MEETING, 4/28/99 85 1 competing for resources -- and in my old job as 2 Director of the Communications office, I was 3 constantly fighting for resources to do that. 4 Everybody has a simple answer: "Put it on the 5 Web, put it on the Web, put it on the Web." And 6 having, you know, one person in our office who's 7 responsible for both our inter- and our 8 intranet -- in fact, we just doubled our staff to 9 two -- does the industry believe that would be a 10 cost that is either acceptable under PDUFA or 11 that a PDUFA amendment or agreement could be made 12 so that PDUFA resources could be used for that? 13 Because as I showed in that slide, the non-PDUFA 14 resources is that little blue box. 15 MR. WESTON: In response to that, I think 16 that's something we could certainly consider. I 17 think in the past couple of years, we've all seen 18 the validity of the Internet being a 19 communications tool, and particularly a two-way 20 communications tool, and I think that's something 21 we could take a look at, yes. 22 MR. ELENGOLD: Okay, so that's that. And 23 given the priorities that we're all faced with 24 making people in companies as well as the FDA, FDAMA STAKEHOLDERS MEETING, 4/28/99 86 1 where do you think that putting that effort is in 2 priority to some of the other tasks we have? 3 MR. WESTON: I think it has a relatively 4 high priority, but I wouldn't necessarily put it 5 above, you know, the approval process. Obviously 6 that's where you -- 7 MR. ELENGOLD: But you would put it slightly 8 above enforcement actions, right? 9 (Laughter.) 10 MR. WESTON: I don't think I dare to 11 comment. 12 MR. ELENGOLD: Okay, that's another thing. 13 You know, since you've made the suggestion, 14 either to the docket or, you know, just in a 15 communication to us you could address, we'd 16 appreciate that. 17 MR. WESTON: We'd be glad to do that. It's 18 the type of thing which I think we'd be willing 19 to look at as part of a partnership too. It's 20 the type of thing where you don't have to 21 necessarily share the entire burden. It's the 22 type of thing which, with the industry or the 23 industry groups, a partnership could be formed 24 because we both came to see the values of these FDAMA STAKEHOLDERS MEETING, 4/28/99 87 1 group. 2 MR. ELENGOLD: John, do you have any 3 questions? 4 MR. MARZILLI: No. I was just going to add, 5 in terms of any of the training and cooperative 6 efforts with Mass. Biotech, surely call the 7 District Office and you can discuss things with 8 us, and coordinate with Gail and the folks in 9 Mark's office as well. So you know we're always 10 available. 11 MS. BOURQUE: Great, and, I mean, in terms 12 of what those presentations will look like, what 13 the science ought to be, I think surely that we 14 just need to sit down and say: What are the 15 areas the reviewers are interested in? What are 16 the areas the industry thinks we should do some 17 more work on? And like I said, finding a site, 18 and this is one facility that I think is a 19 natural, but we can explore that further with 20 UMass. And I think it would be received well 21 from both sides. It's very exciting for us to be 22 able to do something like that. 23 MR. ELENGOLD: Steve, do you have anything? 24 MR. MASIELO: No. FDAMA STAKEHOLDERS MEETING, 4/28/99 88 1 MR. ELENGOLD: Okay, does anybody in the 2 audience have any questions for these speakers? 3 One thing, as we go through this, if you 4 either ask a question or later when we get to the 5 open part, if you make a statement, state your 6 name, who you represent, if anybody. And after 7 you speak, at some point, either on a break or 8 afterward, go over to the Reporter over there and 9 give her a card or identify yourself, because we 10 are transcribing this, and that way it will 11 appear correctly in the record. 12 MR. PIGNATO: Yes, my name is Bill Pignato. 13 I'm with -- the new name now of my company is 14 Bayer Diagnostics, and we manufacture a wide 15 variety of in vitro diagnostics, some of which 16 have had to go before CBER, and our experience 17 with CBER has always been a lot more frustrating 18 than those of CDRH. So I'm certainly encouraged 19 by the initiative of the Device Action Plan, and 20 I'd like to offer a couple of suggestions. And 21 that is, I notice that part of the activity with 22 the Device Action Plan is the development of a 23 number of guidance documents, and I'd like to 24 suggest a different approach in terms of FDAMA STAKEHOLDERS MEETING, 4/28/99 89 1 development of the guidance documents. That is, 2 the experience that I have had with CDRH in 3 participating in the development of a couple of 4 their documents, in fact, a modification 5 document, the working document, and that is that 6 forming working groups in the development of 7 these guidance documents as opposed to the 8 traditional approach of issuing the guidance 9 document and asking for comments. 10 I think that those participants, myself and 11 other people that participated in these working 12 groups with FDA, I think that both parties, both 13 FDA and the industry, were both satisfied with 14 the outcomes in the final product; and I would 15 clearly encourage the agency to give that 16 consideration as well. 17 MR. ELENGOLD: As some here know, we've 18 actually had meetings with the HIMA Board and the 19 Device folks, and I guess Carolyn will get to 20 some of that when she speaks. 21 Anyone else, questions for this panel? Yes, 22 sir? 23 MR. SCHUBERT: Thank you. My name is Dave 24 Schubert. I'm with Genzyme Corporation. I'd FDAMA STAKEHOLDERS MEETING, 4/28/99 90 1 like you to comment on a question that Lisa asked 2 with respect to the Intercenter training on the 3 fast track and accelerated approval process, and 4 where is CBER on that continuum? 5 MR. ELENGOLD: Gail? Yes, we have not 6 started our training on that. It is going to be 7 a module in the revised reviewer training. We 8 have coordinated with CDER as much as we could. 9 They are, you know, on their own initiative doing 10 things. We get the materials. We try and 11 leverage it. Quite frankly, with the device 12 interest right now, we have been concentrating 13 our joint reviewer training with CDRH. But we 14 have talked to Nancy and some of the folks over 15 there, and we would like to leverage it. But 16 right now, we are in the process of completely 17 redoing our reviewer training, and that's why the 18 suggestion on working with Mass. Biotech is so 19 interesting to us, because it does provide us 20 with a current opportunity. But that is 21 something that's interesting, and we'll put it in 22 the record and we'll look at it. 23 Carolyn? You're talking. You can't ask any 24 questions. FDAMA STAKEHOLDERS MEETING, 4/28/99 91 1 MS. JONES: I think it's an interesting 2 concept that Mass. Bio discussed about the 3 reviewer training; but coming from a broader 4 perspective than just a regional trade 5 association, I think it's also important that if 6 you consider that, that there may be issues from 7 biotech companies in California that may not be 8 appropriately totally addressed in anything 9 that's done in a regional setting. So I would 10 say that if you're going to do anything that 11 involves reviewer training where, you know, that 12 might impact companies that aren't going to be 13 present or in the development of that process, 14 that you consider making it a broad training -- 15 MR. ELENGOLD: That was the purpose of my 16 question. 17 MS. JONES: Oh, I missed it. 18 MR. ELENGOLD: Yes, I'm sorry, Carolyn. I 19 asked that. I said, would it be expected to be a 20 regional thing? Because generally when we have 21 partnerships, we put them in the Federal 22 Register, and quite frequently people come from 23 all over, in fact, all over the world, to do 24 that. FDAMA STAKEHOLDERS MEETING, 4/28/99 92 1 MS. JONES: One other question for you, 2 Mark. You talked about budgetary constraints on 3 travel and so on. How would traveling around the 4 country to training programs like that, how would 5 FDA review staff handle that? 6 MR. ELENGOLD: Well, we have two options. 7 The most common option is: We pay for it out of 8 our appropriated funds. It is possible, if a 9 sponsoring group is a group that is eligible for 10 what we call 348 cash-in-kind reimbursement, that 11 we could allow the group. 12 Now, several of the groups -- we have just 13 been working with the Commissioner's office and 14 the Department and have gotten those types of 15 groups extended. It pretty much used to be 16 universities and certain groups that had no 17 membership of companies but only individuals. 18 We've gotten that changed a little bit; and in 19 fact to accommodate that, the PDA has changed 20 their charter to eliminate company memberships so 21 they will qualify. So if an organization like 22 DIA was the sponsor, DIA could provide 23 reimbursement to the government. The way it 24 works is: We cut the travel letter. We turn our FDAMA STAKEHOLDERS MEETING, 4/28/99 93 1 voucher into the FDA, and the FDA then sends a 2 bill to the eligible group. 3 And so that would be the mechanism, but, for 4 example, that would not be available to Mass. 5 Biotech. It would be if DIA or the Parental Drug 6 Association or RAPS, I think RAPS is eligible 7 now, Regulatory Affairs Professionals. 8 So that is one avenue, but again we think 9 the importance is such that we have done a fair 10 amount of allocating travel funds to that. In 11 fact, one of the things we did in CBER this year 12 is, we imposed a percentage travel cut over last 13 year's, and we have that as a reserve fund so 14 it's available so that we in the Director's 15 office can fund travel to important meetings 16 where our message is getting out, and we're 17 hearing what industry folks in academia 18 and industry are telling us. 19 MS. JONES: One final question. Regarding 20 the issue of disseminating information to the 21 public on risks, in your response or in your 22 question, you asked whether PDUFA funds or the 23 priority that MBC would attach to that. Is that 24 an area where the agency would be willing to use FDAMA STAKEHOLDERS MEETING, 4/28/99 94 1 the CRADA concept to allow industry to contribute 2 to it to disseminate the appropriate information 3 if it's not already budgeted for? 4 MR. ELENGOLD: That's something that I was 5 the pet transfer CRADA person for CBER in my last 6 life, so I guess I have a fair amount of 7 knowledge about that. It's an issue I hadn't 8 ever really thought about, Carolyn. And again 9 I'll say the same thing I've said, that anybody 10 who would like to propose such a new mechanism, 11 give us the proposal, the legal background from 12 your counsel's viewpoint, and either submit it to 13 the record or just in a communication to us, and 14 we'll consider it and get back to you or answer 15 it for the record, either way. That's an 16 interesting concept. 17 MR. MARZILLI: Lisa Lopez, okay, Lisa, the 18 microphone. 19 MS. LOPEZ: Lisa Lopez, Vice President and 20 General Counsel of Haemonetics Corporation, and I 21 am on the program later this afternoon. And I 22 apologize, I'm not going to be able to stay. I 23 have a flight. 24 MR. ELENGOLD: Okay, I tell you what. We FDAMA STAKEHOLDERS MEETING, 4/28/99 95 1 will let you do your presentation right now. 2 MS. LOPEZ: Well, I have the remarks that 3 I've left. I did, however, want to ask a 4 question about something that you've said 5 earlier. I know that you're on a tight deadline. 6 MR. ELENGOLD: No, that's okay, that's okay. 7 MS. LOPEZ: You mentioned, Mark, that two 8 years ago there was a crisis of confidence in the 9 blood supply that gave the FDA a real sense of 10 urgency to jump start very, very quick 11 decisions. And my question is that certainly 12 many of us in industry perceive that there is a 13 similar seriousness. I wouldn't characterize it 14 necessarily as a crisis of confidence, but 15 whether it be CJD or EEHP or a proliferation of 16 donor, you know, all of the above, there is the 17 same very strong sense of seriousness attached to 18 issues of blood that we believe give us a great 19 sense of urgency to direct our engineers and our 20 scientists to act quickly, to innovate, to create 21 very, very quickly. And I'm hoping that you will 22 say that the FDA sees the same kind of sense of 23 urgency to make quick decisions. I mean, do you 24 think that we're still in that same similar FDAMA STAKEHOLDERS MEETING, 4/28/99 96 1 period of time that requires of the agency the 2 same sense of urgency that you referred to a 3 couple of years ago? 4 MR. ELENGOLD: Well, if you look at 5 Dr. Henney's priorities for the FDA -- I don't 6 have the list in front of me right here but it's 7 in your pact -- I believe the safety and 8 confidence of the public in the blood supply is 9 one of the five. And therefore we have as our 10 marching orders in implementing the 11 Commissioner's priority anything we can do to 12 increase the safety of and the public confidence 13 in the blood supply. That is one of the major 14 driving forces for the Device Action Plan because 15 we believe that better tests and better devices 16 for processing blood lead to better safety and 17 more confidence. So, yes, that is one of our 18 goals, and it is right on the radar screen. 19 MS. LOPEZ: And my only comment there would 20 be: We would certainly like to see added to that 21 safety and availability of blood. 22 MR. ELENGOLD: Yes, well, that's -- you 23 know, I don't go home one night without hearing a 24 donor request on the radio. And on the NIH FDAMA STAKEHOLDERS MEETING, 4/28/99 97 1 campus where our office is, there's also a sign 2 when you pull in of what type of blood the bank 3 needs. So we're very aware of that, and the 4 availability of blood products is a major concern 5 to us. There's a chronic GG shortage. There's, 6 you know, chronic shortages of component blood, 7 and we realize that the equipment used to process 8 it and the devices used to test it are 9 important. 10 Are you sure you don't want to just take 11 five minutes and summarize your -- 12 MS. LOPEZ: I don't know that I'd be able to 13 do so. 14 MR. MARZILLI: Lisa, are there any comments 15 you want to come up and make? 16 MR. ELENGOLD: Yes, I feel bad about that. 17 Time is not a problem. We'll just cut it out of 18 everybody's lunch. I mean, we're only going up 19 stairs. It's just that we want to make sure 20 people have enough time to take care of their 21 needs, make their phone calls, return the pages 22 they've got. 23 MS. LOPEZ: I apologize. I was directed to 24 actually have prepared written comments. I don't FDAMA STAKEHOLDERS MEETING, 4/28/99 98 1 usually speak this way, but I'll do my best to 2 summarize. As I mentioned, I do represent 3 Haemonetics Corporation. We're a medical device 4 company born in Boston over twenty-five years 5 ago. We're now global with customers throughout 6 the United States, Europe, and Asia, but our 7 headquarters is here, a landmark on Route 128 in 8 Braintree right up the road. 9 Haemonetics has always been associated with 10 invention and innovation, pioneering the 11 collection of specific blood components from 12 healthy donors in the '70s and the '80s, 13 pioneering blood salvage and reinfusion for 14 patients in hospital operating rooms, and most 15 recently we introduced a system for the safe 16 collection of two units of red cells for 17 transfusion from a single donor. This advance 18 will, in our view, improve both the availability 19 and the safety of transfusion medicine 20 practices. 21 Haemonetics is grateful for this opportunity 22 to talk with CBER's leadership. We are 23 profoundly encouraged by the responses FDA has 24 made to FDAMA. We believe that the benefits of FDAMA STAKEHOLDERS MEETING, 4/28/99 99 1 these fundamental changes and the way that FDA 2 interacts with industry will reap benefits for 3 the agency, for industry, and most important, to 4 all of us in this room today, the public. 5 The questions posed to this meeting center 6 around the challenging environment that we in 7 industry share with the FDA, and that's one of 8 unavoidable risk and imperfect science, one where 9 the pressures of cost containment, competition, 10 and technology are fundamentally altering the 11 architecture of our blood products delivery 12 systems. 13 Now, in addition to sharing environmental 14 challenges, we also share a public that is quick 15 to find fault and slow to forgive; and perhaps 16 because of these mutual challenges, industry and 17 FDA are motivated by many of the same goals: 18 Number one, the desire to make devices as safe as 19 possible for patients, donors, and operators. 20 Number two, the need to make sure that our 21 products meet customers needs and expectations. 22 Number three, genuinely, the desire to make the 23 world a better place. And that is FDA and 24 industry's mutual goal. And, number four, the FDAMA STAKEHOLDERS MEETING, 4/28/99 100 1 need to improve operations by adopting what I 2 think we're all comfortable calling so-called 3 "best practices" to meet, in industry's case, 4 the expectations of our shareholders, and in 5 FDA's case, the expectations of its 6 stakeholders. 7 These shared goals are too often overlooked 8 by the media and external constituencies that we 9 also share, patients and their families, blood 10 oversight bodies and other arms of federal and 11 state governments. Because we have shared 12 constituencies, we will improve our 13 communications with them if we send a consistent 14 message, one that says we are doing the best that 15 we can. But we are not perfect. We must be 16 prepared to say that we're sorry when we make a 17 mistake and avoid setting unrealistic zero-risk 18 expectations for our products and services. 19 Because several of the questions for this 20 meeting involve FDA's responsibilities throughout 21 a product's life cycle, I would like to spend 22 just a few moments and explain the unique 23 environment in which Haemonetics operates in the 24 United States with our licensed blood and plasma FDAMA STAKEHOLDERS MEETING, 4/28/99 101 1 customers. The bullets after Premarket Clearance 2 list the channels of communication with the FDA 3 that already exist for Haemonetics and our 4 customers during a product's life cycle. The 5 information gathered via these mechanisms provide 6 an important resource for scientific staff 7 involved in risk-based decision making. 8 Parenthetically, we hope that the 9 information is available to the scientists who 10 could benefit from this exposure, and not just 11 limited to the administrative staff charged with 12 reaching a review and the gathering of these 13 statistics. 14 Before leaving this slide, however, I would 15 like to mention the two-tiered premarket approval 16 process that exists for Haemonetics and 17 our licensed blood plasmal customers because it's 18 unique in the U.S. public health regulatory 19 scheme, and I think in most of the world. 20 Although device or drug manufacturers in other 21 medical fields need only obtain premarket 22 clearance to introduce their products in the 23 United States, this scheme applies to Haemonetics 24 only insofar as our sale of instruments to FDAMA STAKEHOLDERS MEETING, 4/28/99 102 1 unlicensed customers; for example, a hospital 2 customer. But the use of this same -- same -- 3 identical instrument to an unlicensed customer 4 that we sell to a licensed blood or plasma 5 facility is routinely sowed with a second 6 application review, inspection, and approval 7 process. This means that even after a 510(K) 8 review process, which can take up to several 9 years for a device, and longer for NDA review of 10 a new anticoagulant or a storage solution, there 11 is a further delay for a year or more for 12 implementation of the new technologies by 13 licensed users. This translates to up to three 14 years between the time the new technology has 15 completed the R and D cycle and the time it may 16 be utilized by users. 17 We spoke of this a moment ago, but in 18 balancing the public policy considerations of 19 regulating blood in the world we share after 20 AIDS, we almost acknowledge that the risk of 21 indecision or and an unduly delayed decision may 22 be just as dangerous to the public health as a 23 poor decision. And certainly I think all of us 24 in industry would agree with Mark, your remarks, FDAMA STAKEHOLDERS MEETING, 4/28/99 103 1 that a poor product is not one for which we want 2 to expedite approval. But given the worldwide 3 need for safer, higher quality, and sufficiently 4 available blood products, industry must be 5 encouraged to direct all of its resources to be 6 more innovative, to be more creative, to be less 7 constrained by conventional approaches to product 8 design. But for these efforts to result in the 9 kinds of extraordinary public health improvements 10 demanded by the public's sense of urgency about 11 blood safety and availability, they must be 12 coupled with less burdensome paths to regulatory 13 approval. 14 A good example, we believe, was the less 15 burdensome approaches for blood testing which 16 were used very successfully by CBER when it was 17 recognized that the public's urgency for 18 improvements demanded no less. And, similarly, 19 less burdensome approaches for blood collection 20 equipment users could save FDA what we've spoken 21 about today are admittedly very scarce resources 22 without compromising public health. 23 I think we need to remember that in our 24 case, automated blood collection devices have had FDAMA STAKEHOLDERS MEETING, 4/28/99 104 1 a good track record for twenty-five years. That 2 gives FDA a good basis to make informed 3 decisions. 4 Haemonetics would welcome the opportunity to 5 communicate with FDA scientists in a less formal 6 manner outside the context of application review, 7 inspections, or enforcement actions. We would be 8 willing to host scientific visitors from the FDA 9 or come to FDA to demonstrate our technologies 10 and to assist in general training and exchange of 11 ideas and expertise. 12 In addition to improving the scientific 13 knowledge base upon which FDA's decisions are 14 made, we believe that this interaction would 15 prevent misunderstandings, reduce the number of 16 cycles during application review, and foster a 17 more constructive climate for problem-solving. I 18 think these sentiments echo what you've heard 19 from several other speakers. We are genuinely 20 interested in sharing our technology so that FDA 21 staff, whether they be reviewers or enforcement, 22 have hands-on opportunities to really understand 23 the technology out of the context in which there 24 is some question about enforcement or FDAMA STAKEHOLDERS MEETING, 4/28/99 105 1 compliance. 2 FDA's efforts toward harmonization with 3 regulatory authorities in other countries have 4 been encouraging to us, and we hope that they 5 will continue until a -- you know, let's think 6 about this -- single dossier is accepted 7 worldwide. That would be truly extraordinary, 8 and we think that it is possible to do that. 9 Signs of the internal harmonization that 10 have been referred to this morning between CDRH 11 and CBER, as exhibited by the CBER Device Action 12 Plan and what I picked up on the Internet Monday 13 and the Federal Register, are also very, very 14 encouraging. 15 It's also been gratifying to see the 16 comments from the stakeholders meeting last fall 17 now being introduced into working groups at 18 CBER. Everyone inevitably will benefit from 19 these plans. 20 We spoke or I spoke earlier about the layers 21 of regulation. While it may not be possible to 22 eliminate totally the redundancies in premarket 23 clearance for blood technologies and the blood 24 products they manufacture, FDA could make some FDAMA STAKEHOLDERS MEETING, 4/28/99 106 1 approval routes less burdensome for itself and 2 industry by reexamining traditional approaches to 3 regulation, with an eye toward integrating some 4 premarket approval processes and streamlining 5 data submission requirements where the risk is 6 low and the track records have been established. 7 Third-party reviews are being used by CDRH, 8 but to the best of our knowledge, have not been 9 tried in the blood devices sector, and we think 10 that they could be. 11 Finally, thank you very much, FDA, for 12 beginning to move away from the zero risk 13 rhetoric. Particularly for those of us in the 14 blood sector, what I think we remember as a 15 decision paralysis resulting from those years is 16 just beginning to subside, and now it's just 17 decision anxiety for all of us. We think that's 18 a little bit easier to deal with. But perhaps 19 now we can move forward to educate the public and 20 other external constituencies about patient 21 decision making and risk acceptance. 22 In this light, prompting media stories about 23 risk, even TV show story lines, as is being 24 planned for the Hepatitis C campaign, would reap FDAMA STAKEHOLDERS MEETING, 4/28/99 107 1 benefits. But these efforts must be ongoing, and 2 maybe with ongoing efforts, we'll get through to 3 the physicians and, an even tougher act, to the 4 lawyers. 5 In conclusion, thanks for this opportunity 6 to speak today and for the improved 7 communications that we've seen on the Internet. 8 Again, I echo the comments of others. That's a 9 tool that we all utilize daily, and we applaud 10 you for being a leader in that area. 11 Thank you very much. 12 (Applause.) 13 MR. MARZILLI: Okay, thank you very much, 14 folks. I've got a caterer who's been hounding my 15 heels, so if you'd please exit, and people will 16 escort you immediately to the 14th floor for 17 where lunch is being served. 18 (Noon recess.) 19 (Satellite Teleconference.) 20 MR. ELENGOLD: We appreciate everybody 21 coming, and, again, what we had done was figured 22 that we could put any slippage, not that we 23 really anticipated any, in on this end and finish 24 up. And the last speaker we have, and then we'll FDAMA STAKEHOLDERS MEETING, 4/28/99 108 1 open up the floor for questions and comments, is 2 Carolyn Wilson from HIMA. 3 What did I just say? What did I say? I'm 4 sorry. I'm having a real rough day. Anyway, 5 Carolyn is here for HIMA. They are at two of our 6 meetings and somebody there. That shows the way 7 that devices are intrusive into everything we 8 do. 9 Anyway, Carolyn is a former FDA CBER 10 employee, so that's why we're glad she's here. 11 MS. JONES: Thanks, Mark. It's often hard 12 to be sort of the last speaker of the day, so I 13 have been sitting there trying to pare down my 14 comments so that I won't hold you here longer 15 than necessary. 16 I want to thank FDA for the opportunity to 17 comment on the progress in implementing FDAMA. 18 And I'm not going to go into the usual spiel 19 about who HIMA is and what we do and all of 20 that. Needless to say, we represent the medical 21 device industry, a large portion of it, and for a 22 number of our companies, CBER issues are very 23 important. 24 Today FDA is faced with several challenges. FDAMA STAKEHOLDERS MEETING, 4/28/99 109 1 It is charged with implementing a complex and 2 demanding statute. It also wields enormous 3 economic power over a substantial portion of the 4 marketplace. Public expectation of the agency's 5 ability to provide the most technologically 6 advanced products risk-free and immediately can 7 be unrealistic, and the agency is under constant 8 scrutiny by Congress, the public, and we, the 9 stakeholders. 10 And Mark reminded me this morning in his 11 presentation that CBER is faced with an 12 additional challenge because the products that it 13 regulates sort of cross all center bounds. They 14 regulate products that would be considered drugs 15 as well as devices and traditional biologics. 16 I have some overall general comments that 17 apply not specifically to CBER but just to the 18 agency in general. We feel that faced with 19 shrinking resources, increased statutory 20 obligations, and public expectations, we 21 recommend that the agency devote its resources to 22 its core statutory obligations. It needs to 23 focus resources on the highest risk products. It 24 needs to maximize the tools provided by FDAMA. FDAMA STAKEHOLDERS MEETING, 4/28/99 110 1 It needs to continue to seek improvements through 2 re-engineering and management initiatives. It 3 needs to leverage its resources in both the 4 public and private sector. It needs to cease 5 activities that are not essential to carrying out 6 the law, and to seek additional resources from 7 Congress to address the ever-increasing number of 8 issues it needs to deal with, particularly from 9 our perspective, device reviews. 10 We have some ongoing general concerns, and 11 then I'm going to specifically answer the 12 questions that FDA posed in its March Federal 13 Register notices. 14 While the majority of the devices are 15 regulated by CDRH, there have been a number of 16 devices that are regulated by CBER. The device 17 provisions of FDAMA apply to those products as 18 well. Not surprisingly, industry's ongoing 19 concerns with device reviews conducted by CBER 20 don't differ significantly from the concerns we 21 express with the products reviewed by CDRH. 22 Product review times top the list of 23 concerns for manufacturers. Until very recently, 24 because CBER's focus is not primarily devices, FDAMA STAKEHOLDERS MEETING, 4/28/99 111 1 little attention had been paid to medical devices 2 industry's concerns about the ever-increasing 3 product backlogs. 4 Changes are in progress. Mark talked today 5 about the Device Action Plan, and a number of you 6 probably picked up copies of it off the back 7 table. We are really happy to note that the 8 concerns expressed at earlier stakeholders 9 meetings as well as the December Device Action 10 Plan meeting were taken to heart, and FDA has put 11 this Device Action Plan in place. We think it's 12 long overdue and needed to address a broad range 13 of device industry concerns, and we look forward 14 to reading it and providing comments to the 15 agency, and probably meeting with them to discuss 16 our particular concerns with the plan. 17 One of the things before we knew that the 18 plan was going to be issued, we had a concern 19 about the input provided into developing a plan. 20 We wanted to remind CBER of a necessity to 21 communicate, collaborate, and consult with the 22 stakeholders in the development of the plan and 23 with the plan's implementation. We feel it's a 24 challenge for CBER to involve industry as a FDAMA STAKEHOLDERS MEETING, 4/28/99 112 1 partner in the development and implementation, 2 and part of that challenge will be for CBER to 3 think beyond its traditional ways of doing things 4 and allow the stakeholders, both in industry and 5 the blood banking community, to help CBER set 6 realistic science-based goals for its 7 device-related functions. 8 One of the questions put by one of my 9 co-workers had to do with product development 10 times, and I'm not going to go through the 11 aspects of the FDAMA regulations that address 12 product development times, but needless to say, 13 product development times are an important issue 14 for the device industry. As review times go down 15 at CDRH, the product development times go up. We 16 don't want to see the same thing happen at CBER. 17 We have put together what we call a Least 18 Burdensome Industry Task Force and sent some 19 proposals to CDRH on how we feel that least 20 burdensome issues should be addressed, and we 21 urge the agency to consider these proposals, but 22 we also urge CBER to be involved in that 23 process. CBER needs to insure that its reviewers 24 are adequately trained to make appropriate use of FDAMA STAKEHOLDERS MEETING, 4/28/99 113 1 the least burdensome concept. 2 One of the things that we found in trying to 3 gather information from our industry constituents 4 is that a complaint has been that CBER asks for 5 extensive studies when other less burdensome 6 studies could demonstrate the same safety and 7 effectiveness. This often discourages 8 manufacturers, who will often develop and market 9 products that could improve the safety of the 10 nation's blood supply, to market these products 11 outside of the U.S. 12 Again, we recommend that CBER participate in 13 any meetings that the Device Center has with the 14 industry to work out issues related to least 15 burdensome. 16 Although long product review times remain 17 the issue of primary concern, manufacturers also 18 note an apparent disconnect between what 19 manufacturers submit or what they think CBER 20 wants in the product submissions and what CBER 21 actually wants in the submissions. And I'm going 22 to explain a little bit by saying, the example we 23 have been given in-house is that after waiting 24 about six months to receive the first round of FDAMA STAKEHOLDERS MEETING, 4/28/99 114 1 questions on a submission, on average, it will 2 take a manufacturer three to six months to 3 respond to CBER's queries. 4 In our discussions, we found that CBER 5 believes the problem was based on poor product 6 submissions, and that's not borne out by the fact 7 that CBER has refused to file any of these things 8 or anything of that nature. So we sort of think 9 it's based in the idea that maybe there's a lack 10 of guidance out there on CBER's expectations of 11 industry. And so we need to, as industry, to 12 work with CBER to develop guidance so it's very 13 clear on both our parts what's going to be 14 expected and what's going to be the outcome. If 15 CBER is looking for A and we give them B, of 16 course we're not giving them what they need, so 17 we need to be on the same page. 18 Any good plan, one of the things that we 19 talked about in our industry groups, needs some 20 way to measure progress. Traditionally industry 21 has measured FDA progress from origin product 22 review time. Complete timely data on CBER review 23 times is generally not available. CBER should 24 publish its review time metrics on a regular FDAMA STAKEHOLDERS MEETING, 4/28/99 115 1 basis to provide the agency and the industry a 2 yardstick to gauge the progress made. And I was 3 listening to Mark's presentation this morning, 4 and he was talking about how you routinely have 5 those meetings internally to see where the 6 reviews are in-house and, you know, give 7 suggestions to the various divisions on how to 8 improve that process. We'd like to have some 9 access to those review times quarterly, every six 10 months, but some kind of metric so that we know 11 how we're doing and how you're doing. 12 Now, with respect to the specific questions 13 that CBER asked, we will be submitting comments 14 to the docket, a combined set of responses, 15 because we don't think the answers to these 16 questions significantly differ whether you're 17 talking to a CBER audience or whether you're 18 talking to a CDRH audience, so there will be 19 comments submitted to the docket. 20 On the issue of the capacity or capability 21 to incorporate state-of-the-art science into its 22 risk-based decision making, we think one of the 23 issues this question raises as a general matter 24 is the need for FDA to be vigilant in insuring FDAMA STAKEHOLDERS MEETING, 4/28/99 116 1 that it is incorporating the appropriate level of 2 science in its decision-making processes. For 3 instance, the regulatory requirements for a PMA 4 approval incorporate a reasonable assurance of 5 safety and effectiveness standard, not an 6 absolute assurance of safety and effectiveness. 7 FDA must insure that whatever quantum of science 8 it applies to its decision making, it must be 9 within the regulatory construct of the law. 10 Scientifically based conclusions must represent a 11 balance between risks to the public and benefits 12 to the public. 13 In addition, as a government agency there 14 will always be a financial constraint on FDA's 15 ability to hire experts. The agency will seldom 16 be able to compete with the resources of academia 17 or industry. However, the key to incorporating 18 state-of-the-art science into FDA's 19 decision-making process lies in the ability of 20 its reviewers to understand data, interpret 21 results, and ask appropriate questions. FDA 22 should focus on developing and cultivating these 23 skills in its reviewers. 24 Some of the recommendations we're going to FDAMA STAKEHOLDERS MEETING, 4/28/99 117 1 make were addressed in Dr. Henney's presentation, 2 and I was encouraged by that. The specific 3 recommendations we have in those areas consist 4 of: FDA should leverage the industry resources, 5 company tutorials, vendor days, cosponsored 6 educational workshops, et cetera. HIMA proposes 7 that FDA take advantage of industry resources to 8 expand its own scientific knowledge. 9 Dr. Henney addressed the issue of vendor 10 days. Most of the vendor days that we've helped 11 work on have been directed toward CDRH. We would 12 like to see a vendor day that's directed toward 13 CBER, and we would be willing to work with the 14 CBER in the same way we've worked with CDRH to 15 come and set up a vendor day so that your review 16 staff can actually see the technology that they 17 review. It's important to understand that FDA's 18 review is a paper review; and in a non- 19 confrontational environment of a vendor day when 20 you get to talk to the company, you're not 21 reviewing product, it's a relaxed environment, I 22 think the CBER staff would benefit greatly from 23 that interaction. 24 We recommend the cosponsored educational FDAMA STAKEHOLDERS MEETING, 4/28/99 118 1 workshops be another vehicle for dissemination of 2 information, and we at HIMA are working with the 3 agency to develop CRADAs to fund such workshops. 4 We also agree with Dr. Henney that outside 5 experts, government agencies, academia, the 6 private sector, and even the scientific advisory 7 committees, could be used to help build your 8 science base. You know, again, due to the 9 budgetary constrictions, you are not going to be 10 able to compete with industry to obtain the 11 disciplines that you need to do your product 12 reviews. FDA needs to strengthen its use and 13 relationships with its sister organizations, such 14 as the NIH, NSF, and the other organizations that 15 have a scientific base or laboratories and so on 16 to help it through this process. 17 We should also find ways of using 18 consultants and contracting outside the agency to 19 bring in the scientific expertise. 20 We also looked at your conflict of interest 21 policy. We think the current conflict of 22 interest policy prevents FDA from gaining the 23 input from the private sector or using those 24 resources in a way, and we think that FDA should FDAMA STAKEHOLDERS MEETING, 4/28/99 119 1 sort of consider reevaluating the conflict of 2 interest policy to provide a little greater 3 flexibility in your use of outside entities to 4 help you build that science base. 5 We also agree that continuing education is 6 important for your medical staff, for your 7 scientific reviewers; that FDA should at least 8 encourage, if not require, scientists to keep 9 current in the field by taking advantage of 10 seminars or other educational opportunities. 11 One of the other things that we think in 12 industry that we can do is to make use of the 13 collaborative meetings, to make that a learning 14 tool as well, to bring the important people, the 15 experts, the statisticians to these meetings so 16 that these meetings can be productive and provide 17 additional information on the way technology is 18 moving with regard to a particular company 19 submission. Oftentimes I'm hearing from the FDA, 20 and even from industry, that these meetings 21 aren't always as productive as they could be. I 22 think industry needs to take part of the gauntlet 23 here and provide and bring the appropriate people 24 to those meetings, too, so that FDA can learn and FDAMA STAKEHOLDERS MEETING, 4/28/99 120 1 have a correct interaction in those up-front 2 meetings. 3 Another opportunity for FDA to gain the 4 scientific knowledge that it needs is standards 5 development activities. Many scientific experts, 6 including some of FDA's own experts, are involved 7 in developing standards, and it's a really good 8 opportunity for groups to get together their FDA 9 base, their academic base, or their industry base 10 to debate issues in the development of 11 standards. And I think that brings out a lot of 12 information on the technologies that are being 13 addressed, that FDA also has another opportunity 14 for a learning experience there. We would 15 recommend both industry and FDA continue to 16 participate in standards development 17 opportunities. 18 As for question two, what actions do we 19 propose to continue the exchange of information 20 throughout a product's life cycle? This question 21 first asks for ways to improve FDA's access to 22 scientific information. We think the access to 23 scientific information, that issue was addressed 24 in that first question, and we've already listed FDAMA STAKEHOLDERS MEETING, 4/28/99 121 1 out a number of ways you can approach that. 2 I was glad to hear Dr. Henney mention the 3 use of FDA staff, college and training 4 institutions, as an additional mechanism for 5 keeping abreast of what's going on. We recommend 6 that the agency adopt, if it hasn't already done 7 so, something that's used in the industry which 8 is called "train the trainer." Industry, too, 9 has financial constraints often, and they send 10 people to training seminars and standards 11 development activities, and that individual has 12 the responsibility to go back and train the folks 13 who weren't able to attend the meeting, to relay 14 the information that was obtained. FDA needs to 15 make use of that if there are still constraints 16 on traveling to meetings and to different 17 functions. 18 Also, information on product life cycles, 19 manufacturers and companies have annual reports. 20 That's a way of continually tracking information 21 on products and so on. There are more specific 22 recommendations in our written comments. I don't 23 want to keep you here any longer than necessary. 24 The issue of educating the public on the FDAMA STAKEHOLDERS MEETING, 4/28/99 122 1 concept of risk, consumers are increasingly 2 becoming better educated about their own health 3 and their personal medical problems. The 4 availability of the Internet resources can result 5 in patients having sometimes more information 6 than their physicians about a particular device 7 or drug or whatever. This creates a demand in 8 the marketplace for additional information by 9 both consumers and physicians, a demand that will 10 largely be met by the marketplace and not a 11 government agency like FDA. 12 There's no magic bullet that will fully 13 educate the public about how to balance risks and 14 benefits. For CBER, this is particularly 15 difficult because some consumers believe that 16 products, including the nation's blood supply, 17 should be completely risk-free. FDA can play a 18 useful role in educating the public generally 19 about the risks and benefits of the product it 20 regulates and about continuing efforts to reduce 21 those risks. FDA can also work with the medical 22 community to discuss ways of adequately informing 23 patients about the risks and benefits of the 24 products that they proscribe. FDAMA STAKEHOLDERS MEETING, 4/28/99 123 1 Another opportunity for FDA, and I guess 2 industry as well, to provide information to 3 patients about the risks are the use of the 4 various Web sites, and that also is 5 resource-intensive, but, again, that's not a 6 burden FDA must bear alone. Companies also have 7 a responsibility to put important information on 8 their Web sites, or at least FDA could possibly 9 link to some of the company Web sites so that 10 they don't have to provide the information. 11 How to focus resources on the areas of 12 greatest risk to public health? CBER should 13 continue to implement the tools of FDAMA and to 14 adopt, where appropriate, CDRH's re-engineering 15 tools. We think this will free up some of your 16 resources. This includes taking a critical look 17 at ways to expand the list of recognized 18 standards and increase their use by industry, to 19 make optimal use of early collaboration meetings, 20 and to harmonize the regulatory requirements. In 21 perusing your Device Action Plan, these are some 22 of the same things that the plan addresses, and 23 we're glad to see that. 24 As far as training, industry training, FDAMA STAKEHOLDERS MEETING, 4/28/99 124 1 education and communication, in order to maximize 2 the tools at FDAMA and to create the most 3 efficient system possible, FDA staff must be 4 adequately trained in their application. It's 5 not enough for Linda to sit in a stakeholders 6 meeting and outline what's contained in FDAMA. 7 Your front-line reviewers, your inspectional 8 staff, the district offices, need to be 9 thoroughly versed in what's contained in FDAMA 10 and how it should be applied. The industry must 11 also be educated on the tools available as well 12 as the agency expectations. 13 We also look at focusing resources. We've 14 all got to in belt-tightening situations 15 eliminate unnecessary or redundant functions. 16 FDA should closely examine all of its functions 17 and determine which are not essential to carrying 18 out its core statutory obligations. FDA should 19 look to rid itself of all but absolutely 20 necessary functions mandated by law. 21 On the inspectional side, HIMA has 22 participated in several initiatives to improve 23 FDA's device functions. Those comments or 24 testimony with regard to those initiatives are FDAMA STAKEHOLDERS MEETING, 4/28/99 125 1 included in our written comments, and we think 2 that CBER should review those comments and look 3 to see what aspects of those initiatives can be 4 adopted by CBER to enhance its inspectional 5 program as well. 6 On Question 5, enhancing the communication 7 process and allowing ongoing feedback, the 8 statute uses the term "consultation" in 9 connection with FDA's 406(B) obligation. This 10 means more than just listening or reading 11 comments. If Congress had intended the FDA to 12 only seek public comments, it would have said 13 so. Webster defines "consultation" as "Meeting 14 to discuss, decide, or plan." Discussions, 15 decision making, and planning all involve 16 brainstorming and a give-and-take kind of 17 activity. We urge the agency to engage in 18 consultation with its stakeholders that may be 19 more meaningful and productive than the type of 20 consultation exemplified by most of the meetings 21 that we've had with the agency. 22 The other thing that the agency can do is 23 that -- I know HIMA has commented extensively on 24 the regulations, notices, and guidance documents FDAMA STAKEHOLDERS MEETING, 4/28/99 126 1 developed by CDRH to implement FDAMA. It's 2 unclear on our part what input CBER has actually 3 had in the development of a number of these 4 documents, and we'd like to know what your input 5 has been. But the problem is, in some cases it 6 appears that our comments go unacknowledged. 7 While we do not expect that all of our comments 8 would be adopted, we do believe, especially on 9 key issues, the process would benefit from a true 10 dialogue with industry and other interested 11 parties. A true dialogue is especially important 12 when there are documents, from CBER's 13 perspective, that they may be reluctant to 14 adopt. It is important for industry to 15 understand the basis for CBER's reluctance to 16 adopt specific documents. 17 And, again, that goes back to the point: If 18 we had a true consultation, a true dialogue, each 19 of us would know up-front why there's a 20 reluctance. But because of the process that's 21 used currently, we don't. 22 The one thing that we've done at HIMA -- and 23 at some point, Mark, when we have future 24 discussions on CBER's Device Action Plan, we'd FDAMA STAKEHOLDERS MEETING, 4/28/99 127 1 like to be able to share this information -- we 2 sent out a questionnaire to our member companies 3 on their experiences with FDAMA, and we're in the 4 process of collecting those surveys and collating 5 the data. And, again, we will share the results 6 of this questionnaire with the agency, and 7 particularly we want to share the specific 8 questions related to CBER with the CBER folks. 9 In conclusion, we want to thank the agency 10 for this opportunity to provide our ideas and our 11 comments. We look forward to working with CBER 12 to implement the appropriate provisions of FDAMA, 13 to utilize the relevant CDRH re-engineering 14 initiatives, to develop and implement the Device 15 Action Plan that appropriately focuses CBER's 16 device-related functions, so that together we can 17 eliminate the product review backlog and 18 significantly reduce product review times. 19 MR. ELENGOLD: Thank you. I've got a couple 20 questions. 21 MS. JONES: Sure. 22 MR. ELENGOLD: I've got a couple questions. 23 One of the ways that CDRH -- and I'll be fast, 24 too, because I know everybody wants to catch a FDAMA STAKEHOLDERS MEETING, 4/28/99 128 1 plane -- that one of the things CDRH did was 2 down-classify devices. We've looked pretty hard 3 at our inventory of regulated devices, and many 4 of them are treating either people with fatal 5 nontreatable diseases, like in cell separation, 6 or in safety of the blood supply. Could you give 7 me an example that HIMA might think might be a 8 CBER-regulated device that would be eligible for 9 down-classification, what we say in our 10 vernacular as the "tongue depressor bedpan"? I 11 remember when the device amendments were 12 implemented in '76, a lot of things that were 13 relatively simple were classified too high; and 14 in down-classifying them, that's one of the ways 15 CDRH lessened their review workload. But we've 16 had extensive internal discussions over the 17 years, and we, frankly, can see one or two things 18 that might be down-classifiable; but I'm sure 19 that HIMA has had the same discussion. Do you 20 have any ideas on that? 21 MS. JONES: Honestly, we haven't had the 22 discussion about the list of products that could 23 be down-classified. That is a discussion that we 24 can have with our CBER steering committee. We do FDAMA STAKEHOLDERS MEETING, 4/28/99 129 1 feel -- I guess in Lisa Lopez's presentation, she 2 talked about some of the products that you've had 3 extensive experience with in triaging your 4 reviews that may not get to the level of actual 5 down-classification, but the amount of time and 6 effort spent in the review of the products that 7 you have had extensive experience may be 8 lessened. 9 We realize CBER's discomfort with 10 down-classification of instrumentation associated 11 with some of the IVDs and so on; whereas CDRH has 12 down-classified or exempted, really, the 13 instrumentation. And in discussions with 14 Dr. Epstein and his staff, we realized their 15 discomfort with that, and -- 16 MR. ELENGOLD: You have to keep in mind that 17 I've spent the past ten years dealing with four 18 different oversight committees on the safety of 19 the blood supply. The Secretary of the 20 Department of Health and Human Services has 21 publicly stated that the safety of the blood 22 supply is one of her priorities, and Dr. Henney 23 gave it to you as three or four, depending on how 24 you count today. And something as simple as FDAMA STAKEHOLDERS MEETING, 4/28/99 130 1 recently a filter that's been in use for many 2 years, an acceptable manufacturing change was 3 made that led to severe adverse reactions across 4 the country. So we've got to keep in mind -- 5 MS. JONES: But you reviewed that product, 6 didn't you? 7 MR. ELENGOLD: Yes. 8 MS. JONES: And it didn't stop that? 9 MR. ELENGOLD: Yes, that's right, that's 10 right. And that's the problem. So maybe we need 11 more controls and extensive clinical trials 12 before allowing manufacturing changes. I'm just 13 giving you the questions that we get on those 14 issues. 15 MS. JONES: I understand, I understand, 16 but -- 17 MR. ELENGOLD: And we have to strike a 18 balance. 19 MS. JONES: We do have to strike a balance, 20 and we understand that you're not going to catch 21 everything, even in an extensive premarket 22 review. 23 MR. ELENGOLD: That's right, but the reality 24 is, the public has demanded through their elected FDAMA STAKEHOLDERS MEETING, 4/28/99 131 1 representatives that we devote additional 2 resources and additional controls. And that's 3 something that FDA has to face in its life. 4 Let me go on. You've said we've changed our 5 conflict of interest. That's a major concern to 6 us. One of my previous jobs was dealing with 7 what we like to call the "generic events." 8 Now, the problem as I see it and the one 9 I've dealt with is: We go to seek an outside 10 expert that's been to a hypothetical school like 11 Boston University to come into our Advisory 12 Committee as an expert, and we find out that the 13 main expert in the field at BU has been a 14 consultant to another company, and the conflict 15 of interest prohibits us from doing that. Does 16 HIMA believe that its members are willing to 17 waive that type of conflict of interest? 18 MS. JONES: I think on certain levels, yes. 19 The discussions we've had in developing our 20 answers to the questions posed by FDA, the 21 companies indicated that they would be, and that 22 in certain instances, the public disclosure of 23 that information that you have had some dealing 24 with the company, and so on, is what we thought FDAMA STAKEHOLDERS MEETING, 4/28/99 132 1 was more important than waiving, you know, the 2 company rights there. And as long as the 3 conflict or the involvement with the company was 4 adequately disclosed and everybody was singing 5 from the same song sheet, that it would be 6 appropriate. 7 MR. ELENGOLD: Well, perhaps we can work on 8 a pilot on that, and when your members are 9 bringing products to our Advisory Committees, 10 they could suggest experts along with their 11 agreement to waive any conflict, because 12 everybody knows who's working on the alternative 13 products, and I encourage HIMA to back up that 14 with some examples and some working with us 15 because, you know, we don't invent the ethics 16 laws or the conflict of interest requirements. 17 For the main, they are either imposed upon us or 18 demanded by companies to protect their own 19 rights, and that's just another thing that I'd 20 like to see. 21 Training you brought up, training the 22 trainer. I went to train-the-trainer school in 23 1971 or '72 back before we had project hiring and 24 a lot of the people here today were hired. We FDAMA STAKEHOLDERS MEETING, 4/28/99 133 1 have embraced that concept. The problem that we 2 face is that every training that we do, including 3 that type of thing, takes away from review and 4 investigational time. And that's one of the 5 reasons we are really interested in partnering 6 because having our people do the training takes 7 away even more time, and that's one of our 8 concerns with that. We have looked at that. 9 And, finally, you made the comment twice 10 that you think we should stop doing things we 11 don't need to do. My experience over the years 12 is: Anything someone thinks we shouldn't be 13 doing is something that somebody else is 14 demanding we're doing it. And the tautology of 15 that is, you know, we don't need Consumer Affairs 16 people, we don't need Web engineers. And yet all 17 this morning and all last year we heard: "Put it 18 on the Web, expand the Web, increase the Web." 19 So I would just like, you know, as an example one 20 function that we have in CBER that HIMA thinks we 21 could eliminate. 22 MS. JONES: Mark, I did preface my comments 23 by saying that the answers to the question may 24 not specifically relate to CBER, that they are FDAMA STAKEHOLDERS MEETING, 4/28/99 134 1 answers that we think go across FDA quite 2 broadly. We're asking your agency to be quite 3 introspective and to look at things that it 4 thinks, you know, that you're doing. I didn't 5 come prepared today to list out the things that 6 we think are totally unnecessary. I mean, I'm 7 sure that if I got an industry group together, 8 they could probably give me a list. But we're 9 asking the agency to do a self-check and look at 10 those things that you think really don't add a 11 great deal of benefit to the process or those 12 things that are redundant of other things that 13 could be collapsed into one. 14 MR. ELENGOLD: Well, again, I'd really 15 appreciate either a submission or an off-line 16 conversation. 17 MS. JONES: Okay. 18 MR. ELENGOLD: Because the budget situation 19 has really forced us into doing that. I didn't 20 show one of the slides that I usually do show 21 that shows we're spending 40 percent less than 22 our laboratory function in actual dollars, not 23 adjusted dollars, than we were four years ago. 24 We have eliminated a lot of our management FDAMA STAKEHOLDERS MEETING, 4/28/99 135 1 overhead. We've cut travel just this year 25 to 2 30 percent. We're really interested, you know, 3 and again, you know, in what functions industry 4 thinks we can stop doing because we'd like to see 5 if we can stop doing them. But the rhetoric of 6 just, you know, "There are things you can stop 7 doing," we think we've stopped, at least in CBER. 8 And I think Dr. Henney's proposed reorganization 9 of the Commissioner's office, which is 10 eliminating overhead and redundant things there, 11 has also gone a long way to doing that. So I'd 12 really be interested. 13 MS. JONES: I think part of the problem, 14 Mark, as you've seen at earlier stakeholders 15 meetings, is the issue of transparency that you 16 stressed in your presentation. Maybe it's 17 evident to the agency some of the things that 18 you've stopped doing, but because of the lack of 19 transparency, it's not evident to us some of the 20 things you've stopped doing. 21 MR. ELENGOLD: Okay, thanks. 22 John, do you have anything? 23 MR. MARZILLI: As we're getting a mike down 24 to David, I'd just like to make a couple of FDAMA STAKEHOLDERS MEETING, 4/28/99 136 1 comments. One of the things that I think CBER 2 should be applauded on in terms of increasing the 3 science base of the agency and really focusing 4 our resources, and you did mention it earlier, 5 Mark, and that is Team Biologics. I think for 6 the first time in a long time this agency has had 7 a highly focused, well-trained work force to go 8 out there nationwide and to do the fieldwork for 9 CBER, and I know you've played an active role in 10 that, and it's an important aspect. 11 For those of you that have had members of 12 Team Biologics come out, we've really been able 13 to focus our training opportunities on a devoted 14 cadre that are devoted to these products. And 15 Mark has taken a leadership role in that from the 16 Center for Biologics; and as a District Director, 17 I've seen that it's been a tremendous resource 18 boost to me in terms of trying to get my work 19 done in the field organization. I want to 20 compliment you on that. 21 MR. ELENGOLD: Thanks. I was quoted in one 22 of the meetings as saying, "Team Biologics is 23 either way above high technology regulation of 24 the future or something we're going to look back FDAMA STAKEHOLDERS MEETING, 4/28/99 137 1 on as a massive failure," and so far, I've been 2 really happy that I think it is the wave of the 3 future for high-tech regulation. 4 MR. MARZILLI: And the other thing I'd like 5 to add, the technology that we've seen here today 6 in terms of satellite training, and Al Levitt 7 sitting over there is my training officer for the 8 New England District. We have at least two 9 satellite broadcasts a week related to training 10 opportunities within FDA, either seminars that 11 are given by the various centers or other areas 12 of interest to our folks that are usually 13 broadcast in each of the twenty district offices 14 and five regional offices across the country. 15 Locally we record them on videotape and get them 16 out to our district offices, so there is a 17 multiplier effect, and I think we're doing a lot 18 of innovative things. And I'm excited about this 19 Webcast that we saw today. That's the first time 20 I've seen that, and I think that would be an 21 excellent training opportunity for us in the 22 field to get the message out. 23 And most recently our blood bank inspection 24 cadre has an interactive CD-ROM training program FDAMA STAKEHOLDERS MEETING, 4/28/99 138 1 with a little Hector-Hector guy over there that 2 tells you whether or not you did your blood bank 3 inspection right. And there's a lot of high-tech 4 training, and CBER has taken a leadership role in 5 developing that with the field organization, and 6 I really wanted to compliment you guys on it. 7 MR. ELENGOLD: What we did, in fact, to do 8 that was we leveraged -- the CDRH folks have this 9 Tech Center where you saw that satellite 10 broadcast from today, and that is a 11 state-of-the-art network grade facility. And 12 rather than try to develop any of our own, we 13 decided to leverage that, and rather than spend a 14 lot of money on satellite technology, we paid 15 Bell Atlantic to put a fiber line in that runs 16 from the Tech Center to all four of our 17 buildings. And again, at least two, three times 18 a week we use our system to have them down-link 19 to us educational opportunities, NIH grand 20 rounds, association things; and our people can 21 get their continuing medical or pharmacy 22 education by just going down to a conference 23 room. 24 MR. MARZILLI: Okay, David Fleming from FDAMA STAKEHOLDERS MEETING, 4/28/99 139 1 Genzyme had a comment. 2 MR. FLEMING: Mark, let me try to pose one 3 possible issue of one area where possibly CBER 4 and industry can work together, and I guess 5 that's the first point. I think industry, I'm 6 hearing today, wants some more open collaborative 7 dialogue and better communication with CBER, and 8 I think it's improving, but we want to improve it 9 more. And one example is just, again, the long 10 review times. I think we might have different 11 perspectives as to what the issues are. And I 12 think industry sometimes believes that there's a 13 disconnect, there continues to be a disconnect, 14 in that we see it on the submission side between 15 what we feel CBER wants in a submission and what 16 CBER feels that it wants. And what happens is, 17 you end up having six months while CBER is 18 reviewing, and then it comes back to the 19 manufacturer, but it's three to six months to get 20 back because there are unanticipated issues. So 21 I think -- Bill Pignato mentioned it earlier -- I 22 think there's a great interest in working 23 collaboratively on guidance and on guidance 24 documents, and not for industry to go away and do FDAMA STAKEHOLDERS MEETING, 4/28/99 140 1 it, not for CBER to go away and do it, but for 2 both to sit down in some manner that's acceptable 3 and to work these out so that there is a clear 4 commonality that goes into the submission process 5 so that we bring down the review time, bring down 6 the number of rounds, and really get down to 7 where not only is the product going through 8 faster, but you are able to use your resources 9 more effectively. 10 MR. ELENGOLD: Yes, I agree with that. You 11 know, extra rounds of review do cost us money 12 too, and we don't see any great benefit from 13 those. And had I been answering this about a 14 week ago, I would have said I would suggest you 15 put a proposal together and submit it to Becky 16 Devine, our Associate Director for Policy, on a 17 proposed pilot to do that. Unfortunately, Becky 18 has decided to leave the government in June; so 19 in the interim, until someone takes her place, 20 I'll suggest you put a pilot suggestion together, 21 pick a topic, and send it to me, and I'll get it 22 worked on. 23 One other thing that Carolyn Jones brought 24 up, the review metrics issue. We acknowledge FDAMA STAKEHOLDERS MEETING, 4/28/99 141 1 that that's something industry has asked for. 2 We, frankly, do not have a mechanism in place to 3 do the kind of a review metric analysis that I 4 remember doing in the new drug report from twenty 5 years ago and we do in our review performance. 6 We put together a pilot and we're refining it to 7 get the system to work right, and I did present 8 some of those figures out at the HIMA meeting 9 back -- was that a month or so ago? I can't 10 remember. And those are posted on the Web, and 11 they give you the last year's performance, and we 12 will be posting those at least on a quarterly 13 basis. We heard that last year. We're working 14 on it, and we will start doing that. You saw 15 those when I did those. 16 And Steve just wanted to say something just 17 before we get to the next question. 18 MR. MASIELO: I just wanted to mention that, 19 you know, when you talked about scaling back the 20 regulation of various products, something as 21 simple as a pipet tip came into the forefront not 22 too long ago. 23 MR. ELENGOLD: On a Friday night. 24 MR. MASIELO: On a Friday night, yes, where, FDAMA STAKEHOLDERS MEETING, 4/28/99 142 1 you know, a manufacturer's pipet tips weren't 2 picking up enough sample, and that had an impact 3 across the blood industry with some really severe 4 potential consequences. So, you know, even 5 though on its face it might appear like a simple 6 device, it has major impact. 7 MR. ELENGOLD: Nothing but a piece of blown 8 glass, but it was sampling too small an amount. 9 MR. MASIELO: Another thing I wanted to say, 10 we've heard a lot today about making more 11 information available through the Web and all 12 kinds of sources. One of the things that I'm 13 looking at is making sure information that's made 14 available through the recall process is useful 15 information. There's a lot of information that 16 gets out there, and you have to question: Well, 17 just how useful is this to the public? What is 18 the need to know this doing for them? And so 19 we're looking closely at that kind of information 20 to make sure that the stuff that gets out there 21 has some meaning to people and it's not just more 22 info. they've got to sift through to get 23 something useful. So that's something we're 24 looking closely at. I just wanted to mention FDAMA STAKEHOLDERS MEETING, 4/28/99 143 1 that. 2 MS. DeMARINIS: Hi, Anna DeMarinis from 3 bioMerieux and a former CBER person, so please 4 take what I say with a grain of levity. I have 5 two issues on which I want to take issue with 6 you, Mark, two comments that you made. One was, 7 you sort of gently chided Carolyn on her remark 8 that "What would you have us cut out for us to be 9 able to better utilize our existing resources?" 10 And I think Carolyn's response to look within 11 yourself first is a very important one. You 12 said, "What would you have us do? Get rid of 13 consumer affairs, public affairs?" And I know 14 some of those people, and I know that they are 15 very scientifically and technically capable. And 16 I would submit those individuals could be 17 cross-trained to conduct inspections, to be 18 reviewing applications when there's a backlog. 19 Within your organization there are quite a few 20 very talented people that may not be utilized at 21 the present time as effectively as they could be, 22 so I would certainly support Carolyn's suggestion 23 that we would be very happy as an industry group 24 to give you some instructions, some very FDAMA STAKEHOLDERS MEETING, 4/28/99 144 1 constructive and positive suggestions on how you 2 could reorient -- 3 MR. ELENGOLD: Well, that wasn't my point. 4 I mean, folks in ACMA, I mean, Mike Hooten who 5 just retired last month, had done the plague 6 inspection just about every year, even though he 7 was mainly answering Congressionals, and Mary 8 Myers, who's now the office director, was doing 9 prelicense blood bank inspections up to three 10 years ago. I even did one. They even let me do 11 one. 12 The point is: If they do that, then they 13 are not doing the consumer affairs work. I'm not 14 saying that the people couldn't be reprogrammed, 15 but if we stop doing the Web work, the consumer 16 affairs work, you heard the people this morning 17 say: It's FDA's job to post more information. 18 It isn't the matter that we can't reprogram the 19 people. It's that whatever they stop doing, one 20 of our stakeholders will object to. That was the 21 point to that. 22 MS. DeMARINIS: And I think that's a very 23 valid point. 24 MR. ELENGOLD: You know, personally I'd FDAMA STAKEHOLDERS MEETING, 4/28/99 145 1 rather be a full-time compliance officer and 2 write warning letters, something I'm very capable 3 of doing; but most of the time they have me in 4 meetings on budget, you know, so. . . 5 So that was the point. It wasn't that the 6 people aren't multi-talented. It was that 7 anything anybody has ever suggested to us that we 8 stop doing or have stopped doing, we are 9 immediately chided by somebody else: Why did you 10 stop doing that? 11 MS. DeMARINIS: And I think that that 12 further supports the whole notion that we need to 13 meet with all stakeholders regularly and 14 frequently to hash out these issues, because we 15 in industry, we do have to do more with less 16 sometimes. It's a reality of life, so we have to 17 work on it. 18 The other comment that I wanted to make was 19 in response to your comment that if we're sending 20 someone to training, they are not reviewing an 21 application. And I was a former teacher, so 22 again, to me, the whole notion of training being 23 an unnecessary or a frivolous activity is very 24 unsatisfactory because I think if individuals are FDAMA STAKEHOLDERS MEETING, 4/28/99 146 1 properly trained, then they do their work much 2 better. 3 I would throw back the comment to you: 4 Research is another activity that if individuals 5 are doing research, they are not reviewing 6 applications; and yet research, as you shown in 7 your own slides, is a very important training 8 function. So, again, I would submit again that a 9 number of these kinds of issues that tend to fall 10 on the fringes need to be kept in the mix and 11 used as effectively as possible. 12 MR. ELENGOLD: I hope no one took that as 13 belittling training. At the period when I became 14 responsible for the training operation, I don't 15 know, what was that Gail, about four years ago? 16 No, no, I've been in this job two years. What? 17 What? Was it only two and a half? Man! The 18 reorganization for training into my organization, 19 the staffing has increased about 30 percent. The 20 budget has probably tripled. We have gone to the 21 on-line learning. We have gone to orientations 22 by videotape. 23 I think we need much more training. I just 24 meant to say that by having trained the trainer FDAMA STAKEHOLDERS MEETING, 4/28/99 147 1 and -- you know, the joke I hear constantly at -- 2 we have been doing internal stakeholders 3 meetings. We call them "voice your opinion 4 meetings," and it's basically an opportunity for 5 the staff at CBER one office at a time to get up 6 and yell at me. And the one thing I keep hearing 7 is: "The reward for good work is more work." 8 And the problem that we're faced with is, if we 9 put our best people in more training -- I mean, 10 we have been trying to set up this vaccine 11 training course, to give you an idea, with ORA's 12 Team Biologics transfers to the inspections on 13 October 1. And one week is a Ver PAC meeting; 14 one week is a religious holiday; one week is a 15 professional association meeting. And that was 16 the point, that we can only spread our people -- 17 and we'd really, rather than train the trainer, 18 to have our line people do it, one option we have 19 to explore is, rather than using line people and 20 training the trainer, is to get full-time 21 training people that can do the technical 22 training. And that's all. I did not mean to 23 belittle the need for training. I am perhaps one 24 of the most overtrained employees in the federal FDAMA STAKEHOLDERS MEETING, 4/28/99 148 1 government sometimes. 2 MS. DeMARINIS: If you hire full-time 3 trainers, how do you keep the trainers -- you say 4 that you'd only send the trainers to the 5 seminars? 6 MR. ELENGOLD: No, no. No, I mean full-time 7 training people so they can work with the actual 8 product experts and not have to do their own 9 overheads. As I said, we have been doing that 10 more and more, because the training, anybody's 11 who's ever done training, is really the smallest 12 part of your time. It's the logistics, the prep. 13 work, the follow-up work. So that was all I 14 meant by that. I'm sorry, I did not mean to 15 belittle training. I am probably the greatest 16 supporter that we have of it. 17 Anyone else? 18 MR. RIDER: Yes, I'd like to thank all of 19 you for bringing the stakeholders here. As one 20 who represents a stakeholder group, I enjoyed 21 hearing the "early and often" comment on the 22 video in relation to communication. I think that 23 adverse reactions are bad publicity. Loss of 24 market share on products, all of that results FDAMA STAKEHOLDERS MEETING, 4/28/99 149 1 from the lack of early and often communication 2 with stakeholders. 3 I'd also like to encourage, as one that's 4 interested in blood safety, working for a group 5 that has a direct stake in that issue, the 6 involvement of ethicists in relation to the risk, 7 potential risk, and how not only the physical 8 impacts of adverse reactions but psychological, 9 mental health reactions. I deal full time with 10 the impact that that has on families all over 11 this country, and, of course, that impacts on our 12 industry and our bottom line in terms of 13 productivity, because when you decimate family 14 systems' mental health, you have unfortunate 15 spin-off consequences to the economy. But in 16 relation to that, I would say that you have good 17 scientific data base that you can tap into in 18 many professional nonprofit associations for 19 scientific review, such as Physicians for Social 20 Responsibility, who have the empirical training 21 and knowledge and also an ethical basis for which 22 to do some peer review. 23 Thank you. 24 MR. ELENGOLD: Will you identify yourself FDAMA STAKEHOLDERS MEETING, 4/28/99 150 1 for the record, please? 2 MR. RIDER: I am John Rider. I work for the 3 Committee of 10,000. I am an advocate nationally 4 for that organization. 5 MR. ELENGOLD: Thank you. Anyone else? 6 Well, then I will do my thank-yous and then turn 7 it over to John. I just want to thank everyone 8 for coming, first off, and participating. The 9 only way we're going to get where we all want to 10 go is by working together. You know, reasonable 11 people can disagree, and the basis of progress is 12 getting together and reaching compromises and 13 doing what we need to do. 14 I particularly want to thank Paula 15 Fairfield, John, the folks here at BU who have 16 just been wonderful, the AD folks. I do this 17 probably at least once every ten days or so, and 18 this is the most professional, best organized 19 group I've dealt with in probably fifteen, twenty 20 years, and I do appreciate that. 21 I want to thank the folks back in Rockville 22 who did the work, the folks who came up here, 23 Gail and all of her people, Lorrie Harrison, who 24 some of you spoke to in registering for this, FDAMA STAKEHOLDERS MEETING, 4/28/99 151 1 Steve, John, the folks from Winchester, and Bob 2 Miller who have been the butt of several of my 3 jokes just because when I need money, he's the 4 one I give the bank. 5 I appreciate it, and this is not the end of 6 this process. We will be continuing it. 7 One other thing I'll mention is if you look 8 at our Web site, one of the things that I set up 9 that I'm fairly proud of is our automated e-mail 10 system. You can subscribe to those automatically 11 and then get notices of all our guidance 12 documents, meetings, workshops, new initiatives, 13 things we're posting, and I would urge everyone 14 to look and consider signing up for that. 15 It's easy to find me. If anybody wants to 16 contact me, my number is (301)827-0372, and I'm 17 never there because I'm always in budget 18 meetings, so the best way to do it is to send me 19 an e-mail. It's Elengold @CBER.FDA.Gov. I 20 usually try to answer things within a day or two, 21 or get it to the right place, so if you don't 22 know where to start, you're always free to send 23 it to me. 24 And, John, thank you very much. FDAMA STAKEHOLDERS MEETING, 4/28/99 152 1 MR. MARZILLI: Okay, Mark, thank you as 2 well. And I do want to salute the BU staff. I 3 think they did an excellent job. And once again 4 I want to say a special thank-you to Paula 5 Fairfield who has handled this from the very 6 beginning. Paula, my appreciation for the hard 7 work that you've done in putting this whole thing 8 together. 9 Again, we passed out some brochures. They 10 are available in the back of the room. If you 11 want to reach the District Office, we talked 12 about consumer complaints, we have a 1-800 number 13 for consumer complaints, et cetera. 14 Again I want to thank our representatives 15 from CBER who came down today. And in the times 16 of diminishing resources, I want everyone to know 17 that they got up at the crack of dawn and took a 18 flight in and came here from the airport and will 19 be leaving promptly. So we want to -- 20 MR. ELENGOLD: We came in last night. I 21 don't want to go on any false pretenses. We got 22 in at what, 8:00 o'clock last night? 23 MR. MARZILLI: Okay, okay. But I do want to 24 thank you all for coming in and making it into FDAMA STAKEHOLDERS MEETING, 4/28/99 153 1 the meeting and spending the time with us. 2 MR. ELENGOLD: We have done it in one day. 3 Boston is pushing it. 4 MR. MARZILLI: And, folks, your parking 5 stickers should be validated with the word "FDA," 6 and thank you once again for coming and thank you 7 for spending some time with us. 8 (Applause.) 9 * * * 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 1 C E R T I F I C A T E 2 3 4 I, Lee A. Marzilli, Registered 5 Professional Reporter, do hereby certify that the 6 foregoing transcript, Pages 1 through 153 7 inclusive, was recorded by me stenographically 8 and thereafter by me reduced to typewriting and 9 is a true and accurate record of the proceedings 10 to the best of my skill and ability. 11 Dated this 3rd day of May, 1999, at 12 Lexington, Massachusetts. 13 14 15 16 __________________________________ 17 LEE A. MARZILLI REGISTERED PROFESSIONAL REPORTER 18 CERTIFIED REALTIME REPORTER 19 20 21 22 23 24