1 2 3 FDAMA STAKEHOLDER MEETING 4 5 ---oOo--- 6 7 8 April 28, 1999 9 SOUTH SAN FRANCISCO CONFERENCE CENTER 10 255 South Airport Boulevard South San Francisco, California 11 12 13 14 15 REPORTER'S TRANSCRIPT OF PROCEEDINGS 16 17 18 19 20 21 REPORTED BY: CLARE MACY, CSR 5256 (01-76508) 22 23 24 25 1 1 I N D E X 2 3 INTRODUCTION Pat Ziobro 3 San Francisco District Director 4 5 OPENING REMARKS Kathryn C. Zoon, Ph.D. 6 Director, Center for Biologics 6 Evaluation and Research 7 INTERACTIVE SATELLITE TELECONFERENCE (Not reported) 8 STAKEHOLDER PRESENTATIONS 9 ROBERT GARNICK, Ph.D. 21 10 Vice President, Regulatory Affairs Genentech, Inc. 11 CINDY MORROW 33 12 Senior Regulatory Specialist Becton-Dickinson 13 PAUL HOLLAND, M.D. 42 14 Medical Director/CBO Sacramento Medical Foundation 15 Blood Centers 16 OPEN DISCUSSION 54 17 --oOo-- 18 19 20 21 22 23 24 25 2 COMBS & GREENLEY, INC. (415) 512-1234 1 April 28, 1999 P R O C E E D I N G S 9:34 a.m. 2 --oOo-- 3 MS. ZIOBRO: Good morning, everyone. 4 I think we're going to have quite a bunch 5 more people joining us as we get into this morning's 6 program. 7 I'd like to introduce myself. My name is Pat 8 Ziobro, and I'm the district director of the 9 San Francisco District in Alameda. And we're really 10 pleased this morning to be able to cohost one of the 11 live sessions with Kathy Zoon from CBER. I'd like to 12 tell you a little bit about the game plan this morning. 13 Our satellite downlink will begin promptly at 10 o'clock 14 with Dr. Jane Henney, our new commissioner, discussing 15 her vision and priorities and the accomplishments we've 16 made in support of FDAMA. Following Dr. Henney, we'll 17 hear some remarks from Linda Suydam, who is also in the 18 office of the commissioner, who will give us additional 19 remarks about where the agency is headed, obstacles we 20 have. And we will be seeking questions, input and so 21 forth during the teleconference as well. 22 There will be an opportunity to fax and phone 23 in your questions, and I'd like to ask if you have any 24 of those, that you put them on this gray-colored sheet 25 that's in your packet and step outside. Immediately 3 COMBS & GREENLEY, INC. (415) 512-1234 1 outside the door here we have a fax and phone line that 2 we can send those questions in directly. 3 This will be an interactive session, and it's 4 going on all around the country. In addition to this 5 facility here, we have another CBER group on the East 6 Coast in Boston; we have a device group down in 7 San Diego; veterinary medicine in Kansas City; a foods 8 group in Washington; and an ORA group in Washington as 9 well; CBER in Philadelphia. So we have other live 10 sessions in addition to groups that are just hosting the 11 video satellite this morning. 12 Because we have sessions going on all over 13 the country, you understand that it is possible your 14 question may not be answered live while we're on this 15 morning. But I assure you all those questions are going 16 to be kept and answered someplace in those minutes that 17 will issue. The report will probably be on the 18 Internet. Kathy? 19 DR. ZOON: Yes. 20 MS. ZIOBRO: As they have in the past, we 21 have a reporter here who is going to record all the 22 comments and all the live testimony that we're going to 23 have today during the teleconference as well as in this 24 afternoon's session. 25 At the end of the day, I would appreciate if 4 COMBS & GREENLEY, INC. (415) 512-1234 1 you would take the blue sheet of paper in your packet 2 and give us some feedback as to what your thoughts were 3 about today's session. Today is unique in that we are 4 having this all over the country rather than the 5 separate sessions that we held last summer for each of 6 our stakeholder groups. 7 The video conference will go until about 8 noon. We'll take a short break and resume after that 9 break with our session here with Kathy and your 10 particular interests in the CBER program areas. And 11 then I think we'll take a lunch break and come back 12 between 2:00 and 3:00. Is that correct? 13 MR. STRICKLAND: Yes. We will have a panel 14 from 12 to 1 o'clock, and then from 1 clock to 2 o'clock 15 will be lunch, and we'll come back at 2 o'clock and 16 adjourn between 3:00 and 3:30. 17 MS. ZIOBRO: Okay. I'm sure you've all found 18 the rest rooms around the corner as well. 19 Help yourself, get up during the video 20 conference, to some refreshments in the back of the 21 room. 22 And again, this is our opportunity to listen 23 to your concerns. We don't have a whole lot to say. We 24 want to listen. Again, I extend a welcome to all of 25 you, and I know this is going to be an exciting day. 5 COMBS & GREENLEY, INC. (415) 512-1234 1 It's new for us as well. 2 DR. ZOON: Thank you, Pat. 3 First I'd like to welcome everyone. This is 4 a wonderful opportunity to come out to the West Coast to 5 meet with many of our colleagues and to hear how we're 6 doing and what you think we could be doing better, and 7 constructive advice is always welcome, and also to talk 8 with you a little bit about our priorities. 9 But before going onto that, I want to 10 personally thank Pat Ziobro, the district director, and 11 her staff, Kathryn Macropol, Mary Ellen Taylor, and also 12 Mark Roh for helping us put this on out in 13 San Francisco, and Dennis Strickland, who is here, 14 again, is my deputy director of Office of Communications 15 and Manufacturing Assistance. 16 Also here from CBER, Dr. Jerry Donlon, who is 17 deputy director of the Office of Compliance and 18 Biologics Quality, and Dr. Lillian Yen, who is the 19 special advisor on medical devices for biologics, are 20 here. And they will be taking over for me at 1 o'clock 21 because I have to go back for a hearing tomorrow 22 morning. So I need to leave at 1:00 to make my plane to 23 get back for that. 24 But I really appreciate your coming, and 25 Jerry and Lillian will be here subsequently to listen 6 COMBS & GREENLEY, INC. (415) 512-1234 1 and answer any questions you have. So thank you. 2 I would like to give you a brief overview if 3 I can now using some overheads, and I'll speak until 4 10:00. Wherever I am, I will stop. So just to warn you 5 if it sounds like I'm stopping in the middle of 6 something, I probably will be. 7 Part of the outreach that we would like to -- 8 you can leave the lights on. 9 MR. STRICKLAND: Okay. 10 DR. ZOON: That's not necessary to shut them 11 off. 12 I would like to just remind everyone about 13 CBER's mission. And that is the mission of CBER is to 14 protect and enhance the public health through the 15 regulation of biological products and related products 16 including blood vaccines, biological therapeutics -- and 17 I have changed the mission statement. We might have it 18 approved by our organization as a whole to include 19 devices based on comments we had gotten at our last 406B 20 meeting. 21 According to the statutory authorities, the 22 regulation of these products is founded on science and 23 law to insure purity, potency, efficacy and safety and 24 availability. 25 I think what we regulate at CBER is no 7 COMBS & GREENLEY, INC. (415) 512-1234 1 stranger to many of you in the audience. We have a 2 spectrum of products here including blood, blood 3 derivatives, tissues, devices, diagnostics, 4 xenotransplantation and many biotech products. 5 The regulation of these products is based on 6 what we call our biologic Olympic rings, and it's 7 review, research, surveillance, policy and compliance. 8 CBER has prepared a vision statement, and 9 this is very much -- is very consistent with what 10 Dr. Henney will be talking to us today about with 11 respect to focusing on the science base. And that is 12 that CBER advances the public health and merits the 13 public trust through high quality science-based 14 regulation to insure that safe and effective products 15 reach the public as rapidly as possible. CBER 16 demonstrates international leadership in regulation 17 through development of innovative regulatory strategies 18 and standards, a managed regulatory process, coordinated 19 research and the use of partnerships. And partnerships 20 can be with academia, other government agencies, as well 21 as the industry. And many of these partnerships have 22 already been established, and we would like to continue. 23 I'd like to just share briefly our priorities 24 for FY99 as they stand and we have been implementing. 25 One is to implement the FDA Modernization Act, and we've 8 COMBS & GREENLEY, INC. (415) 512-1234 1 been working very diligently on that, and you will hear 2 more regarding that from Dr. Henney. 3 One of the major initiatives that CBER led 4 this year was the fast track program, which is a program 5 for products for severe and life-threatening illnesses. 6 And a guidance document was issued last November which 7 gives comprehensive instructions on that program. And I 8 would refer you to that if you are interested. 9 The next priority was to meet and exceed our 10 PDUFA goals for FY99. And I'm happy to report to you 11 CBER has met all its goals thus far for both FY98, and 12 we are meeting all our milestones for FY99. So I think 13 we're very proud of that and hope that not only the 14 numbers but the spirit of FDA reform is being exhibited 15 in our performance, and we are trying to pay very close 16 attention that we are doing that. 17 Take whatever actions are necessary to assure 18 the safety and the public confidence in the nation's 19 blood supply. 20 A major activity for CBER that was started in 21 the summer of '97 was our blood action plan. This 22 particular plan covers a variety of issues from 23 reinventing our processes, to improving our performance, 24 to getting regulations out. And we have been very 25 successful in this program and have a number of other 9 COMBS & GREENLEY, INC. (415) 512-1234 1 milestones that we will be meeting for this upcoming 2 year. 3 To facilitate the development and approval of 4 significant vaccine, blood and therapeutic products 5 through review, policy formulation, regulation 6 development, et cetera, and to pursue excellence in 7 research that's directly targeted to our regulatory 8 mission. 9 These I believe are fundamentally important. 10 They are in the spirit of FDAMA. I think that we really 11 are looking at trying to see innovative ways not only to 12 reduce the review time for applications for marketing 13 but also looking at the total development time it takes 14 from when an IND is submitted to when the product is 15 actually approved, because that's really where the 16 rubber meets the road. 17 Some of our other priorities are to focus on 18 our information systems, and this includes not only 19 within the center but for our review. We have this as 20 one of our prescription drug producers goals. It's part 21 of that program. We have engaged in working on guidance 22 documents that provide support for the industry and 23 others who use these information systems to give you the 24 standards and how we are going to proceed. We've also 25 spent a great deal of time developing our infrastructure 10 COMBS & GREENLEY, INC. (415) 512-1234 1 at the center improving the capabilities of our 2 equipment so that we will be in a position to receive 3 electronic submissions, both for INDs and BLAs by the 4 year 2000 and continue our effort to have a high quality 5 diverse work force. 6 Well, some of our challenges at CBER are 7 shown in this slide. Our operating budget, while it 8 looks reasonably steady, has had some major challenges 9 especially in the products that are non-PDUFA. That's 10 the purple. And we have had a 40 percent decline in our 11 operating budget over the past five years. And this has 12 taken a fairly heavy toll on some of our non-PDUFA 13 programs. 14 This year we were able to use some of the 15 PDUFA reserve one time to promote and actually give a 16 jump start to the PDUFA II program to insure we could 17 meet the milestones. But I think this will not occur 18 next year, and we need to really be careful to maintain 19 a certain balance on our programs, and I think right now 20 our biggest concern is in the non-PDUFA supported area. 21 If we look at our workload, the workload at 22 CBER has been, if not steady, but a slight increase 23 especially in our investigational new drug applications, 24 IDEs and master files. This year we had 538 new INDs, 25 IDEs and master files submitted. 60 percent of this 11 COMBS & GREENLEY, INC. (415) 512-1234 1 were in biotech products. So I think that's an 2 interesting number. So that two-thirds of what CBER 3 does actually in the investigational area is related to 4 biotech. 5 The number of licenses we had last year has 6 been -- applications received has gone up slightly 7 although the numbers for the biotech applications are 8 about the same. So for FY 98 we had 77 applications 9 received. 10 Just to show you our performance with respect 11 to PDUFA, this gives you full cohort years that we have 12 complete data on. 98 and 99 are still in progress. But 13 as you can see, CBER has met or exceeded all our 14 performance goals. 15 In looking at the future and where are we 16 going, one of the key areas for us to focus on, I 17 believe, to meet the challenges of the new biomedical 18 products coming out into the public as a result of large 19 investments in biomedical research really require an 20 enhancement across FDA, including CBER, of the science 21 base. And this is particularly important to facilitate 22 sound, timely regulatory decisions. 23 I think when you don't have the proper 24 scientific underpinning, one tends to be more 25 conservative and more timid in your decision making 12 COMBS & GREENLEY, INC. (415) 512-1234 1 because you're afraid of making an error. And I think 2 the opportunity to enhance the science, make good 3 scientific judgments, is absolutely necessary for many 4 of us to realize the fruits of the products of new 5 technology. 6 So what are some of the things that we want 7 to do for our science base? 8 One is to really focus this on bringing the 9 new products and improvements to products to the market 10 as rapidly as possible while assuring their safety and 11 efficacy. And second is to make sure that we reduce the 12 risks of the products that are on the market while 13 enabling access. Some of the strategies we're looking 14 at to do that include enhancing research, standards 15 development, surveillance, outreach and premarket 16 review. 17 Many people ask, "Well, does FDA really do 18 research? And why do they do research?" Well, there 19 are some fundamental reasons. One is to facilitate the 20 approval of safe and effective products. Two is to 21 support decisions to withdraw products that are found to 22 be unsafe. And to anticipate public health needs and 23 really provide the support for that decision making and 24 prevention of a public health crisis. It also 25 encourages the adoption of standards and also 13 COMBS & GREENLEY, INC. (415) 512-1234 1 contributes to the development of new products. And 2 probably not insignificantly, it aids in the recruitment 3 and retention of scientists at the agency. 4 Some of the major initiatives that we're 5 currently engaged in at CBER include, as I said, the 6 implementation of FDAMA. We have a strategic plan that 7 we're in the process of implementing. Team Biologics, 8 of which you heard, that we have an active team with 9 CBER and ORA and field in doing a team approach with 10 product and GMP experts and cross-training. And I think 11 that's proceeding quite well. We're almost finished 12 rolling it out. Coming this October, vaccines and other 13 products will be transitioned into Team Biologics, and 14 most of the other products have already been 15 transitioned. 16 We have a tissue action plan, which I won't 17 have time to talk about today, but that's proceeding 18 well. 19 A blood action plan, which I had alluded to 20 previously. 21 And a xenotransplantation action plan to deal 22 with this new technology for potentially using animals 23 as a source of organs and tissues but mindful of the 24 infectious disease risk. 25 And one of the big areas I'd just like to 14 COMBS & GREENLEY, INC. (415) 512-1234 1 mention this morning is device action plan. Last year 2 at the 406B meeting, we had heard your concerns with 3 respect to CBER and its performance regarding the device 4 review and management. We heard you. We put together a 5 device action plan. I'm proud to announce today as of 6 two days ago it has been signed off by myself, Liz 7 Jacobson, Dennis Baker, the new head of -- the new ACRA, 8 Associate Commissioner of Regulatory Affairs, and 9 Dr. Henney. That action plan is now up on the Web. And 10 Dr. Lillian Yen, who is here today, and Dr. Donlon will 11 be happy if this afternoon you have additional questions 12 regarding this plan to be available and discuss it with 13 you. 14 Some of the concerns we had heard that we 15 were trying to respond to were the consistency with 16 CDRH, harmonization on some of the standards both with 17 the review and the oversight -- compliance oversight and 18 inspections, facilitation of reviews, guidance and 19 communications. 20 In the interest of time, because we only have 21 a couple of minutes before Dr. Henney comes on, I would 22 just like to say that this particular plan really 23 focuses on four areas: The CBER-CDRH coordination; 24 review performance; compliance including Team Biologics, 25 and having uniform standards; and outreach and inreach 15 COMBS & GREENLEY, INC. (415) 512-1234 1 both to the outside communities we serve as well as 2 within our own organization to get the very best ideas 3 to work on needs of particular issues. 4 The coordination with CDRH includes adoption 5 of certain guidances that CDRH has already submitted, in 6 which one applied to CBER that should publish shortly 7 we're going to be reviewing the innercenter agreement 8 and working on that. And we're also working very hard 9 on a number of areas in terms of re-engineering our 10 processes as well as having joint training with CDRH and 11 having a web page devoted to the CBER devices. We are 12 also actively engaged in guidance documents as they may 13 be unique to the (unintelligible). 14 In closing, I wanted to just say that we very 15 much value the information and the feedback that we get 16 from these 406B meetings. It's very important for us to 17 hear from you. This is your opportunity particularly 18 today to talk about your experiences, your issues, your 19 concerns and also to give your ideas on how we can do 20 our jobs better, which we will take under serious 21 advisement and discussion. 22 And I think the device action plan is our 23 response to the commitments that we have to seeing that 24 when legitimate issues are brought to us with ideas, we 25 try to incorporate your ideas into what we have 16 COMBS & GREENLEY, INC. (415) 512-1234 1 developed to be responsive. 2 So thank you very much. I appreciate the 3 opportunity to be here. 4 (Clapping) 5 DR. ZOON: Now I hope they start on time. 6 Are there any questions? 7 I'm sure I can answer everything, no. Yes? 8 MS. MAURER: My name is Kerry Maurer of Gene 9 Labs Technologies. My question refers to the fast track 10 program, which I think first off I commend the agency 11 for adopting this type of program, and I use the 12 guideline many times, and I think it's comprehensive. 13 However, I think it's assumed that if the drug is 14 granted fast track that -- or during scientific 15 development or prior to NDA filing that the standard NDA 16 supported studies, (unintelligible) can somehow be waive 17 or postponed into a post-NDA commitment 18 (unintelligible). Is the agency using that vehicle? 19 Activity? Is that something that's really happening, or 20 is that sort of a feeling you get when you get a fast 21 track for your -- 22 DR. ZOON: I'd have to know the specifics. I 23 think depending on the plan you have and how you come 24 into the agency and how you discuss what you think your 25 development plan is, that's something to put on the 17 COMBS & GREENLEY, INC. (415) 512-1234 1 table when you come in to develop that. 2 I encourage many folks when we deal with them 3 that if they actually have a five-year plan that they're 4 discussing with one or more of their products that they 5 actually come in and talk to us about it. One, it helps 6 us to understand what your issues are and what 7 flexibilities you actually have with the particular 8 product, because some of these are very 9 product-specific, and you have to deal with them. In 10 addition, it helps us to understand that there are going 11 to be areas as you go forward and not only for fast 12 track but in your whole development profile what we may 13 need to be looking at down the road because sometimes if 14 standards have not been developed or biomarkers are in 15 the process of being developed, sometimes we can give 16 you advice on that area. Or if there's a big need that 17 we're seeing in certain areas for the development of 18 biomarkers or discussions on others, that puts it on our 19 radar screen so that we can then work with NIH or other 20 interested parties in making that a more public meeting 21 or developing guidance documents, et cetera. 22 So that would be very helpful if you can come 23 in early to give us your development plan, and then we 24 can work through the specifics. 25 MS. MAURER: But if it's a situation where 18 COMBS & GREENLEY, INC. (415) 512-1234 1 you're receiving a fast track designation prior to -- 2 just prior to your NDA filing, say a year or so ahead of 3 time, where you've been working with an accelerated 4 critical development, say under subpart E, or you hadn't 5 worked (unintelligible) for example, is the agency 6 looking towards postponing some of these standards 7 (unintelligible) very long-term expensive studies such 8 as carcinogenicity studies? 9 DR. ZOON: Again, I think we're looking at it 10 in a flexible way because some of them it depends on the 11 nature of the product and what the properties of that 12 product are as whether you can or cannot look at it 13 postapproval, which is what I think you're trying to 14 say. 15 So some of these things I think really 16 depends on what the data you have now are, what some of 17 these issues are with respect to the product in having 18 to manage that. So I can't answer specifically because 19 there's a lot that would come into that. 20 MR. STRICKLAND: Dr. Zoon, we have 30 21 seconds. 22 Let me ask one important thing. We have a 23 transcriber here. So this is part of a public record. 24 And anyone who has questions, please use the mike. And 25 also, can you spell your name for the transcriber in the 19 COMBS & GREENLEY, INC. (415) 512-1234 1 corner so she can get the appropriate spelling of your 2 name for the record? And the same will be true of the 3 presenters, if you can give copies of your presentation 4 to me or to the transcriber. Thank you. 5 (Interactive satellite teleconference) 6 DR. ZOON: I would like to open the 7 stakeholder presentation session. One, if you have any 8 comments that either you didn't get to fax to Dr. Henney 9 or you have other information -- if you have any other 10 information or comments you'd like to submit, Dennis 11 Strickland will be taking those. Dennis, please stand 12 up. Dennis will be taking your comments, and we'll add 13 them to the comments that were received at headquarters. 14 So overall, I think the presentation was -- 15 my own personal view -- very good. I hope it was 16 interesting and informative to everyone and also a good 17 opportunity to hear from Dr. Henney and Ms. Suydam. So 18 hopefully, we'll look forward to your feedback on how 19 effective you think that type of communication is. 20 We have several people that are listed to 21 speak here -- I guess it's this afternoon now, and first 22 is Dr. Rob Garnick. He is the vice president of 23 Regulatory Affairs at Genentech. Rob? 24 MS. ZIOBRO: We'd like to ask if you have a 25 copy of your comments and remarks, that you give them to 20 COMBS & GREENLEY, INC. (415) 512-1234 1 Dennis or to our transcriber so that we'll have them for 2 the record. 3 DR. GARNICK: Thank you very much. And I'd 4 actually like to take the opportunity to thank the FDA, 5 Dr. Henney, Dr. Suydam and you, Kathy, for the 6 opportunity to have this meeting here. And it's really 7 a wonderful opportunity for the stakeholders to provide 8 information and prospective thoughts to the agency about 9 how we as the regulated industry understand the 10 provisions for FDAMA, the work you've been doing with 11 PDUFA, and to provide some thoughts about how we could 12 actually do a better job working together. 13 If I could have the first slide, please. 14 Some of the prospective thoughts that we have 15 actually been considering and providing the agency with, 16 some prospective and positive feedback is the thought of 17 providing and creating technical advisory boards. This 18 will consist of mixed boards containing mixtures of 19 thought leaders from industry, academia and FDA who 20 would recommend to the agency when important national 21 issues need to be discussed in a very open and positive 22 forum. I'm mindful of some of the very positive things 23 that we've had from the biotechnology perspective in the 24 past, the performance of genetic stability as well as a 25 very important one on well-characterized proteins that 21 COMBS & GREENLEY, INC. (415) 512-1234 1 has led to a lot of forward and positive issues that 2 actually have occurred under FDAMA, in particular with 3 respect to fast track. These are really important 4 areas, and at the time I am mindful of the fact that we 5 have had mixed groups. But to codify this and put this 6 into routine operation, I think it would be a very 7 positive and forward-thinking approach for the agency. 8 This would create, I think, very importantly 9 a climate where important issues that are on the 10 forefront of concern from the agency, the public and FDA 11 would be brought forward and discussed, and a very clear 12 risk-based decision making approach can be used. 13 One of the issues that I think is very 14 contemporary right now is the issue of generic 15 biologics. This might be a good opportunity to consider 16 the use of such a technical advisory board. 17 Next slide, please. 18 To answer the question that was asked on 19 reciprocating exchange and integration of scientific 20 information and agency scientists, I think one of the 21 important areas that we might be able to contribute is 22 the advice to hire and maintain experienced and 23 pragmatic staff. And from this standpoint, as we know, 24 many of the regulatory agencies around the world insist 25 upon their staff having had actual industry experience. 22 COMBS & GREENLEY, INC. (415) 512-1234 1 And I can't say enough about the fact that experience in 2 making risk/benefit decisions is a crucial area for us 3 and that the agency really needs to think very clearly 4 and carefully about the ability to hire experienced and 5 pragmatic staff. 6 There's also the opportunity to provide for 7 agency scientists' engagement in laboratory research. I 8 think this is a very critical area. To be able to use 9 the proper judgment to review the very complicated 10 submissions that are being proposed today from the novel 11 sciences that are being developed in the biotechnology 12 area, it's critical that scientists have both the 13 experience and understanding in order to make those 14 judgments. We propose that sabbatical programs be 15 created and that corporate internships be considered 16 where FDA scientists could spend time actually in the 17 regulated industry to be able to learn the state of the 18 art that is being considered at those times. 19 We'd like to propose that scientists from the 20 industry present state of the art symposia to FDA 21 scientists and that potentially we use the technical 22 advisory board as a forum to discuss new information, 23 advise FDA and hold appropriate symposia. 24 Next slide, please. 25 With respect to educating the public on risks 23 COMBS & GREENLEY, INC. (415) 512-1234 1 and benefits, I think it's important to better educate 2 the public on the basis for the approval of new 3 medicines. As we've heard in the video conference by 4 Dr. Henney and others, the public unfortunately does not 5 understand the complexity of the drug development and 6 approval process. And this leads to a lot of confusion 7 and difficulties with respect to reporting adverse 8 reactions and other problems, and for the FDA to take a 9 proactive stance in terms of educating the public would 10 be a very positive and forward-thinking approach. 11 This would provide the public with better 12 information about the pharmaceuticals that they have 13 been prescribed and also for them to understand the 14 risks that are associated with the use of those 15 pharmaceuticals. 16 And one thought would be to look at using the 17 publicly supported forum like National Public Radio or 18 television for patient education to have actual FDA 19 fireside chats. I'm actually mindful of this 20 presentation that we just heard and that having that on 21 a national public television, I think would go a long 22 way to having the public better understand the 23 complexity of drug development and use of 24 pharmaceuticals as well as how best to report adverse 25 reactions when they're observed. 24 COMBS & GREENLEY, INC. (415) 512-1234 1 Next slide, please. 2 A very important issue I think as you pointed 3 out is limited resources. The agency clearly is 4 limited. PDUFA has gone a long way to improve the 5 situation. But as we all know, it is still far from 6 perfect. I think some of the ways in which the agency 7 could use its limited resources in the most productive 8 way would be to partner more actively with product 9 sponsors, to use the advisory committees that are 10 proposed, to establish priorities potentially for fast 11 track products because we are mindful that, as we heard, 12 under FDAMA fast track is a wonderful and powerful 13 addition to our (unintelligible). However, it comes 14 with a cost, in that not all fast track products have as 15 high a priority as others. It is a difficult decision 16 to make with limited priorities. I'm mindful of 17 Dr. Henney's words that priorities priorities priorities 18 are the most important thing before us. 19 It's also important, I think, to have FDA 20 influence the sponsors with respect to what will 21 actually help the reviewers to make their decisions the 22 most appropriate way. FDA could actually sponsor a 23 workshop that would focus on what reviewers want in 24 terms of making their life easier. 25 And a final point is the inspection program. 25 COMBS & GREENLEY, INC. (415) 512-1234 1 I think inspections -- and having been in the regulated 2 industry now for 22 years and having gone through 3 literally hundreds of inspections, I would have to say 4 that the inspection program, while very valuable, may be 5 more important to be applied selectively rather than in 6 a uniform way. The industry does go through -- spends 7 enormous amounts of time on inspections, and not all of 8 the industry are those that need to be inspected more 9 frequently. And that the agency might want to consider 10 an inspection policy where companies with excellent 11 compliance and GMP history are perhaps not as heavily 12 inspected as those who are nowhere near as compliant or 13 have poor GMP experiences. 14 Next slide, please. 15 With respect to stakeholder communications, I 16 think this has been an excellent venue, and I would like 17 to encourage you to continue to seek the stakeholder 18 input, that more and more frequent and early discussions 19 such as these will benefit both the agencies as well as 20 the industry, that we'd like to continue to develop and 21 draft guidance and keep industry informed. And I would 22 also like to reiterate that having the industry 23 participate in the development of these draft guidance 24 documents would, I believe, facilitate the development 25 of these guidances and their acceptance throughout the 26 COMBS & GREENLEY, INC. (415) 512-1234 1 industry. 2 I think to implement modernization 3 effectively and consistently, it's important to 4 harmonize the guidance and process across the centers. 5 At this time, while there is a tremendous value in 6 development of this guidance, it is clearly not 7 harmonized across the various centers of FDA, and this 8 would be very helpful to the industry, particularly 9 those who may deal with biologic drugs as well as 10 devices. 11 To harmonize globally, I think the ICH 12 process is a critical area. FDA has actually led the 13 way in ICH, and this requires a lot of time and effort 14 and dedication. And to continue to provide the 15 horsepower necessary to facilitate the ICH process will 16 make I think the entire situation very productive and 17 positive. 18 Finally, there is the situation of 19 pharmacopeia in that the regulated industry does follow 20 the pharmacopeia and is highly involved with them, and 21 they do provide very excellent guidance. I would like 22 to encourage the agency and all the centers to work 23 closely with pharmacopeia in defined areas where mutual 24 partnership and value can be obtained. 25 In conclusion, I would like to say that I 27 COMBS & GREENLEY, INC. (415) 512-1234 1 think the agency has done a wonderful job implementing 2 FDAMA. I think it has been a hard and difficult road to 3 follow. But your clear wisdom and guidance and 4 leadership in the area is appreciated by the industry. 5 Thank you. 6 DR. ZOON: Thank you. Thank you very much. 7 (Clapping) 8 DR. ZOON: Yes. If I could -- would you take 9 a few questions for clarification? One of the things I 10 would like to ask, when you talk about input into 11 guidances, because of the federal advisory committee on 12 some parts of this is a bit limiting both with the 13 boards and with the ability to really formulate some of 14 these things in an interactive process. And I was 15 wondering -- I love the concept of these. Do you have 16 some suggestions on how you think we could from the 17 perspective, could it be workshops, in ways that we 18 could do the interactions on the scientific issues that 19 would lead into the documents? 20 And secondly, in looking at the technical 21 boards, how do you perceive those to come about in some 22 of the dilemmas we have with respect to other provisions 23 that we need to comply with? 24 DR. GARNICK: It's a good question, and I 25 probably don't have all the answers for it. But I 28 COMBS & GREENLEY, INC. (415) 512-1234 1 remember the well-characterized protein symposia that 2 FDA began a few years ago and the value of that in which 3 you actually had representatives from industry as well 4 as FDA begin to think through and plan that type of 5 meeting. That was a one-of, and it was very valuable. 6 And I think the ramifications of what were done at that 7 meeting we're still developing today. 8 But to codify this type of approach, the 9 development of boards -- and I think you can have boards 10 in the area of clinical studies, free clinical studies, 11 and manufacturing and controls and potentially 12 post-marketing safety. You could develop boards like 13 this that would be standing. The membership could be 14 chosen by FDA. For example, they would be publicized. 15 People would know who are the members. They would 16 probably have some rotation basis. But the challenge to 17 them would be those picked by the agency so that when 18 timely and important issues begin to emerge, and we all 19 see them emerging, that you could be able to get the 20 horsepower of those groups together to decide what the 21 situation really is or isn't, whether a national 22 symposia such as a well-characterized protein, what 23 needs to be held in those areas and to provide you with 24 the guidance in terms of where to go from there. And I 25 think that would help quite a bit. 29 COMBS & GREENLEY, INC. (415) 512-1234 1 With respect to the requirements that you 2 have with disclosure and things like that, I think we 3 would have to work to find -- to work our way around 4 that, but it clearly is possible to be done. 5 DR. ZOON: Thank you. Jerry? 6 DR. DONLON: I just have a few simple 7 questions. One thing in the area of enhancing the 8 science base for the agency or for (unintelligible) -- 9 are there specific disciplinary areas or scientific 10 areas that you recommend we pay attention to or root for 11 or enhance? 12 DR. GARNICK: Actually, I think that from my 13 own experience the agency does find people with good 14 educational backgrounds. But it's the experience base 15 that sometimes is lacking. There are a lot of excellent 16 universities, but they don't teach you what actually 17 happens in real life. And it's people -- I would 18 encourage you to find and hire people who have had 19 experience and who know -- or are more pragmatic in 20 their approach and judgment. And some of the areas in 21 which you might be looking in I think in terms of 22 chemistry, chemistry, biochemistry, clinical trial 23 design, pharmaco (unintelligible). These would be 24 important areas to focus on. 25 DR. DONLON: Would some of the emerging 30 COMBS & GREENLEY, INC. (415) 512-1234 1 technologies in pharmacogenetics, things of that nature, 2 should we be looking to enhance our abilities in those 3 areas as well? 4 DR. GARNICK: Absolutely. I think there's 5 quite a lot of work going on now in the areas of cell 6 and gene therapies. And this is clearly an emerging 7 technology which there are very many new things that 8 need to be discovered and dealt with. And there are a 9 lot of interesting and complicated regulatory aspects to 10 them. 11 So looking for people in those areas I think 12 would also be very valuable. 13 DR. DONLON: Brief question: You mentioned 14 inspection program, the need to perhaps modernize the 15 inspection program in a way. There is an initiative 16 clearly with the foods and the seafood issues by looking 17 at the pass -- applying passive analysis and critical 18 control points type of programs, and devices is looking 19 at piloting that into the device area. What's your 20 sense as far as industry's reception to that type of an 21 approach more broadly in the biotech industry? 22 DR. GARNICK: With respect to the biotech 23 industry, I think to put it in perspective, this is a 24 new industry that people who are involved I think are 25 extremely serious and dedicated to the development of 31 COMBS & GREENLEY, INC. (415) 512-1234 1 new products and (unintelligible) mode. They are 2 particularly mindful, I believe, of FDA guidance and 3 interactions, and they probably are the most 4 inspection-conscious members of the industry. That may 5 or may not be true in all cases. But in general, they 6 are probably very highly inspectional -- inspection 7 concerned and experienced. And they're probably not the 8 problem. The problem may well be elsewhere. And to 9 spend enormous amounts of precious FDA resources, 10 particularly with respect to the new BLA process and 11 under fast track where inspectional issues as well as 12 issues with response to the submission are actually 13 being reviewed, it's probably not the best use of FDA's 14 time. I would concentrate my efforts where the problems 15 really lie, and I think you know from your compliance 16 and GMP experience exactly where they are. 17 DR. DONLON: One other observation. You 18 mentioned we should have a closer working relationship 19 with the pharmacopeia. I just want to point out that 20 Dr. Kenney is past president of the U.S. Pharmocopeia. 21 DR. GARNICK: Yes, I am quite aware of that. 22 I think she has gone a wonderful job in that area. I 23 would really encourage the pharmacopeias and the FDA to 24 find a harmonized ground in which real value could be 25 added to the industry. 32 COMBS & GREENLEY, INC. (415) 512-1234 1 MS. ZIOBRO: Thank you. I'd like to ask our 2 next speaker to come up, Cindy Morrow, who is the senior 3 regulatory specialist at Becton Dickinson. 4 MS. MORROW: Hello. My name is Cindy Morrow, 5 and I'm an employee of Becton Dickinson Biosciences in 6 San Jose. I wish to thank the Center for Biologic 7 Evaluation and Research for providing this opportunity 8 to share our suggestions for FDA's efforts to improve 9 its implementation of the law. I'd also like to thank 10 my mentor and boss, Anna Longwell, who helped me 11 actually prepare these comments. 12 First, I would like to address some ideas of 13 how FDA might expand its capability to incorporate 14 state-of-the-art science into its decisions. 15 CBER is noted for its commitment to biologic 16 science. From the origins at Treasury through its long 17 (and continuing) association with NIH, CBER has been 18 committed to understanding and contributing to advances 19 in pharmacology and molecular and cell biology. 20 However, now CBER must also review devices, ancillary 21 products and combination products, which require 22 additional expertise in such varied disciplines as 23 computer science, polymer and surface chemistry, and 24 many other technologies. We suggest that CBER work more 25 closely with the other FDA centers to acquire this 33 COMBS & GREENLEY, INC. (415) 512-1234 1 expertise. 2 Please take advantage of the resources you 3 already have within FDA, but perhaps use them 4 differently. Also, get more advisory committee members 5 with expertise in the physical sciences and computers. 6 You could also ask manufacturers to provide more 7 information about the basic science and technology 8 involved in the development of their products well in 9 advance of product review. 10 A vendor day is a technique employed by other 11 centers to gain knowledge and allow interaction with 12 industry. This idea could be expanded to a more 13 science-fair-like event, to include discussions on areas 14 of mutual interest for industry, regulators, and the 15 public and provide opportunities for hands-on 16 demonstrations of technology, including instrumentation, 17 hardware, software and product information. 18 It's important that FDA management provide 19 the time and resources to allow all levels of FDA 20 employees to participate in learning opportunities in 21 order to encourage and maintain the good people that you 22 already have employed at FDA. In your hiring, seek out 23 individuals who have both scientific expertise and 24 experience in the practical application of medical 25 products. Look for opportunities for reviewers and 34 COMBS & GREENLEY, INC. (415) 512-1234 1 investigators to participate in externship programs 2 where they can gain experience with medical products and 3 the practice of medicine. 4 Next I would like to address how FDA might 5 incorporate state-of-the-art science into its risk-based 6 decision making especially in the area of new product 7 reviews. 8 We all acknowledge that the rate of 9 scientific discovery and development is accelerating. 10 Under today's product development systems for biologics, 11 or for devices reviewed by biologics, any truly novel 12 product reaching the U.S. market will be at least one 13 generation (or more) removed from state-of-the-art. 14 However, this situation can be beneficial. 15 An extensive program of design and testing is 16 not only a regulatory expectation but has become an 17 industry (and indeed a public) expectation for any truly 18 novel health care product entering our market. 19 One result of this careful and organized 20 approach to product development and evaluation, combined 21 with the almost daily changes in technology and science, 22 is that no product will be state-of-the-art when it 23 reaches the reviewer's hands. If the FDA insists on 24 "state of the art," companies are continually thrown 25 into a round of revisions and validations for each 35 COMBS & GREENLEY, INC. (415) 512-1234 1 significant improvement. And products that will have 2 significant health benefits for patients and their 3 providers will not reach the market in an appropriately 4 timely fashion. 5 FDA should not feel that it alone has to 6 provide incentive to manufacturers for continual product 7 improvement. For high-technology industries making 8 regulated product, there is ample incentive to continue 9 state-of-the-art product development. Our competitors 10 provide this incentive. For most of us, the motto is 11 "improve or die." 12 In review, FDA should principally base its 13 expectations for product performance on what is 14 currently available for use in the U.S. market, not on 15 what is being explored at the NIH or other world-class 16 research institutions. Risk/benefit assessments for 17 marketing permits should not be conducted on what could 18 be developed, but on what is currently available. 19 For issues concerning product safety, FDA 20 should base its review on the very latest information, 21 as long as that information is based on labeled claims 22 for the products, statistically valid scientifically 23 sound studies, and is not anecdotal information, whether 24 obtained from peer-reviewed scientific journals or other 25 sources. 36 COMBS & GREENLEY, INC. (415) 512-1234 1 One use of state-of-the-art science which in 2 the assessment of risk for which FDA deserves 3 commendation is their consideration of new surrogate 4 endpoints for clinical studies and new in vitro 5 analogues for lengthy animal studies. These advances in 6 science serve to shorten testing time and allow 7 innovative products to reach the market sooner, thus 8 shortening the product life cycle while still protecting 9 the public health. We expect FDA will continue to 10 encourage advances in these areas. By encouraging more 11 scientific ways of establishing product performance, FDA 12 will also assure that the product reaching the market is 13 as close to state-of-the-art as it can reasonably be 14 expected. 15 When there are scientific disagreements, we 16 recommend that FDA have available mechanisms to take the 17 issue to an outside scientific review process, short of 18 convening an advisory committee. However, yesterday, I 19 ran across a new CDRH draft guidance on resolving 20 scientific disputes concerning the regulation of medical 21 devices that I'm looking forward to reviewing. I just 22 had a chance to print it out. It showed up on the 23 Internet yesterday. 24 Next, educating the public about risk/benefit 25 analysis. Risk/benefit analysis is not well understood 37 COMBS & GREENLEY, INC. (415) 512-1234 1 by the general public. We see this frequently, when the 2 news of a single disaster with a product outweighs the 3 years of positive health effect obtained by use of the 4 same product. News stories about disasters command 5 attention, while statistics do not get the same 6 coverage. 7 If the FDA wishes to provide outreach to the 8 general public about risk analysis, we suggest an 9 approach that might utilize the Internet to capitalize 10 on some more familiar risk/benefit choices that people 11 have to make every day. It might be possible to utilize 12 FDA's Office of Special Health Issues home page to 13 develop an outreach program that explains risk/benefit 14 analysis in simple terms. 15 The approach might provide examples of what 16 people have to consider when evaluating their own 17 medical treatment options with the help of their 18 physician. For example, what questions they need to ask 19 their doctor and risks and benefits associated with each 20 treatment option. This might be done for key diseases 21 with three or four alternate therapies to help explain 22 the concept of risk evaluation. Then, once the basic 23 idea is established, you could explain how the same 24 techniques are employed by FDA on a more global scale to 25 review therapeutic or diagnostic products aimed at the 38 COMBS & GREENLEY, INC. (415) 512-1234 1 same disease categories. 2 Also, it would be helpful if you could 3 convince nonprofit organizations interested in public 4 health issues to provide a link to this same web page. 5 It would afford greater public access to alternative 6 points of view. 7 Next, improving FDA's focus. In this era of 8 restricted funds, more cooperation between centers and 9 between government agencies seems indicated. 10 If FDA wishes to concentrate more resources 11 on areas of greatest risk to public health, we suggest 12 close cooperation with the Centers for Disease Control, 13 which has long been developing information on public 14 health, and on our most serious public health problems. 15 Once areas of greatest public health risk are agreed 16 upon by FDA, they should be published, and a mechanism 17 for updating these findings should be established. FDA 18 might then consider expanding the Accelerating Approval 19 process to include products which are employed to treat, 20 diagnose or prevent these identified public health 21 problems. 22 Additionally, CBER should work with industry 23 to actively identify and downclassify lower risk devices 24 that have a good record for safety. 25 Also, CBER should work with the CDRH to 39 COMBS & GREENLEY, INC. (415) 512-1234 1 standardize and clarify the "least burdensome" 2 provisions of FDAMA relating to device review and 3 clearance to market. 4 Cooperation between centers is now being 5 attempted more frequently, and we applaud FDA, 6 especially CBER, for their efforts in this area. We 7 believe that more could be done to tap inter-agency and 8 intra-center expertise in the areas of device review, 9 web page design, and communication about processes in 10 general. 11 Finally, enhancing public feedback for FDA 12 communication efforts. We believe that CBER should make 13 better use of its website to obtain feedback. Also, we 14 believe that the website could be updated more 15 frequently and be more transparent in its use. For 16 devices in particular, it would be helpful to provide 17 linkages to relevant guidance developed by CDRH. Just 18 yesterday, I found a Federal Register notice listing 19 guidance documents that were issued by CDRH that apply 20 to medical devices regulated by CBER. That was 21 published on Monday on the website. So you mentioned 22 that. That's very helpful, especially if this 23 information can then be incorporated into your website 24 with links. 25 To obtain public feedback on particular 40 COMBS & GREENLEY, INC. (415) 512-1234 1 topics, it might be possible to post questionnaires to 2 the website with "fill out the blank" type forms that 3 could be returned via electronic mail. However, we have 4 found at Becton Dickinson that many people are unwilling 5 to give completely honest feedback especially internally 6 unless they are assured of anonymity. Therefore, it 7 might be a good idea for the FDA to contract with a 8 third party and have them analyze the report on feedback 9 to questionnaires. 10 We believe that local grassroots groups such 11 as the OCRA group in L.A., the Orange County Regulatory 12 Affairs, discussion group; the PAIR group in the Oakland 13 district, Partners on Industry and Regulators; and IVD 14 Roundtable, for example, in the Baltimore area should be 15 supported and that more districts should be encouraged 16 to form outreach groups with local industry. These 17 provide for valuable interaction and feedback from 18 members of regulated industry to regulators, and vice 19 versa. 20 One area in which more feedback could be 21 solicited is in the development of internal procedures 22 and processes to implement FDAMA at CBER. We hope that 23 CBER will allow greater and earlier stakeholder 24 participation in the development of FDAMA implementation 25 procedures. 41 COMBS & GREENLEY, INC. (415) 512-1234 1 Thank you. 2 DR. ZOON: Thank you very much. I appreciate 3 all those comments. Any clarifications? I think it's 4 clear. 5 (Clapping) 6 DR. ZOON: I'd like to ask Paul Holland, the 7 last scheduled speaker, to please come up. Paul is from 8 Sacramento Medical Foundation Blood Centers. 9 DR. HOLLAND: Thank you, Kathy. I'd like to 10 thank the FDA for holding these sessions. I think they 11 are useful. I appreciate the ones you have had in the 12 past and that you've provided us feedback from those. I 13 think that was very helpful to us all. I'm disappointed 14 and dismayed that more people from blood banking and 15 transfusion medicine, my field, are not here to comment 16 or at least attend. It's a great opportunity to provide 17 your input. 18 In providing my comments today, I hope you'll 19 take them as constructive comments, that they are from 20 our own center, my staff, and not from anyone else. I 21 tried to organize them in response to the questions, and 22 so I'll go through them. 23 The first one is what actions do you propose 24 the agency take to expand FDA's capability to 25 incorporate state-of-the-art science into its risk-based 42 COMBS & GREENLEY, INC. (415) 512-1234 1 decision making? 2 Implement your own quality assurance 3 guidelines -- these were issued in July of '97 -- and 4 put them into your labs and processes at the FDA. They 5 apply to us, and I think they should apply to you, too. 6 Certainly if you adopt a systems approach to 7 FDA's own quality system and operational areas, such as 8 the ISO 9000 model, incorporating principles of 9 continuous process improvement, tracking and trending, 10 et cetera, I think that will help you. 11 We certainly support your goals of 12 maintaining firsthand scientific expertise on relevant 13 technology and diseases. But you need to supplement 14 with experts or by partnering from various fields to 15 expedite evaluations of new applications of old products 16 and the requirements for, in my case, donor blood 17 testing. 18 You can certainly access outside scientists 19 and medical experts. As was said in other ways, I think 20 you might have a scientific advisory committee. You 21 have a blood products advisory committee, but today this 22 has few scientific blood banking transfusion experts on 23 it. 24 I think you need to perform risk assessment 25 based on true hazards or harmful incidents, not just 43 COMBS & GREENLEY, INC. (415) 512-1234 1 every GMP violation. The FDA has made extra work that 2 has nothing to do with minimizing harmful risks. 3 You need to identify errors that present 4 known harmful risks and require only those to be FDA 5 reportable. For example, these would be FDA reportable: 6 A true infectious diseases reactive unit that was 7 issued; a contaminated unit that was issued; untested 8 unit issued; ABO/Rh mislabeling. You really need to 9 minimize FDA reporting to critical issues. 10 Use scientific evidence (by expert consensus) 11 to establish new regulations. 12 Please do not implement precautionary 13 measures without known fact or cause/effect impact that 14 will decrease the donor or donation rates, and by how 15 much. Eliminating eligible donors on speculation or 16 just theoretical possibilities can result in lack of an 17 adequate blood supply, and this could actually result in 18 real patient death, very directly. 19 The next question was what actions do you 20 propose to facilitate the exchange and integration of 21 scientific information to better enable FDA to meet its 22 public health responsibilities throughout a product's 23 life cycle? 24 A specific example: Reconsider the need to 25 continue the requirement for submitting products for 44 COMBS & GREENLEY, INC. (415) 512-1234 1 platelet quality control. Are any discrepancies and 2 perceived failures in counts at CBER due to equipment 3 differences, modes of use? Has this been scientifically 4 investigated? If the facility producing these platelets 5 has adequate data to show the required criteria have 6 been met, why continue this requirement on only this one 7 product? What is the real public health risk? Is there 8 one? The requirement is costly; it uses up a valuable 9 component that patients cannot receive. And we really 10 wonder how meaningful this process is. 11 We think you should establish a hotline, fax 12 line, Internet page, whatever, for the regulated 13 industries to obtain quick answers to questions from an 14 identified pool of FDA subject matter experts. This 15 would really enable greater collaboration with FDA in 16 bringing new products to market to benefit patients. 17 For example, my area again, licensed pediatric platelet 18 dose, a blood product, to streamlining submissions and 19 clarification of new processes coming, like the BLA 20 (Blood License Application). We need to work with you 21 on such issues as a comparability protocol, monographs 22 for standardized blood products, and pilot programs for 23 licensed blood products (like irradiated blood pilot) 24 that you produce. 25 Again, echoing comments of other speakers, 45 COMBS & GREENLEY, INC. (415) 512-1234 1 establish public forums and workshops at national 2 meetings with scientific information presented. The FDA 3 must take quicker actions and finalize documents more 4 quickly. Some items, like the product license 5 applications, are approved after the blood center has 6 moved on to new methodologies. We are no longer using 7 the methodology anymore, and we finally get them 8 approved. 9 We think you should do away with PLAs all 10 together, product license applications. If a center 11 validates and meets the criteria of regulations, why not 12 allow the product to move in interstate commerce in that 13 basis. 14 We would appreciate if you would finalize 15 some of your draft guidelines a little more quickly. As 16 an example, the draft computer guideline is years old, 17 and it still hasn't been finalized. 18 Question No. 3 was what actions do you 19 propose for educating the public about the concept of 20 balancing risks against benefits in public health 21 decision making? 22 I think you need to provide analogies with 23 real-life risks that are undertaken daily. That is, how 24 does the risk compare to driving a car, flying in a 25 commercial airliner, riding a bike, walking up stairs? 46 COMBS & GREENLEY, INC. (415) 512-1234 1 This approach would really, I think, assist the public 2 in gaining a perspective on risk-related issues that are 3 often very emotionally charged. 4 Question 4: What actions do you propose to 5 enable FDA and its product centers to focus resources on 6 areas of greatest risk to the public health? 7 As I said, that's another answer, is really 8 streamline your product licensing for standard blood and 9 blood products to a monograph system of basic 10 specifications. 11 Echoing, again, the comment I made before, 12 eliminate the need to submit actual platelet products to 13 be sent to CBER for quality. 14 On site inspections and overall enforcement 15 via reporting of errors and accidents and recalls focus 16 on minute details, not usually the overall system, or 17 real risk to transfusion recipients. A systems approach 18 to both would allow delineation of isolated events, from 19 true system-wide issues that need to be addressed in a 20 much larger context. 21 We wish you would require that error and 22 accident reporting and recalls only apply to issues that 23 pose real risk (by some predefined criteria) to the 24 public. Some of the errors and accidents we have to 25 report are GMP related only, and almost all donor 47 COMBS & GREENLEY, INC. (415) 512-1234 1 accidents from post-donation information are low risk or 2 have such low potential such as potential malarial 3 exposure travel, subsequent illness. You and we need to 4 focus on higher risk issues for the biggest benefit of 5 the public and really require only reporting if the data 6 are used for some follow-up purpose. Just to gain this 7 data without using them doesn't help any of us. What do 8 you do with this data other than making internal 9 reports? What is it used for? How is it used? I think 10 we need to have you and us have use of that. 11 We suggest to set a timetable for updating 12 all blood and blood product regulations and fold them 13 all together in one set, incorporate all the previous 14 FDA memos that are endorsed into regulations. 15 Make the regulations in the CFR available on 16 the Internet with a search capability by topic and 17 cross-referencing to related topics. 18 We really appreciate your efforts, but we 19 need you to continue to work on decreasing and 20 eliminating the paperwork burden for reporting and 21 licensing. The annual report is one example of 22 additional new reporting requirements that have a 23 significant increase in data handling and reporting to 24 CBER. The new BLA and form 356h will require more data 25 and information to be submitted for product licensing 48 COMBS & GREENLEY, INC. (415) 512-1234 1 than the previous process required. 2 You need to revise the recall regulations to 3 provide more specific criteria based on real risk, for 4 required notifications and recall, and follow-up on the 5 disposition of products. This action would decrease the 6 amount of activity now required for many low risk 7 recalls, which most of which are just GMP breach only. 8 We would appreciate if you would plan the 9 public meetings on new regulations, new guidance 10 documents, new proposed programs to be bi-coastal or via 11 satellite downlink (unintelligible) such as today. Due 12 to the distance and travel expenses, we cannot send a 13 representative to a one-day meeting in the middle of a 14 week on the opposite coast. 15 FDA assessments of fiscal impact and are 16 often totally unrealistic in proposed documents and, we 17 believe, largely unfounded. We need to have you base 18 these on real data, please. 19 As a plea, we'd like you to address, up 20 front, the reimbursement issues of blood centers and 21 hospitals for FDA mandates or recommendations for 22 testing, or product manufacturing, or strongly support 23 new research testing, such as H.I.V. antigen, 24 Nucleo-acid testing, (unintelligible) blood products. 25 We need you to help us, and you need to notify and 49 COMBS & GREENLEY, INC. (415) 512-1234 1 encourage HCFA about adequately reimbursing us for added 2 costs of FDA mandates and recommendations. We too have 3 budget limitations, and we cannot do more with less as 4 you've heard. 5 Most blood centers and hospitals are not 6 for-profit. The decisions for new requirements must 7 include how they are going to be paid for. 8 We'd appreciate if you would eliminate 9 unnecessary activities such as recalls that will not 10 provide a beneficial outcome or prevent harm. Many 11 recalls and component retrievals are useless in really 12 reducing risk. 13 As was mentioned by one of the speakers, 14 there is a coalition for regulatory reform, CFRR. The 15 blood banking community tries to get its comments and 16 concerns in to them and from them to you. But often, 17 they don't seem to have much weight. We are often told 18 that CBER wants to hear individually from centers and 19 from individual people, not the CFRR. We rely on the 20 CFRR to represent us since most of us cannot send 21 representatives to meetings that CFRR would attend. 22 Question No. 5, what actions do you propose 23 for enhancing communication processes that allow for 24 ongoing feedback and/or evaluation of our modernization 25 efforts? 50 COMBS & GREENLEY, INC. (415) 512-1234 1 I think some written surveys to stakeholders 2 seeking input on top of some questions would be 3 worthwhile. 4 We need you to provide feedback from these 5 surveys or meetings by the Internet, written reports, 6 whatever. 7 Setting up an Internet page for a 8 dialogue/feedback on topics or on defined questions that 9 change on some regular basis would be of help. 10 Set up a mechanism for error and accident 11 reporting via Internet with encryption preferable. 12 The new FDA annual report notification of 13 changes process has added pounds of paper work for blood 14 centers. What good is this doing to protect the blood 15 supply or for the center? FDA inspectors can inspect 16 for any and all changes they want during reinspections. 17 What is the value of submitting all this input to help 18 you? Parenthetically, we can't really digest it all. 19 Having inspectors review product validation 20 on site. Can the FDA really manage all the reports it 21 gets and in a timely manner? 22 In general, the comments I'm trying to make 23 are that we really need help from you. We need to help 24 you. No doubt about it. And one of the areas is that 25 when we ask for advice or questions, we would like a 51 COMBS & GREENLEY, INC. (415) 512-1234 1 concrete and specific answer, preferably in writing. So 2 often we get an answer, "that's under review," or "that 3 document will be out soon" or "we're here to help you." 4 Without something in writing in a specific response, we 5 are not helped a great deal. And it should be based on 6 the current regulations. And hopefully, it should be a 7 quick response. 8 All of your biologic regulations need to be 9 updated. Many are archaic. Put them all in one 10 section. Resolve discrepancies between the CFR and FDA 11 memos and guidelines. We need you to take the words 12 "just do it" just as we have to based on scientific 13 information from expert consensus. And if there is no 14 consensus, then I'm not sure we should have such 15 regulations. 16 Our final plea is basically to consider risk 17 in general. I thought one of the most valuable things I 18 learned today was a comment by Dr. Henney. She said 19 "Safety does not mean there is no risk." And we are 20 working harder and harder and spending more and more 21 resources on making the blood supply safer and safer, 22 when we might think that our tax dollars might be better 23 spent on societal issues such as smoking, drugs, guns, 24 poor education, lack of medical access, underage 25 drinking. These are really more worthy topics than 52 COMBS & GREENLEY, INC. (415) 512-1234 1 trying to further minimize the small risk we have from 2 the blood supply, which is extremely safe today. 3 In closing, once again, thank you for the 4 opportunity to make these comments. If you have any 5 further feedback, please, I am happy to answer them, or 6 my staff, especially Sally Morgan-Gannon and Sallie 7 Holliman, who helped me write this statement. 8 Thank you. 9 DR. ZOON: Thank you, Paul. One question 10 that I'd like to ask you is do you think the blood -- in 11 hearing your comments, many of the objectives that we 12 have put forward in the blood action plan, there is a 13 lot of overlap. And my sense is in your review of that, 14 do you think that captures a lot of what you're trying 15 to do? Because that's where we are right now. 16 DR. HOLLAND: I think it does, but I think we 17 have to get on with it. We have to get to it and do it. 18 And some of these suggestions we both agree on; we just 19 need to do them, because it will eliminate your 20 unnecessary work, allow you to have better use of your 21 limited resources, as would be true for us, too. 22 DR. ZOON: Thank you. Do you have any 23 comments? 24 DR. DONLON: Just one observation. You were 25 commenting on the quality assurance practices. The 53 COMBS & GREENLEY, INC. (415) 512-1234 1 agency is initiating an evaluation of a proposal 2 basically to accredit the laboratories in the agency, to 3 accredit them to the ISO 25 or ISO 17025 version of 4 that, so we are moving in that direction. And our 5 center certainly, I think, has taken the lead in that 6 regard. So we are recognizing that we know it's 7 appropriate for industry, certainly appropriate for our 8 laboratories. 9 DR. HOLLAND: Great. I applaud that. Thank 10 you. 11 DR. ZOON: I might also add we had an 12 external review of our entire science program at CBER 13 last year, and one of the recommendations that we have 14 started implementing from that external review was to 15 increase the quality assurance program at the center and 16 with respect to private testing. 17 So those recommendations have been made and 18 instructions to each of the offices to -- as resources 19 permit, to start implementing that recommendation. I 20 think the findings of the plan is being drafted as we 21 speak. 22 So I think that's very timely and very much 23 on target with the external review. So thank you for 24 those comments. 25 DR. HOLLAND: Thank you. 54 COMBS & GREENLEY, INC. (415) 512-1234 1 (Clapping) 2 MS. ZIOBRO: I'd like to ask now, do we have 3 any comments from the rest of our audience here? 4 Margie, would you please come up to the 5 microphone, state your name, who you're with, and spell 6 your name. 7 MS. VASILEVSKY: Okay. My name is Margie 8 Vasilevsky. That's spelled V-A-S-I-L-E-V-S-K-Y. And 9 I'm with Bayer Corporation. I'm a QA manager, and I'm 10 also on the (unintelligible) steering committee 11 representing biologics. On this issue I am representing 12 the West Coast chapter of ISPE. 13 And the issue is that we would like to 14 participate in a rewrite of the 1987 process validation 15 guidelines. We have an advisory board, industry 16 executives, and they overwhelmingly said that their 17 biggest concern is out of control cost as it relates to 18 validation. And we looked into this, and it seems to be 19 the consensus of the industry that there's been an 20 incorrect emphasis on validation, non-value added versus 21 value-added activity. We would like to see it go back 22 to scientific principles that really insure product 23 quality. For example, 80 percent of our time, generally 24 speaking, is spent on IOQ. It should be the other way 25 around. We should be spending 80 percent of the time on 55 COMBS & GREENLEY, INC. (415) 512-1234 1 PQ and on process validation. 2 So that is -- I just had that one issue. 3 DR. ZOON: Thank you. 4 MS. ZIOBRO: Anyone else? 5 Kathy may be able to make her plane now. 6 DR. ZOON: Thank you very much. 7 I just want to say it is a pleasure to be 8 here. Sometimes when you're sitting here and listening 9 to the comments makes you feel a little bit bad, but I 10 know they're given in the right spirit. And we take 11 them that way. So I thank you for that. 12 And if we all can sit and discuss it in a 13 good old-fashioned honest way, I think we will make 14 progress. And we do appreciate that. 15 I would like to thank everybody who spoke up 16 today as well as those of you who have been considering 17 jotting something down to please do so. I really 18 encourage you to because that's the only way we'll 19 really know where your concerns are. We will do our 20 best within our resources to be responsive. 21 I do have to say, especially in the blood 22 area, that has been a problem that we're facing in our 23 resource areas. So we really -- to the level that you 24 can help us, give us your priorities as what needs to be 25 done first, that's always very helpful. We ask the same 56 COMBS & GREENLEY, INC. (415) 512-1234 1 question to the device industry as well, because of the 2 limited resources we have, what is most important to do, 3 so that we can make sure that we're targeting the right 4 things in the right order at the right time. 5 So to all of you who have come, I want to 6 personally thank you. I appreciate it. And you don't 7 need to just wait one time a year to give us your 8 feedback. I think we're willing to accept feedback any 9 time during the year. And our Office of Communication 10 and Manufacturing Assistance with Dennis Strickland, who 11 is here, can give you information to get word back to 12 the agency and CBER on any issues that you might need. 13 I would also like to thank our host, 14 San Francisco District. Thank you so much. And we 15 really appreciate it, Pat. And for all your 16 hospitality. 17 MS. ZIOBRO: And as you suggested, 18 Dr. Holland, we would really like to continue having 19 bi-coastal meetings such as this because that's where 20 the bulk of the industry is. So we appreciate that. 21 I'd like to remind you all to fill out your 22 evaluation of the teleconference because what we hear 23 from you today will govern whether we have more of 24 these. And I think we all agree it was a real 25 beneficial experience for all of us. 57 COMBS & GREENLEY, INC. (415) 512-1234 1 Is there a need for anybody to return after 2 lunch? I see us at a point where we've run out of 3 comments. If you feel you would like to come back for a 4 discussion, we can do that. Is there anybody who feels 5 they would like to come back and have discussion? Okay. 6 Because we want to do what you want to do. 7 All right. I think that will be the end of 8 it. Again, thank you for joining us. We'll see you 9 again soon, I hope. 10 (Proceedings adjourned at 12:56 p.m.) 11 --oOo-- 12 13 14 15 16 17 18 19 20 21 22 23 24 25 58 COMBS & GREENLEY, INC. (415) 512-1234 1 2 CERTIFICATE OF REPORTER 3 4 I, CLARE MACY, a Certified Shorthand 5 Reporter, hereby certify that the foregoing proceedings 6 were taken in shorthand by me, at the time and place 7 therein stated, and that the said proceedings were 8 thereafter reduced to typewriting, by computer, under my 9 direction and supervision; 10 I further certify that I am not of counsel or 11 attorney for either or any of the parties nor in any way 12 interested in the event of this cause, and that I am not 13 related to any of the parties thereto. 14 15 DATED: _____________________, 1999. 16 17 18 19 20 _____________________________ 21 CLARE MACY, CSR #5256 22 23 24 25 59 COMBS & GREENLEY, INC. (415) 512-1234