FOOD AND DRUG ADMINISTRATION CENTER FOR BIOLOGICS EVALUATION AND RESEARCH CENTER FOR DRUG EVALUATION AND RESEARCH FECAL MICROBIOTA FOR TRANSPLANTATION: SCIENTIFIC AND REGULATORY ISSUES CENTER FOR BIOLOGICS, EVALUATION AND RESEARCH (FDA) AND THE NATIONAL INSTITUTE FOR ALLERGY AND INFECTIOUS DISEASES (NIH) [This transcript has not been edited or corrected, but appears as received from the commercial transcribing service. Accordingly, the Food and Drug Administration makes no representation as to its accuracy.] Bethesda, Maryland Thursday, May 2, 2013 A G E N D A Welcome and Opening Remarks: KAREN MIDTHUN, MD Director, CBER/FDA FRED CASSELS, PhD Branch Chief of Enteric and Hepatic Diseases,DMID/NIAID Session I: The Microbiome in Health and Disease Part I: Moderator: MELODY MILLS, PhD NIAID/NIH Panelists: LITA PROCTOR, PhD National Human Genome Research Institute PHILLIP TARR, MD Washington University, School of Medicine in St. Louis YASMINE BELKAID, PhD National Institute of Allergy and Infectious Diseases ERIC G. PAMER, MD Sloan-Kettering Institute VINCENT B. YOUNG, MD, PhD University of Michigan Session II: The Microbiome in Health and Disease Part II Moderator: DAVID RELMAN, MD Panelists: ROBERT BRITTON, PhD Michigan State University LINDA S. MANSFIELD, MS, VMD, PhD Michigan State University EMMA ALLEN-VERCOE, PhD University of Guelph * * * * * P R O C E E D I N G S (8:43 a.m.) MS. MIDTHUN: Good morning, can you hear me? Okay, very good. Well, first off I'd like to welcome all of you. Thank you so much for coming today. I'm Karen Midthun, the Director of the Center for Biologics Evaluation and Research which is one of the Centers within the Food and Drug Administration. And the products that we're going to be discussing today fall within our purview. And I just want to say that it really is a pleasure to be able to bring all of you together. We really see this workshop as an opportunity to foster information exchange regarding the regulatory and scientific issues associated with fecal microbiota for transplantation. Lately, as you know, there has been a lot of interest in this area and using fecal microbiota transplantation to treat recurrent C. difficile infection as evidenced by numerous reports in the popular press, published meta- analyses of clinical use and a recently published open label clinical trial. FDA began receiving inquiries about FMT about a year and a half ago and it raised a number of questions about FDA regulation including when an investigational new drug application is needed. We decided that we should hold a workshop on FMT that would bring together bench scientists, clinical researchers and those with regulatory expertise as well as other stakeholders to discuss various aspects of this quickly evolving field. To this end, FDA, that is the Center for Biologics Evaluation and Research partnered with NIH, in particular NIAID in the Division of Microbiology and Infectious Diseases and it resulted in today's workshop. And I also very much want to thank those who were so integrally involved in developing the agenda for this workshop, engaging all those who we thought would be really important to be able to bring information to this workshop. I think we recognize that it was a lot of work and we're very grateful to the collaboration with NIAID and also with others who have helped bring this together. We're really fortunate in a sense that there is a rapid growth in the application that is that the rapid growth and in the interest in FMT coincides with a scientific revolution that is occurring in terms of understanding the importance of the human microbiome in shaping who we are and how our bodies function. This revolution has been fueled by really amazing technological developments in terms of our abilities to gather vast amounts of DNA sequence data on our microbial partners and by advances in our understanding of how our microbiota influence human health. It's our hope that this growing scientific knowledge in combination with the application of rigorous clinical studies will usher in a new era in the treatment of human disease and the maintenance of human health. Again, I would like to express my appreciation for your participation in this workshop and look forward to a very productive exchange of information and ideas. And with that, I would like to turn the podium over to Dr. Fred Cassels. Thank you so much. DR. FRED CASSELS: Thank you very much, Karen. My name is Fred Cassels. I'm the Chief of the Enteric and Hepatic Diseases Branch or EHDB. I'll be showing great restraint by not using humor related to feces. I'm filling in for Dr. Carole Heilman; she's the Division Director Micro Infectious Diseases of DMID who very much wanted to attend but sends her regrets. DMID supports research to control and to prevent all human infectious disease agents except for HIV where we have a separate division of AIDS. Grants are the foundation of DMID. We also have product development and clinical efforts assisting academics and companies to develop products for the benefit of public health. From our Division I would point out Dr. Richard Gorman who is in the back. He'll be moderating Session III. He's the Associate Director for Clinical Research. From our branch, again dealing with Enteric and Hepatic Diseases Dr. Melody Mills in the front row here who will also be moderating the first session, has worked with Scott Stibitz and the FDA Steering Committee. Melody and Scott are the co-chairs. And her involvement is initially due to her grant portfolio which includes the human gut microbiome but also due to her organizational skills and her passion in this area. I'd also like to point out Dr. Ryan Ranallo in the back. And due to his clostridium difficile portfolio is heavily involved in this area of research as well as product development and testing. Kudos to the FDA for their outreach efforts to result in this type of meeting that includes such a strong scientific base, community component and as well as the regulatory aspects. This is an important topic and it's an important time to address these issues. The Steering Committee I'd also like to applaud for a very well thought out and very comprehensive agenda. The broad range of speakers and stakeholders includes many aspects of the government, Human Genome Research Institute, the Intramural Program within NIAID bringing a research perspective, many from the Extramural NIAID and our group that brings that sort of programmatic perspective and notwithstanding the FDA with their public health and regulatory perspective. Many academics are here, grantees and physicians. Some are treating patients with FMT. Others are conducting clinical trials. Another important aspect of the attendees is industry. They're examining FMT and leveraging all this microbiome data into potential products that hopefully will improve and save lives. So, we also have a healthy mix of PhDs, VMD and many MDs which is very appropriate for this meeting. Much focus will be spent on the current practices although we will have a historical perspective really for the veterinary angle which is important to examine as we look into the future. This field is at a critical stage. Many say fecal transplants are very safe and effective and the interest is heightened as Karen mentioned from New England Journal paper in January. Others are legitimately saying, not so fast. We must examine and assess the risk and benefit. These are legitimate complex issues. Perhaps one solution down the road will be microbial replacement, some mixture of bacteria free of extraneous materials. But this is in the future. This very important meeting will examine in-depth all of these issues without blinking. Let's as a group help and work with the FDA in this incredibly promising area. Thank you. Melody Mills will now moderate the first session entitled the Microbiome in Health and Disease. MS. MILLS: Good morning, everyone. I just have a few logistical issues I need to make clear as we get started. Some housekeeping things as it were. So, first and foremost as you know there's signs saying there's no food and drinks allowed in the auditorium. They're quite serious about this so please don't bring anything in. Please, if you've got something step outside and please take anything with you out of this auditorium so that we're allowed to use it again tomorrow as planned. So, the other thing is to make sure you turn your phones off please. We have a transcriber so if you have any questions it's important to use a microphone. Please identify yourself, give your name and your affiliation and please don't be embarrassed if you forget and I remind you. In terms of the speakers, we have a visual timer set up for you. So, there it's a red, yellow, green. When it turns yellow it means that you have five minutes left in your presentation. There is a pointer up there that you can use, a green pointer. You can also use to advance the slides. You can also use the up and down arrows on the computer. In terms of the microphones at the podium, if you plan to stand still, please try to place yourself in-between the two microphones so that the transcriber and everyone else can hear you. There's also a lavaliere if you prefer to move around. And if anybody needs any help just look at me beseechingly and I'll run up there, okay? So, let's go ahead and get started.