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Science and Regulation of Live Microbiome-Based Products Used UNITED STATES FOOD AND DRUG ADMINISTRATION NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES SCIENCE AND REGULATION OF LIVE MICROBIOME-BASED PRODUCTS USED TO PREVENT, TREAT, AND CURE DISEASES IN HUMANS Rockville, Maryland Friday, April 19, 2019 2 1 PARTICIPANTS: 2 Welcome: 3 CAROLYN D. DEAL, Ph.D. Branch Chief, Sexually Transmitted Diseases 4 Branch Division of Microbiology and Infectious Diseases 5 National Institute of Allergy and Infectious Diseases 6 Introductory Remarks: 7 PETER MARKS, MD 8 Center Director, Center for Biologics Evaluation and Research 9 Food and Drug Administration 10 Keynote Address: 11 Introduction: 12 PAUL CARLSON, Ph.D. Principal Investigator 13 Laboratory of Mucosal Pathogens and Cellular Immunology 14 Center for Biologics Evaluation and Research Food and Drug Administration 15 The Microbiome in Human Health and Disease: A 16 Clinician-Scientist's Perspective: 17 VINCE YOUNG, MD, Ph.D. Professor, Department of Internal 18 Medicine/Infectious Diseases Division Department of Microbiology and Immunology 19 University of Michigan Medical School 20 SESSION 1: Regulatory Framework for "Probiotics" and Live Microbiome-Based Products: 21 Moderator: 22 3 1 PARTICIPANTS (CONT'D): 2 THERESA FINN, Ph.D. Associate Director for Regulatory Policy 3 Office of Vaccines Research and Review Center for Biologics Evaluation and Research 4 Food and Drug Administration 5 Dietary Supplements Containing Probiotics: 6 ROBERT "BOB" DURKIN Deputy Director, Office of Dietary Supplement 7 Programs Center for Food Safety and Applied Nutrition 8 Food and Drug Administration 9 Live Microbiome-Based Products Used to Prevent, Treat, or Cure Diseases in Humans: 10 SHEILA DREHER-LESNICK, Ph.D. 11 Biologist, Division of Bacterial, Parasitic and Allergenic Products 12 Office of Vaccines Research and Review Center for Biologics Evaluation and Research 13 Food and Drug Administration 14 SESSION 2: Safety and Effectiveness of Live Microbiome-Based Products Used to Prevent, Treat, 15 or Cure Diseases in Humans: 16 Part 1: 17 Moderator: 18 SUSAN MCCUNE, MD Director, Office of Pediatric Therapeutics 19 Office of the Commissioner Food and Drug Administration 20 Prevention of Necrotizing Enterocolitis 21 Use of Commercially Available Products to Prevent NBC: 22 4 1 PARTICIPANTS (CONT'D): 2 JOSEF NEU, MD Professor of Pediatrics 3 Director of Neonatology Fellowship Training Program 4 University of Florida 5 Prevention of Diarrhea 6 The Evidence is in for Probiotics to Prevent AAD: What is Holding Up Evidence-Based Use in the USA?: 7 DANIEL "DAN" MERENSTEIN, MD 8 Director of Research Family Medicine Professor of Family Medicine 9 Georgetown University 10 Use of Probiotics in Acute Pediatric Gastroenteritis - Two Large North American 11 Clinical Trails: 12 STEPHEN FREEDMAN, MDCM, MSc Associate Professor, Department of Paediatrics 13 University of Calgary 14 Safety and Effectiveness of Live Microbiome-Based Products Used to Prevent, Treat, or Cure Diseases 15 in Humans: 16 Part 2: 17 Moderator: 18 PAUL CARLSON, Ph.D. Principal Investigator 19 Laboratory of Mucosal Pathogens and Cellular Immunology 20 Center for Biologics Evaluation and Research Food and Drug Administration 21 22 5 1 PARTICIPANTS (CONT'D): 2 Prevention of C. difficile Infection 3 Use of Commercially Available Products to Prevent C. difficile: 4 A. KRISHNA RAO, MD, MS 5 Assistant Professor University of Michigan 6 Overview of Controlled Studies Using FMT for 7 Prevention of C. difficile infection: 8 COLLEEN R. KELLY, MD Associate Professor of Medicine 9 Alpert Medical School of Brown University 10 CMC Considerations for Live Microbiome-Based Product Development: 11 JOHN G. AUNINS 12 Executive Vice President and Chief Technology Officer 13 Seres Therapeutics 14 SESSION 3: Strain Selection for Live Microbiome-Based Products to Prevent, Treat, or 15 Cure Diseases in Humans: 16 Moderator: 17 RYAN RANALLO, Ph.D. Program Officer, Enteric & Hepatic Diseases 18 Branch National Institute of Allergy and Infectious 19 Diseases National Institutes of Health 20 Drugs Based on Rationally Defined Bacterial 21 Consortia: 22 6 1 PARTICIPANTS (CONT'D): 2 BERNAT OLLE, Ph.D. Chief Executive Officer 3 Vedanta Biosciences 4 Development of Defined Consortia for Recurrent C. difficile Infection: 5 ELAINE O. PETROF, MD, MSc, FRCPC, AGAF 6 Department of Medicine/Division of Infectious Diseases 7 Gastrointestinal Diseases Research Unit Queen's University 8 Canada 9 Finding the Needle in the Haystack: Moving From Consortia to Single Strains: 10 NEERAJ "NEIL" SURANA 11 Assistant Professor Departments of Pediatrics, Molecular Genetics & 12 Microbiology Duke University 13 Bacteroides fragilis Used in a Mouse Model of 14 Autism: 15 GREG BATES, DVM Senior Vice President 16 Regulatory Affairs Axial Biotherapeutics 17 L. plantarum to Prevent Sepsis: Timing and 18 Strains Matter: 19 PINAKI PANIGRAHI, MD, Ph.D., FIDSA Professor of Epidemiology, Pediatrics, and 20 Environmental, Agricultural and Occupational Health 21 University of Nebraska Medical Center 22 7 1 PARTICIPANTS (CONT'D): 2 Wrap Up: 3 CAROLYN D. DEAL, Ph.D. Branch Chief, Sexually Transmitted Diseases 4 Branch Division of Microbiology and Infectious Diseases 5 National Institute of Allergy and Infectious Diseases 6 7 8 * * * * * 9 10 11 12 13 14 15 16 17 18 19 20 21 22 8 1 P R O C E E D I N G S 2 MS. DEAL: My name is Carolyn Deal. And 3 on behalf of the National Institute of Allergy and 4 Infectious Diseases, I want to welcome you and 5 thank you all for coming today to this workshop 6 that we're holding jointly with the Food and Drug 7 Administration, the Center for Biologics, on live 8 biotherapeutic products. I think all of us, and 9 certainly by the amount of interest there was in 10 this workshop, we realize that this is a rapidly 11 moving, evolving, and important area. NIAID has 12 supported research in this area for quite a while, 13 mainly in the basic area. And it's exciting to 14 see it evolve from the basic research area into 15 translational work leading to product development. 16 However, we all know this does pose new 17 challenges, questions, but I would say also 18 opportunities. And we hope that these 19 opportunities can lead to new products that will 20 improve public health. For those reasons, NIAID 21 wanted to partner with the FDA to start a 22 discussion with the scientific community and our 9 1 manufacturing partners as to how best to approach 2 the need for rigorous clinical studies to evaluate 3 these products. For this, we know there are two 4 requirements. One is well-characterized products, 5 and the other is well-designed clinical studies 6 with defined end- points. These are some of the 7 topics that we hope that we can discuss today, and 8 get your input and thoughts, and see how we can 9 all collectively move forward. We really look 10 forward to this discussion and hope that everyone 11 at the end of the day will come away with some new 12 ideas. And now, it's my great pleasure to 13 introduce Dr. Peter Marx, who's the Director of 14 CBER, who will go into more detail about today's 15 program. Thank you, Peter, for coming. 16 DR. MARX: And so, good morning. I want 17 to welcome all of you in the room and on the 18 webinar to this workshop on the Science and 19 Regulation of Live Microbiome-Based Products used 20 to prevent, treat, or cure disease in humans. 21 Before I go further, I want to thank colleagues at 22 the National Institute of Allergy and Infectious 10 1 Diseases, and of the Food and Drug Administration 2 for putting together such a stimulating program. 3 We really have a group of presenters assembled 4 today that's highly qualified to discuss the 5 relevant issues. And I hope you'll find all the 6 presentations, panels, and interactive dialogue 7 informative and engaging. Just to orient you to 8 the day, we'll start off with the key-note address 9 by Dr. Vince Young of the University of Michigan. 10 And this will be followed by two presentations on 11 the regulatory framework for probiotics and live 12 microbiome-based products. After the morning 13 break, we'll first hear part of presentations on 14 the safety and effectiveness of live 15 microbiome-based products used to treat, prevent, 16 or cure disease in humans. And these 17 presentations and the discussions will continue 18 after lunch. And then following the afternoon 19 break, we'll hear presentations and a discussion 20 of strain selection for live microbiome-based 21 products to prevent, treat, or cure disease in 22 humans. Now it's certainly true that over the 11 1 past two decades the relevance of the human 2 microbiome to maintain health and to prevent the 3 occurrence of disease has never been more greatly 4 appreciated. And I think, the following, which is 5 quoted from the science journalist, Michael 6 Specter, summarizes this all quite nicely. I 7 think his words are much better than mine could 8 be. "We inherit everyone of our genes, but we 9 leave the womb without a single microbe. As we 10 pass through our mother's birth canal, we begin to 11 attract entire colonies of bacteria. By the time 12 a child can crawl she or he has blanketed by an 13 enormous unseen cloud of microorganisms -- a 14 hundred trillion or more. They're bacteria 15 mostly, but also viruses and fungi, including a 16 variety of yeast. And they come to us from all 17 directions. Other people, food, furniture, 18 clothing, cars, buildings, trees, pets, and even 19 the air we breathe. They congregate in our 20 digestive systems and our mouths, fill the space 21 between our teeth, cover our skin, and line our 22 throats.
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