1 1 FOOD AND DRUG ADMINISTRATION 2 CENTER FOR DRUG EVALUATION AND RESEARCH 3 4 5 6 PHARMACY COMPOUNDING ADVISORY COMMITTEE (PCAC) 7 8 9 Afternoon Session 10 11 12 13 Thursday, June 23, 2016 14 1:00 p.m. to 5:08 p.m. 15 16 17 18 FDA White Oak Campus 19 10903 New Hampshire Avenue 20 Building 31 Conference Center 21 The Great Room (Rm. 1503) 22 Silver Spring, Maryland A Matter of Record (301) 890-4188 2 1 Meeting Roster 2 DESIGNATED FEDERAL OFFICER (Non-Voting) 3 Cindy Hong, PharmD 4 Division of Advisory Committee and Consultant 5 Management 6 Office of Executive Programs, CDER, FDA 7 8 PHARMACY COMPOUNDING ADVISORY COMMITTEE MEMBERS 9 (Voting) 10 Michael A. Carome, MD, FASHP 11 (Consumer Representative) 12 Director of Health Research Group 13 Public Citizen 14 Washington, District of Columbia 15 16 Gigi S. Davidson, BSPh, DICVP 17 (U.S. Pharmacopeial Convention Representative) 18 Director of Clinical Pharmacy Services 19 North Carolina State University 20 College of Veterinary Medicine 21 Raleigh, North Carolina 22 A Matter of Record (301) 890-4188 3 1 John J. DiGiovanna, MD 2 Senior Research Physician 3 DNA Repair Section 4 Dermatology Branch 5 Center for Cancer Research 6 National Cancer Institute 7 Bethesda, Maryland 8 9 Padma Gulur, MD 10 Professor, Department of Anesthesiology and 11 Perioperative Care 12 University of California, Irvine 13 Orange, California 14 15 Stephen W. Hoag, PhD 16 Professor 17 Department of Pharmaceutical Science 18 University of Maryland, Baltimore 19 Baltimore, Maryland 20 21 22 A Matter of Record (301) 890-4188 4 1 William A. Humphrey, BSPharm, MBA, MS 2 Director of Pharmacy Operations 3 St. Jude’s Children’s Research Hospital 4 Memphis, Tennessee 5 6 Elizabeth Jungman, JD 7 Director, Public Health Programs 8 The Pew Charitable Trusts 9 Washington, District of Columbia 10 11 Katherine Pham, PharmD 12 Neonatal Intensive Care Unit Pharmacy Specialist 13 Children’s National Medical Center 14 Washington, District of Columbia 15 16 Allen J. Vaida, BSc, PharmD, FASHP 17 Executive Vice President 18 Institute for Safe Medication Practices 19 Horsham, Pennsylvania 20 21 22 A Matter of Record (301) 890-4188 5 1 Jurgen Venitz, MD, PhD 2 (Chairperson) 3 Associate Professor, Virginia Commonwealth 4 University 5 School of Pharmacy, Department of Pharmaceutics 6 Richmond, Virginia 7 8 PHARMACY COMPOUNDING ADVISORY COMMITTEE MEMBERS 9 (Voting) 10 Donna Wall, PharmD 11 (National Association of Boards of Pharmacy 12 Representative) 13 Clinical Pharmacist 14 Indiana University Hospital 15 Indianapolis, Indiana 16 17 18 19 20 21 22 A Matter of Record (301) 890-4188 6 1 PHARMACY COMPOUNDING DRUGS ADVISORY COMMITTEE 2 INDUSTRY REPRESENTATIVE MEMBERS (Non-Voting) 3 Ned S. Braunstein, MD 4 (Industry Representative) 5 Senior Vice President and Head of Regulatory 6 Affairs 7 Regeneron Pharmaceuticals, Inc. 8 Tarrytown, New York 9 10 William Mixon, RPh, MS, FIACP 11 (Industry Representative) 12 Former Owner 13 The Compounding Pharmacy 14 Hickory, North Carolina 15 16 17 18 19 20 21 22 A Matter of Record (301) 890-4188 7 1 TEMPORARY MEMBERS (Voting) 2 Jeffrey Brent, MD, PhD 3 (Participation in DMPS discussion) 4 Distinguished Clinical Professor of Medicine 5 University of Colorado School of Medicine and 6 Colorado School of Public Health 7 Denver, Colorado 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 A Matter of Record (301) 890-4188 8 1 C O N T E N T S 2 AGENDA ITEM PAGE 3 Expanded Access to Investigational 4 New Drugs 5 Jonathan Jarow, MD 10 6 Clarifying Questions from the Committee 23 7 503A Bulk Drug Substances List 8 FDA Presentations 9 Pyruvic Acid 10 Brenda Carr, MD 36 11 Clarifying Questions from the Committee 46 12 Open Public Hearing 50 13 Committee Discussion and Vote 84 14 503A Bulk Drug Substances List 15 FDA Presentations 16 Tea Tree Oil 17 Hon-Sum Ko, MD 90 18 Clarifying Questions from the Committee 104 19 Nominator Presentations – NCPA 20 Alexander Pytlarz, PharmD 116 21 Committee Discussion and Vote 128 22 A Matter of Record (301) 890-4188 9 1 C O N T E N T S (continued) 2 AGENDA ITEM PAGE 3 503A Bulk Drug Substances List 4 FDA Presentations 5 2,3-Dimercapto-1-propanesulfonic acid (DMPS) 6 Kathy Robie Suh, MD, PhD 140 7 Clarifying Questions from the Committee 148 8 Nominator Presentations - AANP 9 Paul Anderson, ND 157 10 Clarifying Questions from the Committee 165 11 Open Public Hearing 175 12 Committee Discussion and Vote 187 13 Adjournment 201 14 15 16 17 18 19 20 21 22 A Matter of Record (301) 890-4188 10 1 P R O C E E D I N G S 2 (1:00 p.m.) 3 DR. VENITZ: Let's reconvene our meeting, 4 please. Welcome to the afternoon session of the 5 PCAC. We're now going to take a little detour, 6 getting information on expanded access programs. 7 We'll have Dr. Jarow present on expanded access to 8 investigation of new drugs. 9 Dr. Jarow? 10 Presentation – Jonathan Jarow 11 DR. JAROW: Good afternoon, everyone. I'm 12 back, for those of you who were at the last 13 Compounding Advisory Committee meeting. 14 It was felt, after the last session and the 15 questions that came up, that it'd be worthwhile to 16 give an expanded-access IND-for-dummies talk to 17 answer a lot of the outstanding questions that 18 exist. 19 Although I wasn't here this morning, I was 20 at another meeting, I understand that a lot of 21 these issues came up again today. 22 So here's a summary of potential questions A Matter of Record (301) 890-4188 11 1 that people might ask about this process, and I'll 2 give you the short answers here. And then 3 hopefully, you have a copy of my slides because, at 4 the end, there's two slides with resources that you 5 go to for much more in-depth information. 6 But question number 1, is there a model for 7 expanded access to an unapproved drug or a formerly 8 compounded drug? And the answer is yes. 9 The best, the only existent model for 10 something like that right now is domperidone, which 11 recent had the protocol and materials posted online 12 for people to access, but that's in single-patient 13 INDs. 14 I don't think that's necessarily the best 15 model for all situations. And the one that I'm 16 going to put forward today is something called an 17 intermediate-sized access IND. So yes, there is a 18 model. 19 Can the sponsor charge patients for the 20 costs incurred, as well as the drug? And the 21 answer is yes. Can administrative costs be passed 22 on? The answer to that is yes. A Matter of Record (301) 890-4188 12 1 Who can serve as the sponsor of the IND? It 2 could be a manufacturer. It could be individual 3 physicians or other groups, and we'll get into some 4 details later on. 5 How is the drug dispensed? The sponsor 6 dispenses the drug directly or through an 7 investigator. 8 Are multiple courses of treatment possible? 9 The answer to this is also yes, provided applicable 10 requirements are met. This would be part of the 11 protocol. 12 I learned through practice talk internally 13 at FDA -- for those of you who have participated in 14 or run a multicenter clinical trial, this is simple 15 stuff, very routine and easy. 16 For those of you who never done this, it 17 probably seems very opaque and problematic. I'm 18 going to try and clarify this, but I'll also want 19 to say -- and it's going to come up again -- talk 20 to us. Talk to us. We are here to help. 21 So what are the eligibility criteria for an 22 expanded access protocol? One, the indication has A Matter of Record (301) 890-4188 13 1 to be a serious or immediately life-threatening 2 condition. There has to be no comparable or 3 satisfactory alternative therapy. 4 The potential patient benefit justifies the 5 potential risk, and the risks are not unreasonable 6 in the context of the disease or condition to be 7 treated, and it's providing the drug will not 8 interfere with ongoing clinical investigations that 9 could support marketing approval of the expanded 10 access use of that drug. 11 There are multiple types of expanded access. 12 Expanded access is basically access to an 13 unapproved drug, which we're going to call an 14 investigational drug, outside of the clinical trial 15 setting. 16 This is not for research, although 17 frequently the information gathered from expanded 18 access protocols may be used as part of an 19 application. But in general, the intention is, in 20 expanded access, to treat patients. 21 It could be submitted as a freestanding IND 22 or a protocol under an existing IND. They come in A Matter of Record (301) 890-4188 14 1 three flavors; single-patient, which would include 2 both emergency and non-emergency use, intermediate 3 size patient population, and a treatment protocol 4 or IND, which is for more widespread use. 5 For an intermediate-sized access IND, the 6 application must state whether the drug is being 7 developed for marketing.