FDA Briefing Document Pharmacy Compounding Advisory Committee (PCAC) Meeting June 23, 2016 The attached package contains background information prepared by the Food and Drug Administration (FDA) for the panel members of the Pharmacy Compounding Advisory Committee (advisory committee). We are bringing certain compounding issues to this advisory committee to obtain the committee’s advice. The background package may not include all issues relevant to the final regulatory recommendation and instead is intended to focus on issues identified by the Agency for discussion by the advisory committee. The FDA background package often contains assessments and/or conclusions and recommendations written by individual FDA reviewers. Such conclusions and recommendations do not necessarily represent the final position of the individual reviewers, nor do they necessarily represent the final position of the Review Division or Office. The FDA does not intend to issue a final determination on the issues at hand until input from the advisory committee process has been considered, all reviews have been finalized, consultation with the United States Pharmacopeia has occurred, and public comment has been considered through notice and comment rulemaking. The final determination may be affected by issues not discussed at the advisory committee meeting. Table of Contents I. Introduction ................................................................................................................... 3 A. Bulk Drug Substances That Can Be Used by Compounders under Section 503A .............................................................................................................................. 3 B. Expanded Access to Investigational New Drugs ................................................. 4 II. Substances Nominated for Inclusion on the Section 503A Bulk Drug Substances List (in order of discussion at the meeting) .......................................................................... 5 III. Draft Points to Consider................................................................................................ 7 FDA Briefing Document Page 2 June 23, 2016 I. Introduction Section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act) describes the conditions that must be satisfied for human drug products compounded by a licensed pharmacist in a State-licensed pharmacy or Federal facility, or by a licensed physician, to be exempt from the following three sections of the FD&C Act: section 505 (concerning the approval of drugs under new drug applications or abbreviated new drug applications); section 502(f)(1) (concerning the labeling of drugs with adequate directions for use); and section 501(a)(2)(B) (concerning current good manufacturing practice requirements). On November 27, 2013, President Obama signed the Drug Quality and Security Act, legislation that contains important provisions relating to the oversight of compounding of human drugs. Title I of this law, the Compounding Quality Act, created a new section 503B of the FD&C Act under which a compounder can elect to register as an outsourcing facility. Registered outsourcing facilities can compound drugs without receiving patient specific prescriptions or orders. If the conditions under section 503B of the FD&C Act are satisfied, drugs compounded by or under the direct supervision of a licensed pharmacist in a registered outsourcing facility may qualify for exemptions from the new drug approval requirements (section 505 of the FD&C Act), the requirement to label products with adequate directions for use (section 502(f)(1) of the FD&C Act) and the Drug Supply Chain Security Act (section 582 of the FD&C Act). Outsourcing facilities remain subject to current good manufacturing practice (CGMP) requirements. A. Bulk Drug Substances That Can Be Used by Compounders under Section 503A One of the conditions that must be met for a drug product that is compounded using bulk drug substances to qualify for the exemptions in Section 503A of the Act is that a licensed pharmacist or licensed physician compounds the drug product using bulk drug substances that: (1) Comply with the standards of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, if a monograph exists, and the USP chapter on pharmacy compounding; (2) If such a monograph does not exist, are drug substances that are components of drugs approved by the Secretary; or (3) If such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary, appears on a list developed by the Secretary through regulations issued by the Secretary under subsection (c) of section 503A. (See section 503A(b)(1)(A)(i) of the FD&C Act). FDA Briefing Document Page 3 June 23, 2016 FDA is considering those substances nominated for inclusion on the list of bulk drug substances that can be used to compound drug products under section 503A of the FD&C Act. As discussed at the February 2015 PCAC meeting, in the July 2014 Federal Register notice (79 FR 37747) (July 2, 2014) soliciting nominations for the section 503A bulk drug substances list, FDA proposed the following criteria to evaluate the nominated substances: (1) The physical and chemical characterization of the substance; (2) Any safety issues raised by the use of the substance in compounded drug products; (3) Historical use of the substance in compounded drug products, including information about the medical condition(s) the substance has been used to treat and any references in peer-reviewed medical literature; and (4) The available evidence of effectiveness or lack of effectiveness of a drug product compounded with the substance, if any such evidence exists. The agency is considering each criterion in the context of the others and balancing them, on a substance-by-substance basis, in deciding whether a particular substance is appropriate for inclusion on the list. B. Expanded Access to Investigational New Drugs Expanded access, sometimes referred to as “compassionate use,” is the use of an investigational drug outside of a clinical trial, including for emergency use, for the purpose of treating a patient or patients with serious or life-threatening disease(s) or condition(s) who have no acceptable medical options. The use of an investigational drug under expanded access is subject to all applicable requirements regarding informed consent and institutional review board (IRB) review. At previous meetings, there have been discussions about the use of an IND as an option for patients who seek to use drugs that are nominated for, but not placed on, the 503A and 503B bulks lists. At this meeting, the Agency plans to describe additional details about the expanded access program. Further information on the use of INDs is available on the Agency’s website at: http://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse /default.htm FDA Briefing Document Page 4 June 23, 2016 II. Substances Nominated for Inclusion on the Section 503A Bulk Drug Substances List (in order of discussion at the meeting) A. Chrysin (Tab 1) 1. Nominations (Tab 1a) (a) Fagron (b) International Academy of Compounding Pharmacists (c) National Community Pharmacists Association 2. FDA Review (Tab 1b) B. Cesium Chloride (Tab 2) 1. Nominations (Tab 2a) (a) American Association of Naturopathic Physicians (b) Alliance for Natural Health USA (c) Integrative Medical Consortium (d) McGuff Compounding Pharmacy Services, Inc. 2. FDA Review (Tab 2b) C. Sodium Dichloroacetate (Tab 3) 1. Nominations (Tab 3a) (a) McGuff Compounding Pharmacy Services, Inc. (b) Alliance for Natural Health USA (c) Integrative Medical Consortium (d) American Association of Naturopathic Physicians 2. FDA Review (Tab 3b) D. Pyruvic Acid (Tab 4) 1. Nominations (Tab 4a) (a) Fagron 2. FDA Review (Tab 4b) FDA Briefing Document Page 5 June 23, 2016 E. Tea Tree Oil (Tab 5) 1. Nominations (Tab 5a) (a) National Community Pharmacists Association (b) International Academy of Compounding Pharmacists 2. FDA Review (Tab 5b) F. 2,3-Dimercapto-1-propanesulfonic acid (DMPS) (Tab 6) 1. Nominations (Tab 6a) (a) Alliance for Natural Health USA (b) American Association of Naturopathic Physicians (c) Integrative Medical Consortium (d) McGuff Compounding Pharmacy Services, Inc. (e) International Academy of Compounding Pharmacists 2. FDA Review (Tab 6b) FDA Briefing Document Page 6 June 23, 2016 III. Draft Points to Consider A. June 23, 2016, a.m. session Draft points to consider for the PCAC Regarding Whether to Include Certain Bulk Drug Substances on the 503A Bulk List 1. FDA is proposing that chrysin NOT be placed on the list of bulk drug substances that can be used in pharmacy compounding in accordance with section 503A of the FD&C Act (“the 503A bulk list”). Should chrysin be placed on the list? 2. FDA is proposing that cesium chloride NOT be placed on the 503A bulk list. Should cesium chloride be placed on the list? 3. FDA is proposing that sodium dichloroacetate NOT be placed on the 503A bulk list. Should sodium dichloroacetate be placed on the list? ________________________________________________________________________ B. June 23, 2016, p.m. session Draft points to consider for the PCAC Regarding Whether to Include Certain Bulk Drug Substances on the 503A Bulk List 1. FDA is proposing that pyruvic acid for topical use be INCLUDED on the 503A bulk list. Should pyruvic acid for topical use be placed on the list? 2. FDA is proposing that tea tree oil NOT be placed on the 503A bulk list. Should tea tree