The Practice of Compounding, Associated Compounding Regulations, and the Impact on Dermatologists

July 2018 | Volume 17 | Issue 7 | Supplement Individual Articles | 17 | Copyright © July 2018

James Quertermous MD,a Seemal Desai MD,b Julie Harper MD,c Mark Lebwohl MD,d Abel Torres MD,e Leon H. Kircik MDd,f

aLoma Linda University School of Medicine, Loma Linda, CA bInnovative Dermatology, Plano, TX; The University of Texas Southwestern Medical Center, Department of Dermatology, Dallas, TX cDermatology and Skin Care Center of Birmingham, Birmingham, AL dIcahn School of Medicine at Mount Sinai, NY eLoma Linda University School of Medicine, Loma Linda, CA fIndiana School of Medicine, Indianapolis, IN Physicians Skin Care, PLLC, Louisville, KY DermResearch, PLLC, Louisville, KY Skin Sciences, PLLC, Louisville, KY

compounding. Category 2 includes substances that are significant safety concerns and cannot be used in compounding. Category 3 includes ingredients that have insufficient evidence for their safety by FDA standards. Under section 503A of the FDCA, compounding pharmacies may use bulk active ingredients if they meet one of three criteria: the substances comply with USP or NF monograph standards, are FDA-approved human drug products, or FDA category 1 active ingredients.10 Notable medications used in dermatology that appear under 503A Category 1 include cantharidin, capsaicin, glycolic acid, kojic acid, glutathione, and squaric acid dibutyl ester. Under section 503B of the FDA, an outsourcing facility cannot use bulk active ingredients unless they are in FDA category 1 or exist on the FDA drug shortage list when the medication is compounded, distributed, and dispensed.11 The FDA allows for new nominations and re-nominations of bulk drug substances. Following review of these agents, the FDA categorizes the drug and updates the bulk substance list monthly. Currently until the FDA finalizes its lists of bulk active ingredients on the 503A and 503B lists, it does not plan to take action against a compounding facility that does not meet the above stated FDCA conditions so long as the following conditions are met: the active ingredient is manufactured by a company registered with the FDA under section 510 of the FDCA, it includes a valid certificate of analysis, it complies with USP, and is compounded in compliance with other stipulations in the FDCA.10,11Pharmacy and In-Office Compounding Regulations versus Recommendations and How This Affects CliniciansAll physicians must adhere to compounding regulations set forth by the FDA and their respective state medical, pharmacy, and health boards. Legally, pharmacies and clinicians must adhere to regulations, while recommendations that are not set forth by regulations are not binding. Provisions of the DQSA are considered law. For other aspects of the FDCA, however, the FDA has published several draft documents providing guidance on compounding human drug products, prescription requirements, and facilities in which compounding occurs. While these are technically non-binding recommendations, many authorities interpret these draft guidelines as the law. This distinction between recommendations and regulations is often poorly understood in the clinical community, leading to confusion among practitioners on what can and cannot be done in the office setting.Oversight of in-office compounding occurs at the state level by the medical and pharmacy boards. In fact, states are responsible for their own laws and regulations pertaining to compounding medications. Consequently, there is significant inter-state variability on policies related to compounding and often these policies are not specific to nonpharmacists (eg, physicians). In 2016, the U.S. Government Accountability Office (GAO) surveyed state pharmacy boards in all 50 U.S. states on the settings in which drugs are compounded, state laws and policies, and communication between the states and the FDA. Highlights from this survey include: 1) there is a lack of quantitative and qualitative data on compounded drugs within states, 2) less than 20 percent of states reported having physician-specific compounding laws, regulations, and policies, and 3) while most states are satisfied with their communication with the FDA, there are still challenges. Despite these shortcomings, nearly all states reported having drug compounding laws, regulations and policies that are enforceable if upon inspection the state finds the compounding facility noncompliant.12 A second national assessment survey of 43 U.S. states commissioned by the Pew Charitable Trusts highlighted the inter-state variability in policies and dissension from federal law. This survey found that nearly half of the states that responded to the survey required adherence to the USP General Chapter <797> on sterile compounding, 60 percent were not required to report adverse events related to compounding, and 65 percent allowed pharmacies to dispense compounded medications without a prescription. The latter survey responses conflict with recently clarified federal law that commands receipt of a patient-specific prescription prior to dispensing compounded drugs.13The Joint Commission has published a chart called “Pharmacy Rules/Regulations by State for Compliance with USP 797 Medication Compounding” as a resource for pharmacists to clarify the state-specific laws. For instance, in New York, the State Board of Pharmacy oversees compounding in pharmacies and does not require full compliance with the USP General Chapter <797>.5 This chart, however, only references regulations as they pertain to pharmacists and the rules may differ for physicians. According to a representative at the New York State Board of Pharmacy, the New York State Board of Medicine oversees physician compounding and physicians are expected to follow both USP and FDA regulations. This highlights the point that state compounding laws often do not specifically address compounding outside of pharmacies. Physicians must familiarize themselves with their respective state’s regulations and which governing board oversees compounding practices.A major factor influencing a physician’s ability to compound are the upcoming changes to the USP General Chapter <797> Pharmaceutical Compounding – Sterile Preparations. The previous edition of this chapter was published June 2008 and is being updated. Revisions were proposed in September 2015 with plans for these to be finalized in September 2018 after an opportunity for public comment. Proposed revisions include consolidating the previous three compounding sterile preparations (CSPs) risk categories into two categories – Category 1 and Category 2 – based primarily on the conditions under which they are made and the time within which they will be used. Category 1 CSPs have a shorter beyond use date (BUD) and may be prepared in a segregated compounding area; Category 2 CSPs have a longer BUD and must be prepared in a cleanroom environment. For example, Category 1 CSPs are assigned a maximum BUD of 12 hours or less at controlled room temperature or 24 hours or less if refrigerated if made in accordance with all the applicable standards for Category 1 CSPs. Category 2 CSPs have longer BUDs based on