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

the conditions in which they are prepared and stored.14,15 The consequences of these USP revisions remain uncertain, but if state pharmacy boards adopt the finalized USP guidelines, this may impact physician’s ability to continue in-office compounding.PenaltiesCurrent compounding guidelines are evolving rapidly, but it is important for physicians, pharmacies, and healthcare facilities to have a basic understanding of the laws set forth by State and Federalregulatory entities. The FDA conducts for-cause inspections of compounding pharmacies, and FDA will take aggressive action, including enforcement actions, as appropriate, to protect the publichealth. Facility and responsible individuals may be subject to Federal regulatory actions including, but not limited to, a warning letter, seizure of product, fines, and/or injunction, or referral for criminal prosecution by the United States Department of Justice. For example, the FDCA prohibits physicians from regularly compounding prescriptions that are essentially copies of commercially available drugs. A first violation is considered a criminal act and the penalty could include up to a year of imprisonment or a fine of up to $1,000, or both. A second violation is punishable by up to 3 years in prison, a fine of up to $10,000, or both, as well as mandatory exclusion from Medicare and Medicaid.16How Compounding Affects Patient Care in DermatologyAdvocates for dermatology have been involved with educating Congress, FDA, USP, and other policymakers and stakeholders on the differences between low-risk compounding in the medical office versus compounding in commercial facilities. The field of dermatology relies on low-risk in-office compounded medication to provide care to patients; some examples include buffering lidocaine, diluting triamcinolone, and reconstituting botulinum toxin.Many of the agents used by dermatologists are for topical use or for intradermal injection, which inherently carries less risk than medications used for intravenous infusion, intraocular, or intrathecal purposes. It is common practice in dermatology to take multi-use vials of 1% lidocaine with epinephrine and buffer with bicarbonate to reduce pain on injection. This compound has been shown to maintain its anesthetic and vasoconstrictive properties for up to 1 week after being prepared.17 In addition, a 2016 study by Pate et al analyzed syringes of plain 1% lidocaine and 1% lidocaine with epinephrine and/or sodium bicarbonate that were drawn from multi-use vials using routine clinic aseptic technique. They concluded that prefilled lidocaine syringes stored at controlled room temperature or controlled cold temperature are not subject to bacterial or fungal growth after 4 weeks.18 This may be due to the preservatives in multi-use vials and/or the intrinsic antimicrobial properties of lidocaine itself.19 With this information and considering national shortages, it seems reasonable for physicians to add bicarbonate or epinephrine to multi-use vials of lidocaine using aseptic technique in the clinical setting. With growing concerns of the liability associated with compounding, at least one hospital has adopted a one vial, one patient policy to ensure patient safety when injecting medications.20 Misguided legislation surrounding compounding and the associated risks have the potential to encourage other medical facilities to do the same. This superfluous approach is not only wasteful but will also amplify healthcare costs. Access is another major concern if regulations continue to heighten. Dermatologists frequently use compounded medications manufactured from outside sources for office-use. Examples of “office-use” compounded medications include pre-formulated topical numbing creams, compounded wart treatment formulations, and aluminum chloride. When obtained through traditional 503A compounding pharmacies, these frequently utilized drugs may be readily available in small amounts at an affordable price, but now, they must be patient specific. Alternatively, physicians can acquire these compounded drugs at the 503B compounding facilities, but there may be a significant delay, they may only be available in large batches a that create waste and high costs or the medications may not be available at an affordable price. While some of these products may be intended for use in the office, they may also be intended for home use. The physician is held accountable to ensure such products are produced at FDA-registered and-compliant facilities keeping in mind that FDA registration is not synonymous with meeting all FDA requirements outlined in the FDCA. There is concern from the FDA that while compounding without meeting the requirements of 503A or registering as a 503 is illegal, registration is voluntary and there may still be rogue compounding pharmacies supplying medications to unsuspecting physicians. This contradicts FDA position to direct healthcare providers towards more heavily regulated outsourcing facilities,and it creates a hurdle for patient access.Confusion surrounding compounding may discourage dermatologists from compounding in the clinical setting. In particular, dermatologists may be weary to perform such practice out of fear of hefty fines associated with the creation of an essential copy of a commercially available drug. However, if the physician compounds a product that is similar to but slightly different for a particular patient need, this may not be an essential copy. For example, when a surgeon dilutes lidocaine with epinephrine for a patient with a sensitivity to the epinephrine component, this is not an essential copy of a commercially available drug because this cannot be readily purchased. This product is different from the commercial product and is permitted by law so long as the medical necessity is documented.State legislatures, while well intentioned, continue to misinterpret the intent of the DQSA, draft guidance on pharmacy compounding, and recommendations on compounding in insanitary conditions. Already, concerns over patient safety have prompted 27 states to prohibit office-use compounding. Other state pharmacy boards