Legal & Regulatory Developments in 503A Compounding: Part 2 – Shortage List and Other Drug Compounding Updates

There have been numerous legal and regulatory developments over the past year that pertain to 503A pharmacy compounding. In Part 1 of this two-part series, we discussed revisions to the United States Pharmacopeia’s (“USP”) guidelines for sterile and nonsterile compounding and veterinary compounding, as well as the future of interstate distribution following Wellness Pharmacy v. FDA. In Part 2, we review the current state of compounding certain drugs on the shortage list as well as peptides, DTE, semaglutide, β lactams, ibuprofen suspension, and bHRT and proposed legislation to fill regulatory gaps.

Shortage Lists

FDA’s interim Guidance for 503A compounding of shortage drugs was meant to be temporary and withdrawn once COVID-19 is over.[1] The Guidance states that 503A compounders are permitted to compound a drug that is “essentially a copy of a commercially available drug” or for providing a drug to a hospital without a patient-specific prescription if several conditions are met. The drug must be on a list of products used for hospitalized patients with COVID. The list of 14 drugs was last updated in December 2021. 503A pharmacies that compound these products have additional requirements placed on them, such as reporting adverse drug events within 15 days and notification to the State Board of Pharmacy that they are compounding these specific drugs.

Likewise, the FDA 506(E) shortage list is a much larger and ever-changing list of drugs on short supply. The provision of 503A that applies to compounding a drug product that is “essentially a copy of a commercially available drug” does not apply to compounding a drug on the shortage list because FDA does not consider drugs on the list to be “commercially available.”  While these drugs can be compounded by a 503A compounding pharmacy, it must be pursuant to a patient-specific prescription. Proposed legislation, namely, the Patient Access to Urgent Use Pharmacy Act (HR 3662), would waive the patient specific prescription requirement for compounding such drugs. This would fill the regulatory gap for compounding shortage drugs by 503A pharmacy compounders.

Status of Compounding Peptides, DTE, Semaglutide and bHRT

In November 2022, FDA released a Guidance outlining its enforcement discretion policy for compounding of certain β lactams such as amoxicillin which are on shortage.[2] The issue pertained to the inability of 5093A compounders to prepare compounded versions because of the requirement for “complete and comprehensive separation from non-β lactam products.”

Syringes are being compounded for semaglutide and other twin creatins which are on the FDA shortage list due to the popularity of their FDA approved twin indications for both diabetes and weight loss. Since semaglutide is FDA approved and on the shortage list, it can be compounded by 503A compounders for patient-specific prescriptions. The issue, however, is that often what is being compounded is not semaglutide but the sodium salt which is not FDA approved, nor on the shortage list. The patent holder is suing several generic companies for patent infringement.

Peptides with greater than 40 amino acids are considered proteins and biologics which cannot be compounded unless the pharmacy has a biologics license application (“BLA”). Since 503A pharmacies cannot obtain a BLA, this effectively bans them from compounding peptides. Most peptides, even those not considered biologics with less than 40 amino acids, arguably do not meet the legal requirements for compounding (e.g., USP/NF monograph, an ingredient in an FDA-approved drug or on the bulks list). Some are FDA approved and can be compounded. However, it is extremely important to be certain what you are asked to compound falls within the permitted to compound category.

Based on the inactive ingredient thyroglobin, the FDA recently classified desiccated thyroid extract (“DTE”) as a biologic and sent letters to that effect to the National Association of Boards of Pharmacy (“NABP”).[3] Since DTE has a USP/NF monograph, 503A pharmacies have been compounding it. One of the issues here is that the active ingredient does not meet the definition of a biologic, a biologic cannot be classified based on an inactive ingredient which does not even appear in the USP monograph or commercial product labeling. Clearly, the Notice and Comment process proscribed by the Administrative Procedures Act was circumvented and an inactive ingredient is not a protein for the purposes of the statutory definition of a biological product. FDA recently stated it will exercise enforcement discretion with compounders of DTE.

FDA is currently considering placing eleven hormones (e.g., estradiol, estrone, estriol, progesterone, testosterone) used in Compounded Bioidentical Hormone Therapy (“cBHT”) on a “difficult to compound list”, effectively banning compounding of these ingredients. Already banned from compounding are hormones recently classified as biologics which includes such fertility compounds as HCG, FSH and HMG. FDA tried unsuccessfully in 2008 and 2018 to ban bHRT. Grassroots efforts to preserve patient access to bHRT involve a legislative, regulatory and legal multi-prong approach.

In January 2023, FDA issued a Guidance permitting 503B facilities to temporarily compound ibuprofen suspension.[4] In February 2023, FDA updated its Guidance to further bolster access to ibuprofen suspensions by permitting 503B facilities to supply compounded ibuprofen suspension to retail and hospital pharmacies to dispense to patients for home use (i.e. resale). The updated guidance clarifies the beyond use date, specific concentration permitted and requirements for antimicrobial testing.[5] Acetaminophen solution which is also on shortage is not addressed in the new Guidance.

There are certainly many legal and regulatory developments which present opportunities as well as challenges for pharmacy compounders.

How Frier Levitt Can Help

Frier Levitt routinely represents a wide array of compounding pharmacies and has supported the efforts of health professionals and clients to prescribe and compound. In addition to this advocacy work, Frier Levitt can perform due diligence and analyze compounding practices for FDA, USP, and state-specific regulatory compliance, including medical necessity documentation, labeling, reimbursement issues, and infrastructure. We also prepare practice-specific compounding policies and procedures that provide clear guidelines, standards and training for staff. For legal and regulatory advice to address this latest effort to limit compounding, please contact Frier Levitt for more information.

 

[1] Guidance for Industry. Temporary Policy for 503A for Hospitalized Patients During COVID Emergency. Center for Drug Evaluation & Research. Food and Drug Administration. May 21, 2021.

[2] Immediately In Effect Guidance for Industry. Compounding Certain Beta-lactam Products in Shortage Under Section 503A of the Federal Food, Drug, and Cosmetic Act. Center for Drug Evaluation and Research. Food and Drug Administration. Nov 2022.

[3] Letter from Shannon Glueck, Branch Chief, Office of Compounding and Compliance, FDA to Lemrey “Al” Carter, Executive Director, NABP, dated September 16, 2022.

[4] Guidance for Industry. Compounding Certain Ibuprofen Oral Suspension Products Under Section 503B of the Federal Food , Drug, and Cosmetic Act. Center for Drug Evaluation and Research. Food and Drug Administration. January 2023.

[5] Updated February 9, 2023. Replaces January Guidance.

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