On August 8, 2024, the US Food and Drug Administration (FDA) partially revised the availability of certain glucagon-like peptide 1 (GLP-1) medications on the FDA’s shortage list. In particular, FDA updated the availability of certain semaglutide injections and all tirzepatide from “limited availability” to “available.” However, the FDA’s shortage list maintains the status of semaglutide and tirzepatide as “currently in shortage.” As anticipated, the national shortage of certain GLP-1 medications appears to be coming to an end. Other GLP-1 medication active pharmaceutical ingredients (APIs), such as liraglutide, remain listed as “limited availability” in the drug shortage database.
An end to the shortage has important implications for industry stakeholders at various points in the medications’ supply chain. Compounding pharmacies and providers should be aware of the impact this change in shortage status has on their operations.
KEY TAKEAWAYS
- FDA has begun updating the availability status of GLP-1 medications, suggesting that the national shortage is ending.
- Compounding pharmacies should understand the implications of this change for their operations, including a greater need for documenting prescriber determinations of need and/or changing the compounded product.
- FDA’s view on compounding remains focused on safety and necessity, especially during drug shortages.
In Depth
BACKGROUND
Under Section 503A of the Federal Food, Drug, and Cosmetic Act (FDCA), compounded drug products must meet certain conditions to qualify for exemptions from certain statutory requirements concerning compliance with current good manufacturing practices, labeling with adequate directions for use, and new drug applications. The FDCA includes criteria to determine which APIs may be used in compounded human-health medications, including APIs that appear on the FDA shortage list.
FDA places drugs on the shortage list when there is a recognized national shortage of a medication that can impact patient care and treatment plans. Semaglutide and tirzepatide are components of FDA-approved drug products indicated for Type 2 diabetes glycemic control and chronic weight management and have appeared on FDA’s drug shortage list in various forms since 2022. As a result, compounded drug products containing these APIs are eligible for the exemptions under Sections 503A or 503B of the FDCA to ensure continued patient access to the medications, provided the compounders meet all applicable conditions.
Due to the shortage, various GLP-1 medications, including semaglutide, tirzepatide, and liraglutide, became eligible for compounding under the above exception, which has led to an increase in GLP-1 compounding activities. Pharmacies, particularly those operating under Section 503A, ramped up their compounding efforts to meet the demand for the GLP-1 medications. Such pharmacies have argued that this increase in compounding allows patient care to be maintained during a shortage. Compounded medications containing GLP-1 APIs may be lawfully marketed under federal law, subject to certain restrictions on claims of safety and efficacy, as compounded medications are not evaluated by FDA for safety, effectiveness, or quality.
Section 503A
Under Section 503A, a compounded drug product must be compounded by a licensed pharmacist in a state-licensed pharmacy or federal facility or by a licensed physician to qualify for exemptions from the current good manufacturing practice requirements, the labeling of adequate directions for use requirements, and drug approvals under new drug applications or abbreviated new drug applications. Compounding pursuant to 503A is for making and distributing medications based on individual patient prescriptions.
Section 503A restricts the compounding of drugs that are “essentially copies” of a commercially available drug. A compounded medication is essentially a copy if:
- The compounded medication has the same API as the commercially available drug product;
- The APIs have the same, similar, or an easily substitutable dosage strength; and
- The commercially available drug product can be used by the same route of administration as prescribed for the compounded drug.
Under Section 503A, essential copies of commercially available drug products can be compounded as long as the compounding is not done “regularly or in inordinate amounts.” However, FDA does not consider a drug to be commercially available when it appears on FDA’s drug shortages list. Therefore, the “essentially a copy” limitation does not apply to drugs compounded when in shortage. Nevertheless, a compounder would need to ensure all other conditions of Section 503A have been met, including compounding based on a valid prescription for an identified individual patient.
ANALYSIS
Pharmacies and providers relying on the drug shortage exception will need to adapt their practices to comply with the requirements of compounding when a medication is no longer on the shortage list. In a post-shortage scenario, stakeholders also should refer to the FDA guidance titled “Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act” to ensure they are in compliance with the FDCA. For both sterile and nonsterile compounding, it is essential to consider what medications are being batched in the context of FDA’s definition. If the answer to any of the following three questions is “yes,” then the change in shortage status may impact your compounding practices:
- Does your pharmacy prepare compounded medications from APIs of GLP-1s?
- Do you prepare “essentially copies” of GLP-1s?
- Do you prepare significant amounts of compounded medications from APIs to support other facilities in your network?
If you answered “yes” to any of the above questions, the change in shortage status means that your facility must return to traditional methods of compounding GLP-1 medications.
503A Compounding Pharmacies
Traditional methods of compounding for 503A compounding pharmacies include compounding pursuant to a valid prescription for an identified patient and not compounding copies “regularly or in inordinate amounts.” Moreover, to be eligible for compounding at a 503A compounding pharmacy, an API must:
- Be a component of an FDA-approved drug product;
- Have an applicable US Pharmacopeia or National Formulary monograph; or
- Appear on the 503A Bulks List published by the FDA.
If semaglutide and tirzepatide are removed from the FDA’s drug shortage list, 503A compounding pharmacies cannot compound what would be considered “essentially a copy” unless the medication is being made for a patient with a change in formulation that the prescriber determines will provide a significant difference for the identified patient, such as the removal of an inactive ingredient allergen. This significant difference should be documented in the prescription.
McDermott will continue to monitor the shortage status of GLP-1 medications and the impact on the industry.
Michael Chacón, a summer associate in the Washington, DC, office, also contributed to this article.
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