Overview
On October 3, 2024, the US Food and Drug Administration (FDA) revised its shortage categorization of tirzepatide, a glucagon-like peptide 1 (GLP-1) medication, marking the shortage as “resolved” for all presentations of the drug. An end to the shortage has important implications for industry stakeholders at various points in the medication’s supply chain. Compounding pharmacies and providers should be aware of the impact this change in shortage status has on their operations. We discussed the potential effects of a resolution of the shortage in our previous On the Subject entitled “Weight Loss Drug Shortages Will End Soon.”
Update: On October 11, 2024, FDA agreed to reconsider its decision to remove tirzepatide from its drug shortage list in response to the complaint filed by the Outsourcing Facilities Association (OFA) and North American Custom Laboratories, LLC, doing business as FarmaKeio Custom Compounding. The litigation is stayed and tirzepatide remains off the shortage list while FDA reviews its decision (although FDA has indicated it will not take enforcement actions against the plaintiffs). Additionally, following FDA’s October 3 decision, several Congress members sent a letter to the agency encouraging the utilization of data from compounding facilities to help avoid and mitigate drug shortages. The letter also raises specific concerns about the data FDA reviews in establishing the list, urging the agency to review data outside of that which was submitted by the drug manufacturer.
Update: On November 21, 2024, the parties submitted a joint status report stating that the case should remain stayed while FDA continues to evaluate its decision to remove tirzepatide from the shortage list. The parties intend to file a further joint status report by the earlier of December 19, 2024, or within seven days of FDA’s decision on remand. Accordingly, FDA will continue to refrain from enforcement actions against essentially copies of tirzepatide until further notice.
Update: On December 19, 2024, the FDA issued a Declaratory Order confirming FDA’s October decision to remove tirzepatide from the shortage list. FDA stated it has completed its reevaluation of its decision and determined that the information and data provided by the brand manufacturer demonstrate the supply is currently meeting or exceeding demand for tirzepatide. In its Order, FDA extended its enforcement discretion for 503A pharmacies for 60 calendar days from the date of the Order (i.e., until February 18, 2025) and for 503B outsourcing facilities for 90 calendar days (i.e., until March 19, 2025). The litigation filed by the Outsourcing Facilities Association remains ongoing.
In Depth
This October revision updates FDA’s August partial revision of the availabilities for certain semaglutide and tirzepatide presentations. The FDA’s shortage list maintains the status of semaglutide as “currently in shortage,” although only one presentation – Wegovy 0.25 mg/0.5 mL – is marked for limited availability. Other GLP-1 medication active pharmaceutical ingredients, such as liraglutide, remain listed as “limited availability” in the drug shortage database. As anticipated, the national shortage of certain GLP-1 medications appears to be coming to an end.
503A compounding pharmacies will generally no longer be able to rely on the FDA shortage list exception for compounding “essentially copies” of tirzepatide products. This means that in order to regularly compound tirzepatide products (i.e., to fulfill five or more such products per calendar month), compounding pharmacies must ensure that compounded tirzepatide products do not contain the same, similar, or easily substitutable dosage strength, or that such products are not used by the same route of administration as the commercially available product. Otherwise, there must be some other change that a prescriber determines produces a significant difference for the individual patient, documented on the prescription. FDA’s guidance “Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act” indicates that changes fitting that criterion (although we note that such changes are not necessarily applicable to GLP-1 drugs) may include the removal of inactive ingredients due to patient allergy, or change from tablet to liquid form due to patient inability to swallow tablets.
For 503B compounding, outsourcing facilities may continue to dispense essentially copies of compounded tirzepatide products for orders the facility received prior to the shortage resolution for up to 60 days from when tirzepatide was removed from the shortage list (i.e., until December 2, 2024). 503B outsourcing facilities thus have a 60-day sell-through period to fulfill orders for tirzepatide that were received before October 3, 2024. 503B facilities may not compound tirzepatide products for orders received on or after October 3, 2024, and must cease distribution by December 2, 2024. 503B facilities may continue to compound and dispense tirzepatide products that are not essentially copies, as described above.
This change is not without controversy. On October 7, 2024, the OFA and North American Custom Laboratories, doing business as FarmaKeio Custom Compounding, filed a complaint in the US District Court for the Northern District of Texas alleging that FDA’s revision of tirzepatide availability constitutes a final agency action that is arbitrary, capricious, and contrary to law. The complaint cites to Loper Bright, the recent US Supreme Court decision overturning Chevron deference, as support for rejecting FDA’s interpretation of its statutory authority to maintain the shortage list.
We will continue to monitor this litigation, the shortage status of GLP-1 medications, and the impact on the industry.
