Currently, Eli Lilly’s GLP-1 drugs Mounjaro and Zepbound (tirzepatide) are not on the FDA’s shortage list but compounded pharmacies are still making them. That’s unprecedented.
The demand for GLP-1 treatments has been such that shortages of Eli Lilly’s drugs and Novo Nordisk’s Ozempic and Wegovy (semaglutide) have been near-constant since their commercial release. Stepping into this void have been the compounding pharmacies that can produce versions of these drugs—which they are permitted to do for any drug on the FDA’s shortages list if they meet certain federal law requirements.
In early October, when the FDA updated the list to announce that Eli Lilly’s drugs were no longer in shortage, the avenue for compounders to make this drug appeared to be closing. However, there was a swift reaction from compounders, with the Outsourcing Facilities Association (OFA) launching a lawsuit against the FDA. The association asserted that the action was taken without the required notice and despite the agency’s warning over localized supply disruptions.
This led to the FDA reevaluating the move and deciding not to take any action against compounders in the short term, according to a court status report filed Nov. 21.
“It’s a precedent in this area. No one has ever challenged the FDA’s decision to remove a therapy from the drug shortage list,” David Rosen, partner at Foley & Lardner, told BioSpace. “In the past, if the FDA had a reasonable administrative record and a reasoned decision-making process, they got the benefit of the doubt and that was very hard to overcome. With the change in standard due to the Chevron decision, the FDA doesn’t get the deference it used to.”
FDA’s Decision Called Into Question
Before the FDA updated the drug shortage list, there was already friction between the pharma companies producing GLP-1 treatments and the compounding pharmacies. Both Novo Nordisk and Eli Lilly had launched lawsuits against compounding pharmacies over compounded versions of their treatments, suggesting that such versions may not meet the required tolerability, safety and efficacy profiles.
The FDA also expressed concern that some patients and healthcare professionals were considering unapproved versions of GLP-1 drugs for weight loss. The agency noted that this “can be risky” for patients, as these versions do not undergo its review before they are marketed.
Adam Bradbury, an analyst at GlobalData, explained to BioSpace by email that some patients are turning to compounding agencies for various reasons; often it is because they cannot access the branded version “due to a shortage, or other barriers, such as cost and insurance coverage.” However, in certain cases, the FDA has found that compounded versions of the treatments contained too little, too much or no active ingredient at all, or included incorrect or harmful ingredients, he added.
Despite the FDA’s concerns over the safety of the compounded versions, the explicit reason for tirzepatide being pulled from the drug shortage list was that there was now sufficient supply. This decision was made in dialogue with the drug manufacturer, with the agency stating that Eli Lilly had product availability and manufacturing capacity to meet present and projected national demand.
However, in its lawsuit, OFA stated that the FDA failed to propose and give notice of its action, solicit comments from interested parties and explain the rationale behind its final decision, all requirements of the Administrative Procedure Act (APA). Instead, the lawsuit contended that the FDA’s “sole consideration” in deciding the drug shortage had ended was information provided by Eli Lilly, a non-impartial entity.
The Loss of Chevron Deference
The case proposed by OFA was enough for the FDA to initially allow a further 60 days for compounders to complete orders for products made prior to the list change. A month later, the FDA again asked for more time to determine whether tirzepatide should remain off the shortage list, possibly until December 19, according to Bloomberg Law.
Effectively, this means that pharmacies will be able to sell compounded productsdespite the FDA concluding that there is sufficient supply of the commercial product, which Rosen stated is an extremely rare event for the agency. “I’m very surprised that the FDA changed its position,” he said. “I think that the process around removing drug shortages was not well elucidated in any guidance or information. I think that has caused the FDA to take a step back.”
In an emailed comment, Eva Yin, Jonathan Trinhand Daniel Orr of the law firm Wilson Sonsini Goodrich & Rosati stated that the FDA’s decision to update the drug shortage list had previously been a normal activity for the agency, as it could rely on its own interpretation of the statute. However, since the overturning of Chevron deference, it has to follow the APA and that could cause the agency issues in the future, particularly in its ability to quickly and effectively manage the drug shortage list.
To remedy this, the FDA will need to issue new regulations to manage the drug shortage list or Congress will need to provide it more explicit authority, they noted. Until then, “the FDA is going to have to think twice, or even three, or four times, before it removes a product from the shortage list in the future.”
