FDA’s Removal of Semaglutide and the Evolving Tirzepatide Decisions: What Compounders Need to Know

The FDA’s recent decision to remove semaglutide from the drug shortage list marks a significant shift for compounding pharmacies. With manufacturers now able to meet national demand, the emergency compounding protocols are ending, and full regulatory oversight is resuming. Meanwhile, the regulatory status of tirzepatide has been turbulent, with its removal from the shortage list finalized after a temporary hold. These changes carry critical implications for compounding pharmacies, particularly those operating under sections 503A and 503B of the FD&C Act and State Boards of Pharmacy regulations, and have already led to legal challenges, including a pending lawsuit from the Outsourcing Facility Association (OFA) against the FDA.

Semaglutide and Tirzepatide: Transitioning Back to Full Regulation

Semaglutide, a widely used GLP-1 receptor agonist for type 2 diabetes and obesity, has been in shortage since 2022. Now that supply is deemed stable, the FDA has set clear deadlines for compounders. 503A compounders must cease compounding, distributing, or dispensing semaglutide injection products (i.e., essentially a copy of commercially available products) by April 22, 2025, while 503B outsourcing facilities have until May 22, 2025. While local supply fluctuations may persist, the FDA emphasizes that enforcement will resume after these grace periods. Compounders must ensure compliance to avoid regulatory action. The Outsourcing Facility Association (OFA) recently sued the FDA for its decision to remove semaglutide from the drug shortage list.

Tirzepatide’s regulatory path has been more complex. Initially removed from the shortage list, the FDA temporarily placed a hold on its decision before ultimately finalizing its removal. Adding to this complexity is the pending lawsuit filed by the OFA against the FDA, which challenges the abrupt regulatory shift. The OFA argues that the FDA’s decision to remove tirzepatide from the shortage list without sufficient transition time places an undue burden on outsourcing facilities, many of which rely on compounding to meet patient demand.

FDA indicated that 503A compounders should cease compounding tirzepatide (i.e, essentially a copy of commercially available product) by February 18, 2025, while 503B outsourcing facilities have until March 19, 2025. However, the FDA has extended the deadline until the district court issues a decision on the plaintiffs’ preliminary injunction motion, unless that decision is made before the original deadlines, in which case the FDA will adhere to the original timeframes.

These lawsuits may continue to impact regulatory timelines and enforcement policies, and compounders should closely monitor legal developments to stay ahead of any changes.

Challenges from Drug Manufacturers: Difficult-to-Compound Petitions

In addition to regulatory changes and ongoing legal challenges, drug manufacturers Eli Lilly and Novo Nordisk have taken steps to further restrict the compounding of GLP-1 receptor agonists. Eli Lilly has submitted a petition to the FDA requesting that tirzepatide, the active ingredient in Mounjaro® and Zepbound®, be added to the FDA’s Demonstrable Difficulties for Compounding (DDC) list. Similarly, Novo Nordisk has nominated semaglutide, found in Ozempic® and Wegovy®, for inclusion on the same list. If the FDA grants these petitions, these medications would be classified as too complex to compound, effectively prohibiting pharmacists, physicians, and outsourcing facilities from compounding them.

This development could significantly impact compounding pharmacies, further limiting their ability to provide these treatments to patients. If these petitions are approved, it will be crucial for compounders to seek alternative ways to continue serving patients while maintaining full compliance with evolving regulations.

Navigating Compliance: What Compounders Must Do Now

The upcoming regulatory deadlines require immediate action from compounding pharmacies. To ensure compliance, pharmacies must conduct thorough internal audits, evaluating all standard operating procedures (SOPs), quality control measures, and documentation to align with both FDA and state regulatory requirements. Training and education should be a top priority, ensuring that all staff are well-versed in updated compliance protocols, proper documentation, and quality control processes.

Additionally, compounders must closely follow the OFA lawsuit and any subsequent regulatory changes that may result from it. If the lawsuit leads to modifications in compliance deadlines or regulatory requirements, compounders must be prepared to adjust their operations accordingly. Pharmacies must also remain vigilant regarding the difficult-to-compound petitions submitted by drug manufacturers, as a ruling in their favor could permanently restrict compounding of semaglutide and tirzepatide.

Finally, pharmacies must also adhere to state-level regulations, which may impose stricter requirements than federal laws. Compliance with both state and federal standards is essential to avoid potential penalties and ensure continued operations.

The Bigger Picture: Adapting to the New Regulatory Landscape

The FDA’s decisions on semaglutide and tirzepatide reflect a broader trend toward increased regulatory oversight. For compounders, the focus must shift from emergency production to long-term compliance and operational sustainability. By acting now—conducting audits, updating SOPs, and training staff—compounding pharmacies can position themselves for continued success in a stricter regulatory environment.

Regulatory changes are inevitable, but with proactive planning and compliance measures, compounders can navigate these transitions smoothly. The pending OFA lawsuit against the FDA and the difficult-to-compound petitions submitted by major pharmaceutical manufacturers introduce further uncertainty, but those who stay informed and adaptable will be better positioned to comply with any future regulatory shifts. The end of emergency protocols presents both challenges and opportunities. Those who adapt effectively will not only remain compliant but also gain a competitive edge in the evolving pharmaceutical landscape.

How Our Firm Can Help

Navigating the complexities of FDA regulations and compliance requirements can be challenging, but our firm is here to provide the expertise and guidance necessary to ensure your pharmacy remains compliant. We assist compounding pharmacies with regulatory assessments, internal audits, and development of updated SOPs that align with the latest federal and state standards. Our legal team closely monitors regulatory changes and legal challenges, including the OFA lawsuit and the difficult-to-compound petitions, providing real-time updates and strategic advice tailored to your business. We also offer training programs to help staff understand new compliance protocols and maintain operational efficiency.

By partnering with our firm, you can confidently navigate these regulatory transitions, avoid potential legal pitfalls, and maintain compliance with both federal and state regulations. Contact us today to learn how we can support your pharmacy in adapting to the evolving regulatory landscape.