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Understanding tirzepatide compounding restrictions
The FDA’s tirzepatide compounding rules present challenges for pharmacies, with deadlines in February and March of 2025, requiring compliance to avoid legal and regulatory risks.
The FDA officially removed tirzepatide from its drug shortage list on December 19, 2024, but the regulatory environment for compounding pharmacies remains convoluted. Pharmacies that have been compounding tirzepatide under emergency provisions must now prepare for tighter restrictions, legal scrutiny and evolving compliance risks.
While the shortage designation previously allowed 503A and 503B pharmacies to compound tirzepatide without violating FDA regulations, that window is closing. For example, 503A compounding pharmacies must cease producing copies of the drug by February 18, 2025, while 503B outsourcing facilities have until March 19, 2025.
According to Martha M. Rumore, Senior Counsel and pharmacist attorney at Frier Levitt’s Life Sciences Group, compounding will still be permissible under specific conditions, but pharmacies must tread carefully.
FDA’s enforcement timeline
The FDA’s regulatory grace period is designed to allow pharmacies time to transition away from compounding tirzepatide in its most common forms. However, Rumore warns that compliance is not as straightforward as merely ceasing production after these deadlines.
"After February 18, 503A pharmacies may still compound tirzepatide, but they may not compound 'essentially a copy.' Section 503A prohibits compounders from producing drugs that are essentially identical to FDA-approved products unless there is a documented medical necessity," she explained.
A compounded version is considered "essentially a copy" if it meets the following criteria:
- It contains the same active pharmaceutical ingredient (API).
- It has a similar or easily substitutable dosage strength (±10%).
- It shares the same route of administration as the commercially available product.
Pharmacies may still compound tirzepatide under Section 503A if a physician determines a patient requires a significant modification, such as an alternative formulation due to an allergy. However, this justification must be explicitly documented on the prescription.
Legal risks and regulatory crackdowns
Pharmacies that continue to compound tirzepatide beyond the permitted grace period without meeting the necessary exceptions risk severe FDA enforcement actions.
"There is no grace period for pharmacies that fail to meet U.S. Pharmacopeia (UPS) quality standards or use improperly sourced tirzepatide APIs labeled 'for research use only,'" warned Rumore." The FDA will take immediate action against such violations."
Additionally, the FDA has been collaborating with state boards of pharmacy to conduct inspections, often triggered by MedWatch adverse event reports or consumer complaints. Independent pharmacies should be prepared for heightened regulatory scrutiny.
Beyond FDA oversight, brand manufacturers like Eli Lilly have aggressively pursued legal action against compounding pharmacies. The company has sent cease-and-desist letters to compounders, filed lawsuits against clinics and spas distributing unauthorized tirzepatide and even petitioned the FDA to ban compounding of GLP-1 receptor agonists entirely.
"Tirzepatide’s manufacturer has asked the FDA to place the drug on the 'Demonstrably Difficult to Compound List.' If the FDA agrees, all compounding of tirzepatide would be prohibited," Rumore highlighted.
Market growth and competitive pressures
Despite regulatory challenges, the GLP-1 receptor agonist market is projected to reach $157.5 billion by 2035, growing at a compound annual growth rate of 11.1%. This boom is driven by increasing demand for obesity and diabetes treatments, putting additional pressure on independent pharmacies to remain competitive.
Compounded GLP-1 medications, including tirzepatide and semaglutide, remain a cash-pay business, but insurers are beginning to cover certain formulations. With this shift, pharmacy benefit manager (PBM) audits will likely increase, requiring pharmacies to prove clinical necessity and appropriate dispensing practices.
"Many GLP-1s are prescribed off-label, which may prompt post-dispensing reviews by PBMs. Pharmacies should ensure their documentation is airtight," Rumore advised.
Best practices for compliance and risk mitigation
To navigate these regulatory and legal complexities, independent pharmacies must prioritize the following:
- Strict adherence to USP standards. Ensure all compounded formulations meet current good manufacturing practices.
- Supplier due diligence. Vet API sources thoroughly and confirm Certificates of Analysis meet regulatory requirements.
- Cautious marketing strategies. Avoid direct comparisons to brand-name drugs to minimize the risk of trademark infringement claims.
- Comprehensive compliance training. Invest in staff education on evolving federal and state regulations.
- Legal consultation. Seek expert guidance before entering agreements with prescribers, central fill facilities or 503B manufacturers.
The future of compounded GLP-1 medications
The future of compounded GLP-1 drugs remains uncertain, especially as manufacturers push for stricter regulations. Some experts anticipate legal battles between independent pharmacies and pharmaceutical companies, which could shape the regulatory landscape for years to come.
"There’s a lot at stake," Rumore concluded. "Some of the manufacturer’s legal arguments challenge the very nature of pharmaceutical compounding itself. It’s a pivotal time for independent pharmacies, but those who stay vigilant and compliant will continue to play a vital role in patient care."
Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.
