FDA Acts to Restrict Compounding of Popular GLP-1 Therapies from Bulk Substances

The U.S. Food and Drug Administration has proposed excluding semaglutide, tirzepatide, and liraglutide from the 503B bulks list, stating there is no demonstrated clinical need for outsourcing facilities to compound these GLP-1 receptor agonists from bulk active pharmaceutical ingredients (APIs).

The 503B bulks list defines which substances outsourcing facilities may use under Section 503B of the Federal Food, Drug, and Cosmetic Act. In most cases, compounding from bulk substances is not permitted unless the substance appears on the list or the drug is listed on the FDA’s shortage database at the time of compounding, distribution, and dispensing.

No Evidence of Clinical Need

Following a review of nominations and supporting data, the FDA found that none of the three drugs meet the statutory threshold for “clinical need.” This standard requires evidence that an FDA-approved product is medically unsuitable for certain patients and that a compounded version is necessary to address that limitation.

The agency concluded that approved GLP-1 therapies remain suitable across patient populations and that compounded alternatives do not provide distinct clinical benefit. It also clarified that cost, convenience, or supply considerations do not meet the legal definition of clinical need, which is limited to situations involving patient safety or medical necessity.

Regulatory Framework and Safety Risks

Under Section 503B, outsourcing facilities may compound drugs without patient-specific prescriptions for office stock. However, these products do not undergo the same premarket review for safety, efficacy, and quality as FDA-approved medicines.

The FDA emphasized that unnecessary compounding may expose patients to avoidable risks and undermine the drug approval process. Approved drugs are supported by robust clinical evaluation and controlled manufacturing standards, while compounded products from bulk substances do not undergo equivalent premarket scrutiny.

FDA Commissioner Marty Makary stated that compounding from bulk substances is not permitted when approved drugs are available unless a clear clinical need is established, adding that the proposal aims to protect patients while maintaining a science-based and transparent regulatory process.

Public Comment and Next Steps

The agency is inviting public comments through the Federal Register docket until June 30, 2026, after which it will review submissions before issuing a final determination. The FDA continues to evaluate 503B nominations on a rolling basis.

If finalized, the decision would prevent outsourcing facilities from compounding these GLP-1 therapies from bulk substances, reinforcing reliance on approved products except in limited circumstances defined by law.

Intensifying Scrutiny on Compounded GLP-1s

The proposal aligns with a broader enforcement push by the FDA targeting compounded GLP-1 drugs in recent months. The agency has issued warning letters to telehealth platforms and compounders for misleading promotion of semaglutide and tirzepatide as alternatives to approved products, along with other regulatory violations.

As supply of approved GLP-1 therapies stabilizes, the FDA has indicated that routine large-scale compounding is no longer justified outside narrow statutory exceptions. These actions follow reports of inconsistent quality and adverse events linked to some compounded products and have coincided with legal disputes between manufacturers and compounding providers, including cases involving Novo Nordisk and Hims & Hers Health, which have since been resolved.

Reference

FDA Proposes to Exclude Semaglutide, Tirzepatide, and Liraglutide on 503B Bulks List | FDA

Federal Register: List of Bulk Drug Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act