Navigating Compounding Peptides and GLP-1s Through Regulations

Overview of the Regulatory Action

The compounding of glucagon-like peptide-1 (GLP-1) receptor agonists and other peptide-based therapeutics has become one of the most closely watched flashpoints in pharmaceutical regulation over the past two years. A recent Drug Topics report highlights the ongoing challenge facing compounding pharmacies, prescribers, and patients as they attempt to navigate a shifting regulatory landscape shaped by drug shortages, FDA enforcement priorities, and long-standing statutory limits on compounded drugs. While the underlying source article is limited in detail, the topic it addresses reflects a well-documented and rapidly evolving area of federal drug law.

Semaglutide (marketed as Ozempic and Wegovy) and tirzepatide (marketed as Mounjaro and Zepbound) have been listed on the FDA's drug shortage database for extended periods, a status that has historically permitted licensed compounding pharmacies to prepare alternative versions of these medications under specific statutory exemptions. As manufacturers have worked to resolve supply constraints, the FDA has correspondingly moved to remove these agents from the shortage list, triggering a cascade of legal and operational consequences for the compounding industry.

Legal Framework and Authority

Compounded drugs occupy a distinct legal category under the Federal Food, Drug, and Cosmetic Act (FDCA), separate from FDA-approved commercial pharmaceuticals. Two statutory provisions govern this space:

• Section 503A of the FDCA governs traditional compounding by licensed pharmacies and physicians for individual, patient-specific prescriptions. Compounders operating under 503A are exempt from FDA's new drug approval requirements, current good manufacturing practice (CGMP) standards, and labeling mandates, provided they meet conditions including patient-specific prescriptions and restrictions on advertising.
• Section 503B, added by the Drug Quality and Security Act of 2013, created a category of "outsourcing facilities" that may compound drugs in larger batches, without individual prescriptions, for office use by healthcare providers. These facilities must register with the FDA, comply with CGMP requirements, and are subject to more rigorous federal oversight than traditional 503A pharmacies.

Critically, both provisions restrict compounding of drugs that are "essentially copies" of FDA-approved commercial products, with a key exception: compounding is permitted when the approved drug appears on the FDA's official drug shortage list. This shortage-contingent exception is precisely what has enabled widespread compounding of semaglutide and tirzepatide since 2022. Once the FDA determines a shortage has been resolved, that legal justification disappears, and continued compounding of essentially identical formulations becomes vulnerable to enforcement action.

The FDA's authority to determine shortage status, and to remove drugs from that list, stems from its statutory mandate under the FDCA and is informed by manufacturer-reported supply data. The agency's removal of tirzepatide from the shortage list in December 2024, followed by semaglutide products, marked a significant inflection point, prompting immediate industry and legal pushback, including litigation from compounding trade groups such as the Outsourcing Facilities Association.

Industry Implications

The compounding peptide sector, which expanded substantially during the shortage period, now faces significant contraction and legal risk. Thousands of telehealth platforms, medical spas, and compounding pharmacies built business models around lower-cost compounded semaglutide and tirzepatide, often incorporating salt forms such as semaglutide sodium or semaglutide acetate, which manufacturers and the FDA have argued are not appropriate for compounding because they are not the active pharmaceutical ingredient found in the approved product.

This distinction matters legally. The FDA has issued warning letters and public communications asserting that compounding with salt forms of semaglutide does not fall within permissible bulk drug substance exceptions under Section 503A(b)(1)(A) or the corresponding 503B provisions, since these forms have not been demonstrated to be clinically appropriate substitutes and lack an essential inclusion on FDA's 503A/503B bulk substances lists.

Beyond the shortage-status issue, peptide compounders face separate legal exposure around other novel peptides, including retatrutide, cagrilintide, and various growth hormone-releasing peptides, none of which are FDA-approved and thus cannot be compounded from bulk substances unless they appear on FDA's designated bulk drug substances lists under Section 503A or 503B. The FDA has repeatedly signaled skepticism toward compounding unapproved peptides marketed for weight loss, longevity, or muscle growth, citing insufficient safety and efficacy data.

Compliance Considerations

For pharmacies and prescribers operating in this space, several compliance touchpoints demand attention:

• Shortage list monitoring: Compounders must continuously verify a drug's current shortage status, as FDA determinations can change with little advance notice, immediately altering the legality of ongoing compounding operations.
• Bulk substance eligibility: Only substances included on FDA's 503A and 503B bulk drug substance lists, or those meeting narrow exceptions, may lawfully be used in compounding absent an approved drug shortage.
• State board oversight: State boards of pharmacy retain concurrent jurisdiction and have increasingly aligned enforcement priorities with FDA guidance, creating a dual-layer compliance obligation.
• Patient-specific prescribing requirements: 503A compounding requires valid, patient-specific prescriptions; mass-marketed or subscription-based telehealth models compounding peptides in anticipation of demand risk running afoul of this requirement.
• Marketing and labeling restrictions: Compounded drugs cannot be promoted as equivalents or substitutes for FDA-approved products, a restriction frequently implicated in FDA warning letters to peptide clinics and pharmacies.

Looking Ahead

Litigation remains a central variable. Compounding trade associations have challenged FDA's shortage-resolution determinations in federal court, arguing the agency's process lacked adequate transparency and failed to account for continued patient access gaps, particularly for lower-income and uninsured patients unable to afford brand-name GLP-1 therapies priced above $1,000 monthly.

Manufacturers, including Novo Nordisk and Eli Lilly, have pursued parallel legal strategies, filing suits against compounding pharmacies and telehealth companies alleging trademark infringement, false advertising, and unlawful compounding of essentially copied products.

Industry stakeholders should anticipate continued FDA guidance clarifying bulk substance eligibility for popular peptides, potential rulemaking addressing salt-form compounding, and sustained enforcement activity targeting non-compliant telehealth and compounding operations. Patients and prescribers, meanwhile, face a narrowing landscape of lawful compounded alternatives, underscoring the importance of verifying that any compounding pharmacy operates within current FDA and state legal parameters.

This analysis is based on publicly available regulatory information and the referenced Drug Topics report. Readers should consult qualified legal counsel or regulatory professionals regarding specific compliance obligations, as this article does not constitute legal or medical advice.