The U.S. Department of Health and Human Services (“HHS”) has announced a new limited enforcement discretion policy covering six peptide bulk drug substances used in compounding, a significant development for 503A compounding pharmacies and their suppliers. The policy, titled Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances, can substantially reshape the regulatory landscape for peptide compounding in the U.S. It establishes a framework under which HHS does not intend to pursue enforcement action against qualifying 503A compounding pharmacies and licensed physicians for compounding certain peptides that have not yet been formally approved for inclusion on the Food and Drug Administration’s (“FDA”) 503A Bulks List.
The announcement follows recent developments discussed in Frier Levitt’s prior article regarding the Administration’s anticipated peptide enforcement discretion policy, including the July 2026 meeting of FDA’s Pharmacy Compounding Advisory Committee (“PCAC”) and the Administration’s stated interest in expanding patient access to certain compounded peptides.
While the policy represents a potentially transformative development for compounding pharmacies, peptide manufacturers, and active pharmaceutical ingredient (“API”) suppliers, it is not an unrestricted authorization to compound or distribute peptides. Rather, HHS has established a carefully defined framework involving specific peptide identities, permitted routes of administration, API manufacturing standards, extensive testing requirements, and additional reporting obligations.
Which Peptides Are Covered?
The policy identifies six peptide bulk drug substances eligible for enforcement discretion:
| Peptide | Permitted Routes of Administration |
| BPC-157 (acetate) | Subcutaneous, intramuscular, oral, and topical |
| TB-500 (acetate) | Subcutaneous and intramuscular |
| Epitalon (acetate) | Subcutaneous and intramuscular, in intermittent courses |
| Semax (free base) | Intranasal |
| KPV (acetate) | Topical and oral |
| MOTS-c (acetate) | Subcutaneous and intramuscular |
Importantly, the policy does not extend to all forms of these peptides. The policy identifies the specific chemical structures, amino acid sequences, molecular formulas, and molecular weights covered by the enforcement discretion. Pharmacies and suppliers must therefore confirm that the actual peptide substance being manufactured, distributed, or compounded matches the identity specified by HHS.
The policy also does not automatically extend to other popular peptides, including substances that may have been nominated for inclusion on the 503A Bulks List but are not specifically identified.
Why Is HHS Changing Its Approach?
Historically, many peptides have faced significant regulatory obstacles to compounding under Section 503A of the Federal Food, Drug, and Cosmetic Act (“FD&C Act”). Under Section 503A, pharmacies generally may compound using a bulk drug substance only if the substance has an applicable United States Pharmacopeia or National Formulary monograph, is a component of an FDA-approved drug, or appears on FDA’s formally established 503A Bulks List.
For peptides that do not satisfy these criteria, compounding has presented significant regulatory risks, even where the substances have been nominated for inclusion on the Bulks List. The new policy reflects a notable change in HHS’s approach to these substances.
In explaining its decision, HHS expressly acknowledges the widespread use of research-use-only (“RUO”) peptides obtained from foreign manufacturers, as well as the potential safety risks associated with that market. Rather than continuing to restrict access to certain peptides through traditional pharmaceutical compounding channels, HHS has determined that allowing limited compounding under appropriate safeguards may provide patients with a more controlled alternative. HHS also cites additional evidence concerning historical peptide utilization, human exposure, and improved API characterization, including lot-specific certificates of analysis, that was not previously available during FDA’s evaluation of these substances.
Notably, HHS acknowledges that FDA’s Center for Drug Evaluation and Research (“CDER”) had recommended against listing the identified peptides, while PCAC voted in favor of their inclusion. The policy therefore represents an important distinction between FDA’s prior scientific and regulatory assessments and HHS’s decision to exercise enforcement discretion while formal rulemaking continues.
What Conditions Must Compounding Pharmacies Satisfy?
The policy establishes conditions that must be satisfied for a compounder to fall within the announced limited enforcement-discretion framework. Several are particularly significant.
1. APIs Must Originate from FDA-Registered Manufacturers Operating in Compliance with CGMP
The original manufacturer of the peptide bulk drug substance must be registered with FDA under Section 510 of the FD&C Act and comply with applicable current good manufacturing practice (“CGMP”) requirements. The manufacturer’s physical facility location must also appear on the certificate of analysis (“COA”).
Critically, FDA registration of a repacker, relabeler, or distributor is not sufficient by itself. The underlying API manufacturer must independently satisfy the policy’s requirements.
2. APIs Must Be Supported by Extensive Analytical Testing
The policy establishes detailed characterization and testing expectations, including verification of peptide identity, purity, potency, impurities, and potential contaminants. The policy identifies analytical methodologies and quality attributes addressing matters such as peptide sequence, residual solvents, elemental impurities, microbial contamination, bacterial endotoxins, and other peptide-specific characteristics. These requirements go well beyond merely obtaining a generic COA from an API supplier. Pharmacies should carefully evaluate whether their suppliers’ testing and documentation satisfy the policy’s specific expectations.
3. Compounded Products May Contain Only One API
HHS expressly limits enforcement discretion to compounded products containing a single API identified in the policy. This restriction has significant implications for pharmacies currently preparing combination peptide formulations. For example, the policy would not extend to a compounded product combining BPC-157 and TB-500, even though both substances individually appear on the list. This also applies to pharmacies seeking to compound these peptides in combination with other compliant non-peptide APIs.
4. Compounding Must Remain Patient-Specific
The policy applies to State-licensed pharmacies, Federal facilities, and licensed physicians operating under Section 503A. It does not eliminate Section 503A’s patient-specific prescription requirement or authorize unrestricted manufacturing of peptide products for general commercial distribution. Likewise, the policy does not independently extend enforcement discretion to outsourcing facilities operating under Section 503B.
5. Additional Reporting and Labeling Requirements Apply
Compounders are expected to report specified product information, serious adverse events, and product quality issues to FDA and relevant state authorities. Product reporting includes the active ingredient and strength, original API manufacturer and facility identifier, dosage form, and route of administration. Serious adverse events and product quality issues must be reported through FDA’s MedWatch program, and patient labeling must describe procedures for reporting adverse events and quality concerns. The policy also requires compounded products to bear the statement: “This is a compounded drug product. Not for resale.” Finally, the policy includes additional conditions addressing oral bioavailability documentation and the types of drug delivery devices that may be packaged with compounded products.
Significant Implications for API Manufacturers, Repackagers, and Distributors
Although the policy directly addresses enforcement discretion for 503A compounders, its practical implications extend throughout the peptide supply chain. In particular, manufacturers and distributors seeking to supply peptides for human drug compounding will need to distinguish themselves from traditional RUO peptide suppliers.
The policy requires that the original API manufacturer be FDA-registered and CGMP-compliant, and that the API be supported by comprehensive analytical testing. The policy also calls for documentation identifying the manufacturer, manufacturing facility, relevant processing entities, batch information, testing methodologies, and intended use in human drug compounding. Repackagers and resellers must perform and document appropriate validation of both the original manufacturer and its COA.
Manufacturers capable of satisfying these requirements may find significant new commercial opportunities supplying APIs to licensed compounding pharmacies. But it is unlikely that most manufacturers and suppliers currently operating in the RUO market will participate in this new peptide market, as the requirements indicated in the Federal Register notice would necessitate substantial changes to API sourcing, manufacturing practices, quality systems, documentation, and distribution arrangements.
Importantly, the policy does not independently authorize the importation of peptides or excuse manufacturers and distributors from applicable FDA registration, import admissibility, drug supply chain, or state licensing requirements. Foreign manufacturers seeking to participate in this market should carefully evaluate their compliance obligations before shipping peptide APIs into the United States.
Enforcement Discretion Is Not the Same as FDA Approval
Perhaps the most important distinction for pharmacies and suppliers is that the policy does not formally add these six peptides to FDA’s 503A Bulks List. Instead, HHS has announced that, where compliance with the announced requirements is met, it does not intend to pursue enforcement action while FDA continues the rulemaking process, which is estimated to take 12 to 24 months. This distinction matters because enforcement discretion does not amend Section 503A, confer FDA approval on the underlying peptides, or create an enforceable right to compound or distribute the substances.
Furthermore, the Federal Register notice expressly states that the interim policy is not binding on HHS or the public and does not establish legal rights. HHS also reserves the ability to revisit the policy, in whole or in part, if safety signals or product quality concerns arise.
Finally, the policy does not displace independent state pharmacy board requirements. Pharmacies must continue to assess whether their proposed compounding activities are permissible under applicable state law.
Accordingly, while the policy offers a meaningful opportunity for certain pharmacies to resume or initiate peptide compounding, those activities should be undertaken only after careful evaluation of the policy’s conditions and remaining regulatory risks.
What Should Compounding Pharmacies and Peptide Suppliers Do Next?
The Federal Register notice is scheduled for publication on October 30, 2026, under Docket No. HHS-OASH-2026-0496, with a public comment period extending two weeks from publication. The comment period presents an important opportunity for compounding pharmacies, API manufacturers, distributors, prescribers, and other stakeholders to address the policy’s practical implementation, including its testing requirements, reporting obligations, and restrictions on eligible formulations. Stakeholders may also wish to address whether additional peptides should be considered for future enforcement discretion or formal inclusion on the 503A Bulks List.
For now, pharmacies and peptide suppliers should consider taking several immediate steps:
Evaluate product eligibility:
Confirm that each proposed peptide, chemical form, and route of administration falls within the policy.
Review API sourcing arrangements:
Verify original manufacturer registration, CGMP compliance, COA sufficiency, and supplier qualification procedures.
Assess compounding operations:
Confirm compliance with Section 503A, applicable USP standards, patient-specific prescription requirements, and state law.
Implement reporting and labeling procedures:
Establish systems to address the policy’s product reporting, adverse event, quality issue, and labeling requirements.
Monitor further developments:
Follow the comment process, any revisions to the interim policy, and FDA’s continuing 503A Bulks List rulemaking.
How Frier Levitt Can Help
HHS’s new enforcement discretion policy represents an important development for the peptide compounding industry, potentially creating a pathway for greater patient access while imposing substantial compliance obligations on pharmacies and their suppliers. Frier Levitt regularly advises 503A compounding pharmacies, 503B outsourcing facilities, API manufacturers, repackagers, distributors, and healthcare providers regarding FDA compounding requirements, peptide regulation, API sourcing, and federal and state enforcement risks. Our attorneys can assist businesses in evaluating eligibility under the new policy, reviewing manufacturing and supply chain arrangements, assessing compliance with applicable federal and state requirements, and developing strategies to navigate the evolving peptide regulatory landscape.
Contact Frier Levitt to discuss how the new HHS peptide enforcement discretion policy may affect your pharmacy, manufacturing operations, or peptide distribution business.
For additional analysis, visit Frier Levitt’s Peptide Legal and Regulatory Resource Center and Peptides and GLP-1 practice page.
Partner, Chair of the FDA Practice
