HHS Issues Interim Enforcement Discretion Policy for Compounding of 6 Peptides

The U.S. Department of Health and Human Services (HHS) on October 28, 2026, published a notice in the Federal Register announcing an Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances (Policy). The Policy, signed by HHS Secretary Robert F. Kennedy Jr., describes the circumstances in which HHS does not intend to take enforcement action against state-licensed pharmacies, federal facilities and licensed physicians that compound drug products using six peptide bulk drug substances while the list of bulk drug substances that can be used in compounding under Section 503A of the Federal Food, Drug, and Cosmetic Act (FDCA) is developed through rulemaking.

HHS states that by making these peptides more available, the Policy is intended to "discourage the continued, widespread use of certain peptides often labeled as 'research use only' supplied by foreign manufacturers that pose a safety risk to US patients" and give patients "a more controlled alternative." HHS also states that the Policy "advances patient choice and freedom while appropriately protecting patient safety."

Notably, the Policy was issued by the HHS Office of the Secretary rather than the U.S. Food and Drug Administration (FDA), the agency that administers Section 503A. This unusual procedural posture is significant because HHS is creating an interim pathway for access despite FDA scientific reviewers' earlier recommendation against adding these peptides to the 503A Bulks List.

The Policy allows access under specified conditions while leaving the substances' ultimate status to the formal 503A rulemaking process. It follows the July 2026 vote of FDA's Pharmacy Compounding Advisory Committee (PCAC), which recommended adding six of seven reviewed peptides to the 503A Bulks List, as discussed in a previous Holland & Knight alert. It also follows the October 14, 2026, submission of an Interim Access Policy for Compounding Using Certain Peptides to the Office of Management and Budget.

Background

Section 503A exempts certain patient-specific drugs compounded by a licensed pharmacist in a state-licensed pharmacy or federal facility or by a licensed physician from FDA new drug approval, adequate directions for use labeling and current good manufacturing practice (CGMP) requirements, provided certain conditions are met. Among those conditions, a bulk drug substance used in compounding must:

• comply with an applicable U.S. Pharmacopeia or National Formulary monograph, if one exists
• be a component of an FDA-approved drug if no monograph exists, or
• appear on the 503A Bulks List established by regulation

The bulk drug substance must also be manufactured by an establishment registered under Section 510 of the Act and accompanied by a valid certificate of analysis (COA), and the compounded product must be based on a valid patient-specific prescription.

None of the six peptides currently satisfies these criteria. Their removal from FDA's "Category 2" – bulk drug substances that may present significant safety risks – on April 22, 2026, did not change that status. Although FDA's Center for Drug Evaluation and Research recommended against listing the peptides, HHS relies in Appendix B on the PCAC's contrary vote, newly documented historical use, updated lot-specific characterization data and the safeguards built into the Policy's conditions to support interim access.

The Policy

What's in the Covered Peptides and Permitted Routes of Administration Policy

The Policy's 503A Interim Access List (Appendix A) consists of six peptides. Appendix B limits each peptide to a specified form and route of administration:

• BPC-157 Acetate. Subcutaneous, intramuscular, oral and topical dosage forms
• TB-500 Acetate. Subcutaneous or intramuscular injectable dosage forms
• Epitalon Acetate. Subcutaneous or intramuscular injectable dosage forms dispensed in intermittent courses
• Semax (Free Base). Intranasal use
• KPV Acetate. Topical and oral dosage forms
• MOTS-c Acetate. Subcutaneous or intramuscular injectable dosage forms

In each case, the product must be compounded from an active pharmaceutical ingredient (API) accompanied by a COA meeting the conditions of the Policy.

Conditions for Enforcement Discretion

Until a peptide is addressed in a final rule as being included or not included on the 503A Bulks List, HHS does not intend to take action against a state-licensed pharmacy, federal facility or licensed physician compounding a drug product using a covered peptide when all of the following circumstances are present:

1. 503A Interim Access List. The peptide bulk drug substance appears in Appendix A to the Policy.
2. Identity. The peptide has the identity – including amino acid sequence, chemical structure, molecular weight and molecular formula – and route-of-administration limitations described in Appendix B.
3. Characterization. The bulk drug substance comes from an FDA-registered facility and is characterized and identified in a valid COA that includes test results consistent with FDA's existing guidance-based criteria, covering identity, purity, potency and the absence of harmful contaminants such as endotoxins, heavy metals, microbial contamination and impurities.
4. Original Manufacturer. The original manufacturer of the bulk drug substance – not a subsequent packer, repacker, labeler or distributor – is registered with FDA, complies with CGMP and other FDCA requirements, and lists the physical location of its facility on the COA provided to the compounder. If the substance is obtained through an FDA-registered repacker, relabeler or reseller, that entity must itself have performed and documented appropriate vendor validation of the manufacturer and validation of the manufacturer's COA.
5. Reporting. The compounder reports serious adverse events and product quality issues to FDA's MedWatch program and the states where the products are compounded and sent, if different.
6. Labeling. Product labeling includes the statement: "This is a compounded drug product. Not for resale."
7. Single API. The compounded drug product contains only a single API listed in Appendix A.
8. Route of Administration. If a peptide is compounded in an oral dosage form, the compounder is expected to maintain documentation confirming that the specific formulation provided to the patient achieves an adequate level of oral bioavailability in humans.
9. Drug Delivery Device. The only drug delivery device co-packaged with or containing the compounded drug is an FDA 510(k)-cleared syringe.
10. Other FDCA Requirements. The drug product is compounded in compliance with all other applicable FDCA requirements, including the prohibition on compounding under insanitary conditions, Section 503A's patient-specific prescription requirement and state-specific compounding pharmacy requirements (e.g., state boards of pharmacy requirements).

What the Policy Does Not Do

The Policy is narrow. It does not add any peptide to the 503A Bulks List, and compounded products made under it remain unapproved drugs. HHS notes that FDA's future rulemakings may propose adding some or all of these peptides to the list based on the available evidence.

The Policy also does not establish any rights for any person. HHS may revisit it, in whole or in part, if a safety signal or product quality issue arises. The Policy does not extend to research-use-only API, compounding that falls outside its conditions or peptides not listed in Appendix A.

Finally, the Policy addresses only federal enforcement under the FDCA. Moreover, particularly because 503A compounding pharmacies are primarily regulated by state boards of pharmacy and departments of health, the Policy does not displace applicable state laws or prevent state agencies from independently restricting, prohibiting or conditioning the compounding of these peptides.

Takeaways and Considerations

It is worth reemphasizing that this Policy merely reflects only HHS' current and temporary exercise of enforcement discretion. The Policy has no formal effect of law, nor is it binding on HHS or the public. Though the Policy is a welcome development for 503A compounders, it offers temporary protection only to those that satisfy every condition. The resulting framework therefore remains less durable than inclusion on the 503A Bulks List through notice-and-comment rulemaking.

HHS expressly states that the Policy creates no rights and may be revisited, in whole or in part, if safety signals or product quality concerns emerge. Stakeholders should not rely on the Policy as a long-term legal pathway for compounding peptides. Moreover, compounders and their API suppliers should consider the following steps:

• Requalify the Supply Chain. Confirm that each peptide API traces to an FDA-registered, CGMP-compliant original manufacturer whose facility location appears on the COA. Where product is sourced through a repacker, relabeler or reseller, obtain documentation of that entity's vendor validation and COA validation. Discontinue any research-use-only sourcing.
• Audit COAs Against Appendix B. Verify that each COA contains every required data element and test result, identifies the analytical methods used and matches the identity specifications for the covered salt form.
• Update Labeling and Reporting Procedures. Add the required "Not for resale" statement and adverse event reporting instructions to patient labeling and implement MedWatch and state reporting procedures that capture the required product information.
• Maintain Baseline 503A Compliance. Section 503A's other requirements, including the patient-specific prescription requirement and prohibition on insanitary conditions, continue to apply in full.
• Review State Law. Confirm that compounding these peptides is permitted under the pharmacy laws and board of pharmacy rules of each state in which products are compounded or dispensed. State compounding laws generally do not depend on federal legal status, particularly informal federal enforcement discretion and, as FDA has previously acknowledged, state boards of pharmacy will continue to oversee and regulate the practice of pharmacy, including sterile and/or nonsterile compounding.

Next Steps

Written comments may be submitted through Regulations.gov on Docket No. HHS-OASH-2026-0496 through November 13, 2026. Interested parties should also monitor forthcoming FDA rulemaking on the 503A Bulks List and any HHS revisions to the Policy. That rulemaking will be the more consequential long-term action because it will determine whether these peptides become formally eligible for 503A compounding rather than remaining subject to a temporary and revocable policy of enforcement discretion.

The regulatory environment remains fluid. The Policy departs from the recommendations of FDA scientific reviewers and the entity that primarily enforces against compounders at a federal level. Because enforcement discretion depends on full compliance with each condition and can be revisited at any time, compounders, prescribers and API suppliers should keep abreast of ongoing changes.

Holland & Knight's Healthcare Team will continue to monitor these developments. Our attorneys regularly advise compounding pharmacies and API suppliers on supply chain qualification, COA review, labeling and state pharmacy law compliance. If you have questions about how the Policy affects your operations, please contact one of the authors or another member of Holland & Knight's Healthcare Team.

Information contained in this alert is for the general education and knowledge of our readers. It is not designed to be, and should not be used as, the sole source of information when analyzing and resolving a legal problem, and it should not be substituted for legal advice, which relies on a specific factual analysis. Moreover, the laws of each jurisdiction are different and are constantly changing. This information is not intended to create, and receipt of it does not constitute, an attorney-client relationship. If you have specific questions regarding a particular fact situation, we urge you to consult the authors of this publication, your Holland & Knight representative or other competent legal counsel.