HHS Announces Interim Enforcement Discretion for Section 503A Compounding with Certain Peptide Bulk Drug Substances

Key Takeaways

• HHS states that it does not intend to take enforcement action against state-licensed pharmacies, federal facilities, or licensed physicians that compound drug products under FD&C Act section 503A using the six peptide bulk drug substances listed in Appendix A: BPC-157, Epitalon, KPV, MOTS-c, Semax, and TB-500, provided all conditions of the policy are satisfied.
• Discretion applies only if ten conditions are met, including route-of-administration limits, COA and supplier-registration requirements, MedWatch reporting, single-API products, required labeling, and a syringe-only device limit.
• The policy marks an unusual departure by the HHS Secretary from CDER recommendations against listing these six peptides. But the Secretary has done so through conditional federal enforcement forbearance, not by adding the substances to the 503A bulks list. The immediate federal enforcement posture has changed; the underlying statutory status has not. The policy therefore should not be understood as legalizing the covered peptides or making compounding with them compliant with section 503A.
• Because enforcement discretion is not legalization, the policy does not bind state regulators or eliminate private-litigation risk. State authorities may enforce independently applicable state law, and private plaintiffs may attempt to use the peptides' continuing regulatory status in state-law claims, subject to defenses including preemption and the prohibition on private enforcement of the FD&C Act.
• The policy is expressly interim and applies only until each peptide bulk drug substance is addressed in a final rule as included or not included on the section 503A bulk drug substances list (the "503A bulks list"). FDA may propose adding some or all of the listed peptides to that list based on the available evidence.
• HHS reserves the right to revisit the policy, in whole or in part, if a safety signal or product quality issue arises with a compounded drug product within its scope.
• The policy creates no rights and is not binding on HHS or the public. It is issued in draft form, and comments are due on Docket No. HHS-OASH-2026-0496 two weeks after Federal Register publication, November 13, 2026.

Background

On October 30, 2026, the Secretary of Health and Human Services published a notice of availability in the Federal Register (FR Doc. 2026-22192; RIN 0910-ZD94) announcing a draft "Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances." The notice was issued by the HHS Office of the Secretary and signed by Secretary Robert F. Kennedy, Jr.

Section 503A of the FD&C Act provides exemptions from certain provisions of the Act for qualifying compounded drugs, but only if specified conditions are met. For compounding from a bulk drug substance that is neither the subject of an applicable USP or NF monograph nor a component of an FDA-approved drug, the substance must appear on the 503A bulks list established through rulemaking. The six peptides covered by the new policy do not currently satisfy that pathway, which has created significant compliance risk for compounders using them.

HHS acknowledges that compounded drugs are not FDA-approved and therefore are not reviewed by FDA for safety, effectiveness, or quality before marketing. HHS nevertheless concludes, based on the Pharmacy Compounding Advisory Committee (PCAC) proceedings and peptide-utilization data, that there is significant interest in compounding these peptides, given the lack of availability of approved products, and that public comments may provide additional evidence for FDA to consider in rulemaking. HHS describes the interim policy as a means to expand and improve patient access while FDA reviews the substances.

Scope of the Policy

Appendices A and B: Covered Peptides

Appendix A lists six peptide bulk drug substances. Under Appendix B, each is covered only in the specified form and for the specified routes of administration:

Each of the six peptides was in FDA's Category 2 of bulk drug substances nominated for compounding from September 2023 until April 22, 2026. This means that they were evaluated by FDA for inclusion on the 503A bulks list, but FDA identified significant safety risks relating to their use. According to Appendix B, neither the placement in nor the removal from Category 2 changed any peptide's status under section 503A. For each, CDER recommended against listing, while PCAC voted in favor of inclusion. HHS expressly departs from CDER's recommendations, relying on additional characterization information from FDA-registered sources, evidence of historical use, the nature of the identified safety concerns, and the safeguards imposed by the interim policy. The precise rationale varies by peptide.

Conditions for Enforcement Discretion

The policy applies only while a covered peptide has not been addressed in a final rule and only where it is not a component of an FDA-approved drug, is not the subject of an applicable USP or NF monograph, and is not already on the 503A bulks list at 21 CFR 216.23(a). HHS states that it does not intend to take enforcement action when all of the following circumstances are present:

1. The peptide appears in Appendix A.
2. The peptide has the identity described in Appendix B (including amino acid sequence, chemical structure, molecular weight, and molecular formula) and is used only by the routes listed there.
3. The bulk drug substance comes from a facility registered under FD&C Act section 510 and has a valid certificate of analysis (COA) that includes test results consistent with the existing guidance-based criteria described by FDA (see Appendix B).
4. The original manufacturer, not a later packer, repacker, labeler, or distributor, is registered under section 510 and complies with CGMP and other FD&C Act requirements, and its physical location appears on the COA. If the substance is obtained through an FDA-registered repacker, relabeler, or reseller, that entity must have validated the manufacturer and its COA and documented that validation.
5. The compounder reports compounded products, serious adverse events (whether or not drug-related), and product quality issues to FDA's MedWatch program and to the states where the products are compounded and sent (if different). Product reports cover the active ingredient and strength per unit, the original manufacturer with its unique facility identifier, and the dosage form and route. The product labeling provided to the patient should describe the procedure for reporting adverse events and problems with identity, strength, purity, or quality.
6. Labeling states: "This is a compounded drug product. Not for resale."
7. The product contains a single active pharmaceutical ingredient listed in Appendix A.
8. For oral dosage forms, the compounder keeps documentation showing that the formulation achieves adequate oral bioavailability in humans.
9. The only drug delivery device co-packaged with or containing the product is an FDA 510(k)-cleared syringe.
10. The product complies with all other applicable FD&C Act requirements, including the ban on insanitary conditions and section 503A's patient-specific prescription requirement.

HHS states that the policy is intended in part to discourage the continued widespread use of research-use-only peptides supplied by foreign manufacturers that HHS says pose safety risks to U.S. patients, by providing a more controlled compounding alternative subject to the policy's safeguards.

Key Considerations

An Unusual Policy Shift, but Not a Permanent Resolution

The policy materially changes the immediate federal enforcement landscape, but its more important limitation is substantive: enforcement discretion is not legalization. The covered peptides have not been added to the 503A bulks list, and HHS has not otherwise changed the statutory conditions governing compounding from bulk drug substances. Durability is a separate concern. The policy can be narrowed or withdrawn, but the legal-regulatory gap persists for as long as the policy remains in effect.

Secretary-Level Intervention Is Uncommon, but Not Unprecedented

Direct departmental intervention in FDA decision making is uncommon, but it is not unprecedented. In 2011, HHS Secretary Kathleen Sebelius directed FDA to deny unrestricted nonprescription access to Plan B One-Step despite Commissioner Margaret Hamburg's public agreement with FDA scientific staff that the application should be approved. A closer structural analogy may be HHS's 2020 laboratory-developed test (LDT) policy, which barred FDA from requiring premarket review of LDTs without notice-and-comment rulemaking and was withdrawn by HHS approximately 15 months later. The statutory issues were different, but the sequence illustrates that a departmental policy displacing FDA's preferred approach can later be reversed by departmental leadership.

Why the Policy Remains Vulnerable

The principal limitation lies not in the Secretary's supervisory authority over FDA, but in the limited legal work the policy itself performs. FDA is an operating division of HHS, and the Secretary's involvement does not by itself make the policy legally defective. But supervisory authority and enforcement discretion are not substitutes for the statutory process Congress prescribed for establishing the 503A bulks list. HHS can determine how the Department will exercise federal enforcement discretion; it cannot, through that discretion alone, make conduct satisfy a statutory condition that remains unmet.

• HHS has announced conditional federal enforcement forbearance; it has not completed the statutory process for adding these substances to the 503A bulks list. The policy expressly lasts only until each peptide is addressed in a final rule, which may include or exclude the substance. Thus, the central regulatory question remains open, and qualifying for enforcement discretion should not be equated with a determination that the compounded product is lawful under section 503A.
• The adverse scientific record also has not disappeared. CDER recommended against listing each of the six peptides. HHS now identifies additional characterization data, documented historical use, and policy safeguards as grounds for interim enforcement discretion, and in several instances characterizes CDER's safety concerns as mechanistic, inferential, or based on limited information rather than observed harm. That is an important shift in how HHS weighs the record, but it is not the same as FDA determining through the drug-approval process that the peptides are safe and effective.
• Because the policy depends substantially on how current departmental leadership weighs unresolved scientific uncertainty, it is more exposed to a change in leadership or policy than a position embedded in completed rulemaking. A successor administration could revisit the same record without having to withdraw a drug approval or even first amend a final regulation.
• That vulnerability is explicit in the policy itself. HHS calls the policy interim, states that it creates no rights and is not binding on HHS or the public, and reserves the ability to revisit it, in whole or in part, if a safety signal or product quality issue arises.

Duration Is Uncertain

There is no reliable expiration date for enforcement discretion. The policy is tied to future rulemaking, but administrative rulemaking can take substantial time. Duration therefore is a secondary risk: even if the policy remains in place for years, it continues to provide an enforcement accommodation rather than substantive authorization under the 503A bulks-list pathway.

Counseling Takeaway

The most important counseling distinction is between federal enforcement protection and legal authorization. Businesses may be able to operate within HHS's stated enforcement posture if every condition is satisfied, but the covered peptides remain outside the relevant 503A bulks-list pathway unless and until rulemaking changes that status. That distinction matters even if the policy proves durable. Businesses should assess state regulatory requirements and private-litigation exposure independently; avoid describing covered products as "legalized," "FDA approved," or broadly "FDA compliant" merely because they fall within the policy; and structure contracts, investments, inventory, and patient-transition plans to account for both regulatory-change risk and the continuing legal uncertainty.

Enforcement Discretion Is Not Legalization

HHS's policy changes the federal government's enforcement posture; it does not change the underlying statutory status of the six peptides. None has been added to the section 503A bulks list through rulemaking. For a covered peptide that lacks an applicable USP/NF monograph and is not a component of an FDA-approved drug, the relevant statutory bulk-substance condition therefore remains unmet. HHS is instead stating that, when all policy conditions are satisfied, it does not intend to take federal enforcement action on that basis. The policy creates no rights, is not binding on HHS or the public, and should not be characterized as a statutory safe harbor or as making the covered compounding lawful under section 503A.

State Enforcement and Private Litigation Remain Separate Risks

The federal enforcement policy does not bind state boards of pharmacy, medical boards, attorneys general, or other state regulators, and it does not displace independently applicable state law. State authorities therefore may evaluate peptide compounding under their own pharmacy, medical-practice, drug, and consumer-protection requirements, notwithstanding HHS's federal enforcement posture. Nor does the policy immunize participants from private litigation. Plaintiffs may attempt to invoke the products' continuing federal regulatory status in consumer-protection, false-advertising, negligence, or other state-law theories, depending on the facts and jurisdiction. Such claims may face substantial defenses, including preemption and the rule against private enforcement of the FD&C Act, but the HHS policy itself does not eliminate the litigation risk.

Outsourcing facilities

The policy is limited to state-licensed pharmacies, federal facilities, and licensed physicians compounding under section 503A. It does not extend the same enforcement discretion to outsourcing facilities operating under section 503B.

Safety and quality monitoring

HHS expressly identifies safety signals and product quality issues as reasons it may revisit the policy. Robust quality systems, adverse-event surveillance, supplier qualification, and documentation therefore matter not only for patient safety and compliance with the policy, but also because problems in the market could affect the policy itself.

Marketing, telehealth, and related risk

Expanded access to compounded peptides is also likely to increase scrutiny of promotional claims, telehealth prescribing practices, patient-specific prescribing, and bulk-drug sourcing. Marketing should be particularly careful not to convert HHS's limited enforcement position into claims that a peptide is "legal," "FDA approved," or generally "FDA compliant." Companies operating in this space should separately review advertising and claims substantiation, state-law requirements, prescribing and fulfillment practices, supplier qualification, and litigation exposure rather than treating the HHS policy as broader authorization of the surrounding business model.

Next Steps

1. Map current and planned peptide products against the Appendix A list and the permitted routes for each peptide.
2. Audit suppliers and COAs against the Appendix B testing standard, and document vendor validation for any repackers or resellers. Confirm that each COA includes the information Appendix B requires, including the grade statement "Intended for human drug compounding," the original manufacturer's FEI number and address, and a signed CGMP compliance statement. For non-injectable dosage forms, confirm that the COA reports quality tests appropriate to that dosage form, because Appendix B identifies the endotoxin and bioburden criteria as specific to injectables.
3. Update labeling, MedWatch and state reporting procedures, and single-API and syringe-only packaging practices.
4. Consider submitting comments on Docket No. HHS-OASH-2026-0496 via Regulations.gov by November 13, 2026. In particular, stakeholders may wish to address the scientific record, the workability of the conditions, and the treatment of individual peptides in future 503A rulemaking.
5. Before making substantial investments in reliance on the policy, assess state-law and private-litigation exposure independently of HHS's federal enforcement posture; consider regulatory-change termination rights; limit irreversible commitments where feasible; and maintain a practical wind-down plan, including inventory and patient-transition contingencies.
6. Monitor FDA rulemaking on the 503A bulks list and any HHS revisions to the policy. The notice directs readers to the HHS website for the most current version of the policy, so check that version periodically.
7. Strengthen quality, adverse event reporting, state-law compliance, advertising review, and litigation-risk assessment in anticipation of continued regulatory scrutiny.

For further information, the notice lists Victoria Marshall, Office of the Assistant Secretary for Health, 202-690-7694, OASH-RFI@hhs.gov.

This alert is published for informational purposes only and does not constitute legal advice. For questions about the policy or its effect on your business, please contact your Venable LLP relationship attorney.