Key Points

• An HHS interim enforcement discretion policy allows section 503A compounding of six peptides — BPC-157, Epitalon, KPV, MOTS-c, Semax and TB-500 — by state-licensed pharmacies, federal facilities and licensed physicians.
• Enforcement discretion applies only if all 10 conditions are met. These include an FDA-registered manufacturer that complies with CGMP, certificates of analysis (COAs) that meet Appendix B, single-API products, permitted routes of administration and MedWatch adverse event reporting.
• The policy is interim and revocable, does not cover 503B outsourcing facilities or multi-peptide blends, and is meant to move patients from research-use-only peptides to pharmacy-based supply.

The U.S. Department of Health and Human Services (HHS) has issued an interim enforcement discretion policy under which it does not intend to take enforcement action against state-licensed pharmacies, federal facilities or licensed physicians that compound drug products under section 503A of the Federal Food, Drug, and Cosmetic Act using six peptide bulk drug substances: BPC-157, Epitalon, KPV, MOTS-c, Semax, and TB-500.

The policy applies only while the 503A bulks list is developed through rulemaking, and only when 10 conditions are met, covering sourcing, testing, reporting, labeling, formulation, and delivery devices.

The policy is significant for two reasons. First, HHS adopted it even though, for each of the six peptides, FDA’s Center for Drug Evaluation and Research (CDER) had recommended against listing, while the Pharmacy Compounding Advisory Committee (PCAC) voted in favor. Second, HHS presents the policy as a tool to move patients away from “research-use-only” peptides supplied by foreign manufacturers and toward a more controlled, pharmacy-based channel.

The conditions are demanding, however, and the policy may be revisited at any time. Stakeholders should treat it as a narrow, conditional safe harbor, not a broad authorization.

Background: Why These Peptides Needed a Policy

Section 503A exempts compounded drugs from FDA premarket approval (section 505), adequate-directions-for-use labeling (section 502(f)(1)), and current good manufacturing practice (CGMP) requirements (section 501(a)(2)(B)), but only if the statute’s conditions are met. One condition is that a bulk drug substance must (1) comply with an applicable USP or NF monograph, (2) be a component of an FDA-approved drug, or (3) appear on the 503A bulks list that HHS develops by regulation. The six peptides satisfy none of these routes, so absent this policy, products compounded from them would not qualify for the 503A exemptions.

Section 503A also requires that bulk drug substances come from an establishment registered under section 510, be accompanied by valid certificates of analysis (COAs), and be compounded based on a valid patient-specific prescription. These baseline requirements remain in place under the interim policy.

According to the policy, each of the six peptides was placed in FDA’s “Category 2” in September 2023 and was removed on April 22, 2026. The policy states that neither the placement nor the removal changed the substances’ status under section 503A. Removal from Category 2 therefore did not, by itself, make these peptides lawful to compound. The interim policy now fills that gap, subject to its conditions.

Key Provisions of the Interim Policy

Scope and Duration
The policy covers compounding by a State-licensed pharmacy, a Federal facility, or a licensed physician using a peptide bulk drug substance listed in Appendix A that is not the subject of a USP or NF monograph, not a component of an FDA-approved drug, and not on the 503A bulks list at 21 C.F.R. 216.23(a). Enforcement discretion lasts until the peptide is addressed in a final rule as either included in or excluded from the 503A bulks list. HHS may also revisit the policy, in whole or in part, if a safety signal or product quality issue arises with a compounded product within its scope.

The 10 Conditions
Enforcement discretion applies only when all of the following conditions are present:

1. Interim access list. The peptide appears in Appendix A.
2. Identity. The bulk drug substance matches the identity described in Appendix B (including amino acid sequence, chemical structure, molecular weight, and molecular formula) and stays within the route-of-administration limits stated there.
3. Characterization. The substance comes from a section 510-registered facility and has a valid COA with test results consistent with FDA’s guidance-based criteria in Appendix B, including identity, purity, potency, and the absence of contaminants such as endotoxins, heavy metals, microbes, and impurities.
4. Original manufacturer. The original manufacturer (not a later packer, repacker, labeler, or distributor) is registered with FDA, complies with CGMP and other FD&C Act requirements, and has its physical facility location listed on the COA. If the substance is obtained through an FDA-registered repacker, relabeler, or reseller, that entity must itself have performed and documented vendor validation of the manufacturer and of the manufacturer’s COA.
5. Reporting. Compounders report serious adverse events (whether or not considered drug-related) and product quality issues to FDA’s MedWatch program, and to the States where products are compounded and sent. Product reporting must include the active ingredient and its strength per unit; the original manufacturer of the active ingredient, including its unique facility identifier; and the dosage form and route of administration. The procedure for reporting adverse events and quality issues must also appear on the patient labeling.
6. Labeling. Product labeling must state: “This is a compounded drug product. Not for resale.”
7. Single API. The product contains only one active pharmaceutical ingredient (API) from Appendix A. Combination or “stacked” peptide products fall outside the policy.
8. Oral bioavailability. If a peptide is compounded in an oral dosage form, the compounder must keep documentation confirming that the specific formulation achieves an adequate level of oral bioavailability in humans.
9. Delivery device. The only drug delivery device co-packaged with or containing the compounded drug is an FDA 510(k)-cleared syringe.
10. General FD&C Act compliance. The product is compounded in compliance with all other applicable FD&C Act requirements, including the prohibition on insanitary conditions and section 503A’s patient-specific prescription requirement.

Covered Peptides and Permitted Routes

Appendix B sets out a specific salt or free base form and limits the permitted routes of administration for each peptide. Compounders should confirm that both the form and the route match.

For each peptide, HHS cites largely the same three-part rationale: (1) the characterization record has changed since CDER’s review, with lot-specific COAs from FDA-registered facilities supplying test results CDER had found missing; (2) historical use is now documented and quantified; and (3) CDER’s safety concerns were inferential or mechanistic rather than based on observed harm, and the policy’s conditions (lot-level testing, single-API products, and MedWatch reporting) address the remaining risk.

Testing Standard for Peptide COAs

Appendix B includes a detailed testing standard that effectively defines what a “valid” COA must show. Key elements include:

• Identification and primary sequence confirmed by orthogonal methods (at least two independent procedures based on distinct physicochemical principles), with 100% sequence coverage.
• Assay by HPLC or RP-HPLC against an established quantitative reference standard, plus net peptide content testing.
• Additional higher-order structure, aggregate, and biological activity testing for complex peptides of eight amino acids or larger.
• Impurity testing covering peptide-related impurities (ICH Q3A, USP <1503>), nitrosamines (against CDER acceptable intake limits), residual solvents (USP <467>, ICH Q3C(R7)), elemental impurities (USP <232>/<233>, ICH Q3D(R1)), residual TFA, residual fluoride, counter-ion content, and water content.
• Bioburden (USP <61>, <62>, <1111>) and bacterial endotoxin testing (USP <85>), which are identified as critical quality attributes for injectable dosage forms.
• COA content requirements, including the manufacturer’s name, FDA Establishment Identifier (FEI) number, and address; any processing firm and testing laboratory; batch number; dates of synthesis and release; expiration or retest date; the grade statement “Intended for human drug compounding”; the intended dosage form; storage conditions; a CGMP compliance statement; and a signature from the quality unit.
• Identification of each analytical method used, with method validation or verification report numbers, and information on the reference standards used.

Practical Implications and Action Items

Compounding Pharmacies (503A)

• Requalify suppliers. Confirm that each lot comes from an FDA-registered original manufacturer that complies with CGMP and that the COA lists the physical facility location. Research-use-only material, or material without a compliant COA, will not qualify. If you buy through a repacker or reseller, get that entity’s documented vendor validation.
• Review every COA against Appendix B. Compare each COA with the testing standard, including the grade statement, method identification, and dosage-form-specific testing. Topical, oral, and intranasal forms require testing suited to that dosage form, with results reported on the COA.
• Restrict formulations. Limit products to a single listed API, the covered salt or free base form, and the permitted routes. Remove combination peptide products and off-route formulations from your offerings.
• Build oral bioavailability files. If you plan to compound oral BPC-157 or KPV, assess whether you can document adequate oral bioavailability in humans for the specific formulation. Without that documentation, oral products fall outside the policy.
• Update labeling and reporting procedures. Add the required “not for resale” statement and adverse event reporting instructions to patient labeling, and set up procedures for MedWatch and State reporting.
• Confirm State requirements. The policy addresses federal enforcement only. State board of pharmacy rules, licensure requirements for dispensing into other States, and any State restrictions on these substances continue to apply.

Prescribers, Clinics, and Telehealth Platforms

• Patient-specific prescriptions are required. Office stock or anticipatory compounding outside section 503A’s prescription requirement is not covered.
• Physicians who compound are also subject to the conditions. Licensed physicians who compound in-office are within the policy’s scope and must meet all ten conditions, including sourcing, reporting, and labeling.
• Align protocols with the permitted routes and products. For example, Epitalon is covered only for injection in intermittent courses, and Semax only for intranasal use. Multi-peptide blends are outside the policy.
• Review marketing claims. Compounded products remain unapproved drugs that FDA has not reviewed for safety, effectiveness, or quality. Patient-facing materials should not suggest otherwise.

Bulk Suppliers, Manufacturers, and Life Sciences Companies

• Higher market entry requirements. Suppliers that want to serve 503A compounders will need section 510 registration, CGMP compliance, and COAs that meet the Appendix B standard, including the “Intended for human drug compounding” grade statement. Repackers and resellers must document vendor and COA validation.
• Pressure on research-use-only channels. HHS explicitly frames the policy as a way to discourage the use of research-use-only peptides from foreign manufacturers. Companies distributing those products should expect a regulatory environment that increasingly separates compliant compounding supply from research-grade supply.
• Competitive and development considerations. Sponsors developing peptide therapeutics should consider that the policy depends on the absence of an FDA-approved drug containing the substance and on the outcome of 503A bulks list rulemaking. Monitoring those developments is advisable.

Notable Deadlines, Carve-Outs and Areas of UncertaintyTiming

The policy does not state a fixed expiration date or a compliance deadline. We will be watching for additional details once the policy is announced in the Federal Register, which is scheduled to publish on October 30, 2026. It remains in effect until each peptide is addressed in a final 503A bulks list rule, or until HHS revisits it. The policy also does not specify deadlines for submitting adverse event and product reports to FDA and the States. Compounders should adopt conservative internal reporting timelines and monitor FDA for additional guidance. The policy notes that public comments may provide evidence FDA can consider in rulemaking, so interested stakeholders should watch for and consider participating in any notice-and-comment proceeding.

Carve-Outs and Exclusions

• Outsourcing facilities. The policy addresses compounding under section 503A by State-licensed pharmacies, Federal facilities, and licensed physicians. It does not address outsourcing facilities under section 503B.
• Other peptides. Only the six peptides in Appendix A are covered. Other peptides that were in Category 2 or are otherwise in demand remain outside the policy.
• Salt forms. Coverage is limited to the specified form (acetate for five of the six peptides and free base for Semax), even where the PCAC considered both forms.
• Combination products and complex devices. Multi-API products and delivery devices other than a 510(k)-cleared syringe are excluded.

Areas of Regulatory Uncertainty

• Revocability. Enforcement discretion is not a legal entitlement. HHS may revisit the policy if a safety signal or quality issue emerges, and the policy rests on HHS’s judgment rather than CDER’s, given that CDER recommended against listing each peptide. Changes in agency leadership or priorities could also affect how long the policy lasts.
• Intranasal Semax and the syringe condition. The device condition allows only a 510(k)-cleared syringe to be co-packaged with or contain the compounded drug, yet Semax is covered only for intranasal use. The policy does not explain how intranasal products (for example, those using a nasal spray pump) fit within this condition. Compounders should seek clarification or proceed cautiously.
• Oral bioavailability standard. The policy does not define “adequate” oral bioavailability or say what documentation is enough. Separately, the testing standard describes injection as the expected standard route for peptides because of their low oral bioavailability.
• Mechanics of product reporting. The policy requires reporting of “products compounded” to FDA and the States but identifies MedWatch, which is an adverse event and quality reporting program, as the channel. It does not specify a format, frequency, or State recipient for routine product reporting.
• Scope of testing for non-injectable forms. The testing standard is built around injectable critical quality attributes and requires “appropriate” dosage-form-specific tests for other routes without listing them.
• Other enforcement risk. The policy speaks to HHS enforcement against compounders. It does not change State law, and it does not address other theories of liability, such as false or misleading promotional claims, or enforcement against suppliers or distributors that do not meet its conditions.

Conclusion

HHS’s interim policy creates a meaningful but narrow path for 503A compounding of BPC-157, Epitalon, KPV, MOTS-c, Semax, and TB-500. Its benefits are available only to compounders that can show rigorous supply chain qualification, Appendix B-compliant COAs, single-API formulations within the permitted routes, compliant labeling, and active adverse event reporting. Because the policy is interim, revocable, and silent on several operational questions, affected organizations should document compliance with each condition, review supplier and formulation decisions now, and monitor for FDA clarification and 503A bulks list rulemaking.

If you have questions, contact Marc Wagner, at mwagner@foxrothschild.com or another member of the firm’s Health Law team.

This information is intended to inform firm clients and friends about legal developments, including the decisions of courts and administrative bodies. Nothing in this alert should be construed as legal advice or a legal opinion. Readers should not act upon the information contained in this alert without seeking the advice of legal counsel. Views expressed are those of the authors and not necessarily this law firm or its clients.