Dear Secretary Kennedy:

Thank you for the opportunity to provide comments on the Department of Health and Human Services’ (HHS) October 30, 2026, notice announcing an interim enforcement discretion policy concerning the compounding of six peptide bulk drug substances under Section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The policy would allow qualifying state-licensed pharmacies, federal facilities, and licensed physicians to compound products using BPC-157, Epitalon, KPV, MOTS-c, Semax, and TB-500 without HHS pursuing certain enforcement actions while the Food and Drug Administration (FDA) completes its review of the substances for inclusion on the Section 503A bulks list.

Pharmaceutical compounding serves a distinct purpose in the U.S. health care system, providing individualized medications when commercially available products cannot appropriately meet a patient’s clinical needs, such as in cases of allergies or adverse reactions to specific ingredients. Congress recognized the value of this pathway when establishing statutory exemptions for qualifying compounded drugs. Yet those exemptions were not designed to create a substitute for FDA’s drug approval process or to allow for distributing unapproved products.

The October 30 policy undermines this narrow regulatory framework. HHS has articulated a certain concern that patients are obtaining unapproved peptides from questionable sources, including foreign suppliers marketing products for research use. Establishing more reliable channels for patients already using such products, though unapproved, may reduce certain quality risks. Nevertheless, the existence of an unregulated market does not, by itself, justify an expansion of compounding that precedes completion of an established regulatory evaluation process. Nor does evidence of substantial demand establish that the substances are safe or appropriate for clinical use.

HHS should withdraw the interim policy, in line with counsel from FDA’s scientific review team, and require full safety and efficacy testing before allowing these products in the pharmaceutical market. Should the department elect to retain the policy, substantial modifications are warranted to limit its duration, strengthen safety oversight, and prevent enforcement discretion from facilitating widespread commercialization of unapproved drugs

The Policy Risks of Circumventing the Established Regulatory Framework

Section 503A provides qualifying compounded drugs with exemptions from three major requirements of the FD&C Act: FDA premarket approval, current good manufacturing practice (cGMP) requirements, and certain labeling provisions. These exemptions recognize that traditional pharmacy compounding is distinct from commercial drug manufacturing; they are conditioned, however, on compliance with specific statutory requirements, including the receipt of valid patient-specific prescriptions and limitations on the bulk drug substances that may be used.

For bulk substances without an applicable United States Pharmacopeia or National Formulary monograph that are not components of FDA-approved drugs, Congress established a process for determining eligibility through inclusion on the Section 503A bulks list. This process requires scientific evaluation, consultation with the Pharmacy Compounding Advisory Committee (PCAC), and rulemaking.

The six peptides identified in the October 30 policy have not completed this process. Rather than awaiting those determinations, HHS has announced that it will exercise enforcement discretion for qualifying compounders using the substances. Although the policy does not formally add the peptides to the bulks list, its practical effect is to permit their distribution under conditions resembling those ordinarily available to qualifying Section 503A preparations.

There is an important distinction between an agency’s lawful discretion to prioritize enforcement resources and an administrative policy that effectively establishes an alternative pathway around statutory requirements. Enforcement discretion can serve legitimate purposes, particularly during temporary market disruptions or when regulated entities need time to adjust to changes in federal policy. Indeed, FDA has previously used defined periods of enforcement discretion to facilitate transitions following the resolution of pharmaceutical shortages.

The circumstances here are different. None of the six peptides have an FDA-approved counterpart, and their eligibility for the 503A bulks list remains unresolved. The department is not facilitating a transition away from a temporary disruption in the supply of approved products. Instead, it is permitting expanded access to substances whose regulatory evaluation remains incomplete.

This distinction directly impacts regulatory predictability. Congress established the 503A bulks list process to provide a consistent means of determining which substances are appropriate for use under the compounding exemptions. If HHS permits widespread compounding before that process concludes, the department risks diminishing the significance of the eventual regulatory determination. It also establishes an uncertain precedent for similarly situated substances whose manufacturers, compounders, or prospective patients may seek comparable treatment.

HHS should explain why enforcement discretion is necessary before FDA completes its scientific evaluation and why existing statutory procedures are insufficient to address the circumstances identified by the department. Without a compelling justification, maintaining the established process is preferable to creating exceptions whose practical effects may extend well beyond their intended purpose.

Patient Demand and Historical Utilization Cannot Substitute for Scientific Evidence

The October 30 policy follows the July 23–24, 2026, meeting of the PCAC, during which the committee considered whether several peptide bulk drug substances should be included on the 503A bulks list. Although the committee recommended including the six substances subsequently covered by the HHS policy, FDA’s Center for Drug Evaluation and Research (CDER) had recommended against their inclusion. The difference between those recommendations warrants scrutiny.

HHS’ supporting documentation offers substance-specific justifications for the interim policy, citing additional information regarding historical utilization, new product characterization data, and clinical experience. In several instances, the department also distinguishes FDA’s concerns about potential safety risks from observed adverse events in the available clinical record. These considerations are relevant to the ongoing evaluation, but they do not necessarily resolve the underlying scientific questions.

First, historical utilization is not evidence of clinical effectiveness. The fact that a substance has been compounded or administered to patients does not establish that it produces a clinically meaningful benefit. Similarly, greater documentation of historical use may improve FDA’s understanding of existing practices without demonstrating that expanded use is appropriate. The available evidence of effectiveness, or lack thereof, is expressly among the criteria FDA considers when evaluating substances for inclusion on the bulks list under 21 CFR § 216.23(c).

Second, the absence of documented adverse events should not be mistaken for affirmative evidence of safety. Limited clinical exposure, inadequate long-term follow-up, and incomplete adverse event reporting can make uncommon or delayed risks difficult to identify. This is especially consequential when substances are proposed for repeated or extended administration. A lack of observed harm may be reassuring within a particular clinical dataset, but the strength of that conclusion depends on the size, duration, and quality of the underlying evidence.

Third, HHS should avoid relying on safety findings involving related compounds without adequately establishing their relevance to the specific substances subject to enforcement discretion. For example, the policy discussion of TB-500 references human safety experience with its parent protein, while the discussion of MOTS-c cites a randomized trial involving an analogue of the peptide. These findings may provide useful scientific context, but their applicability to the particular substances, formulations, and routes of administration covered by the policy requires additional explanation.

Finally, improvements in product characterization should be distinguished from evidence concerning clinical use. The policy identifies new certificates of analysis and testing information intended to address deficiencies involving identity, purity, potency, and contaminants. Such information can materially improve confidence in the quality of bulk ingredients. It does not, however, establish the appropriate dosage, duration of treatment, potential long-term risks, or effectiveness of a compounded preparation.

To be clear, inclusion on the 503A bulks list does not require the same demonstration of safety and effectiveness necessary for FDA approval of a new drug. The statutory process instead employs a balancing of scientific considerations, including characterization, safety, available efficacy data, and historical use. The concern is that HHS is expanding access before the required balancing process has reached its conclusion.

HHS should provide a more complete, substance-specific explanation of how it assessed the evidence supporting interim access, including how the additional information cited in Appendix B addresses CDER’s concerns and what uncertainties remain. These judgments should be grounded in the available science rather than commercial or consumer interest surrounding the substances.

Enforcement Discretion Could Establish a Parallel Commercial Market for Unapproved Drugs

The distinction between individualized compounding and commercial drug distribution has become increasingly consequential as new business models have expanded access to compounded products. Telehealth platforms, centralized prescribing arrangements, and nationwide pharmacy networks can connect patients with compounded drugs at a scale that was not contemplated when the traditional framework was established.

The recent experience with glucagon-like peptide-1 (GLP-1) drugs illustrates these challenges. During extended shortages, compounding provided an alternative source of medication for some patients. Yet the growth of the market also demonstrated how rapidly temporary accommodation could support a substantial commercial distribution network. As shortages resolved, federal regulators faced increasingly difficult questions about the appropriate boundaries of compounding and the obligations of firms distributing products outside the conventional approval framework.

The circumstances involving the six peptides differ in one particularly important respect: There are no FDA-approved versions of these substances. Consequently, the central concern is not that compounded products will displace approved equivalents. It is that compounding could become an enduring pathway through which drugs are broadly marketed without completing the established regulatory process.

Early commercial responses to the HHS announcement suggest that this possibility is more than theoretical. On November 3, Enhanced announced that it had begun offering all six peptides through its telehealth platform, using licensed clinicians and pharmacies. Hims & Hers has also announced plans for a new peptide-focused business, including potential future access to BPC-157 and TB-500 when regulatory conditions permit.

These announcements do not establish that the companies are violating federal law. Nor does the use of telehealth or standardized clinical protocols necessarily preclude legitimate patient-specific compounding. They do, however, demonstrate how quickly an enforcement policy can influence investment, product development, and distribution decisions.

Such responses raise broader questions about the incentives created by the policy. If a company can develop a substantial market for an unapproved drug through compounding, its incentives to pursue traditional pharmaceutical development may be diminished. Obtaining FDA approval requires extensive investment in clinical research, manufacturing validation, and regulatory review. Compounded products are exempt from several of these obligations when the applicable statutory requirements are satisfied. Expanding the availability of those exemptions risks encouraging businesses to pursue a less burdensome distribution model rather than generate the evidence necessary to support broader clinical use.

This concern should not be confused with opposition to competition or innovative distribution channels. Competition is essential to pharmaceutical access and affordability, but it functions best when participants operate within an understandable and consistently enforced regulatory framework. An expanding market for unapproved drugs is not equivalent to the introduction of approved generic medicines, biosimilars, or novel therapies.

HHS should therefore consider the commercial incentives created by the policy and the potential for patient-specific compounding to become a vehicle for standardized, high-volume distribution. Permitting that development without clear limitations would further blur the line between traditional compounding and commercial manufacturing.

The Proposed Safeguards Do Not Fully Address the Policy’s Shortcomings

The interim policy includes 10 conditions intended to improve the quality and oversight of compounded peptide products. Among them are requirements involving FDA-registered bulk ingredient manufacturers, valid certificates of analysis, reporting of serious adverse events and product quality issues, single-ingredient formulations, specified routes of administration, and compliance with applicable patient-specific prescription requirements.

These are meaningful safeguards. Requiring stronger documentation of ingredient identity and quality is preferable to permitting unrestricted use of substances from poorly characterized sources. Similarly, adverse-event reporting and limitations on product composition may help regulators identify safety concerns and attribute them to particular substances.

Nevertheless, these requirements principally address identifiable quality and distribution risks. They do not resolve the broader uncertainty regarding whether the six substances are appropriate for expanded clinical use.

A certificate of analysis may help establish that an ingredient satisfies particular quality specifications. It does not establish that a finished drug product has undergone FDA review for safety and effectiveness. Manufacturer compliance with cGMP requirements for bulk drug substances likewise should not be confused with the approval and manufacturing requirements applicable to finished commercial drugs.

The reliance on post-market reporting also presents limitations. Although the policy requires reporting of serious adverse events, passive surveillance cannot reliably identify every potential risk, particularly when the underlying patient population, duration of exposure, and frequency of use are poorly understood. Surveillance may identify emerging problems, but it cannot substitute for an adequate prospective evaluation of known uncertainties.

The policy’s labeling requirement deserves additional attention. HHS requires compounded products to bear the statement that they are compounded drugs and not for resale. While appropriate, this language does not clearly communicate that the products have not received FDA approval or that their safety and effectiveness have not been established through the ordinary approval process. Patients should understand these distinctions before electing treatment.

Finally, the policy does not establish a defined calendar-based expiration date. Instead, enforcement discretion is intended to remain available until the relevant substance is addressed through final rulemaking, subject to the department’s ability to revisit the policy if safety or quality concerns emerge. That approach creates uncertainty regarding how long the policy may operate and what circumstances would warrant its modification or termination. A policy described as interim should not be permitted to function indefinitely simply because the underlying rulemaking remains incomplete.

HHS should preserve the safeguards it has identified for appropriate compounding practices while recognizing that those protections are insufficient to justify an open-ended expansion of access.

Recommendations

To preserve the integrity of the drug approval and compounding frameworks, HHS should withdraw the October 30 enforcement discretion policy until FDA completes individual safety and efficacy assessments of the six substances. The department should continue evaluating the additional scientific evidence identified in Appendix B, including information provided through the public comment process, without allowing an interim policy to predetermine the regulatory outcome.

If HHS elects to maintain enforcement discretion in the interim, the following modifications would substantially improve the policy. First, establish a defined duration and transparent termination criteria. Any interim policy should include a fixed expiration date rather than depend solely on completion of future rulemaking. An extension should require a documented justification addressing continued clinical need, updated scientific evidence, and the adequacy of existing safeguards. HHS should also specify the circumstances under which emerging safety concerns would prompt suspension or withdrawal of discretion for an individual substance.

Second, require a clear, substance-specific scientific justification. HHS should publish an assessment addressing the evidence supporting each peptide and permitted route of administration, including the rationale for departing from CDER’s recommendations. The department should identify the clinical uncertainties that remain unresolved and distinguish evidence involving the specific substance from findings involving related molecules or formulations.

Third, strengthen oversight of commercial distribution practices. HHS and FDA should closely evaluate arrangements that facilitate large-scale prescribing and distribution, particularly those involving telehealth intermediaries and standardized treatment protocols. Oversight should focus on whether compounders satisfy existing statutory requirements, including valid patient-specific prescriptions, and whether the scale and practices of distribution remain consistent with the applicable compounding exemptions. Where existing authorities are insufficient to address modern distribution arrangements, HHS should identify those gaps for congressional consideration.

Fourth, improve transparency regarding utilization and safety. The policy’s reporting provisions should be supplemented with clearer expectations concerning prescription volumes, patient exposure, dosage forms, and the duration of treatment. Such information would help regulators distinguish isolated clinical use from widespread commercial distribution and improve interpretation of reported adverse events. HHS should clarify which additional reporting measures can be implemented administratively, and which may require separate rulemaking or legislation.

Fifth, strengthen patient disclosures. Patients receiving these compounded products should receive clear information that the drugs are not FDA-approved and have not undergone the review required for commercial drug approval. Information concerning known risks, limitations of the available clinical evidence, and relevant uncertainties should also be communicated in an understandable manner. HHS should evaluate the appropriate regulatory mechanisms for ensuring consistent disclosures.

These recommendations are intended to preserve legitimate individualized compounding while limiting the potential for an interim enforcement policy to become an enduring substitute for scientific review and regulatory compliance.

Conclusion

HHS has identified a genuine concern regarding patient access to unapproved peptides obtained through poorly regulated distribution channels. The appropriate response, however, should not be to establish another avenue through which substantial commercial markets can develop before the necessary scientific and regulatory questions have been resolved.

Pharmaceutical compounding remains an important clinical tool precisely because federal law permits limited flexibility for circumstances in which conventional drug products cannot appropriately meet patient needs. Its continued utility depends on maintaining meaningful boundaries between individualized preparations and products intended for widespread commercial distribution.

The October 30 policy risks weakening those boundaries while introducing additional uncertainty into an already complicated regulatory framework. HHS should withdraw the policy pending completion of FDA’s substance-specific review and rulemaking or, at minimum, adopt substantially stronger limitations on its duration, scope, and commercial implementation.

Protecting patient access and encouraging pharmaceutical innovation are not competing objectives. Both are better served by a predictable regulatory framework that distinguishes legitimate clinical exceptions from efforts to bypass the standards governing drug development and distribution. We appreciate the agency’s consideration of these comments and would be happy to work with you and agency staff on policies and reforms in the pharmaceutical drug market that advance market competition, access to safe and effective medicines, and affordability policies.