FDA Advisory Committee Recommends Six Peptides for Compounding: What the Evaluation Criteria Tell Us About the Road Ahead

Key Takeaways

• PCAC recommended inclusion of six peptides despite FDA staff opposition. On July 23 and 24, the PCAC voted by margins ranging from 7–4 to 8–6 to recommend the addition of BPC-157, KPV, TB-500, MOTS-c, Epitalon, and Semax to the Section 503A Bulk Drug Substances List (503A Bulks List), while voting against Emideltide (also known as delta sleep-inducing peptide, or DSIP).
• PCAC members who voted in favor placed significant weight on patient-safety concerns about unregulated access. Despite FDA’s conclusions that the peptides were inadequately characterized and lacked robust safety and effectiveness data, several PCAC members reasoned that access through licensed compounding pharmacies and prescribers could provide greater patient protection than the status quo.
• The recommendations are advisory only. FDA retains final authority. PCAC’s votes do not automatically add the substances to the 503A Bulks List, authorize compounding, or constitute FDA approval. Adding a substance to the list first requires notice-and-comment rulemaking.

On July 23 and 24, the Food and Drug Administration’s (FDA) Pharmacy Compounding Advisory Committee (PCAC or Committee) convened for a closely watched two-day meeting to evaluate whether seven peptides should be recommended for inclusion on the list of bulk drug substances that may be used in compounding under Section 503A of the Federal Food, Drug, and Cosmetic Act (503A Bulks List). The peptides were reviewed in both free base and acetate salt forms. Despite FDA’s scientific review team’s opposition to including all seven substances, PCAC voted to recommend that six of the seven peptides be included on the 503A Bulks List. The PCAC recommended the inclusion of the free-base and acetate forms of BPC-157, KPV, TB-500, MOTS-c, Epitalon, and Semax, but voted against recommending the corresponding forms of Emideltide.

The closely divided votes carry significant potential implications for pharmaceutical compounders, life sciences companies, and the broader regulatory landscape. And understanding the evaluation criteria the PCAC applied, and how some Committee members weighed those criteria differently from FDA staff, is essential for stakeholders looking to navigate what comes next.

The Evaluation Framework: How PCAC Assessed Each Peptide

PCAC’s review of each substance was guided by the evaluation criteria FDA applies when determining whether a bulk drug substance should be eligible for compounding under Section 503A. As set forth in FDA’s briefing documents, these criteria include whether the substance:

• Is well characterized physically and chemically.
• Historically has been used in compounding.
• Has available evidence of effectiveness or lack thereof.
• Raises safety concerns associated with the substance’s use in compounding.

The FDA and the PCAC’s treatment of these criteria during the meeting are addressed below.

Physical and Chemical Characterization

Perhaps the most foundational criterion, and the one that generated the most friction between FDA staff and Committee members, was whether each peptide could be adequately identified and characterized. FDA’s multidisciplinary review team emphasized that meaningful quality standards cannot be developed unless a substance’s chemical identity is well established.

FDA staff noted that literature and commercial sources often describe substances under the same common name despite differences in amino-acid sequence or without clearly identifying whether the substance is a free base, salt, or ester. Different salt and ester forms of the same active moiety can exhibit significantly different physicochemical, toxicological, and pharmacokinetic properties. FDA’s briefing materials underscored this point. For example, in its review of BPC-157, the agency noted that it had encountered multiple substances marketed under the same common name that contained different active moieties. Because these common names do not follow established chemical nomenclature standards, such as the United States Adopted Name (USAN), International Nonproprietary Name (INN), or International Union of Pure and Applied Chemistry (IUPAC) conventions, the FDA stated that there may be no reliable basis for ensuring that a given name always identifies the same chemical structure and form. FDA concluded that BPC-157 (free base) and BPC-157 acetate were each “not well-characterized from the physical and chemical characterization perspective,” and reached similar conclusions for the other peptides under review.

FDA further noted that the nomination materials and publicly available information frequently lacked data regarding critical quality attributes, including specific tests for peptide impurities, aggregates, microbial quality, and bacterial endotoxins. The agency identified these gaps as particularly relevant to substances proposed for use in injectable dosage forms, where sterility and endotoxin control are critical safety considerations.

Despite these concerns, Committee members voting in favor generally concluded that the characterization issues did not warrant excluding the substances from the 503A Bulks List. Several placed significant weight on the concern that, without a lawful compounding pathway, patients would continue to obtain peptides from unregulated sources.

Historical Use in Compounding

The historical-use criterion received comparatively little attention during the Committee’s deliberations. In its briefing materials, FDA generally concluded that the available information was too limited to determine the extent to which the peptides had historically been used in compounding. For BPC-157, KPV, TB-500, and MOTS-c, FDA found that the extent of any compounding use was unclear or unknown. Although FDA identified some evidence that Emideltide, Epitalon, and Semax had been compounded since at least 2018, it could not determine which forms were used or how widespread that use had been. FDA also noted that the availability of these peptides through clinics and online sources did not necessarily establish that they were pharmacy-compounded products. Accordingly, the historical-use evidence did not provide clear support for inclusion or resolve the broader data gaps identified by FDA.

Effectiveness Evidence

On the question of effectiveness, PCAC’s deliberations reflected significantly differing approaches among members. FDA scientists concluded in their briefing materials that the peptides lacked sufficient evidence of effectiveness for the uses evaluated. Some Committee members echoed this concern, noting the limited clinical data and uncertainty regarding whether adverse effects would be detected without systematic safety monitoring.

Other Committee members appeared to place greater weight on reported clinical experience and the risks associated with continued gray-market access, despite the absence of affirmative evidence establishing safety and effectiveness. This approach differed materially from the analysis reflected in FDA’s briefing materials.

FDA’s briefing documents further noted that, for each peptide, it is often unclear whether the clinical literature is discussing the salt formulation or the free base, making it difficult to draw reliable conclusions even from the studies that do exist. In addition, many of the clinical studies cited by proponents involved different routes of administration than those proposed for compounded products, adding further uncertainty to the analysis.

As part of its effectiveness and overall risk-benefit analysis, FDA also considered whether FDA-approved therapies are available for the conditions the peptides were proposed to treat. Public health advocates, including the Center for Science in the Public Interest and Public Citizen, argued that approved therapies already exist for many of these conditions, including obesity, wound healing, and inflammatory bowel disease, and that adding peptides to the 503A Bulks List could reduce incentives for sponsors to pursue traditional FDA approval through the Investigational New Drug (IND) pathway. FDA’s briefing documents similarly demonstrated this point by identifying approved drug products for ulcerative colitis (the condition for which BPC-157 was evaluated) and for insomnia (one of the uses evaluated for Emideltide and the primary use evaluated for Epitalon).

Proponents countered that the peptides could serve as complementary tools rather than replacements for approved drugs and that patients should have access to a broader range of therapeutic options within a regulated framework.

Safety Considerations and Data Gaps

FDA’s briefing materials and staff presentations concluded that none of the peptides under review had sufficient evidence to establish their safety for the uses FDA evaluated. A recurring concern across FDA’s briefing documents was immunogenicity risk. The agency noted that peptides administered by injection may present a particular risk of immunogenic responses, especially when peptide impurities and aggregation are not adequately controlled.

For example, for BPC-157, FDA identified findings from repeat-dose toxicity studies that it characterized as potentially clinically relevant, including signals related to altered clotting properties and liver function. FDA also noted that BPC-157’s wound-healing effects may involve upregulation of growth factors and angiogenesis, while its molecular targets and mechanisms of action remain poorly understood. Because BPC-157 has been shown in nonclinical research to activate FAK and paxillin signaling, FDA identified a theoretical concern that it could promote the growth or spread of a tumor or cancer cells. The agency acknowledged, however, that this risk has not been established in humans, and FDA noted that longer-duration toxicity and carcinogenicity studies were unavailable.

For TB-500, which was evaluated primarily for wound healing, FDA reviewers and several Committee members raised concerns about its potential relationship to tumor progression, although FDA acknowledged that no studies had been conducted on TB-500 itself. Several members voting against inclusion found this data gap particularly concerning given the substance’s proposed use as an injectable.

For MOTS-c, a mitochondrial-derived peptide, opponents argued that the substance’s safety profile was too poorly understood to support listing. Some Committee members observed that inclusion could result in broader clinical use without systematic adverse-event reporting mechanisms in place. FDA’s briefing documents reinforced a related point: Section 503A compounders generally are not required to report adverse events to FDA, although FDA encourages voluntary reporting through its MedWatch program.

For Emideltide, FDA found no safety data for the proposed subcutaneous route and concluded that the available intravenous safety data was insufficient. For Epitalon, FDA did not identify clinical safety data in humans, particularly for subcutaneous administration. For Semax, FDA concluded that the available data was insufficient to characterize safety and effectiveness for cerebral ischemia, migraine, and trigeminal neuralgia. Across all three peptides, FDA also identified potential immunogenicity concerns associated with the proposed routes of administration.

Committee members who voted in favor generally acknowledged the data gaps but weighed them against the perceived safety risks of the unregulated gray market, reasoning that access through licensed compounding pharmacies and prescribers could provide greater patient protection than the status quo.

The Role of Unregulated Gray-Market Access in the Committee’s Deliberations

Although it is not one of the four express statutory criteria, the potential risk that patients would continue to turn to unregulated sources emerged as an influential factor in the Committee’s deliberations. Multiple clinicians and PCAC members described encounters with patients who had obtained “research-grade” peptides from overseas or other unregulated vendors, with no assurance of purity, identity, or safety. One Committee member recounted a case in which a patient’s research-grade product was reportedly found to contain MDMA, illustrating potential risks associated with unregulated sourcing.

This patient-safety rationale appeared persuasive to several Committee members, who viewed inclusion on the 503A Bulks List as a potential mechanism that could channel existing consumer demand through licensed compounders and prescribers, despite the absence of robust safety and effectiveness data.

The Votes: A Divided Committee Recommends Six Peptides

The final votes for each peptide reflect how closely divided the Committee was:

The votes recommending inclusion of six peptides ran counter to the recommendation of FDA’s scientific review team. The vote against Emideltide was consistent with FDA staff’s recommendation.

What Do the PCAC Peptide Votes Mean for Life Sciences Companies?

PCAC and FDA staff weighed the evidence differently. The votes may indicate that some Committee members were willing to give greater weight to clinical experience and harm-reduction considerations despite significant gaps in the safety and effectiveness data. Both the FDA staff’s emphasis on established characterization, safety, and effectiveness data and the Committee’s emphasis on real-world clinical experience and patient-access considerations reflect the underlying tensions within the 503A framework. Whether this approach affects FDA’s ultimate decision or future PCAC reviews remains to be seen.

The votes are advisory and non-binding. PCAC’s recommendations do not themselves add the substances to the 503A Bulks List, authorize their compounding, or constitute FDA approval. FDA will determine whether to accept the recommendations and adding a substance to the 503A Bulks List requires notice-and-comment rulemaking. The agency is not legally bound to follow PCAC’s recommendations, although the agency has historically given significant weight to Committee input.

Timing and interim enforcement policy remain open questions. The votes did not change the regulatory status of any of the peptide substances. Stakeholders should monitor whether FDA updates its interim policies while it considers whether to add the substances to the 503A Bulks List through rulemaking. FDA’s next steps are likely to have significant commercial implications for compounders, telehealth prescribers, and active pharmaceutical ingredient suppliers.

The broader policy environment may influence the agency’s next steps. The Department of Health and Human Services (HHS) leadership, including Secretary Robert F. Kennedy Jr., has publicly expressed support for expanded access to peptides. However, the FDA has not yet indicated whether or how that position will affect its response to PCAC’s recommendations.

Public health organizations have cautioned that allowing substances onto the 503A Bulks List without more traditional evidence of effectiveness could create an alternative pathway around the standard drug approval process and reduce incentives to develop these substances through the IND framework. Life sciences companies with products in development should consider how FDA’s ultimate decision could affect competitive dynamics and regulatory strategy.

What Happens Next After PCAC’s Peptide Compounding Recommendations?

PCAC’s July 2026 votes represent a significant potential development for the peptide compounding landscape and the broader relationship between compounding regulation and FDA’s evidentiary standards. However, the recommendations are non-binding, and the substances’ regulatory status will depend on FDA’s subsequent actions. FDA has also announced that it will schedule a follow-on PCAC meeting before the end of February 2027 to review additional peptides–including GHK-Cu, Melanotan II, Cathelicidin (LL-37), Dihexa acetate, and Mechano Growth Factor, Pegylated (PEG-MGF)–which may provide further indication of how the Committee and the agency will approach peptide nominations going forward.

If your organization is navigating the evolving regulatory landscape for compounded peptides, whether as a compounder, active pharmaceutical ingredient supplier, telehealth platform, or life sciences company evaluating competitive or M&A implications, we encourage you to reach out to our team. We are actively monitoring developments and are prepared to help assess the legal, regulatory, and strategic considerations arising from these advisory committee actions.