By: Caitlin A. Koppenhaver
The FDA Pharmacy Compounding Advisory Committee is considering whether BPC-157 free base and BPC-157 acetate should be added to the Section 503A Bulks List. FDA has proposed that neither substance be included. Although the Committee’s vote is advisory, its recommendation will, in part, inform FDA’s ultimate decision. After listening to both public comment and FDA’s presentation, the central concern is not simply that FDA reached a conservative conclusion. It is that FDA’s conclusion appears to be driven by the limited evidentiary frame the agency chose to apply—and is largely devoid of a balanced assessment of the broader record placed before the Committee.
Public Comment Presented a Different Record
The public comment period was largely supportive of a regulated pathway for BPC-157. Aligned trade and professional organizations, clinicians, patient advocates, digital-health companies, researchers, and domestic API manufacturers did not argue that BPC-157 has satisfied the standard required for approval of a new drug. Their position was narrower and more responsive to the actual Section 503A inquiry: patients are already using BPC-157, demand is not disappearing, and exclusion from licensed compounding pushes that use toward unsafe suppliers with substantially fewer controls.
Opponents of inclusion,one with an FDA background, focused on the limited human clinical literature, the limitations of anecdotal and observational evidence, and the concern that inclusion could create a pathway around the traditional FDA drug-approval process. But Section 503A review is not intended to duplicate a new drug application. FDA’s own framework calls for a substance-specific balancing of physical and chemical characterization, historical use, evidence of effectiveness or lack of effectiveness, and safety.
The public testimony also raised a threshold dispute about what evidence FDA actually evaluated.
Multiple speakers sought to make clear on the record that FDA’s briefing materials relied heavily on outdated nomination materials that had previously been withdrawn, while substantial supporting information later submitted to the public docket was not meaningfully addressed in FDA’s presentation.
FDA’s own briefing confirms that the original BPC-157 nominations were withdrawn and that FDA elected to proceed with evaluating BPC-157 free base and acetate on its own initiative. It also confirms that FDA declined to evaluate several proposed uses because the withdrawn nomination materials did not contain enough information for the agency’s review.
That procedural history is critical because deficiencies in a withdrawn nomination package do not necessarily establish that the substance itself cannot be characterized or responsibly compounded. They may establish only that the nomination was incomplete.
During public comment, a presenter stated that their submitted docket includes more than 1,000 pages of clinical records and information reflecting no reported adverse events. The representative also stated that approximately 16 million doses of BPC-157 have been compounded.
FDA’s Foundational Question: What Is BPC-157?
Following public comment, FDA acknowledged the strongly held views on both sides and the recurring demand for quality standards and guardrails. FDA then raised what it characterized as a more foundational issue: What, precisely, is BPC-157?
FDA's position is that “BPC-157” is a common name rather than a recognized USAN, INN, or IUPAC name. According to FDA, multiple salts and derivatives, potentially involving different active moieties, have been commercially described under the same name. The agency also noted inconsistencies regarding amino-acid sequence, composition, and whether the intended substance is BPC-157 acetate, BPC-157 free base, or another derivative.
As FDA summarized during its presentation:
“We can’t create quality standards unless we actually know what it is.”
FDA's position is that a prescriber, pharmacy, API manufacturer, and testing laboratory must all be referring to the same substance. An exact amino-acid sequence, salt form, molecular identity, impurity profile, analytical method, and specification must be established before a Certificate of Analysis has meaningful value. But FDA’s conclusion does not necessarily follow from its premise.
The fact that unregulated sellers use the same informal name for potentially different materials is an argument for a regulated nomenclature and specification—not necessarily an argument for exclusion. FDA is already evaluating and voting separately on BPC-157 free base and BPC-157 acetate. A guarded pathway could identify the precise substance permitted, define the applicable sequence and chemical form, and exclude other derivatives marketed under the broader “BPC-157” name.
In other words, the problem FDA identified is exactly the type of problem that enforceable standards are designed to address.
FDA Extended Its Objection Beyond Nomenclature
FDA concluded that both BPC-157 acetate and BPC-157 free base are not well-characterized. It cited inconsistent naming conventions, limited information regarding impurities, aggregates, bioburden, and bacterial endotoxins, potential immunogenicity for injectable and nasal preparations, and insufficient information regarding oral, transdermal, rectal, and metered-dose spray products.
Some of these are legitimate technical questions. But several are dosage-form or finished-product issues rather than characteristics that necessarily establish that the bulk drug substance itself cannot be adequately defined.
Aggregation and immunogenicity risks for an injectable or nasal spray do not apply identically to an oral capsule, transdermal preparation, or rectal formulation. Questions concerning a pump, container, closure, or metered-dose delivery system are product-development and container-closure-system issues. They may support formulation-specific requirements or restrictions, but they should not automatically be treated as proof that every compounded dosage form involving the bulk substance is inappropriate.
FDA’s analysis effectively aggregates every unresolved question associated with every proposed dosage form and uses the combined uncertainty to support an across-the-board recommendation against both nominated substances. A more disciplined regulatory analysis would ask whether the identified concerns can be separated and addressed through substance-specific and dosage-form-specific limitations.
FDA Relied on Rat and Dog Studies While Significantly Discounting Human Experience
FDA relied in part on pharmacokinetic and toxicology studies conducted in Sprague Dawley rats and Beagle dogs. Those studies included single intramuscular doses at which no acute toxicity or histopathological changes were reported, as well as 28-day intramuscular repeat-dose studies that FDA reviewed for potential safety signals. FDA also acknowledged that the studies did not correspond to many of the nominated routes and were too limited in scope and duration to establish safety for proposed oral, rectal, transdermal, subcutaneous, and nasal use.
The issue is the asymmetry in how FDA appears to weigh different categories of evidence. FDA was prepared to rely on limited animal studies involving routes that did not align with many of the proposed compounded preparations, while assigning far less weight to existing human use, clinical records, practitioner experience, compounding history, and the absence of a clear adverse-event signal described by public commenters.
FDA identified five human clinical studies. It acknowledged that no serious adverse events appeared to have been reported in those studies, but discounted them because the sample sizes were small, the duration was short, and the safety monitoring was limited. FDA also located three FAERS reports, while recognizing that causation was uncertain and that the reports were confounded by incomplete information or use of other products.
The studies do not establish long-term safety or broad effectiveness. But neither do the rat and dog studies establish that BPC-157 is unsafe for the full range of proposed human uses. FDA appears willing to accept uncertainty in nonclinical evidence when that uncertainty supports exclusion, while treating uncertainty in human and real-world evidence as a reason to assign it little or no meaningful weight. That is not a balanced evidentiary analysis.
The Absence of Traditional Trial Data Is Not the Absence of Evidence
FDA may reasonably give randomized controlled trials greater weight than observational records. It may question the reliability of anecdotal reports, retrospective chart reviews, or voluntary adverse-event information.
But the absence of a conventional pharmaceutical-development package should not be treated as the absence of meaningful evidence altogether.
FDA’s own briefing states that 503A compounders generally are not required to report adverse events to FDA and that the agency may therefore be unaware of events unless a report is voluntarily submitted.
That limitation cuts both ways. A limited reporting system means the absence of adverse-event reports does not prove safety. It also means FDA cannot reasonably demand a fully developed post-market dataset while maintaining a regulatory structure that does not systematically collect one.
Several speakers identified this precise problem: a patient improves, a clinician observes it, and the observation is never captured in a usable evidentiary system. The answer should be to create structured reporting and surveillance mechanisms—not to discount the clinical experience because the current system fails to collect it.
The Gray Market Is the Existing Comparator
FDA’s analysis cannot be confined to a theoretical comparison between BPC-157 and an FDA-approved drug. The real-world comparator is often an unregulated online seller offering material labeled “research use only” or “not for human use.”
One domestic API manufacturer stated during public comment that testing of research-use-only products found that some samples did not contain BPC-157 at all. Other speakers questioned FDA’s reliance on materials obtained from suppliers that expressly disclaimed human use.
The broader online environment makes that risk more significant. A 2025 consumer survey cited by the Alliance for Safe Online Pharmacies found that 65% of consumers incorrectly believed that all websites offering online prescription services were reviewed or approved by FDA or state regulators. Scientific terminology, research-use-only disclaimers, and wellness marketing can create an appearance of legitimacy that the product and supply chain do not support.
FDA is correct that quality standards cannot be built around an unidentified substance. But leaving the market to sellers with no meaningful quality system does not solve the identity problem. It compounds it.
The Industry Did Not Ask for the Wild West
The guarded-access position presented by aligned trade and professional organizations was not a request for unrestricted compounding.
One presenter described a narrow “third way”: neither open-ended access nor total exclusion, but a regulated pathway with defined safeguards. The American Peptide Association and other aligned stakeholders have similarly emphasized lawful access, quality controls, clinical oversight, data development, and a workable regulatory framework.
The proposed guardrails included:
- a substance-specific Green List;
- FDA-registered and qualified API manufacturers;
- lot-specific Certificates of Analysis;
- validated identity, purity, and potency testing;
- impurity and aggregation controls;
- sterility and endotoxin testing where applicable;
- stability requirements;
- patient-specific prescriptions;
- clear, non-alarmist disclosures regarding investigational status;
- adverse-event reporting; and
- structured post-market surveillance.
Online-safety and clinical stakeholders have identified substantially similar safeguards, including supplier qualification, identity testing, potency, sterility, endotoxin testing, stability, labeling, valid prescriptions, clinical oversight, and adverse-event reporting. These controls would not eliminate risk. They would create traceability, accountability, and a mechanism for developing the data FDA says is currently missing.
What Is Actually Before the Committee
The evidence supporting BPC-157 is not equivalent to the evidence supporting an FDA-approved drug. That has been acknowledged by nearly every serious participant supporting inclusion. But FDA’s presentation is not simply cautious. PCAC's ultimate recommendation is devoid of a balanced consideration of the full record described during public comment. FDA stated that this is Phase 1 and they will also consider the broader evidence submitted in the totality of evidence in the public domain.
FDA relied heavily on deficiencies in withdrawn nomination materials, limited published literature, and nonclinical studies in rats and dogs. It gave comparatively little visible consideration to voluminous clinical records, widespread existing compounding experience, adverse-event history, analytical information, and the public-health consequences of directing demand toward unregulated sources.
The identity, impurity, aggregation, and immunogenicity questions FDA raised deserve substantive answers. They do not necessarily compel blanket exclusion. They support defining the substance, limiting the permitted formulations, establishing qualified sourcing, and building the reporting infrastructure that currently does not exist.
The central question is not whether BPC-157 has already been “proven” under the new-drug approval standard.
It is whether excluding BPC-157 from licensed patient-specific compounding meaningfully reduces risk—or instead preserves a market in which patients continue to use products of uncertain identity, potency, purity, and sterility with almost no reliable clinical oversight or data collection.
FDA’s current analysis does not adequately confront that question.