50 Shades of Legally Gray: FDA’s Juicy Peptide Cliffhanger

That matters for pharmaceutical, health care, wellness, and longevity players — including compounding pharmacies, telehealth platforms, manufacturers, and patient advocacy groups — because the US Food and Drug Administration (FDA) is not slowing down its scrutiny. 

As we previously wrote, the agency has been actively revisiting how it categorizes peptide substances under Section 503A, the provision of the Federal Food, Drug, and Cosmetic Act (FDCA) that allows state-licensed pharmacies and physicians to compound drugs for individual patients without the new-drug approval process, provided they meet certain conditions. One of those conditions is that the pharmacy or physician use only bulk substances that meet at least one of three criteria: appearing on the FDA’s 503A bulks list, being a component of an FDA-approved drug, or complying with an official compendial monograph. Substances land on the FDA’s radar for the bulks list through a nomination process. Compounders, manufacturers, and other interested parties submit nominations to the FDA, typically through a public docket, along with supporting information about the substance’s chemistry, safety, effectiveness, and historical use in compounding. To help determine which nominated substances belong on that bulks list, the FDA sorts them into Category 1 (under evaluation, and eligible for enforcement discretion while the FDA considers them for the bulks list) or Category 2 (substances the FDA has flagged as presenting significant safety risks, which compounders should avoid).

Whether a peptide sits in Category 1, Category 2, or on the bulks list itself has real, practical consequences for whether compounding pharmacies, prescribing physicians, and telehealth platforms can offer it without inviting enforcement. While the FDA has taken concrete steps toward reworking these categories, it has nonetheless left peptides sitting in a legal gray zone.

From Category 2 to Nowhere (Yet)

In May, the FDA signaled plans to reclassify more than a dozen peptides from 503A Category 2 back to Category 1. As noted, that distinction is important: Category 1 is the more permissive interim bucket for substances the FDA is evaluating for inclusion on the 503A bulks list, while Category 2 is reserved for substances the agency has identified as presenting significant safety risks. The 503A bulks list is the list of bulk drug substances that may be used in traditional 503A compounding when statutory conditions are met, so a peptide’s placement, or absence, directly affects whether compounders can rely on FDA enforcement discretion. The FDA has implemented half of that plan, removing 12 peptides from Category 2. But with the exception of GHK-Cu, none of these peptides have actually landed in Category 1, and none currently appear on any FDA 503A drug substance nomination list.

The unresolved state matters. Under the FDA’s own interim policy on bulk drug substances, enforcement discretion is tied to affirmative Category 1 status or inclusion on the bulks list — not mere removal from Category 2. The FDA no longer flags these 12 peptides as presenting significant safety risks, but it has not affirmatively authorized them for compounding. Entities who treat removal from Category 2 as a green light to compound or market a substanceexpose themselves to real enforcement risk until the FDA formally places a substance in Category 1 or on the 503A bulks list. Importantly, this analysis addresses only traditional 503A compounding; outsourcing facilities operating under Section 503B face a separate framework, and the Category 2 removals do not change that analysis.

The PCAC Calendar Is the Latest Plot Twist

The Pharmacy Compounding Advisory Committee (PCAC) is a standing FDA advisory committee that provides independent expert advice on compounding issues, including which bulk substances merit inclusion on the 503A bulks list, and by statute the FDA must consult the committee (along with the US Pharmacopeia) as part of that evaluation. Critically, though, the PCAC’s recommendations are non-binding: The FDA generally follows the committee’s advice but is not legally required to do so, and the agency will not issue a final determination on any of these substances until it has considered the committee’s input alongside the rest of the administrative record. In connection with each PCAC meeting, the FDA establishes a corresponding public docket where interested parties can submit written comments, data, and other supporting materials for the agency and the committee to consider as part of the record.

The next concrete milestone in this process is procedural, but important. The FDA’s July PCAC meeting on July 23 and 24 will consider BPC-157, KPV, TB-500, and MOTs-C related bulk drug substances on July 23, and emideltide (DSIP), Semax, and Epitalon related bulk drug substances on July 24, all for the 503A bulks list; consistent with the FDA’s standard practice, the parties who originally nominated these substances will have the opportunity to present in support of their nominations at the meeting. A second PCAC meeting, covering cathelicidin (LL-37), GHK-Cu, dihexa acetate, Melanotan II, and pegylated mechano growth factor (PEG-MGF), will be scheduled before the end of February 2027.

The FDA will provide the committee with written comments received by July 9 for the July meeting this month, but the docket (No. FDA-2025-N-6895) remains open, and the agency will still consider comments through July 22 more broadly. With over 1,800 comments already submitted to the docket, stakeholder interest in the fate of these peptides is running high, and the volume alone signals just how closely the broader industry is watching this process. Those with a vested interest in these substances should strongly consider commenting; submissions backed up their positions with clinical data, safety information, and documented patient need may carry the most weight. 

Even a favorable PCAC recommendation does not mean immediate authorization. The FDA would still need to complete formal notice-and-comment rulemaking before adding any substance to the bulks list under 21 C.F.R. § 216.23, a process that has historically taken well over a year. Companies should resist making commercial commitments premised on a favorable outcome that has not yet materialized.

Advertising Risk Will Not Disappear

Even if peptides eventually reach the bulks list, that outcome would not eliminate advertising and promotion risk. The FDA’s ongoing crackdown on GLP-1 marketing, which we covered in in our previous alert, is instructive. The agency has issued dozens of warning letters to telehealth companies and compounders, and has published a dedicated webpage flagging the specific promotional claims it considers misleading: implying FDA approval or review, claiming clinical equivalence to an approved drug, describing a product as a “generic,” misrepresenting sourcing, or overstating active ingredient sameness.

The FDA evaluates these claims under a net-impression standard, meaning that even technically true statements can render a product misbranded under FDCA Section 502(a) if the overall marketing picture is misleading. Companies compounding or marketing peptides should study these warning letters and the FDA’s guidance closely now, well before any bulks list decision, because inclusion on the list will not insulate advertising practices from scrutiny. If anything, it is likely to invite it.

Looking Ahead

Federal movement on peptides is real and unfolding on multiple fronts at once: category status, the PCAC docket, formal rulemaking, and advertising enforcement. Multistate companies face an added layer of complexity, since several states have adopted more restrictive positions on peptide compounding than the federal framework currently reflects. Given this fluid landscape, clients should focus now on careful positioning, a coordinated comment strategy, and rigorous advertising review, rather than premature commercial expansion. We will continue monitoring these developments closely in the coming weeks.