On September 9, 2025, the U.S. Food and Drug Administration (“FDA”) Office of Prescription Drug Promotion (“OPDP”) issued a torrent of untitled letters, 40 in total, just days after rumblings that FDA would be cracking down on direct to consumer (“DTC”) advertising of pharmaceuticals.[1] This enforcement flurry—which we will digest in a later blog post, given its complexity—did not stop there as just a week later, on September 16, 2025, FDA released about 80 warning letters. We have forecasted this for months, and now, we believe this wave of action to be the tip of the enforcement iceberg.[2]
Indeed, this unprecedented number of untitled and warning letters signals a significant shift in the agency’s oversight of pharmaceutical advertising and product marketing, particularly in DTC channels. The majority of the warning letters targeted compounding pharmacies and telehealth companies for misleading claims about compounded drugs, underscoring the FDA’s previously stated and growing concern over consumer confusion and medications that lack FDA approval. The agency is also maintaining strict oversight of human cell and tissue products (HCT/Ps), reinforcing its stance on “homologous use” requirements and regulatory exemptions. Additionally, FDA scrutiny is extending to artificial intelligence platforms, both as subjects of warning letters and as internal tools for monitoring promotional practices.
These enforcement actions serve as a reminder of the importance of adhering to traditional regulatory standards, but also warn of a new enforcement methodology, one that, in the words of Commissioner Makary “will return to the 1990s paradigm of issuing hundreds of enforcement letters each year.” This is certainly above and beyond and keys-in on a view that enforcement authority within FDA is and always has been broad.
Compounding & Telehealth
Notably, the vast majority of warning letters—approximately 58 in total—were issued to a number of well-known compounding pharmacies and telehealth companies for claims relating to compounded GLP-1's, such as semaglutide and tirzepatide, as well as sildenafil and tadalafil. This action follows extensive criticism of the agency for failing to address the proliferation of compounded copycat drugs, particularly for GLP-1s. The letters may signal a new, more aggressive stance by the FDA towards compounders and telehealth companies’ marketing practices.
Overall, the letters follow a similar copy-and-paste format, each alleging that the companies’ marketing materials misbrand their products under Sections 502(a) and 502(bb) of the Federal Food, Drug, and Cosmetic Act (“FDCA”). The core of the accusation is that these claims falsely imply that the compounded drugs are FDA-approved or are the same as the FDA-approved brand-name versions, when they are not.
While many of the letters targeted low-hanging fruit—like advertisements that directly reference brand names, use the word “generic,” or outright claim to be FDA-approved—a closer look reveals some interesting insights into what the agency considers misleading with respect to this class of products. Indeed, the letters show that FDA was not solely focused on what it views as inaccurate statements but also took issue with claims that create a misleading impression, which is likely due to the popularity of these drugs and increased potential for consumer confusion.
For example, several letters flagged the phrase “Clinically Proven” as implying that the compounded product was the same as the FDA-approved version of the drug. Although the letters did not go into detail as to the agency’s reasoning, FDA was likely motivated by the fact that, unlike FDA-approved drugs, a pharmacy or outsourcing facility is not required to complete clinical trials demonstrating safety and efficacy of compounded drugs before they go on the market. Accordingly, while the branded version may be “clinically proven” to have certain benefits, the compounded drug has not necessarily received the same level of testing, and thus, such claims misleadingly imply that the product has the same assurances of safety and efficacy as its branded counterpart.
Additionally, many letters involved claims that the compounded version contains the “exact same active ingredients” as the branded version. While this may be technically true, FDA likely flagged these claims because compounders are not required to obtain active ingredients from the FDA-approved manufacturer; rather, under limited circumstances, compounders may utilize so-called “bulk drug substances” obtained from API manufacturers.[3] FDA’s concerns here may have stemmed from the fact that the average consumer is unlikely to be aware of this method of compounding and might instead assume that they are merely getting a deal on a cheaper, “customized” version of the brand-name product. The agency has repeatedly warned consumers of the inherent risks posed by compounded drugs and corrected misinformation surrounding these products, including reminding consumers that they are not FDA-approved and “should be used only by patients whose medical needs cannot be met by an FDA-approved drug.”[4]
This new wave of warning letters marks a clear shift in the FDA's enforcement strategy for compounded drugs. While the agency has been largely silent on compounder advertising, it's clear FDA is now actively scrutinizing not just what compounding pharmacies say, but also what their advertising implies. This signals a more comprehensive and proactive approach to protecting consumers from misleading claims and potentially dangerous copycat drugs, while also preserving the incentive to engage in the new drug approval process for FDA-approved drugs.
HCT/Ps
Although only one of the slew of warning letters addressed failure to comply with FDA’s regulatory framework for human cell and tissue products (“HCT/Ps”), it was the twelfth of its kind in total this year. FDA alleged that the company’s amniotic membrane products and dermal product violated the FDCA for being marketed/sold without a new drug application (“NDA”) or biologics license application (“BLA”) and do not otherwise qualify for an HCT/P-specific exception to premarket notification under either 21 CFR 1271.10(a) or 21 CFR 1271.15.[5]
In the Warning Letter, FDA alleged that the company’s products failed to satisfy, at least, the “homologous use” criterion under 1271.10(a) because the “labeling, advertising, or other indications of the manufacturer’s objective intent” did not demonstrate that the HCT/Ps were intended to perform “the same basic function or functions in the recipient as in the donor.” Instead, FDA found that amniotic and placental membranes in donors serve as protective nutrient barriers. In contrast, when these tissues are used in the company’s amniotic membrane products, they are intended for wound care applications—such as providing growth factors—which fall outside the same basic function of these membranes. Similarly, FDA found, the dermal membrane in donors serves as protective covering/barrier, while the same tissue, as used in the company’s dermal product, is intended for use in recipients for “supporting revascularization,” which falls outside the same basic function of this membrane.
FDA’s position here aligns with the position it has taken with other companies in the past couple of years—that using amniotic membrane for any purpose other than as a protective barrier is not “homologous use.”
At the beginning of this year, we speculated whether the new administration would be more lax than its predecessor on HCT/Ps, given its touted desire to reduce barrier to entry for certain stem cell therapies,[6] by mid-summer, we were trying to decipher mixed messages,[7] and now, given that this is the twelfth HCT/P-specific warning letter this year, it seems pretty clear that FDA does not intend to unilaterally expand the scope of the regulatory exceptions under 21 CFR 1271.10(a) and/or 1271.15. Perhaps we’ll have to wait on Congress before we see expansion in this space.
AI
Out of the more than eighty warning letters, only one letter was issued for an artificial intelligence (“AI”) platform. FDA’s Center for Devices and Radiological Health (“CDRH”) noted an AI algorithm to screen and diagnose mobility and cognitive health conditions in senior adults constituted diagnostic functions which would require premarket submission prior to marketing. Coupled with FDA’s push to regulate and address AI mental health devices and chatbots, the warning letter suggests AI technologies that target vulnerable populations may be subject to heightened FDA scrutiny.
Perhaps more notable is that FDA appears to have used AI tools to monitor drug ads and potentially generate the warning letters. FDA’s press release announcing its crackdown on DTC advertising stated FDA had already deployed AI and other technology-enabled tools to surveil drug ads. The use of AI in this way is indicative of FDA’s pivot in this administration to focus more on its internal use of AI rather than regulating or providing guidance on the use of AI by industry.
FOOTNOTES
[1] See FDA News Release from September 9, 2025: FDA Launches Crackdown on Deceptive Drug Advertising | FDA . Also, in a statement on X, FDA Commissioner Makary said FDA would be sending approximately 100 enforcement action letters.
[2] See FDA’s Vast Ad/Promo Warning - Enforcement Ramp-Up or PR Nothingburger? | FDA Law Update; What To Expect For Stem Cell Regulation Under Trump Admin - Law360 Healthcare Authority.
[3] See 21 U.S.C. §§ 353a(b)(1)(A) & 353b(a)(2).
[4] See, e.g., FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight Loss | FDA.; Compounding and the FDA: Questions and Answers | FDA; FDA alerts health care providers, compounders and patients of dosing errors associated with compounded injectable semaglutide products | FDA.
[5] Our previous blogs have outlined, in detail, FDA’s regulatory framework for HCT/Ps. See, e.g., FDA Cracking Down on Unapproved HCT/Ps with Fourth Untitled Letter of 2023; What To Expect For Stem Cell Regulation Under Trump Admin.
[6] See What To Expect For Stem Cell Regulation Under Trump Admin.
[7] See What’s Going on with Human Cell and Tissue Products?