FDA in Flux — September 2025 Newsletter

Welcome to FDA In Flux – A Mintz newsletter tracking rapid changes in policy and agency actions that impact medical, life sciences, and consumer product investment decisions and development strategies.

Federal “Crackdown” on DTC Drug Advertisements: Ripple or Sea Change?

What is happening: A flurry of actions concerning prescription drug advertising quickly followed official release of the White House’s Make Our Children Healthy Again strategy report on September 9, 2025. First, President Trump issued a memo instructing Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. and FDA Commissioner Marty Makary to ensure direct-to-consumer (DTC) prescription drug ads are accurate and transparent, including by increasing risk disclosure requirements. Second, FDA announced that it had sent cautionary letters to thousands of pharmaceutical companies, as well as about 100 “cease-and-desist letters” relating to alleged deceptive ads for specific products. HHS also issued a detailed “fact sheet” on the administration’s initiative.

The recipients and content of FDA’s cease-and-desist letters, a mix of untitled and warning letters, are now emerging, with one untitled letter posted on the Center for Biologics website; a large number of untitled letters posted on the Center for Drugs website; and an even larger number of warning letters added to the agency’s central database for warnings. Prominent pharmaceutical manufacturers and telemedicine companies were among the recipients in FDA’s wave of enforcement letters issued on September 9.

Why it matters: The MAHA Commission strategy report calls for “FDA, HHS, the Federal Trade Commission (FTC), and Department of Justice [to] increase oversight and enforcement under current authorities for violations of [DTC] prescription drug advertising laws. Egregious violations demonstrating harm from current practices will be prioritized, including by social media influencers and DTC telehealth companies,” signaling that US health agencies would expand enforcement priorities beyond traditional prescription drug advertisers. Similarly, the HHS fact sheet states that “FDA will close digital loopholes by expanding oversight to encompass all social media promotional activities.” But the cease-and-desist letters issued to date do not explain how the agency is interpreting the Federal Food, Drug, and Cosmetic Act (FD&C Act) to enable enforcement against every entity or person that promotes a prescription drug — not all of whom are directly connected to a manufacturer or distributor — and so far the scope of FTC’s and DOJ’s involvement in these efforts has not been shared publicly.

A wholesale realignment of how the federal government oversees and objects to misleading prescription drug ads has the potential to cause disruption in well-established business models, including not only drug company promotional plans but also those of television broadcasters and advertising agencies that have developed specialized practices for this highly regulated industry. The ramped-up enforcement effort also seems to undercut President Trump’s recent demands that drug companies lower their prices by, in part, setting up “direct-to-consumer and/or direct-to-business distribution models,” which by necessity require some level of DTC promotional messaging to work.

Who may be affected: Enhanced oversight and enforcement of DTC advertising affects all drug and biological product manufacturers and marketers — and apparently all telemedicine companies that offer prescription drugs and all individuals speaking about prescription drugs online with financial incentives — with numerous FDA violation notices already sent out. For drug manufacturers and distributors who generally expend significant resources developing and internally reviewing prescription drug ads, it is unclear whether or how all of them actually may have violated applicable laws, given that the current FDA has not yet changed any drug advertising rules. HHS/FDA’s assertions that there is widespread (or even ubiquitous) deception from highly regulated manufacturers are not consistent with industry best practices that prioritize advertising compliance. But from some of the released cease-and-desist letters it appears that FDA is applying a heightened standard for what constitutes distracting imagery in TV ads and concluding such distractions serve to make the overall message to consumers misleading.

Companies who are alleged to be misbranding their drugs through noncompliant advertising should carefully review the agency’s rationale, factual background, and legal analysis, as the basis for such letters may be weak or may not comport with applicable laws. It also seems unlikely that experienced prescription drug advertising reviewers prepared these 100 or so “cease-and-desist letters” given staff layoffs and other attrition during the first half of 2025. If FDA is using artificial intelligence tools to prepare such letters, there may be significant weaknesses in the agency’s reasoning that letter recipients can push back on.

Other FDA-regulated entities that advertise their products DTC — such as dietary supplement distributors and, increasingly, medical device manufacturers — should take heed of the agency’s statements in the prescription drug space and ensure their content cannot be deemed misleading or deceptive to consumers.

“Adequate Provision” Regulation for DTC Broadcast Ads Likely to Be Revoked

What is happening: As mentioned above, the recent HHS/FDA announcements on prescription drug advertising include a plan by the agency to “initiat[e] rulemaking to close the ‘adequate provision’ loophole created in 1997,” which the government alleges has allowed drug companies “to hide safety information by placing it in another format or location.” The timeframe for initiating such a rulemaking is not specified, and the proposal does not appear on the administration’s Spring 2025 regulatory agenda that was released in early September. Removing this mechanism for complete risk information to be shared outside of the broadcast ad, in favor of requiring prescription drug advertisers to disclose all contraindications, warnings, precautions, and adverse event information (as set forth extensively in an approved drug’s prescribing information) in the ad itself will almost certainly make such ads prohibitively long. Such an outcome would effectively eliminate — or at least severely limit — television and radio prescription drug ads, while incentivizing advertisers to push more promotional content to websites, social media, and other digital commons.

Why it matters: Whether HHS and FDA have authority to implement such strict requirements under the FD&C Act is unclear, especially when the Act expressly requires such ads to contain “information in brief summary relating to side effects, contraindications, and effectiveness.” Following the Supreme Court’s Loper Bright decision limiting federal courts’ obligation to give agencies broad deference to interpret their enabling statutes, a significant rulemaking change like this one requires a compelling justification supported by the actual language of the statute; otherwise it is very likely to be deemed an arbitrary and capricious exercise of agency power. Information shared publicly by HHS and FDA so far does not rise to the level of “compelling” evidence. If FDA proceeds with efforts to change current and long-standing DTC advertising regulations, including but not limited to revoking the “adequate provision” exemption for broadcast ads, lawsuits challenging the agency are likely to follow swiftly.

Who may be affected: If FDA successfully changes the applicable regulations to repeal the “adequate provision” exemption and to require full risk information in broadcast DTC prescription drug ads, it will have a significant impact on physicians and their patients. Effectively banning reasonable-length broadcast prescription drug ads or mandating long, droning descriptions or lists of potential side effects will leave patients less informed about drugs that might help them manage diseases or conditions and leave them largely dependent on physicians for treatment information. Any increased disclosure requirements for DTC ads also will increase costs for drug companies and will reduce product revenue.

Regulatory Revolution: FDA Begins Releasing NDA/BLA CRLs for Unapproved Products

What is happening: FDA has for the first time proactively posted Complete Response Letters (CRLs) for as-yet-unapproved drug and biological products, with 89 new letters issued in 2024 and 2025 now available in the openFDA database. CRLs provide a written explanation for the agency’s decision not to approve a pending New Drug Application (NDA) or Biologic License Application (BLA), most often because of major clinical deficiencies, manufacturing facility deficiencies, product quality deficiencies, and/or data integrity issues. This move comes after decades of debate among stakeholders on the benefits, downsides, and legal authority for FDA to publicly release CRLs for unapproved products.

Why it matters: Historically, the agency had not taken this major transparency step due to concerns about confidential and proprietary information in the CRLs, which is owned by the application’s sponsors, as well as the resource burden that redacting such information could impose on FDA staff if such letters were to be released in “real time.” The sensitivities involved in releasing information about an unapproved NDA/BLA (including BLAs for biosimilar products) led prior FDA commissioners to decide that the administrative burden outweighed the hypothetical benefit from the public seeing FDA’s rationale for declining to approve a new product.

Current HHS and FDA leadership are much less deferential to the concerns of drug developers, however, and an increasing emphasis this year on “radical transparency” signaled that the agency’s historical perspective on the risk-benefit balance with respect to CRLs was inevitably going to change, regardless of whether current FDA regulations permit such disclosure. The action is also consistent with the transparency policies articulated in a Staff Manual Guide issued on August 15 in response to an executive order from President Trump, entitled “Gold Standard Science at FDA.”

Who may be affected: NDA and BLA sponsors are directly affected, and all companies submitting such marketing applications for FDA review should be aware that any future CRL will now become public, as FDA noted in its September 4 announcement that “the agency will promptly release newly issued CRLs.” Many of the companies whose CRLs were recently released have stated publicly that FDA gave no notice before taking this action or any opportunity to ensure that sponsors’ proprietary information was redacted from the CRLs. Accordingly, sponsors should take into account when submitting NDA/BLA applications that CRLs will be published and should be prepared, in the event a CRL is issued, to:

1. characterize FDA’s reasons for declining to approve the product candidate, or the alleged deficiencies in the marketing application, to investors or the public in an accurate and not misleading manner;
2. provide any additional context or clarification about other communications with the agency or actions that may mitigate the summary observations described in the CRL; and
3. consider whether to proactively release their own redacted CRLs, as well as any written responses to FDA, to counteract the public perception that they are “hiding” information.

Further, the agency’s “public good” reasons for releasing CRLs for unapproved drug and biological products seem equally applicable to “not approvable” letters for innovative medical devices and “not substantially equivalent” letters for devices that go through the 510(k) pathway, yet there has been no indication from Commissioner Makary that a parallel initiative may be developed for medical device marketing submissions. Device stakeholders should stay informed and alert about the possibility of similar FDA actions being taken with respect to their pending applications.

As FY25 Ends, the DOJ Consumer Protection Division Winds Down, Leaving an Uncertain Future for FDA-Related Litigation

What is happening: Part of President Trump and Attorney General Pam Bondi’s reorganizational plans for the Department of Justice (DOJ) includes the dissolution of the department’s Consumer Protection Branch (CPB). CPB was established in 1971 to serve as a centralized division for federal government investigations and prosecutions of the FDA laws, as well as other consumer protection-focused laws, such as those administered by the Federal Trade Commission, the Consumer Product Safety Commission, and the Drug Enforcement Administration. Notably, CPB played a key role in the federal government’s response to the opioid epidemic. Notwithstanding those critical functions, public reports earlier this year indicated that all CPB attorneys would be moved to other parts of DOJ’s Civil Division, the Criminal Division and the Federal Programs Branch, with such changes set to be completed by the end of this fiscal year (September 30, 2025).

Why it matters: Defendants in federal investigations involving potential violations of the FD&C Act, the Public Health Service Act, and other laws applicable to FDA-regulated drugs, devices, foods, cosmetics, tobacco products, blood products, radiation-emitting products, and other commodities have benefitted from the specialized legal knowledge housed within the CPB and its ability to coordinate across multiple states or US Attorneys’ offices. The decision to dissolve this function entirely could lead to outcomes such as decentralized (and slower) investigative and enforcement activities, inconsistent interpretations of what are often highly technical regulatory requirements, and variable enforcement priorities. We expect future defendants to experience more disjointed and potentially inconsistent investigations without CPB’s centralized management of cases involving FDA and other federal consumer protection agencies, not to mention its strong working relationships with compliance and legal staff within those agencies.

Who may be affected: All companies operating under any of the FDA or its sister agencies’ laws are affected by this significant and historic DOJ reorganization. Investors and other stakeholders in such entities should be aware that future federal investigations and enforcement actions may be more disruptive, lengthier, more expensive, and potentially more reputationally harmful than they have been in the past. The bottom line for affected companies should be that proactive compliance programs and self-correction of identified issues will be more important than ever following disbanding of the CPB.

FDA Introduces a “New” Collaborative Process for Ultra-Rare Disease Therapies

What is happening: FDA has created the Rare Disease Evidence Principles (RDEP), aiming to make premarket review of drugs and biologics for ultra-rare diseases faster and more predictable. If no adequate therapies exist for a disease, FDA commits to working closely with the sponsor to come to an agreement on the design of a single clinical trial, supplemented with confirmatory evidence, sufficient to meet statutory approval requirements. Eligible products must address a genetic defect that causes a disease affecting a very small population, or “generally fewer than 1,000 [US] patients,” and the disease must cause rapid deterioration and eventual disability or death. Sponsors seeking review under the RDEP must submit a request to the agency before any pivotal trial for the investigational therapy begins, adding a new administrative burden for sponsors. Very few additional details are available.

Why it matters: Although FDA is introducing the RDEP as a newly developed program, it appears simply to name a process that the agency and rare disease therapy developers already engage in. Many drug and biological sponsors have experienced productive, positive interactions with FDA’s review teams to come to agreement on submission strategies involving unique study designs plus confirmatory evidence when an investigational therapy targets an ultra-rare disease. Sponsors historically did not need to formally request access to such a process from the agency as is now being required for the RDEP – the sponsor just proposed alternative ways to meet the “substantial evidence of effectiveness” standard, and the review team worked with the sponsor through meetings and other communications to reach agreement, always subject to final NDA/BLA review. A couple of years ago, the agency issued guidance for industry on how to meet the statutory approval requirement using one clinical trial plus confirmatory evidence.

The announcement of the RDEP, and FDA’s stated commitment to be more flexible and transparent on treatments for ultra-rare diseases, also is puzzling considering the tranche of unapproved product CRLs recently released by the agency (see above). Several of the letters involve investigational therapies targeting rare diseases and provide evidence that the agency is taking a more inconsistent, demanding approach to safety and efficacy data for such therapies than in the past, even when it had reached prior agreements with the sponsor on the totality of the data package required for approval.

Who may be affected: Companies developing drugs and biologics to treat ultra-rare diseases, plus the patient populations for such diseases and their families and caretakers, are most directly affected by the RDEP process. If RDEP in fact produces greater consistency and transparency for sponsors, companies requesting review under the RDEP may experience greater premarket review efficiency and even get their therapies to patients with no other options faster. Such efficiencies would make investment in promising candidates for ultra-rare diseases more attractive. On the other hand, if RDEP makes collaboration with FDA review teams less organic and more burdensome than in the past, and if FDA leadership is inclined to question novel sources of safety and efficacy data for certain therapies (as appears to be the case from recent examples of leadership overriding agency scientists on approval decisions), it could stymie innovation and progress on product candidates to treat ultra-rare diseases. It is also unclear how the RDEP could affect the development of treatments for rare and ultra-rare diseases that do not meet the new program’s criteria, such as those that are not due to a single gene-mutation or whose underlying etiology remains unknown.

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