Last Friday, the Supreme Court delivered a trio of decisions making it easier to litigate against the federal government.  The facts and law in each case matter, and as is often the case when the Supreme Court “decides” an issue, much remains to be seen.  That said, it’s hard to see how the score on Friday wasn’t 3 for regulated industry and 0 for the federal government.

In a pair of 7-2 decisions authored by Justice Kavanaugh, the Court took the more expansive view of who can sue the government.

• In FDA v. R. J. Reynolds Vapor Co., the Court held that the Tobacco Control Act’s language permitting “any person adversely affected” by a denial order permitted not just the applicant, but retailers and an association of retailers to seek judicial review of the order.  While in the present case, the manufacturer, retailer, and trade association were all part of the same lawsuit, nothing in the Court’s decision requires that the applicant be a party to such a challenge.  Nor does the analysis limit the statute’s scope to retailers.  The right of consumers to bring such a statutory action is not addressed, although consumers are much discussed in analyzing prior precedent, but it is hard to see from the Court’s analysis why a consumer disappointed by a denial order would not be able to sue where they resided.
• In Diamond Alternative Energy, LLC v. EPA, the Court held that producers of automobile fuels had Article III standing to challenge EPA’s approval of state regulations requiring automobile manufacturers to manufacture more electric and fewer gasoline powered vehicles. While the legal issue and analysis was different than in FDA v. RJ Reynolds, the outcome was the same, additional parties had the right to challenge government regulation.

Finally, in McLaughlin Chiropractic Associates, Inc. v. McKesson Corp., a 6-3 majority held that notwithstanding statutory language providing “exclusive jurisdiction” in the courts of appeals to set aside final orders of the FCC, a party could challenge the validity of an agency’s interpretation in the district court. In sum, the Court concluded that pre-enforcement review in the courts of appeals was optional but not mandatory, and a party could wait to litigate the issue in an enforcement proceeding.  While this case interpreted the Hobbs Act, the FDC Act, CSA, and other statutes that more directly affect blog readers also contain similar exclusive jurisdiction provisions for certain agency orders. The Court’s analysis preserving the right to contest agency interpretations in district court enforcement proceedings logically extends to those statutes as well.

We’ll be watching to see how these cases play out in the lower courts as parties in litigation with the federal government test their limits.

After teasing a new rapid review pilot program for the past few weeks, on June 17, 2025, FDA officially announced the Commissioner’s National Priority Voucher (“CNPV”) program to expedite new drug and biologic (but not device or drug-device combination product) reviews.  As described in the press release and accompanying FAQ, the CNPV program is designed to reduce review time to 1-2 months following final drug application submission.  This would be substantially shorter than PDUFA goal timelines (including for priority review as it is currently known), which range from 6 months to 12 months from submission.  The CNPV program will begin in 2025, and FDA will give a limited number of vouchers during a first-year pilot phase.  This pilot phase may be followed by an increase in the number of CNPVs issued.

The press release describes the CNPV process as a “team-based review rather than using the standard review system of a drug application being sent to numerous FDA offices.”  This multidisciplinary team will “pre-review” the submitted information and convene for a “1-day ‘tumor board style’ meeting,” drawing on Commissioner Makary’s experience as a surgical oncologist.  As defined by the National Cancer Institute, tumor board meetings convene multidisciplinary specialists to decide on the best treatment plan for new and complex cancer cases.

FDA plans to issue a limited number of vouchers, without specifying an exact number as of yet.  The vouchers will be issued to “companies aligned with U.S. national priorities.”  According to the press release, which uses slightly different language than the FAQ, the Commissioner will establish these national priorities, which may include, but are not limited to:

• Addressing a health crisis in the U.S.
• Delivering more innovative cures for the American people.
• Addressing unmet public health needs.
• Increasing domestic drug manufacturing as a national security issue.

The Commissioner will use “specific criteria” to award the vouchers, and information will be provided in the near future on how companies can apply for a CNPV and “indicate their alignment with the FDA Commissioner’s criteria to meet national priorities.”  Although many of the initial criteria are broadly applicable, and FDA has not indicated that any single criterion is more important than any other, manufacturing in the U.S. may turn out to be a significant differentiator, particularly while numbers of CNPVs are more limited.

According to the press release, “[v]ouchers can be directed by the FDA towards a specific investigational new drug of a company or be granted to a company as an undesignated voucher, allowing a company to use the voucher for a new drug at the company’s discretion and consistent with the program’s objectives.”  As suggested by this language and made clear in the FAQ, there will be “product designated” and “product undesignated” CNPV vouchers.  We look forward to additional information about the scope of each type of voucher and, in particular, the criteria and limitations for product undesignated vouchers.  With the available information, a product undesignated voucher would seem to provide the most flexibility and allow companies to pivot from one program to another in the event of unforeseen circumstances, such as ambiguous clinical trial results or problems with a manufacturing facility.

If a company receives a voucher, it must meet certain requirements to qualify for expedited review: an applicant must submit the CMC portion of its application and draft labeling at least 60 days prior to the final application submission and be available for “ongoing communication with prompt responses to FDA inquiries.”  Commissioner Makary stated that this new program “will allow companies to submit the lion’s share of the drug application before a clinical trial is complete.”  While an interesting idea, it is not clear how that timing would ultimately work in practice and whether this refers to more than the CMC section and labeling being submitted 60 days early.

If a company will not yet know if its clinical trial will be successful when it begins submission of the application, it might result in a situation where “the lion’s share” of an application has been submitted to FDA, and a review initiated, for an application that may never be fully submitted due to disappointing results.  The risk of cashing in a voucher in such a situation would be magnified in the case of a product undesignated voucher that could have been better used on a different program.  This assumes that the early submission would be considered a “use” of the voucher, though it is not clear that this is the intent.  Even if a company decides to wait until it has topline results in hand to decide to use a voucher, the potential for a 1-2 month review could be very valuable.  We also note that the agency has given itself some latitude to extend the review window if the data or application components are insufficient or incomplete, if pivotal trial results are ambiguous, or if the review is particularly complex.

The benefits of the CNPV are not limited to FDA review of marketing applications.  The FAQ states that the CNPV can be applied to a product “at any stage in development.”  Such benefits during the IND phase include “enhanced communication” and “prompt responses.”  Among the questions we have are whether the voucher award criteria will differ for a product in development as compared to at the application submission stage and whether a voucher that is used for enhanced communication benefits during development can carry over to the subsequent review of an application.

Although there are some conceptual similarities with other FDA priority review voucher programs, CNPVs are non-transferrable.  However, they remain valid through changes in company ownership, suggesting they are transferrable through mergers and acquisitions.  Vouchers must also be used within two years following receipt or the voucher will expire, so companies should consider their application submission timelines when applying for the CNPV. Time will tell if this leads to some creative corporate mergers and acquisitions.

The CNPV program appears to share some aspects in common with the Real-Time Oncology Review (“RTOR”) program for cancer drugs and the Split Real Time Application Review (“STAR”) pilot program.  While we await additional details for the CNPV program, these programs might provide a reference for some of the details not yet provided.

The RTOR program also involves the earlier submission of certain information, initially top-line efficacy and safety data to determine eligibility, and, if accepted, a maximum of three presubmissions and a final submission.  As described in guidance, the eligibility criteria for RTOR are as follows:

• Clinical evidence from adequate and well-controlled investigation(s) indicates that the drug may demonstrate substantial improvement on a clinically relevant endpoint(s) over available therapies.
• Easily interpreted clinical trial endpoints (e.g., overall survival, response rates), as determined by the review division and the Oncology Center of Excellence.
• No aspect of the submission is likely to require a longer review time (e.g., requirement for new REMS, advisory committee, etc.).

As described in a 2022 FDA analysis, the median time-to-approval from submission for RTOR applications was 3.3 months, ranging from 0.4 months to 5.9.  As an extreme example, FDA approved a supplement for Adcetris (brentuximab vedotin) for a new indication 11 days following application submission.

Similarly, the STAR pilot program “aims to shorten the time from the date of complete submission to the action date” leveraging an earlier submission of much of the application prior to a final submission. However, there is not much public information about the success of the STAR program, perhaps due to low participation (in November 2024, FDA said that there had been no applications in the STAR program to date).

Unsurprisingly, the criteria for the RTOR and STAR program are relatively similar.  They require clear and robust evidence of efficacy without any aspects that would otherwise delay a review.  The RTOR program has shown that FDA is capable of meeting ambitious review time goals under the right circumstances.  However, given that the CNPV program anticipates allowing the “lion’s share” of the application to be submitted before a trial is complete, there may not be efficacy data available at the time of this submission.  This raises questions about the extent to which the use of the CNPV will depend on evidence of efficacy and how that might affect the ability of a review to be completed in the target timeframe.

We applaud FDA in its efforts to set, and hopefully meet, ambitious goals to approve safe and effective drugs in an expedited fashion.  However, at a time when non-expedited FDA approval decisions are delayed due to heavy workloads, we wonder whether such goals can be regularly met and whether they might come at a cost to non-participating programs.  We will be monitoring this program closely to see how it is implemented.

Special Surveillance List of Chemicals, Products, Materials and Equipment Updated

A “laboratory supply” is any List I or List II chemical, or any chemical, substance, or other item on a special surveillance list published by the Attorney General (delegated to the Drug Enforcement Administration (“DEA”)) of chemicals, products, materials, or equipment used in the illicit manufacture of controlled substances and listed chemicals.  21 U.S.C. § 842(a).  DEA publishes the Special Surveillance List to inform about potential illicit uses of a laboratory supply and reminds that civil penalties may be imposed on businesses that distribute a laboratory supply with reckless disregard for the illegal uses to which it will be put.  21 U.S.C. § 842(a)(11).

There is a rebuttable presumption of reckless disregard if DEA notifies a firm in writing that a laboratory supply it sold has been used by a customer, or distributed further by a customer, “for the unlawful production of controlled substances or listed chemicals a firm distributes and 2 weeks or more after the notification the notified firm distributes a laboratory supply to the [same] customer.”  21 U.S.C. § 842(a).  Distribution of a laboratory supply with reckless disregard subjects the seller of distributor to a civil penalty of not more than $250,000, now $470,640 with inflation.  21 U.S.C. § 842(c)(2)(C).

DEA issued a notice on June 4th effective immediately updating the Special Surveillance List for the second time in less than two years.  Special Surveillance List of Chemicals, Products, Materials and Equipment Used in the Manufacture of Controlled Substances and Listed Chemicals, 90 Fed. Reg. 23,711 (June 4, 2025). DEA published the original Special Surveillance in May 1999.  The agency revised the list in October 2023 when it added twenty-eight chemicals, removed two List I chemicals automatically included as a laboratory supply and added “tableting machines, including punches and dies.”

The newly updated Surveillance List includes chemicals, materials and equipment used in the manufacture, production and distribution of currently abused synthetic drugs like fentanyl, amphetamine, methamphetamine, PCP, LSD, ketamine and others.  Id. at 23,712.  Updating the list, DEA consulted law enforcement officials, forensic laboratory authorities, intelligence groups, drug signature and profiling programs, and international organizations.  Id.  The agency examined clandestine laboratory seizure reports, drug signature and profiling reports, intelligence reports, and scientific literature regarding:

1. Illicit controlled substance and listed chemical production methods;
2. Chemicals, materials, and equipment used in the clandestine production; and
3. Their role and importance in the synthesis of controlled substances and listed chemicals.  Id.

DEA added fourteen additional chemicals to the Surveillance List, updated the listing of a chemical on the list to include its other esters, and removed a List I chemical that is automatically a laboratory supply.  In addition, DEA added binding, disintegrating, filling, flowing, and lubricating agents that are excipients, specifically including products containing:

• Dicalcium phosphate,
• Magnesium stearate,
• Microcrystalline cellulose,
• Silicon dioxide, and
• Stearic acid.  Id.

The Surveillance List continues to include hydrogenators, “tableting machines, including punches and dies,” encapsulating machines and twenty-two liter heating mantels.  Id. at 23,713.

DEA did not touch the Special Surveillance List for over twenty years, and has revised it twice within the past two years.  We think that the agency will revise and update the list more frequently as clandestine manufacturing trends require.

Propionyl Chloride, A Proposed List I Chemical

DEA issued a notice of proposed rulemaking on June 3rd, following its October 12, 2023, advanced notice of proposed rulemaking (“ANPRM”) to regulate propionyl chloride as a List I chemical.  Designation of Propionyl Chloride as a List I Chemical, 90 Fed. Reg. 23,483 (June 3, 2025).  DEA found that propionyl chloride is being used and is important in the illicit manufacture of fentanyl, fentanyl analogues and fentanyl-related substances.  DEA found that propionyl chloride is a replacement for other List I and precursor chemicals in several illicit fentanyl manufacturing methods.  Id. at 23,485, 23,486.  DEA states that without regulations, propionyl chloride is readily available from 43 chemical suppliers.  Id. at 23,486.

Six respondents submitted comments to DEA’s ANPRM: three in support of controlling propionic chloride as a List I chemical, and three opposed.  Three commenters noted that propionyl chloride has legitimate potential use as a reagent for chemical synthesis processes  including in the natural product syntheses of N-deoxymilitarinone A and torrubiellone B, potential pharmaceutical development, resin/materials development, and agricultural chemicals.  One commenter, without providing details, asserted that the chemical may have uses in the medical field.  Id. at 23,486.

DEA does not propose to establish a regulated transaction threshold for propionyl chloride, therefore all transactions would be regulated and subject to DEA registration, recordkeeping, reporting and security requirements.  DEA also does not propose to exempt chemical mixtures containing concentrations of propionyl chloride, though manufacturers may submit an application for exemption from control of their specific product.  Id. at 23,483.  DEA explained that an exemption can be granted if the agency determines that the mixture is formulated such that “it cannot be easily used in the illicit production of a controlled substance and the listed chemical cannot be readily recovered.”  Id. at 23,486.

The proposed placing of propionyl chloride in List I is not subject to Executive Order 14192 requiring the elimination of ten regulations for each new regulation.  Public comments must be submitted electronically or postmarked on or before July 3, 2025.

4-Fluoroamphetamine, A Proposed Schedule I Substance

On June 3rd DEA also issued a notice of proposed rulemaking to control 4-fluoroamphetamine (“4-FA;” 1-(4-fluorophenyl)propan-2-amine), including it salts, isomers, and salts of isomers, in schedule I.  Schedules of Controlled Substances: Placement of 4-Fluoroamphetamine in Schedule I, 90 Fed. Reg. 23,477 (June 3, 2025).

4-FA is a central nervous system stimulant sharing structural and pharmacological similarities with the schedule II stimulants amphetamine and methamphetamine, and the schedule I stimulant 3,4-methylenedioxymethamphetamine, “MDMA”.  In March 2018 the Commission on Narcotic Drugs voted to add 4-FA to schedule II of the 1971 Convention on Psychotropic Substances, requiring signatories including the U.S. to schedule the substance to meet minimum requirements of the treaty.  The treaty requires signatories to implement licensing (registration) requirements to manufacture, distribute, import and export 4-FA, impose 4-FA importing and exporting requirements, and submit reports on 4-FA quantities manufactured, exported and imported as well as stocks to the International Narcotics Control Board.  Scheduling 4-FA in schedule I will enable the U.S. to fulfill its treaty obligations.  Id. at 23,478-79.

In response to a September 2019 DEA request to the Assistant Secretary for Health and Human Services (“HHS”) to conduct a scientific and medical evaluation of 4-FA, HHS recommended that it be placed in schedule I.  Id. at 23,479.  DEA conducted its own eight-factor analysis of 4-FA and found “that the facts and all relevant data constitute substantial evidence of the potential of abuse of 4-FA…[a]s such, DEA hereby proposes to permanently schedule 4-FA as a schedule I controlled substance.”  Id. at 23,481.  DEA also found that 4-FA has a high potential for abuse, no currently accepted medical use in treatment in the U.S. and lacks accepted safety for use under medical supervision, the criteria for schedule I placement.  Id. at 23,482.

Similar to DEA’s ANPRM for propionyl chloride, comments on DEA’s proposed scheduling of 4-FA must be submitted electronically or postmarked on or before July 3, 2025.  And, DEA scheduling actions are not subject to Executive Order 14192.

Thirty two years ago today, on June 10, 1993, Congress passed the landmark National Institutes of Health (NIH) Revitalization Act to remedy historical exclusion of women and minorities from research participation.  The law directed the NIH Director to ensure the inclusion of women and minorities as research subjects in NIH conducted or supported research unless doing so was “inappropriate” with respect to their health.  The law also required such research to be designed to enable a “valid analysis of whether the variables being studied in the trial affect women or members of minority groups, as the case may be, differently than other subjects in the trial.”

Contemporaneous with the NIH Revitalization Act, the Food and Drug Administration (FDA) reversed longstanding guidance categorically excluding non-pregnant women of childbearing potential from phase I and early phase II clinical trials in favor of encouraging women’s participation, requiring gender-based safety and efficacy analyses, and instituting contraception or abstinence stipulations for women of childbearing potential in early trials.

These events marked a turning point in expanding representation in clinical studies and opening the door to more personalized medical care.  Today it is widely accepted that both sex and race may be meaningfully correlated with physiological and pathological functions and that increasing trial representativeness may produce new biologic insights, improve the generalizability of research findings, and yield targeted therapeutic strategies with improved safety and effectiveness. Advancing the frontier of scientific knowledge has been an important rationale for diversifying trials.

Since 1993, Congress has continued to direct the federal government, and in particular FDA, to take steps to close the gap in clinical research representation.  For example:

• The Food and Drug Modernization Act of 1997 (FDAMA) directed FDA to develop guidance on the inclusion of women and minorities in research.
• The Food and Drug Administration Safety and Innovation Act (FDASIA), signed into law in 2012, directed FDA to investigate how well demographic subgroups (sex, age, race and ethnicity) were included in clinical trials to support approval of applications for medical products and whether subgroup-specific safety and effectiveness data were available.
• The FDA Reauthorization Act of 2017 (FDARA) directed FDA to develop guidance to enhance diversity in clinical trials.
• The Food and Drug Omnibus Reform Act of 2022 (FDORA) required sponsors of certain clinical trials for drugs, biologics and devices to submit Diversity Action Plans (DAPs) to improve enrollment of underrepresented populations and to ensure that participants in pivotal clinical trials reflect the demographic diversity of the population that will ultimately use the medical product, if approved. FDORA further directed FDA to issue guidance on the format and content of DAPs.

These legislative mandates in turn resulted in new initiatives by FDA to expand diversity and inclusivity in clinical trials.  In 2016—dubbed the “Year of Clinical Trials Diversity”  by FDA—the agency published two guidance documents in furtherance of FDASIA related to the standardized collection and reporting of race and ethnicity data in submissions of drug and device clinical trials (see our previous blog post on the device guidance here). In 2020, as required by FDARA,  FDA published guidance to enhance diversity in clinical trials that makes recommendations regarding (1) broadening eligibility criteria and avoiding unnecessary exclusions for clinical trials; (2) developing eligibility criteria and improving trial recruitment so the enrolled population better reflects the population most likely to use the drug, if approved; and (3) applying the recommendations for broadening eligibility criteria to clinical trials of drugs intended to treat rare diseases or conditions.

In 2024, FDA issued its long overdue draft guidance on DAPs as required by FDORA (which we blogged about here). Under this guidance, sponsors must submit a DAP to the FDA for a Phase 3 or other pivotal study that describes the sponsor’s enrollment goals for the study disaggregated or tabulated by race, ethnicity, sex, and age group of the clinically relevant population, the sponsor’s rationale for its goals, and an explanation of how the sponsor intends to meet those goals. The draft guidance also encourages sponsors to consider additional factors that may affect clinical outcomes when developing DAP goals (e.g., demographic, socioeconomic, presence of co-morbidities).

FDORA directed FDA to finalize the draft DAP guidance no later than 9 months after closing the comment period, which will be June 26, 2025.

Recent developments give reason for concern about whether FDA will meet this deadline and, more broadly, about whether FDA will continue to implement Congress’ mandates for clinical trial diversity and inclusion.  In January 2025, FDA removed three draft and final guidance documents from its website: the 2024 draft guidance on DAPs; a 2025 draft guidance on sex- and gender-based differences in device development; and a 2020 final guidance on enhancing diversity in clinical trials.  FDA gave no public notice and offered no explanation for its actions.  Following a February 11, 2025 temporary restraining order issued by the U.S. District Court for the District of Columbia the documents were restored with a disclaimer stating: “Any information on this page promoting gender ideology is extremely inaccurate and disconnected from the immutable biological reality that there are two sexes, male and female,” (see 2/15/25 archive of FDA’s draft DAP guidance). As of the date of this blog, the 2024 draft guidance on DAPs and 2020 final guidance on enhancing clinical trial diversity appear to have been removed again (see here and here, respectively).

Ensuring diversity and inclusion in clinical trials is a scientific and public health imperative.  Lack of representation has serious and wide-ranging adverse consequences that include compromising generalizability of clinical research findings, hindering medical innovation, increasing healthcare costs, exacerbating disparities in healthcare, and undermining trust in the research enterprise.

Consistent with its mission to protect and promote public health, FDA has for decades been at the forefront of efforts to expand clinical trial diversity and inclusion.  Although political priorities may shift, continued commitment to its mission—as well as to implementation of Congress’ directives– requires FDA to continue the forward momentum toward greater representation in clinical research.  We hope FDA will issue the final DAP guidance by June 26, as required by Congress, and thereby signal its continued commitment to advancing this goal.

It was about a year and a half ago that we first proclaimed mass hysteria when FTC crossed streams into FDA territory, but perhaps our cries were premature.  As we mentioned last year, a large number of the drug companies targeted by FTC in its Orange Book delisting campaign refused to delist their device patents from the Orange Book.  The FTC took another swing in the courts with an amicus brief in Teva v. Amneal, in which the Court ultimately held that “to qualify for listing, a patent must claim at least what made the product approvable as a drug in the first place—its active ingredient,” but that case didn’t have the effect of causing mass delisting (according to an FTC press release, only about 22 of the 100 patents identified were delisted).  So, as of now, many of the device component patents to which FTC objected remained listed in the Orange Book.

Well, the FTC is back at it—again without the help of FDA.

Armed with the Federal Circuit opinion in Teva v. Amneal, the FTC sent another spate of “warning letters” on May 21, 2025 to Novartis, Amphastar Pharmaceuticals, Mylan Specialty, Covis Pharma, and three Teva entities.  It also notified FDA that it disputes the appropriateness of more than 200 patent listings, most of which FTC “previously disputed” but remain in the Orange Book.  The FTC is again taking the position that “[t]hese patents do not meet the statutory criteria for listing in the Orange Book, as confirmed by a recent ruling in the U.S. Court of Appeals for the Federal Circuit.”

The warning letters and delisting requests are not, in and of themselves, groundbreaking.  They’re mainly a continuation of FTC’s activities from 2023 and 2024.  But what makes them noteworthy is the elephant in the room: the change in administration.  The Press Release makes clear that this is not just a Democrat-led initiative.  The Republican-led FTC is continuing to move the ball forward:

‘The American people voted for transparent, competitive, and fair healthcare markets and President Trump is taking action. The FTC is doing its part,’ said FTC Chairman Andrew N. Ferguson. ‘When firms use improper methods to limit competition in the market, it’s everyday Americans who are harmed by higher prices and less access. The FTC will continue to vigorously pursue firms using practices that harm competition.’

It seems that this FTC isn’t willing to let this go.

Yet mum is the word from FDA.  There was some hope that, with pressure from the FTC, FDA would issue a guidance on whether device patents can be listed in the Orange Book since, after all, the Orange Book is plainly an FDA issue.  But FDA has been radio-silent.  So, the FTC continues on alone.  Down the only road its ever known.  Because, like a drifter, it was born to walk alone.

We have written many posts (here, here, here, and more) about the impact of the reductions in force (RIFs) on various activities across FDA. One area where the RIFs are beginning to have an impact is with respect to Small Business Determination (SBD) requests submitted to CDRH. The Office of Management, which was eliminated in the April 1 RIF, was responsible for processing these requests, and generally did so within 60 days of receipt. It is unclear which group is now reviewing and processing these requests, and the time it will take to do so. (We note that the webpage for the Office of Management is still functional, but has not been updated since January 2024.)

On June 4, CDRH sent out an email stating that it would be updating the CDRH Portal to add new functionality to the SBD feature to allow communications between CDRH and industry in the portal rather than via email. This indicates that CDRH is still reviewing SBDs and looking for ways to facilitate communications. It does not, however, help industry understand how long they can expect to wait for a response.

The SBDs are critically important for many medical device manufacturers. A “small business” is defined as a business, including its affiliates, whose gross receipts and sales are less than $100 million for the most recent tax year. Being granted an SBD provides discounted user fee rates for 510(k)s, de novos, and PMAs, among other submission types. The table below highlights the standard fee versus the small business fee for FY2025 for product authorization submissions.

There are many small start-up companies developing novel, innovative devices that will go through the de novo process. For these entities, the difference between the standard fee and the small business fee is not trivial. Indeed, for companies for whom every dollar is hard earned and every investor is closely watching the spend, a difference of over $120,000 for a de novo submission is significant.

If a small business submits an SBD request relying on the 60-day turnaround in advance of submitting an application to CDRH, and the SBD is delayed, the company may be forced to choose between paying the standard user fee payment or waiting for the granting of the SBD. To make this decision the company will likely need to weigh, among other matters, the strength and complexity of the submission, available funds, and timelines promised to investors and/or Boards of Directors. Companies would also likely need to consider the certainty of starting the review clock, with an eye to having a commercially viable product and being better positioned financially down the road, versus saving money on the submission now but potentially delaying commercial availability. (We acknowledge, of course, that a later submission does not necessarily delay commercial availability-this takes us back to the strength and complexity of the submission.)

We recognize that these decisions are unique to each company and would be happy to help weigh options to determine the best path forward.

Among other things, EO 14212 established the Make America Healthy Again (MAHA) Commission (with HHS Secretary Kennedy as its Chair) and tasked it with a tall order: submission to the President of an Assessment that tackled 10(!) complex public health issues within 100(!) days. Perhaps it was inevitable that the Commission would turn to AI for help, as seems to have been the case in light of media reports that the Assessment as originally published included references that don’t exist. We lawyers have seen that show before.

The process through which the Assessment was developed remains a mystery. Ordinarily, a public health initiative of such magnitude would have been governed by a transparent multi-step process featuring public meetings and drawing on external scientific expertise. In this instance, the Assessment appears to have been developed behind closed doors, and evidently did not undergo an internal or external review thorough enough to capture these errors.

Nevertheless, pursuant to EO 14212, the Commission now has less than 80(!) days to submit to the President a Strategy based on the findings of the Assessment. The Strategy must “address appropriately restructuring the Federal Government’s response to the childhood chronic disease crisis, including by ending Federal practices that exacerbate the health crisis or unsuccessfully attempt to address it, and by adding powerful new solutions that will end childhood chronic disease.” In other words, as you read this, the Assessment’s findings and recommendations are getting baked into federal government policy, for better or worse.

What might that look like for the drug sector? As stated, the primary focus of the Assessment is on chronic diseases, encompassing both their causes and their treatments. The Assessment uses a significant amount of real estate to discuss prescribing practices, alleging that current practices amount to overprescribing. The Assessment highlights various trends related to chronic disease diagnoses (such as increasing rates of autism spectrum disorder and attention deficit hyperactivity disorder) with associated trends in prescribing practices.

This overprescribing relates to a lack of long-term data for either safety (particularly neurodevelopmental) and efficacy for drugs which are nevertheless often prescribed long-term. There are also drugs the Assessment identifies as being used off-label without high-quality evidence or for uses that are approved but without rigorous “true placebo”-controlled trials (namely vaccines) and/or with known safety concerns. Some specific examples cited in the Assessment are the increased use of stimulants to treat ADHD despite evidence they did not improve long-term outcomes, higher rates of antidepressant prescribing despite evidence that psychotherapy is as effective in the short-term and potentially more effective long-term, increased prescribing of antipsychotic medication with many prescribed for off-label conditions in children, and unnecessary antibiotic use that is associated with higher rates of certain chronic conditions. The Assessment states that this prescribing is tantamount to doing direct harm, given the known and unknown risks and benefits of drugs in these contexts of use.

This Assessment does not itself prescribe specific remedies for the ills it diagnoses; those are supposedly coming in the future Strategy document. That leaves us to speculate what the implications of this Assessment will be. Notably, many of the issues regarding drugs are typically considered the practice of medicine, which FDA does not regulate.

However, that does not mean FDA is has no tools to address what the Assessment refers to as the “Overmedicalization of Our Kids.” Therapies for chronic diseases, even in pediatrics, are not approved based on decades-long studies, and this is not likely to change. Indications for chronic diseases do not generally reflect the length of the clinical trial; FDA determines that clinical trials supporting such approvals are of sufficient duration and makes an approval determination. If there are no known or anticipated safety or efficacy concerns from continued use, FDA draft guidance states that the description of the duration of use from the clinical trials should be discussed in the Clinical Studies section of labeling, not in the Indications and Usage section, as it is generally not necessary to limit duration of use in the indication unless it is essential to ensure the safe and effective use of the drug. Likewise, contraindications describe situations in which the drug should not be used because the risk of use clearly outweighs any possible therapeutic benefit; however, this should include only known hazards, and not theoretical possibilities. The Assessment suggests that FDA may be viewing indication claims with greater scrutiny moving forward, either at the time of approval or after, when such information may be available.

Known clinically relevant safety and effectiveness information is generally included in the label under current practices. However, as the Assessment notes, “[t]here are…many possible adverse events for which there is inadequate evidence to accept or reject a causal relationship,” which may otherwise lead manufacturers to opt not to include them in the labeling. This Assessment suggests causation may be viewed using a different standard moving forward, leading to the inclusion of additional information in the Warnings and Precautions or Adverse Reactions sections of drug labeling, or other potential consequences.

FDA also has other tools, such as Risk Evaluation and Mitigation Strategies (REMS), which are implemented to ensure that the benefits of a drug outweigh the risks. However, the most burdensome REMS restrictions, Elements to Assure Safe Use, are intended for situations only where specific serious risks are identified.

Similarly, FDA can use post-marketing requirements (PMRs). PMRs are implemented to assess possible serious risks associated with drugs, which can include assessing known serious risks, assessing signals of serious risks, or identifying an unexpected serious risk when available data indicate the potential for a serious risk. This can resemble enhanced post-marketing surveillance, and it is not difficult to see how the MAHA Assessment may support an increase in their usage where the qualifying criteria are met.

The Assessment does not focus solely on safety. For example, it describes a “replication crisis,” which it suggests should be addressed by government agencies to confirm both safety and efficacy findings from industry-funded research. Such efforts are intended to “improve trust and reliability in basic science and interventions in childhood chronic disease” and may have implications for labeling or continued approvals.

As described here in brief, FDA has a variety of tools that are already in use to address the issues raised in the MAHA Assessment. For example, the Assessment notes that SSRIs carry a Boxed Warning describing the risk of suicidal thinking and behavior in adolescents to facilitate safe prescribing practices. However, if FDA determines that these tools are not sufficient to address the issues described in the Assessment, we may see their use enhanced. Ultimately, FDA has the authority to decide whether benefits of a drug outweigh the risks, either in only limited circumstances, only with appropriate warnings, or in no circumstances, and approvals may be limited or withdrawn. Approvals may also not be made at all or may require more evidence, as we may also see increased pre-approval requirements such as true placebo-controlled trial requirements for vaccines. We will continue to monitor these developments as they come.

We appreciate receiving feedback on our blog posts.  We received a response to our post on the prescribing red flags indicating the likelihood of certain prescriptions filled by Walgreens pharmacies “were invalid because they lacked a legitimate medical purpose or were not issued in the usual course of professional practice.”  Press Release, Walgreens Agrees To Pay Up to $350M for Illegally Filling Unlawful Opioid Prescriptions and Submitting False Claims, U.S. Attorney’s Office, Northern District of Illinois, April 21, 2025, quoted here.

We noted that the Drug Enforcement Administration (“DEA”) had explained in its 2021 Gulf Med Pharmacy decision that prescribing red flags do not prohibit pharmacies from filling a prescription but are potential signs of diversion or risks to patient harm that pharmacists must resolve before filling.  Gulf Med Pharmacy; Decision and Order, 86 Fed. Reg. 72,694, 72,703 (Dec. 22, 2021).  Our reader informed us of two additional prescribing/dispensing red flags that DEA has alleged are “unresolvable” that he wanted to share with the pharmacy community.

The first “unresolvable” red flag is the continued prescribing and dispensing of immediate-release/short-acting opioids after two or three months.  Immediate-release/short-acting opioids act faster than extended-release/long-acting opioids.  DEA alleged that the pharmacy at issue dispensed oxycodone 30 mg., oxycodone/acetaminophen 10/325, hydromorphone 8 mg., and tramadol 50 mg. tablets to patients over the course of many months.  DEA specifically alleged that the pharmacy dispensed immediate-release opioids over a significant period of time, often at the highest strength available and in combination with other immediate-release opioids.

While prescribing immediate-release/short-acting opioids as a red flag is not new, that it is considered “unresolvable” is.  DEA’s position is contrary to statements made in the agency’s 2024 Coconut Grove decision when its expert opined at the hearing that filling immediate-release opioids prescribed and dispensed over a period of one and a half to two years “presented red flags and [the pharmacy] needed to properly resolve these red flags before dispensing.”  Coconut Grove Pharmacy; Decision and Order, 89 Fed. Reg. 50,372, 50,375, (June 13, 2024).  That decision includes a footnote stating that the expert “did not testify as to a specific time period that would cause concern, but made clear that a patient taking immediate-release opioids for ‘30, 60 days maximum’ would be acceptable and that over two years would be ‘very concerning.’”  Id. at 50,374-75 n.18.

The assertion that prescribing immediate-release opioids longer than two or three months is a red flag may have originated with the Center for Disease Control and Prevention (“CDC”) 2022 Clinical Practice Guideline for Prescribing Opioids for Pain.  The Guideline recommends that when clinicians begin opioid therapy for acute pain (of less than one month), subacute pain (of between one to three months) and chronic pain (longer than three months), they should prescribe immediate-release opioids instead of extended release-long-acting opioids.  Deborah Dowell et al., CDC Clinical Practice Guideline for Prescribing Opioids for Pain – United States, 2022, 71 MMWR Recomm. Rep. 1, Recommendation 3.  The Guideline also recommends when diagnosis and severity of acute pain warrant the use of opioids, clinicians should prescribe immediate-release opioids instead of extended-release and long-acting opioids at the lowest effective doses and for no longer than the expected duration of pain severe enough to require opioids to minimize the initiation of long-term opioid use.  Id., Recommendation 1.  However, the 2022 Clinical Practice Guideline, which updated the CDC’s 2016 Guideline, notes that its “recommendations are voluntary and intended to be flexible to support, not supplant, individualized, patient-centered care.”  Id. at Background.

The second “unresolvable” red flag alleged by DEA and shared by our reader was patients continuing to pay cash after the pharmacy filled their second prescription.  While certain circumstances surrounding a patient paying cash for controlled medication may be a prescribing/dispensing red flag, we cannot help but think that there are many legitimate reasons for patients paying cash for it to be patently “unresolvable” after their second fill.

At midnight on Friday, May 30, 2025, the government’s deadline to notice an appeal from the U.S. District Court for the Eastern District of Texas’s decision vacating the LDT Rule lapsed without the government doing so. This means the District Court decision stands, with no further right of appeal, and the LDT Rule remains vacated in its entirety.  As HPM argued in both the groundbreaking citizen petition Jeffrey Gibbs filed thirty-two years ago and the papers we filed on behalf of our clients, Dr. Michael Laposata and the Association for Molecular Pathology in the recent LDT litigation, the Federal, Food, Drug, and Cosmetic Act does not authorize FDA to regulate LDTs as medical devices. Those in the lab industry – and the physicians and patients who rely upon LDTs – are sure to be breathing a well-deserved sigh of relief over this development.

Just before this decisive event, though, FDA released a relatively rare Warning Letter to a manufacturer of research use only (RUO) reagents.  RUO-labeled reagents and materials are often used in LDTs in clinical laboratories.  The letter, which FDA issued on March 31, 2025 (but only posted on its website last week), was only one of two that FDA has sent in the last five years and only one of five that FDA has issued since finalizing its RUO Guidance in November 2013 (see guidance here).

The Warning Letter to DRG Instruments GmbH states that FDA determined the Company’s RUO‑labeled assay was intended for clinical diagnostic use, citing statements on the company’s website and labeling, as well as records that showed distribution to clinical laboratories that did not perform any research. Some of the claims that FDA cited as being for diagnostic use included “Simple and patient-friendly measurement of hormone profiles,” “Provides accurate, low level detection,” and “Can be performed also by patients.”

A striking detail in this Warning Letter was that FDA found it did not matter that the company had certification letters on record that showed at least some of their customers were aware that the products should only be used for research purposes, because FDA’s own “review of these customers’ websites strongly suggests that these customers are engaged in clinical diagnostic testing.”  RUO certification programs were something that FDA had, at one time, recommended.  In the current RUO Guidance, FDA notes that the existence of an RUO certification program would only be viewed as a factor when assessing the intended use of an RUO product.  Indeed, FDA states, “the existence of a certification program alone would not relieve manufacturers from their responsibilities to ensure that their labeling and distribution practices for RUO/IUO products are consistent with the product’s RUO/IUO label.”  The Warning Letter seems to echo this point.  Importantly, FDA did not say that sales to customers who are doing exclusively clinical diagnostics, alone, formed the basis of the agency’s letter.  These, along with the promotional claims formed FDA’s basis for concluding the products were intended for diagnostic use.

Because LDTs for clinical diagnostic use can sometimes include RUO labeled components, FDA may look to increase its scrutiny of these components as a means of tightening its control of the inputs to LDTs. We do not see the release of this Warning Letter as directly related to the LDT litigation, however.  The DRG Warning Letter cited information gathered in a November 2024 inspection and the warning letter itself was issued the same day as Judge Jordan’s decision in the LDT case.  Therefore, the events surrounding this particular Warning Letter preceded the LDT decision.

That being said, we have no doubt that as the door to regulating LDTs directly has closed, absent new legislation, FDA is likely to look for a new door to open.  Greater scrutiny of RUO products and those companies that manufacture them could be one of those doors.  HPM is keeping a watchful eye on the various indirect means by which FDA may try to regulate LDTs. In a follow-up post, we’ll discuss the different avenues FDA could seek to try to regulate LDTs (or components thereof) without new legislation.  Stay tuned.

In a recent letter to FDA Commissioner Dr. Martin Makary, U.S. Senator Dick Durbin (D-IL) expressed concerns over the agency’s ability to regulate direct-to-consumer (“DTC”) prescription drug advertisements following recent workforce reductions.  In his letter, Senator Durbin highlighted FDA’s critical role in ensuring that pharmaceutical advertisements are truthful, not misleading, and provide balanced information and asked a number of questions including those pertaining to the Office of Prescription Drug Promotion’s (“OPDP”) current leadership, the number of employees that lost jobs due to Reductions in Force (“RIF”), and the impact the RIF will have on OPDP’s future activities.

We at HPM have also been wondering about the future of prescription drug promotion and what actions this administration may take on DTC prescription drug ads specifically, especially in light of comments from the U.S. Department of Health and Human Services Secretary, Robert F. Kennedy Jr., stating that he would advise President Trump to ban pharmaceutical advertising on TV.  Commissioner Makary has taken a more subdued stance, stating in a podcast with Megyn Kelly that FDA doesn’t “have any plans to ban direct-to-consumer advertising, but there are some things that we can do to make sure that the information being presented is a complete picture.”  DTC prescription drug ads have also been an area of focus for Congress, with a recent proposal to eliminate tax deductions for expenses related to DTC advertising of Rx drugs.

In 2021, the U.S. Government Accountability Office (“GAO”) published a report finding that, for the years 2016-2018, the pharmaceutical industry spent on average for a sample of 553 drug products approximately $6 billion annually on DTC advertisements, with a significant portion of this spending allocated to television commercials.  Senator Durbin’s letter references a January 2023 study from the Journal of the American Medical Association, which found that more than two-thirds of drugs advertised on television were considered to have “low therapeutic value.”  This raises concerns about the impact of such advertising on public health and taxpayer dollars, especially considering that prescription drugs advertised on television accounted for 58% of Medicare’s overall spending on prescription drugs between 2016 and 2018, according to the 2021 GAO report.

Durbin’s letter addresses FDA’s capacity to oversee the increasing volume of DTC advertisements, particularly on platforms like social media.  He emphasized the need for FDA to modernize its regulatory approach to keep pace with evolving advertising practices and ensure that consumers receive accurate and comprehensive information about prescription medications.  Compounding these concerns is the fact that four of the top officials in OPDP, including the director and deputy director, have left the agency, and regulatory counsel and policy staff involved in OPDP research were laid off as part of the RIF orders.

In addition to his letter to FDA, Senator Durbin has introduced bipartisan legislation aimed at addressing deceptive advertising practices by the pharmaceutical industry.  The “Protecting Patients from Deceptive Drug Ads Online Act,” co-sponsored with Senator Mike Braun (R-IN), seeks to close regulatory gaps by empowering FDA to issue Warning Letters and impose fines on social media influencers and telehealth companies that promote prescription drugs without proper disclosures of risks and side effects.  The bill would also mandate that drug manufacturers report payments to influencers to the federal Open Payments database, similar to current requirements for physicians.

It’s unclear whether there are truly regulatory gaps that require new legislation.  While FDA has historically looked at manufacturer promotion, the language in the Federal Food, Drug, and Cosmetic Act (“FDCA”) provides that it is a “prohibited act” to cause the misbranding of a drug in interstate commerce.  False and misleading prescription drug advertisements misbrand drugs, and the provision in the FDCA need not be limited to those ads published by manufacturers but could apply to anyone facilitating the sale of prescription drugs.  With regard to influencers, the Federal Trade Commission (“FTC”) maintains its Endorsement Guides and, in 2021, sent over 700 Notice of Penalty Offenses letters, a number of which were directed toward pharmaceutical companies.  While FDA may have primary responsibility over prescription drug advertising, FTC also has broad authority over advertising, generally.

Getting back to manufacturer-sponsored DTC promotion, this was clearly a focus of OPDP enforcement in 2024:  four out of the five Untitled Letters issued dealt with DTC promotion and three of these letters specifically targeted advertising that utilized a celebrity.  This year is shaping up a bit differently – with all four OPDP enforcement letters addressing healthcare professional materials (including a speaker slide deck!!).  These bloggers have questions about this noticeable shift and whether it is a sign of new priorities at the agency or a result of OPDP simply clearing its desk of in-process enforcement letters post-RIF.  Some of those questions may be answered soon:  Durbin’s letter concludes by posing several questions to Commissioner Makary concerning the current state and planned future of OPDP and requests responses by June 17, 2025.  HPM will continue to monitor and report on any response from FDA, as well as the evolving landscape of prescription drug advertising.

NB:  As attorneys that work closely with pharmaceutical companies on their product communications, we may (admittedly) be biased, but demonizing pharmaceutical companies and DTC Rx drug ads oversimplifies issues and fails to acknowledge the important role DTC Rx drug ads may play in improving healthcare.  DTC Rx drug ads keep consumers informed about health conditions and available treatments, destigmatize certain conditions, and ultimately encourage consumers to take a more proactive role in their health.  Prescription drugs require a healthcare professional’s involvement, which should quell concerns that the DTC ad is the only education a consumer is receiving about their condition and treatment.  Further, while the nexus between DTC Rx drug ads and drug spend has been a focus, there has been little research on the overall value that greater consumer involvement in healthcare brings.  Maximizing patient clinical outcomes and quality of life may ultimately minimize healthcare resource utilization.  Healthier populations are more productive.  While much has been made about the increase in spending on DTC oncology drug ads, for example, according to NIH research, cancer death rates have been dropping by more than 1.5% annually for the past 15 years and “[e]ach 1% reduction in cancer deaths has a present value of nearly $500 billion to current and future generations of Americans.” (flip the “Health & Economy” piece on the NIH website.)  While we recognize it is a dramatic leap to correlate greater oncology drug (ad) spend with improved cancer outcomes, our point is simply that it is worth considering the overall context of societal costs/gains instead of focusing almost exclusively on pharma ad spend.

On May 8, 2025, FDA announced the successful completion of a generative artificial intelligence (AI) scientific review pilot program aimed at accelerating the review process and an “aggressive” timeline to rollout the use of AI tools across the Agency.  Extolling the “tremendous promise” of the new AI tools and their value in reducing reviewer tasks that “once took days to just minutes,” FDA Commissioner Dr. Martin Makary directed all FDA centers to immediately begin deployment with a goal of full integration by June 30, meaning that by that date all centers “will be operating on a common, secure generative AI system integrated with FDA’s internal data platforms.”

Notably absent from FDA’s announcement were any details about the technology that was deployed in the completed pilot program.  According to the global consulting group ICF, the pilot used an ICF-developed Computerized Labeling Assessment Tool (CLAT) to read drug labels and pinpoint specific items for review, with the goal of improving the effectiveness of the drug labeling review. As described here, CLAT is a tool that processes images of carton and container labeling to identify minimum requirements on the label, identify the availability of objects on an image, color differentiation of strength, missing barcode and orientation, incorrect or missing strength statements, error-prone abbreviations, look-alike labels, and text prominence. Another article about CLAT (available here) suggests FDA’s model will continually learn and improve over time.

Also not addressed in the announcement is whether the Agency-wide rollout will be limited to narrowly focused tasks, such as drug labeling review, or whether it will be applied to broader use cases, e.g., review of a full marketing application.

FDA has been working for years to understand the complexity of AI and how to ensure it functions as intended. As we recently blogged about here and here, FDA has issued guidance on lifecycle management for AI-enabled device software functions.  FDA’s guidance discusses the use of a robust development process to ensure transparency and reduce bias, which has the potential to produce incorrect results in a systematic but unforeseeable way.  With FDA’s aggressive timeline for Agency-wide implementation in less than two months, we wonder if FDA will be able to apply the same lifecycle and data management practices it expects for developers of AI-enabled device software functions.

As FDA knows well, the quality of the data used for training and tuning AI models has an impact on the quality of the output of the AI model. Based on our experience with FDA review of 510(k) applications, a single document may be updated several times over the course of the review, and a document submitted in response to an FDA information request may completely replace a previously submitted document. When developing and implementing AI models for use by FDA in review of 510(k)s and other applications where data can be updated throughout the review process, it will be important to clean the data to remove incorrect or duplicate information prior to training, which may be a manual process that could easily be overlooked with too aggressive a rollout.

FDA’s expectations for what is considered acceptable also change over time or differ between device types for a variety of reasons. When developing an AI model, it will be important to ensure data in the training set represents the current expectations, as training with data from testing to an outdated standard or following a now obsolete guidance will likely lead to the AI model being less useful.

At a high level, and based on the reported outcome of the pilot, the use of AI for reviews across FDA sounds promising. After all, FDA has access to all of the data submitted in applications and all of the review information related to those data. Therefore, it seems reasonable that AI models could be trained on the data, provide useful insights to reviewers, and speed up review times. Another area for which AI models may be suited in the medical device space would be post-market data, such as Medical Device Reports, where the data submitted is in a more standardized format from manufacturer to manufacturer. Applying AI models to review large amounts of data from multiple manufacturers could help FDA identify early signals related to product quality and patient safety.

At the same time, the absence of details about the planned rollout, along with the aggressive timeline, raise potential concerns.  We have all seen AI failures online, some amusing (e.g., is it a Chihuahua or blueberry muffin) and others with more serious implications.  We hope that FDA’s quest for speed does not prevent the Agency from adhering to its own “best practices” expected of industry to ensure any new tools implemented will be truly helpful to the review teams and not undermine the quality of reviews and that FDA provides transparency to industry about what documents in a submission are being reviewed by AI.

In yet another installment of the drama that is Jazz v. Avadel, the Federal Circuit recently reviewed a decision from the U.S. District Court for the District of Delaware that addressed the scope of an injunction under the patent safe harbor imposed on Avadel’s Lumryz (sodium oxybate).   Specifically, the District Court enjoined Avadel from (1) offering open-label extensions to clinical trial participants, (2) applying for FDA approval of Lumryz for idiopathic hypersomnia, and (3) initiating new clinical trials or studies after the Court’s Order.  But because the District Court failed to seriously consider the application of the safe harbor under 35 U.S.C. § 271(e), the Federal Circuit reversed in part, vacated in part, and remanded in part.

As long time readers know, Jazz and Avadel have been fighting a battle over sodium oxybate for a while (see our coverage here, here, and here).  Jazz is the sponsor of two products, Xywav and Xyrem, both of which are approved for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age and older with narcolepsy, and Xywav also is approved for the treatment of Idiopathic Hypersomnia in adults.  Avadel is the sponsor of its own sodium oxybate product, Lumryz, which is also approved in excessive daytime sleepiness in narcolepsy patients older than 7.  Avadel’s product was approved as a 505(b)(2) referencing Xyrem.

Jazz holds a patent that does not cover Xyrem or Xywav and, therefore, is not listed in the Orange Book.  Jazz nonetheless sued Avadel for patent infringement on that patent after Avadel submitted its 505(b)(2), but Avadel claimed the patent was invalid.  After a jury found the patent valid and awarded Jazz royalties for past infringement, the District Court imposed an injunction that prohibited Avadel from seeking approval of Lumryz in idiopathic hypertension; from offering open-label extensions to clinical trial participants; and from initiating new clinical trials or studies after the injunction effective date.  Avadel both appealed and sought an emergency stay in the District Court; the stay was denied.

In this appeal, Avadel argued that the forward-looking injunction is unlawful because it “enjoins Avadel from making, using, and selling Lumryz ‘solely for uses reasonably related to the development and submission of information’ to the FDA . . . in violation of § 271(e)(3)”.  Section 271(e)(3) states: “no injunctive or other relief may be granted which would prohibit the making, using, offering to sell, or selling within the United States or importing into the United States of a patented invention under paragraph (1),” which essentially precludes an injunction against activities protected by the patent safe harbor.

The Federal Circuit agreed with Avadel and reversed the District Court’s injunction prohibiting any new clinical trials as unlawfully overbroad.  Further, the Federal Circuit explained that open label extensions cannot be enjoined without an accusation of infringement and “[o]nly if and when that activity is adjudicated to fall outside the protection of the safe harbor, and only if and when the district court finds the eBay factors to favor an injunction, may it be permanently enjoined.”   Finally, the Court vacated and remanded the injunction prohibiting Avadel from seeking FDA approval of new indications because the submission of the application to FDA is not infringement under § 271(a), as it “is not a making, using, offering to sell, selling, or importing of a patented invention.”  Implicitly, this decision limited the imposition of injunctions that would interfere with patent safe harbor.

The decision leaves open a question posed by Avadel: whether a 505(b)(2) submission is an artificial act of infringement under § 271(e)(2) if there was no Orange Book patent certification.  The Court remanded that back to the District Court to discern, explaining that if it is the submission of the NDA that is the artificial act of infringement, then the District Court’s injunction barring Avadel from seeking FDA approval of any new indications was unlawful because it exceeds the scope of the remedies available to a patent owner for an artificial act of infringement.  If, however, Avadel’s submission of its paper NDA is not an act of infringement under § 271(e)(2), then an injunction could have been appropriate if it would prevent infringement.  In other words, to determine the appropriate remedy, the District Court must determine whether the NDA submission is the artificial act of infringement or the submission of a patent certification.

FDA recently announced, “CEO Forums: An FDA Listening Tour to Engage Pharma CEOs.” These are scheduled to take place in several cities on both coasts in June and July (here).”

This tour to engage with pharmaceutical and biotech CEOs is unprecedented. According to the announcement, Commissioner Makary will be holding these along with Principal Deputy Commissioner Sara Brenner, M.D., M.P.H and Director of FDA’s Center for Biologics Evaluation and Research, Vinay Prasad, M.D., M.P.H.  The stated purpose of them is to gather direct input from biotechnology and pharmaceutical leaders on how the FDA can modernize its regulatory framework to better support innovation and patient access to safe and effective therapies.

Interested parties must meet specific criteria, including having at least one active IND, NDA or BLA, and must register (registration form). Importantly, final eligibility for attendance will be determined by the FDA. Interestingly, leadership from the Center for Drugs is absent and the tour excludes CEOs in the device space.

Here are some of the unanswered questions:

• Is this a listen-only tour? Should executives expect to hear answers to their questions?
• How will industry participants be chosen? Is there a lottery?
• How many will be present in each meeting?
• Will topics need to be submitted ahead of time?
• Will the meeting discussion be made public?
• What is the output of these meetings?

Like you, we are actively seeking answers to these and other questions.

Listening sessions at FDA are not novel. Speaking from my personal experience, as a former Deputy Division Director in OND, attending listening sessions with patients were not just helpful, but often transformative in better understanding unmet need and helping characterize benefit-risk. We at HPM are optimistic that these listening sessions with CEOs can be equally impactful for product development. Given the recent sudden, frequent and often chaotic changes in the Agency, it is critical that the Commissioner hears directly from Industry about their goals, plans, and concerns. We anticipate the CEOs will have many questions for the Commissioner, including:

• Given that approximately 5% of CDER and CBER staff have left the Agency following significant staff reductions, additional staff continue to exit, and the hiring freeze continues, how can he ensure the safety and efficacy of drugs and biologics? How can the agency avoid the seemingly unavoidable delays to user-fee programs and other critical programs?
• Given the departure of staff with significant institutional and historical knowledge, how does he plan on filling this gap while retaining remaining staff with such knowledge?
• How will he ensure the independent, scientific integrity of the review process?
• How does he plan on implementing the framework for his proposal of a regulatory pathway based on a scientifically plausible mechanism?
• How does he plan on implementing AI in regulatory science and application reviews?
• How does he plan to remedy widely reported low morale among review teams?
• What should industry anticipate with respect to upcoming user fee negotiations?

We will follow this closely and hope that the discussion from these meetings is made public so that all stakeholders can benefit.

At our webinar earlier this month, we talked about Administration priorities as they relate to the FDC Act and noted that we expect much to remain the same with respect to enforcement.  One notable exception has been the Administration’s targeting of certain surgical procedures and the use of certain drugs for a particular intended purpose.  Specifically, these are procedures and drugs used in providing what HHS had, until recently, referred to as gender-affirming care.  The gray box at the top of the document at this link shows the change in position.

We’re not trying to bury the lead here, but the battle of labeling these surgical and drug treatments is a political one.  The political battle went into gear on January 28, 2025, with an Executive Order titled “Protecting Children from Chemical and Surgical Mutilation.”  That EO contained instructions to the Department of Justice, including that the:

Attorney General shall:

(a)  review Department of Justice enforcement of section 116 of title 18, United States Code, and prioritize enforcement of protections against female genital mutilation; . . . . [and]

(c)  prioritize investigations and take appropriate action to end deception of consumers, fraud, and violations of the Food, Drug, and Cosmetic Act by any entity that may be misleading the public about long-term side effects of chemical and surgical mutilation[.]

Late last month the Attorney General issued a memo addressing both directives.

• First, it “direct[s] all U.S. Attorneys to investigate all suspected cases of FGM [female genital mutilation]—under the banner of so-called ‘gender-affirming care’ or otherwise—and to prosecute all FGM offenses to the fullest extent possible.”
• Second, it “direct[s] the Civil Division’s Consumer Protection Branch to undertake appropriate investigations of any violations of the Food, Drug, and Cosmetic Act by manufacturers and distributors engaged in misbranding by making false claims about the on- or off-label use of puberty blockers, sex hormones, or any other drug used to facilitate a child’s so-called ‘gender transition.’ Even if otherwise truthful, the promotion of off-label uses of hormones-including through informal campaigns like those conducted by sales reps or under the guise of sponsored continuing medical education courses-run afoul of the FDA’s prohibitions on misbranding and mislabeling.”

The EO and DOJ memo were followed by a May 1, 2025 announcement of a report from the U.S. Department of Health & Human Services purporting to provide a “comprehensive review of the evidence and best practices for promoting the health of children and adolescents with gender dysphoria.”

The clear intended message from the EO and the DOJ memo is that individuals and entities who engage in conduct within their scope may be targeted for criminal investigation and prosecution.  Such a message may understandably deter the targeted conduct to avoid such a risk.

Importantly, that is not the only option, however.  As the Supreme Court has recognized: “The dilemma posed by that coercion—putting the challenger to the choice between abandoning his rights or risking prosecution—is ‘a dilemma that it was the very purpose of the Declaratory Judgment Act to ameliorate.’” MedImmune, Inc. v. Genentech, Inc., 549 U.S. 118, 129 (2007) (quoting Abbott Labs v. Gardner, 387 U.S. 136, 152 (1967)). While ensuring that a pre-enforcement challenge is properly presented to a court is not a simple task, it can be done, and for those interested, there may be much to challenge. The Supreme Court has recognized the ripeness of pre-enforcement challenges to criminal laws in a number of contexts, including where threatened injury is “certainly impending” or there is a “substantial risk that the harm will occur.”  Susan B. Anthony List v. Driehaus, 573 U.S. 149, 158 (2014).  The AG’s memo may well be relevant to establishing an impending and credible threat.

Below, we highlight some of the challenges we would see in the government’s attempt to pursue these cases.

18 U.S.C. § 116(a) – Female Genital Mutilation

This statute, as codified in 1996, criminalizes female genital mutilation (FGM) on any person under the age of 18.  There are at least two issues with DOJ’s planned use of the statute.  First, and more generally, it has already been found unconstitutional by one federal court in the first prosecution of FGM under the statute.  Specifically, in United States v. Nagarwala, 350 F. Supp. 613 (E.D. Mich. 2018), the district court ruled that Congress had exceed its constitutional bounds and had no authority to pass this law under the Necessary and Proper Clause or the Commerce Clause.  While DOJ initially appealed the lower court’s decision to the Sixth Circuit, it later moved to voluntarily dismiss the appeal.  See United States v. Nagarwala, No. 18-1156, 2018 U.S. App. LEXIS 37299 (6th Cir. Mar. 30, 2018).  In a letter to the Senate Judiciary Committee, then-Solicitor General Noel Francisco (part of President Trump’s first administration) wrote that DOJ had determined that the statute lacked a reasonable constitutional defense.  It is hard to see how the statute fairs better under constitutional scrutiny this time around, or why it is necessary to wait for a prosecution to find out.

Second, the memo makes it clear that the intended investigation targets are persons and entities providing medical care, but the statute’s own definition of FGM excludes such care.  FGM is defined as “any procedure performed for non-medical reasons . . . .  18 U.S.C. § 116(e) (emphasis added).  It seems a relatively straightforward legal issue of statutory construction, ripe for pre-enforcement review, whether a medical professional providing medical care according to recognized medical standards within their profession can be subject to prosecution.

Food, Drug & Cosmetic Act

The AG’s memo also cites the FDC Act as a tool for DOJ to “hold accountable medical providers and pharmaceutical companies that mislead the public about the long-term side effects of chemical and surgical mutilations,” although as we noted in the webinar, the Consumer Protection Branch tasked with “undertak[ing] appropriate investigations” of FDC Act violations has been slated for elimination, so that obligation may fall to other DOJ components.  The memo also instructs U.S. Attorneys’ Offices to use the False Claims Act (FCA) to investigate the submission of false claims to federal healthcare programs for non-covered services related to “radical gender experimentation.”  And the memo welcomes qui tam whistleblower suits with knowledge of “such violations.”

As to the FDC Act, substantively, the memo asserts that false claims about on- or off-label use of “puberty blockers, sex hormones, or any other drug used to facilitate a child’s so-called ‘gender transition’” may constitute misbranding under the FDC Act.  And the memo goes one step more arguing that, even if otherwise truthful, promotion of off-label uses of hormones can “run afoul” of FDA prohibitions on misbranding and mislabeling.

Recent precedent allows for misbranding prosecution of firms or their owners that engage in promotion of off-label intended uses, including by looking at truthful, non-misleading speech as evidence of a new intended use.  See United States v. Facteau, 89 F.4th 1, 22-26 (1st Cir. 2023).  However, truthful, non-misleading speech on its own cannot be a criminal act as it is protected under the First Amendment.  Id.  Additionally, courts have generally been even more receptive to pre-enforcement challenges to prosecution that impinges on First Amendment rights.

A pre-enforcement challenge is not the only option, of course.  Defenses can also be raised during an investigation. The memo’s suggested use of the FDC Act to investigate and prosecute misbranding by manufacturers may have precedent, but a misbranding charge against a practitioner who uses drugs or other products in gender-affirming procedures would be subject to multiple legal challenges.  First, the FDC Act is generally designed not to limit or interfere with the general practice of medicine.  See 21 U.S.C. § 396.  Second, absent some kind of contractual relationship between a provider and a manufacturer, a provider is generally immune from misbranding if the provider is not also selling a regulated product.

Nevertheless, individuals and organizations could be in receipt of grand jury or HIPAA subpoenas requesting records, or they could be visited by federal agents.  Healthcare providers and others that find themselves the target of a criminal investigation or recipient of a subpoena related to provision of gender-affirming care would be well-advised to obtain counsel experienced in FDA enforcement and prosecutions under the FDC Act.

Last week, FDA published a Request for Information (RFI) (here) seeking input from the public on its efforts to “to identify and eliminate outdated or unnecessary regulations.”  The Announcement raises several questions and issues for the device industry.

10-for-1 Rule and its effect on de novos.  The RFI reinforces Trumps January 31, 2025 executive order indicating that for every new regulation introduced, at least ten existing regulations must be eliminated (the “10‑for-1 Rule”).  To date, the 10-for-1 Rule does not appear to have impacted the granting of de novo authorization, which by their very process create a new classification regulation. Indeed, since the start of Trump 2, seven de novos have been granted.  The same order was in place during the first Trump Administration, with no actual impact on the issuance of new regulations for de novo authorizations, or any other regulations. During the first Trump Administration, the 10-for-1 Rule seemed to be more in name only when it came to FDA, whereas this administration seems more intent on its deregulatory approach, so we expect it to have more of an impact on FDA governance this time around. We will certainly be keeping a close eye on whether de novos become affected by this policy.

Radical Transparency.  The RFI promises that “HHS will publish annual reports detailing estimated regulatory costs and the specific rules being offset, promoting greater transparency and accountability.”  While transparency is an admirable goal, to date, the administration’s actions have stifled transparency, which will increase regulatory cost and burden for industry.  For example, while FDA updated certain guidance documents to remove terms offensive to this administration, like “gender,” since the start of Trump 2, not a single new device-related guidance has been issued.  Industry relies on guidance documents to understand the Agency’s current policy and practice.  Last fall, CDRH issued its annual guidance agenda (here) with dozens of planned guidance documents on important topics like cybersecurity, artificial intelligence, and device shortages.  It’s unclear if or when CDRH will begin issuing guidance documents again.

Beyond formal guidance documents, industry relies on prompt communication of 510(k) clearance and de novo authorization documents for new devices reviewed by FDA.  Following the April 1 reduction in force (RIF), however, there has been a significant delay in publication of these materials. For example, 510(k) summaries have routinely been posted within one to two weeks of the clearance. In April, not a single 510(k) summary was posted, however.  It wasn’t until early May that all of the 510(k) summaries (or statements) for the nearly 250 510(k)s cleared in April were posted.  As of the date of this post, not a single 510(k) summary has been posted for a 510(k) cleared in May even though the month is over half over.  We’ll be watching carefully to see if the trend of it taking a month or more to post 510(k) summaries continues.

Of the seven de novos granted since the Executive Order, two were issued before the RIF of April 1, and five after. None of the five issued after the RIF have posted classification letters. As we have previously reported, CDRH has a long history of failing to timely post decision summaries. The classification letters, however, were generally reported fairly quickly, within at least a month or so of the decision posting. It is therefore surprising that nearly a month or more has passed for four of these five de novos without any information being posted.

The impact of having no de novo classification letters and a lag in posting 510(k) summaries is significant, and will become more significant over time.  The classification letters are important because they include the special controls with which all similar devices must demonstrate compliance in a future 510(k) submission. It is necessary that the special controls be made publicly available as soon as possible to enable future manufacturers to use the de novo as a predicate device. The 510(k) summaries are similarly crucial to the development of new technologies because they allow companies to make substantial equivalence determinations about recently cleared devices. As FDA stated in guidance in 2023, “newer devices should be compared to the benefits and risks of more modern technology.” (here)

The delay in the availability of these documents may also create more work for CDRH review staff.  It is common for manufacturers, particularly those submitting a 510(k) using a de novo‑authorized device as the predicate, to submit a pre-submission to align on testing strategy and expectations.  Without access to the special controls, manufacturers will have no idea how to approach a pre-submission, which may require CDRH to provide significantly more guidance and direction than if manufacturers had a clear starting point to know at least the types of verification and validation that will be expected.

Deregulation Efforts.  The RFI is not all bad news and irony, though.  If this administration is actually interested in reducing regulatory burdens and getting novel technologies into the hands of providers more quickly, there is plenty of opportunity for CDRH to do so.  Over the last decade or so CDRH has moved away from granting clearance/authorization for new tools, instead forcing sponsors to get new clearances and authorizations for specific indications (e.g., specific patient populations, disease states, and procedures).  One examples of this is with robotic surgical devices, about which we have previously blogged  (here).  Not only has FDA required that each new robotic surgical device be authorized for a specific surgical procedure, FDA has also required that each system go through the de novo process, even if it is intended for the same surgical procedure(s) as an already cleared/authorized system. The administration could do some real good by bringing back the ability to get a tool, like a robotic surgical system, cleared so that those novel tools can be put in the hands of providers.

The RFI is open through July 14, 2025.  Comments can be submitted online through the docket (here) or through an online form specifically created for this effort (here).