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).

On May 21, FDA announced “enhancements” to the Section 804 import program (SIP).  Section 804 of the Federal Food, Drug, and Cosmetic Act provides a pathway for certain prescription drug imports from Canada. The FDA news release provides that FDA is offering to pre-review SIP proposals and meet with individual states and tribes to provide initial feedback on the proposal, with the goal of reducing burden on the state or tribe.  FDA also announced that it is working to develop a “user-friendly” tool to help states in developing proposals and that it will assist states with options to streamline the required cost savings analysis that must be included in such proposals.

The announcement comes a little over a month after President Trump’s April 15 Executive Order (EO), “Lowering Drug Prices by Once Again Putting Americans First.  That EO provided that within 90 days, “the Secretary, through the Commissioner of Food and Drugs, shall take steps to streamline and improve the Importation Program under section 804.”  Presumably, the enhancements noted in FDA’s news release are intended to meet this objective.

While creating a user friendly tool and developing options to streamline the cost savings analysis may assist with expediting state SIP proposal submissions, there are still several hurdles for states and tribes to get over before actually being able to import prescription drugs from Canada.  After the SIP proposal submission, FDA must first authorize the SIP proposal.  From there, the state/tribe must submit a Pre-Import Request to FDA within twelve months of the SIP authorization.  That Pre-Import Request, which requires extensive information, must be granted by FDA before imports can take place.

While we are aware of at least five states that have submitted SIP proposals to FDA, only one state, Florida, has received FDA authorization.  FDA authorized Florida’s SIP proposal in January 2024, three years after the SIP proposal had been submitted to FDA and after Florida filed a lawsuit over FDA’s failure to respond to Florida’s FOIA request for records regarding its proposal.  Despite being a motivated party, Florida still has not begun importing prescription drugs from Canada.  Shortly after the SIP was authorized,  we noted the significant hurdles that remained before Florida could begin to import.  In December 2024, FDA granted Florida a six-month extension to submit its Pre-Import Request.

The Florida case raises real questions about whether the actions announced today, even if they reduce  the timelines for SIP proposal submissions, will meaningfully impact the overall timeline for states to begin importing drugs from Canada.

Following up on Donald Trump’s May 12 Executive Order on Most Favored Nation Prescription Drug Pricing (see our post here), The Department of Health and Human Services today issued a brief press release answering a few of the multitude of questions raised by the Executive Order.  First, most favored nation (“MFN”) pricing will apply only to brand products without generic or biosimilar competition.  In other words, MFN pricing will apply only to single-source innovator drugs, and not to drugs approved under ANDAs or to biosimilars.  The reference foreign countries will include only those in which the drug similarly does not have generic or biosimilar competition.

Second, the MFN target price will be the lowest price in a country that is a member of the Organisation for Economic Co-operation and Development (“OECD”) with a gross domestic product (GDP) per capita of at least 60% of the U.S. GDP per capita.  According to the U.S. Mission to the OECD, the organization currently has 38 member countries.  At the time of CMS’s November 2020 final rule with comment period to implement MFN pricing under Medicare Part B (a rule that was ultimately invalidated by several courts for procedural defects and then withdrawn), CMS had determined that 22 OECD countries had GDP per capita above the 60% threshold.  The 22 countries were identified in the preamble (click here), though that list may have expanded somewhat during the past 4½ years.  Like the previous regulation, the HHS press release states that HHS will use the lowest price among the economic peer countries.  However, a straight comparison between another country’s price and the U.S. price does not take into account differences in purchasing power between the two countries.  To address this problem, the 2020 regulation would have adjusted the comparator country’s price by calculating a ratio of its GDP per capita divided by U.S. GDP per capita, then dividing the country’s price by that ratio.  HHS may use a similar approach in developing its pricing targets under the Executive Order.

Third, the HHS press release, like Executive Order, makes no mention of limiting reduced pricing to Medicare and Medicaid.  On the contrary, the release states that each manufacturer will be expected to commit to lower pricing for all brand products “across all markets . . . .”

The May 12 Executive Order directed HHS, within 30 days, not only to develop MFN targets but to communicate them to pharmaceutical manufacturers.  The next questions likely to be answered are what the nature of those communications will be and which manufacturers will receive them.  To be continued . . . .

Last month the U.S. Attorney’s Office for the Northern District of Illinois announced that Walgreens agreed to pay up to $350,000,000 to resolve allegations that its pharmacies illegally filled millions of invalid prescriptions for opioids and other controlled substances in violation of the federal Controlled Substances Act, and sought payment for filling many of those prescriptions by federal health care programs, violating the False Claims Act.  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.  The government complaint, filed January 16, 2025, and amended April 18th, alleged that Walgreens pharmacies “knowingly filled millions of unlawful controlled substance prescriptions” between August 2012 and March 2023 “despite clear red flags indicating a high likelihood that the prescriptions were invalid because they lacked a legitimate medical purpose or were not issued in the usual course of professional practice.”  Id.

We have regularly posted on recognized prescribing red flags that pharmacists have ignored that resulted in administrative or civil actions by the Drug Enforcement Administration (“DEA”) including against Gulf Med and Coconut Grove pharmacies in Florida and Zarzamora Healthcare LLC in Texas.  We thought that it would be instructive to review the prescribing red flags alleged in the recent high-profile Walgreens settlement and complaint for an insight into current DEA dispensing expectations.

As mentioned in Federal Register Vol. 86, 72703 (December 22, 2021), DEA emphasized in the Gulf Med decision that prescribing “[r]ed flags are circumstances surrounding a prescription that cause a pharmacist to take pause, including signs of diversion or the potential for patient harm.”  While the presence of a dispensing red flag does not prohibit a pharmacist from filling a controlled substance, it “means that there is a potential concern with the prescription, which the pharmacist must address and…make a record of its resolution, assuming it is resolvable.”  Id.

For a controlled substance prescription to be “effective,” that is valid, it must be issued for a legitimate medical purpose by an individual practitioner acting in the usual course of their professional practice.  21 C.F.R. § 1306.04(a).  Prescribers are responsible for the proper prescribing and dispensing of controlled substances, but pharmacists have a corresponding responsibility to ensure that prescriptions they fill are issued for legitimate medical purpose and in the usual course of professional practice.  Id.  As the Walgreen’s Amended Complaint notes, “Pharmacists are professionally educated and trained to recognize and assess red flags and to determine whether a prescription is valid.”  Complaint, ⁋ 82.

The Walgreens Amended Complaint recognizes the following prescribing red flags:

1. Prescribers who prescribe the same medication, with the same directions, for the same quantity, for a large number of individuals. ⁋ 81.
2. Prescriptions of drugs or drug combinations that are frequently sought by individuals known to abuse or misuse prescription drugs, including the combination of an opioid, a benzodiazepine and a muscle relaxant, known as the “trinity.” ⁋⁋ 81, 86, 251.
3. Patients who repeatedly seek early fills of schedule II prescriptions or refills of schedule III-V prescriptions earlier than the date the drug would have run out if taken according to the prescriber’s instructions. ⁋⁋ 81, 89, 251.
4. Opioid prescriptions for high dosages and quantities, including prescriptions that individually or in combination, provide patients with daily dosages of greater than or equal to 300 Morphine Milligram Equivalents (“MMEs”). ⁋⁋ 84, 251.
5. Patients filling prescriptions from multiple prescribers, particularly for the same type of controlled substance or dangerous combinations of drugs. ⁋ 87.
6. Patients filling prescriptions at the same time at multiple pharmacies. ⁋ 88.
7. Patients traveling long distances to the prescriber and/or to the pharmacy. ⁋ 90.
8. Patients paying cash or a cash equivalent for controlled substance prescriptions, especially when they use insurance to pay for other prescriptions. ⁋ 92.

The Walgreens Amended Complaint notes that pharmacists “may be able to resolve a red flag by reviewing the patient’s diagnosis to confirm the drug prescribed is an appropriate treatment for the patient’s condition, reviewing the pharmacy’s dispensing history for the patient or prescriber, contacting the prescriber, or checking the state prescription drug monitoring program (PDMP) database to see all of the prescriptions obtained by the patient.”  ⁋ 93.

As noted in the Press Release, along with the monetary payment, Walgreens entered into a seven-year Memorandum of Agreement (“MOA”) with DEA to implement measures to prevent dispensing controlled substances without resolving red flags.  The MOA requires Walgreens to maintain policies and procedures requiring pharmacists to confirm the validity of prescriptions prior to filling, provide annual training to employees about their obligations related to controlled substances, ensure that staffing is sufficient to enable employees to comply with their obligations and maintain a system that blocks prescriptions issued by prescribers known to write non-legitimate prescriptions.  Walgreens also entered a five-year Corporate Integrity Agreement with Health and Human Services-Office of the Inspector General also related to controlled substance dispensing by its pharmacies.

The Amended Complaint, MOA and Corporate Integrity Agreement provide sound framework for identifying and not filling prescriptions exhibiting red flags.

Operation Stork Speed is a go!

On March 18, 2025, the U.S. Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA) launched a significant initiative called Operation Stork Speed to bolster the availability and safety of infant formula in the United States (see our previous blog post here).

The March announcement outlined six key actions underlying Operation Stork Speed, including the launch of the first comprehensive review of infant formula nutrients (see 21 C.F.R. § 107.100) since 1998.  HHS/FDA explained that such a review would help update the nutrient requirements for infant formulas, ensuring they meet the evolving needs of healthy, full-term infants.

Approximately two months later, HHS/FDA made good on their pledge.  On May 13, 2025, HHS/FDA published in the Federal Register, as well as via an FDA news release, a request for information and data to initiate the nutrient review process for infant formula.  The agency intends to use the collected information to determine what actions, if any, should be taken to update the nutrient requirements.  Purportedly, this review aims to ensure that infant formulas continue to meet the nutritional needs of infants and reflect the latest scientific research.

Specifically, FDA is requesting comments on the below six questions.

• What new scientific data or information since the 1998 comprehensive assessment should we consider regarding nutrient requirements for healthy, full-term infants that are associated with positive short- and/or long-term health outcomes?
• What scientific data or information have emerged since the 1998 comprehensive assessment regarding nutrient intakes for healthy, full-term infants that are associated with poor short- and/or long-term health outcomes?
• Which existing nutrients required in 21 C.F.R. § 107.100 should we review? Please explain your rationale.
• For the nutrients required in 21 C.F.R. § 107.100, what, if any, adjustments should be made to existing minimum or maximum levels? For the 20 nutrients with only a minimum level, which, if any, should have a maximum level added?  Please explain your rationale.  For example, describe how changes might positively impact health outcomes.
• What other nutrients (e.g., docosahexaenoic acid and arachidonic acid) or specifications for nutrients (e.g., ratio of linoleic acid to alpha-linolenic acid), if any, should we consider adding to 21 C.F.R. § 107.100? Please explain your rationale.
• Which nutrients, if any, should we remove from 21 C.F.R. § 107.100? Please explain your rationale.

Any interested parties should submit comments within 120 days of the Federal Register publication.

In his remarks at the Food Drug Law Institute’s Annual Conference last week, Commissioner Makary noted that FDA plans to convene an expert panel in June as part of Operation Stork Speed, but the Agency has not yet formally announced those plans.  Commissioner Makary also acknowledged some consumers’ desire for infant formulas free of certain ingredients such as seed oils.  It is not yet clear how FDA plans to address that issue.  We will continue to monitor Operation Stork Speed’s progress and report on any further developments.

Dr. Marty Makary took the stage on Thursday at the Food and Drug Law Institute’s Annual Conference, continuing the tradition of Commissioners speaking at this event, but with a tone and tempo distinctly his own.

Now firmly in the chair after the agency’s controversial RIFs—which he was quick to remind everyone he did not initiate—Commissioner Makary said that the FDA’s future depends on rebuilding its culture, empowering its staff, and applying his vision of the now oft-repeated “gold standard science and common sense.” The agency, he noted, isn’t a passive inbox for industry petitions. It’s a brand—the greatest in the world, he said—and he thinks that change is needed to live up to that lofty reputation.

Many of the Commissioner’s comments were familiar to those who have followed his podcasts and book rounds: he firmly believes the FDA’s regulatory model needs disruption. Dr. Makary noted that he doesn’t believe that the traditional playbook works for everything—particularly in the case of life-threatening diseases where randomized controlled trials are neither feasible nor humane. “Stage IV cancer should not be approved like a cosmetic,” he quipped, quickly calling to mind his days as an oncological surgeon and the many difficult conversations he had with patients and families with very limited options. Industry can, however, expect smarter tailoring of regulatory frameworks by condition, product type, and risk. He also specifically mentioned rare diseases here, in addition to his example of late-stage illnesses.

While Commissioner Makary reiterated the “no reorganization” refrain that has been consistent since he took the helm, he is interested in reducing internal redundancies and called for more consolidated operations and smarter tech.  He spoke with obvious enthusiasm about the recently announced pilot AI-assisted review and its potential to shave weeks off approval timelines, as he described hearing from one reviewer in the pilot project who said the pilot AI tool completed three days’ work in gleaning salient facts from medical literature in six minutes.

Beyond regulatory work, the Commissioner ventured into what he called “crossing into advocacy,” especially relating to food regulation. Citing the chronic health crisis among children, he challenged attendees to rethink society’s tolerance for environmental and dietary toxins, from petroleum-based food dyes to candy coated in talc. “Kids don’t have a willpower problem,” he said. “We’ve been poisoning them and drugging them at scale.” Expect new expert panels starting in June on infant formula, menopause, and peanut allergies, and a renewed focus on the upstream causes of America’s downstream health costs.

He delivered sharp words on tobacco and e-cigarette imports, warning that foreign manufacturers are gaming our “porous border” by importing products that would be illegal in their own countries. He also promised a clearer vaccine framework from CBER perhaps in a matter of days, a stronger commitment to “the letter and the spirit of Right to Try,” and major investment in post-market safety surveillance via big data.

Commissioner Makary made it clear that he isn’t here to maintain the status quo and he is here to shake loose entrenched assumptions, and remind industry of his view that common sense, in the right hands, can be a regulatory force multiplier. How he will impose common sense on policy will unfold over the next few months.  We’ll be back with updates.