We have reached maximum capacity for this Thursday’s webinar!  We are excited by the large interest in this topic, and are eager to share our insights about the latest changes impacting the FDA-regulated industry.  Registration is closed, but if you would like to be put on a waitlist or receive a recording of the webinar, please contact Amy Vasvary (avasvary@hpm.com).  If your plans have changed and you can no longer attend, please contact Amy so we can open your space to the waitlist.

As a reminder, Hyman, Phelps & McNamara, P.C. is hosting a free webinar on recent and forward-looking enforcement under the Federal Food, Drug & Cosmetic Act on Thursday, May 1, 2025, from 12:00 p.m. to 1:30 p.m. (ET).  Registration is limited, so don’t forget to register here to join us this Thursday.

HPM’s Anne Walsh will moderate a panel discussion with three former DOJ attorneys who all litigated extensively under the FDC Act.  The panel will include J.P. Ellison, a former trial attorney at DOJ’s Consumer Protection Branch (CPB), John Claud, a recent Assistant Director at CPB, and Andrew Hull, a former Assistant U.S. Attorney.

Equipped with significant FDC Act prosecution experience from their years as federal prosecutors, the panelists will address questions about how an FDC Act case is prosecuted, recent FDC Act enforcement cases, and what to expect under the new administration.  The panelists will also share their predictions on the increased role of state agencies and other prosecutions in the FDA space.

We published a version of this post several years back (see here), but recent updates to the law and trends in DEA enforcement merit a refresher.  The stakes are high when a DEA-registered practitioner, pharmacy, distributor, manufacturer, or other registrant receives an Order to Show Cause (or OSC) from DEA.  OSCs often appear without warning and can throw a registrant into a flurry of uncertainty and risk of losing a registration necessary to conduct business.  Failing to respond in a timely or appropriate manner may also result in a waiver of your rights.

If you are in receipt of an Order to Show Cause from DEA and lost as to what it means or what to do, read this short primer to help guide you in making necessary and correct decisions in a prompt manner to protect your business and preserve your rights.

What Is an Order to Show Cause?

An Order to Show Cause is DEA’s official initiation of an administrative proceeding to revoke or suspend an existing DEA registration or deny an application for a DEA registration. By law, DEA must provide you with notice and an opportunity for a hearing before it can take away your registration (or deny your application), so DEA will issue an Order to Show Cause, which explains the legal grounds for revoking or denying a registration and informs you of your right to challenge DEA’s decision.

What Are Your Options When You Receive an Order to Show Cause?

You have several options. The first is to request a hearing before one of DEA’s administrative law judges (ALJs). To preserve your right to a hearing, you must file a request for a hearing with DEA’s Office of Administrative Law Judges within thirty (30) days of service of the Order to Show Cause. A second option is to waive your right to a hearing and simultaneously file a written position statement, again within thirty (30) days of service of the Order to Show Cause. A third option is to ignore the Order to Show Cause, in which case DEA will request a final order based only on DEA’s evidence. Which option is right for you is a decision that is best made after consulting with experienced counsel.

If you decide to request a hearing, DEA’s revised hearing regulations require that you simultaneously file an Answer to the Order to Show Cause.  The Answer must address each factual allegation in the OSC and specifically admit, deny, or state that the party does not have and is unable to obtain sufficient information to admit or deny the allegation.  It is not enough to file a timely request for a hearing; failure to simultaneously file an Answer may result in default, and DEA will deem each factual allegation not denied to be admitted against you.

Failure to file a request for hearing and answer in a timely manner (i.e., 30 days from service) may result in a waiver of the right to a hearing and a default, absent a timely request for an excuse demonstrating good cause.

What Happens If You Request a Hearing?

A timely request for a hearing places your case on the docket of one of the ALJs. The ALJ will issue an order for prehearing statements and schedule a prehearing conference. At the prehearing conference, the ALJ will set a date and location for the hearing.

The hearing closely resembles a trial, but the ALJ (rather than a jury) is the trier of fact. Both the government (represented by DEA counsel) and you will have an opportunity to present your case through witness testimony and record evidence. Hearings can range from half a day to several weeks, depending on the complexity of the case. After the hearing, both parties may submit post-hearing briefs, and the ALJ will issue a recommended decision. The parties may file exceptions to the decision if they believe the ALJ made a factual or legal error in the decision. The recommended decision is submitted to the DEA Administrator who reviews the decision, rules on the exceptions, and issues a final order regarding your registration, either adopting or rejecting the ALJ’s recommended decision.

Not all cases end up going to hearing, however, as DEA is sometimes willing to consider a settlement resolution.

What Happens If You Waive Your Right to a Hearing?

If you choose to forgo a hearing, the government will forward your case with its evidence (along with any timely submitted position statement) to the Administrator. The Administrator will then issue a final order based on the review of the evidence and written statements provided.  Remember that all factual allegations in the Order to Show Cause that have not been denied will be admitted against you.

What Is an Immediate Suspension Order?

An Immediate Suspension Order is the exception to the rule that DEA will not revoke or suspend an existing DEA registration prior to a hearing. An Immediate Suspension Order allows DEA to suspend your registration upon a determination that there is an “imminent danger to the public health and safety.” An Immediate Suspension Order is served along with an Order to Show Cause, allowing you to challenge DEA’s determination that your registration should be revoked, but it takes away your ability to handle controlled substances while your case is pending. As a result, an Immediate Suspension Order can significantly (and immediately) affect your ability to practice medicine or operate your business.

What Is a Corrective Action Plan?

Recipients of an Order to Show Cause (except those also receiving an Immediate Suspension Order) are permitted to submit a Corrective Action Plan. A Corrective Action Plan provides an opportunity for the registrant to demonstrate remedial actions contemplated or taken, and requests DEA to discontinue the Order to Show Cause proceedings. What should be discussed or admitted in a Corrective Action Plan is a decision that likely should be made after seeking advice from an experienced attorney.

Are You Allowed to Have an Attorney Represent You?

You are permitted to proceed on your own (i.e., pro se) or to have an attorney represent you. Because of the complex nature of these proceedings and the stakes involved, representation by a law firm experienced in handling DEA hearings may be a necessity.

What Resources Are Available?

DEA’s Office of Administrative Law Judges has a website containing forms and links to a variety of helpful legal resources, including instructions on filing documents.  We also regularly blog on DEA administrative cases and procedures (see here), and our HPM attorneys have authored articles (see here and here) on the DEA hearing process.  Our experienced HPM attorneys stand ready to defend you or company when you face an Order to Show Cause.

Recent reductions in force (RIFs) and leadership changes at FDA are already affecting key agency functions—and as the administration plans a broader reorganization, the impact will likely grow. One area drawing increasing attention is how these changes will affect the drug development and review process.

As reported by the Wall Street Journal last week, reviews of both innovative and follow-on drugs have been caught in a traffic jam, largely due to a leadership vacuum at the Center for Drug Evaluation and Research (CDER). Senior officials have left, others haven’t been replaced, and internal morale is reportedly “a work in progress”—a euphemism that, frankly, isn’t very euphemistic. That’s all bad news if your timeline depends on FDA sticking to theirs.

The Prescription Drug User Fee Act (PDUFA) sets specific deadlines for FDA to act on applications—typically ten months from the date FDA files the application for standard review and six months for priority review. These timelines are sacred to both R&D teams and Wall Street, and historically, FDA has a solid track record. According to the agency’s own performance reports, FDA has earned an “A” over the past five years, even reaching or exceeding 97% of its review goals for 11 of 12 submission types in 2023.

But, in recent weeks, concerns have mounted that deadlines may slip. While we haven’t seen much slow-down yet in our work at HPM, we are aware of some applications that appear to be idling. A recent Bloomberg Law report noted that staff cuts have left reviewers juggling multiple roles, including some filling in for departed senior leaders while still covering their own work, all without the help of RIFed support staff. One reviewer described the situation as “chaotic,” and another simply said, “We don’t have the bandwidth.”

If you were hoping for signs of stabilization, other recent headlines suggest more turbulence. Reuters reports that FDA recently dismissed most of its user fee negotiators—just as the next PDUFA and GDUFA reauthorization cycles begin. These are the professionals responsible for negotiating how the agency gets funded. Swapping out experienced negotiators at the start of high stakes talks raises legitimate concerns about whether FDA is prepared for the administrative heavy lifting ahead. While a fresh perspective can be valuable, in this case, the agency may be refreshing its roster right into a disadvantage.

Like the WSJ, we believe the impacts of such drastic staff cuts are a near certainty, but we are also cautious not to attribute every delay or unanswered email to the RIF and leadership changes. Some regulatory actions or inactions like the three cited in the WSJ article may not be attributable to anything other than the machinations of a large agency and are of the sort that have plagued clients for years. FDA’s failure to respond to a substantive question in two weeks’ time is hardly cause for concern, the proximity to the RIFs notwithstanding. Exercising a keen eye to discern which actions or inactions are actually being caused by the recent events may aid us in being more effective at combating them.

For companies with pending or planned NDAs or BLAs, this environment calls for both defensive and offensive strategies. First, it’s wise to build in more time for FDA review—even if your data look great and your application is buttoned-up. That’s especially true for applications involving advisory committees, REMS evaluations, or pre-approval inspections. Second, clarity and focus in your pre-submission meetings are more critical than ever. These interactions—already short and highly structured—may now be your best shot at aligning with a stretched agency. And finally, if your business strategy hinges on hitting a PDUFA date, consider engaging regulatory counsel early to spot red flags well in advance. In this climate, getting the first cycle right isn’t just about speed, it’s potentially about survival.

In recent interviews, FDA Commissioner Dr. Marty Makary emphasized that no scientists or reviewers were affected by the RIFs, stating that the layoffs targeted administrative and support roles. He’s also committed to ensuring that remaining scientific staff have the tools they need. But it’s fair to say the full impact on remaining reviewers—now operating without both senior leadership and support infrastructure—has yet to be fully realized.

We’ll be back with more on this.

There is much change happening at FDA. In the wake of the April 1^st reduction in force, there has been a great deal of uncertainty about what the impacts will be. This rings particularly true amongst the rare disease patient community, along with many small biotech companies (and their investors) that take on the risk of developing orphan drugs for exceedingly small patient populations.

For nearly a decade, we at HPM along with the rest of the rare disease community have been advocating for greater consistency in application of scientific judgment and regulatory flexibility in the review of applications for rare diseases (see our call to action here). We knew that expertise in the “science of small trials” comes with years of experience of conducting drug reviews, and that certain review teams within CDER and CBER have more experience overcoming the well-known challenges in rare diseases. Last year, FDA heard this message and established the Rare Disease Innovation Hub to create a greater teamwork approach to considering rare diseases scientific and regulatory issues. But was this new flagship “hub” retained by the new administration?

Patients and their families and caregivers have long fought to have a seat at the table with decision-makers. This has been a slow culture shift to see patients as having a voice, dating back to the HIV/AIDS crisis in the 1980’s, expanded to the cancer advocacy movement in the 1990’s, and now with rare disease patients stepping up to have their voices heard to fill the gaps in the medical literature that is so limited in rare disease. Their advocacy has led to long-standing, highly successful programs (i.e., Patient Listening Sessions and Patient-Focused Drug Development meetings) to more systematically involve patients, allowing them to educate all stakeholders about their lived experiences and treatment needs. But are these programs still operating?

And beyond the RIF, where does rare disease and patient engagement sit in the priorities of newly confirmed Commissioner Makary’s MAHA (Make American Healthy Again) priorities? In this post, we’ve summarized what we’ve learned in the weeks post-RIF, as well as share late-breaking insights from Dr. Makary’s first interview as Commissioner published late last night.

Does the MAHA platform have a plan for those suffering from rare diseases?

As for the Rare Disease Innovation Hub, while those who launched the Hub (previous CDER and CBER Directors, Patrizia Cavazzoni and Peter Marks, along with CBER Deputy Julie Tierney) have departed the Agency, the key person hired to operationalize the Hub, Amy Comstock Rick, the Director of Strategic Coalitions, remains. Other key rare disease functions like the CDER Rare Disease Team (led by Kerry Jo Lee) and the CBER Rare Disease Liaison, Julie Vaillancourt, are still boots on the ground too.

Recent remarks from Amy Comstock Rick signal continuity. Speaking to the Biopharma Congress, she shared that the Hub’s goals of efficiency, centralization and coordination fit with the Trump Administration’s current focus for the FDA (US FDA Rare Disease Innovation Hub’s Goals Align With Trump, Leader Says). Her comments should reassure patients and product developers that the progress made with the launch of the Hub is maintained.

When created in 2024, one of the goals of the Hub was collaboration between CDER and CBER. This goal now seems to align with reported plans to merge the various FDA Centers. Although details of the proposed plan to build a unified therapeutic product center are sparse, one could envision enhanced collaboration across orphan drug and biologic review in furtherance of that common goal.

More recently, in his first interview as Commissioner, Dr. Makary took the opportunity to address the need for therapies for those living with rare diseases, calling out ultra rare patient populations in particular. He shared his vision (the full interview is available here):

When you are talking about rare diseases, a genetic issue that affects 52 kids in the world and that’s a real thing…or 15 kids…, you can’t expect the companies to do a randomized controlled trial. You’ll kill innovation. You’ll kill investment in those innovative ideas. You’ve got to say, “Hey, this is a very difficult condition. It’s incurable. It’s fatal. It’s a permanent disability. We’re going to customize the approval process to the condition. And, so, we’re going to be rolling out a new pathway for drugs, which is a pathway based on a plausible mechanism. If there’s a rare condition or a condition that’s incurable that affects a small number of people, we may be approving drugs based on a plausible mechanism on sort of a conditional basis.

Let’s say there’s a condition that affects 75 people in the world and there’s a treatment that makes sense physiologically. The mechanism is scientifically plausible that this treatment would help these individuals. No one’s forcing these medications on these individuals. If they want to try these new medications even though we don’t have a randomized controlled trial because it’s not feasible, we will allow that and at the same time monitor everybody who gets it so that we can make inferences as soon as the data speaks with a signal in the data.

The approach to development and regulatory pathway to approval for orphan drugs has been ever-evolving since the Orphan Drug Act was passed in 1983. While FDA has a long-standing history of exercising reasonable judgment when considering drugs for rare diseases (see our previous analysis here), asking FDA officials to “color outside of the lines” can only go so far. Dr. Makary’s proposal for a mechanism-based conditional approval approach to ultra-rare disease holds great promise.

We have seen firsthand the dire consequences of trying to apply regulatory standards that date back to the 1960’s (when the “substantial evidence” requirement was first established) to rare disease settings. We have seen development programs be halted despite great promise, and scientists’ life’s work, patients’ sacrifice from participating in trials, and difficult-to-obtain investment dollars be washed away when impractical study designs were expected. As a result of our cumulative experience across many dozens of ultrarare products in development, we at HPM have been advocating for a similar change to the standard of approval of drugs for ultra rare diseases. We want to give FDA review officials the tools they need to be able to reduce barriers and “customize” what development looks like for ultra rare products (see, e.g., coverage of Frank Sasinowski’s remarks at the May 21, 2024 EveryLife Foundation for Rare Diseases Scientific Workshop, Debating a new pathway for ultrarare).

Where does Commissioner Makary see a place for patients and their loved ones?

Based on our experiences working with patient organizations, it appears that both the patient affairs team responsible for Patient Listening Sessions within the Office of the Commissioner, as well as the Patient-Focused Drug Development (PFDD) staff across CDER and CBER are intact and operational. These programs have been successful in systematically eliciting the patient perspective on specific diseases and their treatments. The program helps FDA understand the context in which regulatory decisions are made for new drugs.

The flagship PFDD program, which consists predominantly of patient group-organized Externally-led Patient-Focused Drug Developments meetings (EL-PFDD) has been active. The current webpage for EL-PFDD lists at least 6 upcoming meetings, primarily focused on rare disease populations (Upcoming EL-PFDD Meetings | FDA). We know that at other EL-PFDD meetings have been granted in the last couple of weeks too. Continuation of these meetings in the face of other programmatic cuts is significant and gives us hope that the patient voice will continue to be heard.

Beyond existing programs, yesterday, Dr. Makary announced a new policy on individuals serving on FDA Advisory Committees, which includes an important commitment to include and perhaps expand of patient and caregiver participation. The announcement states, “As part of this effort, the agency will prioritize and elevate the role of patients and caregivers, strengthening the voices of their communities.” FDA has long-included patients and caregivers as voting members on advisory committees for drugs and biologics, as Patient Representatives, however the program staff have often not been given enough time or resources to recruit individuals with direct disease experience to participate on a particular committee. We hope the Commissioner’s prioritization of the patient voice will lead to a better-resourced Patient Representative program.

What should rare disease and patient stakeholders look for from here?

With every new administration comes change. Experience tells us that top-down policy priorities take time to have an impact on the day-to-day review work, if they do at all, as FDA leadership have many competing priorities and there will necessarily be public health emergencies that pull their attention. Ultimately, predictability and continuity of the drug and biologic review work at FDA are what drive investment and, therefore, innovation in medical research. The maintenance of rare disease and patient-focused personnel at FDA, in addition to the scientific and clinical reviewers themselves, many who have been staunch advocates for patients and their families, offers promise that innovation will not slow down.

However, the proof is in the pudding, so the community should keep an eye on the level of engagement review staff are able to maintain (including in-person sponsor meetings with FDA to provide expert guidance) and how well the Agency is able to meet its review timeframes (e.g., PDUFA dates for NDAs and BLAs being reviewed). We can be excited for new policies while also expecting accountability.

With a nod to the immortal phrase, “Bring out your dead!  Bring out your dead!” uttered by body collector Eric Idle, and to the Knights Who Say “Ni!,” from the 1975 comedy romp, Monty Python and the Holy Grail, in calling attention to Drug Enforcement Administration’s 27th National Prescription Drug Take Back Day, we say “Bring out your meds!  To the Feds!” to you.

Unwanted and expired controlled prescription medication languishing in medicine cabinets are prime candidates for theft, misuse and abuse.  DEA and its law enforcement partners will once again host local drop-off locations nationwide for safe disposal of unneeded medication on Saturday, April 26, 2025, from 10:00 a.m. to 2:00 p.m. local time.

DEA holds the ever-popular drug take back event each spring and autumn.  Last October’s Take Back Day collected almost 620,000 pounds, or 314 tons, of unneeded medication at over 4,600 collection sites nationwide.  DEA has collected over 19.2 million pounds, or 9,600 tons, of unneeded medication since 2010.  Additional information about National Prescription Drug Take Back Day, including disposal locations, can be found at: https://www.deadiversion.usdoj.gov/drug_disposal/takeback/takeback.html.  DEA’s Diversion Control website also lists permanent year-round drug disposal locations and provides other disposal information.

So, gather the kids and tell the neighbors, “Bring out your meds!  To the Feds!”

Hyman, Phelps & McNamara, P.C. is hosting a free webinar on recent and forward-looking enforcement under the Federal Food, Drug & Cosmetic Act on Thursday, May 1, 2025, from 12:00 p.m. to 1:30 p.m. (ET) (register here).

Join us as HPM’s Anne Walsh moderates a panel discussion with three former DOJ attorneys who all litigated extensively under the FDCA.  The panel will include J.P. Ellison, a former trial attorney at DOJ’s Consumer Protection Branch (CPB), John Claud, a recent Assistant Director at CPB, and Andrew Hull, a former Assistant U.S. Attorney.

Equipped with significant FDC Act prosecution experience from their years as federal prosecutors, the panelists will address questions about how an FDC Act case is prosecuted, recent FDC Act enforcement cases, and what to expect under the new administration.  The panelists will also share their predictions on the increased role of state agencies and other prosecutions in the FDA space.

We hope you will join us for this exciting and relevant discussion.  Click here to register.

In January 2025, FDA posted the 2024 Annual Report concerning the Accreditation Scheme for Conformity Assessment (ASCA) program as required by Medical Device User Fee Amendments of 2017 (MDUFA IV).   As we previously blogged, under the FDA Reauthorization Act of 2017 (FDARA), FDA committed to establish an ASCA Program using FDA-recognized consensus standards.  The ASCA pilot program concluded in 2023 after seven (7) years based on data demonstrating the pilot’s objectives were met or surpassed.

Under the ASCA program, FDA grants ASCA Recognition to qualified accreditation bodies to accredit testing laboratories, thereby granting the laboratories ASCA Accreditation.  The ASCA accredited testing laboratories perform testing for medical device companies to include in premarket submissions.   A Sponsor can choose to use an ASCA accredited laboratory for basic safety and essential performance and/or biocompatibility testing.

ASCA is designed to

• Enhance confidence in medical device testing;
• Promote consistency and predictability in the premarket review process;
• Encourage effective use of FDA resources;
• Enhance regulatory efficiency; and
• Support international harmonization.

When using ASCA, Summary Test Reports are included in a premarket submission using the format provided in the ASCA standards-specific guidance documents. Summary Test Reports and Declarations of Conformity include all critical data and testing conditions so that full test reports are not needed, making FDA’s review of the data during the submission more efficient.  FDA has stated by including ASCA Summary Test Reports in submissions,  they “will have confidence in the testing laboratories’ test methods and results.”

According to the ASCA 2024 Annual Report, the FDA received seventy-one (71) device submissions that contained ASCA accredited laboratory Summary Test Reports, a significant increase over the five (5) submissions received in 2022. While the number of submissions containing ASCA Summary Test Reports is growing, the numbers still appear to be low given the number of submissions FDA receives for devices that are required to include basic safety and essential performance or biocompatibility  documentation.

The majority of device submissions that included ASCA Summary Test Reports were for basic safety and essential performance, with only 25% for biocompatibility.  The good news is that out of the seventy-one (71) submissions noted in the 2024 Annual Report, only one (1) submission had deficiencies and only one (1) submission required FDA to request a full test report.  The fact that the majority of submissions that included ASCA Summary Test Reports successfully met biocompatibility and basic safety and essential performance requirements—which are areas Sponsors typically receive Additional Information requests—suggests the training provided by ASCA to both laboratories and Sponsors is paying off.  Prior to November 2023, FDA identified administrative and technical deficiencies in approximately 37% of submissions with ASCA Summary Test Reports during the pilot phase of the program.

As of December 2024, there are now 107 testing laboratories under ASCA Accreditation (102 for basic safety and essential performance and five (5) for biocompatibility), which gives Sponsors seeking to avail themselves of the ASCA program many options.  It should be noted, however, six (6) laboratories did request to withdraw from the program, for reasons not disclosed in FDA’s Annual Report.

As FDA’s concerns related to unreliable device biocompatibility testing data continue (see our blog post here), Sponsors may want to consider evaluating if an ASCA accredited testing laboratory could be a means to ensure the quality of their biocompatibility test data. In addition, Sponsors seeking to improve their device submission predictability, may want to consider an ASCA accredited testing laboratory for basic safety and essential performance and biocompatibility testing.

FDA’s Office of Prescription Drug Promotion (OPDP) issued its second Untitled Letter of 2025 to Taiho Oncology (Taiho) for a healthcare provider branded website for its drug LYTGOBI (futibatinib). This letter, dated March 21, 2025, cites Taiho’s false or misleading representations about the benefits of the drug, which is considered misbranding under the Federal Food, Drug, and Cosmetic Act. The letter is notable as it is the second OPDP enforcement letter describing violative promotion about an accelerated approval drug within the last six months. Join us as we break down what went wrong this time.

What Happened?

LYTGOBI was granted accelerated approval for the treatment of adult patients with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma (iCCA) with FGFR2 gene fusions or rearrangements. The FDA’s accelerated approval pathway can allow for earlier approval of drugs intended to treat serious conditions and fill an unmet medical need where approval is based on an effect on a surrogate or intermediate clinical endpoint that is reasonably likely to predict clinical benefit and the predicted clinical benefit is subsequently verified in a post-approval confirmatory trial(s). The Untitled Letter notes that the confirmatory trial for LYTGOBI is currently ongoing and has not been completed; therefore, clinical benefit of LYTGOBI has not yet been confirmed.

OPDP’s concerns center on Taiho’s “Efficacy Results” webpage, which highlights Kaplan-Meier survival curves for progression-free survival (PFS) and overall survival (OS), along with data from additional endpoints, from Taiho’s Phase 2 study, FOENIX-CCA2. The problem? As a single-arm trial (i.e., no comparator arm), FOENIX-CCA2 was not capable of establishing improvement on time-to-event efficacy endpoints such as PFS or OS and, without an appropriate comparator, “it is not possible to determine if the observed effect is attributable to LYTGOBI or to other factor(s), such as the natural history of the disease.” The website also reports a disease control rate (DCR) of 83% based on a non-prespecified follow-up analysis conducted 8 months after the primary analysis. DCR is defined as “the sum of complete response (CR), partial response (PR) and stable disease (SD).” However, the Untitled Letter describes the single-arm FOENIX-CCA2 trial could not establish that the observed SD was attributable to the effect of the drug so the webpage misleadingly suggests that LYTGOBI improves DCR in patients with locally advanced or metastatic iCCA based on a composite of CR, PR, and SD. The Untitled Letter states that a randomized controlled trial would be needed to assess delay in time to disease progression.

Taiho’s website also featured (less prominently) a number of disclaimers such as, “This data presentation is neither intended to draw conclusions regarding the efficacy of LYTGOBI nor to imply that there is a treatment effect of LYTGOBI on these time-to-event endpoints and the results should be interpreted with caution,” and “The extended follow-up data were collected after the primary analysis and are descriptive in nature, and results should be interpreted with caution.”

Not surprisingly, these disclaimers were simply not enough. The FDA emphasizes that intrahepatic bile duct cancers have an estimated 5-year relative survival rate and unresectable, locally advanced or metastatic iCCAs, such as those for which LYTGOBI is conditionally approved, is a serious public health concern where surgery is not an option and treatment for the condition involves serious risks. In such serious cancers, survival data is one of the most critical factors influencing treatment decisions and disclosures of the FOENIX-CCA2 trial’s limitations on the webpage do not correct or mitigate the misleading representations or suggestions of LYTGOBI’s efficacy.

Echoes from Past Warnings

The disclaimers included on the website were likely derived from FDA commentary on previously submitted marketing pieces. According to the Untitled Letter, the FDA previously pointed out concerns about Taiho’s marketing messages, particularly regarding the selective presentation of efficacy data. With this latest Untitled Letter, the Agency is sending another strong signal that failure to correct misleading claims could lead to harsher consequences.

But, where have we heard this all before? The Taiho Letter has almost identical observations to those cited in the 2024 Untitled Letter to Mirati Therapeutics Inc. (Mirati) about a healthcare professional branded website for KRAZATI (adagrasib). Promotion for KRAZATI, which was granted accelerated approval for patients with certain types of non-small cell lung cancer, was objectionable because of claims about DCR, OS and PFS based on a single-arm study. In that case, as in this instance, the inclusion of disclaimers did not mitigate the misleading impression left by the claims.

Both cases involve oncology drugs granted accelerated approval. Accelerated approval requires companies to submit all promotional materials for their product thirty (30) days in advance of the material being used. FDA did not object to the timing of the respective submissions in either letter.

Promoting Accelerated Approval Drugs

Taiho now faces a choice: revise its marketing approach or risk further regulatory action from the FDA.

Separately, these bloggers wonder whether the Untitled Letter to Taiho signals a specific focus on accelerated approval product promotion. Unlike the Untitled Letter to Mirati, the Taiho Letter includes no reference to FDA’s Bad Ad program – indicating that Taiho’s materials were on OPDP’s radar for other reasons. This newest letter makes 1/3 of the letters issued by OPDP over the past 12 months directed toward promotion of accelerated approval drugs. (Lest we be accused of overstating, in absolute numbers this means two out of the six Untitled Letters OPDP has issued.)

Marketing an accelerated approval drug can be messy. Marketers are often put in the difficult position of submitting materials 30 days in advance of use and then having to decide whether to “go live” with those materials when comments have not been received from FDA within that time frame. As readers of enforcement letters, we have the benefit of 20/20 hindsight when looking at promotional material, seeing study limitations disclosures and knowing they were insufficient to contextualize the representations. However, companies oftentimes need to make risk/benefit decisions about how to proceed with messaging and including disclosures/disclaimers is critical to ensuring presentations can be defended as truthful and non-misleading.

While it is our understanding OPDP staff responsible for reviewing advertising and promotional materials were not subject to the April 1 reduction-in-force, other areas of OPDP were impacted, which may lead to longer promotional material review timelines. Given these recent changes, these bloggers wonder whether the Taiho Letter may be the last Untitled Letter we see for some time, as the remaining FDA staff continue to navigate these unprecedented times. While we don’t always see eye-to-eye with OPDP reviewers when determining whether a communication is false or misleading, we’ve always appreciated that their perspective is grounded in FDA’s mission to protect the public health.

Last month, we blogged on the Department of Justice’s (DOJ) abrupt announcement that it had determined that removal restrictions protecting administrative law judges (ALJs) were “unconstitutional” and that DOJ would no longer defend those removal restrictions in court.  We opined that while the impact of this statement was unclear, it was likely that this position would make it more difficult for litigants challenging the constitutionality of a proceeding presided by an ALJ.

That’s precisely what happened in a recent decision out of the U.S. District Court for the District of Rhode Island in a case challenging a DEA ALJ’s authority to preside over a hearing as to whether the plaintiff’s application for a DEA registration should be granted or denied.  In MMJ BioPharma Cultivation, Inc. v. Bondi, No. 24-CA-127 (D.R.I.), the plaintiff—a company seeking to obtain a DEA registration to cultivate marijuana for research purposes—applied for a DEA registration, and then received an order to show cause from DEA as to why the agency should not deny its application.  The plaintiff requested a hearing before an ALJ, but then filed the lawsuit in federal court seeking injunctive relief and arguing that the constraints on the President’s power to remove DEA ALJs are “unconstitutional.”

The Court granted DOJ’s motion to dismiss.  Specifically, the Court held that the plaintiff failed to state a claim for injunctive relief because it did not demonstrate that it would suffer “irreparable harm” absent the requested relief, a key requirement for granting injunctive relief.  The Court noted the difference between “appointment” challenges—contesting the constitutional validity of the appointment of the officer adjudicating a case—and “removal” challenges, which address whether an officer is improperly protected from removal by the President.  The Court explained that just “because an officer is unconstitutionally protected from removal does not mean that they lack constitutional authority to carry out the role for which they were appointed.”  Id. at 5.  Instead, “there must be a showing that the unconstitutional [removal] provision affected or likely will affect the decision.”  Id. at 6.

Because the plaintiff solely pleaded that it was entitled to relief because the DEA ALJ presiding over its case was unconstitutionally protected from removal—and did not allege how these removal protections affected or were likely to affect DEA’s adjudication of its case—the Court dismissed the case.

We will continue monitoring other attempts to challenge the authority of DEA’s ALJs to preside over hearings, but, as we predicted, we expect that other attempts will face similar hurdles.

The recent and drastic Reduction In Force (RIF) at the U. S. Food and Drug Administration (FDA) is already having ripple effects not just internally, but across the broader regulatory and life sciences communities and the public at large. While much of the focus has been on how these cuts may impact application review timelines and industry engagement, see earlier post about the effect on generic drugs, another quieter consequence is emerging – a significant slowdown in the availability of information that FDA is required to produce under the Freedom of Information Act (FOIA).

FOIA is a U.S. federal law enacted in 1967 to promote transparency and accountability in the federal government by granting the public the right to request access to government records, subject to certain exemptions. As it relates to the FDA, FOIA serves as a vital tool for stakeholders – including patients, researchers, and regulated industry – to better understand the Agency’s scientific, policy and regulatory decision-making.

Documents that FDA discloses in response to FOIA requests can vary widely, from inspectional documents, like Form 483s and Establishment Inspection Reports, to correspondence between FDA and sponsors, and can be voluminous, such as 510(k) documents and other review memos. However, not all information contained in FDA records is disclosable. Under the law, FDA can redact or withhold information that falls under one of nine exemptions; the most commonly used exemptions are: information that describes FDA’s internal deliberative processes (Exemption 2), information that is prohibited from disclosure by other laws (Exemption 3), confidential commercial or financial information or trade secrets (Exemption 4), inter-agency and intra-agency communications (Exemption 5), information that could lead to an invasion of personal privacy of individuals (Exemption 6), and records or information compiled for law enforcement purposes (Exemption 7).

As a result of the RIF, stakeholders are now seeing longer wait times for both requested documents via FOIA and proactive disclosures, like approval packages routinely posted on Drugs@FDA which are required under the Food and Drug Administration Amendments Act (FDAAA)  to be posted within 30 calendar days of approval for new products or within 30 calendar days of the third FOIA request for the action package. In some cases, previously routine postings are delayed or going unpublished altogether. We also have heard from the remaining FDA FOIA staff that it could be at least a month before they can even provide a new estimate for when to expect responses under pending FOIA requests. For those requestors who already have been waiting months (or even years) for FDA to provide the documents that FDA put on a “complex” track, the staffing cuts are hugely disappointing.  Although there are avenues for escalating or litigating unreasonable delays for responding to FOIA requests, it is difficult to see how these approaches will be effective as no one may even be available to respond to an appeal until the dust settles.

Transparency has long been a cornerstone of FDA’s public health mission, and one that the new HHS Secretary and FDA Commissioner have reinforced as their priorities. But in these unprecedented times, as the Agency navigates the strain of recent workforce reductions, the ripple effects are increasingly hard to ignore. What began as a staffing challenge is quickly becoming an information bottleneck—one that threatens to erode the transparency that stakeholders rely on. If access to critical regulatory documents continues to slow or stall, the consequences could extend beyond inconvenience, ultimately impacting the ability of patients, providers, and developers to make informed decisions that affect public health.

The FDA Reduction-in-Force (Termination)—or “RIF(T)”—announced last week has resulted in countless stories in the press and on personal LinkedIn accounts from those RIF’d.  As the dust begins to settle and we all assess what this means for the future of FDA and the public health, generally, this blogger wanted to call out one particular division in the Office of Generic Drugs (OGD), funded by user fees under the Generic Drug User Fee Amendments (GDUFA), that was eradicated and what that might mean for the immediate future of generic drugs in America: the Division of Policy Development in the Office of Generic Drug Policy (OGDP), which was created in late 2013/early 2014 in part to implement the first iteration of GDUFA.

OGDP is one of several offices in OGD, and it was composed of three divisions: the Division of Legal and Regulatory Support, the Division of Orange Book Publication and Regulatory Assessment, and the Division of Policy Development (DPD).  As folks steeped in the world of generic drugs and Hatch-Waxman know, there’s a lot that happens before FDA can take action on an ANDA.  And DPD was a significant piece of that puzzle.

Among other things, DPD’s functions included:

• Facilitating the development, clearance, and publication of Product-Specific Guidances (PSGs). This included ensuring FDA consensus on the recommendations in the PSGs and working with the Office of the Commissioner to ensure their timely publication, either in “quarterly batches” of PSGs or as a “stand-alone” PSG when ANDA bioequivalence recommendations may be the subject of a pending Citizen Petition.  Indeed, since 2014, DPD facilitated the publication of 42 quarterly batches and dozens of stand-alone PSGs, plus three one-off batches of PSGs updated to align with recommendations in general guidance documents (g., the ICH M13A batch), totaling more than 3,000 PSGs (including PSG revisions).  About one third of these PSGs are for complex products and many reflect what OGD and DPD learned about the science of equivalence from GDUFA-funded regulatory science research.
• Leading FDA’s implementation of the Drug Competition Action Plan (DCAP). The DCAP was an initiative launched in 2017 to remove barriers to generic drug development, approval, and market entry (see our previous post here).  Under DCAP, DPD published dozens of guidance documents and Manual of Policies and Procedures (MAPPs), and completed many other initiatives in support of increased drug competition (g., facilitating the twice annual updates to the Off-Patent, Off-Exclusivity List).

• Publishing virtually every GDUFA guidance and MAPP since 2014 to fulfill FDA’s GDUFA commitments. Under GDUFA III alone, DPD published 32 GDUFA guidance documents and MAPPs to ensure the successful implementation of GDUFA.  DPD met all of the GDUFA commitments to publish policy documents (Section IX of the GDUFA III Commitment Letter) and published many others the Division determined would provide clarity to the generic drug industry.

• Processing voluntary ANDA withdrawals under 21 C.F.R. § 314.150(c). These Federal Register notices help generic drug sponsors clean up their ANDA portfolios and sometimes lower their GDUFA program fees.  Since 2019, when DPD took over this process, the Division has published more than 600 ANDA withdrawals at the request of generic drug manufacturers.

• Managing the process of issuing Covered Product Authorizations (CPAs) under the CREATES Act. This facilitated generic manufacturer’s access to samples of brand-name drugs not readily available through normal market channels for generic drug development.  Since the inception of the program, DPD reportedly met every GDUFA goal date for timely issuance of a CPA.

• Leading FDA’s policy implementation of the MODERN Labeling Act, the statutory authority allowing FDA to make certain generic drug labeling updates.

• Providing significant policy support to the annual update of the Orange Book Preface.

• Overseeing the development, clearance, and issuance of every policy document FDA issued on generic drugs. And, as you can see from FDA’s 2025 CDER Guidance Agenda, DPD was working on guidance documents from 180-day generic drug exclusivity, 3-year exclusivity, 30-month stays, pediatric exclusivity, comparative analyses for drug-device combination products, and many other guidance documents on generic drug “sameness” (including, we understand, a  revised version of the May 2021 guidance, titled “ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin” that  would have provided scientific and regulatory clarity for the development of ANDAs for generic versions of brand-name GLP-1 drugs.)

DPD also did quite a bit of additional behind-the-scenes work to support and facilitate ANDAs and OGD generally.  For example, DPD worked with subject matter experts from across FDA to clarify the scientific and regulatory pathway for the transition of generic metered-dose inhalers to different propellants, and presented publicly on this topic in December 2024.  But that’s all in the past now.  How these functions critical to the development and approval of generic drugs will now be handled (and by whom) is unclear.  But what seems quite clear is this: generic drug access, availability, and affordability will suffer without DPD.  We can only hope that the powers that be will promptly reconsider this move.

Promotional claims do not receive the most attention with respect to FDA enforcement these days, and veterinary promotion is no exception.  Indeed, most Center for Veterinary Medicine (CVM) Warning Letters arise because products advertised are actually new animal drugs.  But this year, CVM has issued two notable warning letters and one Untitled Letter concerning the promotion of animal drugs that caught our attention because of the level of detail and specificity included.  The detail with which CVM reviewed these promotions is reminiscent of OPDP/DDMAC letters of yore.

Let’s take a look at these letters:

Back in January 2025, CVM issued a Warning Letter to animal drug sponsor Elanco Animal Health.  Elanco is the manufacturer of recently approved Zenrelia (ilunocitinib tablets) (September 2024), which is indicated for “control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age.”  Zenrelia comes with serious warnings, including a boxed warning against the use of Zenrelia during vaccination.  However, several of Zenrelia’s promotional materials—specifically, FDA looked at a consumer-directed website, a product brochure and risk tracker, and a slide deck—omitted the specific phrase “from modified live virus vaccines” from the boxed warning found in the Important Safety Information.   The omission of the one short phrase, the Warning Letter says, is “misleading” because fatalities in the vaccine safety study used to support the New Animal Drug Application “occurred after administration of a MLV DHPP vaccination, a core vaccination for all dogs.”  The omitted phrase therefore provided “material facts that may be relevant to prescribing veterinarians and dog owners.”   CVM also objected to the truncation of other information about the timing of vaccines in these promotional materials.

Zenrelia promotional materials also included claims about clinical data that the Agency found actionable.  The Warning Letter alleged that the veterinarian product website made claims about a Vaccine Safety Study relied upon for approval that directly conflict with the PI.  Further, information presented on the adverse reaction data was inconsistent with the PI.  And, going into detail about the primary effectiveness endpoint, FDA raised concerns about claims allegedly exaggerating the speed of action for Zenrelia (i.e. that it is effective on “Day 1”) and insinuating  misleading comparative claims.

Not long after, in February 2025, FDA raised similar objections to promotional materials for Aurora Pharmaceutical’s three products, Altren (altrenogest) for suppression of estrus in mares, SwineMate (altrenogest) for synchronization of estrus in pigs, and Barrier (imidacloprid and moxidectin) for the prevention of heartworm in dogs, the first two which have “serious user safety warnings” and the third a boxed warning regarding exposure.  Reviewing the company website, CVM determined that it included “false or misleading claims and representations about the safety and effectiveness of these products,” thereby misbranding the product.  With respect to Altren, the webpage fails to contain any risk information, and a Product Sheet presents benefits and effectiveness information in a large, bulleted format while the risk information is in a smaller font on the second page.  It also omits risk information about the handling of the product.  For SwineMate, CVM objected to omission of information related to risks to humans, as well as important animal safety warning language, creating “a misleading impression about the consequences associated with using the drug.” The website also fails to include adequate directions for use.  And its Product Sheet suffers from the same infirmities as the Altren Product Sheet.  Finally, the website for Barrier for Dogs fails to contain any risk information, including the boxed warning from the PI.  And the Barrier Product Sheet included seven pages of benefit information, but risk information is presented only on a single page, in a smaller font, at the end of the brochure.

Finally, CVM issued an Untitled Letter in February 2025 to Zoetis due to promotional claims found on its Petcare YouTube Channel about the Company’s Librela (bedinvetmab injection), Solensia (frunevetmab injection), and Revolution Plus (selamectin and sarolaner topical solution).  FDA here cited false and misleading claims and representations about the risks associated with these products.  Specifically, the Librela ads show before and after treatment with no risk information, thereby making efficacy claims without fair balance, particularly because the Important Safety Information is not visible unless the viewer clicks on the “more” button to expand the text box.  Additionally, a video for Librela and two videos for Solensia contain voice-overs that discuss risk information related solely to the potential for self-injection by veterinary professionals who administer the drug without identification of the risks to the animal.  CVM stated that the “videos are misleading because they are aimed at the pet owner, yet they omit important safety and risk information for the animal species the drug is approved to treat. While there is some animal-related risk information included in superimposed text at the bottom of the video screen for a portion of the video….”  The safety text that is included is also small and difficult to read compared to the effectiveness claims.  Finally, a video for Revolution Plus titled “How to Apply REVOLUTION PLUS to Your Cat” is misleading because pictures of a child hugging a cat to whom Revolution has been applied implies that there are no safety concerns regarding humans interacting with any part of the cat after application of Revolution Plus, which is in direct conflict with the information in the Human Warnings section.

Zoetis and Elanco have previously been the target of CVM complaints about their promotion: Of 10 ULs issued by CVM re advertising since 2014, Zoetis received 4 – one in 2025, 2023, 2018 and 2016 and Elanco received 2 ULs – 1 in 2018 and another in 2015.

The allegations in the Warning Letters are serious, but that’s not why they’re so interesting.  They are that interesting because it’s not every day that we see Warning Letters and Untitled Letters with this level of promotional scrutiny coming out of CVM.  FDA really delved into the claims and the support for the claims on a level typically reserved for human drugs.   FDA’s review here of the claims for these animal products is reflective of the high standards to which FDA holds all promotion—human or otherwise.   We note that CVM has issued even more enforcement actions in 2025 than on the human side: OPDP has issued 2 Untitled Letters so far in 2025 compared with CVM’s 3 enforcement actions.  While OPDP has been scaling back its enforcement, CVM might be stepping it up.

Let this serve as reminder to veterinary companies: FDA is watching.

Come together with leaders from the pharmaceutical, biotechnology, and diagnostic industries to unpack huge changes at the American Conference Institute’s 23rd Advanced Summit on Life Sciences Patents, which is scheduled to take place from May 19-20, 2025 at the New York Bar Association in New York, NY.  In a year of major change and outstanding questions, growing scrutiny on patent protection and drug pricing, and uncertainty around global price control measures and the Inflation Reduction Act, understanding the implications of new leadership and emerging mandates is critical.

Gain insights from leading in-house counsel, patent prosecutors, litigators, and the US Patent and Trademark Office.  In addition, attendees will explore strategies to maximize patent terms, navigate the Unified Patent Court, and address key prosecution challenges.

Hyman, Phelps & McNamara, P.C.’s Kurt R. Karst will speak at a session, titled “Hitting the Books: Examining Orange and Purple Book Delisting from a Patent Prosecutorial Perspective,” along with co-presenters Kim Braslow (Senior Director, IP and Government Affairs, AstraZeneca) and Nicole Woods (Associate Vice President, Assistant General Patent Counsel, Eli Lilly and Company).

FDA Law Blog is a conference media partner. As such, we can offer our readers a special 10% discount.  The discount code is: D10-999-FDA25.  You can access the conference brochure and sign up for the event here.  We look forward to seeing you at the conference!

Last week, the Supreme Court issued a unanimous decision in FDA v. Wages & White Lion Investments, LLC, No. 23-1038 (Apr. 2, 2025) that affirms FDA’s denial of authorization to market flavored vape products. This opinion, which overrules a Fifth Circuit decision that FDA had acted arbitrarily and capriciously in denying premarket tobacco product applications submitted by manufacturers of flavored e-liquids for open-system e-cigarettes, marks the latest development in the ongoing debate and FDA regulation of flavored vape products.

By way of background, when FDA issued its rule in 2016 that deemed e-cigarettes and e-liquids to be tobacco products subject to regulation under the Family Smoking Prevention and Tobacco Control Act of 2009 (TCA), it required manufacturers of these products to obtain marketing authorization by submitting a premarket tobacco product application for their e-cigarette and e-liquid products (you can read more about the so-called “deeming rule” in our prior post here).

Following several years of delayed enforcement, FDA began reviewing a first wave of applications.  To the manufacturers’ chagrin, FDA squarely rejected approximately 1.2 million product applications belonging to 320 applicants—including the respondents—concluding that the manufacturers failed to provide sufficient product-specific scientific evidence to demonstrate enough of a benefit to adult smokers that would overcome the risk posed to youth.  Specifically, FDA cited the lack of “evidence from a randomized controlled trial, longitudinal cohort study, or another reliable and robust method that desert-, candy-, and fruit-flavored products had benefits over an appropriate comparator tobacco-flavored product.”  Id. at 16.

The manufacturers called foul, asserting that they had relied on a number of statements from FDA officials and guidance that suggested such product-specific and comparative scientific evidence would not be necessary.  In a scathing decision, an en banc panel of the Fifth Circuit agreed with the respondents, holding that FDA acted arbitrarily and capriciously and performed a “surprise switch” by “unquestionably chang[ing] its position and then pretend[ing] otherwise.”  (See our prior post on the Fifth Circuit’s decision here).

The Supreme Court overruled the Fifth Circuit, holding that FDA had not acted in an arbitrary and capricious manner.  Noting that respondents challenged the agency’s pattern of seemingly changing requirements and positions, the Court applied its “change-in-position doctrine.”  The doctrine acknowledges that “agencies are free to change their existing policies as long as they provide a reasoned explanation for the change,” “display awareness that they are changing position,” and “consider serious reliance interests.”  Id. at 22.  As a first step, the Court ascertains whether the agency has actually changed an existing policy.

Here, the Court found that FDA had not, in fact, changed an existing policy.  Sorting through a litany of statutory provisions, regulations, guidance documents, and public statements, the Court found that FDA never laid out a clear test on the type of scientific evidence necessary to support the manufacturers’ applications, and that FDA had made no hard-and-fast commitment as to the minimum evidence required for authorization.  The Court held that it was a “fair summary” of FDA’s position that (a) it was not essential for manufacturers to submit evidence based on well-controlled investigations, but (b) if they did not do so, they would have to provide rigorous scientific evidence that the sale of their products would be appropriate for the protection of the public health.  Id. at 28.

In short, FDA had provided “largely noncommittal guidance.”  Id. at 29.  Frustrating as that may be for the manufacturers, FDA’s denial orders did not constitute a change in existing policy.  The Court similarly found that requirements for comparative efficacy studies (comparing the health effects of the manufacturers’ non-tobacco flavored products to those of tobacco-flavored products), and FDA’s general approach of treating “closed” and “open” system flavored e-cigarette products the same, did not constitute a change in policy.

The Court remanded the case to the Fifth Circuit to determine whether FDA had engaged in harmless error when it abandoned a prior requirement that manufacturers submit its marketing plans for their products.

The Court’s decision marks an end to the circuit split caused by the Fifth Circuit’s en banc panel on this specific issue, but we fully expect continued litigation and regulation over this hot topic.  We will continue to monitor these developments as they unfold.