As part of the review of a BLA, NDA, or ANDA, FDA assesses the manufacturing facilities named in the application to determine whether they can perform the proposed manufacturing operations in conformance with CGMP requirements, and whether the data submitted in the application are accurate and complete.  In some cases, FDA determines that information is needed from a pre-approval inspection (PAI) or pre-licensure inspection (PLI) in order to approve or license the product.

Traditionally, this would mean an in-person inspection, but FDA has other options available, as described in the recently published Guidance for Industry on Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications (Alternative Tools Guidance).  While the document provides some meaningful insights, it is largely a repackaging of three existing alternative tools that we’ve blogged about before, now presented specifically in the context of a PAI or PLI:

1. Remote Regulatory Assessment (RRA)
2. Remote Interactive Evaluation (RIE)
3. Mutual Recognition Agreement (MRA)

The first two tools are discussed in relation to each other, and both RRA and RIE are also covered in standalone guidances.  An RRA is an entirely remote evaluation of a facility, which can include a records request under FD&C Action section 704 (a)(4) (21 USC § 374(a)(4)).  An RRA could potentially obviate the need for an in-person PAI/PLI, or could be used to resolve application-specific deficiencies identified during a prior PAI/PLI.

While record requests under section 704(a)(4) are mandatory, an RRA is not itself considered an “inspection”—meaning that no Form FDA 483 will be issued at its conclusion.  As described in the Alternative Tools Guidance, an RRA can also include an RIE during the application assessment.  An RIE could involve, for example, livestreaming a production area so Agency staff can observe a specific manufacturing process.  Unlike RRAs, participation in an RIE is voluntary and largely depends on the facility’s technological capabilities.

The Alternative Tools Guidance addresses inspections conducted by “trusted foreign regulatory partners” (i.e., foreign nations with which FDA has an MRA).  FDA currently has MRAs in place with the European Union, Switzerland, and the United Kingdom.  These agreements allow FDA to legally recognize inspections conducted by those regulators in their respective countries (21 USC § 384e). MRA recognition applies to both same-country inspections (e.g., a Swissmedic inspection of a facility in Switzerland) and third-country inspections (e.g., a Swissmedic inspection of a facility in China).

Under the Food and Drug Omnibus Reform Act (FDORA), enacted December 2022, FDA is required to report the number of routine surveillance and for-cause MRA inspections it has recognized (21 USC § 360(h)(6)(A)(vii).  In FY2023, FDA recognized 199 MRA surveillance inspections; that number increased slightly in FY2024 to 206 inspections.  However, based on the FY2023 and FY2024 data, FDA has yet to recognize any for-cause MRA inspections.  Additionally, while FDORA gave FDA the authority to recognize MRA inspections “in order to facilitate preapproval”, the Agency acknowledges in the Alternative Tools Guidance that it “has not to date recognized PAIs or PLIs conducted by a foreign regulatory authority” (page 8).

Unfortunately,  FDA is not using the Alternative Tools Guidance to announce any plan to expand recognition of MRA inspections.  However, when a facility lacks sufficient FDA inspection history, the Agency may request inspection reports from an MRA partner and use that information to determine whether a PAI or PLI is necessary.  As a longer-term strategy, FDA is also evaluating remote participation in inspections conducted by foreign regulators.

The final section of the Alternative Tools Guidance describes how FDA subject matter experts (SMEs) may participate virtually in a PAI/PLI.  Anyone who has taken part in an FDA surveillance or for-cause inspection knows that investigators often confer with FDA SMEs located off-site.  The new Guidance now provides a framework for remote FDA SMEs to engage directly with the facility staff during a PAI/PLI.  Interestingly, the facility must agree in writing to the use of a remote SME; a firm may decline this request but, as the Guidance notes, doing so may “prolong a decision on an application” ( page 7).

Practically speaking, FDA’s use of alternative tools will be risk-based and remain at the Agency’s discretion.  As the Guidance states, “FDA does not intend to grant requests from applicants or facilities for FDA to use alternative tools” (page 5).  While RRAs may be used to collect information in advance, facilities with no regulatory inspection history or with unresolved compliance issues from prior inspections should still expect an in-person PAI or PLI.

On October 3, 2025, FDLI published an article analyzing Warning Letters (WLs) issued since January 9, 2020 by Hyman, Phelps & McNamara P.C.’s Véronique Li and Jeff Gibbs.

The in-depth analysis identified posting and issuance patterns, the length of time between milestone activities such as the conclusion of some FDA activity (e.g., inspection or promotional review) and issuance of a WL, volume trends over time, and trends in citations.

Given that WLs are issued on average 124 days after an inspection, companies should not interpret the absence of a WL within 30 working days as meaning that no WL is forthcoming. Rather, they should look to observations in the Form FDA 483 and other WLs to aid in predicting whether they are likely to receive one themselves. While the circumstances will vary for individual companies, knowing these patterns can help companies understand the probabilities of different outcomes.

The authors also determined that close-out letters, issued when a response demonstrates that violations have been corrected, or implementation of corrective actions was adequate, or a follow-up inspection does not reveal other significant violations, are becoming rarer. They caution that the number of WLs that have not received a close-out letter will grow unless FDA changes priorities or resource allocations particularly in light of recent reductions in FDA personnel.

FDA has long permitted ANDA applicants to “carve-out” patent-protected uses from product labeling, resulting in differences between the Reference Listed Drug and the ANDA.  Legal challenges to the carve-out are not new: The GSK v. Teva saga, followed by the Amarin v. Hikma litigation, made clear that Reference Listed Drug sponsors are no fans of the carve-out.  But the recent highly-publicized challenges have originated from patent law, essentially taking the position that ANDA manufacturers induce infringement by promoting their carved-out generics as AB-rated or therapeutically-equivalent to the fully-labeled Reference Listed Drugs (even though such a generic is only AB-rated insofar as it is labeled the same as the brand-name drug).  While we’re still waiting to see if the induced infringement theory renders the carve-out effectively dead (and whether legislation will revive it), the D.C. Circuit recently had the opportunity to take on an Administrative Procedure Act (APA) challenge to the carve-out as one of the first suits challenging FDA’s authority after Loper Bright.

In 2024, Novartis sued FDA in the District Court of D.C. under the APA for approving MSN’s ANDA for a generic version of ENTRESTO (sacubitril/valsartan) with a carve-out of a patent-protected use.  Specifically, MSN carved-out a modified dosing regimen for patients not taking other drugs used to treat heart failure.  The generic label included an indication for chronic heart failure with reduced ejection fraction, which was an indication previously on the ENTRESO labeling before the addition of the modified dosing regimen. The proposed label also stated that the generic drug “contains anionic forms of sacubitril and valsartan, and sodium cations.”  Novartis argued that the carve-out was improper, as it both rendered the product less safe and effective than the Reference Listed Drug and impermissibly added words to the indication statement, rather than simply omitting words as permitted under the statute.  Novartis also argued that the complex active ingredient in the Reference Listed Drug is not the same as the active ingredient in the ANDA.

This lawsuit comes on the heels of a 2019 and repeat 2022 Citizen Petition (Docket No. FDA-2022-P-2228), both filed by Novartis, asking FDA to reject any generic version of ENTRESTO that does not present the active ingredients—sacubitril and valsartan—“in the same chemical structure.”  Novartis also asked that FDA prohibit the carve-out of its patented uses from its label, arguing that carving out the modified dosage would impermissibly render the generic version less safe and effective than the Reference Listed Drug.  Finally, Novartis argued that such a carve-out would require the impermissible addition of words to ENTRESTO’s existing label (i.e., the so-called labeling “carve-in” or “chubby label” approach FDA first took with generic SENSIPAR (cinacalcet) Tablets and then discussed later in a Citizen Petition response (Docket No. FDA-2017-P-3672) concerning generic VELCADE (bortezomib) Injection – see our post here).  FDA denied both petitions in July 2024 and approved the MSN ANDA, and Novartis filed this suit seeking to set aside FDA’s denial of the petitions and approval of the ANDA.  Novartis lost in the District Court and immediately appealed.

In this appeal, Novartis asked the Court to resolve two questions:

1. Did FDA approve labeling for generic ENTRESTO that impermissibly deviates from the ENTRESTO label (i.e., labeling carve-out)?
2. Did FDA unreasonably conclude that the generic drug has the same active ingredients as ENTRESTO?

To address the first question, the Court looked at FDA’s reasoning for approving the language change omitting the modified dosing regimen.  While Novartis argued that the omission rendered the generic “less safe or effective” than ENTRESTO in violation of 21 C.F.R. § 314.127(a)(7), the Court found that FDA’s Citizen Petition “analysis turns squarely on the FDA’s expertise in evaluating the clinical significance of drug studies, which” the Court “will not lightly second-guess.”  Indeed, FDA looked at a study relied upon by Novartis showing that patients not taking concomitant heart drugs “might” have fewer side effects with a modified dosing regimen and determined that 1) the study was not sufficient to prove that the dosing regimen would put patients at any greater risk of adverse reaction, and 2) any adverse reaction could be adequately managed through the warnings included in the generic labeling.

The Court also determined that allowing MSN to omit the modified dosing regimen could be “reconciled with [the Agency’s] approval of the regimen for Entresto itself” even though “[b]oth decisions rested on the same titration study.”  Novartis argued that either the results of that study were robust enough to require inclusion of the modified regimen on both labels or its results were inconclusive enough to foreclose the inclusion on either label.  The Court said that FDA’s reasoning that ENTRESTO is safe and effective with the modified regimen “does not foreclose a later determination that the generic equivalence is not ‘less safe or effective’ without it.”  There thus is no unexplained change in the Agency’s position.

Next, the Court looked at the concerns about a difference in indications. Novartis argued that FDA compared the ANDA labeling to an old version of the ENTRESTO labeling, which had an indication only for patients with a reduced ejection fraction.  The Court found that that allegation was wrong: “FDA plainly compared it to Entresto’s current label.”  And, more importantly, the Court found that the addition of four words to the indication section was not impermissible, as those words were added specifically to omit an indication.  “[T]hat is how this scheme is supposed to work; an ANDA applicant may ‘propose labeling for the generic drug that ‘carves out’ from the brand’s approved label the still-patented methods of use.’”

Finally, Novartis challenged FDA’s finding that ENTRESTO and the ANDA have the same active ingredients.  Novartis claimed that ENTRESTO’s active ingredient is a complex, while the ANDA’s is not a complex.  But the Court found that “longstanding FDA regulations and guidance make clear that drugs can have the same active ingredients even if they have different solid-state physical forms or crystal structures” and that “FDA convincingly applied that principle in rejecting Novartis’s request to require generic drugs to have the same co-crystal structure as Entresto.”

The long-short of the decision is that Novartis gave the Court “no reason to question the FDA’s expert judgment regarding these scientific issues.”  Even after Loper-Bright, the Court is going to continue to defer to FDA on matters of science.

Moreover, the carve-out lives on at FDA, even if a few words are necessary to properly carve-out an indication (and even if it can induce infringement).

On September 30, 2025, FDA released a Request for Public Comment: Measuring and Evaluating Artificial Intelligence-enabled Medical Device Performance in the Real-World. Comments are due to the docket by December 1, 2025.

The request for comments is to obtain feedback about the “current, practical approaches to measuring and evaluating the performance of AI-enabled medical devices in the real-world, including strategies for identifying and managing performance drift, such as detecting changes in input and output.” The driving concern appears to be assessing whether the devices “remain safe and effective throughout their life cycle.”

Specifically, the agency is looking for information on methods that are:

• Currently deployed at scale in real-world clinical environments,
• Supported by real-world evidence, and
• Applied in clinical (patient- or health care worker-facing) settings.

While the request sets forth a number of specific questions for consideration—many of which would appear to require disclosure of potentially confidential or proprietary information—a critical and unanswered question relates to how FDA intends to use the information it receives from this request. One paragraph in particular caught this blogger’s attention:

Currently, many AI-enabled medical devices are evaluated primarily through retrospective testing or static benchmarks. While these methods may help establish a baseline understanding of the medical device performance, they are not designed to predict behavior in dynamic, real-world environments. Ongoing, systematic performance monitoring is increasingly recognized as relevant to maintaining safe and effective AI use by observing how systems actually behave during clinical deployment.

While it may be too early to conclude that this language is cause for concern, it certainly should give manufacturers of AI-enabled devices a reason to take a pause and consider submitting comments.  Even assuming it is true that the data and information provided in a premarket submission are not designed or intended to demonstrate long-term safety and effectiveness, it is not clear how FDA intends to remedy this post-hoc. Would FDA try to impose post-market requirements on currently marketed AI-enabled devices even if those devices were authorized without any such requirements? What would be the legal authority for doing so? There could also be impacts on the pre-market side, for example, if FDA takes learnings from this public comment period to impose additional pre-market requirements moving forward that could potentially impact substantial equivalence determinations.

We agree that is it important to determine how to ensure the ongoing safety and effectiveness of AI-enabled devices, but in doing so it will be important not to impose new or different requirements for this particular device type, as that would require statutory changes. We would encourage manufacturers to submit comments emphasizing that post-market obligations for medical devices are appropriate for all device types, including AI-enabled device types, even if the methods for collecting that information may be different. We would be happy to help you with your submission.

On September 11, 2025, Reps. Diana Harshbarger (R-TN) and Buddy Carter (R-GA)—the only two pharmacists in the U.S. House of Representatives—introduced a new bill, titled “Drug Shortage Compounding Patient Access Act” (H.R. 5316), that would expand the ability of compounding pharmacies and outsourcing facilities to compound products during a drug shortage, while also providing these entities with a greater sense of regulatory certainty while trying to serve patients when the FDA-approved supply chain fails.

What Does the Bill Say?

The legislation would codify FDA policies—similar to the temporary policies implemented during the COVID-19 pandemic—that allowed compounding of medications for urgent hospital needs during particular shortage situations.  Specifically, it would:

• Authorize Section 503A pharmacy compounding during shortages:  Allow state-licensed 503A compounding pharmacies to compound FDA-approved drugs that, among other requirements, are on the shortage list for urgent hospital or clinical use when the hospital or clinic has documented that it is not able to procure the drug from the manufacturer or a Section 503B outsourcing facility.  FDA similarly permitted this Section 503A “office use” compounding for hospitals and clinics during the COVID-19 pandemic and also expanded Section 503B outsourcing facilities’ ability to compound COVID-19 medications in short supply.  See our April 2020 blog posts discussing these temporary FDA policies here and here.
• Provide transition periods:  Require a 60-day transition period for Section 503A pharmacies and a 180-day transition period for Section 503B outsourcing facilities to carry on compounding medications once a shortage has been declared resolved.  This appropriately permits compounders to diminish their supplies of API and finished products after the resolution of the shortage.
• Update compounding lists:  Require FDA to annually update the list of 503B bulk drug substances that can be used in compounding, thereby providing further clarity and regulatory certainty for Section 503B outsourcing facilities in more quickly defining what these facilities can—and cannot—compound.
• Improve drug shortage reporting:  Mandate that FDA-approved drug manufacturers report anticipated supply disruptions, including, for the first time, anticipated surges in demand, and that FDA consider “real-world data” from hospitals and patients when designating shortages.
• Provide clarity around monographed dietary supplements:  Allow compounders to use USP/NF monograph dietary supplements in their compounded drug products.  Notwithstanding Section 503A’s use of the term “USP/NF monograph” when addressing what bulk substances may be used in compounding, FDA has limited that term in its non-binding guidance document to mean compounders can only compound USP/NF monograph substances that are the subject of a “drug” and not a “dietary supplement” monograph.  Specifically, FDA historically has stated that FDA interprets “an applicable USP or NF monograph” to mean an official USP or NF drug substance monograph.  “Accordingly, FDA does not consider USP monographs for dietary supplements to be applicable USP or NF monographs within the meaning of section 503A(b)(1)(A)(i)(I).”  FDA, Guidance for Industry, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act at 3 (2025).
• Modernize outdated statutory terms:  Eliminate the decades old, contentiously litigated (to the compounders’ success), and much maligned interstate distribution Memorandum of Understanding requirement and related provisions in Section 503B(b)(3)(B).

Why It Matters

Drug shortages remain a persistent and growing challenge in the U.S. healthcare system, affecting treatments from cancer therapies to commonly used injectables.  Compounding pharmacies and outsourcing facilities have long acted as a critically needed safety net that provides patients access to lifesaving medications—both during the pandemic and, most recently, in the aftermath of the 2024 Western North Carolina floods.

Hurdles Ahead

Despite broad support from pharmacists and patient advocates, the bill likely will face resistance from brand name drug manufacturers, who often push to limit compounding once FDA declares a shortage resolved.  Legal disputes over compounded versions of high-demand and ubiquitously prescribed drugs, such as semaglutide and tirzepatide, highlight the ongoing tension between ensuring needed access to medications and addressing alleged safety concerns.

However, with shortages continuing to disrupt patient care and bipartisan interest in strengthening the pharmaceutical supply chain, the bill could gain important traction as part of broader efforts to bolster domestic drug availability.

On September 29, 2025, FDA announced that it would be expanding its use of “Early Alert” communications for potentially high-risk device recalls, having determined that the pilot of this program was a success. The pilot program, initiated November 21, 2024, sought to minimize the time between FDA’s initial awareness of and public communication of potentially high-risk medical device recalls. Under the pilot, FDA issued Early Alerts for recalls related to a limited subset of medical devices: cardiovascular, gastrorenal, general hospital, obstetrics and gynecology, and urology. As of this latest announcement, FDA will now issue Early Alerts for all medical device recalls that are likely to be classified as the most serious type.

Although FDA already publishes notifications of high-risk recalls after manufacturers submit formal 806 reports and FDA classifies the recall, this process generally results in notifications published 2-3 months after recall letters are sent to customers. Based on our review of recent early alerts issued under the pilot program, FDA has been able to bring this timing in to around 1-3 weeks after initial customer letters. To do this, FDA is likely relying on voluntary pre-notifications by companies of potential recalls before an 806 report has been submitted (and potentially before some companies have determined that a recall is even reportable to FDA).

FDA publicizes these Early Alerts on its website  for all Class I medical device recalls.  FDA includes the status of whether FDA still is “collecting information” about the recall, whether the recall has been confirmed, and whether there is new information that has been updated since the Early Alert first issued.  The database is easily searchable and can be exported to Excel.  The public also can subscribe to receive instant email notifications for new Early Alerts that are issued.

Overall, we do not expect that FDA’s expansion of this pilot program should materially change a company’s process for evaluating whether to initiate a recall or report it to FDA. But, companies should be prepared for FDA to issue public notice of high-risk recalls earlier in the process than before and potentially before a company submits a formal 806 report.

On September 26, 2025, the Department of Commerce published a notice requesting public comment on “an investigation to determine the effects on the national security of imports of personal protective equipment (PPE), medical consumables, and medical equipment including devices.” 90 Fed. Reg. 46383 (Sept. 26, 2025). The investigation was initiated on September 2, 2025, pursuant to section 232 of the Trade Expansion Act, which “allows the President to impose restrictions on goods imports or enter into negotiations with trading partners if the U.S. Secretary of Commerce determines, following an investigation, that the quantity or other circumstance of those imports ‘threaten to impair’ U.S. national security.”

This section 232 investigation certainly is not the first under the Trump administration and almost certainly will not be the last. Devices now find themselves in the company of copper, timber and lumber, semiconductors, pharmaceuticals, trucks, minerals, commercial aircraft and jet engines, polysilicon, unmanned aircraft systems, and wind turbines. Essentially any product regulated by FDA as a medical device is the subject of this investigation, though the notice breaks them down as follows:

• Personal protective equipment (PPE) such as surgical masks, N95 respirators, gloves, gowns, and related medical parts and components;
• Medical consumables including medical/surgical instruments such as syringes, needles, and infusion pumps, supplies such as IV bags, catheters, bandages, and diagnostic and lab reagents;
• Medical equipment, which refers to items such as carriages and wheelchairs, crutches, and hospital beds; and
• Medical devices generally, which tracks the definition in the FDCA and includes “any instrument, apparatus, or machine used in the diagnosis, monitoring, or treatment of medical conditions.” Examples provided include blood glucose monitors, pacemakers, heart valves, hearing aids, x-ray equipment, and MRI machines.

The notice requests comments and information related to potential national security risks associated with medical devices, including:

• Current and projected demand for devices in the United States;
• The extent to which domestic production of devices can meet the domestic demand;
• The role of foreign supply chains in meeting US demand;
• The concentration of US imports of devices from a small number of suppliers or countries and associated risks;
• The impact of “foreign government subsidies and predatory trade practices on the competitiveness” of medical device manufacturers in the US;
• The “economic impact of artificially suppressed prices” of medical devices “due to foreign unfair trade practices and state-sponsored overproduction”;
• The potential for export restrictions by other countries, “including the ability of foreign nations to weaponize their control over supplies” of medical devices;
• The feasibility of increasing domestic production of devices;
• The impact of current trade policies on domestic production of devices and whether tariffs or quotas “are necessary to protect national security”;
• The potential “for foreign control or exploitation of supply chains” for devices; and
• The “ability of foreign persons to weaponize the capabilities or attributes of foreign-built” devices.

The date by which comments must be submitted to the docket is October 17, a very short turnaround. Medical device manufacturers who import products or components from overseas should strongly consider submitting comments. Since implementation of tariffs or quotas under section 232 relies upon a finding of a threat to national security, those comments should establish a record indicating strength and oversight of the foreign supply chain, the systems in place to identify potential “weaponization” of imported devices, and the likely consequences to Americans of imposing tariffs or quotas on critical medical products.  Because the Section 232 investigation provides an opportunity for notice and comment, it may be more difficult to challenge the government’s imposition of these tariffs after this process has completed.

To date, we are not aware of any reason to believe that medical devices manufactured overseas pose, or have posed, a national security threat. Making this assessment will be a nuanced and challenging responsibility.  But if there is any lesson that can be drawn from the 100% tariffs that will go in effect on October 1 for pharmaceuticals, it is that there is room for many exemptions.  The drug tariffs are not going to impact generic drugs, which account for the vast majority of drugs imported to the U.S., nor will they apply to drug from the European Union, which already is subject to a much smaller 15% tariff.  There also is an exemption for those companies that have a U.S.-based manufacturing plant under construction.

Against this backdrop, it is timely that one of the authors of this post, Anne Walsh, an HPM Director and Co-Chair of the IBA Healthcare and Life Sciences Law Committee, is facilitating a panel titled “National security issues, such as biosecurity and supply chain impacts, related to the life science and healthcare sectors.”   Panelists will include Ravi Bharwani, from FDA’s Office of Global Policy and Strategy; Shannon Humphreys from Canada’s Investment Review Directorate; and in-house and outside counsel representing industry from all over the globe.  It will be an opportune and insightful discussion from the government and industry perspective.  Join Anne at the IBA Annual Conference in Toronto on November 4, 2025!

The legal and regulatory landscape for controlled substances is in flux – telehealth prescribing rules have been extended to December 31, 2025, the new “HALT Fentanyl Act” heads to President Trump’s desk, all while recent opioid settlements signal sharper enforcement.  Against this backdrop, the American Conference Institute’s (ACI’s) 7th Annual Summit on Controlled Substances – Regulation, Litigation, and Enforcement is relaunching and is scheduled to take place from January 26-27, 2026 at the Virgin Hotels New York City in New York, NY.  The summit aims to deliver the essential strategies you need to respond, adapt, and lead in the legal and regulatory landscape for controlled substances.

Why You Can’t Miss It:

Hear firsthand from regulators, in-house counsel, compliance leaders, and enforcement specialists. Walk away from tailored sessions that empower you to:

• Decode shifting DOJ & DEA priorities to reduce legal and regulatory exposure
• Prepare for telehealth’s next chapter under the pending Special Registration rule
• Align your SOM programs with new DEA compliance standards
• Manage supply chain and quota risks through smarter strategies
• Stay ahead of the prosecution curve as federal and state enforcement intensifies

What You’ll Gain:

• Forward-looking insights to shape your 2026 legal, compliance, and operations roadmap
• Proven solutions for telemedicine prescribing, enforcement readiness, and enterprise risk
• Trusted expertise from past and current DEA, FDA, DOJ officials, top law firms, and leading in-house teams
• Cross-functional connections spanning pharma, biotech, telehealth, distributors, retail, and government

Hyman, Phelps & McNamara, P.C.’s Andrew J. Hull (and former Assistant U.S. Attorney, United States Attorneys’ Office) will moderate a discussion with the Hon. John Mulrooney, a former DEA Chief Administrative Law Judge (see our previous posts here and here), in a session titled “Perspectives From the Bench: The Ins and Outs of Trying a Diversion Case and Best Practices for Working With Your Outside Counsel.”

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-FDA26.  You can access the conference brochure and sign up for the event here.  We look forward to seeing you at the conference!

In a case involving international horse-doping conspiracies, racetracks, and state horse racing regulators, the Second Circuit expanded the application of the FDC Act’s felony provisions.  There are two forms of criminal penalties for violations of the FDC Act contained in 21 U.S.C. § 333(a): a strict liability misdemeanor and a felony.  Except in cases of repeat convictions, felonies require the government to prove the defendant also acted with “intent to defraud or mislead.”  21 U.S.C. § 333(a)(2).

Despite this specific intent requirement, the FDC Act does not identify who the defendant must intend to defraud or mislead.  Given the FDC Act’s role as a public health and welfare statute, it’s to be expected that the object of the ruse would, at a minimum, be FDA and patients/consumers.  And that’s generally how federal courts have interpreted the intent element.  See, e.g., United States v. Ellis, 326 F.3d 550, 554 (4th Cir. 2003) (upholding a felony conviction where evidence supported that defendant intended to defraud or mislead FDA by failing to register his establishment with the FDA); United States v. Haga, 821 F.2d 1036, 1041 (5th Cir. 1987) (explaining that FDC Act felony prosecutions are ordinarily premised on intent to defraud or mislead “purchasers”).  Over the years, federal prosecutors have sought—and federal courts have granted—an expansion of this element to include intent to defraud or mislead other federal or state regulators tied to consumer food and drug laws or the practice of medicine.  See, e.g., United States v. Kaplan, 836 F.3d 1199, 1214 (9th Cir. 2016) (upholding felony conviction on evidence of intent to defraud or mislead the state medical board); United States v. Mitcheltree, 940 F.2d 1329 (10th Cir. 1991) (holding that the object of the intent to defraud or mislead can be an “identifiable drug regulatory agency involved in consumer protection”).

The Second Circuit’s recent decision in United States v. Fishman, No. 22-cr-1600 (2d Cir. Sept. 22, 2025), interpreted the application of the intent element to apply to additional types of state regulators.  Fishman, a licensed veterinarian, developed performance enhancing drugs (PEDs) that could not be detected in a drug test.  For years, he worked with a racehorse trainer, Navarro, to distribute these PEDs to dope horses entered into races around the world (you can read more about the doping scheme here and here).  Navarro pleaded guilty, but Fishman and his salesperson went to separate trials where they were both convicted of conspiracy to manufacture and distribute misbranded or adulterated drugs with intent to defraud or mislead.

On appeal, the defendants challenged the district court’s jury instructions that felony intent to defraud or mislead could be satisfied by evidence that defendants acted with intent to “defraud state horse racing regulators.”  The defendants argued that the FDC Act’s purpose is not to regulate the competitive integrity of horse racing.  Instead, they contended, the purpose and structure of the FDC Act is to protect consumers and purchasers, leaving only three categories of possible victims: (1) the horse trainers who purchased the PEDs (but they did so knowingly and were not deceived); (2) the horses (defendants argued they were incapable of being defrauded or misled); and (3) the FDA or “other comparable state agencies that regulate drugs, as opposed to governmental entities that regulate racing.”  Id. at 16-17.

Sadly, the Second Circuit did not contemplate the weighty philosophical question of whether a horse can be deceived or misled.  But it did reject the defendants’ argument that only a state agency that regulates drugs could trigger the intent element.  In upholding the defendants’ convictions, the court stated:

[W]e do not agree . . . that the [FDC Act] reaches only fraudulent or misleading conduct directed at certain targets.  What matters under this statute is not the identity of the target of a defendant’s intent to defraud or deceive.  What matters is the connection between the fraudulent intent and the offense of adulteration and misbranding: Was the misbranding undertaken with the intent to deceive?

Id. at 17.  In other words, the object of the fraudulent action is irrelevant for determining the scope of the felony.  Instead, the important issue is whether the violation of the FDC Act is “connected” to the intent to defraud or mislead some government agency.  Because the evidence at trial supported that some state racing regulators prohibit administering unapproved drugs to horses, the court upheld the conviction because the fraudulent intent of defendants was linked to the misbranding of the PEDs.  Id. at 24-25.

Bottom line: by refusing to limit the type of government regulators that can be the object of an intent to defraud or mislead, the Fishman decision provides a broad application of what constitutes a felony under the FDC Act.  While the Second Circuit was careful to talk only about state regulators in its analysis, the decision leaves open the possibility that the government could pursue felony charges where there is evidence of intent to defraud or mislead parties other than government actors or consumers as long as there is a connection between the FDC Act violation and the fraudulent intent.  The court’s reasoning presents a slippery slope with no clear stopping point.  As the Supreme Court noted about a decade ago, the FDC Act’s primary purpose is “to protect the health and safety of the public at large.”  POM Wonderful LLC v. Coca-Cola Co., 573 U.S. 102, 108 (2014).  Recognizing that primary purpose, other courts may rein in such a broad interpretation of the intent element by holding that only evidence of intent to defraud or mislead parties tied to public health and safety—not horse racing or other activities—can satisfy this type of FDC Act felony conviction.

The California Board of Pharmacy (the “Board”) implemented a novel approach to address employee theft as one aspect of the opioid epidemic in 2018 by requiring pharmacies and clinics to reconcile their quarterly schedule II inventories.  The approach was novel because to our knowledge, no other regulator, not the Drug Enforcement Administration (“DEA”), not other states, require pharmacies and clinics to physically inventory controlled substances, then reconcile those inventories with receipts and dispositions.  DEA registrants, for example, are only required to take a physical inventory of all controlled substances on-hand at least once every two years and there is no reconciliation requirement.  21 C.F.R. § 1304.11(c).  Most states mirror the federal biennial inventory requirement.

Inventory Activities and Reconciliation Reports

In 2018 the Board reasoned “[by] requiring at least a quarterly inventory of all Schedule II controlled substances, pharmacists, pharmacies, and clinics will be better equipped to spot and stop employee drug diversion from the pharmacy earlier and prevent excessive drug losses from occurring.”  Initial Statement of Reasons, Reconciliation and Inventory Report of Controlled Substances, California Board of Pharmacy, 1.  We blogged at the time on the new requirement here.

Four years later in 2022 the Board significantly expanded the inventory activities and inventory reconciliation requirements for additional “federal controlled substances.”  Cal. Code regs. tit. 16, § 1715.65.  “Inventory activities” include inventory and all other functions sufficient to identify controlled substance losses, and policies and procedures must identify such functions outside of the required inventory reconciliation process.  Id. § 1715.65(a)(3)(B).  California pharmacies and clinics must now create inventory reconciliation reports for:

a. Federal schedule II controlled substances, at least once every three months;

b. These non-schedule II substances in the following strengths per tablet, capsule, other unit, or specified volume, at least once every 12 months:

• • • Alprazolam (1 mg./unit);
    • Alprazolam (2 mgs./unit);
    • Tramadol (50 mgs./unit); and
    • Promethazine/Codeine (6.25 mgs. Promethazine and 10 mgs Codeine per 5 mgs. of product)

c.  All other controlled substances:

• • • No later than three months after discovery of a “reportable loss” (discussed later);
    • Such reports must cover the period from the last physical count of the drug before the loss through the discovery date; or
    • At least once every two years. Id. § 1715.65(a).

Inpatient hospital pharmacies are required to prepare inventory reconciliation reports of federal schedule II substances, and the specific alprazolam, tramadol, and promethazine with codeine formulations quarterly.  The reports must “include controlled substances stored within the pharmacy, within each pharmacy satellite location, and within each drug storage area in the hospital under the pharmacy’s control.”  Id. § 1715.65(g).

Pharmacy and clinic policies and procedures must include inventory activities and inventory reconciliation reports.  The Pharmacist-in-Charge (“PIC”) or consulting pharmacist must review all inventory activities and inventory reconciliation reports.  Id. § 1715.65(b).  Inventory reconciliation reports must include:

1. An actual physical count rather than an estimate of federal controlled substances in inventory;

• • • Inpatient hospitals and licensed correctional pharmacies using automated delivery systems may account for their inventory by other than a physical count; and
    • An individual who takes the inventory must sign and date the inventory or the report that contains it;

2. A review of all acquisitions and dispositions of every “federal controlled substance” covered by the report since the last inventory reconciliation report covering the controlled substance;
3. A comparison between the physical counts and acquisitions/dispositions to determine variances between what must be accounted for with what is accounted for;
4. Identification of all records used to compile the report;

• • • The records must be maintained and readily retrievable in the pharmacy or clinic for three years;

5. Identification of each individual involved with preparing the report;
6. Possible causes of overages; and
7. Date and signature of the PIC or professional director if a clinic. Id. § 1715.65(c), (e)(1).

So, California pharmacies and clinics must take a physical inventory for all controlled substances depending upon their schedules unless there is a reportable loss.  Then, in creating inventory reconciliation reports, they must conduct what amounts to accountability audits to determine whether they can account for all controlled substances handled since the prior inventory.  Depending on controlled substance quantities and the underlying records, whether maintained in hardcopies or electronically, it may be more advantageous and less burdensome for pharmacies and clinics to take inventories and create inventory reconciliation reports more frequently than annually or biennially.  More frequent reconciliations will detect potential variances earlier and will not require pharmacies or clinics to reconstruct activities for so long a period.

Reporting Losses

Pharmacies and clinics must report identified losses and known causes to the Board within 30 days of discovery unless the loss was caused by theft, diversion or self-use, which require reporting within 14 days of discovery.  Id. § 1715.65(d).

An “owner” of a pharmacy or clinic must report each controlled substance loss to the Board identifying every substance, quantity and strength.  Id. § 1715.6(a) and (b).  The Board has identified reportable controlled substance losses not attributed to theft, diversion or self-use.  Losses not attributable to these specific causes must be reported if they are equal to or exceed:

1. 99 tablets, capsules or other oral medication dosage units;
2. 10 units of single-dose injectable medications, lozenges, film such as oral, buccal and sublingual, suppositories, or patches; or
3. 2 or more multi-dose vials, infusion bags or any other unit. Id. § 1715.6(a)(1).

Any other loss of a controlled substance regardless of quantity attributed to employee theft must be reported to the employee’s licensing board.  Id. § 1715.6(a)(2).  Any other loss the PIC determines is significant must also be reported.  Id. § 1715.6(a)(3).  The Board has clarified reportable quantities of controlled substance formulations regardless of schedule.  In contrast, DEA requires registrants to report all thefts and any “significant losses” regardless of schedule or quantity.  21 C.F.R. § 1301.76(b).

FDA’s September 22, 2025 News Release and announcement in a prepublication Federal Register notice (to be published on September 24, 2025) that GlaxoSmithKline’s (“GSK’s”) Wellcovorin (leucovorin calcium) Tablets, EQ 5 mg base and EQ 25 mg base, which was approved under NDA 018342 (initially approved on July 8, 1983), would be reapproved took the pharmaceutical industry and the food and drug law bar by surprise.  After all, it’s a pretty rare occurrence that an application for which FDA has officially withdrawn approval is brought back to life—and with the same NDA number instead of under a new NDA number.  But, it is possible.  As FDA’s regulation at 21 C.F.R. § 314.150(c) explains:

FDA will withdraw approval of an application or abbreviated application if the applicant requests its withdrawal because the drug subject to the application or abbreviated application is no longer being marketed, provided none of the conditions listed in paragraphs (a) and (b) of this section applies to the drug.  FDA will consider a written request for a withdrawal under this paragraph to be a waiver of an opportunity for hearing otherwise provided for in this section. Withdrawal of approval of an application or abbreviated application under this paragraph is without prejudice to refiling. [(emphasis added)]

And, as FDA explained in the Agency’s Federal Register notice, there is authority under 21 C.F.R. § 314.160 for reapproving a withdrawn NDA:

The most recently approved labeling for Wellcovorin (leucovorin calcium) tablets, EQ 5 mg base and EQ 25 mg base, stated that the drug products were indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists.  In the Federal Register of September 22, 1999, FDA announced that it was withdrawing approval of NDA 018342 after GSK notified the Agency that Wellcovorin (leucovorin calcium) tablets, EQ 5 mg base and EQ 25 mg base, were no longer marketed and requested that the approval of the application be withdrawn under 21 CFR 314.150(c).  Subsequently, in the Federal Register of April 28, 2017, FDA announced its determination that Wellcovorin (leucovorin calcium) tablets, EQ 5 mg base and EQ 25 mg base, were not withdrawn from sale for reasons of safety or effectiveness under 21 CFR 314.161.

Under 21 CFR 314.160, FDA, on its own initiative or upon request of an applicant, may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval.  With respect to leucovorin calcium tablets, FDA has conducted a systematic analysis of literature published between 2009-2024 and has determined that the information supports a finding that orally administered leucovorin calcium tablets improve certain symptoms in adults and pediatric patients with cerebral folate deficiency (CFD). . . .

Subsequent to the approval of NDA 018342 for Wellcovorin (leucovorin calcium) tablets, EQ 5 mg base and EQ 25 mg base, that is being announced in this Notice, FDA intends to request that GSK submit a prior approval supplemental NDA to revise the prescribing information for Wellcovorin (leucovorin calcium) tablets, EQ 5 mg base and EQ 25 mg base, to include the essential scientific information needed for the safe and effective use of these drug products for the treatment of CFD in adults and pediatric patients.

GSK has already stated that the company “will submit a supplemental New Drug Application (sNDA) for Wellcovorin (leucovorin) to update the label to include an indication for the treatment of cerebral folate deficiency (CFD).”

Historically—at least since about 2009 when FDA began using the record-keeping system for drug applications known as DAARTS (Document Archiving, Reporting and Regulatory Tracking System) (see our prior post here)—FDA has required the submission of a new NDA (and assigned a new NDA number) when confronted with the reapproval of a previously withdrawn NDA.  From what we understand, DARRTS has limitations that prevent reusing a previously withdrawn NDA number.  Apparently, in the pre-DARRTS system FDA used, known as COMIS (Center-wide Oracle-based Management Information System), a withdrawn NDA number could be resurrected.

How FDA avoided the DAARTS system limitation is unclear, but it is the reuse of the Wellcovorin NDA number “018342” that piqued this blogger’s interest.  Why?  Because there’s an unanswered question about the payment of the PDUFA application fee for what was presumably a resubmitted and reapproved NDA 018342.  (By the by, there’s also an unanswered question about what, if any, data—clinical, non-clinical, and manufacturing—was resubmitted and reapproved under NDA 018342, particularly given that GSK has stated that the company “does not manufacture or market leucovorin, which is available in generic formulations in the US.”  Is it the same data included in the NDA approved 42+ years ago?  And if so, then how the heck did those data meet FDA’s enhanced 2025 standards??)

Under the statute, the PDUFA application fee, which stands at $4,310,002 in Fiscal Year 2025 for an application requiring clinical data and $2,155,001 for an application not requiring clinical data, must be paid by “[e]ach person that submits, on or after September 1, 1992, a human drug application. . . .”  The statute includes an exception for a previously filed application, which states:

(C) EXCEPTION FOR PREVIOUSLY FILED APPLICATION.—If a human drug application was submitted by a person that paid the fee for such application, was accepted for filing, and was not approved or was withdrawn prior to approval (without a waiver), the submission of a human drug application for the same product by the same person (or the person’s licensee, assignee, or successor) shall not be subject to a fee under subparagraph (A). [(Emphasis added)]

That exception does not apply here.  NDA 018342 was submitted to FDA in 1979, amended in November 1980 to add an additional 25 mg strength, and approved on July 8, 1983.  That’s nearly a decade before PDUFA was enacted.  Given that fact, NDA 018342 cannot be a “human drug application [that] was submitted by a person that paid the fee for such application.”

So, did GSK pay the the Fiscal Year 2025 PDUFA application fee for Wellcovorin NDA 018342?  Maybe we will find out soon if FDA posts an Approval Package for the new approval.  If not, then how could FDA lawfully allow an exception?  Or perhaps it could be an oversight?  We’re waiting with bated breath. . . .

While we wait, perhaps ponder this: Why would FDA go through such an obtuse resurrection process—and one not requested by GSK—when the statute already provides a route to update the labeling of generic Wellcovorin without GSK having to do anything at all?

We’re talking about the “Making Objective Drug Evidence Revisions for New Labeling Act of 2020” (or “MODERN Labeling Act”), which was passed as part (Section 324) of the Consolidated Appropriations Act, 2021 (Public Law No. 116-260).

The MODERN Labeling Act amended the FDC Act to add Section 503D, titled “Process to Update Labeling for Certain Generic Drugs,” to provide a process to update the labeling for generic drugs where approval of the brand-name drug has been withdrawn for other than safety or effectiveness reasons.  (Sound familiar??)  Specifically, a “covered drug” eligible to go through the label update process outlined in the statute is one:

(A) for which there are no unexpired patents included in the [Orange Book] and no unexpired period of exclusivity;

(B) for which the approval of the application has been withdrawn for reasons other than safety or effectiveness; and

(C) for which—

(i)(I) there is new scientific evidence available pertaining to new or existing conditions of use that is not reflected in the approved labeling;

(II) the approved labeling does not reflect current legal and regulatory requirements for content or format; or

(III) there is a relevant accepted use in clinical practice that is not reflected in the approved labeling; and

(ii) updating the approved labeling would benefit the public health.

Assuming FDA considered the MODERN Labeling Act here for generic Wellcovorin, then why not take this pathway?  Is it that the process required by the statute is too long?  Or maybe there were concerns about the “Approval Standard” “Rule of Construction” added to FDC Act § 503D by the MODERN Labeling Act: “This section shall not be construed as altering the applicability of the standards for approval of an application under section 505.  No order shall be issued under this subsection unless the scientific evidence supporting the changed labeling meets the standards for approval applicable to any change to labeling under section 505.”

The American Conference Institute’s (ACI’s) Pharma & Biotech Patent Litigation USA forum is scheduled to take place from October 14-15, 2025 at 3 Times Square in New York, NY.  Billed as “the new US Gold Standard event for pharma and biotech patent litigation,” ACI’s Forum on Pharma and Biotech Patent Litigation USA brings together leaders in life sciences patent litigation for a two-day deep dive into winning patent litigation strategies.  ACI’s highly skilled faculty – comprised of premier in-house and law firm patent litigation counsel – will bring you up to date on the latest challenges in life sciences patent litigation.  This is your one-stop shop for updates, analyses, networking, and strategies to keep you in control of the patent.

Key highlights at this year’s event include:

• Lightning round session on emerging trends in Hatch-Waxman litigation
• Analysis of new Orange Book and related combination product patent concerns
• Dance lessons: what steps have we learned through 15 years of BPCIA litigation?
• Amgen, Cellect, Amneal, Xencor and More! Understand how these cases are game changers to your patent litigation strategies
• Pharma and biotech patents in antitrust the crosshairs: looking beyond the settlement to new anticompetitive challenges
• Remedies and damages: evaluating at the wide swath of possibilities, options, and penalties for patent infringement

Attend and gain insights into new legal theories for your patent case in chief, as well as analyses of substantive case law, and practical litigation strategies and takeaways for your next patent trial and proceedings.  Hyman, Phelps & McNamara, P.C.’s Kurt R. Karst will speak on a panel along with Polsinelli PC’s Chad Landmon and Venable LLP’s Christina Schwarz, titled “Exploring New Litigation Concerns from Amneal and the FTC’s Latest Call for Orange Book Delistings.”

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-FDA26.  You can access the conference brochure and sign up for the event here.  We look forward to seeing you at the conference!

On September 19, 2025, FDA published in the Federal Register a final rule reverting the regulatory definition of “in vitro diagnostic products” (IVD products) in 21 C.F.R. § 809.3 to the text as it existed prior to the effective date of the May 2024 LDT Rule.

As we suspected when we blogged on the OIRA notice for this action, this new rule implements the March 31, 2025 Federal District Court decision vacating the LDT Rule, by removing the words “including when the manufacturer of these products is a laboratory,” which the LDT Rule added to the IVD products definition. In a footnote, the new rule notes that reverting the regulation’s text also changes the updated reference to the statutory definition of “device” from “section 201(h)(1)” back to “section 201(h),” which is less specific but still accurate.

Because the LDT Rule was already vacated by a Federal Court, FDA determined that this new rule is exempt from notice and comment rulemaking under 5 U.S.C. 553(b)(B), as it would be “impracticable, unnecessary, or contrary to the public interest” to follow such procedures.

The new rule provides an economic analysis of the impact of the LDT Rule not being in effect. Though it uses the primary estimates for the benefits and costs reported in the May 2024 LDT Rule, it adds that:

Portions of the broader benefit and cost uncertainty ranges overlap, thus indicating the possibility of negative net benefits of the Rule and positive net benefits of its no longer being in effect. Moreover, the quantitative estimates omit various regulatory consequences that are especially challenging to assess, such as any possible effect on innovation related to laboratory-developed tests (LDTs) associated with the Rule.

Plaintiffs argued in their case against the LDT Rule that FDA understated the costs associated with the rule by several orders of magnitude.  Although quite belated, it is nevertheless gratifying to see FDA acknowledge that its economic impact analysis did not adequately consider other critical factors such as the effect of the rule on innovation.

The new rule is signed by HHS Secretary Kennedy, which is unusual insofar as the FDA Commissioner almost always signs rules originating from FDA. It’s unclear what, if anything, this move is intended to signal, though it’s certainly consistent with this Administration’s general effort to centralize regulatory authority and decisionmaking and Secretary Kennedy’s specific penchant for directing FDA priorities, including its regulation of food and color additives and direct-to-consumer pharmaceutical advertising.

There are officially signs of life for FDA’s rare pediatric disease priority review voucher (RPD PRV) program!  On September 17, the House Committee on Energy and Commerce marked up the Give Kids a Chance Act of 2025 (H.R. 1262), legislation that would reauthorize FDA’s RPD PRV program and strengthen the agency’s authority in several related areas.  The bipartisan bill originally was a piece of a broader healthcare package that nearly passed late last year but was sidelined in the closing days of the 118^th Congress.  The current iteration of this bill has languished for over seven months since being introduced in the House of Representatives and referred to the House Committee on Energy and Commerce on February 12. Notably, the bill has accumulated 285 cosponsors, which amounts to over 65% of the total number of voting members of the Chamber, which indicates substantial support despite this inaction.

At the heart of the bill is the revival of the RPD PRV program, which expired in part in December 2024; this date marked the deadline by which a drug product could be designated as treating a rare pediatric disease.  Looming now is the second deadline date in the law: the sunset to receive an RPD PRV, with eligible applications needing to be approved by September 30, 2026.  Originally created in 2012, the program was designed to incentivize the development of treatments for rare pediatric diseases by awarding transferable (i.e., saleable) vouchers that allow faster FDA review of future products.  To date, 56 vouchers have been issued across roughly 40 rare conditions—including sickle cell disease, AADC deficiency, spinal muscular atrophy, Duchenne muscular dystrophy, and Friedreich’s ataxia—creating significant financial incentives to bring much-needed therapies to patients that might not otherwise have been developed.  As we previously blogged, an analysis from National Organization for Rare Disorders found that among the 39 rare pediatric diseases for which vouchers had been awarded at that time, only three had any FDA-approved products on the market before the program’s enactment, suggesting that the incentive has been very effective.  If enacted, the program would be extended through September 30, 2029.  Notably, the bill as currently drafted would do away with the two-part deadline (first for designation and then for approval) as it currently exists, replacing it with a single deadline date after which FDA cannot award vouchers.

There was enthusiasm late last year when the committee unanimously advanced a similar bill in 2024 prior to the December 2024 expiration of the first deadline date in the law, reflecting the bipartisan appeal of incentivizing pediatric rare disease research.  However, given the lack of further action and even less up until this point in 2025, patient advocacy groups have had to champion reauthorization.  See, for example, this call to action by the EveryLife Foundation for Rare Diseases (“EveryLife Foundation Asks Advocates to Urge Your Member of Congress to Support the Reauthorization of the Rare Pediatric Disease PRV Program”).  Patient advocates, including HPM’s own James Valentine, have echoed and amplified this sentiment.  In his remarks to the Rare Disease Congressional Caucus Briefing last week, Mr. Valentine stated that “the Rare Pediatric Disease Priority Review Voucher program [and] patient-focused drug development initiatives—all reflect bipartisan recognition that rare disease drug development is different, and that patients must have a central voice.”

Beyond RPD PRVs, the Give Kids a Chance Act would expand FDA’s oversight and clarify certain of its regulatory authorities:

• Pediatric cancer trials:  FDA could require pediatric studies of combination therapies of certain molecularly targeted cancer drugs when the drugs are owned by the same company or are generics.
• Enforcement authority:  FDA could take enforcement action against drugmakers that fail to meet pediatric study obligations under PREA, aligning these requirements with other post-market study mandates.
• Orphan drug exclusivity:  The bill would codify FDA’s interpretation of orphan drug exclusivity (i.e., seven-year market exclusivity for orphan drugs prevents the approval of the same drug for the “same approved use or indication within such rare disease or condition,” as opposed to the previous and more general “same disease or condition.”).  The bill also defines the term “approved use or indication.” This would narrow the scope of exclusivity so that it applies only to the indication rather than the entire designated disease (as previously discussed here).
• Organ transplant system:  The legislation authorizes FDA to collect registration fees from Organ Procurement and Transplantation Network members—a public-private partnership that manages the U.S. organ donation and transplantation system—to fund transplant operations.
• Global presence:  FDA would be permitted to establish an office in a country that is a party to the Abraham Accords (i.e., Israel and four Arab nations: the United Arab Emirates, Bahrain, Sudan, and Morocco). This provision is intended to enhance supply chain security and leverage innovation in the region, according to a cosponsor.

The bill’s markup signals fresh momentum for legislation that stalled at the end of 2024, when broader negotiations were derailed.  For rare disease product developers, the bill offers the continuation of a powerful incentive that patients and their families, drug developers, and other stakeholders have been pleading for. Given this momentum from a wide variety of stakeholders, including the numerous cosponsors, we can only hope that the provisions beyond RPD PRV reauthorization do not create further roadblocks to getting this program back on the books as soon as possible.

With the RPD PRV program’s sunset roughly a year away, a failure to reauthorize—and soon—may force many companies to make the difficult choice of rushing to submit their NDA/BLA in the coming months or early 2026.  Rushed submissions could lead to a wave of applications that do not have the benefit of full clinical or CMC datasets or vetting with FDA (e.g., via multiple interactions post-Phase 3).  In turn, this could create a high-risk situation in which 2026 may be marked by more applications receiving Complete Response Letters, which is not an efficient use of industry or FDA resources.

In the long term, it would be a tragedy for patients who might not benefit from therapies that would otherwise have been developed if the appropriate incentive was in place. We will never know the cost of the uncertainty this has caused, including, at minimum, delays in getting such therapies to patients suffering from serious or life-threatening diseases who need them. FDA has been doing its part to encourage the continuation of the program, primarily by continuing to grant rare pediatric disease designations past the December 2024 deadline. Now it is Congress’s turn to act, and quickly; the clock is ticking.

Late last week, FDA launched its real-time adverse event reporting dashboard for cosmetic products, the FDA Adverse Event Reporting System (FAERS) Public Dashboard for Cosmetic Products. This marks another step in Commissioner Makary’s “radical transparency” initiative. FDA promotes the digital site as an “interactive tool designed to facilitate the public’s ability to query real-time adverse event data on cosmetic products,” as the dashboard allows anyone to search, filter, and download adverse event data for cosmetics and beauty merchandise. Reports update daily rather than quarterly, giving the public immediate access to safety information that was previously buried in government databases.

Aside from the timeliness of the updates, this is a shift from the old world of cosmetic safety reporting. Previously, adverse event data lived in the CFSAN Adverse Event Reporting System (CAERS), was updated quarterly, and was accessible mainly through Freedom of Information Act (FOIA) requests or specialized industry databases. Now, a quick search can reveal a product name and every reported reaction in real-time. The dashboard consolidates both mandatory serious adverse event reports under 21 U.S.C. § 364a and voluntary reports from consumers, healthcare professionals, and salon workers.

The dashboard also reveals the scope of industry compliance after the passage of the Modernization of Cosmetics Regulation Act of 2022 (MoCRA), with nearly 46,000 adverse event reports submitted since the law’s mandatory reporting took effect in December 2023. There has been some hand-wringing about whether MoCRA enforcement might weaken under potential budget cuts and staffing reductions at FDA, but this activity suggests that at least the reporting requirements remain a priority for both industry and the agency.

The new system creates both challenges and opportunities for cosmetic companies of all sizes, though. The good news here is that the FDA clearly states these reports aren’t verified, and they don’t indicate the agency has concluded a product caused any adverse event. There’s a disclaimer users have to affirmatively click through that reads that submission of an adverse event report “does not constitute an admission that the facility, importer, distributor, packer, manufacturer or product caused or contributed to the event.” The dashboard also includes appropriate disclaimers about data limitations and the difference between correlation and causation.

However, competitors can now monitor products’ safety profiles as easily as checking stock prices, while consumers may make purchasing decisions based on what they read in the dashboard, including what may be raw, unverified reports. And the public nature of this unvetted data creates real litigation risks for companies, as trial attorneys may use raw adverse event reports in product liability cases without regard for the FDA’s disclaimers about causation.

Companies still need robust systems to collect, investigate, and classify adverse events within the required 15-day reporting window. Determining whether a consumer complaint rises to the level of a serious adverse event requiring FDA notification is often a complex judgment call that requires legal and regulatory expertise. Most companies have already set up monitoring systems to track both their own products and competitors’ safety profiles post-MoCRA, but here “radical transparency” means internal adverse event processes had better be rock-solid, to include training staff on proper classification protocols and ensuring robust documentation.

The dashboard doesn’t change what constitutes a serious adverse event under MoCRA, but it certainly raises the stakes for getting it right. We’ll report back on the effects the new system will have on the industry.