With each new year comes a new set of accompanying challenges, from tackling the latest innovations to new incarnations of old issues. 2025 will be no exception to this rule, and with its arrival we examine FDA’s activities in 2024 in the drug development space with an eye toward what 2025 may bring us, ranging from administrative changes at the US Food and Drug Administration (FDA), issues of clinical trial design and drug development, expedited programs, to Hatch-Waxman Act considerations.
As we have previously written, the ongoing change in presidential administration is poised to have impacts at FDA. While generally the vast majority of FDA staff remain unchanged through these transitions, a number of appointed positions typically change between administrations. For such appointed positions (e.g., FDA Commissioner), until a position is formally and “permanently” filled by the appointment (and as applicable the Senate confirmation) process, roles may be filled and held on an interim or acting basis. Once nominated, confirmed, and sworn into office, the Secretary of Health and Human Services, FDA Commissioner, and other political appointees begin the day-to-day tasks of working with other department- and agency-level appointed officials and career federal employees. This transition period can last weeks or months and varies from administration to administration depending on the speed and success of the appointment and confirmation process.
Looking specifically at FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER), while not staffed with political appointees, 2025 has already brought some shifts in leadership. CDER Center Director Dr. Patrizia Cavazzoni, CBER Deputy Center Director Dr. Celia Witten, CDER Deputy Center Director Dr. Douglass Throckmorton, and former CDER Deputy Center Director Dr. Bob Temple recently announced departures from FDA. Not only do these longtime FDA leaders take with them a wealth of experience and knowledge, but it also remains to be seen who will permanently take the reins in these critical positions or whether the leadership structure in either center may shift in light of these departures, whether formally or in practice.
While much of FDA’s activities will remain ongoing during an administration transition (e.g., review and assessment of pending applications, inspections, other enforcement actions), some activities, such as publication of new regulations or guidance documents, may slow down or pause completely for a period. Despite temporary election- and transition-related changes in publication cadence, historically the content of FDA’s issued policy documents have not been overwhelmingly influenced by the then-FDA Commissioner. Naturally, each commissioner and administration will hold varying priorities and issues of focus during their time leading the agency. The transition process in the weeks and months after being sworn in provides a new commissioner with the opportunity to develop and communicate their own priorities and plans for the agency during their tenure; precisely how this takes shape varies from administration to administration.
For example, in 2024 FDA published a new guidance document “Addressing Misinformation About Medical Devices and Prescription Drugs.” While working to ensure that truthful medical product information is available to prescribers and patients has been a longstanding priority for FDA—and with the rapid evolution of electronic communication on medical products by manufacturers and third parties alike being brought into focus in recent years (each topics of this recently published guidance)—the specific focus and framing with respect to “misinformation” may have been a reflection of one of Commissioner Robert Califf’s stated priorities while at FDA.
FDA continued its work elsewhere in the drug promotion space in 2024, which will no doubt remain an area of interest in 2025. Notably, FDA finalized “Communications from Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products,” following a 2023 draft guidance on the same topic. While the final guidance included a handful of notable shifts in content, the overall policy of clarifying a zone of nonenforcement from FDA for certain unapproved uses of approved medical products remains unspecified. Among other things, enforcement activities from FDA in coming years may shed a light on the size of this zone and the impact of working close to its boundaries.
In 2024, FDA also continued its work on drug and biologic regulation: for example, in the nonprescription drug product space, FDA finalized a long-awaited regulation establishing a pathway for approving nonprescription drugs with added safety measures known as Additional Conditions for Nonprescription Use (ACNUs). As we previously wrote, we may begin to see how industry and FDA will implement this pathway and the extent to which this rule may broaden the nonprescription drug market.
Keeping up with many a year’s trend, advanced manufacturing also remained an area of interest for FDA in 2024, including FDA’s draft guidance on its platform technology designation program (discussed here). Under this guidance, sponsors can request that FDA designate technologies used in approved therapeutic applications (NDAs, ANDAs, and BLAs) as a platform technology to allow more efficient leveraging of that technology in future applications. In late 2024, FDA also finalized a guidance describing its Advanced Manufacturing Technologies Designation Program (draft guidance discussed here). In some ways a sister program to the platform technologies designation program, this program provides a pathway for designation of certain novel advanced manufacturing processes and the guidance describes designation processes and benefits. Together, these programs and publications display an ongoing focus on advances in manufacturing technologies and efforts by FDA to provide some degree of incentives for manufacturers to develop and employ them. This space will likely remain a focus going forward at least in the near term.
In the paragraphs that follow, we take a deeper lookback at three key themes of FDA activity in drug development in 2024.
In 2024, FDA continued on its trajectory of dedicating much of its guidance efforts to the area of drug development. While FDA also issued multiple guidances on developing products for specific disease states, this suite of guidances provided the agency’s thinking around new ways to more efficiently develop the necessary safety and efficacy data to meet its substantial evidence standard more broadly.
For instance, three guidances further expanded on FDA’s prior efforts with respect to real-world data and evidence. In the post-market study context, FDA adopted the ICH M14 guidance on General Principles on Plan, Design and Analysis of Pharmacoepidemiological Studies that Utilize Real-World Data for Safety Assessments of Medicines, which aims to create international standards with respect to the “planning, designing, and analyzing observational (non-interventional) pharmacoepidemiological studies that utilize fit-for-purpose data for safety assessment of medicines (drugs, vaccines, and other biological products).” It provides best practices for these studies to streamline study development and regulatory assessments and improve the ability for such studies to be used to support international regulatory decision-making.
Also in the post-market context, FDA published a guidance on Assessing Electronic Health Records and Medical Claims Data to Support Regulatory Decision-Making, which discusses such topics as the selection of data sources, definition development and validation, data traceability and quality, data curation, and use of the development information in a final data analysis set when assessing new uses of approved products and post-market study requirements. Third, FDA’s guidance on real-world evidence considerations for non-interventional studies (discussed here) provides the agency’s recommendations to sponsors who may be considering submitting observational and non-interventional studies to FDA to support a demonstration of substantial evidence of effectiveness or product safety. It details considerations regarding study design and analysis that sponsors should consider for studies that assess the use of a marketed drug during routine medical practice.
FDA’s guidance on Integrating Randomized Controlled Trials for Drug and Biological Products into Routine Clinical Practice (on which we previously wrote) further aims to provide advice to sponsors to employ more streamlined trial protocols that can be incorporated into regular clinical practice when assessing new uses of approved drugs or investigational drugs with an adequately characterized safety profile. This may include the use of real-world data in patient health records along with procedures conducted by a patient’s local healthcare provider. Per FDA, such studies “may improve convenience and accessibility for participants and allow for enrollment of more representative populations, resulting in more generalizable trial results. Leveraging established health care institutions and existing clinical expertise in the medical community can reduce startup times and speed up enrollment.”
Such an approach is similar to another 2024 final guidance promulgated by FDA on the conduct of decentralized trials or trials with decentralized study elements (previously discussed here), which, like the integration of trials in routine clinical practice, may “enhance convenience for trial participants, reduce the burden on caregivers, and facilitate research on rare diseases and diseases affecting populations with limited mobility or limited access to traditional clinical trial sites. This may help improve trial participant engagement, recruitment, enrollment, and retention of a more representative trial participant population to improve the strength and generalizability of the evidence produced by the trial.”
Supporting these guidances is FDA’s adoption of Annex 2 to ICH E6(R3) on Good Clinical Practice, “address[ing] the GCP considerations that arise from the increased use of a wider range of design elements and data sources [and] provid[ing] additional GCP considerations, focusing on examples of trials that incorporate decentralised elements, pragmatic elements and/or real-world data (RWD).” The Annex touches on everything from institutional review board (IRB) review, informed consent, oversight, safety assessments, and study design to investigational product management, privacy, and data considerations. These guidances indicate an awareness by FDA of the significant need to make trials more efficient, accessible, and representative.
More specifically with respect to the representativeness of trials, FDA issued its draft guidance on Diversity Action Plans (discussed here) in 2024, which, once finalized, will become a mandatory aspect of drug development. Diversity Action Plans are intended “to increase enrollment of participants who are members of historically underrepresented populations in clinical studies to help improve the strength and generalizability of the evidence for the intended use population” by taking into account representativeness and enrollment in terms of age, sex, racial, and ethnic demographics. FDA further encourages sponsors to consider factors such as geography, gender identity, socioeconomic status, sexual orientation, lactation and pregnancy, disabilities, and co-morbidities, which may support subgroup analyses. Further complementing the Diversity Action Plan guidance was FDA’s guidance on collection of race and ethnicity data in clinical trials, which data can prove important to assessing the impact of intrinsic and extrinsic factors on responses to drug products as well as in identifying population-specific signals.
In the same vein of ensuring trials measure data elements that matter in the course of clinical practice, one short guidance issued this year that is specific to oncology may take on increased importance in the coming years and may indicate an evolving trend given the potential emphasis that the incoming administration may place on patient experience and voice. Specifically, FDA’s draft guidance on core patient reported outcomes in cancer clinical trials addresses instrument selection, trial design, and data collection considerations concerning a patient’s health-related quality of life, including disease-related symptoms, symptomatic adverse events, overall side effect impacts, physical functioning, and role (i.e., work and activities of daily living) functioning. Given that FDA’s Oncology Center of Excellence tends to be a forerunner when it comes to clinical trial matters, this is an area that sponsors across disease areas should be on the lookout for as consideration for endpoints other than disease cure or reduction may take on increasing importance.
In addition to the more novel areas outlined above, FDA’s guidance efforts over the past year focused on more traditional aspects of clinical trials, including clinical trial conduct and good clinical practices. This includes guidances on informed consent, charging for investigational drugs, and the use of data monitoring committees (discussed here). One particular area of emphasis has been study and data integrity. For instance, FDA’s draft guidance on protocol deviations provides “recommendations to assist sponsors, clinical investigators, and [IRBs] in defining, identifying, and reporting protocol deviations in clinical investigations.” FDA’s guidance on data integrity for in vivo bioavailability and bioequivalence studies (discussed here) provides recommendations on test site management and quality systems to ensure data integrity. (Notably, while this guidance only applies to bioavailability and bioequivalence studies, its recommendations have broad applicability.)
Moreover, in its guidance on clinical investigation electronic systems, records, and signatures, FDA addresses its requirements under Part 11 of its regulations with respect to when electronic systems, records, and signatures will be considered trustworthy, reliable, and equivalent to paper documents. While study and data integrity have always been of paramount importance to FDA, the number of recent guidances in this area may indicate an increased focus and consideration of integrity challenges that may accompany the growing complexity of clinical trials and their conduct.
Further reflecting the growing complexity of clinical trials, FDA issued a 2024 draft guidance on the conduct of multiregional oncology clinical development programs (discussed here). While this guidance is only directly related to oncology studies, given the increasingly global nature of clinical trials and especially pivotal clinical trials, sponsors in other disease states may also find the guidance useful insofar as it advises on considerations with respect to whether multiregional trials may be appropriate at all, factors to consider when determining whether foreign populations may be representative of the US disease state population, what FDA would consider to be a sufficient number of US participants to ensure a robust assessment of safety and effectiveness, and considerations for foreign site selection. This guidance is yet another piece in the puzzle of the longstanding movement toward globalization of clinical trials, which also includes FDA’s promulgation of 12 ICH-related guidances.
One final category of guidances from 2024 reflecting the growing complexity of products in development were two guidances in the combination product space. One guidance on essential drug delivery outputs for drug delivery devices addressed key aspects of a drug delivery device’s performance, including recommendations regarding design outputs, and information and data that is required to be submitted in investigational and marketing applications as well as applications for product changes following initial approval. FDA’s second guidance on use-related risk analyses, which predominantly applies to combination products but can also have applicability to standalone drug and biologic products, discusses the purpose and content of use-related risk analysis and how it can be used in conjunction with other information to determine if human factors data is needed. Similar guidances will take on even greater importance in the coming years as more and more complex combination products are developed, including products that leverage the potential of AI and machine learning platforms and devices.
Overall, FDA’s guidance efforts with respect to therapeutic development struck a balance this last year between providing further or more detailed guidance with respect to more traditional GCP areas while also trying to provide insight and increased predictability concerning more novel or new methods that may be used for data development. This is likely a theme that we will continue to see in the coming years as FDA delves deeper into areas such as the use of AI during drug development (e.g., just after the new year FDA published its guidance on considerations for use of AI to support regulatory decision-making) and ways to more efficiently design and conduct clinical trials.
FDA’s various expedited drug development programs are a perennial focus for FDA and industry alike given their impacts on innovative drug development. Following on the heels of congressional attention at the tail end of 2022 that provided FDA with revised authorities for its accelerated approval program, FDA recently published a long-awaited guidance on “Accelerated Approval – Expedited Program for Serious Conditions,” which works to fulfill a congressional obligation and describes conditions applicable to the initial grant of an accelerated approval (including with respect to endpoints, evidentiary thresholds, and confirmatory trials) as well as procedures to be employed in the event of a proposed withdrawal of a product approved under the pathway.
In addition to the new processes FDA plans to employ in connection with a withdrawal of accelerated approval, the guidance collates and summarizes policies and information around the initial grant of an approval that appear to be largely drawn from FDA’s experience and previous decision-making employing the pathway. Notably, the guidance did not address when and how FDA may (or may opt not to) exercise its regulatory discretion in determining whether to withdraw a product from the market when the confirmatory trial has not met its prespecified endpoints. This omission is highlighted given the number of confirmatory studies that reached and are reaching their completion dates as well as the seeming increase in activity and advisory committee hearings around these studies.
Complementing this guidance, FDA also published a draft guidance in January 2025 detailing the agency’s policies in implementing its new statutory authority regarding whether and the extent to which confirmatory trials must be underway prior to approval under the accelerated approval pathway. As expected, FDA has indicated that in most instances it will require confirmatory studies be underway prior to approval under accelerated approval, with some limited exceptions. When FDA will require confirmatory studies to be in place should be a point of discussion between sponsors and the agency during development-stage meetings.
The new statutory authority also provided FDA with expanded command over civil monetary penalties relating to the conduct and reporting of accelerated approval post-marketing confirmatory studies, on which topic FDA announced a planned guidance in 2024. Whether the guidance will be published in 2025, and whether its publication or approach will be impacted by the recent US Supreme Court decision in SEC v. Jarkesy (which held the Seventh Amendment entitles a defendant to a jury trial when SEC seeks civil penalties for securities fraud, thus forbidding SEC from seeking such penalties through its own in-house administrative enforcement proceedings, which lack juries), remains to be seen.
Relatedly, FDA has also stated that it is working on a guidance describing an evidentiary framework for biomarker qualification. In recent years, FDA has expanded its use of the accelerated approval space beyond its origins in infectious disease and its traditional focus in oncology. As this trajectory is likely to continue, we expect this to remain an active area of interest and development for FDA, industry, and other stakeholders in the coming year.
Looking more broadly at the expedited programs space, FDA has noted that it is working on two additional guidance documents that it did not publish in 2024. The first is a planned guidance covering FDA’s various priority review voucher programs more generally. This would be a welcome addition to FDA’s expedited programs guidances insofar as it provides transparency, clarity, and consistency across FDA’s various priority review voucher programs, in particular if the voucher programs for rare pediatric diseases and/or medical countermeasures are renewed by Congress in 2025. The second guidance FDA has said was in the works would relate to its qualified infectious disease product (QIDP) designation program, which relates to incentives for the development of certain antibacterial and antifungal drug products. Whether this would amount to a revision of the existing QIDP guidance or whether FDA has additional updates in the expedited programs space remains to be seen.
Due in large part to the broad focus on drug pricing issues over the last several years, fostering FDA’s biosimilars and generic drug programs has been a near-constant FDA priority. As FDA often reminds us, however, it does not directly regulate drug pricing, and many of its policy advancements in this arena have focused on the related area of drug access issues. Looking ahead to 2025, drug access issues will likely remain an FDA focus, in particular from the Office of Generic Drugs (OGD) and the Office of Therapeutic Biologics and Biosimilars, even if the direct issue of drug pricing, and therefore at least some of the focus, may fall to other parts of government.
Biosimilars: FDA continued its pattern of making steady advancements for the biosimilars program in 2024; specifically, FDA advanced its policy of lessening the distinctions between (and data requirements for) biosimilars and interchangeable biosimilars to stimulate market access. As we have previously written, FDA also issued 2024 guidance on advertising and promotion of biologics, biosimilars, and interchangeable biosimilars to caution industry about making product comparisons. We may see continued attention to this issue in 2025 as FDA’s post-marketing experience with the range of follow-on biological products continues to grow and their presence in the market matures. In this arena, FDA’s 2024 CDER guidance agenda noted the agency was working on a guidance document for first interchangeable exclusivity, which would provide much-needed transparency in the space for biosimilar developers.
Looking further into the horizon, FDA has been promising rulemaking in the biologics and biosimilar space, termed as “biologics modernization” by FDA. If issued, this proposed rulemaking could significantly impact biologics and biosimilar development, review, and approval. 2025 also marks the start of negotiations between FDA and industry for the fourth iteration of BsUFA, the biosimilar user fee program, and while publicly released descriptions of user fee negotiations through meeting minutes are notoriously thin, we may start to get an initial sense of how the user fee program may evolve as it continues to mature.
Hatch-Waxman and Generics: FDA’s generic drug program was very active in 2024 and its developments largely represented a continuation of previous years’ work to encourage robust market competition for prescription drugs. FDA’s OGD continued to prioritize the efficient and timely approval of ANDAs (both for first-time generics and products already subject to generic competition), the conversion of tentative approvals to final approvals, the issuance of literally hundreds of initial and revised product-specific guidances (PSGs) for bioequivalence studies, and the convening of pre-ANDA meetings to aid in product development. OGD also continued to implement the current and third iteration of GDUFA, its user fee program,, which is due to begin negotiations in 2025 for reauthorization scheduled in 2027. Some of these efforts involved updating existing policies to conform to the commitments made in the GDUFA III commitment letter, including revisions by the FDA to its “ANDA Submissions - Amendments to Abbreviated New Drug Applications Under GDUFA,” “Controlled Correspondence Related to Generic Drug Development,” and “ANDA Submissions - Amendments and Requests for Final Approval to Tentatively Approved ANDAs” guidances.
Still other GDUFA III implementation efforts resulted in the publication of new guidances describing program enhancements. For example, FDA issued “Review of Drug Master Files in Advance of Certain ANDA Submissions Under GDUFA,” which describes when an early FDA assessment of a Type II active ingredient Drug Master File (DMF) may be requested for certain qualifying ANDAs. FDA also issued “Product-Specific Guidance Meetings Between FDA and ANDA Applicants Under GDUFA,” which describes FDA’s implementation of certain performance goals, timeframes, and procedures for scheduling and conducting meetings with FDA on the impact of PSGs or proposals for alternative methods of meeting the ANDA bioequivalence requirement. FDA also issued “Requests for Reconsideration at the Division Level Under GDUFA” describing its implementation of GDUFA III commitments relating to requests for reconsideration of OGD’s regulatory decisions, including instances where such a request may receive a goal date from FDA and related processes and procedures.
FDA issued several other guidances impacting generic drug development, review, and approval timelines. Notably, FDA published “Content and Format of Composition Statement and Corresponding Statement of Ingredients in Labeling in NDAs and ANDAs,” a draft guidance equally applicable to NDA and ANDA applicants that emphasizes the importance of accuracy and completeness of ingredient information in FDA-approved drug labeling and the consistency between this information and other information submitted to FDA in the underlying application. For ANDAs, active ingredient sameness is a requirement for approval, and, depending on the drug product being developed, inactive ingredient qualitative and quantitative sameness may also be required. As a result, FDA has identified that access to accurate ingredient information for a reference listed drug (RLD) may be a contributor to timely and efficient generic drug development. While Congress has considered legislation in this space, to date nothing has been enacted, and this guidance may represent an effort by FDA to address these issues in the interim.
FDA also published “Revising ANDA Labeling Following Revision of the RLD Labeling,” which finalized a 2022 draft guidance on the same topic. The guidance highlights another regulatory hurdle that has at times stymied timely generic drug approval, namely meeting the “same labeling” requirement when the underlying RLD presents labeling changes during FDA’s review of the ANDA. While the guidance maintains this statutory obligation, it also seeks to clarify the process for ANDA applicants. Other guidances covered bioequivalence-specific topics involving Data Integrity, Expedited Safety Reports, Testing Samples, and immediate-release solid oral dosage forms.
Looking ahead to 2025, unfinished business from FDA’s 2024 guidance agenda includes several unpublished guidances that would be particularly impactful in the Hatch-Waxman and ANDA space. On its agenda was a revision to a foundational guidance related to distinctions between ANDAs submitted under Section 505(j) of the Federal Food, Drug, and Cosmetic Act and NDAs submitted under Section 505(b)(2). It’s unclear how major the intended revisions would be, but is worth keeping tabs on in any event. Turning to core Hatch-Waxman issues, FDA also planned guidances on 30-month stays and the submission of patent information for listing in FDA’s Orange Book. Both of these areas remain important after more than four decades of the Hatch-Waxman Act and are frequent sources of litigation and the generation of novel issues impacting both innovator and follow-on drug development programs.
Orange Book patent listing practices have in years past been an area of particular focus, a concentration likely to continue into 2025 given the Federal Trade Commission’s interest under its antitrust authority, and active litigation concerning the scope of patents that should be listed in the Orange Book. Further clarity regarding these listing obligations would be a welcome, and overdue, addition to FDA’s guidance arsenal. Finally, of note, FDA also indicated that a new guidance was in the works covering Hatch-Waxman three-year exclusivity for new clinical investigations, another frequently challenged area of FDA regulation where transparency of process and policy has been long-awaited by industry and other stakeholders. Whether these agenda items are achieved in 2025 or whether any of these are impacted by the ongoing changes in FDA and CDER leadership remain to be seen.
Looking ahead to 2025, important appointed positions, such as FDA Commissioner, are likely to be filled, but it remains to be seen who precisely will be at the helm, let alone what their priorities may be and how those might impact current ongoing work of the FDA staff. Compounding these unknowns, FDA center leadership also wields significant impact on center priorities and direction. With the aforementioned CDER and CBER departures and leadership changes, the impacts of these transitions will no doubt be felt in 2025.
For example, it’s unlikely policy advances in the application of AI to medical product development will slow in the coming year given its increasing focus, rapid development, and ever-expanding use by drug, biologics, and device developers. In early 2025, FDA delivered on much-anticipated draft guidance covering the use of AI to support regulatory decision-making for drugs and biologics. Questions remain surrounding whether this or other similarly situated policy advancements may be impacted by the pending administration change, either due to changing priorities of the next FDA Commissioner, leadership within CDER or CBER, or the broader administration.
Regarding broader FDA initiatives, 2025 will mark a critical time for its various user fee agreements and commitments. FDA’s over-the-counter user fee program is due for its first reauthorization from the US Congress by September 30, 2025. Other major user fee programs covering drugs and biologics, medical devices, biosimilars, and generic drugs (PDUFA, MDUFA, BsUFA, and GDUFA, respectively) are all slated for 2025 to kick off negotiations between FDA and regulated industry of updated commitment letters for these programs scheduled for Congress reauthorization in 2027.
Finally, a broad lookback at FDA in 2024 cannot overlook the sea change that the US Supreme Court brought to administrative law generally in its decision Loper Bright, which overturned the four decades old Chevron framework that (until 2024) dictated often significant deference to agency interpretations of its statutory authorities. While the direct impacts of Loper Bright—and the resulting diminishment of deference to agency actions—on FDA decision- and policy-making may, as yet, be difficult to quantify, they will no doubt reverberate in the years to come. In 2024, we saw many legal challenges to FDA action, and policies started invoking Loper Bright across many areas of FDA regulation, including drug compounding and shortages, exclusivities, and even the applicability of specific regulatory frameworks to specific medical products. In 2025, we may begin to see how courts react to these and other challenges and begin to have greater visibility into how FDA is changing its practices in reaction to the decision itself.
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