What’s Been Happening at the FDA Lately: A Roundup
The past several weeks have been among the most eventful (and chaotic) in recent FDA history. Here's what's been happening.
As you might have noticed, there’s a lot going on at the FDA these days.
Between major leadership departures, the rollout of a first-of-its-kind regulatory pathway for ultra-rare diseases, the launch of a unified adverse event monitoring system, expanding internal use of artificial intelligence, and user fee reauthorization negotiations now entering the home stretch, there is an enormous amount for the regulated industry to track and prepare for.
Here’s a look at the key developments and what they mean for industry, written for busy professionals who need the news tied together into something digestable.
CBER Director Vinay Prasad is leaving, again
Vinay Prasad, M.D., the director of the FDA’s CBER, is leaving the agency at the end of April, marking his second departure from the role in under a year. Prasad, who also holds the title of Chief Medical and Scientific Officer, will return to his academic position at the University of California, San Francisco.
In a post on X, Commissioner Marty Makary credited Prasad with implementing four major reforms during his tenure: the shift to a single pivotal trial standard, the Commissioner’s National Priority Voucher program, a risk-stratified COVID-19 vaccine framework, and the plausible mechanism pathway for ultra-rare diseases.
But Prasad’s time at CBER was anything but smooth. His tenure was marked by a series of controversies over rare-disease drug decisions that drew bipartisan criticism from Congress.
Maybe most notably, CBER under Prasad clashed publicly with UniQure over the company’s Huntington’s disease gene therapy, AMT-130. Long story short, UniQure had understood it had the agency's prior agreement to use an external control arm for its approval application, but CBER reversed course and demanded a new randomized controlled trial involving sham surgery, a decision that generated significant backlash from the rare disease community and investors alike.
It’s hard to argue the UniQure situation wasn’t part of a broader pattern. CBER issued complete response letters to several other rare disease programs, including therapies from Replimune and Capricor, that were criticized for a lack of clear communication during the review process. The agency also initially refused to file Moderna’s mRNA flu vaccine application, an unusual move that was reversed after the White House reportedly intervened.
At a Senate hearing in February, both Republican and Democratic lawmakers were unusually aligned in their criticism of CBER’s decision-making, highlighting what they described as inconsistency between the agency’s rhetoric about speeding rare disease treatments and the actions coming out of drug reviews.
Leadership turnover in general
Prasad’s departure is part of a pretty staggering pattern of leadership turnover at the top levels of the FDA. Consider the timeline here:
Peter Marks, the longtime CBER director, resigned in early 2025 over disagreements with HHS leadership on vaccine policy.
Prasad was brought in to replace him but left in July 2025 over the Sarepta Duchenne muscular dystrophy dispute, only to be reinstated two weeks later.
George Tidmarsh briefly led both CBER and the Center for Drug Evaluation and Research (CDER) before being placed on administrative leave amid concerns about his personal conduct.
Richard Pazdur, the respected longtime oncology regulator, was named CDER director but retired after less than a month, reportedly due to concerns about political interference in the agency’s scientific process.
Tracy Beth Hoeg became the fifth person to hold the CDER director role in 2025.
The churn can create real challenges for FDA operations and for the regulated industry. Companies navigating critical regulatory milestones, whether in late-stage development, pre-submission meetings, or post-market compliance, are dealing with an agency where institutional knowledge at the leadership level is being regularly disrupted. Analysts have noted that this volatility has kept companies uncertain about their developmental direction and contributed to investor hesitancy in the biologics space.
There are also open questions about who is actually making key decisions at the FDA right now.
Recent personnel moves at HHS (including the installation of Chris Klomp as a senior counselor acting as a chief of staff, and the elevation of Kyle Diamandis and Grace Graham as FDA senior counselors at HHS) suggest that decision-making authority may be shifting away from Commissioner Makary and toward HHS and the White House. Whether this represents a deliberate effort to provide additional oversight or a signal that Makary’s authority is being constrained remains to be seen.
For the CBER director vacancy specifically, the pool of willing and qualified candidates may be limited. After this many high-profile departures, several under clouds of controversy, recruiting from the industry or the private sector may be a hard sell. One plausible scenario is that Tracy Beth Hoeg, the current acting CDER director, could shift into the CBER role, with the agency then seeking a permanent CDER director separately.
The plausible mechanism framework: a new pathway for ultra-rare disease therapies
On February 23, the FDA released draft guidance on its much-anticipated plausible mechanism framework, a pathway designed to facilitate the approval of individualized therapies for patients with ultra-rare genetic conditions where traditional randomized controlled trials are not feasible due to extremely small patient populations.
Makary and Prasad had previewed the pathway in a New England Journal of Medicine article published in November 2025, but the draft guidance provides substantially more operational detail.
While FDA leaders have indicated the framework could theoretically apply to any drug modality, the guidance focuses specifically on two platforms: genome editing products (such as CRISPR-based therapies) and antisense oligonucleotides (ASOs). These modalities receive the most detailed treatment, signaling that the FDA sees them as the primary vehicles for individualized therapies in the near term.
Several aspects of the guidance are noteworthy for sponsors:
A statutory basis for approval: The FDA is relying on its existing standard of an adequate and well-controlled clinical investigation with confirmatory evidence, reinterpreting what those terms mean in the context of ultra-rare, individualized therapy. So, this is not a new statutory authority, but a reframing of existing law to accommodate extremely small patient populations.
Platform approach potential: For gene editing products, the guidance describes how sponsors can leverage proof-of-concept data across multiple clinical programs (for example, by swapping out a guide RNA or tweaking the editor while sharing foundational data). Critically, the FDA describes how in vitro data can be used to add product variants targeting different gene mutations to an existing biologics license application (BLA) after an initial approval. This hints at a platform model where the path to authorization for subsequent similar products is streamlined, maybe significantly so.
Scope uncertainty: There’s a disconnect between the written guidance which is narrowly focused on therapies for individual patients or very small groups and public statements from FDA leaders, who have suggested the framework could apply to more prevalent conditions. How the agency draws that line in practice will be an important area to watch. Comments on the draft guidance are due April 27, 2026.
The shift to a single pivotal trial standard
Alongside the plausible mechanism guidance, Makary and Prasad’s February 2026 NEJM article announced another big policy shift: the FDA’s default position going forward will be that one adequate and well-controlled study, combined with confirmatory evidence, will serve as the basis for marketing authorization of new drugs.
This is maybe less of a shift than it might initially appear. The FDA has had the statutory authority to approve drugs based on a single trial for nearly 30 years, and data shows the agency already accepts single trials in roughly 66% of cases for new molecular entities, particularly in rare disease and oncology. The change here is in making this the default rather than the exception, and in extending the principle more broadly to common diseases and conditions.
For companies, there are several practical considerations to work through:
Guidance gap: At this point, the single-trial standard exists only as an NEJM opinion article co-authored by two officials, one of whom is departing the agency. Companies want to see formal guidance with real specificity about when the FDA will accept one trial versus two, and under what conditions.
Consistency across review divisions: The FDA has a wide array of internal review divisions, each with its own culture and standards. A company with a broad portfolio could find some divisions fully embracing the single-trial approach while others continue to insist on two trials. Without a mechanism for ensuring consistency, the policy risks creating more confusion than clarity.
Cost implications: If a company shifts its development strategy from two medium-sized Phase 3 studies to one very large pivotal trial, and the FDA subsequently decides it needs additional data, the company could end up with a larger trial plus a supplemental study (a potentially more expensive scenario than the two-trial approach it replaced).
International harmonization: Most companies are not developing products solely for the U.S. market. Evidence packages need to be acceptable to the EMA, PMDA, Health Canada, the TGA, and other international regulators. A shift away from a known evidentiary standard introduces regulatory uncertainty across all of these jurisdictions, even if the ultimate single-trial standard may be favorable for the sponsor.
Moderna’s experience is instructive here. The company appeared to submit evidence that should have aligned with the new standard, but was effectively told the FDA would not even review the data. The lesson for industry: watch the actions, not just the words.
AI is getting operationalized at the FDA
The FDA’s internal use of AI has been a priority of the Makary administration, and recent months have brought meaningful new details about what that looks like in practice.
Elsa and the shift from Claude to Gemini
The FDA’s primary AI tool is Elsa, a platform containing multiple foundational large language models that launched agency-wide in mid-2025. Internal data indicates that more than 70% of FDA staff now use Elsa voluntarily. The tool assists with reading, writing, summarizing, safety profile assessments, label comparisons, and supporting nonclinical database development.
A significant supply-chain disruption affected FDA’s AI stack in late February. Because Claude had been one of the models available within Elsa, FDA said it was implementing a ‘phase transition’ away from that component, with Gemini positioned to play a larger role.
This raises important questions about model dependency: if an agency’s workflows are built on a particular AI model and that model suddenly becomes unavailable, can it disrupt entire operational pipelines?
Agentic AI deployment
In December 2025, the FDA expanded its AI capabilities by deploying agentic AI, or systems capable of planning, reasoning, and executing multi-step tasks across all agency departments. The rollout leverages Google’s Gemini enterprise platform and is designed for more complex workflows than Elsa’s standard generative AI capabilities. The agency launched a two-month Agentic AI Challenge, encouraging staff to develop new use cases, with demonstrations planned for the FDA Scientific Computing Day.
At the FDA’s Rare Disease Day event on February 23, specific details emerged about how AI is being used in product reviews.
The Office of Oncologic Diseases is conducting a pilot using Elsa to support pediatric study plan reviews. Pediatric oncologists with AI expertise developed specialized prompts, tested them against previously reviewed study plans across multiple models, and are now rolling those prompts out to broader review staff. Reviewers are using the AI-assisted approach in parallel with traditional review processes and providing standardized feedback on the results.
This measured, incremental rollout stands in contrast to some of the more ambitious messaging from agency leadership about AI’s potential to dramatically accelerate reviews. In practice, the approach appears cautious and duplicative by design—running AI alongside human review rather than replacing it.
A key concern from industry: the FDA has not announced any formal procedure for disclosing when AI is used in product reviews. Companies that meticulously scrutinize FDA correspondence and action packages to ensure accuracy may now face uncertainty about whether the language in those documents was generated by a human reviewer, an AI, or some combination of the two. This transparency question could well surface during the upcoming user fee reauthorization discussions in Congress.
FDA-EMA collaboration on AI
Internationally, the FDA and the European Medicines Agency (EMA) are collaborating on the regulatory use of AI. Last year, the two agencies published guiding principles on AI in drug development, and a coordinated AI glossary is expected this year to establish shared terminology. The EMA’s Novel Data Steering Group recently published a comprehensive work plan covering how it intends to integrate AI considerations into its regulatory framework over the coming years, including alignment with the EU AI Act.
AEMS: a unified Adverse Event Monitoring System
On March 11, the FDA launched the Adverse Event Monitoring System (AEMS), a unified platform that consolidates what had been a fragmented patchwork of seven separate adverse event databases into a single streamlined dashboard.
The system already includes reports for drugs, biologics, vaccines, cosmetics, and animal food, with medical devices, human foods, dietary supplements, and tobacco products slated for integration by the end of May 2026.
The legacy systems being retired include FAERS (the FDA Adverse Event Reporting System for drugs and biologics), VAERS (the Vaccine Adverse Event Reporting System, co-owned with CDC), and AERS (the animal drug adverse event system). The agency says the consolidation will save approximately $120 million over five years, down from the roughly $37 million per year it costs to operate the fragmented systems.
The most consequential change for industry is the shift from quarterly data releases to real-time publication of adverse event reports. Under the previous framework, the delay in data availability led to a high volume of Freedom of Information Act requests from companies and researchers seeking the latest safety information ahead of quarterly reports. AEMS should significantly reduce that administrative burden.