Policy initiatives have come fast and furious at the FDA this year. While guidances on rare diseases and vaccines have consumed most of the ink, policy shifts aimed at improving FDA efficiencies and reshoring U.S. manufacturing also got some attention. Here, BioSpace rounds up more than a dozen initiatives relevant to the biopharma industry.
From vaccines to rare diseases and the phasing out of animal testing requirements, it was a busy year for biopharma on the policy front as Health Secretary Robert F. Kennedy Jr. and his team at HHS made their mark on the FDA, CDC and National Institutes of Health.
Many of the FDA’s 2025 guidances have focused on accelerating the path of cell and gene therapies to the market—particularly those intended for rare and ultrarare diseases. In a year where controversy is almost expected with every news announcement, the need for more and more-effective therapies for rare conditions may be the one area on which Americans of every political stripe can agree.
Analysts and other FDA watchers who spoke with BioSpace see the momentum generated in this area in 2025 continuing into the new year. “I do think that, given what we’re seeing from FDA, rare orphan diseases as an area” of great interest for biopharma and investors will persist into 2026, Graig Suvannavejh, managing director of Equity Research at Mizuho Securities, told BioSpace. Married with reports that the FDA will soon begin requiring only one pivotal trial as opposed to the standard two, “this would make it seem ripe for rare orphan [diseases],” he added.
Another key area of focus for the HHS under Kennedy—with his long history of antivaccine activism—has been in the vaccines space. On April 30, the Health department announced it would require all new vaccines be tested in placebo-controlled trials before they are approved, a “radical departure” from past practices, an HHS spokesperson told The Washington Post at the time. Earlier this month, Kennedy’s reformulated CDC Advisory Committee on Immunization Practices made another radical departure from the norm, voting to delay the hepatitis B vaccine from birth to two months of age for some infants.
“Obviously [Kennedy is] driving a lot of this, from vaccine policy to staffing and everything like that,” Chad Landmon, Hatch-Waxman & Biologics chair at Polsinelli Law Firm, told BioSpace, “so I think it’ll be interesting to see how that continues, whether the same people continue in those roles.”
BioSpace has compiled a review of our coverage of this year’s key policy initiatives. We will continue to update this tracker as we move into 2026 and see what comes next.
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Randomized Trials To Be Required for CAR Ts
December 8
Randomized, controlled clinical trials will be the FDA’s preferred approach to assessing CAR T cell therapies, Center for Biologics Evaluation and Research (CBER) director Vinay Prasad and three co-authors wrote in a Perspective piece in the Journal of the American Medical Association. Single-arm trials with no controls —the type on which the approvals for the seven currently marketed products were based—will no longer be sufficient. The FDA will also look at the therapy’s benefit in terms of patient survival or on time to the development of a particular event when considering approval, according to the authors.
Prasad and colleagues noted in the piece that while the FDA is adjusting its processes to “exercise regulatory flexibilities, when necessary,” it also needs to “maintain the high evidentiary standards for approval.”
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FDA To Reduce Pivotal Trial Requirement From Two to One
December 4
In possibly its biggest overarching pivot of 2025, the FDA is planning to require only one pivotal trial, as opposed to two, for companies seeking approval of a new drug. While not yet an official policy—the change was communicated by FDA Commissioner Marty Makary to STAT News in an interview—he told the publication it will be finalized in the next three to six months.
“You can achieve the same statistical power with one trial as you would with two,” Makary told STAT.
While analysts and other insiders positioned the proposed change as a major coup—biopharma consultant David Alderman in a LinkedIn post called it the “biggest jailbreak in biotech history”—other experts told STAT they were confused because the FDA already allows flexibility in situations where running two trials would be impractical or infeasible.
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FDA Unveils Plausible Mechanism Pathway for Rare Diseases
November 13
Makary and Prasad introduced the plausible mechanism approval pathway for rare diseases. Writing in The New England Journal of Medicine, Makary and Prasad said the new pathway would expedite treatments “for products where a randomized trial is not feasible.”
In an interview with Fox News in April, Makary introduced the concept of a “conditional approval” pathway for treatments for rare diseases with extremely small patient populations. When the detailed pathway was announced seven months later, Makary and Prasad referenced Baby KJ, a patient with the ultrarare disease CPS1 deficiency whose condition was treated with a custom gene editing therapy. To qualify for the new plausible mechanism pathway, therapies must meet several conditions similar to KJ’s, including targeting known biological causes for a specific disease, and sponsors must produce post-marketing data to show real-world efficacy.
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Guidance To Prevent Refusal-to-File (RTF) Letters
October 23
The FDA released draft guidance to help biopharma companies understand what the agency considers to be a complete regulatory submission, and conversely, what will result in a refusal-to-file (RTF) letter. The guidance also explains the difference between filing issues that would result in an RTF and review issues that would result in a rejection.
Recommendations include that a drugmaker not submit “materially incomplete or inadequately organized” applications, and that applications using a “single adequate and well-controlled clinical investigation” as the sole basis for approval will be RTF’d if the FDA and the applicant had previously agreed on the need for more than one such study.
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Abbreviated NDAs Aim To Speed U.S. Generics
October 3
Just over a week after its guidances for speeding the development of CGT therapies, the FDA on Oct. 3 introduced a new program for accelerating the generic drug industry in the U.S., both on the R&D and manufacturing sides.
The agency’s new program includes a quicker review of abbreviated new drug applications—specific regulatory filings for generics—though the FDA did not say by how much it would accelerate review processes. Reviews for generic medicines generally take about 10 months.
To qualify for that speedier review, companies must conduct their bioequivalence studies in the U.S. and “exclusively” source their active pharmaceutical ingredients from within the country as well. The finished dosage form must also be made locally.
2025 data showed that most generics are manufactured China and India, representing 22% and 44% of the global market, respectively.
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FDA Seeks To Streamline Cell, Gene and Regenerative Therapies
September 24
In a set of three separate draft recommendations, the FDA published new thinking on how to accelerate development of cell and gene therapies and regenerative medicines.
These guidances covered a range of topics, including leveraging “innovative” study designs that use patients’ status prior to a trial as their own control. Other recommendations included using historical or real-world data as controls, allowing mid-trial modifications as studies generate data and deploying new mathematical frameworks to model progressions of a disease to chart the therapy’s efficacy.
The agency also addressed diseases with small study populations, stating that early-stage trials could be enough to establish a product’s efficacy given “appropriate quality controls,” as well as post-marketing requirements for CGT products approved under accelerated pathways.
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FDA Cracks Down on “Deceptive” Drug Advertising
September 9
The FDA on Sept. 9 announced it was sending approximately 100 cease-and-desist letters to pharmaceutical companies with what it called “deceptive advertisements.” The agency would also initiate rulemaking to close the “adequate provision” loophole, created in 1997, that has allowed pharma companies to advertise their drugs without fully disclosing risks, “fueling inappropriate drug use and eroding public trust,” according to the FDA’s statement.
However, according to experts involved with writing the 1997 regulation who spoke with BioSpace, it was not a loophole. Instead, it was a deliberate and carefully crafted law that struck a happy medium between the demands for marketing new drugs and informing patients.
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FDA Unveils Rare Disease Evidence Principles
September 4
The FDA’s Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER) on Sept. 4 jointly unveiled a new framework intended to streamline the approval of therapies for ultrarare diseases.
The Rare Disease Evidence Principles (RDEP) will allow companies developing certain therapies to file for approval under an investigational new drug application using only a single-arm trial. This will apply to sponsors developing drugs for diseases that affect a “very small, rare disease population . . . generally less than 1,000 persons in the United States,” according to the FDA’s announcement. Qualifying conditions must also be linked to a known genetic defect and characterized by progressive functional deterioration leading to disability or death “in a relatively short period of time.” The targeted diseases should also lack “adequate” alternative therapies.
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FDA Pledges to Release CRLs in Real Time
September 4
The FDA promised that, going forward, it would release new complete response letters (CRLs) to the public “promptly after they are issued to sponsors.”
In July, in a bid for “radical transparency,” the FDA released a bundle of more than 200 CRLs from a variety of drug and biological products applications submitted to the agency between 2020 and 2024. Big Pharmas like Eli Lilly and Regeneron were represented, as well as smaller biotechs like Sarepta. At the time, the FDA said the CRLs released were an “initial batch” without elaborating on its plans.
Alongside the FDA’s September announcement, it released a second cache of heavily redacted CRLs, for products including Lykos Therapeutics’ MDMA-based therapy for posttraumatic stress disorder and Stealth BioTherapeutics’ elamipretide for Barth syndrome, approved later that month on a second try.
As of December, the archive of CRLs has grown to 392.
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FDA Introduces PreCheck Program To Boost US Drug Manufacturing
August 7
The FDA unveiled the PreCheck program with the intention of supporting biopharma companies as they build new facilities in the U.S. The PreCheck program provides manufacturers with more frequent FDA communication at critical development stages, including facility design, construction, and pre-production. A second Application Submission Phase centers around streamlining development of the Chemistry, Manufacturing, and Controls section of the application through pre-application meetings and early feedback.
The program follows an executive order issued by President Donald Trump in May instructing the FDA to cut down on the 5–10 years it currently takes to build pharmaceutical manufacturing plants in the U.S. The EO also set the table for the FDA to implement surprise inspections on foreign plants, as opposed to the planned visits that are the current standard operating practice. “A scheduled visit is no inspection,” Makary said from the White House on May 5. The order will also see inspectors spend less time in the countries where the inspections take place, allowing them to “get in and out,” conducting more inspections with the same amount of resources, Makary said.
The action is just one of many Trump has undertaken this year aimed at onshoring pharmaceutical manufacturing.
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Commissioner’s National Priority Voucher Program Introduced
June 17
The FDA’s Commissioner’s National Priority Voucher (CNPV) program is intended to shorten review timelines for certain drugs from 10–12 months to 1–2 months. The initiative streamlines reviews by assembling a team-based review in a one-day “tumor board style” meeting, rather than shuttling applications sequentially through offices of the agency.
For drugs to be awarded a CNPV, they must be “aligned with U.S. national priorities,” according to the FDA. Those priorities could include addressing a national health crisis, delivering “more innovative cures for the American people,” addressing an unmet public need or increasing domestic drug manufacturing.
The FDA announced an initial batch of nine recipients in October, with an additional six awarded in November. A month later, the agency awarded its first CNPV approval of a generic antibiotic produced by USAntibiotic.
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FDA Allows Drug Imports From Canada
May 21
Drug pricing has been a top agenda item for the first year of President Trump’s second term. In May, Trump signed an executive order instructing U.S. health agencies to attempt to lower drug prices through whatever means are available to them.
The FDA responded to that memo with a guidance that allowed states and Indigenous tribes to import prescription drugs from Canada, with the aim of lowering drug prices “without imposing additional risk to public health and safety.”
In its announcement, the FDA said it anticipated meeting with states that expressed interest in the import program in the fall, though no such meetings have been announced.
The Canadian government, for its part, made it clear that it would not export drugs to the U.S. “if that sale would cause or worsen a drug shortage in Canada,” according to a statement provided to BioSpace at the time.
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HHS Requires Placebo-Controlled Trials for New Vaccines
April 30
The Department of Health and Human Services announced it would require all new vaccines be tested in placebo-controlled trials before they are approved. While vaccines for new pathogens are already tested against placebo, new vaccines for other diseases are evaluated against existing interventions, largely for ethical reasons. The new policy “forces researchers to unethically withhold proven protection from some patients, all under the guise of ‘scientific rigor,’” Larry Bucshon, a cardiothoracic surgeon and former Congressman, wrote in an opinion article for STAT News.
An HHS spokesperson told The Washington Post that the flu vaccine would be exempt from the new requirement as it “has been tried and tested for more than 80 years.” In a note to investors on May 1, analysts at Leerink Partners called the new policy “negative news for vaccine manufacturers,” including Merck, BioNTech and Moderna.
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Restricting Pharma Representation on Adcomms
April 17
One of FDA Commissioner Marty Makary’s earliest moves was to limit the ability of pharmaceutical company employees to serve on agency advisory committees. Even on committees where they are statutorily allowed to serve, the FDA said it would “prioritize and elevate” others on adcomms, particularly patients and caregivers.
The agency noted that the change in policy did not preclude employees of regulated companies from attending or presenting to adcomms, and that exceptions could be made to allow their service on committees if they had unique expertise on a topic. This change was an early example of Makary’s efforts to “boost public trust” in the FDA, as the agency’s announcement put it.
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FDA To Begin Phasing Out Animal Testing
April 10
In a move the FDA and U.S. government had been building toward for years, the agency announced plans to phase out its animal testing requirements for monoclonal antibodies and other drugs. The FDA plans to replace these animal models with “more effective, human-relevant methods,” such as AI-based computational models of toxicity, organ-on-a-chip systems and organoids.
By leveraging nonanimal models, in addition to real-world human data, “We can get safer treatments to patients faster and more reliably, while also reducing R&D costs and drug prices,” Makary said in a prepared statement. “It is a win-win for public health and ethics.”
