While every incoming presidential administration brings new leadership and mandates for federal agencies, few years have been as tumultuous as this one, with even typically mundane events like the annual FDA flu vaccine meeting making mainstream headlines.
In this new environment where change is constant, industry stakeholders should learn to pivot and adapt, said Aman Khera, a regulatory, science and innovation consultant to the pharma and biotech industry.
“It’s a new FDA,” Khera said.
Despite the various uncertainties, it’s also a time where she sees “an opportunity.”
“If they’re saying [they’re] doing things a little differently [but are] open to suggestions … we need to start asking them: Can you please help strategize with us?” she suggested. “Stop thinking ‘us and them’ and start thinking more strategically.”
To better understand how to work productively with the agency going forward, it’s helpful to dig into the most impactful changes from the last year. Here, Khera points to 2025’s biggest shifts inside the FDA for pharma and what opportunities they could bring.
More flexibility for rare diseases
Stealth BioTherapeutics’ recent FDA approval for the Barth syndrome treatment Forzinity was hailed as a signal that the regulator might adopt new flexibility in trial design for ultra-rare conditions. This new openness was notable for drug developers in the ultra-rare disease space working with far few trial participants.Just a month after waving Forzinity across the finish line, the FDA took its flexibility ethos a step further when it proposed a “plausible mechanism” pathway for approving personalized therapies.
This pathway would be reserved for products “where a randomized trial is not feasible” and would prioritize rare diseases that are fatal or can cause severe disabilities in children, FDA Commissioner Dr. Marty Makary and CBER Director Dr. Vinay Prasad wrote in the New England Journal of Medicine. How will this new approach play out in the real world?
Despite Makary and Prasad’s article, the FDA hasn’t issued guidance for what a plausible mechanism pathway will look like in practice.
“The article was great,” Khera said. “We now need true guidance for industry. When you say you're going to be flexible, how flexible are you going to be?”
Meanwhile, the agency’s rare pediatric priority review voucher program, which already existed and also aimed to incentivize product development for rare pediatric diseases, expired at the end of last year, leaving rare disease drug developers who want to leverage the policy in limbo. But legislative efforts to extend it through the Give Kids a Chance Act was unanimously passed in the House this week, sending the bill to the Senate for a vote.
Staffing shakeups
The FDA’s new top brass largely fits into the MAHA agenda of scrutinizing industry ties, questioning scientific norms and taking a more critical stance on vaccines.
But controversial leadership isn’t the only staffing change that could impact the pharma industry. The agency has also faced mass layoffs, resignations of qualified staff, a federal hiring freeze and worries about a potential brain drain, especially in the vaccine space.
FDA staffing uncertainties recently prompted a letter to Makary from the advocacy group No Patient Left Behind, which was signed by dozens of biotech execs expressing concern about the agency’s ability to function. Despite industry handwringing and an overall slowdown in the rate of FDA approvals, Khera said that in her experience, it’s generally been business as usual when working with the agency, even during the recent government shutdown.
“Review teams were still up and running … and we're not seeing the delays,” she said.
For companies worried about FDA hiccups, Khera recommends communicating with the agency early and often, while requesting meetings and ongoing feedback.
America-first incentives
While the White House has successfully struck deals with pharma companies to lower drug prices and boost U.S. manufacturing, the FDA is getting in on the “America-first” style action, too, through vouchers and other programs.
For example, the new FDA PreCheck program aims to strengthen the domestic pharmaceutical supply chain by “increasing regulatory predictability and facilitating the construction of manufacturing sites in the United States.” There’s also a new abbreviated new drug applications pilot program that aims to provide faster reviews for generic companies who test and manufacture their products in the U.S.
Perhaps the program that’s gotten the most attention is the new National Priority Voucher program, which shortens FDA review time from between approximately 10 and 12 months to between one and two months following a sponsor’s final drug application submission. The FDA said it would award the vouchers to “companies aligned with U.S. national priorities,” such as addressing unmet public health needs and increasing domestic drug manufacturing.
But these recent efforts are already facing scrutiny.
After the agency issued two batches of vouchers — which targeted products for nicotine vaping addiction, infertility, obesity and drug-resistant tuberculosis — Rep. Frank Pallone Jr. (D-NJ) and Sen. Bernie Sanders (I-VT) wrote in a letter to Makary that the program lacks Congressional authorization and raises “significant concerns” that it “will enable corruption by creating a new, lucrative gift for drugmakers and allies politically favored by President Trump.”
They also argued that the program’s expedited reviews have “absurdly short timelines that are inconsistent with those in the user fee agreements.”
Pulling back the curtain on FDA rejections
In July, the FDA published more than 200 complete response letters issued between 2020 and 2024 in an effort to embrace what it called “radical transparency.” By publishing the FDA notices informing companies that their new drug or biologics license application was rejected, the FDA aims to provide more insight into agency decision-making.
According to the FDA, “sponsors often misrepresent the rationale behind FDA’s decision to their stakeholders and the public.” The agency also cited a 2015 analysis showing that “sponsors avoided mentioning 85% of the FDA’s concerns about safety and efficacy when announcing publicly that their application was not approved.”
Although trade secrets and confidential commercial information were redacted from the published CRLs, companies are still likely to be uncomfortable with the CRLs being published. But pharma can take advantage of the situation by reviewing other companies’ CRLs to learn more about the FDA’s thinking and sticking points when reviewing applications, Khera said.
“We're getting competitive intelligence — [just] in a different way,” Khera said.
