The FDA’s new investigational new drug pilot program—one part of HHS’s broader clinical trial modernization initiatives—has lofty goals to expedite first-in-human trials of novel drugs, but experts say it won’t tip the scales much on its own.
Reactions to the Department of Health and Human Services’ new clinical trial modernization initiative have been mixed. On one hand, biotech and regulatory leaders are on board with a pilot program to speed early trials in hopes of bringing them back to the U.S. But former regulators point to roadblocks to running first-in-human trials that are beyond the FDA’s control.
“FDA is not the primary source of most delays in early phase clinical trials,” Harpreet Singh, a former division director of oncology at FDA, told BioSpace. The major delays instead occur at the site level, she said.
Announced June 22, Operation TrialBlazer is an HHS-wide initiative that seeks to reduce the time from drug identification to Phase 1 trials and expedite early clinical development timelines by as much as a year. By simplifying the investigational new drug (IND) application and approval process, the health department—including the FDA—aim to make the U.S. more competitive as an ideal location to run these trials.
“America should be the best place in the world to develop new medicines, yet we have built a system that drives too much clinical research overseas,” Health Secretary Robert F. Kennedy Jr. said in a prepared statement alongside the pilot’s announcement.
Indeed, in 2010, less than 8% of global clinical trials were run in China, according to an April report by the National Bureau of Economic Research; by 2020, the Asian nation had overtaken the U.S. in annual registered trials. China’s National Medical Products Administration has also overtaken the FDA in terms of cancer approvals, greenlighting 94 oncology drugs between 2020 and 2025 compared to the 87 that entered the U.S. market in the same timeframe, per a new Health Affairs Scholar study.
“There’s no question that we’re losing Phase 1 trials,” Hilary Marston, a principal at Canal Row Advisors and former chief medical officer at the FDA, said during a panel discussion at the BIO International Convention in San Diego last month.
The reasons for this are clear, added Singh, now chief medical officer at the global CRO Precision for Medicine. For companies considering starting an early-phase trial in either Spain, Australia or China versus the U.S., “all three, besides the U.S., are going to come in more quickly, more cost effective and with less administrative burden, and that is the reason why we’re having difficulty retaining our foothold in early phase drug development,” she explained.
Marston said she was “heartened” by the TrialBlazer announcement, but there’s a lot of nuance to weed through. Indeed, both Marston and Singh expressed concerns over whether the FDA’s efforts would be enough to shift the clinical trial landscape.
“I still am not fully clear on how HHS will address the major issues,” Singh said.
FDA targets IND and pre-IND processes
Operation TrialBlazer acknowledges the complexity of the problem, with the program entailing several parallel initiatives across HHS agencies aimed at accelerating the launch of early clinical trials. During an FDA town hall session at BIO 2026, acting Center for Biologics Evaluation and Research (CBER) Director Karim Mikhail highlighted two key elements of the FDA’s new IND program. First, the agency is launching a new rolling submission process for INDs, so companies can submit their applications piecemeal and receive feedback on them. The FDA is also working to streamline the requirements of the IND submission itself.
“If you look at the IND guidances we have, they have not been designed for Phase 1, first-in-human IND submission . . . it doesn’t really specify what is necessary when you’re submitting for Phase 1,” Mikhail said. He emphasized that the information released so far is just the beginning. “It’s not like it’s one and done, and we’re finished with streamlining requirements. We will continue to do that.”
Saol Therapeutics CEO Dave Penake agreed that the current IND requirements are cumbersome compared to other nations, particularly Australia. “There are a lot of non-clinical data that are required in the U.S. before you have your first-in-human dosing that are not required until Phase 2 in some other countries,” he said.
A second step of the FDA’s initiative, Mikhail continued, is to improve the process before an IND is even submitted. The acting CBER director lamented the fact that sponsors only get a single pre-IND meeting with the FDA. “You have this one chance, and one chance only, to be in front of the FDA with all your questions . . . and that’s a very big, honestly tough position for a CEO,” he said. “We are trying to break this mold. We’re trying to say the FDA doesn’t need to be in the way, because our advice in pre-IND is consultative in nature.”
Marston acknowledged that faster clearance of tools for use in preclinical and IND-enabling studies could help, but she cautioned that one of the reasons China is able to quickly get investigational drugs into human studies is through investigator-initiated trials and other pathways that don’t involve the country’s Center for Drug Evaluation (CDE).
“We’re not going to be as fast as China, right?” Marston said. “I think we just need to recognize that, but we can get much closer, and there are other reasons to do research here.”
IRBs, site issues and other challenges
At Precision for Medicine, Singh and her team have often placed early-phase trials in Australia or Europe based on client preference, she said, “and that has been predicated on speed and cost and high-quality data being generated.”
But rather than anything to do with INDs, Singh attributed the slower pace of entering human drug testing primarily to lengthy site activation timelines, site infrastructure challenges and associated costs, and institutional review board (IRB) processes. IRBs are federally mandated committees that review and monitor human clinical trials funded by the federal government or regulated by the FDA. The committees are typically operated within academic institutions or healthcare systems or as independent organizations, whether those be nonprofits or for-profit third-party providers.
“Until we take care of the site issues, we’re getting nowhere,” agreed Marston, pointing to lengthy and complex protocols that can prove prohibitive to efficient research.
The FDA’s guidance document acknowledges these issues. Beyond the changes to IND processes, “The pilot will also be used to explore creative ways to address the delays that occur after an IND is granted, from IRB approval to site contracting and patient enrollment, which has become a rate-limiting step in the efficiency of U.S. clinical trial initiation.”
Currently, some IRBs wait for an IND to be approved by the FDA before reviewing a clinical trial protocol, while non-federally funded sites may conduct an independent review, resulting in “inconsistent timelines and an administrative burden,” according to the FDA’s program overview.
Under TrialBlazer, the agency is considering implementing a single Institutional Review Board (sIRB) model where there would be one IRB of record for all of a program’s sites.
“We have really substantial delays associated with just IRBs, and each institution having its own request to the protocol,” Saol’s Penake said. “I could definitely see how 6 to 12 months could get knocked off here if you just did central IRBs.”
In 2022, the FDA issued a proposed rule to require the use of a single IRB for review of multisite studies conducted under an IND, with certain exceptions, according to Claire Davies, a shareholder at Polsinelli law firm.
“The Operation TrialBlazer roadmap appears to contemplate moving that proposal forward, and requiring a single IRB for multi-site studies should reduce duplicative review,” Davies told BioSpace in an email.
Heidi Gertner, a partner at Hogan Lovells, agreed. “They’re right in thinking this could be a problem that could be addressed by requiring one IRB to review. . . . I can see what they’re getting at,” she told BioSpace. “We hear companies complain all the time about how long it takes for IRB review, and especially when it’s a multisite study, and especially when it’s multi-jurisdictional. It’s a hassle to get all the IRB approvals in place before starting.”
In practice, however, Gertner raised the concern that trial sites may not be eager to cede their authority in this way. “Usually, IRBs don’t really want to give up their oversight,” she said, because it involves their institution, employees and processes.
Open for comment
At BIO 2026, Acting Center for Drug Evaluation and Research (CDER) Director Michael Davis emphasized that FDA is but one piece of the TrialBlazer initiative. “This is really a whole of HHS effort,” Davis said.
For example, the multi-department effort also includes the NIH’s National Center for Advancing Translational Sciences, which is working to accelerate CRISPR-based therapies for patients with rare diseases, according to HHS’ announcement. Meanwhile, the National Cancer Institute is working with cancer centers, researchers and other stakeholders to streamline clinical trial activation and improve enrollment in cancer studies.
Even within the FDA, TrialBlazer is a collaboration between CDER and CBER, leadership emphasized at BIO 2026. The result “was really a package of initiatives, with the expedited IND pilot as being one,” Davis said.
He spoke of an internal FDA town hall where agency leadership addressed some 2,000 staffers and “really laid out the problems of what the country is facing,” including visuals showing the rates at which different phases of clinical trials are shifting overseas. “My sense is many people might not really appreciate the scope of this problem,” Davis said, but as staffers gain that appreciation, “they see that this is truly a priority.”
FDA leadership is now seeking feedback from those staffers, as well as from the public. “We really want to hear ideas that people have,” Davis said, “because this is a challenge that we’re all really taking seriously.”
Singh—who was a primary reviewer of INDs during her time at FDA, at one point overseeing the review of up to 20 applications per week—said that one way FDA could improve would be “to give more autonomy to our very experienced early phase drug developers that sit in biotech and sit in big pharma, and to not basically line-item review and edit every detail of the protocols.”
“Most FDA staff physicians, the majority of them . . . have not spent time in industry developing drugs,” she continued. “In biotech and in big pharma, most people that I have encountered have substantial drug development experience.”
The purpose of an IND is to ensure patient safety, Singh added. “When you get your IND-cleared letter, the top of the letter says, ‘Safe to Proceed.’” But she is increasingly seeing that “the scope of the commentary and the changes that FDA requests sponsors to make . . . go somewhat beyond the scope of ensuring patient safety.”
The public comment period for the IND initiative ended July 22. Other programs under Operation TrialBlazer will remain open for feedback into August and September.
