FDA Voices
America Must Address Early Clinical Development
By: Karim Mikhail, B. Pharm, MSc, Acting Director of the Center for Biologics Evaluation and Research
The Problem: America is at Risk of Being Left Behind
America is losing ground on clinical trials. Phase 1 trials that may take up to two years to complete here in the United States are completed in nine months in China, threatening America’s leadership in scientific innovation. To combat this, President Trump and Secretary Kennedy have directed the U. S. Food and Drug Administration to use every tool at its disposal to reverse this trend.
The consequences are broad. Patients lose access to investigational therapies and may have to travel abroad to enroll. The FDA’s ability to shape science and oversee safety diminishes when trials move overseas. For investors, slower and less predictable U.S. regulatory timelines push early-stage capital, along with jobs and intellectual property, to other countries.
Why the Current Pre-IND Process Isn't Optimal
Outdated Process, Growing Demand: The pre-Investigational New Drug (IND) application process was built for a simpler era. Drug development has grown more complex, diverse, and voluminous, particularly with novel modalities like cell and gene therapies, and the current system cannot meet that demand at scale.
Unclear Requirements Drive Over-Submission: Existing guidance wasn’t written specifically for Phase 1 trials, leaving sponsors uncertain about what FDA actually needs. Fearing clinical holds, they routinely over-submit data, creating unnecessary delays that better clarity on phase-appropriate requirements could eliminate.
One Pre-IND Meeting Isn’t Enough: The single pre-IND advisory meeting is expected to resolve nonclinical, clinical, and Chemistry, Manufacturing and Controls (CMC) questions all at once. For complex or novel products, one non-binding interaction is rarely sufficient; the process lacks the iterative collaboration sponsors may need to prepare strong submissions.
Post-IND Delays Compound the Problem: Even after an IND is permitted to be issued, trials face additional structural delays: Institutional Review Board (IRB) review, site contracting, enrollment, and clinical activation. These bottlenecks, the target of HHS’ Operation TrialBlazer, are systemic, not intentional failures.
FDA’s Solution: Reimagining the IND Process Through Clarifying Requirements and Launching the Expedited IND Pilot
The FDA is responding to these challenges with a coordinated set of solutions, acting on President Trump’s mandate to tear down bureaucratic barriers to innovation.
First, we are clarifying IND requirements to reflect what is scientifically appropriate for first-in-human (FIH) Phase 1 trials, prioritizing patient safety while eliminating the ambiguity that drives over-submission. This is not a one-time fix, but an ongoing commitment to ensure phase-appropriate expectations keep pace as modalities and scientific understanding evolve.
Second, we plan to use the Expedited IND Pilot to unlock the power of American innovation by enlisting expert Qualified Research Institutions (QRIs), such as academic medical centers, contract research organizations, and other organizations with deep subject matter area expertise, to take on the role of a scientific partner during IND preparation. This tests a specific hypothesis: allowing QRIs to provide substantive, iterative, discipline-specific guidance that sponsors need in real time can accelerate review, answer regulatory questions earlier, and accelerate time to FIH trial initiation. All without compromising patient safety.
Third, because QRIs bring specialized and substantial scientific expertise to the preparation process, the FDA plans to review and accept individual components of an IND submission as they are completed, rather than waiting for a complete package. This rolling review model fundamentally changes the timeline. Issues are identified and resolved in real time, the risk of a clinical hold at the end of the process decreases, and the path from scientific discovery to FIH trial becomes faster, more predictable, and more collaborative. Taken together, these three shifts are the architecture of the Expedited IND Pilot.
The way this would work starts with sponsors partnering with prospective QRIs with the necessary expertise, capabilities, and regulatory experience to advance sponsors’ development programs. These pairs would apply through a forthcoming pilot application. Those QRIs would then support sponsors through pre-IND preparation and validating the IND components and data before they reach the FDA, helping to ensure that submissions arrive complete, meeting regulatory standards, and with scientific recommendations from qualified external experts.
This pilot also changes the path of the submission itself. The logic begins with sequencing. In a well-designed FIH program, the nonclinical package is typically the first body of evidence ready for review, establishing the scientific rationale and safety basis for proceeding to humans. CMC data follows as product characterization matures. Clinical protocols and safety information come last, informed by what the nonclinical and manufacturing data have established. Today’s process ignores this natural sequence, requiring sponsors to hold everything until the full package is assembled. The rolling submission process allows sponsors and their QRI partner to submit individual components of an IND submission on a rolling basis with the FDA providing feedback on each as it arrives. The formal 30-day review clock would only begin when the final component of the IND is submitted. This means the FDA is engaged throughout development, not just at the end. Potential issues, disagreements, or questions are surfaced and solutioned earlier, ultimately accelerating IND submission.
Finally, the pilot will also test whether a QRI can be not just a scientific partner in IND preparation, but an operational partner in trial initiation. A QRI that has established relationships with IRBs, or that operates clinical trial sites directly, can reduce the post-IND delay. IRB review can begin earlier in the process, informed by the same scientific preparation that shaped the IND submission. Site contracting can be initiated before the FDA’s review clock has even started. And site activation can proceed in parallel rather than in queue. This is where the full value of the QRI model is realized; not only does it improve the quality and speed of what goes to the FDA, it accelerates what happens after the FDA provides a regulatory decision.
The FDA’s Request for Information for this Pilot
We released a Request for Information because we want a pilot design that reflects the real needs of sponsors and patients. The details described are open to discussion.
We are genuinely open to new thinking about how QRI-sponsor-FDA relationships should work, what research capabilities matter most, how submission components should be structured, and what success looks like across different therapy areas and modalities. On August 6, the FDA is holding the Expedited IND Pilot Program Educational Webinar for Stakeholders to clarify the intent behind the program, the purpose of the RFI, and answer specific stakeholder questions that might influence your feedback on the RFI.
Ultimately, this overdue modernization is only happening because of the decisive leadership of the Trump Administration. For years, Washington inertia allowed bureaucratic red tape to stall progress while foreign adversaries gained ground. By finally cutting through this stagnation to execute President Trump’s directive to Make America Healthy Again, the FDA is not just updating a process — we are reclaiming our edge over foreign competitors, keeping high-paying scientific jobs on our shores, and delivering life-saving therapies to American patients months ahead of schedule.