FDA Makes Case for Overhauling Early Clinical Development to Reclaim US Leadership

In a new post on FDA Voices, Karim Mikhail, BPharm, MSc, acting director of the Center for Biologics Evaluation and Research (CBER), made a direct case for why the US needs to overhaul its early clinical development process, and outlined how the FDA plans to address it.¹

The main concern is timeline. Phase I trials that may take up to two years to complete in the US are completed in nine months in China. The consequences, Mikhail wrote, extend beyond competitive optics: 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; and slower, less predictable US regulatory timelines push early-stage capital, jobs, and intellectual property to other countries.

Why the current system falls short

Mikhail identified four structural problems with the existing pre-Investigational New Drug (IND) process.

The first is that the process was built for a simpler era. Drug development has grown more complex and voluminous, particularly with novel modalities like cell and gene therapies, and the current system cannot meet that demand at scale.

The second is that unclear requirements drive over-submission. Existing guidance was not written specifically for Phase I trials, leaving sponsors uncertain about what the FDA actually needs. Fearing clinical holds, sponsors routinely submit more data than necessary, creating delays that better clarity on phase-appropriate requirements could eliminate.

The third is that a single pre-IND advisory meeting is expected to resolve nonclinical, clinical, and chemistry, manufacturing, and controls questions all at once—an expectation that is rarely realistic for complex or novel products.

The fourth is that even after an IND is permitted, trials face additional structural delays in IRB review, site contracting, enrollment, and clinical activation—systemic bottlenecks that compound the earlier inefficiencies.

The Expedited IND Pilot

The FDA's response centers on three shifts that together form the architecture of the Expedited IND Pilot.

First, the agency is clarifying IND requirements to reflect what is scientifically appropriate for first-in-human Phase I trials, eliminating the ambiguity that drives over-submission while maintaining patient safety.

Second, the pilot enlists qualified research institutions (QRIs)—academic medical centers, CROs, and other organizations with deep subject matter expertise—as scientific partners during IND preparation. These QRIs would provide iterative, discipline-specific guidance to sponsors in real time, with the goal of answering regulatory questions earlier and accelerating time to first-in-human trial initiation.

Third, because QRIs bring specialized 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. Issues would be identified and resolved in real time, reducing the risk of a clinical hold at the end of the process.

"The path from scientific discovery to first-in-human trial becomes faster, more predictable, and more collaborative," Mikhail wrote in the article.

The rolling submission process is designed to follow a logical sequence: the nonclinical package first, establishing the scientific rationale and safety basis for proceeding to humans; chemistry, manufacturing, and controls data next as product characterization matures; and clinical protocols and safety information last. The formal 30-day review clock would only begin when the final component is submitted.

The pilot would also test whether QRIs can serve as operational partners in trial initiation—using their established relationships with institutional review boards (IRBs) and clinical trial sites to begin IRB review and site contracting before the FDA's review clock has even started.

The FDA released a request for information (RFI) on the pilot and held an educational webinar for stakeholders on August 6 to clarify the program's intent and answer questions that might inform public feedback on the RFI.

Earlier steps toward a more continuous development model

Earlier in April, the FDA launched two proof-of-concept real-time clinical trials as an early step toward a more continuous clinical development model. The agency announced that proof-of-concept studies sponsored by two large pharma companies would transmit safety signals and endpoint data in real time to regulators, and issued an RFI to inform a broader pilot program.²

In an exclusive interview with Applied Clinical Trials at this year’s DIA Global Annual Meeting, Kevin Bugin, head of global regulatory policy and intelligence at Amgen and executive sponsor of TransCelerate's Embedded Pragmatic Trials initiative, offered important context on what the real-time initiative is actually designed to do.³

"They're not focused on what I'd call real-time clinical trial data streaming to the FDA," he said. "They're really focused on signals—and those signals are intended to inform critical decisions. If anything, they're focused on real-time evidence generation for regulatory-grade decision making.”

On data quality, Bugin pushed back on a deeply ingrained industry habit. "The modus operandi for many, many years has been to generate more data, then do a lot of data cleanup and data management to ensure that data will be high quality. What we're hearing from regulators is: no, you need to focus on the right data at the right time and in the right standard. That quality comes from quality-by-design thinking, not something you can build in after the study is over."

References

1. America Must Address Early Clinical Development. FDA Voices. August 5, 2026. Accessed August 7, 2026. https://www.fda.gov/news-events/fda-voices/america-must-address-early-clinical-development
2. FDA Launches Proof-of-Concept Real-Time Clinical Trials. Applied Clinical Trials. April 29, 2026. Accessed August 7, 2026. https://www.appliedclinicaltrialsonline.com/view/fda-real-time-clinical-trials
3. Applied Clinical Trials at the 2026 DIA Global Annual Meeting: Conversations on Data, Outsourcing, and the Patient Voice. Applied Clinical Trials. June 26, 2026. Accessed August 7, 2026. https://www.appliedclinicaltrialsonline.com/view/applied-clinical-trials-2026-dia-global-annual-meeting-data-outsourcing-patient-voice