Sponsors working outside the US to accelerate first-in-human studies could miss the many new flexibilities the US FDA offers, the agency’s head of cell and gene therapy application reviews said.
Key Takeaways
- Acting OTP Director Vijay Kumar said that overseas first-in-human studies may not provide a long-term benefit.
- He said sponsors would forego the advantages of modernization programs at the FDA, such as the CNPV program and plausible mechanism framework.
- Kumar also listed many FDA concerns about initiating first-in-human trials outside the US, including product quality and data interpretability, as well as manufacturing.
Sponsors pursuing first-in-human studies outside the US may find that the time saved reaching the IND stage is “counterproductive” to the overall development program, Vijay Kumar, acting director of the Food and Drug Administration Office of Therapeutic Products, said.
“There is a big modernization that is currently underway in the FDA,” Kumar said during a May 6 Friends of Cancer Research meeting on accelerating CAR-T therapy development. “We have a slew of initiatives and pilots affecting every discipline.”
Kumar listed several programs, including the Commissioner’s National Priority Voucher, the plausible mechanism framework, animal-testing alternatives, CMC flexibilities, the single-pivotal trial policy, real-time clinical trials, and the unified adverse event analysis platform.
“I’m just mentioning a few here,” he said. “If the companies are engaging with consultants and CROs that are not up to date on all of these modernization efforts, the sponsors may do studies outside the US, and there may be a short-term benefit, but in the long run it might prove counterproductive to them.”
The FOCR meeting allowed Kumar to make some of the most in-depth and widest-ranging comments about regulatory issues thus far during his tenure as acting OTP director. He discussed pivotal trial expectations for CAR-T therapies, the importance of CMC preparation, the role of regulatory flexibility and feedback on pediatric rare disease trials.
Kumar became head of OTP in June 2025, jumping up several layers of management after departures early in the Trump Administration.
The widespread attention to China’s emergence as a leader in first-in-human studies meant Kumar was prepared to discuss the topic at the FOCR meeting. When asked he referred to prepared notes.
Kumar listed “a host of concerns” that the trend towards initiating studies outside the US raises for the FDA.
“We acknowledge that early-phase studies conducted outside the US are driven in a large part by operational considerations related to cost, faster enrollment of a diverse population, and the intent of regulatory convergence,” Kumar said. “From a regulatory perspective, we have a host of concerns on several key areas related to product quality and interpretability of scientific data on safety and efficacy.”
“We have manufacturing concerns [including] adherence to risk-based, phase-appropriate cGMP manufacturing chain integrity and facility inspectability,” Kumar said.
In addition, “we have concerns on adequacy of the non-clinical safety package, particularly toxicology studies,” he added. “We have concerns on Good Clinical Practice and data integrity with verifiable efficacy data. Study oversight for safety with local ethics standards and investigator accountability is another concern. We have concern on the informed consent process, specifically discussion of alternate therapies, communication of novel and unfamiliar risks, and commitment to long-term follow-up.”
“But most importantly, we also have concerns about the applicability of the ex-US data to the US population, not just based on the demographics, but also baseline characteristics, definitions of refractoriness, and availability of standard of care therapies,” Kumar said. “The reduced US site experience in early phase studies can also delay the US experience in the Phase III site initiations.”
Indeed, FDA officials have warned about studies conducted entirely in China for several years. Former Oncology Center of Excellence Director Richard Pazdur said the agency will take a hard line on trial site selection and demand multi-regional trials that could show generalizability to US patients.
Congress also is growing concerned about clinical trials conducted in China. Rep. Andy Harris, R-MD, inserted report language in the FY 2027 House FDA appropriations bill stating the agency could not accept, review or consider “any covered clinical data generated by a clinical investigation site” in China, Iran, North Korea and Russia to support an IND.
The ban would take effect one year after the bill is enacted. The FDA also would be required to write guidance on the issue.
The House Appropriations Committee approved the amended bill and sent it to the full chamber for consideration on April 29.