Legislators appears eager to build on the US Food and Drug Administration’s plans to expedite IND reviews in the upcoming user fee reauthorization cycle.
During a July 15 hearing on the FDA’s role in maintaining US leadership in biomedical innovation, House Energy and Commerce Health Subcommittee Chair Morgan Griffith, R-VA, discussed the importance of reforms to the clinical trial process and effectively promised Congress would attach significant legislation to the prescription drug user fee renewal bill.
He said the PDUFA reauthorization “is not limited to just extending the status quo.”
Griffith referenced the Health and Human Services Department’s Operation TrialBlazer initiative, which is aimed at revitalizing first-in-human studies in the US. The initiative includes a proposed expedited IND pilot program, where the FDA would establish a rolling submission process to expedite the initiation of first-in-human studies and reduce the number of clinical holds.
Operation TrialBlazer was mentioned frequently throughout the hearing, especially by Republican members.
“It is important that we begin to have these conversations as this subcommittee looks ahead to FDA’s user fee reauthorizations next year, especially as initiatives like Operation TrialBlazer demonstrate that an approach to maintaining America’s competitive edge involving improving the efficiency and efficacy of drug development,” Griffith said.
The FDA on July 27 also released several final guidances on cancer clinical trial eligibility requirements that were connected to the Operation Trialblazer effort. (See sidebar.)
Risk-Based Approach For INDs
Griffth wants to develop a risk-based approach to IND requirements that would create a “second standard” for low-risk development programs.
He said it “bothers” him that the FDA maintains the same “standard process” for INDs regardless of risk and asked whether a “second standard” should be considered for lower-risk development programs.
“It’s one of the things … I’ve been toying with in my mind,” Griffith said.
The hearing was part of a broader set of potential congressional actions attempting to counter the threat of China as an emerging global leader in early-stage studies. Committee ranking member Diana DeGette, D-CO, also disclosed that the FDA’s new leadership team is backing away from some of the informal policy pronouncements made by former Commissioner Martin Makary.
Witnesses at the hearing agreed IND reforms are a “good start” in maintaining US leadership in biomedical development, but suggested more could be done to shorten the time to first-in-human trials.
When asked about a risk-based approach to INDs, Cynthia Verst, IQVIA president of design and delivery innovation, research and development solutions, said “Having the ability to be more weighted and adaptive … and being very focused on that risk-based profile will enable us to speed along processes and reviews, but not jeopardize patient safety nor data integrity.”
Verst said in her opening remarks that the time needed to complete an IND package, not the FDA review process, is the key delay of first-in-human trials and leading sponsors to start their Phase I trials outside the US.
“Consistently, our sponsors, particularly emerging biopharma companies who drive over 75% of the global Phase I starts, cite time and resources to assemble the IND package itself as the barrier to initiate trials in the US,” she said. “Many start their first trial ex-US while concurrently building their full IND package here.”
Streamlining Process Could Delay FDA Feedback
Verst said a potential issue with streamlining the IND process is delayed sponsor feedback from the FDA.
“This ‘fit for first-in-human focus’ at the IND application review will defer important conversations later in development,” she said. That will “require more flexibility and capacity for FDA reviewers to provide that scientific advice as assets advance.”
We “may certainly gain more first-in-human trials with speed to signal, but see costly rework and delays in later stages,” Verst added.
Verst recommended more funding for the FDA and incentives for sponsors.
“Congress should consider supporting the FDA efforts to adapt rolling review practices and increase capacity for scientific advice, perhaps offering additional interactions for early-stage companies who commit to start their trials first in the US,” she said.