HHS 'Operation TrialBlazer' Pairs Expedited IND Pilot With Single-Trial Evidence Guidance

The US Department of Health and Human Services has launched "Operation TrialBlazer," a set of measures intended to shorten drug development from the investigational new drug (IND) stage to late-stage trials, with the Food and Drug Administration proposing a pilot for first-in-human studies and reissuing draft guidance on approvals based on a single pivotal trial. The initiatives were announced on Monday, June 22, as reported by Regulatory Focus, the news service of the Regulatory Affairs Professionals Society.

HHS Secretary Robert Kennedy Jr. framed the effort around research moving abroad. "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," Kennedy said, according to Regulatory Focus, which reported that he said the pilot aims to counter the trend of trials moving to China.

A pilot for first-in-human trials

FDA opened a public docket seeking comment on a proposed Expedited Investigational New Drug pilot program. Under the proposal, drug companies would partner with qualified research institutions, such as academic medical centers or contract research organizations, to develop Phase 1 IND submissions for first-in-human trials, using a rolling submission platform with the goal of minimizing clinical holds, Regulatory Focus reported. Comments on the pilot are due July 22.

The agency also announced a draft guidance on using a quantitative systems pharmacology approach to help set the minimum anticipated biological effect level dose in first-in-human trials, with comments due July 24, and a revised master protocols draft guidance that adds material on basket trials. It launched a Phase 1 IND Navigator webpage, updated its webpage on chemistry, manufacturing and controls information for first-in-human INDs, and opened a Phase 1 contact center, according to the report.

One pivotal trial plus confirmatory evidence

The late-stage piece is a revised draft guidance, "Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products," issued jointly by FDA's drug and biologics centers and its Oncology Center of Excellence. On its guidance page, FDA says the document "clarifies how sponsors can rely on one adequate and well-controlled clinical investigation with confirmatory evidence to satisfy the substantial evidence of effectiveness standard."

FDA said it revised and reissued the draft in response to public comments and to changes in drug development, citing advances in understanding of biological processes and the increasing availability of high-quality data. When final, the guidance will replace the 1998 guidance "Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products." Regulatory Focus noted that former FDA Commissioner Marty Makary had announced plans last year to move away from the agency's traditional expectation of two adequate and well-controlled trials, but that draft guidance implementing the policy had not been published until now. Comments on the draft are due August 24, under docket FDA-2019-D-4964.