Regulatory Uncertainty Emerges Across the Drug Development Lifecycle

In a recent video interview with Applied Clinical Trials, Charlie Paterson, partner at PA Consulting, discussed how reduced FDA capacity and significant staff turnover in 2025 have reshaped regulatory engagement and operational planning for clinical trials. Paterson explained that sponsors are facing longer timelines for meetings and decisions, prompting greater upfront investment in submissions and more conservative planning. He also outlined how slower FDA guidance is influencing trial design choices, limiting adoption of innovative approaches, and driving sponsors to rely on precedent and non-US regulatory frameworks. The conversation explored where regulatory uncertainty is most acute across the development lifecycle and how evolving risk tolerance at the FDA could further globalize clinical trial strategies.

Editor's note: This transcript is a lightly edited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

ACT: With FDA policy momentum rebuilding slowly, where are sponsors most likely to face regulatory uncertainty during development?

Paterson: It’s really across the board. It’s hard to pinpoint a single area. Organizations are seeing uncertainty during initial applications and feedback, leading to more conservative holds before studies even begin.

Further downstream, during tech transfer and the period between last patient last visit and approval, timelines are also elongating because capacity can’t meet volume. That’s driving concern and pushing activity outside the US.

Some organizations are considering ex-US studies for initial phases. Even with initiatives like the single pivotal trial concept, confidence requirements may still demand larger samples and longer timelines. As a result, organizations are delaying submissions, spending more time planning, or seeking guidance from other jurisdictions.

Two or three years ago, we might have seen more ambitious, accelerated US-based studies. Today, organizations are benchmarking against more rigorous jurisdictions to ensure confidence.