Accelerate RARE: PDUFA VIII Working Group

2:00 - 5:00 pm EST on Monday, September 8, 2025

Objective:

Develop stakeholder consensus on regulatory priorities for rare disease–specific enhancements to PDUFA VII.

Prepare a briefing document and publish a realistic roadmap to meaningfully accelerate rare disease clinical development.

PDUFA & Rare Disease Today:

PDUFA (Prescription Drug User Fee Act) is reauthorized every 5 years; PDUFA VII runs through Sept 2027. It funds FDA review resources and pilot programs

Rare disease innovations under PDUFA VII include:

  • Rare Disease Endpoint Advancement (RDEA) pilot

  • Split Real-Time Application Review

  • Increased rare disease reviewer training

Expedited pathways (Fast Track, Breakthrough, Priority Review, Accelerated Approval) already enable approvals ~3–5 years faster in oncology and rare disease

U.S. HHS is pushing for even faster rare disease approvals at the FDA—signaling openness to bold reforms.

Possible Enhancements for PDUFA VIIII (2027)

(Ten ideas to start a discussion, in no particular order)

1. “Ultra-Rare Fast-Track” Program

  • For diseases with < 500 patients globally.

  • Offer rolling reviews from pre-clinical data onwards.

  • Permit Phase Ib approvals based on strong mechanistic biomarkers and RWD, with conditional post-marketing safety/efficacy.

2. Built-in Bayesian Adaptive Designs

  • Mandate adaptive design guidance and FDA review of statistical tools.

  • Sponsors receive “design concurrence letters” early to overlay Phase II data onto Phase III, accelerating final approval

3. Endpoint Innovation Accelerator

  • Extend RDEA to a formal Endpoint Acceleration Program with FDA-supported multi-stakeholder consortia crafting and validating surrogate endpoints in advance.

4. RWE-Powered Label-to-Market Model

  • Create a streamlined path: data from natural history RWD → conditional label → traditional approval pegged to RWE from registries and decentralized trials within 18 months

5. Trial Inclusion/ Exclusion Criteria

  • Issue guidance on broadening eligibility criteria and designing more inclusive rare disease trials.

  • Fund pilots testing alternative enrollment models and train FDA staff to encourage flexible, patient-centered criteria.

  • Require structured patient feedback on inclusion/exclusion criteria during regulatory meetings to ensure criteria reflect real-world needs.

6. Standardization of Clinical Trial Logistics

  • Develop and promote standardized CTAs and operational templates (e.g., DOA logs) to accelerate trial startup.

  • Expand FDA guidance to enable and encourage central IRB use across rare disease and decentralized trials.

  • Support interoperability of EDC and eSource systems, allowing electronic transfer of validated source data without duplication.

  • Fund a federal framework on third-party research home health, clarifying institutional liability and PI oversight requirements to expand trial access.

7. Elite Priority Review Vouchers

  • Award higher-value vouchers for ultra-rare (or first-in-class rare) approvals.

  • Offer bonus incentives (e.g., fee waivers) for pooled manufacturing and multi-arm trials.

8. Agency Capacity & Pre-Submission Governance

  • Require rare disease review liaisons and reserve Rapid Response Teams for these submissions.

  • Guarantee FDA responds to PMR/CMC/CMC midcycle within 30 days—enabling faster approvals

9. Global Harmonization & Mutual Recognition

  • Allow FDA to rely on EMA, PMDA, Health Canada rolling reviews under confidentiality frameworks.

  • Sponsors could access multi-agency scientific advice and synchronized approval timelines.

10. Accelerated Withdrawal Pathway

  • Create a Fast Withdrawal Track with pre-agreed criteria (e.g., futility triggers, safety flags) to ensure conditional approvals don’t linger unnecessarily .

Discussion Agenda