FDA Introduces “Plausible Mechanism” Pathway to Accelerate Approval of Ultra-Rare and Personalized Gene Therapies

November 2025 · Silver Spring, Maryland — The U.S. Food and Drug Administration (FDA) has announced a new “Plausible Mechanism” approval pathway to accelerate the review and authorization of ultra-rare and individualized genetic therapies, including so-called “N-of-1” treatments tailored to single patients.

The new framework, launched by the FDA’s Center for Biologics Evaluation and Research (CBER), provides a science-based yet flexible route for developers of customized gene therapies addressing unique or extremely rare mutations. The initiative aims to shorten time-to-treatment while maintaining safety and quality standards.

Photo by U.S. Food and Drug Administration

Under this mechanism, FDA reviewers may rely on biological plausibility and preclinical data as sufficient evidence to support clinical use or emergency administration in exceptional cases. This marks a shift from traditional large-scale trials toward mechanistic validation in assessing safety and therapeutic rationale.

The guidance also outlines expectations for small-scale GMP manufacturing, quality documentation, and long-term follow-up in individualized therapies — signaling the agency’s effort to modernize regulation for emerging personalized genetic medicine.

Industry Background: Manufacturing Capabilities for Personalized Therapies

The introduction of this pathway underscores the growing need for flexible, compliant, and rapid manufacturing systems capable of supporting small-batch, patient-specific therapies.

Hillgene, a biotechnology company specializing in cell and gene therapy CDMO services, is actively developing modular viral vector production platforms and digitalized bioprocess control systems that align with FDA’s evolving regulatory direction.

Hillgene’s platform integrates GMP-compliant micro-scale manufacturing and rapid analytical validation, designed to accelerate translational studies and personalized therapy delivery.

Photo by Toon Lambrechts on Unsplash

Source: BioPharma Dive, “FDA introduces ‘Plausible Mechanism’ pathway to speed ultra-rare gene therapy approvals,” November 12, 2025.