Considerations for the use of the Plausible Mechanism Framework to Develop Individualized Therapies that Target Specific Genetic Conditions with Known Biological Cause February 2026

GUIDANCE DOCUMENT

• Docket Number: FDA-2026-D-1256
• Issued by: Center for Biologics Evaluation and Research; Center for Drug Evaluation and Research

The purpose of this guidance is to describe considerations for generating substantial evidence of effectiveness and evidence of safety for individualized therapies based on a plausible mechanism framework. The plausible mechanism framework outlines a set of recommendations to help developers of individualized therapies generate sufficient clinical safety and efficacy data to demonstrate that a drug or biological product is safe and effective for the intended use, and that the product can be manufactured to regulatory quality standards. These data are used to support approval or licensure of an individualized therapy for a specific indication. This includes a careful evaluation of the results of nonclinical and clinical data and chemistry, manufacturing, and controls (CMC) data necessary to support product quality.

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