QSP-Based Dose Selection for Minimum Anticipated Biological Effect Level (MABEL) in FIH Trials - Draft Guidance

Key changes

Introduction of QSP-based modeling for MABEL dose selection; emphasis on human-relevant biological data over traditional animal toxicity for starting dose justification; recommendations for IND submission data packages.

PV impact

The guidance enhances early-stage safety assessment by providing a robust framework for dose selection in FIH trials, which is critical for preventing over-exposure and managing safety risks in human participants. It encourages the use of human-relevant biological modeling (QSP) to justify safety margins, impacting the pharmacovigilance planning for early clinical development.

Exact policy details

Publication Date

June 2026

Applies to: All regulatory submissions utilizing the guidance.

Content current as of: 06/25/2026 · p. 1 · High · Source

Comment Period for Draft Guidance

30 days from publication in the Federal Register

Applies to: Stakeholders wishing to provide comments.

Comments and suggestions regarding this draft document should be submitted within 30 days of publication in the Federal Register. · p. 1 · High · Source

Docket Number

FDA-2026-D-6539

Applies to: Referenced for comments submission.

All written comments should be identified with this document's docket number: FDA-2026-D-6539. · p. 1 · High · Source

Guidance Status

Not for implementation; Contains non-binding recommendations.

Applies to: All users of the guidance document.

Draft - Not for implementation. Contains non-binding recommendations. · p. 1 · High · Source

Extracted documents

• Guidance for Industryhtmlhtml · high · 1 page
• Download the Draft Guidance Documentpdfpdf_text · high · 13 pages
• Search for FDA Guidance Documentshtmlhtml · high · 1 page
• Advisory Committee Guidance Documentshtmlhtml · high · 1 page