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Safety Labeling Changes—Implementation of Section 505(o)(4) of the FD&C Act: Draft Guidance for Industry

DraftCenter for Biologics Evaluation and Research Center for Drug Evaluation and Research09/18/2025

Description

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Safety Labeling Changes—Implementation of Section 505(o)(4) of the Federal Food, Drug, and Cosmetic Act." This draft guidance provides information on the implementation of the statutory provision that authorizes FDA to require application holders for certain drug and biological products to make labeling changes based on new safety information that becomes available after approval of the drug that FDA determines should be included in the labeling of the drug. This guidance is being updated and reissued in draft to, among other things, include the addition of information related to Congress’ 2018 changes to the definition of adverse drug experience regarding reduced effectiveness and make other changes to reflect current Agency processes and procedures regarding safety labeling changes. This draft guidance revises and, when finalized, will replace the guidance for industry entitled "Safety Labeling Changes—Implementation of Section 505(o)(4) of the FD&C Act" issued in July 2013.

Scope & Applicability

Product Classes

3
Prescription drug products

Products with approved NDAs or ANDAs subject to SLC provisions.

Biological products

development program for drug and biological products

Reference listed drug

The drug referenced by an ANDA.

Stakeholders

3
Application holder

The entity responsible for responding to SLC notifications and orders.; Entity responsible for submitting labeling supplements or rebuttals; Entity responsible for submitting labeling supplements and appeals

Drug Risk Management Board

Internal FDA board providing input on labeling extensions

advisory committee

External body providing input on labeling changes

Regulatory Context

Attributes

1
Reduced Effectiveness

Can form the basis for regulatory action if it meets the definition of a serious adverse drug experience

Identified Hazards

Hazards

3
Serious Risk

Associated with the use of a drug that FDA becomes aware of post-approval

Unexpected Serious Risk

A risk not previously identified or expected based on the drug's profile

new safety information

Information triggering the need for safety labeling changes

Related CFR Sections (3)

See Also (8)