FDA updates SOPP 8412 on product labeling review
The FDA’s Center for Biologics Evaluation and Research (CBER) has issued Version 10 of SOPP 8412 – “Review of Product Labeling”, effective March 12, 2026.
This Standard Operating Policy and Procedure (SOPP) provides guidance for CBER staff on the review of labeling for human drug and biologic products, including combination products submitted under BLA, NDA, and ANDA pathways.
Scope and applicability
The SOPP applies to:
Labeling submitted within original applications and supplements
Patient-oriented labeling submitted with human factors study protocols for combination products
It does not apply to medical devices, including IVDs, or to labeling submitted in annual reports under separate procedures.
Key elements of the labeling review process
The document outlines how FDA reviews labeling to ensure:
Information is accurate and not misleading
Content is understandable for intended users, including healthcare professionals and patients
Compliance with applicable regulations, including 21 CFR Part 201
Labeling reviewed includes:
Prescribing information (PI)
Medication Guides and Patient Package Inserts
Instructions for Use (IFU)
Package and container labels
Submission and format requirements
Structured Product Labeling (SPL) in XML format is required for submissions
Applicants are recommended to provide an annotated Word version for review
Labeling discussions are conducted using track changes (redline/strikeout)
Labeling changes and submissions
Depending on the type of change, labeling updates must be submitted as:
Prior Approval Supplements (PAS)
Changes Being Effected (CBE)
Or within an annual report
At the time of initial product distribution, applicants must submit:
Final content of labeling (SPL format)
Final printed labeling, including package and container representations
This is defined as the First Use Notification.
Review responsibilities
The SOPP defines roles across the review process, including:
Regulatory Project Manager (RPM) – coordination and communication
Clinical, statistical, pharmacology, toxicology, and CMC reviewers – verification of scientific accuracy
Advertising and Promotional Labeling Branch (APLB) – review of naming, readability, and promotional compliance
Additional procedural elements
Coordination is required when multiple labeling supplements are under review
Additional labeling supplements should not be submitted while safety-related changes are under review
Promotional labeling must be submitted using FDA Form 2253
Background
Labeling requirements are established under the FD&C Act and Public Health Service Act, and implemented through regulations including 21 CFR Part 201.
This update reflects current FDA procedures for labeling review within CBER.
For full details, read the document below.
