Proposed Revision of USP <1225> Published in the Pharmacopeial Forum

In the Pharmacopeial Forum, PF 51(6), a proposed revision of USP General Chapter <1225> has been published, which will also receive a new title: from Validation of Compendial Procedures to Validation of Analytical Procedures.

According to the briefing notes, the revision “adapts the chapter to its common usage for validation of both noncompendial and compendial analytical procedures and provides connectivity to related USP chapters.”

The proposal aims to align the chapter more closely with the principles of ICH Q2(R2) Validation of Analytical Procedures and to integrate it more clearly into the analytical procedure life cycle described in USP <1220> Analytical Procedure Life Cycle. The revised chapter is also intended to complement the newly introduced chapter <1221> Ongoing Procedure Performance Verification.

Key Structural and Content Changes

The revision introduces and expands several central concepts:

• Reportable Result (RR) is emphasized as the definitive output supporting batch release and compliance decisions.
• Fitness for Purpose is positioned as the overarching goal of validation, focusing on decision-making confidence rather than isolated parameter checks.
• Replication Strategy is now linked to control of RR uncertainty, not simply to predefined numbers of injections or preparations.
• Statistical Intervals (confidence, prediction, tolerance) are introduced as tools for evaluating precision and accuracy in relation to decision risk.
• Combined evaluation of accuracy and precision is described in more detail than in previous versions.

The chapter continues to allow both minimal (traditional) and enhanced (ATP-based) validation approaches, but clarifies how acceptance criteria should be linked to performance requirements of the RR regardless of the chosen strategy.

New Structure

The new proposal is structured as follows:

1. INTRODUCTION

    1.1 Scope

2. GENERAL CONSIDERATIONS

    2.1 Roadmap of Topics Related to Procedure Validation Principles and Practices
    2.2 Fitness for Purpose
    2.3 Validation Strategy and Study Design
    2.4 Analytical Procedure Performance Characteristics
    2.5 Validation Protocol and Documentation of Validation Results
    2.6 Analytical Procedure Control Strategy and System Suitability Tests
    2.7 Knowledge Management
    2.8 Compendial Analytical Procedures

3. VALIDATION TEST, METHODOLOGIES, AND EVALUATION

    3.1 Specificity and Selectivity
    3.2 Range
    3.3 Precision and Accuracy

APPENDIX 1—EXAMPLE OF PRECISION STUDY

APPENDIX 2—ESTABLISHING VALIDATION ACCEPTANCE CRITERIA USING PROBABILITY OF OOS

APPENDIX 3—VALIDATION DESIGN TO MANAGE THE RISKS ASSOCIATED WITH USING INTERVALS

APPENDIX 4—TYPES OF INTERVALS AND THEIR INTERPRETATIONS

    Individual Performance Characteristics for Accuracy and Precision
    Combined Performance Characteristics for Accuracy and Precision
    Choosing an Approach

REFERENCES

Other Chapters Influenced by the Revision

The proposal is accompanied by briefing notes identifying other chapters and monographs that either reference <1225> directly or may be indirectly affected by the revised terminology and concepts. These include, among others:

• <1210> Statistical Tools for Procedure Validation
• <1010> Analytical Data—Interpretation and Treatment
• <1033> Biological Assay Validation
• <1039> Chemometrics
• <1226> Verification of Compendial Procedures
• <1467> Residual Solvents—Verification of Compendial Procedures and Validation of Alternative Procedures
• <1469> Nitrosamine Impurities

Comments

The draft is currently open for stakeholder feedback within the usual USP comment period. Comments can be submitted until 31 January 2026.

The full draft is available (after registration) in the Pharmacopeial Forum.