New USP Chapter <1221> on Ongoing Procedure Performance Verification (OPPV) Published for Comment

In Pharmacopeial Forum 51(4), the USP proposes a new General Chapter <1221> titled  Ongoing Procedure Performance Verification.

According to the briefing notes, "this new chapter on ongoing procedure performance verification (OPPV) is an essential component (Stage 3) of the framework outlined in Analytical Procedure Life Cycle <1220>."  It further notes that "the USP Measurement and Data Quality Expert Committee, in collaboration with the USP Statistics Expert Committee, acknowledges that life cycle concepts will continue to evolve as ICH Q2(R2), ICH Q12, and ICH Q14 are implemented across the pharmaceutical industry. USP <1221> will be reviewed going forward to ensure alignment with ICH implementation best practices."

OPPV is designed to ensure analytical procedures continue to meet performance expectations during routine use, either by confirming compliance with a predefined Analytical Target Profile (ATP) or, in its absence, by applying risk-based verification criteria.

Unlike routine control methods such as system suitability tests, OPPV employs proactive, data-driven monitoring to detect trends, assess risks, and support continuous improvement. It integrates control charts, performance metrics, and risk assessments to manage quality and business risks while supporting both procedure optimization and regulatory compliance.

The chapter also emphasizes the use of accumulated knowledge, including from platform technologies, to support comparability assessments and life cycle management. A risk-based implementation strategy is recommended, considering criticality of attributes, complexity of procedures, and availability of control data.

Chapter <1221> is structured as follows:

• 1. Introduction – Outlines the purpose of OPPV and its role in Stage 3 of the analytical procedure life cycle.
• 2. Considerations for Implementing OPPV – Discusses when and how to apply OPPV, including procedure criticality factors and integration with existing control strategies.
• 3. Risk-Based Performance Monitoring Plans for Analytical Procedures – Describes how to design monitoring programs using appropriate performance metrics and data sources.
• 4. Analytical Procedures Statistical Process Control – Introduces statistical tools such as control charts and trending rules to monitor performance.
• 5. Performance Assessment and Continuous Improvement of Analytical Procedures – Focuses on ongoing evaluation of procedure performance, precision, accuracy, and opportunities for improvement.
• Appendix 1: Statistical Details – Statistical details and control chart methodology (Shewhart, CUSUM, EWMA, etc.).
• Appendix 2: Examples – Example 1: HPLC–UV Analytical Procedure for the Assay of an API in a Product and Example 2: Life Cycle Approach of OPPV for a Bioassay.
• References – A list of foundational literature, standards, and scientific sources supporting the concepts in the chapter (e.g., Montgomery’s Statistical Quality Control, ISO 7870-2, Westgard and Nelson rules).

The proposal is open for public comment until 30 September 2025, and the draft is available on the USP Pharmacopeial Forum website.