A Risk Assessment and Risk-Based Approach Review of Pre-Use/Post-Sterilization Integrity Testing (PUPSIT)

Abstract

In January 2023, ICH Q9 was updated to include expanded guidance on risk-based decision-making, emphasizing its application in informing science-driven and strategic decisions. The revised guidance highlights that while quality risk management can aid decision-making, it does not eliminate the industry's obligation to comply with regulatory requirements. This article introduces a framework for evaluating the risks and benefits of pre-use/post-sterilization integrity testing (PUPSIT) using risk management principles. It provides a structured approach to assess the acceptability of alternative methods to the EU Annex 1 PUPSIT requirement, which acknowledges that PUPSIT may not always be feasible due to constraints such as the filtration of small solution volumes. In such cases, Annex 1 permits alternative approaches if a comprehensive risk assessment is conducted and effective controls are implemented to mitigate the risk of non-integral filtration systems. The proposed framework considers three critical domains-patient safety, process integrity, and regulatory compliance-to ensure decisions are well-informed and balanced. By applying this science- and risk-based approach, organizations can navigate PUPSIT requirements effectively, ensuring compliance while addressing operational limitations.

Keywords: Annex 1; Integrity testing; PUPSIT; QRM; Risk assessment; Risk-based approach; Sterility assurance; Sterilizing filtration.