Filter Integrity Testing in Biopharmaceuticals: A Comprehensive Review of Methods, Challenges, and Future Directions

Abstract

Filter Integrity Testing (FIT) serves as a cornerstone of sterility assurance in pharmaceutical manufacturing, validating sterilizing-grade filters' performance throughout their lifecycle. This article examines FIT methodologies, equipment selection, and implementation challenges specific to biopharmaceuticals and advanced therapeutics. The article explores critical timing considerations for testing, non-destructive verification methods, and the complexities of closed-system cell therapy manufacturing. It addresses regulatory interpretation disparities while highlighting industry harmonization initiatives aimed at standardizing practices. The emergence of digital quality systems, computational modeling, and artificial intelligence applications demonstrates the evolution of FIT toward more predictive, data-driven approaches. Through critical analysis of technical limitations and case studies, this article provides a framework for implementing robust integrity testing strategies that balance regulatory compliance, operational efficiency, and patient safety in increasingly complex therapeutic modalities.