Failure Mode and Effects Analysis of High-Performance Liquid Chromatography Systems: A Systemic Reliability and Risk Mitigation Approach

Abstract

High-Performance Liquid Chromatography (HPLC) is one of the most widely used analytical techniques in pharmaceutical, biomedical, environmental, and chemical laboratories due to its high precision, sensitivity, and reproducibility. Despite its widespread application, the increasing complexity of modern HPLC systems introduces numerous systemic vulnerabilities that can adversely affect analytical performance, operational reliability, and regulatory compliance. This study presents a comprehensive Failure Mode and Effects Analysis (FMEA) of HPLC systems, focusing on non-operator-induced failures associated with mechanical, fluidic, electronic, and digital subsystems. A hybrid qualitative-quantitative framework based on ISO 31010 risk assessment principles was employed to identify potential failure modes and evaluate their associated risks using Severity (S), Occurrence (O), and Detection (D) indices. Risk Priority Numbers (RPNs) were subsequently calculated to prioritize critical system vulnerabilities. The analysis revealed that column clogging, pump seal degradation, and check-valve malfunction constitute the most significant risks affecting HPLC performance. Column clogging recorded the highest RPN value (240), indicating a substantial threat to system reliability and analytical accuracy. The study further demonstrates how predictive maintenance strategies, reliability engineering principles, and Internet of Things (IoT)-enabled monitoring systems can enhance early fault detection and support proactive maintenance planning. The proposed hybrid reliability framework provides a practical approach for improving equipment availability, reducing downtime, and strengthening quality assurance in both advanced and resource-constrained laboratory environments. The findings highlight the importance of integrating risk assessment, predictive diagnostics, and digital monitoring technologies to ensure sustainable HPLC system performance and regulatory compliance.