Impact of calibration frequency on accuracy of critical biochemical analytes: Review article

Calibration of laboratory instruments is a cornerstone of analytical quality assurance in clinical biochemistry. In tertiary-care hospital laboratories, where decisions are frequently made using critical biochemical analytes (electrolytes, glucose, creatinine, liver function tests, etc.), calibration frequency directly influences analytical bias, precision, and ultimately patient safety. This review synthesizes current evidence on how calibration intervals affect measurement accuracy across common biochemical analytes, examines analyte-specific drivers of calibration drift, and outlines practical, risk-based strategies for setting calibration frequency in high-throughput hospital settings. We review technical factors (instrument design, reagent stability, ISE membrane drift), operational factors (workload, reagent-lot changes), and regulatory guidance (CLSI, ISO 15189, CLIA) that inform calibration policies. Studies demonstrate that ion-selective electrode (ISE)-based electrolytes often require multiple calibrations per day due to membrane and reference electrode drift, while many enzymatic photometric assays (glucose, ALT/AST) may remain stable for 24–72 hours depending on reagent and instrument stability. Lot-to-lot variability of reagents and calibrators and environmental conditions (temperature, humidity, power instability) are significant contributors to calibration failure. Risk-based approaches combining scheduled calibrations, QC-triggered recalibration, multi-point calibrations, reagentlot verification, and use of third-party reference materials optimize accuracy while limiting resource waste. Emerging approaches automated self-calibration, QC analytics and predictive AI models — show promise in tailoring calibration frequency dynamically. For tertiary-care laboratories, calibration strategies should be analyte-specific, evidence-based, and linked with continuous QC monitoring to ensure results remain within allowable total error and biological variation limits. We conclude with practical recommendations for laboratories pursuing efficient, patient-safety-focused calibration practices.