Regulatory and Validation Issues for Biosensors and Related Bioanalytical Technologies

Biosensor-based clinical diagnostics is a dynamic and rapidly evolving area. Biosensors and bioanalytical technologies have the potential to decrease detection time, lower the detection limit, increase specificity and sensitivity, and allow high-throughput analysis of biologically important molecules. These characteristics position biosensors as extremely powerful tools for in vitro diagnostics (IVD). The main safety concerns of using biosensors in IVD arise from the risk of misdiagnosis due to a false-positive or false-negative result, leading to improper patient management and, in some cases, inappropriate public health response. To reduce risk to public health associated with this type of devices, standardization organizations and regulatory agencies, such as the United States Food and Drug Administration (US FDA), developed guidelines, standards, operating procedures, and performance criteria applicable to major aspects of biosensors manufacturing and use. Since numerous design variations of biosensors for IVD were developed in recent years, in some cases, it is still left to the manufacturer to determine the best methods to attain quality objectives. However, it is mandatory that the key quality system requirements are met or exceeded to enable development of a safe and effective diagnostics device. In this chapter we overview the key regulatory and validation issues affecting overall performance of biosensors for IVD, such as intended use, accuracy, reproducibility, analytical sensitivity/specificity, cross-reactivity, interference, sample matrix effects, limits of detection/quantitation, linearity, range, diagnostic sensitivity/specificity, diagnostic efficiency, and predictive positive/negative values. Keywords: bioanalytical method validation; clinical test validation; analytical performance; clinical performance