SCOPE

There is growing impetus to develop improved biomarkers for drug safety: to make medicines safer, to reduce the growing costs of drug development, and to catalyze improved disease diagnosis and patient care. Even though we have largely relied on the same biomarkers for decades, we now have new technologies for biomarker discovery and development such as inexpensive genome sequence analyses, and gene expression technologies, multiplexed protein analytics, and multiple imaging modalities. The history of safety biomarker development illustrates the current state of affairs, and the opportunities and challenges for additional biomarkers.

We will address the nature of safety biomarkers, the current status of these tools, the difficulties and recent successes in biomarker development, and the outlook for qualifying new safety biomarkers for utility in regulated phases of drug development. To limit the scope of this discussion, we define safety biomarkers as measurable molecules or characteristics that provide information regarding the health and physiological function of an organism following exposure to a drug or drug candidate. Biomarkers may be indicators of injury (e.g., proteins released into serum), of exposure (e.g., DNA adducts), or of susceptibility (e.g., a DNA polymorphism). This review will focus on safety biomarkers that describe active responses to injury, as well as the passive consequences of injury such as loss of organ function and release of contents from dying cells. Focus will be on safety biomarkers as molecules or images that indicate adverse events in drug-treated animals or patients, rather than models as surrogates.