Qualification of translational safety biomarkers

Exp Biol Med (Maywood). 2021 Nov;246(22):2391-2398. doi: 10.1177/15353702211002153. Epub 2021 Mar 23.

Abstract

Safety biomarkers are important drug development tools, both preclinically and clinically. It is a straightforward process to correlate the performance of nonclinical safety biomarkers with histopathology, and ideally, the biomarker is useful in all species commonly used in safety assessment. In clinical validation studies, where histopathology is not feasible, safety biomarkers are compared to the response of standard biomarkers and/or to clinical adjudication. Worldwide, regulatory agencies have put in place processes to qualify biomarkers to provide confidence in the manner of use and interpretation of biomarker data in drug development studies. This paper describes currently qualified safety biomarkers which can be utilized to monitor for nephrotoxicity and cardiotoxicity and ongoing projects to qualify safety biomarkers for liver, skeletal muscle, and vascular injury. In many cases, the development and use of these critical drug development tools is dependent upon partnerships and the precompetitive sharing of data to support qualification efforts.

Keywords: Biomarker qualification; drug development tools; drug-induced tissue injury; novel methodologies; safety biomarkers; translational biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Biomarkers, Pharmacological / analysis*
  • Cardiotoxicity / diagnosis
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Drug Development / methods
  • Drug Development / standards*
  • Drug-Related Side Effects and Adverse Reactions / diagnosis*
  • Humans
  • Rats
  • Vereinigte Staaten
  • United States Food and Drug Administration / standards

Substances

  • Biomarkers, Pharmacological