The use of emerging safety biomarkers in nonclinical and clinical safety assessment - The current and future state: An IQ DruSafe industry survey

Regul Toxicol Pharmacol. 2021 Mar:120:104857. doi: 10.1016/j.yrtph.2020.104857. Epub 2020 Dec 31.

Abstract

Pharmaceutical and biotechnology companies rarely disclose their use of translational emerging safety biomarkers (ESBs) during drug development, and the impact of ESB use on the speed of drug development remains unclear. A cross-industry survey of 20 companies of varying size was conducted to understand current trends in ESB use and future use prospects. The objectives were to: (1) determine current ESB use in nonclinical and clinical drug development and impact on asset advancement; (2) identify opportunities, gaps, and challenges to greater ESB implementation; and (3) benchmark perspectives on regulatory acceptance. Although ESBs were employed in only 5-50% of studies/programs, most companies used ESBs to some extent, with larger companies demonstrating greater nonclinical use. Inclusion of ESBs in investigational new drug applications (INDs) was similar across all companies; however, differences in clinical trial usage could vary among the prevailing health authority (HA). Broader implementation of ESBs requires resource support, cross-industry partnerships, and collaboration with HAs. This includes generating sufficient foundational data, demonstrating nonclinical to clinical translatability and practical utility, and clearly written criteria by HAs to enable qualification. If achieved, ESBs will play a critical role in the development of next-generation, translationally-tailored standard laboratory tests for drug development.

Keywords: Clinical; DruSafe; Drug development; Emerging safety biomarkers; Nonclinical; Qualification; Survey.

MeSH terms

  • Animals
  • Biomarkers, Pharmacological / metabolism*
  • Clinical Trials as Topic / methods
  • Clinical Trials as Topic / standards*
  • Drug Evaluation, Preclinical / methods
  • Drug Evaluation, Preclinical / standards
  • Drug Industry / methods
  • Drug Industry / standards*
  • Drug-Related Side Effects and Adverse Reactions / diagnosis
  • Drug-Related Side Effects and Adverse Reactions / metabolism*
  • Drug-Related Side Effects and Adverse Reactions / prevention & control
  • Forecasting
  • Humans
  • Pharmaceutical Preparations / metabolism
  • Surveys and Questionnaires*
  • Tissue Distribution / drug effects
  • Tissue Distribution / physiology

Substances

  • Biomarkers, Pharmacological
  • Pharmaceutical Preparations