Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Nov;246(22):2391-2398.
doi: 10.1177/15353702211002153. Epub 2021 Mar 23.

Qualification of translational safety biomarkers

John-Michael Sauer  1 , Amy C Porter  1
Affiliations
Review

Qualification of translational safety biomarkers

John-Michael Sauer et al. Exp Biol Med (Maywood). 2021 Nov.

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.

PubMed Disclaimer

Conflict of interest statement

DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Proposed decision tree for clinical use of kidney safety CM in Phase 1 NHV trials.
See this image and copyright information in PMC

References

    1. Sauer J-M, Porter AC. The regulatory acceptance of translational safety biomarkers. Curr Opin Toxicol 2020; 23–24:80–6
    1. US Food and Drug Administration. Critical Path Initiative – FDA’s Critical Path Initiative, www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative/ucm0766... (2004, accessed 27 July 2016)
    1. European Medicines Agency. Qualification of novel methodologies for drug development: guidance to applicants, www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_... (2014, accessed 9 May 2016)
    1. Japan Pharmaceuticals and Medical Devices Agency. PMDA Record of the Consultation on Pharmacogenomics/Biomarkers, www.pmda.go.jp/files/000160006.pdf (2010, accessed 19 May 2017)
    1. Leptak C, Menetski JP, Wagner JA.Aubrecht J, Brady L, Brumfield M, Chin, WW, Hoffman S, Kelloff G, Lavessari G, Ranganthan R, Sauer J-M, Sistare FD, Zabka T, Wholley D. What evidence do we need for biomarker qualification? Sci Transl Med November 2017; 9:22 - PubMed

Publication types

MeSH terms

Substances