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.
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)
5.
LeptakCMenetskiJPWagnerJAAubrecht 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
US Food and Drug Administration. Biomarker Qualification: Evidentiary Framework Guidance for Industry and FDA Staff DRAFT GUIDANCE, www.fda.gov/media/119271/download (2018, accessed 2 March 2020).
OtsuboY.Use of pharmacogenomics and biomarkers in the development of new drugs for Alzheimer disease in Japan. Clin Ther2015;
37:1627–31
13.
U.S. Food and Drug Administration. Review of qualification data for biomarkers of nephrotoxicity submitted by the predictive safety testing consortium, www.fda.gov/media/87781/download (2009, accessed 17 August 2020)
U.S. Food and Drug Administration. Biomarker Qualification Decision: Urinary Clusterin and Renal Papillary Antigen (RPA-1), www.fda.gov/media/82521/download (2010, accessed 3 March 2020)
U.S. Food and Drug AdministrationC for DE and FDA Qualification of Composite Measure of 6 urinary biomarkers to aid in detection of kidney tubular injury in Phase 1 trials of healthy volunteers, www.fda.gov/media/115690/download (2018, accessed 21 January 2020)
YamauraYKankiMSasakiDNakajima M, Unami A.
Serum miR-206 as a biomarker for drug-induced skeletal muscle injury in rats. J Toxicol Sci2020;
45:503–13
20.
RiddellELenihanD.The role of cardiac biomarkers in cardio-oncology. Curr Probl Cancer2018;
42:375–85
21.
UpshawJN.The role of biomarkers to evaluate cardiotoxicity. Curr Treat Options Oncol2020;
21:79
22.
U.S. Food and Drug Administration. Review of qualification data for cardiac troponins, www.fda.gov/media/87774/download (2011, accessed 20 August 2020).
23.
US Food and Drug Administration. Biomarker Qualification Decision: serum/plasma cTnT and cTnl, www.fda.gov/media/83152/download (2012, accessed 3 March 2020).
24.
YuanLKaplowitzN.Mechanisms of drug induced liver injury. Clin Liver Dis2013;
17:507–18
25.
MastorodemosVZaganasISpanakiCBessa M, Plaitakis A.
Molecular basis of human glutamate dehydrogenase regulation under changing energy demands. J Neurosci Res2005;
79:65–73
26.
McGillMRJaeschkeH.Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res2013;
30:2174–87
U.S. Food and Drug Administration. Qualification Plan Determination: DDTBMQ000050 (GLDH), www.fda.gov/media/138320/download (2020, accessed 29 July 2020)
30.
U.S. Food and Drug Administration. LOI determination Letter: DDTBMQ000081 – Amendment 1 (SKM plasma biomarkers), www.fda.gov/media/139662/download (2020, accessed 29 July 2020)
31.
US Food and Drug Administration. FDA LOI Decision Letter for TransBioLine Biomarkers of Drug-Induced Vascular Injury (DIVI), https://www.fda.gov/media/135116/download (2020, accessed 15 April 2020).
