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The Predictive Safety Testing Consortium: safety bio-markers, collaboration, and qualification

John-Michael Sauer, Elizabeth G Walker, Amy C Porter

Article ID: 116
Vol 1, Issue 1, 2016, Article identifier:34-45

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The Predictive Safety Testing Consortium (PSTC) is one of nine consortia comprising the Critical Path Institute (C-Path), a non-profit organisation launched in 2005 and dedicated to playing the role of a catalyst in the development of new approaches that advance medical innovation and regulatory science. C-Path achieves this by lead-ing teams that share data, knowledge and expertise resulting in sound, consensus-based science. PSTC is a unique, public-private partnership that brings pharmaceutical companies together to share and validate safety testing methods under the advisement of worldwide regulatory agencies, including the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). The eighteen corporate members of PSTC share a common goal: to find improved safety testing methods and approaches utilizing fluid-based safety biomarkers which accurately predict drug-induced tissue injury. Specifically, the primary goal of PSTC is the qualification of novel translational safety biomarkers for use in early clinical trials in order to ena-ble safer investigations and development of new drug candidates. This manuscript describes the critical importance of improved safety biomarkers to the drug development process and the present state of the biomarker qualification process with regulatory agencies. In addition, the work that the PSTC and its collaborative partners have done and con-tinue to do to identify and qualify more selective and specific safety biomarkers is highlighted. Finally, successes in-cluding the recently adopted regulatory Letter of Support and ongoing efforts to better define the regulatory qualifica-tion process and an integrated translational safety strategy are also discussed.


safety biomarker; biomarker qualification; letter of support; translation; target organ; therapeutic index; drug development tool; context of use

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Parekh A, Buckman-Garner S, McCune S, et al. 2015, Catalyzing the critical path initiative: FDA’s progress in drug development activities. Clinical Pharmacology & Therapeutics, vol.97(3): 221–233.

FDA biomarker qualification context of use n.d., viewed May 20, 2015,

FDA Drug Development Tools (DDT) letters of support n.d., viewed May 20, 2015,

EMA qualification of novel methodologies for medicine development n.d., viewed May 20, 2015,

Critical Path Institute’s predictive safety testing consor-tium. regulatory successes n.d., viewed May 20, 2015,

Dennis E H, Walker E G, Baker A F, et al. 2013, Op-portunities and challenges of safety biomarker qualifica-tion: perspectives from the predictive safety testing con-sortium. Drug Development Research, vol.74(2): 112–126.

Mattes W B and Walker E G, 2009, Translational toxi-cology and the work of the predictive safety testing consortium. Clinical Pharmacology & Therapeutics, vol.85(3): 327–330.

Stephenson D and Sauer J-M, 2014, The predictive safety testing consortium and the coalition against major diseases. Nature Reviews Drug Discovery, vol.13(11): 793–794.

Walker E G, Brumfield M, Compton C, et al. 2014, Evolving global regulatory science through the volunta-ry submission of data: a 2013 assessment. Therapeutic Innovation & Regulatory Science, vol. 48(2): 236–245.

Critical Path Institute’s Predictive Safety Testing Con-sortium. Translational safety strategies accelerating drug development: Collaborative structure successes n.d., viewed May 20, 2015,

FDA Qualification of Seven Biomarkers of Drug- In-duced Nephrotoxicity in rats, 2008 n.d., viewed May 20, 2015,

EMA Final Conclusions on the Pilot Joint EMEA/FDA VXDS Experience on Qualification of Nephrotoxicity Biomarkers, 2008 n.d., viewed May 20, 2015,

PMDA Record of the Consultation on Pharmacogenom-ics/Biomarkers, 2010 n.d., viewed May 20, 2015,

FDA Biomarker Letter of Support for urinary osteopon-tin (OPN) and neutrophil gelatinase-associated lipoca-lin (NGAL), 2014 n.d., viewed May 20, 2015,

EMA Letter of Support for PSTC translational Drug- Induced Kidney Injury (DIKI) biomarkers osteopontin (OPN) and neutrophil gelatinase-associated lipocalin (NGAL), 2014 viewed May 20, 2015,

Bonventre J V, Vaidya V S, Schmouder R, et al. 2010, Next-generation biomarkers for detecting kidney toxici-ty. Nature Biotechnology, vol.28(5): 436–440.

Dieterle F, Sistare F, Goodsaid F, et al. 2010, Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consor-tium. Nature Biotechnology, vol.28(5): 455–462.

Dieterle F, Perentes E, Cordier A, et al. 2010, Urinary clusterin, cystatin C, [beta]2-microglobulin and total protein as markers to detect drug-induced kidney injury. Nature Biotechnology, vol.28(5): 463–469.

Goodsaid F and Papaluca M, 2010, Evolution of bio-marker qualification at the health authorities. Nature Biotechnology, vol.28(5): 441–443.

Mattes WB, Walker EG, Abadie E, et al. 2010, Research at the interface of industry, academia and regulatory science. Nature Biotechnology, vol.28(5): 432–433.

Ozer J S, Dieterle F, Troth S, et al. 2010, A panel of uri-nary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function. Nature Biotechnology, vol.28(5): 486–494.

Sistare F D, Dieterle F, Troth S, et al. 2010, Towards consensus practices to qualify safety biomarkers for use in early drug development. Nature Biotechnology, vol.2(5): 446–454.

Vaidya V S, Ozer J S, Dieterle F, et al. 2010, Kidney in-jury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification stu-dies. Nature Biotechnology, vol.28(5): 478–485.

Warnock D G and Peck C C, 2010, A roadmap for bio-marker qualification. Nature Biotechechnology, vol.28(5): 444–445.

Yu Y, Jin H, Holder D, et al. 2010, Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury. Nature Biotechnology, vol.28(5): 470–477.

FDA Biomarker Letter of Support for plasma/serum myosin light chain 3 (Myl3), skeletal muscle troponin I (sTnI), fatty acid binding protein 3 (Fabp3), and crea-tine kinase, muscle type (CK-M, the homodimer CK- MM). n.d., viewed May 20, 2015,

EMA Letter of Support for skeletal muscle injury bio-markers, 2015. Viewed May 20, 2015,

Mikaelian I, Cameron M, Dalmas DA, et al. 2014, The Vascular Injury Working Group of the Predictive Safety Consortium. Nonclinical Safety Biomarkers of Drug- induced Vascular Injury: Current Status and Blueprint for the Future. Toxicologic Pathology, vol.42(4): 635–657.

Fielden M R, Nie A and McMillian M, 2008, Interlabo-ratory evaluation of genomic signatures for predicting carcinogenicity in the rat. Toxicological Sciences, vol.103(1): 28–34.

Fielden M R, Adai A, Dunn R T 2nd, et al. 2011, De-velopment and evaluation of a genomic signature for the prediction and mechanistic assessment of nongenotoxic hepatocarcinogens in the rat. Toxicological Sciences, vol.124(1): 54–74.

Innovative Medicines Initiative’s Safer and Faster Evi-dence-based Translation. IMI’s SAFE-T project enters formal collaboration with C-Path safety project. viewed May 20, 2015,

Amur S, LaVange L, Zineh I, et al. 2015, Biomarker Qualification: Toward a multi-stakeholder framework for biomarker development, regulatory acceptance, and utilization. Clinical Pharmacology & Therapeutics, vol.98(1): 34–46.

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