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Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium


The first formal qualification of safety biomarkers for regulatory decision making marks a milestone in the application of biomarkers to drug development. Following submission of drug toxicity studies and analyses of biomarker performance to the Food and Drug Administration (FDA) and European Medicines Agency (EMEA) by the Predictive Safety Testing Consortium's (PSTC) Nephrotoxicity Working Group, seven renal safety biomarkers have been qualified for limited use in nonclinical and clinical drug development to help guide safety assessments. This was a pilot process, and the experience gained will both facilitate better understanding of how the qualification process will probably evolve and clarify the minimal requirements necessary to evaluate the performance of biomarkers of organ injury within specific contexts.

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Figure 1: Flow charts explaining the proposed limited clinical translational use of the new renal biomarkers.


  1. Goodsaid, F. & Papaluca, M. Evolution of biomarker qualification at the health authorities. Nat. Biotechnol. 28, 441–443 (2010).

    Article  CAS  Google Scholar 

  2. Altar, C.A. et al. A prototypical process for creating evidentiary standards for biomarkers and diagnostics. Clin. Pharmacol. Ther. 83, 368–371 (2008).

    Article  CAS  Google Scholar 

  3. Ozer, J.S. A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function. Nat. Biotechnol. 28, 486–494 (2010).

    Article  CAS  Google Scholar 

  4. Varghese, S.A. et al. Urine biomarkers predict the cause of glomerular disease. J. Am. Soc. Nephrol. 18, 913–922 (2007).

    Article  CAS  Google Scholar 

  5. Comper, W.D., Hilliard, L.M., Nikolic-Paterson, D.J. & Russo, L.M. Disease-dependent mechanisms of albuminuria. Am. J. Physiol. Renal Physiol. 295, F1589–F1600 (2008).

    Article  CAS  Google Scholar 

  6. Trof, R.J., Di Maggio, F., Leemreis, J. & Groeneveld, A.B. Biomarkers of acute renal injury and renal failure. Shock 26, 245–253 (2006).

    Article  CAS  Google Scholar 

  7. Dieterle, F. et al. Urinary clusterin, cystatin C, β2-microglobulin and total protein as markers to detect drug-induced kidney injury. Nat. Biotechnol. 28, 463–469 (2010).

    Article  CAS  Google Scholar 

  8. DeLong, E.R., DeLong, D.M. & Clarke-Pearson, D.L. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44, 837–845 (1988).

    Article  CAS  Google Scholar 

  9. Harrell, F. Regression Modeling Strategies (Springer, New York, 2001).

    Book  Google Scholar 

  10. Lee, J.W. et al. Fit-for-purpose method development and validation for successful biomarker measurement. Pharm. Res. 23, 312–328 (2006).

    Article  CAS  Google Scholar 

  11. Sistare, F. et al. Towards consensus practices to qualify safety biomarkers for use in early drug development. Nat. Biotechnol. 28, 446–454 (2010).

    Article  CAS  Google Scholar 

  12. Bonventre, J.V., Vaidya, V.S., Schmouder, R., Feig, P. & Dieterle, F. Next-generation biomarkers for detecting kidney toxicity. Nat. Biotechnol. 28, 436–440 (2010).

    Article  CAS  Google Scholar 

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Authors and Affiliations



Members of the PSTC Nephrotoxicity Working Group compiling the submission for biomarker qualification: F.D., F.S., J.S.O., C.P.W., W.B., A.S., M.J.S., J.V., S.S., D.L.G., J.A.P., G.M., K.C., D.L., E.H., M.S., D.E., D.H., D.A.-C., Y.-Z.G., K.L.T., P.L.G., J.-M.V., S.T., D.B., D.R.-G., G.B., M.A.D., J.A., J.E.MD., L.S.-D., L.O., M.G., M. Papaluca, S.J., E.A.B., S.A.B., V.G.B., N.C., J.W., D.H., S.S., J.L., P.R., E.W. and W.M.; members of the FDA Biomarker Qualification Review Team, reviewing the submission for biomarker qualification: F.G., D.J.-K., A.F.D., E.A.H., M.B., A.T., P.H., D.T., S.X., W.T. and N.X.; members of the EMEA Biomarker Qualification Review Team, reviewing the submission for biomarker qualification: M. Papaluca, J.-M.V., E.A., R.M., S.V., B.F., B.S.L., P.K., M. Pasanen and K.P.

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Correspondence to Frank Dieterle.

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Competing interests

F.D., G.M., K.C. and D.L. are employees of Novartis; F.S., D.H., S.T., Y.-Z.G., N.C. and D.L.G. are employees of Merck; W.B., A.S., M.J.S. and S.S. are employees of ClinXus; C.P.W. is an employee of Van Andel Research Institute; W.B. is an employee of Grand Valley Medical Specialists; A.S. is an employee of Spectrum Health; M.J.S. is an employee of Innovative Analytics; J.V. and L.S. are employees of Hoffman-La Roche; J.A.P. and S.J. are employees of Boehringer Ingelheim; E.H., M.G. and V.G.B. are employees of Sanofi-Aventis; M.S., J.E.M. and S.S. are employees of Johnson & Johnson; D.E. is an employee of GlaxoSmithKline; D.A.-C. is an employee of Amgen; D.B. is an employee of Bristol-Myers Squibb; D.R.-G., L.O. and S.A.B. are employees of Pfizer; G.B. and M.P. are employees of AstraZeneca; J.A. is an employee of Eli Lilly; E.A.B., J.W., D.H. and J.L. are employees of Abbott; J.S.O. was an employee of Merck.

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Dieterle, F., Sistare, F., Goodsaid, F. et al. Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium. Nat Biotechnol 28, 455–462 (2010).

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