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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Author notes

    • Josef S Ozer

    Present address: Dynamics and Metabolism, PGRD, Pfizer, Andover Laboratories, Andover, Massachusetts, USA.


  1. Novartis Pharma AG, Basel, Switzerland.

    • Frank Dieterle
    • , Gérard Maurer
    • , Kevin Carl
    •  & David Laurie
  2. Department of Investigative Laboratory Sciences, Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania, USA.

    • Frank Sistare
    • , Josef S Ozer
    •  & David L Gerhold
  3. US Food and Drug Administration, Silver Spring, Maryland, USA.

    • Federico Goodsaid
    • , Karol L Thompson
    • , Peter L Goering
    • , David Jacobson-Kram
    • , Albert F Defelice
    • , Elizabeth A Hausner
    • , Melanie Blank
    • , Aliza Thompson
    • , Patricia Harlow
    • , Douglas Throckmorton
    • , Shen Xiao
    • , Nancy Xu
    •  & William Taylor
  4. European Medicines Agency, London, UK.

    • Marisa Papaluca
    • , Jean-Marc Vidal
    • , Eric Abadie
    • , Romaldas Maciulaitis
    • , Spiros Vamvakas
    • , Bruno Flamion
    • , Beatriz Silva Lima
    • , Peter Kasper
    • , Markku Pasanen
    •  & Krishna Prasad
  5. ClinXus, Grand Rapids, Michigan, USA.

    • Craig P Webb
    • , William Baer
    • , Anthony Senagore
    • , Matthew J Schipper
    •  & Stefan Sultana
  6. Van Andel Research Institute, Grand Rapids, Michigan, USA.

    • Craig P Webb
  7. Grand Valley Medical Specialists, Grand Rapids, Michigan, USA.

    • William Baer
  8. Spectrum Health, Grand Rapids, Michigan, USA.

    • Anthony Senagore
  9. Innovative Analytics, Inc., Kalamazoo, Michigan, USA.

    • Matthew J Schipper
  10. Hoffman-La Roche, Basel, Switzerland.

    • Jacky Vonderscher
    •  & Laura Suter
  11. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA.

    • Jonathan A Phillips
    •  & Supriya Jayadev
  12. Sanofi-Aventis, Malvern, Pennsylvania, USA.

    • Ernie Harpur
    • , Magalie Guffroy
    •  & Valérie G Barlow
  13. Johnson & Johnson, San Diego, California, USA.

    • Manisha Sonee
    • , James Eric McDuffie
    •  & Sandra Snook
  14. GlaxoSmithKline, King of Prussia, Pennsylvania, USA.

    • Daniela Ennulat
  15. Department of Biometrics, Merck Research Laboratories, West Point, Pennsylvania, USA.

    • Dan Holder
  16. Amgen, Inc., Thousand Oaks, California, USA.

    • Dina Andrews-Cleavenger
  17. Schering-Plough Research Institute, Summit, New Jersey, USA.

    • Yi-Zhong Gu
    •  & Nathaniel Collins
  18. Nephrology Clinic of Kaunas Medical University Clinics, Department of Basic and Clinical Pharmacology of Kaunas Medical University and State Medicines Control Agency, Kaunas, Lithuania.

    • Romaldas Maciulaitis
  19. University of Kuopio, Department of Pharmacology and Toxicology, Kuopio, Finland.

    • Markku Pasanen
  20. Department of Pathology, Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania, USA.

    • Sean Troth
  21. Bristol-Myers Squibb, Princeton, New Jersey, USA.

    • Denise Bounous
  22. Pfizer, Inc., Groton, Connecticut, USA.

    • Denise Robinson-Gravatt
    • , Leslie Obert
    •  & Sven A Beushausen
  23. AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, UK.

    • Graham Betton
    •  & Mark Pinches
  24. National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

    • Myrtle A Davis
  25. Eli Lilly and Co., Indianapolis, Indiana, USA.

    • Jackie Akunda
  26. Abbott Laboratories, Abbott Park, Illinois, USA.

    • Eric A Blomme
    • , Jeff Waring
    • , David Honor
    •  & Jinhe Lee
  27. Critical Path Institute, Tucson, Arizona, USA.

    • Phil Rossi
    • , Elizabeth Walker
    •  & William Mattes
  28. Present affiliation: Merck Research Laboratories, Summit, New Jersey, USA.

    • Yi-Zhong Gu
    •  & Nathaniel Collins


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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.

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.

Corresponding author

Correspondence to Frank Dieterle.

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