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

Nature Biotechnology volume 28, pages 455–462 (2010)Cite this article

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Abstract

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.

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Author information

Author notes

  1. Yi-Zhong Gu & Nathaniel Collins

    Present address: Present affiliation: Merck Research Laboratories, Summit, New Jersey, USA.,

  2. Josef S Ozer

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

Authors and Affiliations

  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. Department of Basic and Clinical Pharmacology of Kaunas Medical University and State Medicines Control Agency, Nephrology Clinic of Kaunas Medical University Clinics, Kaunas, Lithuania

    Romaldas Maciulaitis

  19. Department of Pharmacology and Toxicology, University of Kuopio, 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

Authors
  1. Frank Dieterle
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  2. Frank Sistare
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  3. Federico Goodsaid
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  4. Marisa Papaluca
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  5. Josef S Ozer
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  6. Craig P Webb
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  7. William Baer
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  8. Anthony Senagore
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  9. Matthew J Schipper
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  10. Jacky Vonderscher
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  11. Stefan Sultana
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  12. David L Gerhold
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  13. Jonathan A Phillips
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  14. Gérard Maurer
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  15. Kevin Carl
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  16. David Laurie
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  17. Ernie Harpur
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  18. Manisha Sonee
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  19. Daniela Ennulat
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  20. Dan Holder
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  22. Yi-Zhong Gu
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  23. Karol L Thompson
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  27. Romaldas Maciulaitis
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  28. David Jacobson-Kram
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  29. Albert F Defelice
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  30. Elizabeth A Hausner
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  31. Melanie Blank
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  32. Aliza Thompson
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  33. Patricia Harlow
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  35. Shen Xiao
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  36. Nancy Xu
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  37. William Taylor
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  38. Spiros Vamvakas
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  39. Bruno Flamion
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  40. Beatriz Silva Lima
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  41. Peter Kasper
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  42. Markku Pasanen
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  43. Krishna Prasad
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  44. Sean Troth
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  45. Denise Bounous
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  46. Denise Robinson-Gravatt
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  47. Graham Betton
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  48. Myrtle A Davis
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  49. Jackie Akunda
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  50. James Eric McDuffie
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  51. Laura Suter
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  52. Leslie Obert
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  53. Magalie Guffroy
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  54. Mark Pinches
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  55. Supriya Jayadev
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  56. Eric A Blomme
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  58. Valérie G Barlow
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  59. Nathaniel Collins
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  63. Jinhe Lee
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  65. Elizabeth Walker
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  66. William Mattes
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Contributions

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.

Corresponding author

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). https://doi.org/10.1038/nbt.1625

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