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Method Validation and Measurement of Biomarkers in Nonclinical and Clinical Samples in Drug Development: A Conference Report

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Biomarkers are increasingly used in drug development to aid scientific and clinical decisions regarding the progress of candidate and marketed therapeutics. Biomarkers can improve the understanding of diseases as well as therapeutic and off-target effects of drugs. Early implementation of biomarker strategies thus promises to reduce costs and time-to-market as drugs proceed through increasingly costly and complex clinical development programs. The 2003 American Association of Pharmaceutical Sciences/Clinical Ligand Assay Society Biomarkers Workshop (Salt Lake City, UT, USA, October 24–25, 2003) addressed key issues in biomarker research, with an emphasis on the validation and implementation of biochemical biomarker assays, covering from preclinical discovery of efficacy and toxicity biomarkers through clinical and postmarketing implementation. This summary report of the workshop focuses on the major issues discussed during presentations and open forums and noted consensus achieved among the participants on topics from nomenclature to best practices. For example, it was agreed that because reliable and accurate data provide the basis for sound decision making, biomarker assays must be validated in a manner that enables the creation of such data. The nature of biomarker measurements often precludes direct application of regulatory guidelines established for clinical diagnostics or drug bioanalysis, and future guidance on biomarker assay validation should therefore be adaptable enough that validation criteria do not stifle creative biomarker solutions.

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Abbreviations

AAPS:

American Association of Pharmaceutical Sciences

BQL:

below quantifiable limit

CDER:

Center for Drug Evaluation and Research

CMS:

Centers for Medicare & Medicaid Services

CLAS:

Clinical Ligand Assay Society

CLIA:

Clinical Lab Improvement Amendments

GLP:

good laboratory practices

LBABFG:

Ligand Binding Assay Bioanalytical Focus Group

LOD:

lower limit of detection

LLOQ:

lower limit of quantification

NCCLS:

National Committee for Clinical Laboratory Standards

PD:

pharmacodynamic

PK:

pharmacokinetic

OIVD:

Office of in Vitro Diagnostics Device Evaluation and Safety

QCs:

quality controls

ULOQ:

upper limit of quantification

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Author information

Authors and Affiliations

  1. MDS Pharma Services, Lincoln, Nebraska, USA

    Jean W. Lee

  2. Bristol-Myers Squibb, Princeton, New Jersey, USA

    Russ S. Weiner & Ole L. Vesterqvist

  3. Trimeris Inc., Durham, North Carolina, USA

    Jeff M. Sailstad

  4. LINCO Diagnostic Services, St. Charles, Missouri, USA

    Ronald R. Bowsher

  5. Jasper Clinic, Kalamazoo, Michigan, USA

    Dean W. Knuth

  6. Eli Lilly and Company, Indianapolis, Indiana, USA

    Peter J. O’Brien & Sunil Kadam

  7. Walter Reed Army Hospital, Bethesda, Maryland, USA

    Jean L. Fourcroy

  8. Merck and Company, Inc., West Point, Pennsylvania, USA

    Rakesh Dixit & John A. Wagner

  9. GlaxoSmithKline, Research Triangle Park, North Carolina, USA

    Lini Pandite

  10. Millenium Pharmaceuticals, Cambridge, Massachusetts, USA

    Robert G. Pietrusko

  11. Pfizer Global Research, Groton, Connecticut, USA

    Holly D. Soares & David M. Potter

  12. Genetech, Inc., South San Francisco, California, USA

    Valerie Quarmby

  13. University of Louisville, Louisville, Kentucky, USA

    James L. Witliff

  14. MD Anderson Hospital, University of Texas, Austin, Texas, USA

    Herbert A. Fritche

  15. Food and Drug Administration, Rockville, Maryland, USA

    Timothy O’Leary

  16. Molecular Staging Inc., New Haven, Connecticut, USA

    Lorah Perlee

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  1. Jean W. Lee
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  2. Russ S. Weiner
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  19. Sunil Kadam
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  20. John A. Wagner
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Correspondence to Jean W. Lee.

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Lee, J., Weiner, R., Sailstad, J. et al. Method Validation and Measurement of Biomarkers in Nonclinical and Clinical Samples in Drug Development: A Conference Report. Pharm Res 22, 499–511 (2005). https://doi.org/10.1007/s11095-005-2495-9

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  • DOI: https://doi.org/10.1007/s11095-005-2495-9

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