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Pharmaceutical Research, Volume 23, No. 2, February 2006 (# 2006)
DOI: 10.1007/s11095-005-9045-3Research PaperFit-for-Purpose Method Development and Validation
for Successful Biomarker MeasurementJean W. Lee,1,16,17 Viswanath Devanarayan,2 Yu Chen Barrett,3 Russell Weiner,3 John Allinson,4
Scott Fountain,5 Stephen Keller,6 Ira Weinryb,7 Marie Green,8 Larry Duan,9 James A. Rogers,10
Robert Millham,10 Peter J. OBrien,11 Jeff Sailstad,12 Masood Khan,13 Chad Ray,14 and John A. Wagner15Received July 28, 2005; accepted October 7, 2005Abstract. Despite major advances in modern drug discovery and development, the number of new drugapprovals has not kept pace with the increased cost of their development. Increasingly, innovative usesof biomarkers are employed in an attempt to speed new drugs to market. Still, widespread adoption ofbiomarkers is impeded by limited experience interpreting biomarker data and an unclear regulatoryclimate. Key differences preclude the direct application of existing validation paradigms for druganalysis to biomarker research. Following the AAPS 2003 Biomarker Workshop (J. W. Lee, R. S.Weiner, J. M. Sailstad, et al. Method validation and measurement of biomarkers in nonclinical andclinical samples in drug development. A conference report. Pharm Res 22:499Y511, 2005), these and
other critical issues were addressed. A practical, iterative, Bfit-for-purpose^ approach to biomarkermethod development and validation is proposed, keeping in mind the intended use of the data and theattendant regulatory requirements associated with that use. Sample analysis within this context of fit-forpurpose method development and validation are well suited for successful biomarker implementation,allowing increased use of biomarkers in drug development.KEY WORDS: assay validation; biomarkers; drug development; fit-for-purpose method development
and validation.1 Formerly MDS Pharma Services, Lincoln, Nebraska, USA.2 Merck and Company, Inc., Blue Bell, Pennsylvania, USA.3 Bristol-Myers Squibb, Princeton, New Jersey, USA.4 BAS Analytics Ltd., Kenilworth, UK.5 Pfizer Global Research and Development, Ann Arbor, Michigan, USA.6 Protein Design Labs, Inc., Fremont, California, USA.7 Wyeth Research, Collegeville, Pennsylvania, USA.8 Millenium Pharmaceuticals, Cambridge, Massachusetts, USA.9 Quest Pharmaceutical Services, Newark, Delaware, USA.10 Pfizer Global Research and Development, GrotonYNew London, Connecticut, USA.11 Therakos, Inc., Exton, Pennsylvania, USA.12 Trimeris Inc., Morrisville, North Carolina, USA.13 Covance Laboratories, Inc., Chantilly, Virginia, USA.14 Eli Lilly and Company, Indianapolis, Indiana, USA.15 Merck and Company, Inc., Rahway, New Jersey, USA.16 Present Address: 1 Amgen Center Drive, Mailstop 30E-3-B, Thousand Oaks, California 91320, USA.17 To whom correspondence should be addressed. (e-mail: [email protected])ABBREVIATIONS: AAPS, American Association of Pharmaceutical Sciences; BQL, below quantifiable...