October 24 - 25, 2003

AAPS Workshop on Method Validation and Measurement of Biomarkers in Non-clinical and Clinical Samples in Drug Development

Grand America Hotel

Salt Lake City, UT, USA

Biomarkers are used in rational drug development from discovery in lead selection and optimization, non-clinical models, clinical trials and post approval monitoring. Results from efficacy and toxicity biomarkers help risk-assessment to weed out the undesirable candidates early, conserving resources for the right drugs’ development, identify the responder patients, and monitor for therapeutic dose adjustment. The study objectives vary at different studies and phases and so are the issues for the measurements to meet the study intent. The majority of biomarkers are endogenous macromolecules analyzed by immunoassay and bioassay. The endogenous heterogeneity poses analytical challenges, raising questions about GLP-compliance of the methods.

The NIH and FDA laboratories have embarked on biomarkers research. A workgroup had provided definitions of biomarkers¹. Routine and esoteric assays of biomarkers are performed in clinical chemistry laboratories for diagnostic purposes. The AAPS Ligand Binding Assay Bioanalytical Focus Group is supporting this workshop to bring the biomarkers laboratory practitioners together to share experience, identify specific challenges and issues of biomarkers at various phases of drug development, and brainstorm the best practices to produce adequate data that are clinical and statistical meaningful. In order to facilitate the multi-facet discussions from the pharmaceutical and diagnostic disciplines CLAS (Clinical Ligand Assay Society) is invited to co-sponsor this workshop, scientists from the FDA and NIH will be invited to participate. The program will have breakaway sessions of subgroups in Non-clinical, Clinical and Post-approval Phases to identify specific issues, desirable states and plan of actions to achieve the desirable states.

1) Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89-95.

Workshop Goals and Objectives:

• Clarify nomenclature of biomarkers and overview of biomarker application in various clinical drug development phases.
• Discuss approaches in analytical validation procedures of biomarkers.
• Share experience and case studies at nonclinical, clinical and post-approval drug development phases by laboratory practitioners.
• Share experience and perspectives by scientists from regulatory agencies.
• Breakaway group discussions on the best practices to produce clinical and statistical meaningful data to meet study objectives.
• Possible consensus of biomarkers method validation at different development phases.