Biocon Bristol-Myers Squibb Research and Development Center,
India
Shashwati Basak obtained her PhD from Indian Institute of Science,
Bangalore, India. She carried out postdoctoral research from The Salk
Institute for Biological Sciences, San Diego and Stanford School of
Medicine, Palo Alto. Research in these two places was focused on
understanding the role of tumor suppressor p53 in Cancer Signaling
Pathways. She worked as a Research Scientist in the Veterans Affairs
Medical Center, San Francisco, before moving into the current role as a
Lead Investigator in Early Clinical and Translational Research, Biocon
Bristol-Myers Squibb Research and Development Center, Bangalore. Current
research interests involve assay development and qualification for
Clinical Biomarkers and its use in clinical sample analysis during drug
development.
Abstract
Biomarkers play a significant role during
all phases of drug discovery and development. Clinical biomarker-based
studies provide early information on target engagement, help guide
rational selection of drug combinations, optimization of dose and
schedule, serve as tools for stratifying patients and has the potential
to predict clinical outcome. A “fit-for purpose” assay development and
validation to meet the clinical requirements plays an important role in
biomarker estimation. While a rigorous validation is usually not
required for discovery-phase work, as a drug progresses into preclinical
and early-phase clinical evaluation, more thorough method validation
increasingly becomes valuable.
The real-time quantitative polymerase chain reaction (qPCR) technology
is accurate, sensitive and fast and has become the method of choice for
clinical biomarker detection and quantification. Numerous quality issues
may arise throughout the entire workflow influencing the accuracy of
the qPCR results and the reliability of the data interpretation and
conclusions. Development and use of qPCR technology for robust, accurate
and reliable method is required for the emerging “fit-for-purpose”
biomarker assay qualification. Key factors influencing assay performance
such as sample matrix, sample preparation, experimental precision,
reproducibility, sensitivity, specificity, dilution linearity and
dynamic range and their impact on the assay outcome will be discussed.
Based on these, we will put forth recommendations for consideration and
optimization while qualifying a qPCR-assay for analysis of clinical
samples. As biomarkers become integrated into drug development and
clinical trials, assay qualification becomes important with an
increasing emphasis on establishing standardized guidelines for
analytical methods.
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