Sunday April 29 2018, 2pm-5pm
SC6: Practical Considerations for Biomarker Bioanalysis
Introduction
Biomarkers play a critical role in improving the drug development process. Practical utility of a biomarker is dependent on successful measurement of biomarker in the biological matrix. Bioanalytical strategy begins with the understanding of physiology or underlying biology of the disease for which the drug is being developed for.
This course will summarize importance of biomarkers in biopharma industry versus clinical settings along with various terminology used in biomarker bioanalysis. In addition, the course will describe potential pitfalls of overlooking the biology versus benefits of understanding biology in biomarker analysis. Bioanalytical challenges and practical solutions will be described.
Agenda
Chairperson
Darshana Jani, Associate Director, Global Lead Biologics, Clinical Assay Group, Global Product Development, Pfizer
Recommendations for Selection and Characterization of Protein Biomarker Calibration Standards
Paul Rhyne, PhD, Vice President, Biological Development Services
Quantitative protein biomarker assays are an integral part of drug development and rely on protein calibrators for quantitation. There is an industry-wide challenge in finding reliable and well characterized calibrators with supporting documentation that are suitable for biomarker assays. This presentation will present several case studies showing common issues with calibrators and the resolutions that were applied. Finally, a set of recommendations for selection and characterization calibrators will be presented.
Validation of Ligand Binding Biomarker Assay Challenges and Solutions
Stephanie Fraser, PhD, Associate Research Fellow, Pfizer
Practical Approaches to Protein Biomarker Quantification by LC-MS
Tim Sikorski, PhD, Investigator, Exploratory Biomarkers, GlaxoSmithKline
I will provide an introduction to the different LC-MS workflows available for targeted biomarker analysis and discuss the tradeoffs that are often required when picking one strategy over another. I will then discuss lessons learned during study sample analysis using different LC-MS platforms. Finally, I will highlight some systematic method development strategies our group has developed to ensure accuracy of measurements of endogenous protein and minimize unforeseen obstacles during study support.
Biomarker Quantitation by LC-MS-Solutions to Challenges
Fizal Nabbie, PhD, Bristol-Meyers Squibb
Hybrid methodologies such as Immunocapture (IC)-LC-MS are on the rise in support of small and large molecule pharmaceutical development. In this talk we will discuss how LC-MS was applied to help resolve issues in challenging ligand-binding assays. Through case studies we will show how the hybrid assay format was used to resolve challenging issues encountered in different Biomarker assays.
Biographies
Darshana Jani, Associate Director, Global Lead Biologics, Clinical Assay Group, Global Product Development, Pfizer
Darshana Jani has nearly 25 years of practice in the academic and biotechnology field. Throughout her tenure at Genzyme, Medimmune, BiogenIdec until present employment as Senior Manager at Pfizer. She has supported clinical and pre-clinical trials, in addition to post marketing studies inclusive of Safety, Immunogenicity, PK, Efficacy, and Biomarker analysis. Darshana has risen from the ranks, at the outset developing and applying boianalytical methods, while assuming numerous responsibilities germane to regulatory compliance of the validation and application of group procedure. She has guided bioanalytical lab groups, been held responsible for overseeing all phases of drug recovery and development; a task which incorporated product characterization, potency determination, immunogenicity testing, as well as surrogate maker discovery.
Paul Rhyne, PhD, Vice President, Biological Development Services
Dr. Paul Rhyne is the Chief Scientific Officer and Vice President of Bioanalytical Operations at Biologics Development Services (BDS). He obtained his PhD in Cellular Immunology from the University of Tennessee at Memphis and gained post-doctoral experience in Virology at St. Jude Children’s Research Hospital. Dr. Rhyne began his career in industry working in a biotechnology company focused on early cancer detection technologies and in the commercial antibody industry where he developed a commercial product line using Luminex-based biomarker assays for the measurement of phosphorylated proteins. He joined Bristol-Myers Squibb pharmaceutical company and established a clinical biomarker assay group that developed and validated assays for BMS clinical trials. Dr. Rhyne continued to expand his career in the contract research organization industry as a Senior Scientific Technical Director at Tandem Laboratories (Covance/Lab Corp) and at Q2 Solutions (IMS-Quintiles) overseeing method development and validation of Biomarker, PK, and Immunogenicity assays. Dr. Rhyne jointed BDS in 2017 and is responsible for the scientific oversight and conduct of all bioanalytical analysis and operations.
Tim Sikorski, PhD, Investigator, Exploratory Biomarkers, GlaxoSmithKline
After graduating from the University of Pennsylvania, Tim completed his PhD at Harvard University, where he developed proteomic methods to study the dynamics of protein complexes during transcription. Tim joined GSK in October of 2011 as a member of the Biological Mass Spectrometry group in Molecular Discovery Research. There, he developed mass spectrometry-based methods to map post-translational modifications, such as acetylation and phosphorylation, on a proteome-wide scale for mechanism-of-action studies and to identify potential biomarkers. In January 2016, Tim transitioned to the Exploratory Biomarkers Group, where he has been working on developing novel methods for measuring endogenous protein and metabolite biomarkers in systemic matrices to support early Experimental Medicine clinical trials. These assays are serving as important pharmacodynamic endpoints in proving target engagement and mechanisms of action of GSK medicines.
Fizal Nabbie, PhD, Bristol-Myers Squibb
Fizal has over 30 years in the Pharmaceutical industry, in different disciplines, and he successfully supported development of many pharmaceutical compounds during his career. Fizal has had a long career at Bristol-Myers Squibb and currently holds the position of Senior Research Investigator. In 2006 and again in 2015, Fizal won the “Excellence in Ligand Binding Assays” awards at AAPS conferences. Fizal received his PhD in cell and molecular biology from the University of the Sciences, Philadelphia.