This chapter explains how immunoassays and other ligand-binding assays are applied during the different stages of drug identification and development in the pharmaceutical industry. The importance of the need to change paradigms to address the requirements of biologic development is stressed and the trends reflecting that need are described. Methods used in high-throughput screening to identify target compounds are reviewed. Lead optimization, the next phase, is described in detail and examples of how specific biomarkers benefited from thorough characterization during this phase are provided. The use of safety biomarkers and the subject of assay validation are described. The different stages of clinical studies are explained including how immunoassays are used to define and understand pharmacokinetics and pharmacodynamics. The implications for laboratories that provide the tests are explained, particularly the differences from routine diagnostic testing.

Jeff Sailstad has over 34 years of experience in the pharmaceutical and biotechnology industries. His “large pharma” experience (24 years) included Burroughs Wellcome, Glaxo Wellcome and Glaxo SmithKline. In 2002 Jeff began consulting part-time, while working at Trimeris, a biotech company, as the Manager of Bioanalytical Chemistry. During his career, Jeff has managed bioanalytical lab groups responsible for all phases of drug discovery and development. This included PK, PD, immunogenicity testing, and support for surrogate maker discovery. In December 2006, Jeff moved on to consulting full-time and incorporated Sailstad and Associates.

Dr. Ronald R. Bowsher has worked in the pharmaceutical industry in the area bioanalytical methods development for nearly 40 years. He received a B.S in chemistry and M.S. and Ph.D. degrees in biochemistry from the Indiana University School of Medicine. Currently, he serves as Partner and President at B2S Consulting^®, Partner and CSO at B2S Labs, and as a Senior Advisor for Ligand Binding Assays at AIT Bioscience. Prior to joining the CRO industry, Dr. Bowsher retired from the Lilly Research Laboratories after 31 years. He has published more than 200 manuscripts and abstracts. In 2004, Dr. Bowsher was elected as a Fellow of the American Association of Pharmaceutical Scientists (AAPS). In 2008, he was awarded an AAPS Presidential citation for work in establishing educational training programs and received the AAPS BIOTEC distinguished service award in 2011. In 2012 he received the Distinguished Alumnus Award, School of Science, Indiana University-Purdue University (IUPUI).

Dr. Omar Laterza, Ph.D., DABCC is Director of Immunochemistry and Mass Spectrometry at the Clinical Development Laboratory (CDL) at Merck. He joined Merck in 2003 where he has been responsible for biomarker discovery, development and validation, primarily for early phase clinical studies. Dr. Laterza obtained his Ph.D in Biochemistry at Colorado State University and a post-doctoral fellowship in Clinical Chemistry at Washington University, School of Medicine, in St. Louis, Missouri. Prior to working at Merck, he was an Instructor of Pathology at The Johns Hopkins School of Medicine and Director of the General Chemistry section of the Core Lab at The Johns Hopkins Hospital. He is the author of multiple publications, review articles and co-inventor in patents and patents applications for biomarkers of brain injury and micro RNAs as biomakers of tissue injury. He is a diplomat of the American Board of Clinical Chemistry (DABCC) and a Fellow of the American Academy of Clinical Biochemistry (FACB).

William Nowatzke, PhD, DABCC is Director of the Ligand Binding Assay Laboratory at Worldwide Clinical Trials (WCT) in Austin Texas. Dr. Nowatzke has spent fifteen years learning, conducting, and advancing the field of bioanalysis to support biological therapeutic drug development programs. After receiving a PhD in chemistry, Dr. Nowatzke completed a postdoctoral fellowship in clinical chemistry, subsequently directing esoteric and immunoassay testing for late phase efficacy assessments under CLIA regulations. Subsequently, he was recruited to establish a GLP-regulated laboratory, providing immunoassay oversight for preclinical and clinical biological therapeutic drug development programs. Dr. Nowatzke has industry experience supporting both pharmacokinetic and anti-drug antibody analytical programs.

Ligand binding assay, immunoassay, pharmaceutical, drug, development, screening, receptor, preclinical, clinical, drug discovery, time-resolved fluorescence, fluorescence resonance energy transfer, turbidimetry, nephelometry, enzyme-multiplied immunoassay technique (EMIT), fluorescence polarization, radioimmunoassay, cloned enzyme donor immunoassay (CEDIA), flow cytometry, cell-based assay, amplified luminescent proximity homogeneous assay, AlphaLISA, biomarker, validation, pharmacokinetics, limit of detection, limit of quantification, immunogenicity, anti-drug antibody, anti-therapeutic antibody, laboratory-developed test, Clinical Laboratory Improvement Amendments (CLIA), lead optimization.