AAPS Advances in the Pharmaceutical Sciences Series

Transcription

1 AAPS Advances in the Pharmaceutical Sciences Series Volume 21 Editors-in-chief Daan J.A. Crommelin, Utrecht University, Utrecht, Utrecht, The Netherlands Robert A. Lipper, Back Cove Pharma, LLC, Waldoboro, ME, USA

2 The AAPS Advances in the Pharmaceutical Sciences Series, published in partnership with the American Association of Pharmaceutical Scientists, is designed to deliver volumes authored by opinion leaders and authorities from around the globe, addressing innovations in drug research and development, and best practice for scientists and industry professionals in the pharma and biotech industries. More information about this series at

3 Russell Weiner Marian Kelley Editors Translating Molecular Biomarkers into Clinical Assays Techniques and Applications 123

4 Editors Russell Weiner Translational Biomarkers and Personalized Medicine Edison, NJ USA Marian Kelley MKelley Consulting LLC West Chester, PA USA ISSN ISSN X (electronic) AAPS Advances in the Pharmaceutical Sciences Series ISBN ISBN (ebook) DOI / Library of Congress Control Number: American Association of Pharmaceutical Scientists 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG Switzerland

5 The original version of the bookfrontmatter was revised: The volume number of the book was corrected. The Erratum to the bookfrontmatter is available at / _19

6 Preface The science of drug development is an evolutionary one, something we can see clearly in the world of biomarkers. Not so long ago the concept of using biomarkers in drug development was relegated to a few research-only kits. Bioanalysis in support of drug development focused solely on the pharmacokinetics (PK) of new drug entities. Unfortunately, PK-only approaches can no longer support today s drug development targets. While drug pipelines were full, and research was thriving, very few new drugs were being approved. To address the high attrition of drug development projects and attempt to improve the success rates, the FDA implemented the Critical Path Initiative in The FDA s strategy was to drive innovation by using the newest tools to more successfully translate discovery into viable therapies. Integrating biomarkers into the drug development process, especially in the pre-phase 3 stage, was central to the initiative. The challenges of including biomarkers in drug development were daunting until insightful colleagues started breaking it down to usable building blocks. A groundbreaking paper authored by Dr. Jean Lee and associates (2006) cited the need to improve the efficiency and economy of drug development by the use of well-validated biomarkers and biomarker assays. Workshops were developed, many notably led by Dr. Ron Bowsher, to help researchers understand the difference between a well-developed biomarker and a well-developed biomarker assay. This concept was solidified by Dr. Woodcock (2009) in a pivotal white paper which re-emphasized the need for an iterative method development process following the progress of the New Drug Entity through the drug development continuum and by the publication in 2011 by the ICH of the E16 Guidance for the Industry describing the requirements for biomarkers used in regulated submissions. Biomarker research has become such an integral facet of drug development that some pharmaceutical companies have implemented a policy of requiring a biomarker (target engagement, pharmacodynamics, and patient selection) to be included in all programs as a gating item to move into clinical development. The world of biomarkers has exploded in both depth and breadth. A cursory look over the table of contents in this e-book provides a thumbnail sketch of the innovation taking place in the modern day vii

7 viii Preface bioanalytical lab to help produce new drug entities quickly and efficiently. Finally, to illustrate the importance of using biomarkers to drive clinical development, the FDA issued a draft bioanalytical method validation guidance in 2013 that will now contain a biomarker section describing the fit-for-purpose need to validate biomarker methods when using the data to support a regulatory submission. Edison, USA West Chester, USA Russell Weiner Marian Kelley

8 Contents Fit-for-Purpose Validation Chad Ray Biomarkers in Drug Discovery and Development: Pre-analytical and Analytical Considerations R. Aleks Davis, Andrew P. Mayer and Ronald R. Bowsher Biomarker Discovery Omar F. Laterza and Xuemei Zhao Application of Quantitative Biomeasures in Early Drug Discovery Scott T. Fountain and Paolo Vicini Biomarkers in Discovery and Preclinical Phase During Drug Development Jean W. Lee Incorporating Clinical Biomarkers into Clinical Trials Paul W. Rhyne Perspectives on Tissue Biobanking for Personalized Medicine Uma Prabhakar The Role of Commercial Biomarker Assay Kits in Preclinical and Clinical Trials William Nowatzke and Ronald R. Bowsher Quantification of Protein Biomarkers Using Liquid Chromatography Tandem Mass Spectrometry Hendrik Neubert LC/MS Methods for Small Molecule Biomarkers Michael P. Sullivan Application of Cell-Based Assays in Clinical Trials Manjula P. Reddy and Amy Kate Sasser ix

9 x Contents New Technologies for Cellular Analysis Peter J. O Brien, Tim Wyant and Virginia Litwin Current Flow Cytometry Methods for the Clinical Development of Immunomodulatory Biologics Richard Wnek, Michelle Tseng and Dianna Wu Key Mass Spectrometry Techniques Used in Clinical Biomarker Research Mingxiang Lin Clinical Genomic Biomarker Assay Development: Technologies and Issues Ken C.N. Chang and Matthew J. Marton Implementation of Immunohistochemistry Assays for Clinical Trial Sample Analyses Marisa Dolled-Filhart, Usha Singh, Dianna Wu and K. Emancipator Managing Biomarker Outsourcing: CRO Evaluation, Streamline Outsource Process, and Quality Management Jeffrey A. Tsou In Situ Hybridization in Clinical Biomarker Development Usha Singh, Marisa Dolled-Filhart and Dianna Wu Erratum to: Translating Molecular Biomarkers into Clinical Assays.... E1 Russell Weiner and Marian Kelley Index

10 Editors and Contributors About the Editors Russell Weiner is a senior level biopharmaceutical professional with expertise in pharmaceutical and biologic drug development, clinical trial conduct, regulated bioanalysis, use of biomarkers in early clinical decision making and developing companion diagnostic strategies. He is the Executive Director and head of Clinical Bioanalytical, Biomarkers and Companion Diagnostics team at Daiichi Sankyo Inc. He acquired his Ph.D. at the Albany Medical College. Dr. Weiner led clinical development teams responsible for transitioning therapeutics from discovery through phase two proof-of-concept studies. With over 40 publications, he is also part of the Foundation of the NIH Cancer Steering Committee for The Biomarkers Consortium. Marian Kelley is a leading expert in biotherapeutic drug development through biomarker application and assay analysis. She is the President and Founder of MKelley Consulting, LLC, a company that provides bioanalytical support in drug development through the validation of biomarker methods, immunogenicity studies, and cell-based assays. Her areas of expertise include immunogenicity assay screening, pharmacokinetics, and immunology. She was previously the Chair of the Ligand Binding Assay Bioanalytical Focus Group Steering Committee for the AAPS. Kelley is coauthor or coeditor of over a number of publications. She is also an extensively experienced trainer in validation of methods and quality control. Contributors Ronald R. Bowsher B2S Consulting, Indianapolis, IN, USA; B2S Consulting and AIT Bioscience, Franklin, IN, USA Ken C.N. Chang Translational Molecular Biomarkers, Merck & Co., Rahway, NJ, USA xi

11 xii Editors and Contributors R. Aleks Davis B2S Life Sciences, Franklin, IN, USA Marisa Dolled-Filhart Translational Biomakers, Merck & Co., Rahway, NJ, USA; Translational Medicine, Merck & Co., Rahway, NJ, USA K. Emancipator Translational Biomakers, Merck & Co., Rahway, NJ, USA Scott T. Fountain Pharmacokinetics, Dynamics and Metabolism New Biological Entities, Pfizer Worldwide Research and Development, San Diego, CA, USA; Encinitas, CA, USA Omar F. Laterza Translational Molecular Biomarkers, Merck Research Laboratories, Rahway, NJ, USA Jean W. Lee BioQualQuan, Camarillo, CA, USA Mingxiang Lin Analytical Research & Development, Merck & Co., Rahway, NJ, USA Virginia Litwin Department of Hematology/Flow Cytometry, Covance Inc., Indianapolis, IN, USA Matthew J. Marton Translational Molecular Biomarkers, Merck & Co., Rahway, NJ, USA Andrew P. Mayer GlaxoSmithKline Pharmaceuticals Research and Development, King of Prussia, PA, USA Hendrik Neubert Biomedicine Design, Pfizer Worldwide Research and Development, Andover, MA, USA William Nowatzke Radix BioSolutions, Georgetown, TX, USA Peter J. O Brien Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer, San Diego, CA, USA Uma Prabhakar BRIM Biotechnology Inc, Taipei, Taiwan, People s Republic of China Chad Ray Pfizer, San Diego, CA, USA Manjula P. Reddy Oncology Translational Research, Janssen Research and Development, Janssen Pharmaceutical Companies of Johnson and Johnson, LLC, Spring House, PA, USA Paul W. Rhyne Immunoassay Services, Q 2 Solutions, Marietta, GA, USA Amy Kate Sasser Oncology Translational Research, Janssen Research and Development, Janssen Pharmaceutical Companies of Johnson and Johnson, LLC, Spring House, PA, USA Usha Singh Translational Medicine, Merck & Co., Rahway, NJ, USA; Translational Biomakers, Merck & Co., Rahway, NJ, USA

12 Editors and Contributors xiii Michael P. Sullivan Department of Bioanalytical Sciences, Worldwide Clinical Trials, Austin, TX, USA Michelle Tseng Amerimmune Immunology Laboratory, O & O Alpan, LLC, Fairfax, VA, USA Jeffrey A. Tsou Department of Reproductive and Genetic Health, Illumina, San Diego, CA, USA Paolo Vicini Pharmacokinetics, Dynamics and Metabolism New Biological Entities, Pfizer Worldwide Research and Development, San Diego, CA, USA; MedImmune, Cambridge, UK Richard Wnek Translational Molecular Biomarkers, Merck & Co., Inc., Rahway, USA Dianna Wu Translational Biomakers, Merck & Co., Rahway, NJ, USA; Oncology Translational Research, Janssen Research and Development, Spring House, USA; Translational Medicine, Merck & Co., Rahway, NJ, USA Tim Wyant Department of Translational Medicine, Curis Inc., Lexington, MA, USA Xuemei Zhao Translational Molecular Biomarkers, Merck Research Laboratories, Rahway, NJ, USA