1st Edition

Translational Medicine Optimizing Preclinical Safety Evaluation of Biopharmaceuticals

Edited By Joy A. Cavagnaro, Mary Ellen Cosenza Copyright 2022
    542 Pages 22 Color & 30 B/W Illustrations
    by CRC Press

    542 Pages 22 Color & 30 B/W Illustrations
    by CRC Press

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    Translational Medicine: Optimizing Preclinical Safety Evaluation of Biopharmaceuticals provides scientists responsible for the translation of novel biopharmaceuticals into clinical trials with a better understanding of how to navigate the obstacles that keep innovative medical research discoveries from becoming new therapies or even making it to clinical trials. The book includes sections on protein-based therapeutics, modified proteins, oligonucleotide-based therapies, monoclonal antibodies, antibody–drug conjugates, gene and cell-based therapies, gene-modified cell-based therapies, combination products, and therapeutic vaccines. Best practices are defined for efficient discovery research to facilitate a science-based, efficient, and predictive preclinical development program to ensure clinical efficacy and safety.

    Key Features:

    • Defines best practices for leveraging of discovery research to facilitate a development program
    • Includes general principles, animal models, biomarkers, preclinical toxicology testing paradigms, and practical applications
    • Discusses rare diseases
    • Discusses "What-Why-When-How" highlighting different considerations based upon product attributes.
    • Includes special considerations for rare diseases

    About the Editors

    Joy A. Cavagnaro is an internationally recognized expert in preclinical development and regulatory strategy with an emphasis on genetic medicines.. Her 40-year career spans academia, government (FDA), and the CRO and biotech industries. She was awarded the 2019 Arnold J Lehman Award from the Society of Toxicology for introducing the concept of science-based, case-by-case approach to preclinical safety evaluation, which became the foundation of ICH S6. She currently serves on scientific advisory boards for advocacy groups and companies and consults and lectures in the area of preclinical development of novel therapies.

    Mary Ellen Cosenza is a regulatory toxicology consultant with over 30 years of senior leadership experience in the biopharmaceutical industry in the U.S., Europe, and emerging markets. She has held leadership position in both the American College of Toxicology (ACT) and the International Union of Toxicology (IUTOX) and is also an adjunct assistant professor at the University of Southern California where she teaches graduate-level courses in toxicology and regulation of biologics.

    Chapter 1.1     Case-By-Case Approach:  Historical Perspective     

    Joy Cavagnaro

    Chapter 1.2     Selection of Relevant Animal Models/Species          

    D. Blasnet, M. Di Piazza and E. Musvasva

    Chapter 1.3     Dose Extrapolation to Humans for Novel Biologics 

    John T. Sullivan

    Chapter 1.4     READY, AIM, FIRE! The Importance of Strategic Drug Development Plans        

    Patricia D. Williams

    Chapter 1.5     Global Regulatory Expectations and Interactions     

    Mary Ellen Consenza

    Chapter 2.1     "Key Considerations in the Chemistry, Manufacturing and Controls (CMC) of BioPharmaceuticals"      

    Sara McKenzie and Ed Branson

    Chapter 2.2     Preclinical Toxicology Testing Paradigms    

    Joy Cavagnaro

    Chapter 2.3     Inhalation Delivery of Biologics        

    Stephanie F. Greene  and Gregory L. Finch

    Chapter 2.4.1  Nonclinical Considerations for Biopharmaceutical Comparability Assessment       

    Christopher E. Ellis and Melanie T. Hartsough

    Chapter 2.4.2  Immunogenicity of Therapeutic Proteins      

    Steven J. Swanson

    Chapter 2.4.3  Testing for Off-Target Binding         

    Diana M. Norden and Benjamin J. Doranz

    Chapter 2.4.4  Reproductive, Developmental, & Juvenile Toxicity Assessments  and Practical Applications           

    Christopher J Bowman and Gerhard F. Weinbauer

    Chapter 2.4.5  Biosimilar Products — A Review of Past and Current Regulatory Approval Standards for Preclinical Safety Studies      

    A. Kimzey, K. Mease, B. Mounho-Zamora, *M. Wood

    Chapter 2.4.6  Nonclinical Safety Strategy for Combinations of Biopharmaceuticals or Biopharmaceutical with Small Molecular Weight Compound    

    Maggie Dempster and Helen G. Haggerty

    Chapter 2.4.7  Due Diligence Regulatory and Preclinical focus      

    Janet Nokleby

    Chapter 2.5     Regulatory Toxicology for Biopharmaceuticals: Preparing for Pre-IND Interactions and Avoiding IND Pitfalls for Oncology and Non-Oncology Products  

    Janice Lansita, Andrew McDougal, Jane Sohn and Shawna Weis

    Chapter 2.6     Outsourcing and Monitoring Preclinical Studies Including GLP Considerations    

    P. Mookherjee

    Chapter 3.1     Nonclinical Development of Peptides and Therapeutic Proteins      

    Melanie T. Hartsough

    Chapter 3.2     Antibodies (Abs) and Related Products Containing Complementarity Determining Regions (CDRs)           

    Michael W. Leach

    Chapter 3.3     Nonclinical Safety Evaluation of Therapies for Rare Diseases         

    K. McKeever and T. MacLachlan

    Chapter 3.4     Development of Antibody Drug Conjugates 

    Stanley A. Roberts, Simon Chivers, Anu Connor, Hadi Falahatpisheh, Magali Guffroy, Anthony J. Lee,  Lise I. Loberg, Colin Phipps, Sherry L. Ralston, Melissa M. Schutten,  Nicola J. Stagg, Jay Tibbitts

    Chapter 3.5     Preventive and Therapeutic Vaccines

    S.D. Klas and D.L. Novicki

    Chapter 3.6     Understanding the Nonclinical Safety Consdierations for Therapeutic Oligonucleotides           

    Patrik Andersson, Cathaline den Besten, Scott P. Henry, Arthur A. Levin

    Chapter 3.7     Cellular-based Therapies        

    Ellen G. Feigal, Mary Ellen Cosenza

    Chapter 3.8     Considerations in the Preclinical Development of Gene Therapy Products 

    Joy Cavagnaro

    Chapter 3.9     Genome-Editing Technologies          

    Kathleen Meyer-Tamaki

    Chapter 4.1     Nonclinical Development of Anti-Cancer Biotherapeutics   

    Marque Todd, Cris Kamperschroer, Jonathan Heyen, Rafael Ponce and Timothy MacLachlan

    Chapter 4.2     Non-Clinical Safety Evaluation of Immunomodulatory Biological Therapeutics for the Treatment of Immune-Mediated Diseases    

    Frank R. Brennan

    Chapter 4.3     Nonclinical Safety Program Considerations for Biologic Therapeutics for Neurodegenerative Conditions     

    D.N. Hovland, Jr., B.B. Smith and C.W. Chen

    Chapter 4.4     Nonclinical Development of Biologics for Infectious Diseases        

    B.B. Smith


    Joy A. Cavagnaro, PhD, DABT, ATS, RAC, FRAPS is the President of Access BIO where she consults on science-based preclinical development strategies for novel drug, biologics and device combinations.  She received her PhD in Biochemistry from the University of North Carolina at Chapel Hill. Her career spans academia, the CRO and biotechnology industries and government. During her tenure at CBER/FDA she was appointed to the SBRS and served as FDA’s safety topic lead and rapporteur for “ICH S6.” She was the first to advocate the “case-by-case” rational science-based approach to preclinical safety evaluation.  In 2011 she received SOT’s Biotechnology Specialty Section First Career Achievement Award and in 2019 the Society’s Arnold J. Lehman Award recognizing individuals who have made significant contributions to risk assessment and/or the regulation of chemical agents, including pharmaceuticals. She is Founder and Past Chair of the leadership committee of BioSafe, an expert preclinical science committee within BIO. She is a Past Chair of the Clinical and Regulatory Affairs Committee and Translational Science & Product Development Committee of the ASGCT.  She was a member of the NTP Scientific Advisory Committee on Alternative Toxicological Methods and is an advisor and member of the Grants Working Group of the California Institute of Regenerative Medicine.   She serves on multiple SAB’s including Odylia Therapeutics a non-profit corporation devoted to moving ultra-rare inherited retinal diseases ‘from science to humans’ and consults and lectures internationally on translation and risk assessment of novel therapies.  She is a past chair of CRRI, an independent investigational review board and is currently a member of Advarra IRB. She has co-authored numerous white papers, articles and book chapters related to various aspects of preclinical safety assessment.  The book she edited “Preclinical Safety Evaluation of Biopharmaceuticals A Science-Based Approach to Facilitating Clinical Trials” published by John Wiley & Sons, NJ, 2008, is commonly referred to as the “BioBible”.


    Mary Ellen Cosenza, PhD, DABT, ATS, ERT, RAC is a regulatory consultant with over 30 years of senior leadership experience in the biopharmaceutical industry in the U.S., Europe, and emerging markets. Before becoming a consultant, she served as the Executive Director, U.S. Regulatory Affairs, at Amgen, Inc. During her 20-year tenure at Amgen, she led the International Emerging Markets Regulatory Department and served as an Executive Director of Global Regulatory Affairs and Safety.  In addition to her leadership roles in Regulatory Affairs, she also served as the Senior Director of Toxicology at Amgen. Prior to joining Amgen, she served as a Principal Scientist for the Medical Research Division of American Cyanamid Company (now Pfizer).  Mary Ellen is a founding member of BIO’s BioSafe Preclinical Expert group. She was also a member of an Expert Working Group, operating under the auspices of the International Conference on Harmonization (ICH) for ICH M3(R2). She has been awarded the ACT Mildred Christian Women’s Leadership in Toxicology Award (2019) and SOT’s Biotechnology Specialty Section Career Achievement Award (2015). Mary Ellen is a Diplomat of the American Board of Toxicology, a Fellow of the Academy of Toxicological Sciences, member of the Society of Toxicology (SOT), Drug Information Association (DIA) and Regulatory Affairs Professional Society (RAPS) and holds Regulatory Affairs Certification for both the U.S. and EU.  Mary Ellen has been an active member of the American College of Toxicology (ACT) and has served as a member of the ACT Education Committee, as Councilor, as Treasurer and President of the College. She is currently the Treasurer of the International Union of Toxicology (IUTOX). She is also an adjunct assistant professor at the University of Southern California where she teaches graduate level courses in toxicology and regulation of biologics. Mary Ellen received her PhD in Toxicology from St. John’s University, New York, and her MS in Regulatory Science from the University of Southern California, Los Angeles.