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.

part Part I|52 pages


chapter 1|3 pages

Case-by-Case Approach

A Historical Perspective
ByJoy A. Cavagnaro

chapter 2|20 pages

Selection of Relevant Animal Models/Species

ByD. Blanset, M. Di Piazza, E. Musvasva

chapter 3|8 pages

Dose Extrapolation to Humans for Novel Biologics

ByJohn T. Sullivan

chapter 4|10 pages

Ready, Aim, Fire! The Importance of Strategic Drug Development Plans

ByPatricia D. Williams

chapter 5|8 pages

Global Regulatory Expectations and Interactions

ByMary Ellen Cosenza

part Part II|172 pages


chapter 7|6 pages

Preclinical Toxicology Testing Paradigms

ByJoy A. Cavagnaro

chapter 8|15 pages

Inhalation Delivery of Biologics

ByStephanie F. Greene, Gregory L. Finch

chapter 9|8 pages

Nonclinical Considerations for Biopharmaceutical Comparability Assessment*

ByC. E. Ellis, M. T. Hartsough

chapter 10|18 pages

Immunogenicity of Therapeutic Proteins

BySteven J. Swanson

chapter 11|14 pages

Testing for Off-target Binding

ByDiana M. Norden, Benjamin J. Doranz

chapter 12|18 pages

Reproductive, Developmental, and Juvenile Toxicity Assessments

ByChristopher J. Bowman, Gerhard F. Weinbauer

chapter 13|13 pages

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

ByA. Kimzey, K. Mease, B. Mounho-Zamora, M. Wood

chapter 15|5 pages

Due Diligence Regulatory and Preclinical Focus

ByJanet Nokleby

chapter 16|11 pages

Cytokine Assessments

ByFlorence G. Burleson, Stefanie C.M. Burleson, Gary R. Burleson

part III|194 pages

Product Attributes

chapter 19|8 pages

Nonclinical Development of Peptides and Therapeutic Proteins

ByMelanie T. Hartsough

chapter 21|10 pages

Nonclinical Safety Evaluation of Therapies for Rare Diseases

ByK. McKeever, T. MacLachlan

chapter 22|28 pages

Development of Antibody-Drug Conjugates 1

ByStanley 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 23|30 pages

Preventive and Therapeutic Vaccines

ByD.L. Novicki, Sheri D. Klas

chapter 24|24 pages

Understanding the Nonclinical Safety Considerations for Therapeutic Oligonucleotides

ByCathaline den Besten, Scott P. Henry, Arthur A. Levin

chapter 25|22 pages

Cellular-Based Therapies

ByEllen G. Feigal, Mary Ellen Cosenza

chapter 26|15 pages

Considerations in the Preclinical Development of Gene Therapy Products

ByJoy A. Cavagnaro

chapter 27|22 pages

Genome Editing Technologies

ByKathleen Meyer-Tamaki

part IV|93 pages

Practical Applications

chapter 28|29 pages

Nonclinical Development of Anticancer Biotherapeutics

ByMarque Todd, Cris Kamperschroer, Rafael Ponce, Timothy MacLachlan, Jonathan Heyen

chapter 30|16 pages

Nonclinical Safety Program Considerations for Biologic Therapeutics for Neurodegenerative Conditions

ByD.N. Hovland, B.B. Smith, C.W. Chen

chapter 31|7 pages

Nonclinical Development of Biologics for Infectious Diseases

ByB.B. Smith