Preclinical Safety Evaluation of Biopharmaceuticals

A Science-Based Approach to Facilitating Clinical Trials
1. Auflage 2008
ISBN: 978-0-470-10884-0
Verlag: Wiley

Buch, Englisch, 1080 Seiten, Format (B × H): 165 mm x 236 mm, Gewicht: 1565 g

"The goal is to provide a comprehensive reference book for the preclinicaldiscovery and development scientist whose responsibilities span target identification, lead candidate selection, pharmacokinetics, pharmacology, and toxicology, and for regulatory scientists whose responsibilities include the evaluation of novel therapies."
—From the Afterword by Anthony D. Dayan

Proper preclinical safety evaluation can improve the predictive value, lessen the time and cost of launching new biopharmaceuticals, and speed potentially lifesaving drugs to market. This guide covers topics ranging from lead candidate selection to establishing proof of concept and toxicity testing to the selection of the first human doses. With chapters contributed by experts in their specific areas, Preclinical Safety Evaluation of Biopharmaceuticals: A Science-Based Approach to Facilitating Clinical Trials: - Includes an overview of biopharmaceuticals with information on regulation and methods of production
- Discusses the principles of ICH S6 and their implementation in the U.S., Europe, and Japan
- Covers current practices in preclinical development and includes a comparison of safety assessments for small molecules with those for biopharmaceuticals
- Addresses all aspects of the preclinical evaluation process, including: the selection of relevant species; safety/toxicity endpoints; specific considerations based upon class; and practical considerations in the design, implementation, and analysis of biopharmaceuticals
- Covers transitioning from preclinical development to clinical trials
This is a hands-on, straightforward reference for professionals involved in preclinical drug development, including scientists, toxicologists, project managers, consultants, and regulatory personnel.

Autoren/Hrsg.

Cavagnaro, Joy A

Fachgebiete

• Technische Wissenschaften Verfahrenstechnik | Chemieingenieurwesen | Biotechnologie Kosmetische Technologie
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizin, Gesundheitswesen Biomedizin, Medizinische Forschung, Klinische Studien
• Technische Wissenschaften Verfahrenstechnik | Chemieingenieurwesen | Biotechnologie Pharmazeutische Technologie

Inhaltsverzeichnis

Foreword xi
Joy A. Cavagnaro, PhD, DABT, RAC, and Anthony D. Dayan, LLB, MD, FRCP, FRCPath, FFOM, FFPM, FIBiol

Acknowledgments xix

Contributors xxi 

Part I Background 1

1. Biopharmaceuticals: Definition and Regulation 3
Lincoln Tsang, PhD, FRSC, FIBiol, FRPharmS (Arnold and Porter, London, UK), and Nathan Cortez (Southern Methodist University)

2. Methods of Production of Biopharmaceutical Products and Assessment of Environmental Impact 21
Patricia D. Williams, PhD (Summit Drug Development Services)

Part II Principles of Preclinical Development 43

3. The Principles of ICH S6 and the Case-by-Case Approach 45
Joy A. Cavagnaro, PhD, DABT, RAC (Access BIO)

4. Implementation of ICH S6: EU Perspective 67
Peter R. Ryle, PhD, DipRCPath (Tox), FRCPath (PR BioServices), and David J. Snodin, PhD, FRSC, MChemA, MSc (Parexel Consulting)

5. Implementation of ICH S6: Japanese Perspective 93
Takahiro Nakazawa, PhD (Eli Lilly Japan)

6. Implementation of ICH S6: US Perspective 111
Mary Ellen Cosenza, PhD, MS, DABT, RAC (Amgen)

Part III Current Practices in Preclinical Development 123

7. Comparison of Preclinical Development Programs for Small Molecules (Drugs/Pharmaceuticals) and Large Molecules (Biologics/Biopharmaceuticals): Studies, Timing, Materials, and Costs 125
Christopher Horvath, DVM, MS, DACVP (Archemix Corp.)

8. Demonstration of Comparability of a Licensed Product after a Manufacturing Change 161
Richard M. Lewis, PhD (Access BIO)

Part IV Selection of Relevant Species 179

9. Selection of Relevant Species 181
Meena Subramanyam, PhD, Nicola Rinaldi, PhD, Elisabeth Mertsching, PhD, and David Hutto, PhD, DVM (Biogen Idec)

10. Tissue Cross-Reactivity Studies for Monoclonal Antibodies: Predictive Value and Use for Selection of Relevant Animal Species for Toxicity Testing 207
William C. Hall, VMD, PhD, DACVP (Hall Consulting Inc.), Shari A. Price-Schiavi, PhD, DABT (Charles River Laboratories—PAI), Joan Wicks, DVM, PhD, DACVP (Charles River Laboratories—PAI), and Jennifer L. Rojko, DVM, PhD, DACVP (Charles River Laboratories—PAI)

11. Physiologic IgG Biodistribution, Transport, and Clearance: Implications for Monoclonal Antibody Products 241
Jennifer L. Rojko, DVM, PhD, DACVP, and Shari Price-Schiavi, PhD, DABT (Charles River Laboratories—PAI)

12. The Role of Pharmacokinetics and Pharmacodynamics in Selecting a Relevant Species 277
Martin D. Green, PhD (FDA), and Melanie Hartsough, PhD (Biologics Consulting Group, Inc.)

13. Use of Animal Models of Disease in the Preclinical Safety Evaluation of Biopharmaceuticals 293
Johan te Koppele, PhD (TNO Quality of Life) and Renger Witkamp, PhD (Wageningen University, The Netherlands)

Part V Safety/toxicity Endpoints 309

14. Safety Pharmacology: Similarities and Differences between Small Molecules and Novel Biopharmaceuticals 311
Edward W. Bernton, MD (Pathway Pharmacology)

15. Genetic Toxicology Testing of Biopharmaceuticals 337
David Jacobson-Kram, PhD, DABT, and Hanan Ghantous, PhD, Dabt (fda)

16. General Toxicity Testing and Immunotoxicity Testing for Biopharmaceuticals 343
Jeanine L. Bussiere, PhD, DABT (Amgen)

17. Reproductive Toxicity Testing for Biopharmaceuticals 357
Pauline L. Martin, PhD (Centocor Research and Development Inc.)

18. Reproductive/Developmental Toxicity Assessment of Biopharmaceuticals in Nonhuman Primates 379
Gerhard F. Weinbauer, PhD, Werner Frings, PhD, Antje Fuchs, PhD, Michael Niehaus, PhD, and Ingrid Osterburg (Covance, Germany)

19. Preclinical Evaluation of Cancer Hazard and Risk of Biopharmaceuticals 399
Joy A. Cavagnaro, PhD, DABT, RAC (Access BIO)

20. Immunogenicity of Therapeutic Proteins and the Assessment of Risk 475
Huub Schellekens, MD, PhD (Utrecht University), and Wim Jiskoot, PhD (Leiden University)

21. Assessment of Autoimmunity and Hypersensitivity 487
Jacques Descotes, md, PharmD, PhD, and Thierry Vial, md
(Poison Centere and Pharmacovigilance Unit, Lyon, France)

Part VI Specific Considerations Based on Product Class 499

22. Current Practices in the Preclinical Safety Assessment of Peptides 501
Shawn M. Heidel, DVM, PhD, and Todd J. Page, PhD (Eli Lilly)

23. Enzyme Replacement Therapies 517
Laura Andrews, PhD, DABT (Genzyme), and Michael O’Callaghan, DVM, PhD, MRCVS (Genzyme)

24. Toxicology of Oligonucleotide Therapeutics and Understanding the Relevance of the Toxicities 537
Arthur A. Levin, PhD, DABT (Biotech & Pharmaceutical Consulting), and Scott P. Henry, PhD, DABT (Isis)

25. Preclinical Safety Evaluation of Biological Oncology Drugs 575
Theresa Reynolds, BA, DABT (Genentech)

26. Preclinical Safety Evaluation of Monoclonal Antibodies 587
George Treacy, MS, and Pauline Martin, PhD (Centocor
Research and Development)

27. Immunomodulatory Biopharmaceuticals and Risk of Neoplasia 601
Peter J. Bugelski, PhD, FRCPath, Clifford Sachs, PhD, DABT, Joel Cornacoff, DVM, PhD, DABT, Pauline Martin, PhD, and George Treacy, MS (Centocor Research and Development)

28. Strategy Considerations for Developing the Preclinical Safety Testing Programs for Protein Scaffold Therapeutics 633
Stanley A. Roberts, PhD, DABT, Gary Woodnutt, PhD, and Curt W. Bradshaw, PhD (CovX Research, LLC)

29. Preclinical Safety Evaluation of Immunotoxins 649
Jennifer G. Brown, PhD, Joycelyn Entwistle, PhD, Nick Glover, PhD, and Glen C. MacDonald, PhD (Viventia Biotech, Inc)

30. Preclinical Safety Evaluation of Blood Products 669
Richard M. Lewis, PhD (Access BIO)

31. Preclinical Safety Evaluation of Viral Vaccines 683
A. Marguerite Dempster, PhD, DABT, and Richard Haworth, FRCPath, DPhil (GlaxoSmithKline)

32. Preclinical Safety Evaluation of Biopharmaceuticals 713
Mercedes A. Serabian, MS, DABT, and Ying Huang, PhD (FDA)

33. Considerations in Design of Preclinical Safety Evaluation Programs to Support Human Cell-Based Therapies 749
Joy A. Cavagnaro, PhD, DABT, RAC (Access BIO)

34. Preclinical Safety Evaluation of Biopharmaceuticals: Combination Products (Biologic/Device) 783
Bruce Babbitt, PhD, and Barry Sall (Parexel Consulting)

35. Tissue Engineered Products: Preclinical Development of Neo-Organs 799
Timothy A. Bertram, DVM, PhD, and Manuel Jayo, DVM, PhD (Tengion)

Part VII Preclinical Study Design, Implementation, and Analysis 827

36. GLP Requirements and Current Practices 829
Tanya Scharton-Kersten (Novartis)

37. Preclinical Safety Study Design Templates and Estimated Costs 851
Gary W. Wolfe, PhD, DABT (Summit Drug Development Services)

38. Practical Considerations in the Design of Preclinical Safety Assessments for Biopharmaceuticals 913
Damon R. Demady, PhD (Knopp Neurosciences)

39. Survey of Preclinical Toxicology Programs for Approved Biopharmaceuticals 931
Anita Marie O’Connor, PhD (Anita O’Connor Consulting, LLC)

Part VIII Transitioning From Preclinical Development to Clinical Trials 969

40. Science and Judgment in Establishing a Safe Starting Dose for First-in-Human Trials of Biopharmaceuticals 971
Jennifer Visich, PhD (Genentech), and Rafael Ponce, PhD, DABT (Zymogenetics)

Part IX Afterword 985

A Retrospective 987
Anthony D. Dayan, LLB, MD, FRCP, FRCPath, FFOM, FFPM, FIBiol

Index 999

Über Autor(innen)

Joy A. Cavagnaro, PhD, is the President of Access BIO, a consultancy specializing in science-based regulatory strategies and product development services. She has over twenty-five years of experience in biotech spanning academia, the CRO and biotech industries, and government. During her tenure at the FDA, Dr. Cavagnaro served as rapporteur for ICH S6. She is founder and past chair of the BIO Preclinical Safety Expert Group (BioSafe) and was the U.S. BIO Representative to the 2006 ABPI/BIA Early Stage Clinical Trials Taskforce.Dr. Cavagnaro is currently North American Chair of the Drug Information Association–Biotech SIAC and Chair of the Clinical and Regulatory Affairs Committee of the American Society of Gene Therapy. She serves on a number of scientific advisory boards and lectures internationally in the area of preclinical development of novel therapies.