Tested and proven solutions to the challenges of biological drug product development

Biological drug products play a central role in combating human diseases; however, developing new successful biological drugs presents many challenges, including labor intensive production processes, tighter regulatory controls, and increased market competition. This book reviews the current state of the science, offering readers a single resource that sets forth the fundamentals as well as tested and proven development strategies for biological drugs. Moreover, the book prepares readers for the challenges that typically arise during drug development, offering straightforward solutions to improve their ability to pass through all the regulatory hurdles and deliver new drug products to the market.

Biological Drug Products begins with general considerations for the development of any biological drug product and then explores the strategies and challenges involved in the development of specific types of biologics. Divided into five parts, the book examines:

• Part 1: General Aspects
• Part 2: Proteins and Peptides
• Part 3: Vaccines
• Part 4: Novel Biologics
• Part 5: Product Administration/Delivery

Each chapter has been prepared by one or more leading experts in biological drug development. Contributions are based on a comprehensive review and analysis of the current literature as well as the authors' first-hand experience developing and testing new drugs. References at the end of each chapter serve as a gateway to original research papers and reviews in the field.

By incorporating lessons learned and future directions for research, Biological Drug Products enables pharmaceutical scientists and students to improve their success rate in developing new biologics to treat a broad range of human diseases.

WEI WANG, PhD, is a Research Fellow for Pfizer BioTherapeutics Pharmaceutical Sciences. In addition, Dr. Wang is Adjunct Professor in the School of Pharmacy and Health Sciences at the University of the Pacific.

MANMOHAN SINGH, PhD, is Head of Technical Development at Novartis Vaccines and Diagnostics. Dr. Singh has authored over 120 peer-reviewed manuscripts, reviews, and book chapters in the area of vaccine formulations and adjuvant research. He is also an Adjunct Professor at the Eshelman School of Pharmacy at University of North Carolina, Chapel Hill.

Dedication

Preface

Part 1. General Aspects 1

Chapter 1. An Overview of Discovery and Development Process For Biologics 3
Heather H. Shih, Paula Miller and Douglas C. Harnish

Chapter 2. Nonclinical Safety Assessment of Biologics, Including Vaccines 31
Liangbiao George Hu, David W. Clarke

Chapter 3 Clinical Assessment of Biologics Agents 57
Lesley Ann Saketkoo, Shikha Mittoo and Luis R. Espinoza

Chapter 4. Key Regulatory Guidelines for Development of Biologics In The U.S. And Europe 75
Richard Kingham, Gabriela Klasa and Krista Hessler Carver

Chapter 5. Landscape and Consideration of Intellectual Property for Development Of Biosimilars 111
Srikumaran Melethil

Chapter 6. Scientific Aspects of Sterility Assurance, Sterility, Asepsis, and Sterilization 133
James E. Akers and James P. Agalloco

Part 2. Proteins/Peptides 163

Chapter 7. Cell Cell Culture Processes in Monoclonal Antibody Production 165
Feng Li, Amy (Yijuan) Shen and Ashraf Amanullah

Chapter 8. Protein/Peptide Purification and Virus Reduction 203
Beckley K. Nfor, Esteban Freydell and Marcel Ottens

Chapter 9. Chemical and Genetic Modification 233
M Farys, C Ginn, G Badescu, K Peciak, E Pawlisz, H Khalili and S Brocchini

Chapter 10. Analytical Characterization of Proteins/Peptides 285
Yajun Jennifer Wang and Brian Hosken

Chapter 11. Protein/Peptide Formulation Development 323
Satoshi Ohtake and Wei Wang

Chapter 12. Regulatory Strategies and Lessons in the Development Of Biosimilars 367
Umang S. Shah

Part 3. Vaccines 409

Chapter 13. Vaccine Development – History, Current Status and Future Trends 411
Leo Van Der Pol and Jean-Pierre Amorij

Chapter 14. Role and Application of Adjuvants and Delivery Systems in Vaccines 437
Rajesh K. Gupta

Chapter 15. Methods for Characterizing Proteins in Aluminum Adjuvant Formulations 469
Martinus A.H. Capelle, Emilie Poirier and Tudor Arvinte

Part 4. Novel Biologics 487

Chapter 16. The State Of The Art and Future of Gene Medicines 489
Frank Jacobs, Stephanie C. Gordts and Bart De Geest

Chapter 17. Nucleic Acid Vaccines 531
Rachel Buglione-Corbett, John Suschak, Shixia Wang and Shan Lu

Chapter 18. Multifunctional Polymeric Nano-Systems for Rna Interference Therapy 569
Arun Iyer, Shanthi Ganesh, Qiong L. Zhou and Mansoor Amiji

Chapter 19. Advent and Maturation of Regenerative Medicine 601
Abner M. Mhashilkar and Anthony Atala

Part 5. Product Administration/Delivery 629

Chapter 20. Conventional and Novel Container Closure/Delivery Systems 631
Joseph Wong and Mahesh V. Chaubal

Chapter 21. Controlled-Release Systems for Biologics 655
Mayura Oak, Rhishikesh Mandke, Buddhadev Layek, Gitanjali Sharma and Jagdish Singh

Chapter 22. Routes of Delivery for Biological Drug Products 677
Darrell J. Irvine, Xingfang Su and Brandon Kwong

INDEX 725