Formulation and Process Development Strategies for Manufacturing Biopharmaceuticals

A real-world guide to the production and manufacturing of biopharmaceuticals

While much has been written about the science of biopharmaceuticals, there is a need for practical, up-to-date information on key issues at all stages of developing and manufacturing commercially viable biopharmaceutical drug products. This book helps fill the gap in the field, examining all areas of biopharmaceuticals manufacturing, from development and formulation to production and packaging.

Written by a group of experts from industry and academia, the book focuses on real-world methods for maintaining product integrity throughout the commercialization process, clearly explaining the fundamentals and essential pathways for all development stages. Coverage includes:

• Research and early development phase–appropriate approaches for ensuring product stability

• Development of commercially viable formulations for liquid and lyophilized dosage forms

• Optimal storage, packaging, and shipping methods

• Case studies relating to therapeutic monoclonal antibodies, recombinant proteins, and plasma fractions

• Useful analysis of successful and failed products

Formulation and Process Development Strategies for Manufacturing Biopharma-ceuticals is an essential resource for scientists and engineers in the pharmaceutical and biotech industries, for government and regulatory agencies, and for anyone with an interest in the latest developments in the field.

Part I Preformulation and Development of Stability Indicating Assays: Biophysical Characterization Techniques.

1. The Structure of Biological Therapeutics (Sherry Martin-Moe, Y. John Wang, Tim Osslund, Tahir Mahmood, Rohini Deshpande, and Susan Hershenson).

2. Chemical Instability in Peptide and Protein Pharmaceuticals (Elizabeth M. Topp, Lei Zhang, Hong Zhao, Robert W. Payne, Gabriel J. Evans and Mark Cornell Manning).

3. Physical Instability in Peptide and Protein Pharmaceuticals (Byeong Chang and Bernice Yang).

4. Immunogenicity of Therapeutic Proteins (Steven J Swanson).

5. Preformulation Research: Assessing Protein Solution Behavior Early During Therapeutic Development (Bernardo Perez-Ramirez, Nicholas Guziewicz and Robert Simler).

6. Formulation Development of Phase I/II Biopharmaceuticals: An Efficient and Timely Approach (Nicholas W. Warne).

7. Late Stage Formulation Development and Characterization of Biopharmaceuticals (Adeolla O Grillo).

8. An Empirical Phase Diagram/ High Throughput Screening Approach to the Characterization and Formulation of Biopharmaceuticals (Sangeeta B. Joshi; Akhilesh Bhambhani; Yuhong Zeng; and C. Russell Middaugh).

9. Fluorescence and Phosphorescence Methods to Probe Protein Structure and Stability in Ice: the Case of Azurin (Giovanni Strambini).

10. Applications of Sedimentation Velocity Analytical Ultracentrifugation (Tom Laue).

11. Field Flow Fractionation with Multi-angle Light Scattering for Measuring Particle Size of Virus-like Particles (Joyce A Sweeney and Christopher Hamm).

12. Light Scattering Techniques and their Application to Formulation and Aggregation Concerns (Philip Wyatt and Michael Larkin).

Part 2 Development of a Formulation for Liquid Dosage Form.

13. Efficient Approaches to Formulation Development of Biopharmaceuticals (Rajiv Nayar and Mitra Mosharraf).

14. Prediction of Protein Aggregation Propensities from Primary Sequence Information (Mark Cornell Manning, Gabriel J. Evans, Cody M. Van Pelt and Robert W. Payne).

15. High Concentration Antibody Formulations (Steven J. Shire, Jun Liu, Wolfgang Friess, Susanne Matheus and Hanns-Christian Mahler).

16. Development of Formulations for Therapeutic Monoclonal Antibodies and Fc Fusion Proteins (Sampath kumar Krishnan, Monica M. Pallitto and Margaret S. Ricci).

17. Reversible Self-Association of Pharmaceutical Proteins: Characterization and Case Studies (Vikas K. Sharma, Harminder Bajaj and Devendra S. Kalonia).

Part 3 Development of Formulation for Lyophilized Dosage Form.

18. Design of a Formulation for Freeze Drying (Feroz Jameel and Mike J. Pikal).

19. Protein Conformation and Reactivity in Amorphous Solids (Lei Zhang, Sandipan Sinha and Elizabeth M. Topp).

20. The Impact of Buffer on Solid-State Properties and Stability of Freeze-Dried Dosage Forms (Evgenyi Y. Shalaev and Larry A. Gatlin).

21. Stabilization of Lyophilized Pharmaceuticals by Control of Molecular Mobility: Impact of Thermal History (Suman Luthra and Micheal J. Pikal).

22. Structural Analysis of Proteins in Dried Matrices (Andrea Hawe, Sandipan Sinha, Wolfgang Friess and Wim Jiskoot).

23. The Impact of Formulation and Drying Processes on the Characteristics and Performance of Biopharmaceutical Powders (Vu L. Truong and Ahmad M. Abdul-Fattah).

Part 4 Manufacturing Sciences.

24. Manufacturing Fundamentals for Biopharmaceuticals (Maninder Hora).

25. Protein Stability during Bioprocessing (Mark Cornell Manning, Gabriel J. Evans and Robert W. Payne).

26. Freezing and Thawing of Protein Solutions (Satish Singh and Sandeep Neema).

27. Strategies for Bulk Storage and Shipment of Proteins (Feroz Jameel, Chakradhar Padala and Theodore W. Randolph).

28. Drying Process Methods for Biopharmaceutical Products: An Overview (Ahmad M. Abdul-Fattah and Vu L. Truong).

29. Spray Drying of Biopharmaceuticals and Vaccines (Jim Searles and Govindan (Dan) Mohan).

30. Development and Optimization of Freeze Drying Process (Feroz Jameel and Jim Searles).

31. Considerations for Successful Lyophilization Process Scale-up, Technology Transfer and Routine Production (Samir Sane and Chung C. Hsu).

32. Process Robustness in Freeze-Drying of Biopharmaceuticals (D.Q. Wang, D. MacLean and X. Ma).

33. Filling Processes and Technologies for Liquid Biopharmaceuticals (Ananth Sethuraman, Xiaogang Pan, Bhavya Mehta and Vinay Radhakrishnan).

34. Leachables and Extractables (Jim Castner, Pedro Benites and Michael Bresnick).

35. Primary Container/Closure Selection for Biopharmaceuticals (Olivia Henderson).

36. Pre-filled Syringes for Biopharmaceuticals (Robert Swift and Robin Hwang).

37. Impact of Manufacturing Processes on the Drug Product Stability and Quality (Nitin Rathore, Rahul S. Rajan and Erwin Freund).

Index.

Feroz jameel, PhD, is Principal Scientist for Drug Product Process Development at Amgen, involved in the development of biopharmaceutical products and the develop-ment of new technologies to enhance drug product manufacturing. Dr. Jameel is the recipient of the Parenteral Drug Association's 1999 Fred Simon Award for the Best Paper Published in the PDA Journal of Pharmaceutical Science and Technology.

SUSAN HERSHENSON, PhD, is Vice President for Pharmaceutical and Device Development at Genentech. She has more than fifteen years' experience in the area of formulation and delivery, including development of protein and small molecule therapeutics.