Development and Manufacture of Protein Pharmaceuticals

1 Preformulation Studies as an Essential Guide to Formulation Development and Manufacture of Protein Pharmaceuticals.- 1. Introduction.- 2. Protein Structural Characterization and Conformational Stability.- 3. Protein Size, Quaternary Structure, Aggregation State, and Solubility.- 4. Degradative Covalent Reactions and Their Effect on Physicochemical and Biological Properties of Proteins.- 5. Conclusions.- References.- 2 Formulation Development of Protein Dosage Forms.- 1. Introduction.- 2. Why Proteins Present Unique Challenges to the Development Scientist.- 3. General Formulation Principles for Proteins.- 4. Why Packaging, Processing, and Formulation Are Interrelated.- 5. Commercially Available Protein Dosage Forms.- 6. Chemical Stabilization.- 7. Physical Stabilization.- 8. Formulation Approaches for Solving Physical Stability Problems.- 9. Additives for Antimicrobial Preservation.- 10. Other Additives.- 11. Packaging.- 12. Interface between Formulation Development and Manufacturing.- 13. Quality Considerations during Formulation Development.- 14. Examples of Formulation Problems.- References.- 3 Aseptic Processing of Protein Pharmaceuticals.- 1. Introduction.- 2. Aseptic Processing of Solution, Lyophilized, and Suspension Dosage Forms.- 3. Unique Challenges in the Aseptic Processing of Protein Pharmaceuticals.- 4. Developing Aseptic Processes for Drug Product Manufacturing.- 5. Conceptual Framework for Drug Product Process Validation.- References.- 4 Fundamentals of Thermal Sterilization Processes.- 1. Introduction.- 2. Effects of Heat on Living Cells.- 3. Factors Affecting Resistance of Microorganisms to Thermal Inactivation.- 4. Thermal Inactivation of Microorganisms.- 5. Sterility Assurance.- 6. Thermal Inactivation Kinetics.- 7. Sterilization Cycle Development.-8. Sterilization Engineering.- 9. Parametric Release of Terminally Sterilized Drug Products.- 10. Summary.- References.- 5 Membrane Filtration.- 1. Introduction.- 2. Overview of Filtration Membranes.- 3. Membrane Filtration Theory.- 4. The Practice of Sterile Filtration.- Appendix: Definition of Terms.- References.- 6 Fundamentals of Freeze-Drying.- 1. Introduction.- 2. Overview of the Freeze-Drying Process.- 3. The Freezing Process.- 4. Material Characterization.- 5. The Drying Process.- 6. Stability of Freeze-Dried Formulations.- 7. Summary.- References.- 7 Quality Assurance and Quality Control for Biopharmaceutical Products.- 1. Introduction.- 2. Defining Quality Assurance and Quality Control in Biopharmaceutical Companies.- 3. Involvement of Quality in Biopharmaceutical Manufacturing Control.- 4. Overall Quality Control Strategy for Biopharmaceutical Products.- 5. Closing Comments on Quality in Biopharmaceutical Companies.- References.- 8 Regulatory Considerations in the Development of Protein Pharmaceuticals.- 1. Introduction.- 2. Biotechnology Product Development.- 3. Production Variables.- 4. Manufacturing Process Issues.- 5. Product Quality Attributes.- 6. Evolution of the New Regulatory Paradigm.- 7. Conclusion.- References.