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In this era of biotechnology there have been many books covering the fundamentals of recombinant DNA technology and protein chemistry. However, not many sources are available for the pharmaceutical develop ment scientist and other personnel responsible for the commercialization of the finished dosage forms of these new biopharmaceuticals and other products from biotechnology. This text will help to fill this gap. Once active biopharmaceutical molecules are candidates for clinical trial investigation and subsequent commercialization, a number of other activities must take place while research and development on these molecules continues. The active ingredient itself must be formulated into a finished dosage form that can be conveniently used by health care professionals and patients. Properties of the biopharmaceutical molecule must be clearly understood so that the appropriate finished product formulation can be developed. Finished product formulation development includes not only the chemical formulation, but also the packaging system, the manufacturing process, and appropriate control strategies to assure such good manufacturing practice attributes as safety, identity, strength, purity, and quality.
List of contents
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.
Summary
In this era of biotechnology there have been many books covering the fundamentals of recombinant DNA technology and protein chemistry. However, not many sources are available for the pharmaceutical develop ment scientist and other personnel responsible for the commercialization of the finished dosage forms of these new biopharmaceuticals and other products from biotechnology. This text will help to fill this gap. Once active biopharmaceutical molecules are candidates for clinical trial investigation and subsequent commercialization, a number of other activities must take place while research and development on these molecules continues. The active ingredient itself must be formulated into a finished dosage form that can be conveniently used by health care professionals and patients. Properties of the biopharmaceutical molecule must be clearly understood so that the appropriate finished product formulation can be developed. Finished product formulation development includes not only the chemical formulation, but also the packaging system, the manufacturing process, and appropriate control strategies to assure such good manufacturing practice attributes as safety, identity, strength, purity, and quality.
