BookNicholas W. Warne, Hanns-Christian Mahler, editors.
Summary: In this volume, the authors discuss the many significant challenges currently faced in biotechnology dosage form development, providing guidance, shared experience and thoughtful reflection on how best to address these potential concerns. As the field of therapeutic recombinant therapeutic proteins enters its fourth decade and the market for biopharmaceuticals becomes increasingly competitive, companies are increasingly dedicating resources to develop innovative biopharmaceuticals to address unmet medical needs. Often, the pharmaceutical development scientist is encountering challenging pharmaceutical properties of a given protein or by the demands placed on the product by stability, manufacturing and preclinical or clinical expectations, as well as the evolving regulatory expectations and landscape. Further, there have been new findings that require close assessment, as for example those related to excipient quality, processing, viscosity and device compatibility and administration, solubility and opalescence and container-closure selection. The literature varies widely in its discussion of these critical elements and consensus does not exist. This topic is receiving a great deal of attention within the biotechnology industry as well as with academic researchers and regulatory agencies globally. Therefore, this book is of interest for business leaders, researchers, formulation and process development scientists, analytical scientists, QA and QC officers, regulatory staff, manufacturing leaders and regulators active in the pharmaceutical and biotech industry, and expert reviewers in regulatory agencies.
Contents:
Intro; Preface; Contents; Contributors; Abbreviations; Formulation Development of Biologics; 1 Introduction into Formulation Development of Biologics; Abstract; 1.1 Introduction; 1.2 Formulation Development Strategies and Approaches; 1.2.1 Protein Formulation: Beyond Stabilization; 1.2.2 Components of a Protein Formulation; 1.2.2.1 Active Pharmaceutical Ingredient and Drug Substance; 1.2.2.2 Excipients; 1.2.2.3 Primary Packaging Material; 1.2.3 Preformulation; 1.2.4 Formulation Development; 1.2.4.1 Formulation Development Strategies; 1.2.4.2 Early Stage Formulation Development. 1.2.4.3 Late-Stage Formulation Development1.2.4.4 Formulation Development After Commercialization; 1.3 Challenges During Formulation Development; 1.3.1 Amount and Quality of DS; 1.3.2 Selection of Analytical Methods and Stress Conditions; 1.3.2.1 Analytical Methods; 1.3.2.2 Stability Testing and Forced-Degradation Studies; 1.3.3 Manufacturability and Formulability; 1.3.4 Data Handling and Analysis; 1.4 Conclusions; References; Further Reading; Challenges with Excipients; 2 Polysorbate Degradation and Quality; Abstract; 2.1 Introduction; 2.2 Chemical Structure, Synthesis and Composition. 2.2.1 Structure Heterogeneity in PS20 and PS802.3 Use in Biotherapeutics; 2.4 Interaction of Nonionic Surfactants with Proteins; 2.5 Interactions of Protein-Surfactant Mixtures at Interfaces; 2.6 Pharmacopoeia Requirements and Commercially Available Grades of Polysorbate; 2.7 Stability and Degradation in Formulations; 2.8 Mechanistic Pathways of Polysorbate Degradation; 2.9 Hydrolysis; References; 3 Sucrose and Trehalose in Therapeutic Protein Formulations; Abstract; 3.1 Introduction; 3.2 Physical Properties; 3.2.1 Introduction; 3.2.2 Solution-State Properties; 3.2.3 Solid-State Properties. 3.2.4 Chemical Properties3.3 Use in Formulations and Stabilization Mechanisms; 3.3.1 Liquid State; 3.3.2 Frozen State; 3.3.3 Lyophilized State; 3.4 Regulatory and Safety Aspects; 3.4.1 Regulatory Aspects; 3.4.2 Safety Aspects; 3.5 Summary and Recommendations; References; High Concentration Proteins; 4 Introduction to High-Concentration Proteins; Abstract; 4.1 Overview of Recombinant Therapeutic Proteins; 4.1.1 Antibody Therapeutics; 4.1.2 Concentration Ranges of Marketed Biotherapeutics; 4.2 Need for High-Concentration Protein Products; 4.2.1 Routes of Administration. 4.2.2 High Dose Requirement4.2.3 Long-Term Drug Administration; 4.2.4 Manufacturing Cost; 4.3 Overall Challenges in Developing High-Concentration Products; 4.3.1 Theoretical Considerations; 4.3.2 Physical Properties and Influencing Factors of High-Concentration Proteins; 4.3.2.1 Solution Viscosity; 4.3.2.2 Protein Conformation; 4.3.2.3 Aggregation Tendency; 4.3.2.4 Factors Influencing Protein-Protein Interactions; 4.3.3 Major Challenges; 4.3.3.1 Formulation Development; 4.3.3.2 Process Development; 4.3.3.3 Drug Administration; 4.4 Future Directions.