Practical Aspects of Vaccine Development: The Practical Aspects

Practical Aspects of Vaccine Development provides an academic and industry perspective on vaccine development and manufacturing. With the increasing complexity of vaccine products in development, there is a need for a comprehensive review of the current state of the industry and challenges being encountered. While formulation scientists working in biotherapeutic development may be familiar with proteins, vaccines present unique challenges. Vaccines include a wide range of components including proteins, polysaccharides, protein-polysaccharide conjugates, adjuvants, and more. The container closure system may also be unique, and the product may require freezing storage or lyophilization based on the stability of the vaccine components. Based on the route of delivery, novel technologies and devices may be required. Covering formulation development, manufacture, and delivery considerations of vaccine production, this book is essential to formulation scientists, researchers in vaccine development throughout medical and life sciences, and advanced students. Includes formulation considerations for various vaccine types, including proteins, polysaccharides, conjugates, and live vaccines Covers process development for solution, suspension, and lyophilized products Explores the future of vaccines, including multi-component vaccines and novel delivery mechanisms/devices Front Cover Practical Aspects of Vaccine Development Practical Aspects of Vaccine Development Copyright Contents Contributors Preface Acknowledgments 1 - Introduction to vaccine development Vaccines: the greatest advancement of modern medicine A brief historical review The foundation of vaccine development A summary of current strategies in vaccine development Adjuvants Summary References 2 - Overview of vaccine adjuvants Introduction General classification of vaccine adjuvants Specific types of adjuvants Aluminum salts Emulsion adjuvants Lipid-based adjuvants Immune potentiators Combination adjuvants Future considerations in the development of adjuvants Conclusions Trademark statement References 3 - Formulation design considerations and good practice for live attenuated vaccine development Introduction Live-attenuated vaccines Development of products with the end in mind The product target product profile The product quality target product profile Product critical quality attributes Analytics for formulation Stability assessment and temperature selection Development by design Excipient options Excipient considerations Rational design of formulations for live-attenuated vaccines A quality by design formulation development approach A sequential quality-by-design approach to formulation development Scoping studies Screening studies Categorical excipient choices for vaccine–excipient compatibility in prototype formulation selection Excipient concentration ranges and other process and device parameters Optimization of concentrations, processes and devices using response surface method study designs Central composite design Box–Behnken design Screening and optimization of formulations only (mixture designs) Optimal or custom designs Definitive screening designs Postoptimization: model validation, verification, and confirmation Predicted design and control space selection and quality risk assessment using graphical and numerical optimization Predicted design and control space selection and quality risk assessments using simulation and soft tools Formulation and process validation (robustness designs) Summary References 4 - Subunit-based vaccines: challenges in developing protein-based vaccines Introduction Similarities of vaccine proteins to therapeutic proteins Pneumococcal protein-based vaccine development Pneumococcal virulence factors Licensed pneumococcal vaccines Recombinant pneumococcal proteins as vaccine candidates Alternative approaches for pneumococcal vaccines Chlamydia trachomatis vaccine development Protective immunity against Chlamydia trachomatis Chlamydia trachomatis vaccine candidates Ricin vaccine development Ricin vaccine candidates Norovirus vaccine development NoV vaccine candidates Clostridium difficile vaccine development Clostridium difficile vaccine candidates Overarching problems in vaccine development Acknowledgments References 5 - QbD approach to formulation development for protein-based vaccines Scope and challenges of protein bases formulation development Quality by design as a guiding principle in vaccine formulation development Preformulation studies Formulation development and optimization studies Definition of appropriate dosage form Development of formulation composition Multicomponents vaccines formulation development Formulation optimization: formulation space definition Compatibility studies for reconstituted vaccines Conclusion Acknowledgments References 6 - pDNA and mRNA vaccines Introduction A brief history of vaccination Advantages of nucleic acid–based vaccination Harnessing and directing immune responses Production—speed and scale Native endogenous protein translation pDNA and mRNA vaccination; a two-horse race? Basic biology of pDNA and mRNA vaccines Structure of pDNA vectors Structure of mRNA pDNA and mRNA pharmacology pDNA and mRNA vaccine immunogenicity Nucleic acid vaccine development DNA vaccines—how far from clinic? Delivery strategies Formulation approaches DNA vaccine clinical trials mRNA vaccines—delivering the messenger The challenges of in vivo delivery “Naked” mRNA vaccine delivery Nanoparticle delivery systems for mRNA Lipid nanoparticles for mRNA delivery Delivering mRNA ligand-based nanoparticle RNA vaccine clinical trials Process development; scalability and manufacturability pDNA plasmid vaccine manufacture mRNA vaccine manufacture The future of nucleic acid vaccines The first responder to epidemic threats—a vaccine on-demand? Beyond viruses Beyond vaccination Concluding remarks References 7 - Antigen–adjuvant formulations—key considerations Introduction Considerations for antigen–adjuvant compatibility Aluminum adjuvant considerations Emulsion adjuvant considerations Lipid-based adjuvants Drug product design and considerations for dose preparation and administration Container closure Lyophilization of antigen–adjuvant formulation considerations Formulation considerations for lyophilization Vaccine antigens Antigen–adjuvant combinations (adjuvanted vaccines) Summary References 8 - Suspension properties and characterization of aluminum-adjuvanted vaccines Introduction Aluminum-containing adjuvant structure Principles of suspension behavior Theory of stability Controlled flocculation Properties and characterization Chemical composition and structure Particle size characterization Laser diffraction Flow imaging microscopy Sedimentation Sediment Microcomputed topography Surface charge Zeta-potential Point of zero charge Rheology Surface area Adsorption Spectroscopy Considerations in vaccine development Formulation Shear Redispersion Conclusion References 9 - Effect of shipping stresses on suspension vaccines Introduction Interplay between particle size, charge, and settling rate Effect of shipping stress on thermodynamic suspension stability Impact of individual shipping stresses on redispersion time Mitigation strategy to reduce high redispersion time Impact of shipping temperature on suspension vaccines Summary and recommendations References 10 - Control strategy development guide for vaccine drug product Introduction to control strategy approach Control strategy considerations How to develop control strategy Cause-and-effect matrix and risk assessment Application of control strategy concept Control strategy considerations Drug substance container Considerations for control at drug substance versus drug product site Control strategy construction through cause-and-effect matrix Amount of drug substance added to drug substance container Amount transferred from drug substance container to compounding tank Mixing speed and time for adjuvant and final bulk vaccine In-process controls and application of process analytical technology Process analytical technology application Raw material control strategy Control strategy for protein concentration Constructing final control strategy Summary and considerations for control strategy References 11 - Lyophilized vaccine development Introduction Overview of lyophilization formulation and process Freezing Primary drying Secondary drying Vaccine-specific considerations Conjugates and multivalent conjugate vaccines Live-attenuated Subunit vaccines Inactivated vaccines Antigen adjuvant lyophilization Novel vaccine Considerations for lyophilization cycle scale-up Summary References 12 - Conventional and nontraditional delivery methods and routes of vaccine administration The choice: the importance of the correct delivery system for an effective vaccination Conventional delivery methods: subcutaneous and intramuscular route Intramuscular delivery system Subcutaneous delivery system Limits of the conventional delivery system Epidermis and dermis as new sites of vaccine delivery Permeabilization of the skin Abrasion Chemical enhancers Thermal ablation Sonophoresis Electroporation Jet injectors Microneedles Solid microneedles Coated microneedles Dissolving microneedles Hollow microneedles Hydrogel-forming microneedles Other areas of the body as targets for vaccine delivery Nasal mucosa delivery Oral mucosa delivery Conclusion References Index A B C D E F G H I J L M N O P Q R S T U V W X Z Back Cover