This book addresses the stabilization of vaccine powders by spray drying and provides an overview of the current state of the art on a laboratory and industrial scale. The book aims to familiarize readers with the advances in vaccine spray drying technology to understand its application potential better. In particular, the book addresses the design of aseptic spray dryers, parameters affecting the spray drying process, sterile powder processing, cleaning procedures, and powder filling. In addition, different drying technologies for the production of dry powder vaccines are compared to discuss the unique capabilities of spray drying as a particle technology for vaccines. Special attention is given to research studies on spray-dried vaccines published over the past 30 years, with key findings from laboratory research to clinical trials. Potential applications of spray-dried vaccines and routes of administration are presented in detail. Finally, an outlook is given on how close the aseptic spray-drying of vaccines is to the market and the challenges that need to be overcome to be commercially successful. The book's target audience is academics, researchers, vaccine developers, industry experts, students, and possibly funders, including government agencies, who are active in the field. In addition, the book is a reference source for those involved in the vaccine formulation and biopharmaceutical processing industry.
Author(s): Cordin Arpagaus
Publisher: Springer
Year: 2023
Language: English
Pages: 609
City: Cham
Preface
The Global Race for the COVID-19 Vaccine
Spray Drying Technology as an Option for Future Thermostable Vaccines
My Motivation for Writing this Book
The Target Audience of this Book
Special Thanks and Dedication
Acknowledgments
About This Book
Contents
About the Author
Nomenclature
1 A Short Introduction to Vaccines
Abstract
1.1 Vaccines Safe Lives
1.2 Global Vaccination Coverage
1.3 Herd Immunity
1.4 Types of Vaccines
1.5 Vaccine Development Process
1.6 Vaccine Market and Growth
1.7 Vaccine Suppliers and Sales Numbers
1.8 Cooperations to Improve Vaccines Accessibility
1.9 Vaccine Prices
1.10 Summary of the Introduction
References
2 Thermostability of Vaccines
Abstract
2.1 Recommended Storage Conditions and Administration Routes
2.2 Heat and Freeze Stability of Vaccines
2.3 Excursus: Thermostability of COVID-19 Vaccines
2.4 Cold Chain and the Long Road to Vaccination
2.5 Wastage of Vaccines Due to Heat and Freeze Exposure
2.6 Suggested Improvements to Vaccine Products
2.7 Lessons Learned on Vaccine Stabilization
2.8 Characteristics of an Ideal Vaccine
2.9 VIPS—The Vaccine Innovation Prioritisation Strategy
2.10 The Controlled Temperature Chain (CTC)
2.11 Why Consider a Controlled Temperature Chain (CTC)?
2.12 Economic Benefits of Thermostable Vaccines in the CTC
2.13 CTC-Approved Vaccines and Pipeline
2.14 Summary
References
3 Drying Technologies for Vaccines
Abstract
3.1 Considerations for Dry Powder and Liquid Vaccine Formulations
3.2 Dry Powder Vaccine Stabilization Mechanisms
3.2.1 Water Replacement Hypothesis
3.2.2 Glass Dynamics or Vitrification Hypothesis
3.2.3 Excursus: Sugar Stabilization of the Resurrection Plant and Tardigrades
3.2.4 Excipients and Glass Transition Temperature
3.2.5 Drying Paths in a Sucrose-Water State Diagram
3.3 Freeze Drying of Vaccines
3.3.1 Principle and Benefits of Freeze Drying
3.3.2 A Short Market Review of Lyophilized Drugs
3.3.3 WHO Prequalified Lyophilized Vaccines and Manufacturers
3.3.4 Challenges in the Production of Freeze-Dried Vaccines
3.4 Spray Drying
3.4.1 Principle of Spray Drying
3.4.2 Process Parameters
3.4.3 Temperature Profile of Dry Powder Vaccine During Spray Drying
3.4.4 Droplet Size
3.4.5 Particle Formation in a Spray Dryer
3.4.6 Stickiness, Glass Formation, Residual Moisture, and Reconstitution Time
3.4.7 Product Stresses During Spray Drying
3.4.8 Comparison of Spray Drying to Freeze Drying
3.5 Spray Freeze Drying of Vaccines
3.5.1 Principle and Comparison to Spray Drying
3.5.2 Applications of Spray Freeze-Dried Vaccines
3.5.3 Equipment for Spray Freeze Drying
3.6 Vacuum Foam Drying of Vaccines
3.7 Supercritical Fluid Drying Technology
3.8 Overall Comparison of Drying Technologies for Vaccines
3.9 Excursus: Alternative Drying Technologies for Vaccines
3.9.1 Drying of Spray Dried Vaccine Powders in Rapid Dissolving Oral Thin Films
3.9.2 Drying of Vaccines by Thin-Film Freezing
3.9.3 Drying of Vaccines as Low-Cost Sugar Pills
3.9.4 Drying of Vaccines on a Fiber Membrane
3.9.5 Drying of Vaccines in a Porous Sponge in a Syringe
3.9.6 Drying of Vaccines at Room Temperature in Laminar Air
3.9.7 Drying of Vaccines as Microarray Patches
3.9.8 Summary and Conclusions
References
4 Aseptic Spray Drying Technology
Abstract
4.1 A Short History of Aseptic Spray Drying
4.2 Clean Areas for Aseptic Spray Drying
4.3 System Configurations for Aseptic Spray Dryers
4.3.1 Concept of an Aseptic Spray Dryer System
4.3.2 Open-Cycle System
4.3.3 Closed-Cycle System
4.4 Components of an Aseptic Spray Dryer
4.4.1 Drying Chamber and Connections
4.4.2 Nozzles
4.4.3 Filtration
4.4.4 Cyclone Collection
4.5 Cleaning, Sterilization, and Testing of an Aseptic Spray Dryer
4.5.1 Cleaning-In-Place (CIP)
4.5.2 Sterilization-In-Place (SIP)
4.5.3 Sterility Testing with Bacteria
4.6 Sterile Powder Processing
4.6.1 Aseptic Handling of the Spray-Dried Powder
4.6.2 Aseptic Powder Transfer to Filling Line
4.6.3 Aseptic Powder Filling into Dosage Formats
4.7 Laboratory-Scale Spray Dryers Used in Vaccine Research
4.8 Excursus: Mini Spray Dryer B-290 Options for Working with Low Bioburden
4.8.1 Sterilization of Components
4.8.2 Pressure Mode
4.8.3 Inlet HEPA Filter
4.8.4 Outlet HEPA Filter
4.8.5 Sterile Compressed Air for Atomization
4.8.6 Sterile Liquid Filtration
4.8.7 Sterilization of Nozzles
4.8.8 Powder Collection
4.8.9 Optional High-Performance Glass Cyclone
4.8.10 Cleaning of Glass Parts, Metal Parts, and O-rings
4.8.11 Optional Cleaning-In-Place (CIP) Glassware
4.8.12 Optional Insulation for the Spray Drying Cylinder
4.8.13 Optional Brown Glass for Protection of Light-Sensitive Products
4.8.14 Materials in Contact with the Product
4.8.15 Installation in a Biosafety Cabinet and Enclosures
4.9 Commercial-Scale Spray Dryer Equipment
4.9.1 Spray Dryer Equipment Market
4.9.2 Aseptic Spray Drying Equipment and Service Providers
4.9.3 Excursus: Particle Engineering Technologies from Nova Laboratories Ltd.
4.10 Summary
References
5 Design of Experiment Studies and Scale-Up
Abstract
5.1 Quality by Design (QbD) Approach
5.2 Design of Experiments (DOE) Studies of Spray-Dried Vaccines
5.3 Analytical Methods to Characterize Spray-Dried Vaccines
5.4 Scale-Up of Spray-Dried Vaccines
5.5 Excursus: Scale-Up from Mini Spray Dryer B-290 to Mobile Minor
5.6 Summary and Conclusions
References
6 Applications of Spray-Dried Vaccines
Abstract
6.1 Excursus: Commercialized Spray-Dried Pharmaceutical Products
6.2 Excursus: Examples of Spray-Dried Inhalable Drugs
6.3 Excursus: Single-Use Dry Powder Inhalers for Pulmonary Delivery
6.4 Excursus: Review Articles and Books on (Bio)pharmaceutical Spray Drying
6.5 Statistics of Publications on Spray-Dried Vaccines
6.6 Influenza Virus Vaccines
6.6.1 A Short Introduction to Seasonal Influenza
6.6.2 Influenza Vaccine Types
6.6.3 Research on Spray-Dried Influenza Vaccines
6.6.4 Discussion of Spray-Dried Influenza Vaccine Results
6.6.5 Conclusions on Spray-Dried Influenza Vaccines
6.7 Measles Vaccines
6.7.1 A Short Introduction to Measles Vaccines
6.7.2 Research on Spray-Dried Measles Vaccines
6.7.3 Conclusions on Spray-Dried Measles Vaccine
6.8 Hepatitis B Vaccines
6.8.1 A Short Introduction to Hepatitis B
6.8.2 Research on Spray-Dried Hepatitis B Vaccines
6.8.3 Conclusions on Spray-Dried Hepatitis B Vaccines
6.9 Tuberculosis Vaccines
6.9.1 A Short Introduction to Tuberculosis
6.9.2 Research on Spray-Dried Tuberculosis Vaccines
6.9.3 Conclusions and Outlook on Spray-Dried Tuberculosis Vaccines
6.10 Human Papillomavirus Vaccines
6.10.1 A Short Introduction to Current HPV Vaccines
6.10.2 Research on Spray-Dried HPV Vaccines
6.10.3 Conclusions and Future View on Spray-Dried HPV Vaccines
6.11 Cholera Vaccines
6.11.1 A Short Introduction to Current Cholera Vaccines
6.11.2 Research on Spray-Dried Oral Cholera Vaccines
6.11.3 Conclusions on Spray-Dried Cholera Vaccines
6.12 Anthrax Vaccines
6.12.1 A Short Introduction to Anthrax
6.12.2 Research on Spray-Dried Anthrax Vaccines
6.12.3 Conclusions on Spray-Dried Anthrax Vaccines
6.13 Typhoid Vaccines
6.13.1 A Short Introduction to Typhoid
6.13.2 Research on Spray-Dried Typhoid Vaccines
6.13.3 Conclusions on Spray-Dried Typhoid Vaccines
6.14 Diphtheria, Tetanus, Pertussis, and Hib Vaccines
6.14.1 A Short Introduction to Diphtheria, Tetanus, Pertussis, and Hib
6.14.2 Research on Spray-Dried Diphtheria, Tetanus, Pertussis, and Hib Vaccines
6.14.3 Conclusions on Spray-Dried DTP/Hib Vaccines
6.15 Rotavirus Vaccines
6.15.1 A Short Introduction to Rotavirus Vaccines
6.15.2 Research on Spray-Dried Rotavirus Vaccines
6.15.3 Conclusions on Spray-Dried Rotavirus Vaccines
6.16 Poliovirus Vaccines
6.17 Vesicular Stomatitis Virus Vaccines
6.18 Herpes Simplex Virus Vaccines
6.19 Norovirus Vaccines
6.19.1 A Short Introduction to Norovirus and Its Disease Burden
6.19.2 Norovirus Vaccines
6.19.3 Research on Spray-Dried Norovirus Vaccines
6.20 Human Immunodeficiency Virus Vaccines
6.21 Newcastle Disease Virus Vaccines
6.21.1 A Short Introduction to Newcastle Disease and Vaccines
6.21.2 Research on Spray-Dried Newcastle Disease Vaccines
6.21.3 Conclusions on Spray-Dried Newcastle Disease Vaccines
6.22 Tularemia Vaccines
6.22.1 A Short Introduction to Tularemia
6.22.2 Research on F. Tularensis Vaccines
6.22.3 Research on Spray-Dried F. Tularensis Vaccine
6.23 Pneumococcal Disease Vaccines
6.23.1 A Short Introduction to Pneumococcal Disease and Vaccines
6.23.2 Research on Spray-Dried Pneumococcal Vaccines
6.23.3 Conclusions on Spray-Dried Pneumococcal Vaccines
6.24 Meningococcal Disease Vaccines
6.24.1 A Short Introduction to Meningococcal Disease and Vaccines
6.24.2 Research on Spray-Dried Meningococcal Vaccine
6.25 mRNA Vaccines
6.25.1 A Short Introduction to mRNA Vaccines
6.25.2 Research on Lyophilized mRNA Vaccines
6.25.3 Research on Spray-Dried mRNA Vaccines
6.25.4 Conclusions and Future View on Spray-Dried mRNA Vaccines
References
7 Conclusions and Future Perspectives of Spray-Dried Vaccines
Abstract
7.1 Motivation of Spray Drying Vaccines
7.2 Drying Technologies for Vaccine Formulations
7.3 Aseptic Spray Drying Considerations
7.4 Spray Dryer Models Used in Vaccine Research
7.5 Scale-Up of Spray-Dried Vaccines
7.6 Design of Experiments (DOE) and Quality by Design (QbD)
7.7 Application Spectrum of Spray-Dried Vaccines
7.8 Excipients Used for Improving Spray-Dried Vaccine Stability
7.9 Spray Drying Temperatures for Vaccines
7.10 Particle Size and Morphologies of Spray-Dried Vaccines
7.11 Long-Term Storage Stability of Spray-Dried Vaccines
7.12 Administration Routes of Spray-Dried Vaccines
7.13 Challenges and Proposed Solutions for Spray-Dried Vaccines
7.14 Future Perspectives of Spray-Dried Vaccines
References
