How to Design and Implement Powder-to-Tablet Continuous Manufacturing Systems

1st Edition - March 29, 2022
Editors: Fernando Muzzio, Sarang Oka
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 1 3 4 7 9 - 5
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 1 3 4 8 0 - 1

How to Design and Implement Powder-to-Tablet Continuous Manufacturing Systems provides a comprehensive overview on the considerations necessary for the design of continuou… Read more

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How to Design and Implement Powder-to-Tablet Continuous Manufacturing Systems provides a comprehensive overview on the considerations necessary for the design of continuous pharmaceutical manufacturing processes. The book covers both the theory and design of continuous processing of associated unit operations, along with their characterization and control. In addition, it discusses practical insights and strategies that the editor and chapter authors have learned. Chapters cover Process Analytical Technology (PAT) tools and the application of PAT data to enable distributed process control.

With numerous case studies throughout, this valuable guide is ideal for those engaged in, or learning about, continuous processing in pharmaceutical manufacturing.

Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
About the Expertise in Pharmaceutical Process Technology Series
Foreword
Chapter 1. Introduction
1. Foreword—our journey in CM
2. The many benefits of continuous solid dose manufacturing
3. The engineering toolbox, applied to pharmaceutical manufacturing process design
Chapter 2. Characterization of material properties
1. Introduction
2. Summary of the characterization techniques and their description
3. Developing a material property database
4. Multivariate analysis
5. Application of material property databases
6. Conclusions
Chapter 3. Loss-in-weight feeding
1. Introduction
2. Characterization of loss-in-weight feeders
3. Effect of material flow properties on loss-in-weight feeding
4. Modeling of loss-in-weight feeders
5. Conclusions
Chapter 4. Continuous powder mixing and lubrication
1. Fundamentals of powder mixing
2. Modes of powder mixing
3. Mixing in continuous tubular blenders
4. Lubrication in continuous tubular blenders
5. Role of delumping in continuous powder mixing
6. Other topics
7. Conclusions
Chapter 5. Continuous dry granulation
1. Introduction
2. Roller compaction
3. Milling
4. Roller compaction characterization and micromechanical modeling
5. Granule characterization after milling
6. Models for milling
7. Conclusions
Chapter 6. A modeling, control, sensing, and experimental overview of continuous wet granulation
1. Introduction
2. Experimental design
3. Process modeling
4. Case studies
5. Conclusions
Chapter 7. Continuous fluid bed processing
1. Introduction
2. Basics of fluidized beds
3. Drying background and theory
4. Granulation drying background and theory
5. Commercial application
6. Why batch
7. Continuous processes in other industries
8. Traditional continuous fluid bed design
9. Adaptation to pharmaceutical processing
10. Traceability
11. Other continuous granulation methods
12. Summary and conclusion
Chapter 8. Continuous tableting
1. Fundamentals of tableting
2. Phenomenological modeling of compaction
3. Characterization of compaction operations
4. Characterization of tablets in continuous manufacturing
5. Control
6. Designing an experimental plan for continuous tableting
7. Conclusions
Chapter 9. Continuous film coating within continuous oral solid dose manufacturing
1. Fundamentals of continuous coating within continuous manufacturing
2. Goals of continuous film coating
3. Expectations of continuous coaters
4. Types of batch and continuous coaters used in continuous processes
5. Controls and process analytical technology
6. Conclusions
Chapter 10. Role of process analytical technology in continuous manufacturing
1. Introduction/background
2. Method development and life cycle considerations for PAT in CM
3. PAT in a CM commercial control strategy
4. Case studies
5. Conclusions
Chapter 11. Developing process models of an open-loop integrated system
1. Introduction
2. Loss-in-weight feeder
3. Continuous blender
4. Roller compactor
5. Continuous wet granulator
6. Fluidized bed dryer
7. Conical screen mill
8. Tablet press
9. Integration
10. Conclusions
Chapter 12. Integrated process control
1. Introduction
2. Design of the control architecture
3. Develop integrated model of closed-loop system
4. Implementation and verification of the control framework
5. Characterize and verify closed-loop performance
6. Conclusions
Chapter 13. Applications of optimization in the pharmaceutical process development
1. Introduction
2. Optimization objectives in pharmaceutical process development
3. Applications of data-driven models in optimization
4. Optimization methods in pharmaceutical processes
5. A case study of the optimization of a continuous direct compaction process
6. Discussion and future perspectives
Chapter 14. Regulatory considerations for continuous solid oral dose pharmaceutical manufacturing
1. Introduction
2. Definitions
3. Regulatory considerations for designing and implementing a continuous manufacturing process for SODs
4. Manufacturing changes for continuous processes
5. Discussions with regulators
Chapter 15. Continuous manufacturing process development case study
1. Introduction
2. Criteria for product selection
3. General approach and description of the process development, Process Analytical Technology development, and feasibility studies with academic partners
4. Janssen's continuous manufacturing line design was based on academic partner's continuous manufacturing line
5. A project that led to the first batch-to-cm process transformation approved by the US Food and Drug Administration
6. Project development team plan and key deliverables
7. The control strategy and the evaluation of failure modes as an integral part of process development activities
8. Feeder performance study and material transfer study
9. Engineering run and first evaluation of the mechanically integrated line
10. Residence time distribution studies and evaluation of process factors' effect on the Residence Time Distribution model
11. Observations from fully automated confirmation batch
12. Validation and continued process verification stages
13. Prezista 600mg continuous manufacturing supplemental new drug application approved: this is just the beginning
Chapter 16. Orkambi: a continuous manufacturing approach to process development at Vertex
1. Introduction
2. Continuous manufacturing equipment and process development
3. Continuous manufacturing and cGMPs
4. Control strategy implementation at Vertex
5. Life cycle management and PAT model maintenance
6. Conclusion and lessons learned
Chapter 17. Outlook—what comes next in continuous manufacturing (and in advanced pharmaceutical manufacturing)
Index

Fernando Muzzio

Fernando Muzzio is a Distinguished Professor at Rutgers University. For the last 22 years, pharmaceutical product and process design has been Professor Muzzio’s main research and educational focus. His research interests comprise continuous manufacturing, powder mixing, powder flow, segregation, compression, mixing and flow of liquids and suspensions, capsule filling, tablet dissolution, and tablet coating. Dr. Muzzio has published more than 260 research papers in this area and his h-index is currently 45. He is a frequent advisor and lecturer at FDA events, and in 2010 he was appointed a voting member of the FDA committee on Pharmaceutical Sciences and Clinical Pharmacology. Professor Fernando Muzzio is also the director of the National Science Foundation Engineering Research Center on Structured Organic Particulate Systems. The center, which has a total budget in excess of $8 million per year, focuses on pharmaceutical product and process design, with special emphasis on continuous manufacturing, particle engineering, and personalized medicine. The FDA and 45 companies, including Amgen, Vertex, Lilly, Pfizer, Merck, Bristol-Myers Squibb and more, are currently members of the center.

Affiliations and expertise

Distinguished Professor, Pharmaceutical Engineering Training Program, Department of Chemical and Biochemical Engineering, Director, NSF ERC on Structured Organic Particulate Systems PhD, Rutgers University, Piscataway, NJ, USA

Sarang Oka

Dr. Sarang Oka is a Senior Manager at Hovione where he heads the continuous drug product manufacturing area at Hovione's site in East Windsor, New Jersey, overseeing all technical functions including manufacturing, process development, and process analytical technology (PAT). Dr. Oka received his PhD in Chemical Engineering from Rutgers University. His thesis focused on continuous powder mixing and granulation, and examined the role of continuous manufacturing in enabling direct compression of otherwise directly incompressible formulations. He was also part of the team at Rutgers University and NSF ERC-SOPS that helped develop Prezista, the first FDA approval for a batch-to-continuous conversion of a drug product. Dr. Oka holds a BS in chemical engineering from Mumbai University.

Affiliations and expertise

Senior Manager, Drug Product Continuous Manufacturing, Hovione, East Windsor, New Jersey, USA

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