Currently, there are no textbooks on drug product manufacturing technology transfer that incorporate the latest regulatory expectations. Recent guidance from regulatory bodies such as the US FDA, EMEA, WHO, and PIC/S has adopted the ICH Lifecycle approach harmonizing concepts across regulatory guidance. This allows organizations to align their technology transfer activities for all regulated markets. However, there is a need for consensus and direction in approaching technology transfer, particularly in understanding how to manage the scale-up effects to ensure regulatory compliance.
This textbook offers technology transfer solutions and guidance to the pharmaceutical industry. The chapters provide a systematic understanding of applying the technology transfer concepts in pharmaceutical manufacturing, promoting standardization within the industry. Since Stage 1b is not specified in detail within the regulations, pharmaceutical organizations are left to determine the requirements of the stage. The need to justify the methodologies and utilization of sound science makes it more demanding. The textbook’s authors provide innovative solutions for technology transfer challenges, making it a comprehensive reference document. The approaches can be applied to both small-molecule and large-molecule drug product manufacturing segments, addressing the unmet needs of the industry.
Author(s): Ajay Babu Pazhayattil, Sanjay Sharma, Joe Paul Philip, Michelle Gischewski-Silva, Marzena Ingram
Series: AAPS Introductions in the Pharmaceutical Sciences, 10
Publisher: Springer-AAPS
Year: 2023
Language: English
Pages: 157
City: Arlington
Forewords
Preface
Contents
About the Authors
Chapter 1: Current Status of Technology Transfer
Introduction
Survey Results
Additional Insights
Conclusion
References
Chapter 2: Quality by Design (QbD) Process Design
Introduction
A Quality-by-Design Approach
Active Pharmaceutical Ingredient (API), the Excipients, and the Packaging Components
Formulation Development
Formulation Studies
Process Development
Design of Experiments (DoE)
Analytical Quality by Design (AQbD) Based Test Method Development
Risk Assessment
Establishing Control Strategy
Conclusion
References
Chapter 3: Quality Risk Management (QRM)
Introduction
Traditional QRM Tools
Semi-Quantitative Risk Assessment (SQRA) Methodology
Define Scope and Review Relevant Product/Process Information
CQA Identification
Material Attribute (MA)/Process Parameter (PP) Identification
MAs/PPs Classification and Risk Factor Assignment
Calculating Risk Ratio
Risk Assessment Chart
Comparison
Relevance of Data-Driven Tools
Conclusion
References
Chapter 4: Technology Transfer Process
Introduction
Technology Transfer Phases
Phase I: Project Initiation
Phase II: Project Proposal
Phase III: Project Transfer
Phase IV: Project Review
Planning
Transfer
Post-transfer
R&D to Site Transfer
Site-to-Site Transfer
References
Chapter 5: Scaling-Up of Solid Orals: Granulation, Drying, Size Reduction, Blending, Compression, and Coating Technologies
Equipment Classification: SUPAC
Scale-Up Basic Approach
Batch Size Calculation
Granulation Technologies
High Shear Granulation (RMG-Rapid Mixer Granulator)
Granule Growth Mechanism
Nucleation
Coalescence
Effect of Feed Material on Granule Growth in High Shear Mixer
Granulation Endpoint
Scale-Up Approach 1 from Horsthius et al. (1993)
Scale-Up Approach 2 from Rekhi et al. (1996)
Scale-Up Approach 3, Using Power Number Correlations Landin, M., P. York, M.J. Cliff (1996)
Drying Technologies
Granulation, Drying, e.g., Fluid-Bed Processors
FBP- Scale-Up Calculation
Scale Up/Down of Batch Size
Size Reduction/Separation Technologies
Screen Milling-e.g., Comil Selection and Studies
Blending and Mixing Technologies
Fixing the Batch Size
Compression Technologies
Encapsulation Technologies
Challenges
References
Chapter 6: Qualification, Continued Process Verification, and Lifecycle Management
Introduction
Stage 2a
Process Performance Qualification Prerequisites
PPQ Protocol and Reports
Determining the Number of Batches
Sampling Strategies
Post PPQ Stage 3a Assessment
Statistical Assessment
Stage 3b Routine Monitoring
ICHQ12: Product Lifecycle Management
Established Conditions and PACMP
References
Chapter 7: Continuous Improvement Case Study: Transforming Legacy Products
Introduction
Method
Material Attributes and Formulation Monitoring
Upstream Sifting and Milling Process Monitoring
Mixing Process Parameter Monitoring
Discharge Parameter Monitoring
Filling Parameter Monitoring
Stage 3 Data Analysis
Determining Sources of Variability
Variance Component Analysis of Uniformity Results
References
Appendices
Appendix I: Technology Transfer Documents (TTD) Checklist
Appendix II: Technology Transfer Protocol (TTP)
Appendix III: Check-List for First Exhibit Batch Start-Up
Appendix IV: Case Study of Roller Compaction Process from Development to Scale-Up
Summary of the Selected Process After Development
Index
