Technology Transfer: Drug Product Manufacturing Process

Description

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. 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