How to Integrate Quality by Efficient Design Qbed in Product Development

Description

The development of a robust drug product requires juggling many competing priorities such as overcoming scientific challenges, following regulatory requirements, and managing business-related concerns. Unfortunately, despite large resources spent on R&D, multifactor productivity of pharmaceuticals is on the decline for several years now. Because of this business reality, pharmaceutical companies have seen a notable change in the traditional operating model and footprint over the past couple of decades. Outsourcing, in particular, has emerged as a successful business model for many pharmaceutical companies looking for ways to strategically increase their R&D capabilities and to augment their in-house resources. How to Integrate Quality by Efficient Design (QbED) in Product Development bridges the gap between theory and practice when it comes to strategic decision-making in a pharmaceutical research scenario. This book will introduce the concept of QbED and focus on various aspects such as patient-centric product designs, platform-based manufacturing technologies, business acuity, and regulatory strategies to balance the challenges in outsourcing with the need for strategic and statistically sound experiments rooted in good science. Detailed discussions will cover pharmaceutical business models, regulatory approval process, quality by design (QbD), business analytics, and manufacturing excellence specifically for small molecules and solid oral dosage forms. With the addition of case studies, flowcharts, diagrams, and data visualizations, How to Integrate Quality by Efficient Design (QbED) in Product Development will be a practical reference to help professionals working in the area of pharmaceutical drug development, strategy, and outsourcing management. Part of the Expertise in Pharmaceutical Process Technology series edited by Michael LevinIntegrates pharmaceutical business models, economics, and outsourcing-related challenges into pharmaceutical product developmentDiscusses relevant literature references in quality risk management, business strategy, QbD, and product developmentProvides decision-making flowcharts, conceptual diagrams, and data visualizations to make the book useful, easy to read, and to understand Cover Principles of Parenteral Solution Validation Copyright Dedication Contents List of Contributors Editor Biographies About the Expertise in Pharmaceutical Process Technology Series Format Subject Matter Target Audience Introduction References Further Reading 1 Process Validation: Design and Planning Part 1: Background—The Need for Process Understanding Why Is Aseptic Process Validation so challenging? Process Validation, Process Capability, and Process Control Role of Process Understanding Process Life Cycle Approach Proper Process Design as the Key to Process Performance Assurance: Sterility by Design Using a Line of Sight Approach Defining Process Requirements The Role of Process Design and Planning in Validation: Basis of Design Timely User Requirement Specification Equipment and Facility Qualification Mapping the Process Periodic Assessment and Requalification Aseptic Practices: A Key Element in the Validation of Aseptic Processes First Air Principles References 2 Aseptic Process Validation: Aseptic Process Simulation Design Microbial Contamination Case Study: Sterile Vessel Holding Qualification Question #1: How Did the Interior of the Vessel Become Contaminated? The More Challenging Question Is #2: If the Conclusions Are Correct, Then Why Did the Initial Media Fills Pass? Aseptic Process Simulation Study Design Aseptic Process Simulations Performance Schedule and Frequency Media Fills Run Number Inclusion of Process Steps “Worst-Case” Parameters or Conditions Fill Volume Duration Interventions Intervention Evaluation and Risk Assessment Methods Incubation Growth Promotion Studies Preincubation Inspection and Rejection Postincubation Inspection Acceptance Criteria Filled Unit Accountability Failure Investigation Aborted and Invalid Media Fills Special Considerations Powder Filling Ointment Filling Lyophilized Product Filling Anaerobic Processes Conclusion References 3 Quality Risk Management of Parenteral Process Validation, Part 1: Fundamentals Quality Risk Management and Process Validation Overview: Risk Management Evolution Principles of Risk Management and the Quality Risk Management Life Cycle Risk: Understanding Hazard, Harm, and Controls Risk Management: The Fine Print Risk Team Membership Goal, Scope, and Boundaries Exploring the Process Map The Risk Question and Tool Selection Scales for Assessing Risk Quality Risk Management Life Cycle Risk Assessment Risk Control Risk Communication Risk Review Conclusion References 4 Equipment Cleaning Process Establishing Limits References Further Reading 5 Quality Risk Management of Parenteral Process Validation, Part 2: A Risk-Based Quality Management System Overview Deviation Management Low Risk Deviation Medium Risk Deviation High Risk Deviation Corrective and Preventive Action Risk Benefit Analysis Change Control Change Control and Corrective and Preventive Action Effectiveness Monitoring Self-Inspection Process Define Key Quality Management Systems Define Functional Area Categories Perform Risk Assessment Using Compliance Scoring Criteria Risk Factors and Scoring Determine Audit Frequency Using Risk Matrix Develop Audit Schedule; Review Annually Summary References Further Reading 6 Use of Statistics in Process Validation Overview Use of Statistics in Parenteral Process Validation—Ten Basic Concepts First Concept—A Concept of Statistical Inference Second Concept—Graph It First! Third Concept—Let DataTalk to You! Fourth Concept—Normality? Fifth Concept—Descriptive Statistics Sixth Concept—Control Charting Seventh and Eight Concepts—Tolerance and Capability Ninth Concept—Hypothesis Testing Tenth Concept—Design of Experiments Conclusion References Further Reading 7 Process Validation Stage 1: Parenteral Process Design Introduction Into Pharmaceutical Development Master Planning, Organization, and Schedule Planning Risk/Impact Assessment Process/System Design Perform Risk Assessment (Identification of Critical Quality Attributes and Critical Process Parameters) Design of Experiments Developing Control Strategies and Determine Process Design Scale-Up and Technology Transfer Stage 1: Design of Experiments Case Study Final Notes About Stage 1 Process Design References 8 Process Validation Stage 2: Parenteral Process Performance Qualification General Principles of Stage 2 Life Cycle Approach to Process Validation for Parenteral Products The Line of Sight Approach to Process Understanding and Process Validation Stage 2: Process Qualification Some Points to Consider for the Qualification of Equipment and Systems Critical Utilities Clean Rooms and Classified Areas Component Preparation Product Sterilization and Filtration Moist Heat Sterilization Dry Heat Sterilization Radiation and Ethylene Oxide Sterile Filtration Filling Equipment and Systems Inspection, Labeling, and Secondary Packaging Systems Lyophilization Material Storage, Handling, and Transport Testing Laboratories Additional Parenteral Processes Cleaning Validation Computer System Validation Terminal Sterilization Container Closure Integrity Periodic Assessment and Requalification Stage 2b—PPQ or Process Performance Qualification Number of Batches Conclusion References Further Reading 9 Process Validation Stage 3: Continued Process Verification Introduction Definitions Typically Used in Process Validation Determining When Continued Process Verification Starts Legacy Systems Versus New Systems Continued Process Verification Strategy and Enhanced Sampling Maintenance of Validation and Change Control, and Periodic Assessment Develop Control Rules for Continued Process Verification Develop Strategies for Continued Process Verification Examples of Case Study Evaluations for Parenteral Products Conclusion References 10 Preuse/Poststerilization Integrity Testing of Sterilizing Grade Filter Introduction Possible Reasons to Apply Preuse/Poststerilization Integrity Testing The Risks Attached to Preuse/Poststerilization Integrity Testing Recommendations References 11 Environmental Monitoring References Further reading 12 Isolators Further Reading 13 Post Aseptic Fill Sterilization and Lethal Treatment Introduction Sterilization and Lethal Treatment Post Aseptic Fill Sterilization Post Aseptic Fill Lethal Treatment Parametric Release Summary Conclusion Index