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. Cover How to Integrate Quality by Efficient Design (QbED) in Product Development Copyright Dedication How To use Biography of Bhavishya Mittal Foreword Acknowledgments About the Expertise in Pharmaceutical Process Technology series 1. Format 2. Subject matter 3. Target audience 1 - Healthcare: a societal benchmark 1.1 Introduction 1.1.1 Global health—a sacred promise 1.1.2 Sustainable global health: a work in progress 1.2 An overview of the pharmaceutical industry 1.2.1 From botanicals to alkaloids 1.2.2 Impact of healthcare and pharmaceuticals on US economy 1.2.3 Impact on stock market 1.3 Trials and tribulations of pharmaceutical industry 1.3.1 Trend #1: fluctuations in pharmaceuticals’ financial fortunes 1.3.1.1 General trends 1.3.1.2 Blockbuster drugs era 1.3.1.3 Renewed focus 1.3.2 Trend #2: Outsourcing. Outsourcing Outsourcing! 1.3.2.1 Early days 1.3.2.2 Emergence of modern CDMO industry 1.3.2.3 Postfinancial crisis growth 1.3.3 Trend #3: increase in mergers and acquisitions 1.3.4 What’s next—integrating our knowledge to enhance decision-­making 1.4 Summary List of abbreviations References 2 - Pharmaceuticals: a highly innovative business 2.1 Introduction 2.1.1 Powerhouses of innovation—Apple versus Pfizer 2.1.2 Pharmaceutical innovation—a societal necessity 2.1.3 Sustainable Development Goals—a global call for urgent action 2.1.4 Global healthcare 2.2 Healthcare statistics of United States 2.2.1 Role of Centers for Medicare and Medicaid Services in healthcare administration 2.2.2 Historical THE statistics in United States 2.2.3 Projected THE in United States till 2026 2.2.4 Impact of THE statistics on pharmaceuticals 2.3 Development of innovative pharmaceutical products 2.3.1 Business proposition of pharmaceuticals 2.3.2 Innovative products 2.3.3 Patent protections of innovative products 2.3.4 Generic products 2.4 Summary List of abbreviations References 3 - Pharmaceutical productivity: challenges and opportunities 3.1 Introduction 3.1.1 DNA—the building block of life 3.1.2 Implications for pharmaceutical manufacturing—integrate learning 3.2 Measurement of productivity 3.2.1 Multifactor productivity 3.2.2 Multifactor productivity trends in US manufacturing sector 3.2.3 Multifactor productivity in pharmaceuticals 3.3 Hurdles in pharmaceutical innovation 3.3.1 Understanding of disease and potential cure 3.3.2 Disproportionate market sizes 3.3.3 Rate of attrition in R&D and clinical trials 3.3.4 Special characteristics of healthcare market 3.4 Ongoing measures to improve pharmaceutical R&D’s efficiency 3.4.1 Generation of new supply chain based on pharmaceutical outsourcing 3.4.2 Augmenting R&D portfolios through research collaborations 3.4.3 In-­licensing and partnerships of potentially viable assets 3.5 Summary List of abbreviations References 4 - QbD: a welcome evolution 4.1 Introduction 4.1.1 A $11 fix that was ignored 4.1.2 Implications for pharmaceutical manufacturing—never take quality for granted 4.2 Quality—a word with multiple definitions 4.2.1 When quality implies excellence 4.2.2 When quality implies value 4.2.3 When quality implies conformance to specifications 4.2.4 When quality implies meeting and/or exceeding customers’ expectations 4.3 Pharmaceutical quality 4.3.1 Enforcement of pharmaceutical quality (1906–38) 4.3.2 Enforcement of pharmaceutical quality (1962–present) 4.3.3 Enforcement of pharmaceutical quality in modern times 4.4 Pharmaceutical quality by design 4.4.1 Fundamental documents 4.4.2 QbD objectives 4.4.3 QTTP, CQAs, and CPPs 4.4.4 Quality risk management and risk assessment 4.4.5 Risk management methodology 4.4.6 Failure mode and effects analysis 4.4.7 Design space 4.4.8 Control strategy 4.4.9 Pharmaceutical quality system 4.5 Summary List of abbreviations References 5 - QbED: an emerging concept 5.1 Introduction 5.1.1 Global Positioning system 5.1.2 Implications for pharmaceutical manufacturing—remain competitive 5.1.3 QbED—merging business acuity with rational design approach 5.2 Need for QbED based on regulatory and compliance trends 5.2.1 Annual rate of Type 1 new drug application approvals is constant 5.2.2 More companies are getting Type 1 new drug application approvals 5.2.3 Increased reliance on foreign manufacturing facilities 5.2.4 Poor compliance with Current Good Manufacturing Practices 5.2.5 Bifurcation of institutional knowledge 5.2.6 Poor clinical performance despite label claims 5.3 Applying QbED through The Juran Trilogy® 5.3.1 Cost of Poor Quality 5.3.2 Chronic waste 5.3.3 Decoding The Juran Trilogy® for pharmaceuticals 5.4 Summary List of abbreviations References 6 - Adaptive product designs: a wave of the future 6.1 Introduction 6.1.1 The hundred years’ war 6.1.2 Implications for pharmaceutical manufacturing—build design flexibility 6.1.3 Traditional development models in pharmaceuticals 6.1.4 Statistics of the rate of drug failure 6.2 Integrating rational product design with adaptive product designs 6.2.1 A background to adaptive product design 6.2.2 Product configuration 6.2.3 Customer-­driven manufacturing 6.2.3.1 Assemble-­to-­order 6.2.3.2 Make-­to-­order 6.2.3.3 Engineer-­to-­order 6.2.4 Modularity-­based manufacturing practices 6.2.5 Product lifecycle management 6.3 Adaptive product design for pharmaceuticals 6.3.1 APD approaches 6.3.2 Quality Function Deployment 6.3.3 Product versus process platforms 6.4 Summary List of abbreviations References 7 - Patient-­centric drug product designs: a business necessity 7.1 Introduction 7.1.1 The power of customer-­centric innovation 7.1.2 Implications for pharmaceutical manufacturing—anticipate end use 7.2 Patient adherence to medication—a persistent and costly issue 7.2.1 Factors affecting medication adherence 7.2.2 Understanding the patients and their needs 7.2.3 Patient-­centric pharmaceutical drug product design 7.3 Enhancement of medication adherence through dosage form design 7.3.1 Compliance issues with physical size of dosage forms 7.3.2 Dosage form size and shape selection 7.3.3 Palatability 7.4 Enhancement of medication adherence through FDC and modified release formulations 7.4.1 Fixed dose combinations—a growing necessity 7.4.2 Modified release dosage forms 7.5 Enhancement of robustness of use through flexible dosing 7.5.1 Underlying problem: variability in dose response 7.5.2 Precision dosing: a potential solution 7.6 Enhancement of robustness of use through packaging 7.6.1 Key design requirements for primary packaging 7.6.2 Selection of packaging materials 7.7 Summary List of abbreviations References 8 - Manufacturing excellence: only road to continual improvement 8.1 Introduction 8.1.1 Japan—maintaining market dominance through manufacturing excellence 8.1.2 Implications for pharmaceutical manufacturing—embrace TQM philosophy 8.1.3 Lean Six Sigma—an extension of total quality management 8.1.4 Value stream mapping—a framework for manufacturing excellence 8.2 Clinical trials—the marketplace for formulators 8.2.1 Background on clinical trials 8.2.2 Reduction of bias in clinical trials 8.2.3 A review of ClinicalTrials.gov 8.2.4 Clinical trials are becoming more global 8.2.5 Clinical trials are long and getting longer 8.3 Accurate forecasting—the “oil” of a well-­oiled machine 8.3.1 Challenges with accurate forecasting in clinical trials 8.3.2 Constraint #1—limited availability of drug substance 8.3.3 Constraint #2—limited investment in rational product development 8.3.4 Constraint #3—limited investment in manufacturability evaluation 8.4 Continuous process evaluation and improvements 8.5 Summary List of abbreviations References 9 - Case studies and supplemental resources 9.1 Case study #1—global distribution of healthcare 9.2 Case study #2—addressing productivity issues 9.3 Case study #3—impact of drug recall 9.4 Case study #4—strategies to extend patent life 9.5 Case study #5—non-­Type 1 NDA approval trends 9.6 Case study #6—design of experiments in pharmaceutical development 9.7 Case study #7—modernizing drug development 9.8 Case study #8—clinical trial designs 9.9 Case study #9—process monitoring using control charts 9.10 Case study #10—integration of operations management in decision-­making List of abbreviations References Index A B C D E F G H I J L M N O P Q R S T U V W Back Cover