Process Architecture in Biomanufacturing Facility Design

Essential information for architects, designers, engineers, equipment suppliers, and other professionals who are working in or entering the biopharmaceutical manufacturing field

Biomanufacturing facilities that are designed and built today are radically different than in the past. The vital information and knowledge needed to design and construct these increasingly sophisticated biopharmaceutical manufacturing facilities is difficult to find in published literature--and it's rarely taught in architecture or design schools. This is the first book for architects and designers that fills this void. Process Architecture in Biomanufacturing Facility Design provides information on design principles of biopharmaceutical manufacturing facilities that support emerging innovative processes and technologies, use state-of-the-art equipment, are energy efficient and sustainable, and meet regulatory requirements.

Relying on their many years of hands-on design and operations experience, the authors emphasize concepts and practical approaches toward design, construction, and operation of biomanufacturing facilities, including product-process-facility relationships, closed systems and single use equipment, aseptic manufacturing considerations, design of biocontainment facility and process based laboratory, and sustainability considerations, as well as an outlook on the facility of the future.

• Provides guidelines for meeting licensing and regulatory requirements for biomanufacturing facilities in the U.S.A and WHO--especially in emerging global markets in India, China, Latin America, and the Asia/Pacific regions

• Focuses on innovative design and equipment, to speed construction and time to market, increase energy efficiency, and reduce footprint, construction and operational costs, as well as the financial risks associated with construction of a new facility prior to the approval of the manufactured products by regulatory agencies

• Includes many diagrams that clarify the design approach

Process Architecture in Biomanufacturing Facility Design is an ideal text for professionals involved in the design of facilities for manufacturing of biopharmaceuticals and vaccines, biotechnology, and life-science industry, including architects and designers of industrial facilities, construction, equipment vendors, and mechanical engineers. It is also recommended for university instructors, advanced undergraduates, and graduate students in architecture, industrial engineering, mechanical engineering, industrial design, and industrial interior design.

Auteur

Jeffery Odum, CPIP is the Managing Partner of the Strategic Manufacturing Concept Group, and a Global Technology Partner at NNE in the US Office located in Durham, North Carolina and a Teaching Fellow in the BTEC program at North Carolina State University. Michael C. Flickinger, PhD is the Associate Director for Academic Programs at the Golden LEAF Biomanufacturing Training and Education Center (BTEC) and a Professor of Chemical and Biomolecular Engineering at North Carolina State University, Raleigh, North Carolina.

Contenu
Contributors xv

Foreword xvii

Preface xix

1 Introduction to Biomanufacturing **1
**Mark F. Witcher

1.1 Introduction 1

1.2 The Basics Constituents of Biopharmaceuticals 2

1.2.1 Proteins 3

1.2.2 Nucleic Acids (DNA and RNA) 5

1.2.3 Cells 6

1.3 Enterprise Element #1Manufacturing Processes 8

1.3.1 ProcessUnit Operations 8

1.3.2 Upstream ProcessesInoculum through Production Bioreactor 9

1.3.3 Upstream ProcessesHarvest and Recovery 12

1.3.3.1 Normal Filtration 12

1.3.3.2 Centrifuge 13

1.3.3.3 Cell Disruption 13

1.3.4 Downstream Processes 13

1.3.4.1 Viral Clearance 14

1.3.4.2 Tangential Flow Filtration 15

1.3.4.3 Chromatography 16

1.3.5 Process Performance and Control 19

1.3.6 ProcessEquipment 22

1.3.7 ProcessMaterials 23

1.4 Enterprise Element #2Manufacturing Facility 23

1.4.1 FacilityLayout 23

1.4.2 FacilityEnvironment 25

1.4.3 Clean Rooms/CNC Spaces 25

1.4.4 HVACHeating Ventilation and Air-Conditioning 26

1.4.5 Surfaces 30

1.4.6 FacilityUtilities Systems 30

1.4.7 FacilityControl Systems 31

1.5 Enterprise Element #3Manufacturing Infrastructure 31

1.5.1 InfrastructurePeople (Operating Staff) 32

1.5.2 InfrastructureEnterprise Practices and Procedures 32

1.6 Controlling the Manufacturing Enterprise 33

1.7 Summary 35

References 36

2 ProductProcessFacility Relationship **39
**Jeffery Odum

2.1 Introduction 39

2.2 The Characteristics of Biological Therapeutic Products 40

2.3 Understanding the Attributes 42

2.3.1 Product Quality Attributes 44

2.3.2 Process Parameters 44

2.3.3 Facility Attributes 45

2.4 Factors that Impact Facility Design 46

2.4.1 Facility Types 47

2.4.1.1 Product Development Facilities 47

2.4.1.2 Pilot/Clinical 49

2.4.1.3 Commercial Manufacturing 54

2.4.2 Comparisons of the Facility Types 54

References 54

3 Regulatory Considerations of Biomanufacturing Facilities **55
**Kip Priesmeyer

3.1 Introduction 55

3.2 Regulatory Uncertainty, A Two-Way Street 56

3.3 Design with the Patient in Mind: Assess the Patient, Product, Process, and Plant 58

3.4 Laws, Regulations, and Guidelines: Historical Background 60

3.5 Global Guidance Documents 64

3.6 Quality Systems and Risk Management 66

3.7 Product Changeover and Regulatory Assessment of Cleaning Validation 70

3.8 Control Strategy 74

3.9 Contract Manufacturing Organizations 77

3.10 FDA Inspections of Biopharm Facilities and Regulators' Priorities 80

3.11 Regulatory Meetings 84

3.12 Conclusion 85

References 88

4 Biopharmaceutical Facility Design and Validation **91
**Jeffery Odum

4.1 Introduction 91

4.2 Designing for Compliance 92

4.2.1 Facility Considerations 93

4.2.2 ProductProcessFacility Integration 94

4.2.3 The Role of Quality by Design 94

4.3 Risk Management 102

4.4 Qualification/Verification 105

4.5 Process Validation 110

4.6 List of Abbreviations 113

References 115

5 Closed Systems in Bioprocessing **117
**Jeffery Odum

5.1 Introduction 117

5.2 Definition of Closed Systems 117

5.3 Closed System Design 119

5.4 Impact on Facility Design 121

5.5 Impact on Operations 123

5.6 Summary 127

References 127 **6 Aseptic Manufacturing Considerations for ...