Cell Therapy (eBook)

Preface 6
Acknowledgments 8
Contents 9
Contributors 11
Acronyms 14
Part I Regulatory 18
1 Regulation of Cell Product Manufacturing and Delivery: A United States Perspective 19
History of Cell Therapy Development 19
U.S. Food and Drug Administration (FDA) 20
History of Regulation of Cell Therapies 20
CBER 21
CDRH 22
CDER 22
Combination Products 22
The IND Process 23
Who Needs an IND? 23
IND Sponsor/Investigator 23
Requesting a Meeting 23
Pre-IND Meeting 24
IND Submission 25
Chemistry, Manufacturing, and Control (CMC) Section 26
Chemistry and Manufacturing Introduction 28
Drug Substance 28
Drug Product 28
Placebo 28
Labeling 28
Pharmacology/Toxicology (Pharm/Tox) Section 29
Cross-Referencing 29
Type V Master File 29
Filing an IND 30
IND Maintenance 30
Current Good Manufacturing Practice (cGMP)and Cell Product Manufacturing 31
The IND/GMP Continuum 33
GMP Components 34
Staff Training 34
SOP Development 34
Processing Records 34
Equipment Records, Calibration, and Cleaning 35
Facility Requirements 35
Validation Procedures 35
Quality Assurance (QA)/Quality Control Program 35
Management Systems 35
Controlled Labeling Operations 36
Release Criteria Principles 36
Delivery of Cellular Products 37
Conclusion 38
Special Considerations: Umbilical Cord Blood 38
References 39
2 The Regulatory Situation for Academic Cell Therapy Facilities in Europe 42
The European Union (EU) Directive on Quality and Safety of Tissue and Cells 42
The EU Medicinal Products Directive 45
Advanced Cell Therapies 47
An Example of European Regulatory Status The Situation in France 48
Links 50
References 50
3 A Regulatory System for Cell and Tissue Therapies: Proposed Approach in Australia 51
Introduction 51
A Digression The Regulation of Therapeutic Goods in Australia 53
Current Regulation of Biological Therapies in Australia 54
Development of a Regulatory Framework for Celland Tissue Therapies in Australia 56
Assessment of the Manufacturing Process 60
Oversight of Clinical Development 60
Conclusion 61
References 61
Part II GMP Facility Design 63
4 University of Minnesota - Molecular and Cellular Therapeutics (MCT) 64
Overview 64
Facility Design 65
Aspects of Facility Design 66
References 68
5 University of Pittsburgh Cancer Institute - Hematopoietic Stem Cell Laboratory (HSC Lab)/Immunological Monitoring and Cellular Products Laboratory (IMCPL) 70
Introduction 70
Heating, Ventilation, and Air Conditioning (HVAC) System 71
Hematopoietic Stem Cell Laboratory (HSC Lab) 72
Immunological Monitoring and Cellular Products Laboratory (IMCPL) 74
Laboratory Features: What We Would Retain and What We Would Change 76
References 77
6 Baylor College of Medicine - Center for Cell and Gene Therapy (CAGT) 79
Introduction 79
Vector Production Facility (VPF) 82
Cell Processing Facility (CPF) 83
The New CAGT Facilities 89
General Comments 89
7 Design of a New GMP Facility - Lessons Learned 90
Introduction 90
Part III Professional Cell Therapy Standards 96
8 AABB Cell Therapy Standards 97
AABB: History and Evolution 97
Development and Evolution of Standards 98
Quality Systems Approach to Cellular Therapies 99
Transparency in Standards-Setting 100
Assessing Conformance to Standards 103
Accreditation 103
Validation of Assessments 104
Technical Highlights of the Third Edition 104
References 105
9 Professional Standards for Cellular Therapies: Foundation for the Accreditation of Cellular Therapy (FACT) 106
Historical Background 106
FACT Standards 108
FACT-JACIE International Standards for Cellular Therapy Product Collection, Processing, and Administration 109
NetCord-FACT International Standards for Cord Blood Collection, Processing, Testing, Banking, Selection, and Release 110
Accreditation 111
References 114
Part IV Facility Operations 116
10 Standard Operating Procedures 117
Introduction 117
Types of SOPs 118
Document Control 119
Numbering Systems for SOPs 119
Formatting and Content of SOPs 120
Writing SOPs 121
Validation Plans 122
Document Approval 123
New SOPs 123
Revised SOPs 123
Retired SOPs 125
Document Distribution and Availability 125
Production Batch Records (PBR) 125
Training Documentation 126
Archival of SOPs 126
Annual Review 126
Useful Literature 128
11 Staffing, Training, and Competency 129
Introduction 129
Analysis 130
Job Description 130
Training Regulations 132
Design of Training Program 133
The Adult Learner 135
e-Learning 136
Development 137
Implementation 138
Evaluation 138
Competence 138
Remediation 140
Recordkeeping 141
Conclusion 141
References 141
12 Cleaning Procedures 143
Choices and Getting Started 143
Schedules and Practices 146
Validation of Cleaning 148
Equipment Cleaning 149
Changeover Procedures 151
Summary 151
Useful Literature 152
13 Environmental Monitoring 153
Regulations 153
Good Tissue Practices (GTP) 153
Good Manufacturing Practices (GMP) 154
Academic GMP and GTP 154
Elements of Environmental Monitoring 156
Air Handling 156
Monitoring Frequency 158
Changeover Procedures 159
Interpretation of Data 159
Databases 161
Summary 163
Useful Literature 163
14 Supply Management 164
Regulatory Requirements 164
Good Tissue Practice (GTP) Regulations 164
Good Manufacturing Practice (GMP) Regulations 165
Establishing a System 166
Approved Supplies 167
Supply Release Specifications 167
Parts Lists 170
Receipt of Supplies 170
Supply Release 173
Storage 173
Released Supply Management 173
Formulations 175
Reagents Prepared In-House 176
Expired Materials 176
Updates 176
Useful Literature 177
15 Facility Equipment 178
Introduction 178
Equipment Selection 178
Design Qualification (DQ) 178
Choosing Equipment 179
Capital Budgeting 180
Warranties and Service Contracts 181
Qualification 182
Qualification Versus Validation 182
Installation Qualification (IQ) 183
Operational Qualification (OQ) 183
Process/Performance Qualification (PQ) 184
Operator Qualification 185
Equipment Prioritization and Backup 185
Quality Control (QC) and Documentation 186
Retiring Equipment 188
Regulations and Standards 189
References 192
16 Quality 194
Introduction 194
Designing a Quality Management Program 195
Monitoring Quality Systems 196
Audits 198
Improving Cellular Therapy Services 201
Quality Improvement 202
Conclusions 203
References 203
17 Product Manufacturing 205
Design of the Manufacturing Procedure 205
Production Monitoring 209
Review 210
Release Testing 212
Ancillary Records 216
Product Storage and Release 216
Conclusion 218
References 218
18 Product Review, Release, and Administration 220
Understanding Product Review and Release 220
Regulatory Issues 221
Product Review and Documentation 222
Product Testing for Release 223
Sterility Testing 226
Mycoplasma Testing 226
Purity 227
Viability 227
Identity Testing 227
Out-of-Specification (OOS) Results 229
Product Release, Transportation, and Shipment 230
Administration 231
Conclusions 231
References 232
19 Use of a Facility Master File to Facilitate Regulatory Submissions for Cell Therapy Products 234
Definition and Types of Master Files 234
Use and Content of the Cell Therapy Facility Master File 235
Writing the Cell Therapy Facility Master File 238
Options for Use of Master File as a Formal FDA Submission Versus an Internal Document 239
Summary 240
References 241
Appendix A Template Form referred to in Chapter 15 - Facility Equipment 242
Form A 242
Appendix B Template Form referred to in Chapter 15 - Facility Equipment 243
Form B -- Equipment Discard 243
Appendix C Template Form referred to in Chapter 15 - Facility Equipment 245
Form C -- Quality Control of Laboratory Scales 245
Appendix D Template Form referred to in Chapter 15 - Facility Equipment 246
From D -- Sample Policy New Equipment Qualification 246
Appendix E Template Form referred to in Chapter 15 - Facility Equipment 247
From E – Sample QC SOP Quality Control Procedure for Scale 247
Index 249