Kooperativer Bibliotheksverbund

UID:

Format: 1 online resource (xix, 335 pages) : , illustrations

ISBN: 0-12-802840-8 , 0-12-802826-2

Note: Includes index. , Cover -- Title page -- Copyright page -- Dedication -- Contents -- Contributors -- Foreword -- Chapter 1 - MSCs Translational Process -- 1.1 - MSCs and global clinical investigations -- 1.1.1 - Translation Challenges for MSCs -- 1.1.2 - Regulatory Classification of MSCs -- 1.1.3 - Regulatory Process for Clinical Investigations -- 1.2 - Preclinical studies -- 1.2.1 - Regulatory Requirements for Preclinical Studies -- 1.2.2 - Proof-of-Concept Studies/Animal Models -- 1.2.3 - Safety Studies/GLP Requirements -- 1.3 - Chemistry, manufacturing, and control -- 1.3.1 - Regulatory Requirements -- 1.3.2 - MSC Source Material -- 1.3.3 - Ancillary Materials -- 1.3.3.1 - Medium and supplements -- 1.3.3.2 - Fetal bovine serum versus xenogeneic-free alternatives -- 1.3.3.3 - Adhesion proteins and microcarriers -- 1.3.3.4 - Antibiotics -- 1.3.4 - Excipients Used in Final MSC Product Formulation -- 1.3.5 - MSC Manufacturing Process -- 1.3.5.1 - MSC in-process and final product release testing -- 1.4 - Clinical protocol -- 1.4.1 - Regulatory Requirements -- 1.4.2 - Clinical Protocol Consideration -- 1.5 - Implementation of MSC clinical investigation -- 1.5.1 - Implementation of Regulatory Process -- 1.5.2 - Implementation-Contracts -- 1.5.3 - Clinical Implementation -- 1.6 - Standardization efforts around MSCs -- 1.7 - Summary -- Abbreviations -- References -- Chapter 2 - Preclinical Animal Testing Requirements and Considerations -- 2.1 - Introduction -- 2.2 - Preclinical study conduct -- 2.2.1 - Documentation -- 2.2.2 - Staff Qualifications -- 2.2.3 - Facilities -- 2.2.4 - Equipment, Supplies, and Reagents -- 2.2.5 - Preclinical Study Cellular Product -- 2.2.6 - Preclinical Study Protocol -- 2.3 - Proof-of-concept studies -- 2.3.1 - Preliminary Efficacy Studies -- 2.3.2 - Animal Model of Disease -- 2.3.3 - Selection of an Appropriate Animal Model. , 2.3.4 - Preliminary Evaluation of Safety -- 2.3.5 - In Vitro Assessments -- 2.3.6 - Cell-Based Assays -- 2.4 - Preclinical safety studies -- 2.4.1 - Preclinical Safety Assays -- 2.4.2 - Preclinical Assessments in Animals -- 2.4.3 - Preliminary Safety in Animals -- 2.4.4 - Use of Hybrid Pharmacology/Toxicity Study Design -- 2.5 - Preclinical safety protocol design -- 2.5.1 - Protocol Design -- 2.5.2 - Cellular Therapy Product Dose Selection -- 2.5.3 - Study Endpoints -- 2.5.4 - Materials -- 2.6 - Conclusions -- References -- Chapter 3 - Delivery and Tracking Considerations for Cell-Based Therapies -- 3.1 - Introduction -- 3.2 - Cell delivery -- 3.2.1 - Intravascular Infusion -- 3.2.1.1 - Intravenous infusion -- 3.2.1.2 - Intraarterial infusion -- 3.2.2 - Direct Tissue Injection -- 3.2.2.1 - Intramuscular injection -- 3.2.2.2 - Intraparenchymal injection -- 3.2.3 - Scaffold-Based Delivery -- 3.2.4 - Trans-Mucosal Delivery -- 3.3 - Cell tracking -- 3.3.1 - Photon-Emitting Contrast Agents -- 3.3.1.1 - Positron emission tomography -- 3.3.2 - Single-Photon Emission Computed Tomography -- 3.3.3 - Bioluminescence -- 3.3.4 - Fluorescence Imaging -- 3.3.5 - Tissue Contrast Agents -- 3.3.5.1 - Magnetic resonance imaging -- 3.4 - Conclusions -- References -- Chapter 4 - Allogeneic Versus Autologous Mesenchymal Stromal Cells and Donor-to-Donor Variability -- 4.1 - Introduction -- 4.2 - Immunogenicity of MSCs -- 4.3 - Clinical considerations for the use of MSCs in transplantation -- 4.3.1 - MSC Cotransplantation in Allogeneic Hematopoietic Stem Cell Transplantation -- 4.3.1.1 - Clinical trials of MSCs to promote engraftment -- 4.3.1.2 - Considerations for MSC donor source in Hematopoietic Stem Cell Transplantation -- 4.3.2 - Considerations for MSC Donor Source in Solid Organ Transplantation -- 4.4 - MSC donor-to-donor variability -- 4.4.1 - Donor Age and Sex. , 4.4.2 - Underlying Disease -- 4.4.3 - Inherent Donor Differences -- 4.5 - Conclusion -- Abbreviations -- References -- Chapter 5 - Mesenchymal Stromal Cell Production in Academic Centers: Challenges and Opportunities -- 5.1 - Introduction -- 5.2 - Approach to manufacturing -- 5.2.1 - General Considerations -- 5.2.1.1 - Evaluation of research and preclinical studies -- 5.2.1.2 - Scale-up and optimization -- 5.2.1.3 - Methods validation -- 5.2.2 - MSC-Specific Considerations -- 5.2.2.1 - Source material and selection of donor -- 5.2.2.2 - Culture container/device -- 5.2.2.3 - Culture medium and supplements -- 5.2.2.4 - Culture schema -- 5.2.2.5 - Cryopreservation -- 5.2.2.6 - Quality control and lot release testing -- 5.2.2.7 - Summary -- 5.2.3 - Challenges -- 5.2.3.1 - Assembly of the team -- 5.2.3.2 - Funding -- 5.2.3.3 - Balancing workload -- 5.2.3.4 - Other challenges -- 5.2.4 - Opportunities -- 5.3 - Conclusion -- Abbreviations -- References -- Chapter 6 - Bioreactor for Scale-Up: Process Control -- 6.1 - Introduction -- 6.2 - Seed train -- 6.3 - Considerations for microcarrier selection -- 6.3.1 - Experimental Strategies for Microcarrier Selection -- 6.4 - In-process culture control: options and components -- 6.4.1 - Offline Measuring Methods -- 6.4.2 - Automated Sampling Systems -- 6.4.3 - Online Measuring Methods -- 6.5 - Platform components -- 6.5.1 - Growth Medium -- 6.5.2 - Vessel -- 6.5.2.1 - Mechanically driven bioreactors -- 6.5.2.1.1 - Stirred-tank bioreactors -- 6.5.2.1.2 - Rocker bioreactors -- 6.5.2.2 - Hydraulically driven bioreactors -- 6.5.2.2.1 - Pall Xpansion multiplate bioreactor system -- 6.5.2.2.2 - Fixed-bed bioreactors -- 6.5.2.2.3 - Hollow fiber bioreactors -- 6.5.3 - Controller -- 6.6 - Scalability/comparability -- 6.7 - Downstream processing -- 6.7.1 - Cell Detachment -- 6.7.2 - Microcarrier Removal. , 6.7.3 - Cell Washing and Concentration -- 6.7.3.1 - Tangential flow filtration -- 6.7.3.2 - Centrifugation -- 6.7.4 - Fill -- 6.7.5 - Visual Inspection -- 6.8 - Process optimization -- 6.9 - Feeding control -- 6.9.1 - Batch Versus Fed-Batch Versus Continuous Perfusion -- 6.10 - Conclusion -- References -- Chapter 7 - GMP Requirements -- 7.1 - Introduction -- 7.2 - The elements of cGMP -- 7.3 - Quality -- 7.4 - Staff qualifications -- 7.5 - Facilities -- 7.6 - Materials management -- 7.7 - Manufacturing activities -- 7.8 - Release testing -- 7.9 - Testing resources -- 7.10 - The chemistry, manufacturing, and control section of the IND -- 7.11 - Documentation -- 7.12 - Audits -- 7.13 - Post-CMC manufacturing changes -- 7.14 - Summary -- Acknowledgments -- References -- Chapter 8 - Mesenchymal Stromal Cells and the Approach to Clinical Trial Design: Lessons Learned From Graft Versus Host ... -- 8.1 - Introduction -- 8.2 - MSCs and GVHD -- 8.2.1 - Diagnosis and Immunobiology of Acute GVHD -- 8.2.2 - Current Preemptive Strategies -- 8.2.3 - Current Therapeutic Strategies -- 8.2.4 - MSCs in GVHD -- 8.3 - Translational challenges of MSCs for GVHD -- 8.3.1 - Relevance of Preclinical Studies of MSCs in GVHD -- 8.3.2 - Source of MSCs and Donor Selection in GVHD -- 8.3.3 - Fresh or Frozen? -- 8.3.4 - Potency and Release Criteria -- 8.3.5 - Biodistribution, Fate, and Longevity -- 8.3.6 - Intellectual Property and Funding -- 8.3.7 - Clinical Trial Parameters -- 8.3.8 - Control Arm -- 8.3.9 - Patient Eligibility -- 8.3.10 - Endpoint Selection -- 8.3.11 - Stratification -- 8.4 - Overcoming translational pitfalls -- 8.5 - Conclusions -- References -- Chapter 9 - Regulatory Pathway for Mesenchymal Stromal Cell-Based Therapy in the United States -- 9.1 - Introduction -- 9.2 - Regulatory plan -- 9.3 - Regulatory pathway -- 9.3.1 - Interactions With CBER and OCTGT. , 9.4 - Pre-IND meeting -- 9.5 - IND submission -- 9.6 - IND content-chemistry, manufacturing, and controls -- 9.7 - IND content-pharmacology and toxicology -- 9.8 - Cross-referencing -- 9.9 - FDA action on an IND application -- 9.10 - IND maintenance -- 9.11 - Moving to a clinical trial -- 9.12 - Trial design considerations -- 9.13 - Data and adverse event monitoring -- 9.14 - Conclusions -- Suggested Reading -- References -- Chapter 10 - Global Regulatory Perspective for MSCs -- 10.1 - Introduction -- 10.2 - Medicinal product legislation applicable to mesenchymal stromal cell products -- 10.2.1 - United States -- 10.2.2 - European Union -- 10.2.3 - Japan -- 10.2.4 - Australia -- 10.2.5 - Canada -- 10.2.6 - Korea -- 10.2.7 - Use of Medicinal Products Prior to Marketing Authorization -- 10.3 - Product development: from nonclinical studies to clinical trials to marketing authorization -- 10.3.1 - Guidance on Achieving Quality, Safety, and Efficacy When Developing Mesenchymal Stromal Cell Products -- 10.3.2 - The Common Technical Document -- 10.4 - CMC and quality development -- 10.4.1 - Good Manufacturing Practice -- 10.5 - Safety studies and nonclinical development -- 10.5.1 - Good Laboratory Practice -- 10.6 - Clinical development -- 10.6.1 - Good Clinical Practice -- 10.7 - Incentives and accelerated approval schemes applicable to mesenchymal stromal cell products -- 10.7.1 - United States -- 10.7.1.1 - Orphan drug designation -- 10.7.1.2 - Expedited programs for serious conditions -- 10.7.2 - European Union -- 10.7.2.1 - Orphan designation -- 10.7.2.2 - Alternative routes to marketing authorization -- 10.7.2.2.1 - Conditional marketing authorisation -- 10.7.2.2.2 - Marketing authorisation under exceptional circumstances -- 10.7.2.3 - Accelerated assessment -- 10.7.2.4 - Adaptive Pathways -- 10.7.3 - Japan -- 10.7.3.1 - Orphan drugs. , 10.7.3.2 - Expedited conditional approval of regenerative medicinal products.

Language: English

UID:

Format: 1 Online-Ressource (XII, 246 p. 35 illus., 33 illus. in color)

ISBN: 9783319974217

Series Statement: Advances in Experimental Medicine and Biology 1098

Additional Edition: Erscheint auch als Druck-Ausgabe ISBN 978-3-319-97420-0

Additional Edition: Erscheint auch als Druck-Ausgabe ISBN 978-3-319-97422-4

Language: English

DOI: 10.1007/978-3-319-97421-7

URL: Volltext  (URL des Erstveröffentlichers)

UID:

Format: Online-Ressource (XXVI, 695 p. 61 illus., 40 illus. in color, digital)

ISBN: 9781461457114 , 1299197302 , 9781299197305

Series Statement: Stem Cell Biology and Regenerative Medicine

Content: Mesenchymal Stromal Cell (MSC) biology has been studied for more than 4 decades and the cells have been investigated for potential clinical applications for more than 15 years. Progress has become exponential over the past decade due mainly to the broad therapeutic potential of these cells. However, MSC studies have also been subject to controversy and increasing scrutiny as new mechanisms of action are reported and ever-expanding therapeutic applications pursued. In this book, leading authorities from all over the world, who are actively involved in this field, provide state-of-the-art knowledge of the basic biology, translational requirements and latest clinical experience with MSCs. This cutting edge book is the ideal resource for scientists and clinicians interested in pursuing an important and rapidly developing field of research that will eventually help patients and address urgent unmet medical needs.Features include:Coverage of the biology of MSCs, latest understanding of mechanisms of action, and role in tissue homeostasis and regenerationIdentifying the potential of MSCs in proceeding from bench to bedside from regulatory , GMP production, ethical and safety aspects Critical analysis of clinical studies and the potential of MSCs to treat a wide variety of human diseases and tissues.

Note: Includes bibliographical references and index , pt. I. Basic biology -- pt. II. From bench to bedside -- pt. III. Clinical applications. , MSCs in regenerative medicine: A perspective -- MSCs: Changing hypotheses, paradigms, and controversies on mechanisms of action in repairing tissues -- MSCs:  the need to rethink -- Characterization of MSCs: From early studies to the present -- MSCs as therapeutics -- MSC niche for hematopoiesis -- Immunomodulatory properties of MSCs -- MSCs and the innate immune system: A balancing act -- MSCs: paracrine effects -- Cross-talk between MSCs and their environments -- Human MSCs from bone marrow, umbilical cord blood and adipose tissue: all the same? -- MSCs in solid tumors and hematological malignancies: from basic biology to therapeutic potential -- MSC studies in large animal Models -- Defining the potential of MSCs with a prenatal large animal Model -- Bench-to-bedside development of MSC based therapies: A multidisciplinary approach -- GMP production of MSCs -- MSCs: The USA regulatory perspective -- MSCs: Clinical applications and European regulatory aspects -- Stem cell treatments around the world: boon or bane? -- Safety issues in MSC therapy -- In Vivo imaging of MSCs -- National Heart, Lung, and Blood Institute support of cellular therapies regenerative medicine -- MSC therapy of inborn errors -- MSCs for enhancement of hematopoietic progenitor cell engraftment and poor graft function -- MSCs for graft-versus-host disease -- MSCs in paediatric hematopoietic stem cell transplantation -- MSCs for ex vivo expansion of umbilical cord blood cells -- MSCs for autoimmune disorders -- MSCs for induction of solid organ allograft acceptance -- MSCs for gastrointestinal disorders -- MSCs for cardiac repair -- MSCs for acute lung injury -- MSCs for diabetes -- MSCs for renal repair -- MSCs for the treatment of stroke, spinal cord injury, and traumatic brain injury: From bench work to clinical trials -- MSCs in reconstructive surgery -- MSCs in orthopedic surgery -- Adipose tissue derived MSCs: Moving to the clinic.

Additional Edition: ISBN 9781461457107

Additional Edition: Buchausg. u.d.T. ISBN 978-1-461-45710-7

Language: English

DOI: 10.1007/978-1-4614-5711-4

URL: Volltext

URL: Volltext  (lizenzpflichtig)

URL: Cover

UID:

Format: 1 online resource (xix, 335 pages) : , illustrations

ISBN: 0-12-802840-8 , 0-12-802826-2

Note: Includes index. , Cover -- Title page -- Copyright page -- Dedication -- Contents -- Contributors -- Foreword -- Chapter 1 - MSCs Translational Process -- 1.1 - MSCs and global clinical investigations -- 1.1.1 - Translation Challenges for MSCs -- 1.1.2 - Regulatory Classification of MSCs -- 1.1.3 - Regulatory Process for Clinical Investigations -- 1.2 - Preclinical studies -- 1.2.1 - Regulatory Requirements for Preclinical Studies -- 1.2.2 - Proof-of-Concept Studies/Animal Models -- 1.2.3 - Safety Studies/GLP Requirements -- 1.3 - Chemistry, manufacturing, and control -- 1.3.1 - Regulatory Requirements -- 1.3.2 - MSC Source Material -- 1.3.3 - Ancillary Materials -- 1.3.3.1 - Medium and supplements -- 1.3.3.2 - Fetal bovine serum versus xenogeneic-free alternatives -- 1.3.3.3 - Adhesion proteins and microcarriers -- 1.3.3.4 - Antibiotics -- 1.3.4 - Excipients Used in Final MSC Product Formulation -- 1.3.5 - MSC Manufacturing Process -- 1.3.5.1 - MSC in-process and final product release testing -- 1.4 - Clinical protocol -- 1.4.1 - Regulatory Requirements -- 1.4.2 - Clinical Protocol Consideration -- 1.5 - Implementation of MSC clinical investigation -- 1.5.1 - Implementation of Regulatory Process -- 1.5.2 - Implementation-Contracts -- 1.5.3 - Clinical Implementation -- 1.6 - Standardization efforts around MSCs -- 1.7 - Summary -- Abbreviations -- References -- Chapter 2 - Preclinical Animal Testing Requirements and Considerations -- 2.1 - Introduction -- 2.2 - Preclinical study conduct -- 2.2.1 - Documentation -- 2.2.2 - Staff Qualifications -- 2.2.3 - Facilities -- 2.2.4 - Equipment, Supplies, and Reagents -- 2.2.5 - Preclinical Study Cellular Product -- 2.2.6 - Preclinical Study Protocol -- 2.3 - Proof-of-concept studies -- 2.3.1 - Preliminary Efficacy Studies -- 2.3.2 - Animal Model of Disease -- 2.3.3 - Selection of an Appropriate Animal Model. , 2.3.4 - Preliminary Evaluation of Safety -- 2.3.5 - In Vitro Assessments -- 2.3.6 - Cell-Based Assays -- 2.4 - Preclinical safety studies -- 2.4.1 - Preclinical Safety Assays -- 2.4.2 - Preclinical Assessments in Animals -- 2.4.3 - Preliminary Safety in Animals -- 2.4.4 - Use of Hybrid Pharmacology/Toxicity Study Design -- 2.5 - Preclinical safety protocol design -- 2.5.1 - Protocol Design -- 2.5.2 - Cellular Therapy Product Dose Selection -- 2.5.3 - Study Endpoints -- 2.5.4 - Materials -- 2.6 - Conclusions -- References -- Chapter 3 - Delivery and Tracking Considerations for Cell-Based Therapies -- 3.1 - Introduction -- 3.2 - Cell delivery -- 3.2.1 - Intravascular Infusion -- 3.2.1.1 - Intravenous infusion -- 3.2.1.2 - Intraarterial infusion -- 3.2.2 - Direct Tissue Injection -- 3.2.2.1 - Intramuscular injection -- 3.2.2.2 - Intraparenchymal injection -- 3.2.3 - Scaffold-Based Delivery -- 3.2.4 - Trans-Mucosal Delivery -- 3.3 - Cell tracking -- 3.3.1 - Photon-Emitting Contrast Agents -- 3.3.1.1 - Positron emission tomography -- 3.3.2 - Single-Photon Emission Computed Tomography -- 3.3.3 - Bioluminescence -- 3.3.4 - Fluorescence Imaging -- 3.3.5 - Tissue Contrast Agents -- 3.3.5.1 - Magnetic resonance imaging -- 3.4 - Conclusions -- References -- Chapter 4 - Allogeneic Versus Autologous Mesenchymal Stromal Cells and Donor-to-Donor Variability -- 4.1 - Introduction -- 4.2 - Immunogenicity of MSCs -- 4.3 - Clinical considerations for the use of MSCs in transplantation -- 4.3.1 - MSC Cotransplantation in Allogeneic Hematopoietic Stem Cell Transplantation -- 4.3.1.1 - Clinical trials of MSCs to promote engraftment -- 4.3.1.2 - Considerations for MSC donor source in Hematopoietic Stem Cell Transplantation -- 4.3.2 - Considerations for MSC Donor Source in Solid Organ Transplantation -- 4.4 - MSC donor-to-donor variability -- 4.4.1 - Donor Age and Sex. , 4.4.2 - Underlying Disease -- 4.4.3 - Inherent Donor Differences -- 4.5 - Conclusion -- Abbreviations -- References -- Chapter 5 - Mesenchymal Stromal Cell Production in Academic Centers: Challenges and Opportunities -- 5.1 - Introduction -- 5.2 - Approach to manufacturing -- 5.2.1 - General Considerations -- 5.2.1.1 - Evaluation of research and preclinical studies -- 5.2.1.2 - Scale-up and optimization -- 5.2.1.3 - Methods validation -- 5.2.2 - MSC-Specific Considerations -- 5.2.2.1 - Source material and selection of donor -- 5.2.2.2 - Culture container/device -- 5.2.2.3 - Culture medium and supplements -- 5.2.2.4 - Culture schema -- 5.2.2.5 - Cryopreservation -- 5.2.2.6 - Quality control and lot release testing -- 5.2.2.7 - Summary -- 5.2.3 - Challenges -- 5.2.3.1 - Assembly of the team -- 5.2.3.2 - Funding -- 5.2.3.3 - Balancing workload -- 5.2.3.4 - Other challenges -- 5.2.4 - Opportunities -- 5.3 - Conclusion -- Abbreviations -- References -- Chapter 6 - Bioreactor for Scale-Up: Process Control -- 6.1 - Introduction -- 6.2 - Seed train -- 6.3 - Considerations for microcarrier selection -- 6.3.1 - Experimental Strategies for Microcarrier Selection -- 6.4 - In-process culture control: options and components -- 6.4.1 - Offline Measuring Methods -- 6.4.2 - Automated Sampling Systems -- 6.4.3 - Online Measuring Methods -- 6.5 - Platform components -- 6.5.1 - Growth Medium -- 6.5.2 - Vessel -- 6.5.2.1 - Mechanically driven bioreactors -- 6.5.2.1.1 - Stirred-tank bioreactors -- 6.5.2.1.2 - Rocker bioreactors -- 6.5.2.2 - Hydraulically driven bioreactors -- 6.5.2.2.1 - Pall Xpansion multiplate bioreactor system -- 6.5.2.2.2 - Fixed-bed bioreactors -- 6.5.2.2.3 - Hollow fiber bioreactors -- 6.5.3 - Controller -- 6.6 - Scalability/comparability -- 6.7 - Downstream processing -- 6.7.1 - Cell Detachment -- 6.7.2 - Microcarrier Removal. , 6.7.3 - Cell Washing and Concentration -- 6.7.3.1 - Tangential flow filtration -- 6.7.3.2 - Centrifugation -- 6.7.4 - Fill -- 6.7.5 - Visual Inspection -- 6.8 - Process optimization -- 6.9 - Feeding control -- 6.9.1 - Batch Versus Fed-Batch Versus Continuous Perfusion -- 6.10 - Conclusion -- References -- Chapter 7 - GMP Requirements -- 7.1 - Introduction -- 7.2 - The elements of cGMP -- 7.3 - Quality -- 7.4 - Staff qualifications -- 7.5 - Facilities -- 7.6 - Materials management -- 7.7 - Manufacturing activities -- 7.8 - Release testing -- 7.9 - Testing resources -- 7.10 - The chemistry, manufacturing, and control section of the IND -- 7.11 - Documentation -- 7.12 - Audits -- 7.13 - Post-CMC manufacturing changes -- 7.14 - Summary -- Acknowledgments -- References -- Chapter 8 - Mesenchymal Stromal Cells and the Approach to Clinical Trial Design: Lessons Learned From Graft Versus Host ... -- 8.1 - Introduction -- 8.2 - MSCs and GVHD -- 8.2.1 - Diagnosis and Immunobiology of Acute GVHD -- 8.2.2 - Current Preemptive Strategies -- 8.2.3 - Current Therapeutic Strategies -- 8.2.4 - MSCs in GVHD -- 8.3 - Translational challenges of MSCs for GVHD -- 8.3.1 - Relevance of Preclinical Studies of MSCs in GVHD -- 8.3.2 - Source of MSCs and Donor Selection in GVHD -- 8.3.3 - Fresh or Frozen? -- 8.3.4 - Potency and Release Criteria -- 8.3.5 - Biodistribution, Fate, and Longevity -- 8.3.6 - Intellectual Property and Funding -- 8.3.7 - Clinical Trial Parameters -- 8.3.8 - Control Arm -- 8.3.9 - Patient Eligibility -- 8.3.10 - Endpoint Selection -- 8.3.11 - Stratification -- 8.4 - Overcoming translational pitfalls -- 8.5 - Conclusions -- References -- Chapter 9 - Regulatory Pathway for Mesenchymal Stromal Cell-Based Therapy in the United States -- 9.1 - Introduction -- 9.2 - Regulatory plan -- 9.3 - Regulatory pathway -- 9.3.1 - Interactions With CBER and OCTGT. , 9.4 - Pre-IND meeting -- 9.5 - IND submission -- 9.6 - IND content-chemistry, manufacturing, and controls -- 9.7 - IND content-pharmacology and toxicology -- 9.8 - Cross-referencing -- 9.9 - FDA action on an IND application -- 9.10 - IND maintenance -- 9.11 - Moving to a clinical trial -- 9.12 - Trial design considerations -- 9.13 - Data and adverse event monitoring -- 9.14 - Conclusions -- Suggested Reading -- References -- Chapter 10 - Global Regulatory Perspective for MSCs -- 10.1 - Introduction -- 10.2 - Medicinal product legislation applicable to mesenchymal stromal cell products -- 10.2.1 - United States -- 10.2.2 - European Union -- 10.2.3 - Japan -- 10.2.4 - Australia -- 10.2.5 - Canada -- 10.2.6 - Korea -- 10.2.7 - Use of Medicinal Products Prior to Marketing Authorization -- 10.3 - Product development: from nonclinical studies to clinical trials to marketing authorization -- 10.3.1 - Guidance on Achieving Quality, Safety, and Efficacy When Developing Mesenchymal Stromal Cell Products -- 10.3.2 - The Common Technical Document -- 10.4 - CMC and quality development -- 10.4.1 - Good Manufacturing Practice -- 10.5 - Safety studies and nonclinical development -- 10.5.1 - Good Laboratory Practice -- 10.6 - Clinical development -- 10.6.1 - Good Clinical Practice -- 10.7 - Incentives and accelerated approval schemes applicable to mesenchymal stromal cell products -- 10.7.1 - United States -- 10.7.1.1 - Orphan drug designation -- 10.7.1.2 - Expedited programs for serious conditions -- 10.7.2 - European Union -- 10.7.2.1 - Orphan designation -- 10.7.2.2 - Alternative routes to marketing authorization -- 10.7.2.2.1 - Conditional marketing authorisation -- 10.7.2.2.2 - Marketing authorisation under exceptional circumstances -- 10.7.2.3 - Accelerated assessment -- 10.7.2.4 - Adaptive Pathways -- 10.7.3 - Japan -- 10.7.3.1 - Orphan drugs. , 10.7.3.2 - Expedited conditional approval of regenerative medicinal products.

Language: English

UID:

Format: 1 online resource (xix, 335 pages) : , illustrations

ISBN: 0-12-802840-8 , 0-12-802826-2

Note: Includes index. , Cover -- Title page -- Copyright page -- Dedication -- Contents -- Contributors -- Foreword -- Chapter 1 - MSCs Translational Process -- 1.1 - MSCs and global clinical investigations -- 1.1.1 - Translation Challenges for MSCs -- 1.1.2 - Regulatory Classification of MSCs -- 1.1.3 - Regulatory Process for Clinical Investigations -- 1.2 - Preclinical studies -- 1.2.1 - Regulatory Requirements for Preclinical Studies -- 1.2.2 - Proof-of-Concept Studies/Animal Models -- 1.2.3 - Safety Studies/GLP Requirements -- 1.3 - Chemistry, manufacturing, and control -- 1.3.1 - Regulatory Requirements -- 1.3.2 - MSC Source Material -- 1.3.3 - Ancillary Materials -- 1.3.3.1 - Medium and supplements -- 1.3.3.2 - Fetal bovine serum versus xenogeneic-free alternatives -- 1.3.3.3 - Adhesion proteins and microcarriers -- 1.3.3.4 - Antibiotics -- 1.3.4 - Excipients Used in Final MSC Product Formulation -- 1.3.5 - MSC Manufacturing Process -- 1.3.5.1 - MSC in-process and final product release testing -- 1.4 - Clinical protocol -- 1.4.1 - Regulatory Requirements -- 1.4.2 - Clinical Protocol Consideration -- 1.5 - Implementation of MSC clinical investigation -- 1.5.1 - Implementation of Regulatory Process -- 1.5.2 - Implementation-Contracts -- 1.5.3 - Clinical Implementation -- 1.6 - Standardization efforts around MSCs -- 1.7 - Summary -- Abbreviations -- References -- Chapter 2 - Preclinical Animal Testing Requirements and Considerations -- 2.1 - Introduction -- 2.2 - Preclinical study conduct -- 2.2.1 - Documentation -- 2.2.2 - Staff Qualifications -- 2.2.3 - Facilities -- 2.2.4 - Equipment, Supplies, and Reagents -- 2.2.5 - Preclinical Study Cellular Product -- 2.2.6 - Preclinical Study Protocol -- 2.3 - Proof-of-concept studies -- 2.3.1 - Preliminary Efficacy Studies -- 2.3.2 - Animal Model of Disease -- 2.3.3 - Selection of an Appropriate Animal Model. , 2.3.4 - Preliminary Evaluation of Safety -- 2.3.5 - In Vitro Assessments -- 2.3.6 - Cell-Based Assays -- 2.4 - Preclinical safety studies -- 2.4.1 - Preclinical Safety Assays -- 2.4.2 - Preclinical Assessments in Animals -- 2.4.3 - Preliminary Safety in Animals -- 2.4.4 - Use of Hybrid Pharmacology/Toxicity Study Design -- 2.5 - Preclinical safety protocol design -- 2.5.1 - Protocol Design -- 2.5.2 - Cellular Therapy Product Dose Selection -- 2.5.3 - Study Endpoints -- 2.5.4 - Materials -- 2.6 - Conclusions -- References -- Chapter 3 - Delivery and Tracking Considerations for Cell-Based Therapies -- 3.1 - Introduction -- 3.2 - Cell delivery -- 3.2.1 - Intravascular Infusion -- 3.2.1.1 - Intravenous infusion -- 3.2.1.2 - Intraarterial infusion -- 3.2.2 - Direct Tissue Injection -- 3.2.2.1 - Intramuscular injection -- 3.2.2.2 - Intraparenchymal injection -- 3.2.3 - Scaffold-Based Delivery -- 3.2.4 - Trans-Mucosal Delivery -- 3.3 - Cell tracking -- 3.3.1 - Photon-Emitting Contrast Agents -- 3.3.1.1 - Positron emission tomography -- 3.3.2 - Single-Photon Emission Computed Tomography -- 3.3.3 - Bioluminescence -- 3.3.4 - Fluorescence Imaging -- 3.3.5 - Tissue Contrast Agents -- 3.3.5.1 - Magnetic resonance imaging -- 3.4 - Conclusions -- References -- Chapter 4 - Allogeneic Versus Autologous Mesenchymal Stromal Cells and Donor-to-Donor Variability -- 4.1 - Introduction -- 4.2 - Immunogenicity of MSCs -- 4.3 - Clinical considerations for the use of MSCs in transplantation -- 4.3.1 - MSC Cotransplantation in Allogeneic Hematopoietic Stem Cell Transplantation -- 4.3.1.1 - Clinical trials of MSCs to promote engraftment -- 4.3.1.2 - Considerations for MSC donor source in Hematopoietic Stem Cell Transplantation -- 4.3.2 - Considerations for MSC Donor Source in Solid Organ Transplantation -- 4.4 - MSC donor-to-donor variability -- 4.4.1 - Donor Age and Sex. , 4.4.2 - Underlying Disease -- 4.4.3 - Inherent Donor Differences -- 4.5 - Conclusion -- Abbreviations -- References -- Chapter 5 - Mesenchymal Stromal Cell Production in Academic Centers: Challenges and Opportunities -- 5.1 - Introduction -- 5.2 - Approach to manufacturing -- 5.2.1 - General Considerations -- 5.2.1.1 - Evaluation of research and preclinical studies -- 5.2.1.2 - Scale-up and optimization -- 5.2.1.3 - Methods validation -- 5.2.2 - MSC-Specific Considerations -- 5.2.2.1 - Source material and selection of donor -- 5.2.2.2 - Culture container/device -- 5.2.2.3 - Culture medium and supplements -- 5.2.2.4 - Culture schema -- 5.2.2.5 - Cryopreservation -- 5.2.2.6 - Quality control and lot release testing -- 5.2.2.7 - Summary -- 5.2.3 - Challenges -- 5.2.3.1 - Assembly of the team -- 5.2.3.2 - Funding -- 5.2.3.3 - Balancing workload -- 5.2.3.4 - Other challenges -- 5.2.4 - Opportunities -- 5.3 - Conclusion -- Abbreviations -- References -- Chapter 6 - Bioreactor for Scale-Up: Process Control -- 6.1 - Introduction -- 6.2 - Seed train -- 6.3 - Considerations for microcarrier selection -- 6.3.1 - Experimental Strategies for Microcarrier Selection -- 6.4 - In-process culture control: options and components -- 6.4.1 - Offline Measuring Methods -- 6.4.2 - Automated Sampling Systems -- 6.4.3 - Online Measuring Methods -- 6.5 - Platform components -- 6.5.1 - Growth Medium -- 6.5.2 - Vessel -- 6.5.2.1 - Mechanically driven bioreactors -- 6.5.2.1.1 - Stirred-tank bioreactors -- 6.5.2.1.2 - Rocker bioreactors -- 6.5.2.2 - Hydraulically driven bioreactors -- 6.5.2.2.1 - Pall Xpansion multiplate bioreactor system -- 6.5.2.2.2 - Fixed-bed bioreactors -- 6.5.2.2.3 - Hollow fiber bioreactors -- 6.5.3 - Controller -- 6.6 - Scalability/comparability -- 6.7 - Downstream processing -- 6.7.1 - Cell Detachment -- 6.7.2 - Microcarrier Removal. , 6.7.3 - Cell Washing and Concentration -- 6.7.3.1 - Tangential flow filtration -- 6.7.3.2 - Centrifugation -- 6.7.4 - Fill -- 6.7.5 - Visual Inspection -- 6.8 - Process optimization -- 6.9 - Feeding control -- 6.9.1 - Batch Versus Fed-Batch Versus Continuous Perfusion -- 6.10 - Conclusion -- References -- Chapter 7 - GMP Requirements -- 7.1 - Introduction -- 7.2 - The elements of cGMP -- 7.3 - Quality -- 7.4 - Staff qualifications -- 7.5 - Facilities -- 7.6 - Materials management -- 7.7 - Manufacturing activities -- 7.8 - Release testing -- 7.9 - Testing resources -- 7.10 - The chemistry, manufacturing, and control section of the IND -- 7.11 - Documentation -- 7.12 - Audits -- 7.13 - Post-CMC manufacturing changes -- 7.14 - Summary -- Acknowledgments -- References -- Chapter 8 - Mesenchymal Stromal Cells and the Approach to Clinical Trial Design: Lessons Learned From Graft Versus Host ... -- 8.1 - Introduction -- 8.2 - MSCs and GVHD -- 8.2.1 - Diagnosis and Immunobiology of Acute GVHD -- 8.2.2 - Current Preemptive Strategies -- 8.2.3 - Current Therapeutic Strategies -- 8.2.4 - MSCs in GVHD -- 8.3 - Translational challenges of MSCs for GVHD -- 8.3.1 - Relevance of Preclinical Studies of MSCs in GVHD -- 8.3.2 - Source of MSCs and Donor Selection in GVHD -- 8.3.3 - Fresh or Frozen? -- 8.3.4 - Potency and Release Criteria -- 8.3.5 - Biodistribution, Fate, and Longevity -- 8.3.6 - Intellectual Property and Funding -- 8.3.7 - Clinical Trial Parameters -- 8.3.8 - Control Arm -- 8.3.9 - Patient Eligibility -- 8.3.10 - Endpoint Selection -- 8.3.11 - Stratification -- 8.4 - Overcoming translational pitfalls -- 8.5 - Conclusions -- References -- Chapter 9 - Regulatory Pathway for Mesenchymal Stromal Cell-Based Therapy in the United States -- 9.1 - Introduction -- 9.2 - Regulatory plan -- 9.3 - Regulatory pathway -- 9.3.1 - Interactions With CBER and OCTGT. , 9.4 - Pre-IND meeting -- 9.5 - IND submission -- 9.6 - IND content-chemistry, manufacturing, and controls -- 9.7 - IND content-pharmacology and toxicology -- 9.8 - Cross-referencing -- 9.9 - FDA action on an IND application -- 9.10 - IND maintenance -- 9.11 - Moving to a clinical trial -- 9.12 - Trial design considerations -- 9.13 - Data and adverse event monitoring -- 9.14 - Conclusions -- Suggested Reading -- References -- Chapter 10 - Global Regulatory Perspective for MSCs -- 10.1 - Introduction -- 10.2 - Medicinal product legislation applicable to mesenchymal stromal cell products -- 10.2.1 - United States -- 10.2.2 - European Union -- 10.2.3 - Japan -- 10.2.4 - Australia -- 10.2.5 - Canada -- 10.2.6 - Korea -- 10.2.7 - Use of Medicinal Products Prior to Marketing Authorization -- 10.3 - Product development: from nonclinical studies to clinical trials to marketing authorization -- 10.3.1 - Guidance on Achieving Quality, Safety, and Efficacy When Developing Mesenchymal Stromal Cell Products -- 10.3.2 - The Common Technical Document -- 10.4 - CMC and quality development -- 10.4.1 - Good Manufacturing Practice -- 10.5 - Safety studies and nonclinical development -- 10.5.1 - Good Laboratory Practice -- 10.6 - Clinical development -- 10.6.1 - Good Clinical Practice -- 10.7 - Incentives and accelerated approval schemes applicable to mesenchymal stromal cell products -- 10.7.1 - United States -- 10.7.1.1 - Orphan drug designation -- 10.7.1.2 - Expedited programs for serious conditions -- 10.7.2 - European Union -- 10.7.2.1 - Orphan designation -- 10.7.2.2 - Alternative routes to marketing authorization -- 10.7.2.2.1 - Conditional marketing authorisation -- 10.7.2.2.2 - Marketing authorisation under exceptional circumstances -- 10.7.2.3 - Accelerated assessment -- 10.7.2.4 - Adaptive Pathways -- 10.7.3 - Japan -- 10.7.3.1 - Orphan drugs. , 10.7.3.2 - Expedited conditional approval of regenerative medicinal products.

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