Nonclinical Evaluation Studies of Cellular and Gene Therapy Products: Strategies, Models, and Regulatory Frameworks systematically explores the nonclinical evaluation of Cell and Gene Therapies (CGT) products, emphasizing risk mitigation and innovation. The book provides comprehensive coverage, including 20+ chapters spanning preclinical toxicology, pharmacokinetics, and novel evaluation models. It is the first book to integrate organ-on-chip models into CGT evaluation, reflecting FDA/NMPA modernization initiatives. It includes practical guidance on addressing CRISPR off-target effects, immunogenicity, and long-term carcinogenicity risks.
1. Title of Book - p. i 2. Cover image - p. i 3. Title page - p. ii 4. Table of Contents - p. iii 5. Copyright - p. iv 6. Editorial Committee - p. xi 7. Preface - p. xv 8. Chapter 1. Overview of Cellular and Gene Therapy Products - p. 1 9. Chapter 2. Safety Risk Considerations of Cellular and Gene Therapy Products - p. 85 10. Chapter 3. Overview of Administrative Regulation for Cellular and Gene Therapy Products - p. 107 11. Chapter 4. Quality Control of Cellular and Gene Therapy Products - p. 169 12. Chapter 5. Nonclinical Toxicology Studies for Cellular and Gene Therapy Products - p. 205 13. Chapter 6. Research Progress on In Vivo Animal Models for the Evaluation of Cellular and Gene Therapy Products - p. 259 14. Chapter 7. Research Progress on In Vitro Organoid and Organ-on-a-Chip Models for the Evaluation of Cellular and Gene Therapy Products - p. 285 15. Chapter 8. Evaluation Research on Delivery Systems for Cellular and Gene Therapy Products - p. 313 16. Chapter 9. Immunogenicity Evaluation - p. 377 17. Chapter 10. Pharmacokinetic Research and Evaluation - p. 427 18. Chapter 11. Tumorigenicity/Oncogenicity Evaluation of Cellular and Gene Therapy Products - p. 471 19. Chapter 12. Integration Site Analysis and Off-target Analysis of Cellular and Gene Therapy Products - p. 523 20. Chapter 13. Nonclinical Evaluation of Stem Cell-Based Products - p. 547 21. Chapter 14. Nonclinical Evaluation of CAR-T Products - p. 601 22. Chapter 15. Nonclinical Evaluation Studies of Oncolytic Viruses - p. 637 23. Chapter 16. Nonclinical Evaluation of Gene-Editing Products - p. 681 24. Chapter 17. Nonclinical Evaluation Studies of Nucleic Acid Drugs - p. 723 25. Chapter 18. Nonclinical Evaluation Studies of Extracellular Vesicle-Based Drugs - p. 767 26. Chapter 19. Nonclinical Evaluation Studies of Red Cell Therapeutics Products - p. 821 27. Chapter 20. Nonclinical Research and Evaluation of Combination Therapies - p. 855 28. Case Studies - p. 897 29. HEMACORD – An Allogeneic Hematopoietic Reconstitution Stem Cell Drug Approved by the U.S. FDA for Treating Patients with Malignant Hematologic Disorders, Hurler Syndrome (MPS I), Krabbe Disease, X-Linked Adrenoleukodystrophy, Primary Immunodeficiencies, Bone Marrow Failure, and Beta Thalassemia - p. 897 30. References - p. 901 31. Alofisel – A Stem Cell Medicinal Product Approved by the EU EMA for the Treatment of Complex Perianal Fistulas in Adult Patients with Non-active/Mildly Active Crohn's Disease - p. 901 32. Review and Approval Outcome - p. 902 33. Holoclar – A Stem Cell Medicinal Product Approved by the EU EMA for Corneal Lesions with Limbal Stem Cell Deficiency - p. 917 34. Review and Approval Outcome - p. 917 35. References - p. 925 36. Non-Clinical Safety Evaluation of the CAR-T-19A Cell Product - p. 926 37. Non-Clinical Safety Evaluation of the BCMA-Targeted CAR-T Cell Product (Abecma) - p. 927 38. Non-Clinical Safety Evaluation of the BCMA-Targeted CAR-T Cell Product (Carvykti) - p. 928 39. Pharmacodynamic Study of CD20-Targeted CAR-T Cell Product in Non-Hodgkin Lymphoma - p. 929 40. Pharmacodynamic Study of a Pancreatic Cancer-Targeted CAR-T Cell Product in Tumor-Bearing Mice - p. 930 41. References - p. 932 42. Section 5 Application Cases of Organoid and Organ-on-a-Chip Technologies - p. 932 43. References - p. 936 44. Section 5 Case Study – LNP - p. 936 45. References - p. 954 46. Section 4 Pharmacokinetic Study Cases and Analysis - p. 954 47. References - p. 963 48. Section 5 Pharmacokinetic Studies of Oligonucleotide Drugs - p. 964 49. References - p. 967 50. Section 6 Metabolite Analysis Research for mRNA Drugs - p. 967 51. References - p. 970 52. Section 5: Case Studies - p. 970 53. References - p. 975 54. Section 5 Analysis of Marketed Stem Cell Product Case Studies - p. 976 55. References - p. 986 56. Section 6 Examples of Nonclinical Safety Evaluation for CAR-T Cell Products - p. 986 57. Section 9 Case Example of Nonclinical Safety Evaluation for an OV Product - p. 992 58. References - p. 995 59. Section 4 R&D Case Study - p. 996 60. References - p. 1000 61. Section 6 Examples of Nonclinical Safety Evaluation for RBC-Based Therapy Products - p. 1000 62. References - p. 1003 63. Section 2 Nonclinical Research Strategies for Drug Combinations - p. 1004 64. Index - p. 1009
Nonclinical Evaluation Studies of Cellular and Gene Therapy Products: Strategies, Models, and Regulatory Frameworks systematically explores the nonclinical evaluation of Cell and Gene Therapies (CGT) products, emphasizing risk mitigation and innovation. The book provides comprehensive coverage, including 20+ chapters spanning preclinical toxicology, pharmacokinetics, and novel evaluation models. It is the first book to integrate organ-on-chip models into CGT evaluation, reflecting FDA/NMPA modernization initiatives. It includes practical guidance on addressing CRISPR off-target effects, immunogenicity, and long-term carcinogenicity risks.
1. Title of Book - p. i 2. Cover image - p. i 3. Title page - p. ii 4. Table of Contents - p. iii 5. Copyright - p. iv 6. Editorial Committee - p. xi 7. Preface - p. xv 8. Chapter 1. Overview of Cellular and Gene Therapy Products - p. 1 9. Chapter 2. Safety Risk Considerations of Cellular and Gene Therapy Products - p. 85 10. Chapter 3. Overview of Administrative Regulation for Cellular and Gene Therapy Products - p. 107 11. Chapter 4. Quality Control of Cellular and Gene Therapy Products - p. 169 12. Chapter 5. Nonclinical Toxicology Studies for Cellular and Gene Therapy Products - p. 205 13. Chapter 6. Research Progress on In Vivo Animal Models for the Evaluation of Cellular and Gene Therapy Products - p. 259 14. Chapter 7. Research Progress on In Vitro Organoid and Organ-on-a-Chip Models for the Evaluation of Cellular and Gene Therapy Products - p. 285 15. Chapter 8. Evaluation Research on Delivery Systems for Cellular and Gene Therapy Products - p. 313 16. Chapter 9. Immunogenicity Evaluation - p. 377 17. Chapter 10. Pharmacokinetic Research and Evaluation - p. 427 18. Chapter 11. Tumorigenicity/Oncogenicity Evaluation of Cellular and Gene Therapy Products - p. 471 19. Chapter 12. Integration Site Analysis and Off-target Analysis of Cellular and Gene Therapy Products - p. 523 20. Chapter 13. Nonclinical Evaluation of Stem Cell-Based Products - p. 547 21. Chapter 14. Nonclinical Evaluation of CAR-T Products - p. 601 22. Chapter 15. Nonclinical Evaluation Studies of Oncolytic Viruses - p. 637 23. Chapter 16. Nonclinical Evaluation of Gene-Editing Products - p. 681 24. Chapter 17. Nonclinical Evaluation Studies of Nucleic Acid Drugs - p. 723 25. Chapter 18. Nonclinical Evaluation Studies of Extracellular Vesicle-Based Drugs - p. 767 26. Chapter 19. Nonclinical Evaluation Studies of Red Cell Therapeutics Products - p. 821 27. Chapter 20. Nonclinical Research and Evaluation of Combination Therapies - p. 855 28. Case Studies - p. 897 29. HEMACORD – An Allogeneic Hematopoietic Reconstitution Stem Cell Drug Approved by the U.S. FDA for Treating Patients with Malignant Hematologic Disorders, Hurler Syndrome (MPS I), Krabbe Disease, X-Linked Adrenoleukodystrophy, Primary Immunodeficiencies, Bone Marrow Failure, and Beta Thalassemia - p. 897 30. References - p. 901 31. Alofisel – A Stem Cell Medicinal Product Approved by the EU EMA for the Treatment of Complex Perianal Fistulas in Adult Patients with Non-active/Mildly Active Crohn's Disease - p. 901 32. Review and Approval Outcome - p. 902 33. Holoclar – A Stem Cell Medicinal Product Approved by the EU EMA for Corneal Lesions with Limbal Stem Cell Deficiency - p. 917 34. Review and Approval Outcome - p. 917 35. References - p. 925 36. Non-Clinical Safety Evaluation of the CAR-T-19A Cell Product - p. 926 37. Non-Clinical Safety Evaluation of the BCMA-Targeted CAR-T Cell Product (Abecma) - p. 927 38. Non-Clinical Safety Evaluation of the BCMA-Targeted CAR-T Cell Product (Carvykti) - p. 928 39. Pharmacodynamic Study of CD20-Targeted CAR-T Cell Product in Non-Hodgkin Lymphoma - p. 929 40. Pharmacodynamic Study of a Pancreatic Cancer-Targeted CAR-T Cell Product in Tumor-Bearing Mice - p. 930 41. References - p. 932 42. Section 5 Application Cases of Organoid and Organ-on-a-Chip Technologies - p. 932 43. References - p. 936 44. Section 5 Case Study – LNP - p. 936 45. References - p. 954 46. Section 4 Pharmacokinetic Study Cases and Analysis - p. 954 47. References - p. 963 48. Section 5 Pharmacokinetic Studies of Oligonucleotide Drugs - p. 964 49. References - p. 967 50. Section 6 Metabolite Analysis Research for mRNA Drugs - p. 967 51. References - p. 970 52. Section 5: Case Studies - p. 970 53. References - p. 975 54. Section 5 Analysis of Marketed Stem Cell Product Case Studies - p. 976 55. References - p. 986 56. Section 6 Examples of Nonclinical Safety Evaluation for CAR-T Cell Products - p. 986 57. Section 9 Case Example of Nonclinical Safety Evaluation for an OV Product - p. 992 58. References - p. 995 59. Section 4 R&D Case Study - p. 996 60. References - p. 1000 61. Section 6 Examples of Nonclinical Safety Evaluation for RBC-Based Therapy Products - p. 1000 62. References - p. 1003 63. Section 2 Nonclinical Research Strategies for Drug Combinations - p. 1004 64. Index - p. 1009
