FDA's Drug Review Process and the Package Label provides guidance to pharmaceutical companies for writing FDA-submissions, such as the NDA, BLA, Clinical Study Reports, and Investigator's Brochures. The book provides guidance to medical writers for drafting FDA-submissions in a way more likely to persuade FDA reviewers to grant approval of the drug. In detail, the book reproduces data on efficacy and safety from one hundred different FDA-submissions (NDAs, BLAs). The book reproduces comments and complaints from FDA reviewers regarding data that are fragmentary, ambiguous, or that detract from the drug's approvability, and the book reveals how sponsors overcame FDA's concerns and how sponsors succeeded in persuading FDA to grant approval of the drug. The book uses the most reliable and comprehensive source of information available for writing FDA-submissions, namely text and data from NDAs and BLAs, as published on FDA's website. The source material for writing this book included about 80,000 pages from FDA's Medical Reviews, FDA's Clinical Pharmacology Reviews, and FDA's Pharmacology Reviews, from one hundred different NDAs or BLAs for one hundred different drugs. Each chapter focuses on a different section of the package label, e.g., the Dosage and Administration section or the Drug Interactions section, and demonstrates how the sponsor's data supported that section of the package label.
1. Chapter 1. Introduction to Regulated Clinical Trials - p. 1 2. Chapter 2. FDA’s Decision-Making Process When Assessing Ambiguous Data - p. 23 3. Chapter 3. Food Effect Studies - p. 35 4. Chapter 4. Dose Modification and Dose Titration - p. 101 5. Chapter 5. Contraindications - p. 153 6. Chapter 6. Animal Studies - p. 187 7. Abstract - p. 187 8. I Introduction - p. 187 9. II No Observed Adverse Effect Level (NOAEL) - p. 194 10. III Calculating the Safety Margin - p. 197 11. IV Use in Specific Populations Section of the Package Label - p. 201 12. V Animal Data from FDA’s Reviews Find a Corresponding Disclosure in the Package Label (Small Molecule Drugs) - p. 202 13. VI Animal Data from FDA’s Reviews Find a Corresponding Disclosure in the Package Label (Biologics) - p. 232 14. VII Concluding Remarks - p. 252 15. Chapter 7. Drug–Drug Interactions: Part One (Small Molecule Drugs) - p. 255 16. Abstract - p. 255 17. I Introduction - p. 255 18. II Background on Cytochrome P450 Enzymes and Drug Transporters - p. 266 19. III P-Glycoprotein - p. 269 20. IV Integrated Picture of P-Glycoprotein’s Influence on Drug Exposure - p. 274 21. V Clearance of Drugs by Conjugation Catalyzed by UDP-glucuronosyltransferase - p. 277 22. VI Metabolites of Study Drugs - p. 279 23. VII Drug Clearance - p. 282 24. VIII Published Clinical Studies on Drug–Drug Interactions - p. 283 25. IX Drug–Drug Interactions in FDA’s Clinical Pharmacology Reviews - p. 284 26. X Organic Anion Transporter Polypeptide (OATP) Data - p. 330 27. XI A Small Molecule Drug Can Stimulate the Catabolism of Its Own Self - p. 331 28. XII Concluding Remarks - p. 332 29. Appendix A - p. 335 30. Chapter 8. Drug–Drug Interactions: Part Two (Therapeutic Proteins) - p. 337 31. Chapter 9. Immunosuppression, Drug-Induced Hypersensitivity Reactions, and Drug-Induced Autoimmune Reactions - p. 387 32. Chapter 10. Drug Class Analysis - p. 441 33. Abstract - p. 441 34. I Introduction - p. 441 35. II Off-Target Adverse Events - p. 444 36. III Short Examples of Drug Class Analysis - p. 447 37. IV First-in-Class and increased need for an Advisory Committee - p. 450 38. V Drugs for Cancer - p. 451 39. VI Drugs for Indications Other Than Cancer - p. 483 40. VII Concluding Remarks - p. 509 41. Chapter 11. Relatedness - p. 513 42. Chapter 12. Adjudication of Clinical Data - p. 549 43. Chapter 13. Coding - p. 575 44. Chapter 14. Pooling - p. 609 45. Index - p. 625
FDA's Drug Review Process and the Package Label provides guidance to pharmaceutical companies for writing FDA-submissions, such as the NDA, BLA, Clinical Study Reports, and Investigator's Brochures. The book provides guidance to medical writers for drafting FDA-submissions in a way more likely to persuade FDA reviewers to grant approval of the drug. In detail, the book reproduces data on efficacy and safety from one hundred different FDA-submissions (NDAs, BLAs). The book reproduces comments and complaints from FDA reviewers regarding data that are fragmentary, ambiguous, or that detract from the drug's approvability, and the book reveals how sponsors overcame FDA's concerns and how sponsors succeeded in persuading FDA to grant approval of the drug. The book uses the most reliable and comprehensive source of information available for writing FDA-submissions, namely text and data from NDAs and BLAs, as published on FDA's website. The source material for writing this book included about 80,000 pages from FDA's Medical Reviews, FDA's Clinical Pharmacology Reviews, and FDA's Pharmacology Reviews, from one hundred different NDAs or BLAs for one hundred different drugs. Each chapter focuses on a different section of the package label, e.g., the Dosage and Administration section or the Drug Interactions section, and demonstrates how the sponsor's data supported that section of the package label.
1. Chapter 1. Introduction to Regulated Clinical Trials - p. 1 2. Chapter 2. FDA’s Decision-Making Process When Assessing Ambiguous Data - p. 23 3. Chapter 3. Food Effect Studies - p. 35 4. Chapter 4. Dose Modification and Dose Titration - p. 101 5. Chapter 5. Contraindications - p. 153 6. Chapter 6. Animal Studies - p. 187 7. Abstract - p. 187 8. I Introduction - p. 187 9. II No Observed Adverse Effect Level (NOAEL) - p. 194 10. III Calculating the Safety Margin - p. 197 11. IV Use in Specific Populations Section of the Package Label - p. 201 12. V Animal Data from FDA’s Reviews Find a Corresponding Disclosure in the Package Label (Small Molecule Drugs) - p. 202 13. VI Animal Data from FDA’s Reviews Find a Corresponding Disclosure in the Package Label (Biologics) - p. 232 14. VII Concluding Remarks - p. 252 15. Chapter 7. Drug–Drug Interactions: Part One (Small Molecule Drugs) - p. 255 16. Abstract - p. 255 17. I Introduction - p. 255 18. II Background on Cytochrome P450 Enzymes and Drug Transporters - p. 266 19. III P-Glycoprotein - p. 269 20. IV Integrated Picture of P-Glycoprotein’s Influence on Drug Exposure - p. 274 21. V Clearance of Drugs by Conjugation Catalyzed by UDP-glucuronosyltransferase - p. 277 22. VI Metabolites of Study Drugs - p. 279 23. VII Drug Clearance - p. 282 24. VIII Published Clinical Studies on Drug–Drug Interactions - p. 283 25. IX Drug–Drug Interactions in FDA’s Clinical Pharmacology Reviews - p. 284 26. X Organic Anion Transporter Polypeptide (OATP) Data - p. 330 27. XI A Small Molecule Drug Can Stimulate the Catabolism of Its Own Self - p. 331 28. XII Concluding Remarks - p. 332 29. Appendix A - p. 335 30. Chapter 8. Drug–Drug Interactions: Part Two (Therapeutic Proteins) - p. 337 31. Chapter 9. Immunosuppression, Drug-Induced Hypersensitivity Reactions, and Drug-Induced Autoimmune Reactions - p. 387 32. Chapter 10. Drug Class Analysis - p. 441 33. Abstract - p. 441 34. I Introduction - p. 441 35. II Off-Target Adverse Events - p. 444 36. III Short Examples of Drug Class Analysis - p. 447 37. IV First-in-Class and increased need for an Advisory Committee - p. 450 38. V Drugs for Cancer - p. 451 39. VI Drugs for Indications Other Than Cancer - p. 483 40. VII Concluding Remarks - p. 509 41. Chapter 11. Relatedness - p. 513 42. Chapter 12. Adjudication of Clinical Data - p. 549 43. Chapter 13. Coding - p. 575 44. Chapter 14. Pooling - p. 609 45. Index - p. 625
