Rare diseases, such as sickle cell disease and thalassemia, affect up to 30 million people in the United States and at least 300 million across the globe. Congress called on the U.S. Food and Drug Administration (FDA) to sponsor a National Academies study on processes for evaluating the safety and efficacy of drugs for rare diseases or conditions in the United States and the European Union. The resulting report provides recommendations for enhancing and promoting rare disease drug development by improving engagement with people affected by a rare disease, advancing regulatory science, and fostering collaboration between FDA and the European Medicines Agency.

Contents

• The National Academies of SCIENCES • ENGINEERING • MEDICINE
• COMMITTEE ON PROCESSES TO EVALUATE THE SAFETY AND EFFICACY OF DRUGS FOR RARE DISEASES OR CONDITIONS IN THE UNITED STATES AND THE EUROPEAN UNION
• Reviewers
• Acknowledgments
• Preface
• Acronyms and Abbreviations
• Summary
  • REGULATORY FLEXIBILITIES, AUTHORITIES, AND MECHANISMS
  • USE OF ALTERNATIVE AND CONFIRMATORY DATA
  • FDA AND EMA COLLABORATION
• 1. Introduction
  • CLINICAL TRIALS FOR RARE DISEASES AND CONDITIONS
  • CONTEXT FOR THIS STUDY
  • STUDY APPROACH
  • REFERENCES
• 2. FDA Flexibilities, Authorities, and Mechanisms
  • DRUG REVIEW AND APPROVAL
  • DESIGNATION FOR RARE DISEASE PRODUCTS
  • EXPEDITED REGULATORY PROGRAMS
  • Priority Review
  • Regenerative Medicine Advanced Therapy
  • Oncology Center of Excellence Programs
  • Orphan Drugs and Expedited Review
  • INCLUSION OF PEDIATRIC POPULATIONS
  • STAKEHOLDER ENGAGEMENT
  • SELECT RARE DISEASE PROGRAMS
  • TRANSPARENCY
  • SUMMARY OF CONCLUSIONS AND RECOMMENDATIONS
  • REFERENCES
• 3. EMA Flexibilities, Authorities, and Mechanisms
  • DRUG REVIEW AND APPROVAL
  • ORPHAN MEDICINE DESIGNATION
  • EXPEDITED REGULATORY PROGRAMS
  • STAKEHOLDER ENGAGEMENT
  • RARE DISEASE INITIATIVES
  • TRANSPARENCY
  • REFERENCES
• 4. Alternative and Confirmatory Data
  • GUIDANCE ON ALTERNATIVE AND CONFIRMATORY DATA
  • SOURCES OF ALTERNATIVE AND CONFIRMATORY DATA
  • TRENDS IN REGULATORY USE
  • Expanding the Use of Alternative and Confirmatory Data
  • NOVEL APPROACHES FOR DATA ANALYSIS
  • Bayesian Statistical Methods
  • Network Meta-Analysis
  • Randomization-Based Inference
  • Quantitative Systems Pharmacology
  • BIOMARKERS
  • OPPORTUNITIES TO ENHANCE INNOVATION
  • SUMMARY OF CONCLUSIONS AND RECOMMENDATIONS
  • REFERENCES
• 5. FDA and EMA Collaboration
  • SIMILARITIES AND DIFFERENCES BETWEEN FDA AND EMA
  • COLLABORATION BETWEEN REGULATORY AGENCIES
  • OPPORTUNITIES FOR ENHANCED COLLABORATION
  • SUMMARY OF CONCLUSIONS AND RECOMMENDATIONS
  • REFERENCES
• Appendix A. Biographical Sketches of Committee Members and Staff
• Appendix B. Disclosures of Unavoidable Conflicts of Interest
• Appendix C. Public Meeting Agendas
• Appendix D. Centre for Innovation in Regulatory Science Data Analysis Methodology
• Appendix E. Qualitative Interview Summary and Methodology
• Appendix F. Non-Exhaustive List of Patient Focused Drug Development Meetings and Patient Listening Sessions for Rare Diseases Between 2013 and 2023
• Appendix G. List of Orphan Approvals by FDA or EMA Between 2018 and 2022
• Appendix H. Select Examples of Rare Disease Drug Products
• Appendix I. FDA and EMA Resources, Policies, and Programs Relevant for Drug Development for Rare Diseases and Conditions

Suggested citation:

National Academies of Sciences, Engineering, and Medicine. 2024. Regulatory processes for rare disease drugs in the United States and European Union: Flexibilities and collaborative opportunities. Washington, DC: The National Academies Press. https://doi.org/10.17226/27968.

Digital Object Identifier: https://doi.org/10.17226/27968

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