The emerging multidisciplinary field of regenerative engineering is devoted to the repair, regeneration, and replacement of damaged tissues or organs in the body. To accomplish this it uses a combination of principles and technologies from disciplines such as advanced materials science, developmental and stem cell biology, immunology, physics, and clinical translation. The term "regenerative engineering" reflects a new understanding of the use of tissue engineering for regeneration and also the growing number of research and product development efforts that incorporate elements from a variety of fields. Because regenerative engineered therapies rely on live cells and scaffolds, there are inherent challenges in quality control arising from variability in source and final products. Furthermore, each patient recipient, tissue donor, and product application is unique, meaning that the field faces complexities in the development of safe and effective new products and therapies which are not faced by developers of more conventional therapies. Understanding the many sources of variability can help reduce this variability and ensure consistent results. The Forum on Regenerative Medicine hosted a public workshop on October 18, 2018, in Washington, DC, to explore the various factors that must be taken into account in order to develop successful regenerative engineering products. Invited speakers and participants discussed factors and sources of variability in the development and clinical application of regenerative engineering products, characteristics of high-quality products, and how different clinical needs, models, and contexts can inform the development of a product to improve patient outcomes. This publication summarizes the presentation and discussion of the workshop.

Contents

• The National Academies of SCIENCES • ENGINEERING • MEDICINE
• PLANNING COMMITTEE ON EXPLORING SOURCES OF VARIABILITY RELATED TO THE CLINICAL TRANSLATION OF REGENERATIVE ENGINEERING PRODUCTS
• FORUM ON REGENERATIVE MEDICINE
• Reviewers
• Acknowledgments
• Acronyms and Abbreviations
• 1. Introduction and Overview
  • DEVELOPING REGENERATIVE ENGINEERING PRODUCTS
  • ORGANIZATION OF THE WORKSHOP AND PROCEEDINGS
• 2. Sources of Variability Associated with Regenerative Therapies: Lessons from Case Studies
  • CASE STUDY 1: VARIABILITY IN THE USE OF MESENCHYMAL STEM CELLS FOR TREATING CARDIOMYOPATHY
  • CASE STUDY 2: SOURCES OF VARIABILITY IN PRECLINICAL AND CLINICAL RESEARCH ON STEM CELL THERAPIES FOR ALS
  • CASE STUDY 3: VARIABILITY IN THE DEVELOPMENT OF CAR T CELL THERAPY
  • DISCUSSION
• 3. Factors Contributing to Patient Variability
  • UNDERSTANDING THERAPEUTIC MECHANISMS
  • OUTCOME VARIABILITY IN CARDIOVASCULAR STEM CELL TRIALS
  • ACCEPTABLE RESULTS FROM UNACCEPTABLE VARIABILITY
  • ALLOGENEIC CELL THERAPY FOR DEGENERATIVE DISC DISEASE
• 4. Addressing Variability in Donor Tissues and Cells
  • THE CHALLENGE OF VARIABILITY IN CAR T CELL MANUFACTURING
  • IDENTIFYING AND PROCESSING CELLS FOR REGENERATIVE THERAPIES
  • Sources of Variation in Cell Sourcing and Selection
  • THE ROLE OF PRESERVATION IN THE VARIABILTY OF REGENERATIVE MEDICINE PRODUCTS
  • DISCUSSION
• 5. Addressing Variability and Meeting Quality Expectations in the Manufacturing Setting
  • ADDRESSING VARIABILITY IN CELL AND GENE THERAPY MANUFACTURING
  • USING ELEMENTS OF QUALITY BY DESIGN TO MANAGE VARIABILITY
  • ADVANCES IN TISSUE CRYOPRESERVATION
  • DISCUSSION
• 6. Exploring Variability and Its Impact on Product Regulation and Outcomes
  • VENTRIGEL: A CASE EXAMPLE OF A REGENERATIVE ENGINEERING THERAPY
  • VARIABILITY OF REGENERATIVE ENGINEERING PRODUCTS AND THE REGULATORY APPROVAL PATHWAY
• 7. Potential Next Steps to Consider for Addressing Variability
  • CROSSCUTTING TOPIC DISCUSSION
  • FINAL THOUGHTS
• References
• Appendix A. Workshop Agenda
• Appendix B. Speaker Biographical Sketches
• Appendix C. Statement of Task
• Appendix D. Registered Attendees

Suggested citation:

Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2019. Exploring sources of variability related to the clinical translation of regenerative engineering products: Proceedings of a workshop. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/25371.

Digital Object Identifier: https://doi.org/10.17226/25371

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