Exploring Sources of Variability Related to the Clinical Translation of Regenerative Engineering Products : Proceedings of a Workshop

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 conventionaltherapies. 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-qualityproducts, 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. Table of ContentsFront Matter1 Introduction and Overview2 Sources of Variability Associated with Regenerative Therapies: Lessons from Case Studies3 Factors Contributing to Patient Variability4 Addressing Variability in Donor Tissues and Cells5 Addressing Variability and Meeting Quality Expectations in the Manufacturing Setting6 Exploring Variability and Its Impact on Product Regulation and Outcomes7 Potential Next Steps to Consider for Addressing VariabilityReferencesAppendix A: Workshop AgendaAppendix B: Speaker Biographical SketchesAppendix C: Statement of TaskAppendix D: Registered Attendees