NSF/FDA SIR: Designing for Degradation: A framework for Predicting in vivo Degradation and Mechanical Property Changes in Degradable Polymers

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The commercialization of new medicines and medical devices often involves the use of degradable polymers. Over the last 50 years, a tremendous volume of physical property, processing and safety data has been built up globally about a very small library of degradable materials. Entire industries in medical devices, biomedical implants and drug delivery have been built and sustained on these data sets. However, there are emerging applications and routes of investigation in which the known library of materials will not work. The inability to design for degradation in polymeric devices and drug delivery remains one of the most significant barriers to industrial innovation in this area. As a result of this barrier, pre-clinical testing and development efforts remain empirical (trial and error) which is slow, expensive, and frequently pushes companies to utilize materials that have been used in other devices that have gained regulatory approval to lessen risk. The goal of this one-year FDA scholar in residence project is to initiate a framework for correlating in vitro to in vivo, i.e., in the lab to in the body, degradation behavior based on studies in a series of fully resorbable degradable polymer materials. A benchmarked and validated framework that would create an in vitro in vivo correlation (IVIVC) in new and emerging libraries of materials would be an invaluable tool to all stakeholders in academia, industry and regulatory agencies seeking to accelerate produced development timelines, increase safety and reduce regulatory risk. The project will also establish a robust collaboration between the FDA and the Investigator’s lab and provide a unique training experience for a graduate student who will in turn use experiences gained at the FDA to mentor high school, undergraduate and graduate students.This project is focused on developing correlations of water transport, degradation properties and time dependent changes in mechanical properties in amino acid-based poly(ester urea)s. Many properties of polymers affect how fast it degrades. The challenge for developing IVIV correlations is that in vitro tests, designed to develop semi-empirical models, do not accurately predict degradation rates that occur in vivo. This is primarily due to complicated dynamic processes that cannot be easily captured within static models. The in vitro and in vivo data collected in this proposal will provide the initial data sets needed to establish this framework and aid the FDA in advancing regulatory science that will be needed to ensure the safe use of hydrolytically degradable polymer in future generations of implants. Materials designed to create a range of water transport and mechanical properties will be subjected in vitro to accelerated and physiological degradation conditions and the molecular mass, molecular mass distribution, mechanical and physical properties will be tracked over time and benchmarked against in vivo subcutaneous implants in an animal model. The proposed research will impact the biomaterials community by helping to establish a framework for building IVIVC for degradation and the associated changes in the mechanical properties of amino acid-based poly(ester urea)s. This work will be done in collaboration with staff at CDRH/FDA, who have extensive regulatory science experience in chemistry and processing of polymer-based medical devices and combination products. The data generated will help the FDA generate fundamental and regulatory science knowledge for evaluating medical products fabricated using new degradable polymers and processing technologies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.